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Sutton TL, Patel RK, Watson KM, Gardner IH, Herzig DO, Tsikitis VL, Chen EY, Mayo SC. Liver-First Resection in Patients With Synchronous Colorectal Liver Metastases Is Associated With Inferior Recurrence-Free Survival: Reconsidering the Importance of the Primary Cancer. Dis Colon Rectum 2025; 68:32-40. [PMID: 39264063 DOI: 10.1097/dcr.0000000000003518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/13/2024]
Abstract
BACKGROUND Synchronous colorectal liver metastases may be managed with primary-first, simultaneous, or liver-first resection. Relative oncologic outcomes based on treatment sequencing are understudied. OBJECTIVE This study aimed to assess oncologic survival outcomes in patients with synchronous colorectal liver metastases managed with each of the 3 treatment strategies, with respect to early or delayed removal of the primary tumor. DESIGN Retrospective analysis of the prospectively maintained database, with 1:1 propensity score matching of relevant clinicopathologic variables comparing liver-first to primary-first/simultaneous approaches. SETTINGS Single-institution, tertiary cancer center. PATIENTS Patients undergoing curative-intent hepatectomy for synchronous colorectal liver metastases from 2003 to 2019. MAIN OUTCOME MEASURES Overall and recurrence-free survival. RESULTS Of 151 patients, 23% (n = 35) had liver-first and 77% (n = 116; primary-first = 93 and simultaneous = 23) had primary-first/simultaneous approaches. The median follow-up was 45 months. Recurrence-free survival was worse for liver-first versus primary-first/simultaneous groups (median 12 versus 16 months, p = 0.02), driven by 3-year extrahepatic recurrence-free survival of 19%, 58%, and 50% for liver-first, primary-first, and simultaneous groups, respectively. Three-year overall survival was not significantly different at 86%, 79%, and 86%, respectively. Oncologic outcomes did not differ significantly between primary-first and simultaneous groups (all p > 0.4). Matching yielded 34 clinicopathologically similar patients per group (liver-first = 34, primary-first = 28, simultaneous = 6). The liver-first approach was associated with shorter recurrence-free survival (median 12 versus 23 months, p = 0.004), driven by extrahepatic recurrence-free survival (3 years: 20% versus 55%, p = 0.04). Overall survival was not significantly different at 3 years (79% versus 80%, p = 0.95) or 5 years (59% versus 59%, p > 0.99). LIMITATIONS This study has a retrospective design and a limited sample size. CONCLUSIONS A liver-first approach is associated with worse recurrence-free survival compared to primary-first or simultaneous resection, driven by extrahepatic recurrence. A prospective study of whether oncologic risk is associated with leaving the primary in situ is needed. Multidisciplinary treatment sequencing and enhanced postoperative surveillance for patients receiving liver-first resection are recommended. See Video Abstract . LA RESECCIN DEL HGADO PRIMERO EN PACIENTES CON METSTASIS HEPTICAS COLORRECTALES SINCRNICAS SE ASOCIA CON UNA SUPERVIVENCIA INFERIOR SIN RECURRENCIA RECONSIDERACIN DE LA IMPORTANCIA DEL CNCER PRIMARIO ANTECEDENTES:Las metástasis hepáticas colorrectales sincrónicas se pueden tratar con resección primaria, simultánea o hepática. Los resultados oncológicos relativos basados en la secuenciación del tratamiento están poco estudiados.OBJETIVO:Este estudio tuvo como objetivo evaluar los resultados de supervivencia oncológica en pacientes con metástasis hepáticas colorrectales sincrónicas tratadas con cada una de las tres estrategias de tratamiento, con respecto a la extirpación temprana o tardía del tumor primario.DISEÑO:Análisis retrospectivo de una base de datos mantenida prospectivamente, con coincidencia de propensión 1:1 de variables clínico-patológicas relevantes que comparan enfoques de hígado primero con enfoques primarios primero/simultáneos.AJUSTES:Centro oncológico terciario de una sola institución.PACIENTES:Pacientes sometidos a hepatectomía con intención curativa por metástasis hepáticas colorrectales sincrónicas entre 2003 y 2019.MEDIDAS PRINCIPALES DE RESULTADOS:Supervivencia general y libre de recurrencia.RESULTADOS:De 151 pacientes, el 23% (n=35) tuvo un abordaje hepático primero y el 77% (n=116; primario primero=93 y simultáneo=23) tuvo un abordaje primario primero/simultáneo. La mediana de seguimiento fue de 45 meses. La supervivencia libre de recurrencia fue peor para los grupos de hígado primero versus primario primero/simultáneo (mediana 12 versus 16 meses, p = 0,02), impulsada por la supervivencia libre de recurrencia extrahepática a tres años del 19%, 58% y 50% para grupos de hígado primero, primario primero y simultáneo, respectivamente. La supervivencia general a tres años no fue significativamente diferente: 86%, 79% y 86%, respectivamente. Los resultados oncológicos no difirieron significativamente entre los grupos primario-primero y simultáneo (todos p > 0,4). El emparejamiento produjo 34 pacientes clínico-patológicamente similares por grupo (hígado primero = 34, primario primero = 28/simultáneo = 6). El enfoque de hígado primero se asoció con una supervivencia libre de recurrencia más corta (mediana de 12 frente a 23 meses, p = 0,004), impulsada por la supervivencia libre de recurrencia extrahepática (3 años: 20 % frente a 55 %, p = 0,04). La supervivencia general no fue significativamente diferente a los 3 años (79% versus 80%, p = 0,95) o a los 5 años (59% versus 59%, p > 0,99).LIMITACIONES:Este estudio tiene un diseño retrospectivo y un tamaño de muestra limitado.CONCLUSIONES:Un enfoque de hígado primero se asocia con una peor supervivencia libre de recurrencia en comparación con la resección primaria o simultánea, impulsada por la recurrencia extrahepática. Es necesario un estudio prospectivo sobre si el riesgo oncológico se asocia con dejar el primario in situ . Se recomienda la secuenciación del tratamiento multidisciplinario y una vigilancia posoperatoria mejorada para los pacientes que reciben una primera resección del hígado. (Traducción-Yesenia Rojas-Khalil ).
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Affiliation(s)
- Thomas L Sutton
- Division of General Surgery, Department of Surgery, Oregon Health and Science University, Portland, Oregon
| | - Ranish K Patel
- Division of General Surgery, Department of Surgery, Oregon Health and Science University, Portland, Oregon
| | - Katherine M Watson
- Division of General Surgery, Department of Surgery, Oregon Health and Science University, Portland, Oregon
| | - Ivy H Gardner
- Division of General Surgery, Department of Surgery, Oregon Health and Science University, Portland, Oregon
| | - Daniel O Herzig
- Division of General Surgery, Department of Surgery, Oregon Health and Science University, Portland, Oregon
- Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon
| | - V Liana Tsikitis
- Division of General Surgery, Department of Surgery, Oregon Health and Science University, Portland, Oregon
- Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon
| | - Emerson Y Chen
- Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon
- Division of Hematology/Oncology, Department of Medicine, Oregon Health and Science University, Portland, Oregon
| | - Skye C Mayo
- Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon
- Division of Surgical Oncology, Department of Surgery, Oregon Health and Science University, Portland, Oregon
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Tanaka Y, Nakanishi R, Sato S, Otake A, Ryujin K, Ikeda S, Ebata Y, Harima T, Natsugoe K, Yoshiyama T, Shin Y, Kawazoe T, Kudo K, Zaitsu Y, Hisamatsu Y, Ando K, Nakashima Y, Itoh S, Oki E, Oda Y, Yoshizumi T. RAS mutant transverse colon cancer with multiple liver metastases achieving long-term disease-free survival with postoperative maintenance therapy with aflibercept + FOLFIRI and four repeated radical resections: a case report. Surg Case Rep 2024; 10:231. [PMID: 39377932 PMCID: PMC11461724 DOI: 10.1186/s40792-024-02033-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 09/25/2024] [Indexed: 10/09/2024] Open
Abstract
BACKGROUND Management of patients with colorectal liver metastases (CRLMs) requires a multidisciplinary approach. For patients with progression of RAS mutant tumors, the choice of angiogenesis inhibitors can be controversial. Here, we report a patient with RAS mutant CRLMs achieving long-term disease-free survival with repeated R0 resections and perioperative treatment, especially aflibercept + FOLFIRI (5-fluorouracil, levofolinate, irinotecan), which may have prevented long-term recurrence. CASE PRESENTATION The patient was a 37 year-old woman diagnosed with RAS mutant transverse colon cancer with 19 LMs. As the metastases were limited to the liver, we introduced systemic chemotherapy aiming at conversion surgery. After six cycles of bevacizumab + FOLFOXIRI (5-fluorouracil, levofolinate, oxaliplatin, irinotecan), we performed partial hepatectomy for all LMs, and left hemicolectomy for the primary tumor after another four cycles of bevacizumab + FOLFIRI. Three months after surgery, the patient presented with massive ovarian metastases with carcinomatous ascites. We conducted bilateral oophorectomy, and initiated aflibercept + FOLFIRI therapy considering the possibility of resistance to bevacizumab. The patient was recurrence-free for 2 years during aflibercept + FOLFIRI treatment. After its discontinuation, two distant metastases developed. Both were resectable and the patient achieved recurrence-free survival of 2 years and 3 months after the last operation (6 years since initiation of treatment), without additional chemotherapy. CONCLUSIONS We believe that multidisciplinary treatment aimed at complete resection could lead to long-term survival even in patients with repeated recurrence of CRLMs. Aflibercept + FOLFIRI could be effective in controlling metastasis of RAS mutant colon cancer even after treatment with bevacizumab.
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Affiliation(s)
- Yasushi Tanaka
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
| | - Ryota Nakanishi
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Shota Sato
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Akihiko Otake
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Keiichiro Ryujin
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Shinichiro Ikeda
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yuho Ebata
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Tomoya Harima
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Keita Natsugoe
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Takayuki Yoshiyama
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yuki Shin
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Tetsuro Kawazoe
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Kensuke Kudo
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yoko Zaitsu
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yuichi Hisamatsu
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Koji Ando
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yuichiro Nakashima
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Eiji Oki
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan
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Serradilla-Martín M, Villodre C, Falgueras-Verdaguer L, Zambudio-Carroll N, Castell-Gómez JT, Blas-Laina JL, Borrego-Estella V, Domingo-del-Pozo C, García-Plaza G, González-Rodríguez FJ, Montalvá-Orón EM, Moya-Herraiz Á, Paterna-López S, Suárez-Muñoz MA, Alkorta-Zuloaga M, Blanco-Fernández G, Dabán-Collado E, Gómez-Bravo MA, Miota-de-Llamas JI, Rotellar F, Sánchez-Pérez B, Sánchez-Cabús S, Pacheco-Sánchez D, Rodríguez-Sanjuan JC, Varona-Bosque MA, Carrión-Álvarez L, de la Serna-Esteban S, Dopazo C, Martín-Pérez E, Martínez-Cecilia D, Castro-Santiago MJ, Dorcaratto D, Gutiérrez-Díaz ML, Asencio-Pascual JM, Burdío-Pinilla F, Carracedo-Iglesias R, Escartín-Arias A, Ielpo B, Rodríguez-Laiz G, Valdivieso-López A, De-Vicente-López E, Alonso-Orduña V, Ramia JM. Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project). Cancers (Basel) 2024; 16:1676. [PMID: 38730631 PMCID: PMC11082946 DOI: 10.3390/cancers16091676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 04/21/2024] [Accepted: 04/25/2024] [Indexed: 05/13/2024] Open
Abstract
(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.
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Affiliation(s)
- Mario Serradilla-Martín
- Department of Surgery, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain;
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- Department of Surgery, School of Medicine, University of Granada, 18016 Granada, Spain
| | - Celia Villodre
- Department of Surgery, Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain; (C.V.); (J.M.R.)
- ISABIAL, Instituto de Investigación Sanitaria y Biomédica de Alicante, 03010 Alicante, Spain
- Department of Surgery, Universidad Miguel Hernández, 03202 Alicante, Spain
| | | | | | | | | | | | | | - Gabriel García-Plaza
- Department of Surgery, Hospital Universitario Insular, 35016 Las Palmas de Gran Canaria, Spain;
| | | | - Eva M. Montalvá-Orón
- Department of Surgery, Hospital Universitario y Politécnico La Fe, IIS La Fe, Ciberehd ISCIII, 46026 Valencia, Spain;
| | - Ángel Moya-Herraiz
- Department of Surgery, Hospital Universitario de Castellón, 12004 Castelló de la Plana, Spain;
| | - Sandra Paterna-López
- Department of Surgery, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain;
| | - Miguel A. Suárez-Muñoz
- Department of Surgery, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain;
| | | | | | | | - Miguel A. Gómez-Bravo
- Department of Surgery, Hospital Universitario Virgen del Rocío, 41013 Sevilla, Spain;
| | | | - Fernando Rotellar
- Department of Surgery, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
| | - Belinda Sánchez-Pérez
- Department of Surgery, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain;
| | - Santiago Sánchez-Cabús
- Department of Surgery, Hospital Universitario de la Santa Creu i Sant Pau, 08041 Barcelona, Spain;
| | | | | | - María A. Varona-Bosque
- Department of Surgery, Hospital Universitario Nuestra Señora de la Candelaria, 38010 Santa Cruz de Tenerife, Spain;
| | | | | | - Cristina Dopazo
- Department of Surgery, Hospital Universitario Vall d’Hebron, 08035 Barcelona, Spain;
| | - Elena Martín-Pérez
- Department of Surgery, Hospital Universitario La Princesa, 28006 Madrid, Spain; (E.M.-P.); (D.M.-C.)
| | - David Martínez-Cecilia
- Department of Surgery, Hospital Universitario La Princesa, 28006 Madrid, Spain; (E.M.-P.); (D.M.-C.)
- Department of Surgery, Hospital Universitario Virgen de la Salud, 45004 Toledo, Spain
| | | | - Dimitri Dorcaratto
- Department of Surgery, Hospital Clínico Universitario, 46010 Valencia, Spain;
| | | | | | - Fernando Burdío-Pinilla
- Department of Surgery, Hospital Universitario del Mar, 08003 Barcelona, Spain; (F.B.-P.); (B.I.)
| | | | | | - Benedetto Ielpo
- Department of Surgery, Hospital Universitario del Mar, 08003 Barcelona, Spain; (F.B.-P.); (B.I.)
- Department of Surgery, Hospital Universitario de León, 24008 León, Spain
| | - Gonzalo Rodríguez-Laiz
- Department of Surgery, Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain; (C.V.); (J.M.R.)
| | | | | | - Vicente Alonso-Orduña
- Department of Medical Oncology, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain;
| | - José M. Ramia
- Department of Surgery, Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain; (C.V.); (J.M.R.)
- ISABIAL, Instituto de Investigación Sanitaria y Biomédica de Alicante, 03010 Alicante, Spain
- Department of Surgery, Universidad Miguel Hernández, 03202 Alicante, Spain
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Zlotnik O, Krzywon L, Bloom J, Kalil J, Altubi I, Lazaris A, Metrakos P. Targeting Liver Metastases to Potentiate Immunotherapy in MS-Stable Colorectal Cancer-A Review of the Literature. Cancers (Basel) 2023; 15:5210. [PMID: 37958384 PMCID: PMC10649257 DOI: 10.3390/cancers15215210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 10/26/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
Immunotherapy has revolutionized the treatment of several cancers, including melanoma and lung cancer. However, for colorectal cancer, it is ineffective for 95% of patients with microsatellite-stable disease. Recent evidence suggests that the liver's immune microenvironment plays a pivotal role in limiting the effectiveness of immunotherapy. There is also evidence to show that targeting liver metastases with locoregional therapies, such as surgery or irradiation, could potentiate immunotherapy for these patients. This review presents evidence from preclinical studies regarding the underlying mechanisms and from clinical studies that support this approach. Furthermore, we outline potential directions for future clinical trials. This innovative strategy could potentially establish immunotherapy as an effective treatment for MS-stable colorectal cancer patients, which are currently considered resistant.
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Affiliation(s)
- Oran Zlotnik
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
- Division of General Surgery, McGill University, Montreal, QC H4A 3J1, Canada;
| | - Lucyna Krzywon
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
| | - Jessica Bloom
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
| | - Jennifer Kalil
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
- Division of General Surgery, McGill University, Montreal, QC H4A 3J1, Canada;
| | - Ikhtiyar Altubi
- Division of General Surgery, McGill University, Montreal, QC H4A 3J1, Canada;
| | - Anthoula Lazaris
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
| | - Peter Metrakos
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
- Division of General Surgery, McGill University, Montreal, QC H4A 3J1, Canada;
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Keogh C, O’Sullivan NJ, Temperley HC, Flood MP, Ting P, Walsh C, Waters P, Ryan ÉJ, Conneely JB, Edmundson A, Larkin JO, McCormick JJ, Mehigan BJ, Taylor D, Warrier S, McCormick PH, Soucisse ML, Harris CA, Heriot AG, Kelly ME. Redo Pelvic Surgery and Combined Metastectomy for Locally Recurrent Rectal Cancer with Known Oligometastatic Disease: A Multicentre Review. Cancers (Basel) 2023; 15:4469. [PMID: 37760439 PMCID: PMC10527388 DOI: 10.3390/cancers15184469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/29/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023] Open
Abstract
INTRODUCTION Historically, surgical resection for patients with locally recurrent rectal cancer (LRRC) had been reserved for those without metastatic disease. 'Selective' patients with limited oligometastatic disease (OMD) (involving the liver and/or lung) are now increasingly being considered for resection, with favourable five-year survival rates. METHODS A retrospective analysis of consecutive patients undergoing multi-visceral pelvic resection of LRRC with their oligometastatic disease between 1 January 2015 and 31 August 2021 across four centres worldwide was performed. The data collected included disease characteristics, neoadjuvant therapy details, perioperative and oncological outcomes. RESULTS Fourteen participants with a mean age of 59 years were included. There was a female preponderance (n = 9). Nine patients had liver metastases, four had lung metastases and one had both lung and liver disease. The mean number of metastatic tumours was 1.5 +/- 0.85. R0 margins were obtained in 71.4% (n = 10) and 100% (n = 14) of pelvic exenteration and oligometastatic disease surgeries, respectively. Mean lymph node yield was 11.6 +/- 6.9 nodes, with positive nodes being found in 28.6% (n = 4) of cases. A single major morbidity was reported, with no perioperative deaths. At follow-up, the median disease-free survival and overall survival were 12.3 months (IQR 4.5-17.5 months) and 25.9 months (IQR 6.2-39.7 months), respectively. CONCLUSIONS Performing radical multi-visceral surgery for LRRC and distant oligometastatic disease appears to be feasible in appropriately selected patients that underwent good perioperative counselling.
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Affiliation(s)
- Cian Keogh
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
- Department of Surgery, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
- School of Medicine, University of Queensland, Brisbane 4072, Australia
| | - Niall J. O’Sullivan
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - Hugo C. Temperley
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - Michael P. Flood
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
| | - Pascallina Ting
- Department of Surgery, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
| | - Camille Walsh
- Department of Surgery, Hôpital Maisonneuve-Rosemont, Montreal, QC H1T 2M4, Canada
| | - Peadar Waters
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
| | - Éanna J. Ryan
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - John B. Conneely
- Department of Surgery, Mater Misericordiae University Hospital, D07 R2WY Dublin, Ireland
| | - Aleksandra Edmundson
- Department of Surgery, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
| | - John O. Larkin
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - Jacob J. McCormick
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
| | - Brian J. Mehigan
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - David Taylor
- Department of Surgery, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
| | - Satish Warrier
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
| | - Paul H. McCormick
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - Mikael L. Soucisse
- Department of Surgery, Hôpital Maisonneuve-Rosemont, Montreal, QC H1T 2M4, Canada
| | - Craig A. Harris
- Department of Surgery, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
| | - Alexander G. Heriot
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
| | - Michael E. Kelly
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
- Trinity St. James Cancer Institute, D08 W9RT Dublin, Ireland
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Herrero Fonollosa E, Galofré Recasens M, Zárate Pinedo A, García Domingo MI, Camps Lasa J, Pardo Aranda F, Espin Álvarez F, Cugat Andorrà E. Long-term results of liver-first approach strategy in patients with advanced synchronous liver metastases from colorectal cancer. Cir Esp 2023; 101:341-349. [PMID: 35667607 DOI: 10.1016/j.cireng.2022.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 04/15/2022] [Indexed: 05/16/2023]
Abstract
BACKGROUND The "liver-first" approach (LFA) is a strategy indicated for advanced synchronous liver metastases (ASLM) from colorectal cancer (CRC). Includes neoadjuvant chemotherapy, resection of the ASLM followed by CRC resection. METHODS Retrospective descriptive analysis from a prospective database of hepatectomies from liver metastases (LM) from CRC in two centers. Between 2007-2019, 88 patients with CRC-ASLM were included in a LFA scheme. Bilobar (LM) was present in 65.9%, the mean number of lesions was 5.5 and mean size 42.7 mm. Response to treatment was assessed by RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier survival curves. RESULTS Seventy-five of 88 patients (85.2%) completed the LFA. RECIST evaluation showed partial response in 75.7% and stable disease in 22.8%. Severe morbidity rate (Clavien-Dindo ≥ IIIA) after liver and colorectal surgery was present in 29.4% and 9.3%, respectively. There was no 90-day postoperative mortality in both liver and colorectal surgeries. Recurrence rate was 76%, being the liver the most frequent site, followed by the pulmonary. From the total number of recurrences (106) in 56 patients, surgical with chemotherapy rescue treatment was accomplished in 34 of them (32.1%). The mean PFS was 8.5 and 5-year OS was 53%. CONCLUSIONS In patients with CRC-ASLM the LFA allows control of the liver disease beforehand and an assessment of the tumor response to neoadjuvant chemotherapy, optimising the chance of potentially curative liver resection, which influences long-term survival.
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Affiliation(s)
- Eric Herrero Fonollosa
- Unidad de Cirugía HBP, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitari Mútua Terrassa, Terrassa, Barcelona, Spain.
| | - María Galofré Recasens
- Unidad de Cirugía HBP, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitari Mútua Terrassa, Terrassa, Barcelona, Spain
| | - Alba Zárate Pinedo
- Unidad de Cirugía HBP, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Maria Isabel García Domingo
- Unidad de Cirugía HBP, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitari Mútua Terrassa, Terrassa, Barcelona, Spain
| | - Judith Camps Lasa
- Unidad de Cirugía HBP, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitari Mútua Terrassa, Terrassa, Barcelona, Spain
| | - Fernando Pardo Aranda
- Unidad de Cirugía HBP, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Francisco Espin Álvarez
- Unidad de Cirugía HBP, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Esteban Cugat Andorrà
- Unidad de Cirugía HBP, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitari Mútua Terrassa, Terrassa, Barcelona, Spain; Unidad de Cirugía HBP, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
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Liu LL, Sun JD, Xiang ZL. Survival nomograms for colorectal carcinoma patients with lung metastasis and lung-only metastasis, based on the SEER database and a single-center external validation cohort. BMC Gastroenterol 2022; 22:446. [PMID: 36335295 PMCID: PMC9636633 DOI: 10.1186/s12876-022-02547-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 10/19/2022] [Indexed: 11/06/2022] Open
Abstract
Background We analysed the survival of colorectal cancer (CRC) patients with lung metastasis and lung-only metastasis and determined the risk factors for lung metastasis in CRC patients. Methods Data from colorectal cancer patients with lung metastasis diagnosed from 2010 to 2015 were obtained from the SEER database. Survival was analysed using the Kaplan–Meier method and log-rank test, the Cox proportional hazards regression model, and a competing risk model. The predictive ability of the nomgram was assessed by the concordance index (C-index) and calibration curves. The data from the SEER database for the period 2016–2019 was used as an external validation set. The characteristics of 70 CRC patients treated at Shanghai East Hospital between 2016 and 2019 were retrospectively analysed and data from China was chosen as an external validation set. Results The median survival time for colorectal cancer patients with lung metastasis was 12 months, while this value was 24 months in patients with lung-only metastasis. Among all CRC patients with lung metastasis, age, grade, T stage, N stage, presence of liver, brain or bone metastasis, anatomic site and surgery were related to overall survival (OS). In CRC patients with lung-only metastasis, age, T stage, marital status, chemotherapy and surgery were independent prognostic factors affecting OS. Two nomograms predicting OS were established, with great discrimination (C-index between 0.67 and 0.81) and excellent calibration. Factors including age, race, sex, tumour grade, T stage, N stage, presence of liver, brain or bone metastasis, marital status, insurance status and anatomic location were related to the occurrence of lung metastasis in CRC patients. Conclusion We developed two reliable clinical prediction models among CRC patients to predict the OS rates in patients with lung metastasis and lung metastasis only. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02547-9.
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Ozair A, Collings A, Adams AM, Dirks R, Kushner BS, Sucandy I, Morrell D, Abou-Setta AM, Vreeland T, Whiteside J, Cloyd JM, Ansari MT, Cleary SP, Ceppa E, Richardson W, Alseidi A, Awad Z, Ayloo S, Buell JF, Orthopoulos G, Sbayi S, Wakabayashi G, Slater BJ, Pryor A, Jeyarajah DR. Minimally invasive versus open hepatectomy for the resection of colorectal liver metastases: a systematic review and meta-analysis. Surg Endosc 2022; 36:7915-7937. [PMID: 36138246 DOI: 10.1007/s00464-022-09612-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 09/05/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND While surgical resection has a demonstrated utility for patients with colorectal liver metastases (CRLM), it is unclear whether minimally invasive surgery (MIS) or an open approach should be used. This review sought to assess the efficacy and safety of MIS versus open hepatectomy for isolated, resectable CRLM when performed separately from (Key Question (KQ) 1) or simultaneously with (KQ2) the resection of the primary tumor. METHODS PubMed, Embase, Google Scholar, Cochrane CENTRAL, International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov databases were searched to identify both randomized controlled trials (RCTs) and non-randomized comparative studies published during January 2000-September 2020. Two independent reviewers screened literature for eligibility, extracted data from included studies, and assessed internal validity using the Cochrane Risk of Bias 2.0 Tool and the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed using risk ratios (RR) and mean differences (MD). RESULTS From 2304 publications, 35 studies were included for meta-analysis. For staged resections, three RCTs and 20 observational studies were included. Data from RCTs indicated MIS having similar disease-free survival (DFS) at 1-year (RR 1.03, 95%CI 0.70-1.50), overall survival (OS) at 5-years (RR 1.04, 95%CI 0.84-1.28), fewer complications of Clavien-Dindo Grade III (RR 0.62, 95%CI 0.38-1.00), and shorter hospital length of stay (LOS) (MD -6.6 days, 95%CI -10.2, -3.0). For simultaneous resections, 12 observational studies were included. There was no evidence of a difference between MIS and the open group for DFS-1-year, OS-5-year, complications, R0 resections, blood transfusions, along with lower blood loss (MD -177.35 mL, 95%CI -273.17, -81.53) and shorter LOS (MD -3.0 days, 95%CI -3.82, -2.17). CONCLUSIONS Current evidence regarding the optimal approach for CRLM resection demonstrates similar oncologic outcomes between MIS and open techniques, however MIS hepatectomy had a shorter LOS, lower blood loss and complication rate, for both staged and simultaneous resections.
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Affiliation(s)
- Ahmad Ozair
- Faculty of Medicine, King George's Medical University, Uttar Pradesh, Lucknow, India
| | - Amelia Collings
- Department of Surgery, Indiana University, Indianapolis, IN, USA
| | - Alexandra M Adams
- Department of Surgery, Brooke Army Medical Centre, Fort Sam Houston, San Antonio, TX, USA
| | - Rebecca Dirks
- Department of Surgery, Indiana University, Indianapolis, IN, USA
| | - Bradley S Kushner
- Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Iswanto Sucandy
- Digestive Health Institute, AdventHealth Tampa, Tampa, FL, USA
| | - David Morrell
- Department of Surgery, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Ahmed M Abou-Setta
- Department of Community Health Sciences, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Timothy Vreeland
- Department of Surgery, Brooke Army Medical Centre, Fort Sam Houston, San Antonio, TX, USA
| | - Jake Whiteside
- Department of Surgery, Indiana University, Indianapolis, IN, USA
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Mohammed T Ansari
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Sean P Cleary
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Eugene Ceppa
- Department of Surgery, Indiana University, Indianapolis, IN, USA
| | | | - Adnan Alseidi
- Department of Surgery, University of California San Francisco, San Francisco, CA, USA
| | - Ziad Awad
- Department of Surgery, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA
| | - Subhashini Ayloo
- Department of Surgery, Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Joseph F Buell
- Division of Surgery, Mission Healthcare System, HCA Healthcare, Asheville, NC, USA
| | - Georgios Orthopoulos
- Department of Surgery, University of Massachusetts Chan Medical School-Baystate, Springfield, MA, USA
| | - Samer Sbayi
- Department of Surgery, Renaissance School of Medicine, Stony Brook University, New York, NY, USA
| | - Go Wakabayashi
- Center for Advanced Treatment of Hepatobiliary and Pancreatic Diseases, Department of Surgery, Ageo Central General Hospital, Ageo City, Japan
| | - Bethany J Slater
- Department of Surgery, University of Chicago Medicine, Chicago, IL, USA
| | - Aurora Pryor
- Department of Surgery, Stony Brook University, Stony Brook, NY, USA
| | - D Rohan Jeyarajah
- Department of Surgery, TCU School of Medicine, and Methodist Richardson Medical Center, 2805 East President George Bush Highway, Fort Worth, TX, USA.
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Herrero Fonollosa E, Galofré Recasens M, Zárate Pinedo A, García Domingo MI, Camps Lasa J, Pardo Aranda F, Espin Álvarez F, Cugat Andorrà E. Análisis retrospectivo de los resultados a largo plazo de la estrategia inversa en pacientes con cáncer colorrectal y enfermedad hepática metastásica sincrónica avanzada. Cir Esp 2022. [DOI: 10.1016/j.ciresp.2022.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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10
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Hedrick TL, Zaydfudim VM. Management of Synchronous Colorectal Cancer Metastases. Surg Oncol Clin N Am 2022; 31:265-278. [DOI: 10.1016/j.soc.2021.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Burasakarn P, Thienhiran A, Hongjinda S, Fuengfoo P. Evaluating the Outcomes of Liver‐first Approach for Liver Metastases due to Colorectal Cancer: A Systematic Review and Meta‐analysis. SURGICAL PRACTICE 2022. [DOI: 10.1111/1744-1633.12556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Pipit Burasakarn
- Division of HPB Surgery, Department of Surgery, Phramongkutklao Hospital, Thung Phaya Thai Ratchathewi, Bangkok Thailand
| | - Anuparb Thienhiran
- Division of HPB Surgery, Department of Surgery, Phramongkutklao Hospital, Thung Phaya Thai Ratchathewi, Bangkok Thailand
| | - Sermsak Hongjinda
- Division of HPB Surgery, Department of Surgery, Phramongkutklao Hospital, Thung Phaya Thai Ratchathewi, Bangkok Thailand
| | - Phusit Fuengfoo
- Division of HPB Surgery, Department of Surgery, Phramongkutklao Hospital, Thung Phaya Thai Ratchathewi, Bangkok Thailand
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12
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Zeyara A, Torén W, Søreide K, Andersson R. The liver-first approach for synchronous colorectal liver metastases: A systematic review and meta-analysis of completion rates and effects on survival. Scand J Surg 2021; 111:14574969211030131. [PMID: 34605325 DOI: 10.1177/14574969211030131] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Patients presenting with synchronous colorectal liver metastases are increasingly being considered for a curative treatment, and the liver-first approach is gaining popularity in this context. However, little is known about the completion rates of the liver-first approach and its effects on survival. METHODS A systematic review and meta-analysis of liver-first strategy for colorectal liver metastasis. The primary outcome was an assessment of the completion rates of the liver-first approach. Secondary outcomes included overall survival, causes of non-completion, and clinicopathologic data. RESULTS Seventeen articles were amenable for inclusion and the total study population was 1041. The median completion rate for the total population was 80% (range 20-100). The median overall survival for the completion and non-completion groups was 45 (range 12-69) months and 13 (range 10.5-25) months, respectively. Metadata showed a significant survival benefit for the completion group, with a univariate hazard ratio of 12.0 (95% confidence interval, range 5.7-24.4). The major cause of non-completion (76%) was liver disease progression before resection of the primary tumor. Pearson tests showed significant negative correlation between median number of lesions and median size of the largest metastasis and completion rate. CONCLUSIONS The liver-first approach offers a complete resection to most patients enrolled, with an overall survival benefit when completion can be assured. One-fifth fails to return to intended oncologic therapy and the major cause is interim metastatic progression, most often in the liver. Risk of non-completion is related to a higher number of lesions and large metastases. The majority of studies stem from primary rectal cancers, which may influence on the return to intended oncologic therapy as well.PROSPERO id no: 170459.
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Affiliation(s)
- Adam Zeyara
- Department of Surgery, Ystad Hospital, Ystad, Sweden Department of Clinical Sciences, Lund University, Lund, Sweden
| | - William Torén
- Department of Clinical Sciences, Lund University, Lund, Sweden Department of Surgery, Skåne University Hospital, Lund, SwedenKjetil Søreide
| | - Kjetil Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Roland Andersson
- Department of Surgery, Skåne University Hospital, Lund SE-222 42, Sweden
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13
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Micro-positron emission tomography imaging of angiogenesis based on 18F-RGD for assessing liver metastasis of colorectal cancer. Hepatobiliary Pancreat Dis Int 2021; 20:345-351. [PMID: 33753000 DOI: 10.1016/j.hbpd.2021.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 03/03/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Positron emission tomography (PET) imaging is a non-invasive method to visualize and quantify the tumor microenvironment. This study aimed to explore the feasibility of 18F-AIF-NOTA-E[PEG4-c(RGDfk)]2 (denoted as 18F-RGD) PET quantitative parameters to distinguish the angiogenesis in colorectal cancer (CRC) mice which has different metastatic potential. METHODS Twenty LoVo and twenty LS174T of CRC liver metastases animal models were established by implantation of human CRC cell lines via intrasplenic injection. Radiotracer-based micro-PET imaging of animal model was performed and the uptake of 18F-RGD tracer in the tumor tissues was quantified as tumor-to-liver maximum or mean standardized uptake value (SUVmax or SUVmean) ratio. Pearson correlation was used to analyze the relationship between radioactive parameters and tumor markers. RESULTS The SUVmax and SUVmean ratios of LoVo model were significantly higher than those of LS174T in both liver metastasis and primary tumor lesions (P < 0.05). A significant difference was observed in both vascular endothelial growth factor (VEGF) and Ki67 expressions between LoVo and LS174T primary tumors (P < 0.05). The tumor-to-liver SUVmax or SUVmean ratio of 18F-RGD showed a moderate correlation with VEGF expression (r = 0.5700, P = 0.001 and r = 0.6657, P < 0.001, respectively), but the SUVmean ration showed a weak correlation with Ki67 expression (r = 0.3706, P < 0.05). The areas under the receiver operating characteristic (ROC) curves of 18F-RGD SUVmean ratio, SUVmax ratio for differentiating LoVo from LS174T tumor were 0.801 and 0.759, respectively. CONCLUSIONS The tumor-to-liver SUVmean ratio of 18F-RGD was a promising image parameter for the process of monitoring tumor angiogenesis in CRC xenograft mice model.
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Nagata K, Shinto E, Shiraishi T, Yamadera M, Kajiwara Y, Mochizuki S, Okamoto K, Einama T, Kishi Y, Ueno H. Mesothelin Expression is Correlated with Chemoresistance in Stage IV Colorectal Cancer. Ann Surg Oncol 2021; 28:8579-8586. [PMID: 34318385 DOI: 10.1245/s10434-021-10507-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 07/04/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Mesothelin (MSLN) is a cell-surface glycoprotein present on mesothelial cells; its expression in several epithelial cancers generally portends an unfavorable prognosis. We investigated MSLN as a surrogate chemopredictive biomarker and examined the impact of MSLN expression in stage IV colorectal cancer (CRC). METHODS We recruited 254 patients with CRC who received systemic chemotherapy following primary tumor resection between 2000 and 2019. Resected specimens were immunostained for MSLN and stratified by MSLN expression. The associations of tumor MSLN expression with tumor response in metastatic lesions and survival were evaluated. RESULTS Of the 247 patients with stage IV CRC, 41 (16.1%) and 213 (83.9%) had high and low MSLN expression, respectively. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, the investigator-assessed objective response rate was 22.0% in the high MSLN expression group and 45.5% in the low MSLN expression group (p = 0.0050). The disease control rates in these groups were 65.9% and 85.9%, respectively (p = 0.00019). In the patients with high MSLN expression, the conversion rate among those with initially unresectable metastases was 0% versus 14% in the patients with low MSLN expression (p = 0.0053). The median overall survival (OS) was 1.5 years (95% confidence interval [CI] 1.1-2.8) in the high MSLN expression group versus 2.6 years (95% CI 2.2-3.0) in the low MSLN expression group. The 3-year OS rates in these groups were 23.5 and 41.5%, respectively (p = 0.0120). CONCLUSIONS High MSLN expression is correlated with chemoresistance and poor prognoses in stage IV CRC.
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Affiliation(s)
- Ken Nagata
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Eiji Shinto
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
| | - Takehiro Shiraishi
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Masato Yamadera
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Yoshiki Kajiwara
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Satsuki Mochizuki
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Koichi Okamoto
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Takahiro Einama
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Yoji Kishi
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
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Osei-Bordom DC, Kamarajah S, Christou N. Colorectal Cancer, Liver Metastases and Biotherapies. Biomedicines 2021; 9:894. [PMID: 34440099 PMCID: PMC8389538 DOI: 10.3390/biomedicines9080894] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 07/13/2021] [Accepted: 07/21/2021] [Indexed: 12/01/2022] Open
Abstract
(1) Background: colorectal cancer (CRC) is one of the deadliest causes of death by cancer worldwide. Its first main metastatic diffusion spreads to the liver. Different mechanisms such as the epithelial-mesenchymal transition and angiogenesis are the characteristics of this invasion. At this stage, different options are possible and still in debate, especially regarding the use of targeted therapeutics and biotherapies. (2) Methods: A review of the literature has been done focusing on the clinical management of liver metastasis of colorectal cancer and the contribution of biotherapies in this field. (3) Results: In a clinical setting, surgeons and oncologists consider liver metastasis in CRC into two groups to launch adapted therapeutics: resectable and non-resectable. Around these two entities, the combination of targeted therapies and biotherapies are of high interest and are currently tested to know in which molecular and clinical conditions they have to be applied to impact positively both on survival and quality of life of patients.
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Affiliation(s)
- Daniel-Clement Osei-Bordom
- Department of General Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, UK; (D.-C.O.-B.); (S.K.)
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK
- NIHR Birmingham Biomedical Research Centre, Centre for Liver and Gastroenterology Research, University of Birmingham, Birmingham B15 2TT, UK
| | - Sivesh Kamarajah
- Department of General Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, UK; (D.-C.O.-B.); (S.K.)
| | - Niki Christou
- Department of General Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, UK; (D.-C.O.-B.); (S.K.)
- Department of General Surgery, University Hospital of Limoges, 87000 Limoges, France
- EA3842 CAPTuR Laboratory “Cell Activation Control, Tumor Progression and Therapeutic Resistance”, Faculty of Medicine, 2 Rue du Docteur Marcland, 87025 Limoges, France
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Martin J, Petrillo A, Smyth EC, Shaida N, Khwaja S, Cheow HK, Duckworth A, Heister P, Praseedom R, Jah A, Balakrishnan A, Harper S, Liau S, Kosmoliaptsis V, Huguet E. Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol 2020; 11:761-808. [PMID: 33200074 PMCID: PMC7643190 DOI: 10.5306/wjco.v11.i10.761] [Citation(s) in RCA: 130] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/14/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation.
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Affiliation(s)
- Jack Martin
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Angelica Petrillo
- Department of Precision Medicine, Division of Medical Oncology, University of Campania "L. Vanvitelli", Napoli 80131, Italy, & Medical Oncology Unit, Ospedale del Mare, 80147 Napoli Italy
| | - Elizabeth C Smyth
- Department of Oncology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Nadeem Shaida
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - Samir Khwaja
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - HK Cheow
- Department of Nuclear Medicine, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Adam Duckworth
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Paula Heister
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Raaj Praseedom
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Asif Jah
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Anita Balakrishnan
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Simon Harper
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Siong Liau
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Vasilis Kosmoliaptsis
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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Kelly ME, Aalbers AGJ, Abdul Aziz N, Abecasis N, Abraham‐Nordling M, Akiyoshi T, Alberda W, Albert M, Andric M, Angenete E, Antoniou A, Auer R, Austin KK, Aziz O, Baker RP, Bali M, Baseckas G, Bebington B, Bednarski BK, Beets GL, Berg PL, Beynon J, Biondo S, Boyle K, Bordeianou L, Bremers AB, Brunner M, Buchwald P, Bui A, Burgess A, Burger JWA, Burling D, Burns E, Campain N, Carvalhal S, Castro L, Caycedo‐Marulanda A, Chan KKL, Chang GJ, Chew MH, Chong PC, Christensen HK, Clouston H, Codd M, Collins D, Colquhoun A, Corr A, Coscia M, Coyne PE, Creavin B, Croner RS, Damjanovic L, Daniels IR, Davies M, Davies RJ, Delaney CP, Denost Q, Deutsch C, Dietz D, Domingo S, Dozois EJ, Duff M, Eglinton T, Enrique‐Navascues JM, Espin‐Basany E, Evans MD, Fearnhead NS, Flatmark K, Fleming F, Frizelle FA, Gallego MA, Garcia‐Granero E, Garcia‐Sabrido JL, Gentilini L, George ML, Ghouti L, Giner F, Ginther N, Glynn R, Golda T, Griffiths B, Harris DA, Hagemans JAW, Hanchanale V, Harji DP, Helewa RM, Heriot AG, Hochman D, Hohenberger W, Holm T, Hompes R, Jenkins JT, Kaffenberger S, Kandaswamy GV, Kapur S, Kanemitsu Y, Kelley SR, Keller DS, Khan MS, Kiran RP, et alKelly ME, Aalbers AGJ, Abdul Aziz N, Abecasis N, Abraham‐Nordling M, Akiyoshi T, Alberda W, Albert M, Andric M, Angenete E, Antoniou A, Auer R, Austin KK, Aziz O, Baker RP, Bali M, Baseckas G, Bebington B, Bednarski BK, Beets GL, Berg PL, Beynon J, Biondo S, Boyle K, Bordeianou L, Bremers AB, Brunner M, Buchwald P, Bui A, Burgess A, Burger JWA, Burling D, Burns E, Campain N, Carvalhal S, Castro L, Caycedo‐Marulanda A, Chan KKL, Chang GJ, Chew MH, Chong PC, Christensen HK, Clouston H, Codd M, Collins D, Colquhoun A, Corr A, Coscia M, Coyne PE, Creavin B, Croner RS, Damjanovic L, Daniels IR, Davies M, Davies RJ, Delaney CP, Denost Q, Deutsch C, Dietz D, Domingo S, Dozois EJ, Duff M, Eglinton T, Enrique‐Navascues JM, Espin‐Basany E, Evans MD, Fearnhead NS, Flatmark K, Fleming F, Frizelle FA, Gallego MA, Garcia‐Granero E, Garcia‐Sabrido JL, Gentilini L, George ML, Ghouti L, Giner F, Ginther N, Glynn R, Golda T, Griffiths B, Harris DA, Hagemans JAW, Hanchanale V, Harji DP, Helewa RM, Heriot AG, Hochman D, Hohenberger W, Holm T, Hompes R, Jenkins JT, Kaffenberger S, Kandaswamy GV, Kapur S, Kanemitsu Y, Kelley SR, Keller DS, Khan MS, Kiran RP, Kim H, Kim HJ, Koh CE, Kok NFM, Kokelaar R, Kontovounisios C, Kristensen HØ, Kroon HM, Kusters M, Lago V, Larsen SG, Larson DW, Law WL, Laurberg S, Lee PJ, Limbert M, Lydrup ML, Lyons A, Lynch AC, Mantyh C, Mathis KL, Margues CFS, Martling A, Meijerink WJHJ, Merkel S, Mehta AM, McArthur DR, McDermott FD, McGrath JS, Malde S, Mirnezami A, Monson JRT, Morton JR, Mullaney TG, Negoi I, Neto JWM, Nguyen B, Nielsen MB, Nieuwenhuijzen GAP, Nilsson PJ, O’Connell PR, O’Dwyer ST, Palmer G, Pappou E, Park J, Patsouras D, Pellino G, Peterson AC, Poggioli G, Proud D, Quinn M, Quyn A, Radwan RW, van Ramshorst GH, Rasheed S, Rasmussen PC, Regenbogen SE, Renehan A, Rocha R, Rochester M, Rohila J, Rothbarth J, Rottoli M, Roxburgh C, Rutten HJT, Ryan ÉJ, Safar B, Sagar PM, Sahai A, Saklani A, Sammour T, Sayyed R, Schizas AMP, Schwarzkopf E, Scripcariu V, Selvasekar C, Shaikh I, Hellawell G, Shida D, Simpson A, Smart NJ, Smart P, Smith JJ, Solbakken AM, Solomon MJ, Sørensen MM, Steele SR, Steffens D, Stitzenberg K, Stocchi L, Stylianides NA, Sumrien H, Sutton PA, Swartking T, Taylor C, Tekkis PP, Teras J, Thurairaja R, Toh EL, Tsarkov P, Tsukada Y, Tsukamoto S, Tuech JJ, Turner WH, Tuynman JB, Vasquez‐Jimenez W, Verhoef C, Vizzielli G, Voogt ELK, Uehara K, Wakeman C, Warrier S, Wasmuth HH, Weber K, Weiser MR, Wheeler JMD, Wild J, Wilson M, de Wilt JHW, Wolthuis A, Yano H, Yip B, Yip J, Yoo RN, van Zoggel D, Winter DC. Simultaneous pelvic exenteration and liver resection for primary rectal cancer with synchronous liver metastases: results from the PelvEx Collaborative. Colorectal Dis 2020; 22:1258-1262. [PMID: 32294308 DOI: 10.1111/codi.15064] [Show More Authors] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 03/24/2020] [Indexed: 02/08/2023]
Abstract
AIM At presentation, 15-20% of patients with rectal cancer already have synchronous liver metastases. The aim of this study was to determine the surgical and survival outcomes in patients with advanced rectal cancer who underwent combined pelvic exenteration and liver (oligometastatic) resection. METHOD Data from 20 international institutions that performed simultaneous pelvic exenteration and liver resection between 2007 and 2017 were accumulated. Primarily, we examined perioperative outcomes, morbidity and mortality. We also assessed the impact that margin status had on survival. RESULTS Of 128 patients, 72 (56.2%) were men with a median age of 60 years [interquartile range (IQR) 15 years]. The median size of the liver oligometastatic deposits was 2 cm (IQR 1.8 cm). The median duration of surgery was 406 min (IQR 240 min), with a median blood loss of 1090 ml (IQR 2010 ml). A negative resection margin (R0 resection) was achieved in 73.5% of pelvic exenterations and 66.4% of liver resections. The 30-day mortality rate was 1.6%, and 32% of patients had a major postoperative complication. The 5-year overall survival for patients in whom an R0 resection of both primary and metastatic disease was achieved was 54.6% compared with 20% for those with an R1/R2 resection (P = 0.006). CONCLUSION Simultaneous pelvic exenteration and liver resection is feasible, with acceptable morbidity and mortality. Simultaneous resection should only be performed where an R0 resection of both pelvic and hepatic disease is anticipated.
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Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey. HPB (Oxford) 2020; 22:728-734. [PMID: 31601509 DOI: 10.1016/j.hpb.2019.09.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 08/07/2019] [Accepted: 09/16/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND We examined surgeon practice intentions and barriers to performing simultaneous resections for colorectal cancer with synchronous liver metastases. METHODS We electronically surveyed North American surgeons who provide colorectal cancer care with a pilot-tested questionnaire. Four clinical scenarios of increasing complexity were presented. Perceived outcomes of and barriers to simultaneous resection were assessed on a 7-point Likert scale. We compared results between general and hepatobiliary surgeons. RESULTS Responses (rate 20%, 234/1166) included 50 general and 134 hepatobiliary surgeons. High likelihood scores for support of simultaneous resection among general and hepatobiliary surgeons, respectively, included the following for: minor liver and low complexity colon, 83% and 98% (p < 0.001); minor liver and rectal resection, 57% and 73% (p = 0.042); complex liver and low complexity colon resection, 26% and 24% (p = 0.858); and, complex liver and rectal resection, 11% and 7.0% (p = 0.436). Among hepatobiliary surgeons, the most common barriers to simultaneous resections were patient comorbidities and lung metastases, whereas certain general surgeons additionally identified transfer of care. CONCLUSIONS Surgeon support for simultaneous resection was high for cases with minor hepatectomy, and low for cases involving major hepatectomy. These results suggest that clinical trials should involve patients with limited disease to evaluate post-operative complications and cost.
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Du Pasquier C, Roulin D, Bize P, Sempoux C, Rebecchini C, Montemurro M, Schäfer M, Halkic N, Demartines N. Tumor response and outcome after reverse treatment for patients with synchronous colorectal liver metastasis: a cohort study. BMC Surg 2020; 20:78. [PMID: 32306936 PMCID: PMC7169034 DOI: 10.1186/s12893-020-00738-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 04/06/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The reverse treatment of patients with synchronous colorectal liver metastases (CRLM) is a sequential approach with systemic chemotherapy first, followed by liver resection, and finally, primary tumor resection. The aim of this study was to assess the feasibility, the radiological and pathological tumor response to neoadjuvant therapy, recurrence rates and long-term survival after reverse treatment in a cohort study. METHODS Data from patients with CRLM who underwent a reverse treatment from August 2008 to October 2016 were extracted from our prospective hepato-biliary database and retrospectively analyzed for response rates and survival outcomes. Radiological tumor response was assessed by RECIST (Response Evaluation Criteria In Solid Tumor) criteria and pathological response according to TRG (Tumor Regression Grade). Disease-free and overall survival were estimated with Kaplan-Meier survival curves. RESULTS There were 44 patients with 19 rectal and 25 colonic tumors. The reverse treatment was fully completed until primary tumor resection in 41 patients (93%). Radiological assessment after chemotherapy showed 61% of complete/partial response. Pathological tumor response was major or partial in 52% of patients (TRG 1-3). Median disease-free survival after primary tumor resection was 10 months (95% CI 5-15 months). Disease-free survival at 3 and 5 years was 25% and 25%, respectively. Median overall survival was 50 months (95% CI 42-58 months). Overall survival at 3 and 5 years was 59% and 39%, respectively. CONCLUSION The reverse treatment approach was feasible with a high rate of patients with complete treatment sequence and offers promising long-term survival for selected patients with advanced simultaneous colorectal liver metastases.
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Affiliation(s)
- Céline Du Pasquier
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland.,Department of Pathology, Lausanne University Hospital (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Didier Roulin
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland.,Department of Pathology, Lausanne University Hospital (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Pierre Bize
- Department of Radiology, Lausanne University Hospital (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Christine Sempoux
- Department of Pathology, Lausanne University Hospital (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Caterina Rebecchini
- Department of Pathology, Lausanne University Hospital (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Michael Montemurro
- Department of Medical Oncology, Lausanne University Hospital (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Markus Schäfer
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Nermin Halkic
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland
| | - Nicolas Demartines
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
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20
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Kurbatov V, Resio BJ, Cama CA, Heller DR, Cha C, Zhang Y, Lu J, Khan SA. Liver-first approach to stage IV colon cancer with synchronous isolated liver metastases. J Gastrointest Oncol 2020; 11:76-83. [PMID: 32175108 DOI: 10.21037/jgo.2020.01.03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background The only possibility for cure in patients with colon adenocarcinoma (CAC) with isolated liver metastases (ILM) is resection of both primary and metastatic tumors. Little is known about the implication of the sequence in which a colectomy and hepatectomy are performed on outcomes. This study analyzes whether resection sequence impacts clinical outcomes. Methods The National Cancer Database was queried for CAC cases with hepatic metastases from 2010-2015 with exclusion of extrahepatic metastases. We compared patients treated with a liver-first approach (LFA) to those treated with a colectomy-first or simultaneous approach using Kaplan Meier and multivariable Cox proportional hazards analysis. Results In 21,788 CAC patients identified, the LFA was uncommon (2%), but was associated with higher rates of completion resection of remaining tumor (41% vs. 22%, P<0.001). Patients selected for LFA were younger, less comorbid, and more commonly received upfront chemotherapy (P<0.05). The LFA was associated with increased median survival [34 months, 95% CI (30.5-39.6 months) vs. 24 months, 95% CI (23.7-24.6 months), logrank P<0.001] and decreased risk of death [HR 0.783; 95% CI (0.67-0.89), P=0.001]. Conclusions The LFA to CAC with synchronous ILM is uncommon but is associated with greater likelihood of receiving chemotherapy prior to surgery and increased survival in selected candidates.
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Affiliation(s)
- Vadim Kurbatov
- Department of Surgery, Yale School of Medicine, New Haven, CT, USA
| | - Benjamin J Resio
- Department of Surgery, Yale School of Medicine, New Haven, CT, USA
| | - Cara A Cama
- Department of Surgery, Yale School of Medicine, New Haven, CT, USA
| | | | - Charles Cha
- Section of Surgical Oncology, Yale School of Medicine, New Haven, CT, USA
| | - Yawei Zhang
- Section of Surgical Outcomes and Epidemiology, Department of Surgery, Yale School of Medicine, New Haven, CT, USA
| | - Jun Lu
- Department of Genetics, Yale School of Medicine, New Haven, CT, USA
| | - Sajid A Khan
- Section of Surgical Oncology, Yale School of Medicine, New Haven, CT, USA
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21
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A meta-analysis of liver-first versus classical strategy for synchronous colorectal liver metastases. Int J Colorectal Dis 2020; 35:537-546. [PMID: 31955217 DOI: 10.1007/s00384-020-03503-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/08/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND This study aimed to compare the perioperative outcomes of liver-first (LFS) and classical (CS) strategy for the management of synchronous colorectal liver metastases (sCRLM). METHOD A literature search was performed in PubMed, Scopus, and Cochrane databases, in accordance with the PRISMA guidelines. The odds ratio, weighted mean difference, and 95% confidence interval were evaluated by means of the random-effects model. RESULTS Ten articles met the inclusion criteria, incorporating 3656 patients. Patients in the LFS group reported increased size of sCRLM and a higher rate of major hepatectomies. This study reveals comparable overall survival and disease-free survival at 1, 3, and 5 years postoperatively between the two strategies. Moreover, the mean operative time, length of hospital stay, the incidence of severe complications, and the 30-day and 90-day mortality were similar between the two groups. The mean intraoperative blood loss was significantly increased in the LFS group. CONCLUSION These outcomes suggest that both approaches are feasible and safe. Given the lack of randomized clinical trials, this meta-analysis represents the best currently available evidence. However, the results should be treated with caution given the small number of the included studies. Randomized trials comparing LFS to CS are necessary to further evaluate their outcomes.
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22
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Ren L, Zhu D, Benson AB, Nordlinger B, Koehne CH, Delaney CP, Kerr D, Lenz HJ, Fan J, Wang J, Gu J, Li J, Shen L, Tsarkov P, Tejpar S, Zheng S, Zhang S, Gruenberger T, Qin X, Wang X, Zhang Z, Poston GJ, Xu J. Shanghai international consensus on diagnosis and comprehensive treatment of colorectal liver metastases (version 2019). Eur J Surg Oncol 2020; 46:955-966. [PMID: 32147426 DOI: 10.1016/j.ejso.2020.02.019] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Accepted: 02/17/2020] [Indexed: 12/17/2022] Open
Abstract
The liver is the most common anatomical site for hematogenous metastases from colorectal cancer. Therefore effective treatment of liver metastases is one of the most challenging elements in the management of colorectal cancer. However, there is rare available clinical consensus or guideline only focusing on colorectal liver metastases. After six rounds of discussion by 195 clinical experts of the Shanghai International Consensus Expert Group on Colorectal Liver Metastases (SINCE) from 29 countries or regions, the Shanghai Consensus has been finally completed, based on current research and expert experience. The consensus emphasized the principle of multidisciplinary team, provided detailed diagnosis approaches, and guided precise local and systemic treatments. This Shanghai Consensus might be of great significance to standardized diagnosis and treatment of colorectal liver metastases all over the world.
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Affiliation(s)
- Li Ren
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dexiang Zhu
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Al B Benson
- Division of Hematology/Oncology, Northwestern Medical Group, Chicago, USA
| | - Bernard Nordlinger
- Surgery Department, Hospital Ambroise-Pare, Boulogne-Billancourt, France
| | | | - Conor P Delaney
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - David Kerr
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Heinz-Josef Lenz
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, China
| | - Jianping Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jin Gu
- Department of Colorectal Surgery, Peking University Cancer Hospital, Beijing, China; Department of Colorectal Surgery, Peking University Shougang Hospital, Beijing, China
| | - Jin Li
- Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China
| | - Petrv Tsarkov
- Clinic of Colorectal and Minimally Invasive Surgery, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Sabine Tejpar
- Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium
| | - Shu Zheng
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Suzhan Zhang
- Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | | | - Xinyu Qin
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xishan Wang
- Department of Colorectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Graeme John Poston
- Surgery Department, Aintree University Hospital, School of Translational Studies, University of Liverpool, Liverpool, UK.
| | - Jianmin Xu
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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Škrbić V, Simatović M, Janjić G, Šaran D. Surgical treatment of colorectal cancer metastases. SCRIPTA MEDICA 2020. [DOI: 10.5937/scriptamed51-26579] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
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Engstrand J, Strömberg C, Nilsson H, Freedman J, Jonas E. Synchronous and metachronous liver metastases in patients with colorectal cancer-towards a clinically relevant definition. World J Surg Oncol 2019; 17:228. [PMID: 31878952 PMCID: PMC6933908 DOI: 10.1186/s12957-019-1771-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 12/16/2019] [Indexed: 12/17/2022] Open
Abstract
Background Approximately 25% of patients with colorectal cancer (CRC) will have liver metastases classified as synchronous or metachronous. There is no consensus on the defining time point for synchronous/metachronous, and the prognostic implications thereof remain unclear. The aim of the study was to assess the prognostic value of differential detection at various defining time points in a population-based patient cohort and conduct a literature review of the topic. Methods All patients diagnosed with CRC in the counties of Stockholm and Gotland, Sweden, during 2008 were included in the study and followed for 5 years or until death to identify patients diagnosed with liver metastases. Patients with liver metastases were followed from time of diagnosis of liver metastases for at least 5 years or until death. Different time points defining synchronous/metachronous detection, as reported in the literature and identified in a literature search of databases (PubMed, Embase, Cochrane library), were applied to the cohort, and overall survival was calculated using Kaplan-Meier curves and compared with log-rank test. The influence of synchronously or metachronously detected liver metastases on disease-free and overall survival as reported in articles forthcoming from the literature search was also assessed. Results Liver metastases were diagnosed in 272/1026 patients with CRC (26.5%). No statistically significant difference in overall survival for synchronous vs. metachronous detection at any of the defining time points (CRC diagnosis/surgery and 3, 6 and 12 months post-diagnosis/surgery) was demonstrated for operated or non-operated patients. In the literature search, 41 publications met the inclusion criteria. No clear pattern emerged regarding the prognostic significance of synchronous vs. metachronous detection. Conclusion Synchronous vs. metachronous detection of CRC liver metastases lacks prognostic value. Using primary tumour diagnosis/operation as standardized cut-off point to define synchronous/metachronous detection is semantically correct. In synchronous detection, it defines a clinically relevant group of patients where individualized multimodality treatment protocols will apply.
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Affiliation(s)
- Jennie Engstrand
- Division of Surgery, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, 182 88, Stockholm, Sweden.
| | - Cecilia Strömberg
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Henrik Nilsson
- Division of Surgery, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, 182 88, Stockholm, Sweden
| | - Jacob Freedman
- Division of Surgery, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, 182 88, Stockholm, Sweden
| | - Eduard Jonas
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,Surgical Gastroenterology Unit, Department of Surgery, Groote Schuur Hospital, University of Cape Town Health Sciences Faculty, Cape Town, South Africa
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25
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Zhang MY, Zhang RJ, Jiang HJ, Jiang H, Xu HL, Pan WB, Wang YQ, Li X. 18F-fluoromisonidazole positron emission tomography may be applicable in the evaluation of colorectal cancer liver metastasis. Hepatobiliary Pancreat Dis Int 2019; 18:164-172. [PMID: 30850340 DOI: 10.1016/j.hbpd.2019.02.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 02/12/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND Positron emission tomography (PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18F-fluoromisonidazole (FMISO) PET quantitative parameter of maximum standardized uptake value (SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer (CRC) in mice. METHODS Colorectal liver metastases (CRLM) xenograft models were established by injecting tumor cells (LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. 18F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. 18F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the 18F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1α (HIF-1α) and serum starvation-induced glucose transporter 1 (GLUT-1) was evaluated using Pearson correlation analysis. RESULTS Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, 18F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between 18F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between 18F-FMISO SUVmax ratio and HIF-1α or GLUT-1 expression in tumor-bearing tissues. CONCLUSIONS 18F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.
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Affiliation(s)
- Ming-Yu Zhang
- Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
| | - Rong-Jun Zhang
- Key Laboratory of Nuclear Medicine of the Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China
| | - Hui-Jie Jiang
- Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
| | - Hao Jiang
- Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
| | - Hai-Long Xu
- Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
| | - Wen-Bin Pan
- Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
| | - Yi-Qiao Wang
- Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
| | - Xin Li
- Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
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26
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Krell RW, D'Angelica MI. Treatment sequencing for simultaneous colorectal liver metastases. J Surg Oncol 2019; 119:583-593. [DOI: 10.1002/jso.25424] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 02/08/2019] [Indexed: 12/20/2022]
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Chow FCL, Chok KSH. Colorectal liver metastases: An update on multidisciplinary approach. World J Hepatol 2019; 11:150-172. [PMID: 30820266 PMCID: PMC6393711 DOI: 10.4254/wjh.v11.i2.150] [Citation(s) in RCA: 137] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 11/24/2018] [Accepted: 12/05/2018] [Indexed: 02/06/2023] Open
Abstract
Liver metastasis is the commonest form of distant metastasis in colorectal cancer. Selection criteria for surgery and liver-directed therapies have recently been extended. However, resectability remains poorly defined. Tumour biology is increasingly recognized as an important prognostic factor; hence molecular profiling has a growing role in risk stratification and management planning. Surgical resection is the only treatment modality for curative intent. The most appropriate surgical approach is yet to be established. The primary cancer and the hepatic metastasis can be removed simultaneously or in a two-step approach; these two strategies have comparable long-term outcomes. For patients with a limited future liver remnant, portal vein embolization, combined ablation and resection, and associating liver partition and portal vein ligation for staged hepatectomy have been advocated, and each has their pros and cons. The role of neoadjuvant and adjuvant chemotherapy is still debated. Targeted biological agents and loco-regional therapies (thermal ablation, intra-arterial chemo- or radio-embolization, and stereotactic radiotherapy) further improve the already favourable results. The recent debate about offering liver transplantation to highly selected patients needs validation from large clinical trials. Evidence-based protocols are missing, and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team.
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Affiliation(s)
| | - Kenneth Siu-Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, the University of Hong Kong, Hong Kong, China
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Lee RM, Cardona K, Russell MC. Historical perspective: Two decades of progress in treating metastatic colorectal cancer. J Surg Oncol 2019; 119:549-563. [PMID: 30806493 DOI: 10.1002/jso.25431] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 02/11/2019] [Accepted: 02/12/2019] [Indexed: 12/11/2022]
Abstract
Colorectal cancer is the third most commonly diagnosed cancer in the United States. While screening methods strive to improve rates of early stage detection, 25% of patients have metastatic disease at the time of diagnosis, with the most common sites being the liver, lung, and peritoneum. While once perceived as hopeless, the last two decades have seen substantial strides in the medical, surgical, and regional therapies to treat metastatic disease offering significant improvements in survival.
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Affiliation(s)
- Rachel M Lee
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Kenneth Cardona
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Maria C Russell
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
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Noninvasive evaluation of 18F-FDG/ 18F-FMISO-based Micro PET in monitoring hepatic metastasis of colorectal cancer. Sci Rep 2018; 8:17832. [PMID: 30546057 PMCID: PMC6292879 DOI: 10.1038/s41598-018-36238-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 11/15/2018] [Indexed: 12/19/2022] Open
Abstract
This study aimed to explore the application of two radiotracers (18F-fluorodeoxyglucose (FDG) and 18F-fluoromisonidazole (FMISO)) in monitoring hepatic metastases of human colorectal cancer (CRC). Mouse models of CRC hepatic metastases were established by implantation of the human CRC cell lines LoVo and HT29 by intrasplenic injection. Wound healing and Transwell assays were performed to examine cell migration and invasion abilities. Radiotracer-based cellular uptake in vitro and micro-positron emission tomography imaging of liver metastases in vivo were performed. The incidence of liver metastases in LoVo-xenografted mice was significantly higher than that in HT29-xenografted ones. The SUVmax/mean values of 18F-FMISO, but not 18F-FDG, in LoVo xenografts were significantly greater than in HT29 xenografts. In vitro, LoVo cells exhibited stronger metastatic potential and higher radiotracer uptake than HT29 cells. Mechanistically, the expression of HIF-1α and GLUT-1 in LoVo cells and LoVo tumor tissues was remarkably higher than in HT29 cells and tissues. Linear regression analysis demonstrated correlations between cellular 18F-FDG/18F-FMISO uptake and HIF-1α/GLUT-1 expression in vitro, as well as between 18F-FMISO SUVmax and GLUT-1 expression in vivo. 18F-FMISO uptake may serve as a potential biomarker for the detection of liver metastases in CRC, whereas its clinical use warrants validation.
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de Jong MC, Beckers RCJ, van Woerden V, Sijmons JML, Bemelmans MHA, van Dam RM, Dejong CHC. The liver-first approach for synchronous colorectal liver metastases: more than a decade of experience in a single centre. HPB (Oxford) 2018; 20:631-640. [PMID: 29456199 DOI: 10.1016/j.hpb.2018.01.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2017] [Revised: 10/19/2017] [Accepted: 01/18/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND The feasibility of the liver-first approach for synchronous colorectal liver metastases (CRLM) has been established. We sought to assess the short-term and long-term outcomes for these patients. METHODS Outcomes of patients who underwent a liver-first approach for CRLM between 2005 and 2015 were retrospectively evaluated from a prospective database. RESULTS Of the 92 patients planned to undergo the liver-first strategy, the paradigm could be completed in 76.1%. Patients with concurrent extrahepatic disease failed significantly more often in completing the protocol (67% versus 21%; p = 0.03). Postoperative morbidity and mortality were 31.5% and 3.3% following liver resection and 30.9% and 0% after colorectal surgery. Of the 70 patients in whom the paradigm was completed, 36 patients (51.4%) developed recurrent disease after a median interval of 20.9 months. The median overall survival on an intention-to-treat basis was 33.1 months (3- and 5-year overall survival: 48.5% and 33.1%). Patients who were not able to complete their therapeutic paradigm had a significantly worse overall outcome (p = 0.03). CONCLUSION The liver-first approach is feasible with acceptable perioperative morbidity and mortality rates. Despite the considerable overall-survival-benefit, recurrence rates remain high. Future research should focus on providing selection tools to enable the optimal treatment sequence for each patient with synchronous CRLM.
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Affiliation(s)
- Mechteld C de Jong
- Department of Surgery - Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
| | - Rianne C J Beckers
- Department of Radiology - Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands; GROW - School for Oncology & Developmental Biology, Maastricht University, Maastricht, The Netherlands
| | - Victor van Woerden
- Department of Surgery - Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands
| | - Julie M L Sijmons
- Faculty of Health, Medicine & Life Sciences - Maastricht University, The Netherlands
| | - Marc H A Bemelmans
- Department of Surgery - Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands
| | - Ronald M van Dam
- Department of Surgery - Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands
| | - Cornelis H C Dejong
- Department of Surgery - Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands; NUTRIM - School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
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31
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Berardi G, De Man M, Laurent S, Smeets P, Tomassini F, Ariotti R, Hoorens A, van Dorpe J, Varin O, Geboes K, Troisi RI. Radiologic and pathologic response to neoadjuvant chemotherapy predicts survival in patients undergoing the liver-first approach for synchronous colorectal liver metastases. Eur J Surg Oncol 2018; 44:1069-1077. [PMID: 29615295 DOI: 10.1016/j.ejso.2018.03.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 02/26/2018] [Accepted: 03/09/2018] [Indexed: 02/07/2023] Open
Abstract
PURPOSE To investigate the short- and long-term outcomes of liver first approach (LFA) in patients with synchronous colorectal liver metastases (CRLM), evaluating the predictive factors of survival. METHODS Sixty-two out of 301 patients presenting with synchronous CRLM underwent LFA between 2007 and 2016. All patients underwent neoadjuvant chemotherapy. After neoadjuvant treatment patients were re-evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). Liver resection was scheduled after 4-6 weeks. Changes in non-tumoral parenchyma and the tumor response according to the Tumor Regression Grade score (TRG) were assessed on surgical specimens. Primary tumor resection was scheduled 4-8 weeks following hepatectomy. RESULTS Five patients out of 62 (8.1%) showed "Progressive Disease" at re-evaluation after neoadjuvant chemotherapy, 22 (35.5%) showed "Stable Disease" and 35 (56.5%) "Partial Response"; of these latter, 29 (82%) showed histopathologic downstaging. The 5-year survival (OS) rate was 55%, while the 5-year disease-free survival (DFS) rate was 16%. RECIST criteria, T-stage, N-stage and TRG were independently associated with OS. Bilobar presentation of disease, RECIST criteria, R1 margin and TRG were independently associated with DFS. Patients with response to neoadjuvant chemotherapy had better survival than those with stable or progressive disease (radiological response 5-y OS: 65% vs. 50%; 5-y DFS: 20% vs. 10%; pathological response 5-y OS: 75% vs. 56%; 5-y DFS: 45% vs. 11%). CONCLUSIONS LFA is an oncologically safe strategy. Selection is a critical point, and the best results in terms of OS and DFS are observed in patients having radiological and pathological response to neoadjuvant chemotherapy.
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Affiliation(s)
- Giammauro Berardi
- Dept. of General Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital and Medical School, C. Heymanslaan 10, Ghent 9000, Belgium
| | - Marc De Man
- Dept. of Oncology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Stéphanie Laurent
- Dept. of Oncology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Peter Smeets
- Dept. of Radiology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Federico Tomassini
- Dept. of General Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital and Medical School, C. Heymanslaan 10, Ghent 9000, Belgium
| | - Riccardo Ariotti
- Dept. of General Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital and Medical School, C. Heymanslaan 10, Ghent 9000, Belgium
| | - Anne Hoorens
- Dept. of Pathology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Jo van Dorpe
- Dept. of Pathology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Oswald Varin
- Dept. of Gastroenterology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Karen Geboes
- Dept. of Oncology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Roberto I Troisi
- Dept. of General Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital and Medical School, C. Heymanslaan 10, Ghent 9000, Belgium; Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
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Feo L, Polcino M, Nash GM. Resection of the Primary Tumor in Stage IV Colorectal Cancer: When Is It Necessary? Surg Clin North Am 2017; 97:657-669. [PMID: 28501253 DOI: 10.1016/j.suc.2017.01.012] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Management of metastatic colorectal cancer requires accurate staging and multidisciplinary evaluation, leading to a consensus treatment plan with the ultimate goal of increasing survival and improving the quality of life, while taking into consideration the patient's performance status, disease burden, and goals of care. Since the introduction of multidrug chemotherapeutic regimens, survival of patients with metastatic colorectal cancer has improved. Many patients with unresectable disease are undergoing surgery for asymptomatic primary tumors despite evidence that it is usually a futile intervention. Palliative measures for local control of the primary tumor include colonic stents, laser therapy, and fulguration.
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Affiliation(s)
- Leandro Feo
- Colorectal Service, Department of Surgery, Catholic Medical Center, 100 McGregor Street, Suite 3100, Manchester, NH 03102, USA
| | - Michael Polcino
- Division of Colorectal Surgery, St. Barnabas Hospital, 4422 Third Avenue, Bronx, NY 10457, USA
| | - Garrett M Nash
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1233 York Avenue, New York, NY 10065, USA.
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Tinguely P, Fusaglia M, Freedman J, Banz V, Weber S, Candinas D, Nilsson H. Laparoscopic image-based navigation for microwave ablation of liver tumors-A multi-center study. Surg Endosc 2017; 31:4315-4324. [PMID: 28342124 DOI: 10.1007/s00464-017-5458-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Accepted: 02/03/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Stereotactic navigation technology has been proposed to augment accuracy in targeting intrahepatic lesions for local ablation therapy. This retrospective study evaluated accuracy, efficacy, and safety when using laparoscopic image-guided microwave ablation (LIMA) for malignant liver tumors. METHODS All patients treated for malignant liver lesions using LIMA at two European centers between 2013 and 2015 were included for analysis. A landmark-based registration technique was applied for intraoperative tumor localization and positioning of ablation probes. Intraoperative efficiency of the procedure was measured as number of registration attempts and time needed to achieve sufficient registration accuracy. Technical accuracy was assessed as Fiducial Registration Error (FRE). Outcome at 90 days including mortality, postoperative morbidity, rates of incomplete ablations, and early intrahepatic recurrences were reported. RESULTS In 34 months, 54 interventions were performed comprising a total of 346 lesions (median lesions per patient 3 (1-25)). Eleven patients had concomitant laparoscopic resections of the liver or the colorectal primary tumor. Median time for registration was 4:38 min (0:26-19:34). Average FRE was 8.1 ± 2.8 mm. Follow-up at 90 days showed one death, 24% grade I/II, and 4% grade IIIa complications. Median length of hospital stay was 2 days (1-11). Early local recurrence was 9% per lesion and 32% per patient. Of these, 63% were successfully re-ablated within 6 months. CONCLUSIONS LIMA does not interfere with the intraoperative workflow and results in low complication and early local recurrence rates, even when simultaneously targeting multiple lesions. LIMA may represent a valid therapy option for patients with extensive hepatic disease within a multimodal treatment approach.
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Affiliation(s)
- Pascale Tinguely
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, University of Bern, 3010, Bern, Switzerland.
| | - Matteo Fusaglia
- ARTORG Center for Biomedical Engineering Research, University of Bern, 3010, Bern, Switzerland
| | - Jacob Freedman
- Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88, Stockholm, Sweden
| | - Vanessa Banz
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, University of Bern, 3010, Bern, Switzerland
| | - Stefan Weber
- ARTORG Center for Biomedical Engineering Research, University of Bern, 3010, Bern, Switzerland
| | - Daniel Candinas
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, University of Bern, 3010, Bern, Switzerland
| | - Henrik Nilsson
- Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88, Stockholm, Sweden
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You YN, Eng C, Aloia T. Multidisciplinary management of stage IV colon cancer. SEMINARS IN COLON AND RECTAL SURGERY 2016. [DOI: 10.1053/j.scrs.2016.04.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Lim C, Doussot A, Osseis M, Salloum C, Gomez Gavara C, Compagnon P, Brunetti F, Calderaro J, Azoulay D. Primary Tumor Versus Liver-First Strategy in Patients with Stage IVA Colorectal Cancer: A Propensity Score Analysis of Long-term Outcomes and Recurrence Pattern. Ann Surg Oncol 2016; 23:3024-3032. [DOI: 10.1245/s10434-016-5265-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Malouf P, Gibbs P, Shapiro J, Sockler J, Bell S. Australian contemporary management of synchronous metastatic colorectal cancer. ANZ J Surg 2016; 88:71-76. [PMID: 27122066 DOI: 10.1111/ans.13619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Revised: 03/23/2016] [Accepted: 03/28/2016] [Indexed: 11/30/2022]
Abstract
INTRODUCTION This article outlines the current Australian multidisciplinary treatment of synchronous metastatic colorectal adenocarcinoma and assesses the factors that influence patient outcome. METHODS This is a retrospective analysis of the prospective 'Treatment of Recurrent and Advanced Colorectal Cancer' registry, describing the patient treatment pathway and documenting the extent of disease, resection of the colorectal primary and metastases, chemotherapy and biological therapy use. Cox regression models for progression-free and overall survival were constructed with a comprehensive set of clinical variables. Analysis was intentionn-ton-treat, quantifying the effect of treatment intent decided at the multidisciplinary team meeting (MDT). RESULTS One thousand one hundred and nine patients presented with synchronous metastatic disease between July 2009 and November 2015. Median follow-up was 15.8 months; 4.4% (group 1) had already curative resections of primary and metastases prior to MDT, 22.2% (group 2) were considered curative but were referred to MDT for opinion and/or medical oncology treatment prior to resection and 70.2% were considered palliative at MDT (group 3). Overall, 83% received chemotherapy, 55% had their primary resected and 23% had their metastases resected; 13% of resections were synchronous, 20% were staged with primary resected first and 62% had only the colorectal primary managed surgically. Performance status, metastasis resection (R0 versus R1 versus R2 versus no resection), resection of the colorectal primary and treatment intent determined at MDT were the most significant factors for progression-free and overall survival. CONCLUSIONS This is the largest Australian series of synchronous metastatic colorectal adenocarcinoma and offers insight into the nature and utility of contemporary practice.
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Affiliation(s)
- Phillip Malouf
- Department of Colorectal Surgery, St George Hospital, Sydney, New South Wales, Australia
| | - Peter Gibbs
- Department of Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Jeremy Shapiro
- Department of Medicine, Monash University, Melbourne, Victoria, Australia
| | - Jim Sockler
- Programming and Statistics, Datapharm Australia, Sydney, New South Wales, Australia
| | - Stephen Bell
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Melbourne, Victoria, Australia
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Ratti F, Catena M, Di Palo S, Staudacher C, Aldrighetti L. Impact of totally laparoscopic combined management of colorectal cancer with synchronous hepatic metastases on severity of complications: a propensity-score-based analysis. Surg Endosc 2016; 30:4934-4945. [PMID: 26944725 DOI: 10.1007/s00464-016-4835-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Accepted: 02/15/2016] [Indexed: 12/23/2022]
Abstract
BACKGROUND Thanks to widespread diffusion of minimally invasive approach in the setting of both colorectal and hepatic surgeries, the interest in combined resections for colorectal cancer and synchronous liver metastases (SCLM) by totally laparoscopic approach (TLA) has increased. Aim of this study was to compare outcome of combined resections for SCLM performed by TLA or by open approach, in a propensity-score-based study. STUDY DESIGN All 25 patients undergoing combined TLA for SCLM at San Raffaele Hospital in Milano were compared in a case-matched analysis with 25 out of 91 patients undergoing totally open approach (TOA group). Groups were matched with 1:2 ratio using propensity scores based on covariates representing disease severity. Main endpoints were postoperative morbidity and long-term outcome. The Modified Accordion Severity Grading System was used to quantify complications. RESULTS The groups resulted comparable in terms of patients and disease characteristics. The TLA group, as compared to the TOA group, had lower blood loss (350 vs 600 mL), shorter postoperative stay (9 vs 12 days), lower postoperative morbidity index (0.14 vs 0.20) and severity score for complicated patients (0.60 vs 0.85). Colonic anastomosis leakage had the highest fractional complication burden in both groups. In spite of comparable long-term overall survival, the TLA group had better recurrence-free survival. CONCLUSION TLA for combined resections is feasible, and its indications can be widened to encompass a larger population of patients, provided its benefits in terms of reduced overall risk and severity of complications, rapid functional recovery and favorable long-term outcomes.
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Affiliation(s)
- Francesca Ratti
- Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy.
| | - Marco Catena
- Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy
| | - Saverio Di Palo
- Gastrointestinal Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy
| | - Carlo Staudacher
- Gastrointestinal Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy
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Wang K, Liu W, Yan XL, Xing BC. Role of a liver-first approach for synchronous colorectal liver metastases. World J Gastroenterol 2016; 22:2126-2132. [PMID: 26877617 PMCID: PMC4726685 DOI: 10.3748/wjg.v22.i6.2126] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 09/11/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the feasibility and survival outcomes of a liver-first approach.
METHODS: Between January 2009 and April 2013, 18 synchronous colorectal liver metastases (sCRLMs) patients with a planned liver-first approach in the Hepatopancreatobiliary Surgery Department I of the Beijing Cancer Hospital were enrolled in this study. Clinical data, surgical outcomes, morbidity and mortality rates were collected. The feasibility and long-term outcomes of the approach were retrospectively analyzed.
RESULTS: Sixteen patients (88.9%) completed the treatment protocol for primary and liver tumors. The main reason for treatment failure was liver disease recurrence. The 1 and 3 year overall survival rates were 94.4% and 44.8%, respectively. The median survival time was 30 mo. The postoperative morbidity and mortality were 22.2% and 0%, respectively, following a hepatic resection, and were 18.8% and 0%, respectively, after a colorectal surgery.
CONCLUSION: The liver-first approach appeared to be feasible and safe. It can be performed with a comparable mortality and morbidity to the traditional treatment paradigm. This approach might offer a curative opportunity for sCRLM patients with a high liver disease burden.
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Welsh FKS, Chandrakumaran K, John TG, Cresswell AB, Rees M. Propensity score-matched outcomes analysis of the liver-first approach for synchronous colorectal liver metastases. Br J Surg 2016; 103:600-6. [PMID: 26864820 DOI: 10.1002/bjs.10099] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Revised: 10/06/2015] [Accepted: 12/02/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND Liver resection before primary cancer resection is a novel strategy advocated for selected patients with synchronous colorectal liver metastases (sCRLM). This study measured outcomes in patients with sCRLM following a liver-first or classical approach, and used a validated propensity score. METHODS Clinical, pathological and follow-up data were collected prospectively from consecutive patients undergoing hepatic resection for sCRLM at a single centre (2004-2014). Cumulative disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were calculated by means of Kaplan-Meier analysis. Survival differences were analysed in the whole cohort and in subgroups matched according to Basingstoke Predictive Index (BPI). RESULTS Of 582 patients, 98 had a liver-first and 467 a classical approach to treatment; 17 patients undergoing simultaneous bowel and liver resection were excluded. The median (i.q.r.) BPI was significantly higher in the liver-first compared with the classical group: 8·5 (5-10) versus 8 (4-9) (P = 0·030). Median follow-up was 34 months. The 5-year DFS rate was lower in the liver-first group than in the classical group (23 versus 45·6 per cent; P = 0·001), but there was no difference in 5-year CSS (51 versus 53·8 per cent; P = 0·379) or OS (44 versus 49·6 per cent; P = 0·305). After matching for preoperative BPI, there was no difference in 5-year DFS (37 versus 41·2 per cent for liver-first versus classical approach; P = 0·083), CSS (51 versus 53·2 per cent; P = 0·616) or OS (47 versus 49·1 per cent; P = 0·846) rates. CONCLUSION Patients with sCRLM selected for a liver-first approach had more oncologically advanced disease and a poorer prognosis. They had inferior cumulative DFS than those undergoing a classical approach, a difference negated by matching preoperative BPI.
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Affiliation(s)
- F K S Welsh
- Hepatobiliary Unit, Hampshire Hospitals NHS Foundation Trust, Aldermaston Road, Basingstoke RG24 9NA, UK
| | - K Chandrakumaran
- Hepatobiliary Unit, Hampshire Hospitals NHS Foundation Trust, Aldermaston Road, Basingstoke RG24 9NA, UK
| | - T G John
- Hepatobiliary Unit, Hampshire Hospitals NHS Foundation Trust, Aldermaston Road, Basingstoke RG24 9NA, UK
| | - A B Cresswell
- Hepatobiliary Unit, Hampshire Hospitals NHS Foundation Trust, Aldermaston Road, Basingstoke RG24 9NA, UK
| | - M Rees
- Hepatobiliary Unit, Hampshire Hospitals NHS Foundation Trust, Aldermaston Road, Basingstoke RG24 9NA, UK
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Sabbagh C, Cosse C, Ravololoniaina T, Chauffert B, Joly JP, Mauvais F, Regimbeau JM. Oncological strategies for middle and low rectal cancer with synchronous liver metastases. Int J Surg 2015; 23:186-93. [DOI: 10.1016/j.ijsu.2015.08.034] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 08/03/2015] [Accepted: 08/22/2015] [Indexed: 01/20/2023]
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Dimitroulis D, Moris D, Pikoulis E, Spartalis E, Kontadakis G, Vrugt B, Valsami S, Kouraklis G. Variable Pringle Maneuvers and Effect on Intestinal Epithelium in Rats. A Pilot Experimental Study in Rats. PLoS One 2015; 10:e0140707. [PMID: 26496481 PMCID: PMC4619866 DOI: 10.1371/journal.pone.0140707] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Accepted: 09/28/2015] [Indexed: 02/07/2023] Open
Abstract
Background It is observed that combined liver and colon surgery especially when this includes major liver resection with Pringle maneuver (PM) performance does not have a favorable outcome. Aim of our experimental study is to investigate the impact of portal triad occlusion on the large bowel and intra-abdominal inflammation and potent protective effects of the variants of (PM) in the combined surgical cases. Materials and Methods Forty-four rats were divided into four groups. In group A (control group), 1cm of the left partial colon was resected and then an end-to-end anastomosis was performed. In group B, a continuous PM for 30 minutes was performed followed by resection of 1cm of the left colon and an end-to-end anastomosis. In group C, the left colonic resection and anastomosis was performed after intermittent PM (IPM), which was 10 minutes PM followed by 5 minutes reperfusion repeated for three circles. In group D, an ischemic preconditioning for 10 minutes was initially performed followed by 5 minutes reperfusion and then continuous PM for 30 minutes. Finally the rats in group D underwent a 1cm left colonic resection and an end-to-end anastomosis. Results The percentage of colitis was higher in the B group (P = 0,19). The percentage of inflammation was not significantly higher even when we compared all “occlusion” groups (B+C+D) with the sham group. No evidence of pancreatitis was found in the sham group whereas amylase and lipase levels were higher in Groups B, C and D together (P = 0,0267). The comparison of group A to group B showed a significant difference (P = 0,0014) caused by continuous PM for 30 minutes, but there was no such result after IPM. Conclusions Major liver resections are performed with PM in order to minimize intra-operative blood loss. In the combined cases of colon surgery and major liver resections where PM is needed our results showed that IPM presents with better outcome and could be preferred compared with the other PM variants.
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Affiliation(s)
- Dimitrios Dimitroulis
- Second Department of Propedeutic Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Demetrios Moris
- First Department of Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
- * E-mail:
| | - Emmanouil Pikoulis
- First Department of Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Eleftherios Spartalis
- Second Department of Propedeutic Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Kontadakis
- Second Department of Propedeutic Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Bart Vrugt
- Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital Zürich, Zürich, Switzerland
| | - Serena Valsami
- Second Department of Propedeutic Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Gregory Kouraklis
- Second Department of Propedeutic Surgery, "Laikon" General Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Laparoscopic Approach for Primary Colorectal Cancer Improves Outcome of Patients Undergoing Combined Open Hepatic Resection for Liver Metastases. World J Surg 2015; 39:2573-82. [DOI: 10.1007/s00268-015-3127-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Waisberg J, Ivankovics IG. Liver-first approach of colorectal cancer with synchronous hepatic metastases: A reverse strategy. World J Hepatol 2015; 7:1444-1449. [PMID: 26085905 PMCID: PMC4462684 DOI: 10.4254/wjh.v7.i11.1444] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 02/22/2015] [Accepted: 04/14/2015] [Indexed: 02/06/2023] Open
Abstract
Recently, there has been a change in the strategy of how synchronous colorectal hepatic metastases are attributed to the development of more valuable protocols of chemotherapy and radiotherapy for neoadjuvant treatment of colorectal neoplasms and their hepatic metastases. There is a consensus that patients with synchronous colorectal hepatic metastases have lower survival than those with metachronous colorectal hepatic metastases. Currently, controversy remains concerning the best approach is sequence in a patient with colorectal cancer and synchronous hepatic metastases resection. To obtain a better patient selection, the authors have suggested the initial realization of systemic chemotherapy in the circumstance of patients with colorectal tumor stage IV, since these patients have a systemic disease. The rationale behind this liver-first strategy is initially the control of synchronous hepatic metastases of colorectal carcinoma, which can optimize a potentially curative hepatic resection and longstanding survival. The liver-first strategy procedure is indicated for patients with colorectal hepatic metastases who require downstaging therapy to make a curative liver resection possible. Thus, the liver-first strategy is considered an option in cases of rectal carcinoma in the early stage and with limited or advanced synchronous colorectal hepatic metastases or in case of patients with asymptomatic colorectal carcinoma, but with extensive liver metastases. Patients undergoing systemic chemotherapy and with progression of neoplastic disease should not undergo hepatic resection, because it does not change the prognosis and may even make it worse. To date, there have been no randomized controlled trials on surgical approach of colorectal synchronous hepatic metastases, despite the relatively high number of available manuscripts on this subject. All of these published studies are observational, usually retrospective, and often non-comparative. The patient selection criteria for the liver-first strategy should be individualized, and the approach of these patients should be performed by a multidisciplinary team so its benefits will be fully realized.
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Management of the Primary Colorectal Cancer and Synchronous Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2015. [DOI: 10.1007/s11888-015-0273-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Ahmed S, Bathe O, Berry S, Buie D, Davies J, Doll C, Dowden S, Gill S, Gordon V, Hebbard P, Jones E, Kennecke H, Koski S, Krahn M, Le D, Lim H, Lund C, Luo Y, Mcffadden A, Mcghie J, Mulder K, Park J, Rashidi F, Sami A, Tan KT, Wong R. Consensus statement: the 16th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Saskatoon, Saskatchewan; September 5-6, 2014. ACTA ACUST UNITED AC 2015; 22:e113-23. [PMID: 25908916 DOI: 10.3747/co.22.2362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The 16th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Saskatoon, Saskatchewan, September 4-5, 2014. The Consensus Conference is an interactive, multidisciplinary event attended by health care professionals from across western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) involved in the care of gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer.
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Affiliation(s)
- S Ahmed
- Saskatchewan: Medical Oncology (Ahmed, Sami) and Radiation Oncology (Le), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Pathology (Jones), University of Saskatchewan, Regina; Surgery (Luo), Diagnostic Radiology (Rashidi), and Interventional Radiology (Tan), University of Saskatchewan, Saskatoon
| | - O Bathe
- Alberta: Department of Surgery (Bathe, Buie), University of Calgary, Calgary; Radiation Oncology (Doll) and Medical Oncology (Dowden), Tom Baker Cancer Centre, University of Calgary, Calgary; Medical Oncology (Koski, Mulder), Cross Cancer Centre, University of Alberta, Edmonton
| | - S Berry
- Ontario: Medical Oncology (Berry), Sunnybrook Odette Cancer Centre, University of Toronto, Toronto
| | - D Buie
- Alberta: Department of Surgery (Bathe, Buie), University of Calgary, Calgary; Radiation Oncology (Doll) and Medical Oncology (Dowden), Tom Baker Cancer Centre, University of Calgary, Calgary; Medical Oncology (Koski, Mulder), Cross Cancer Centre, University of Alberta, Edmonton
| | - J Davies
- British Columbia: Medical Oncology (Davies), BC Cancer Agency-Centre for the Southern Interior, Kelowna; Medical Oncology (Gill, Kennecke, Lim, Mcghie), BC Cancer Agency, University of BC, Vancouver; Radiation Oncology (Lund), BC Cancer Agency-Fraser Valley Cancer Centre, Fraser Valley; Surgical Oncology (Mcffadden), BC Cancer Agency, Vancouver
| | - C Doll
- Alberta: Department of Surgery (Bathe, Buie), University of Calgary, Calgary; Radiation Oncology (Doll) and Medical Oncology (Dowden), Tom Baker Cancer Centre, University of Calgary, Calgary; Medical Oncology (Koski, Mulder), Cross Cancer Centre, University of Alberta, Edmonton
| | - S Dowden
- Alberta: Department of Surgery (Bathe, Buie), University of Calgary, Calgary; Radiation Oncology (Doll) and Medical Oncology (Dowden), Tom Baker Cancer Centre, University of Calgary, Calgary; Medical Oncology (Koski, Mulder), Cross Cancer Centre, University of Alberta, Edmonton
| | - S Gill
- British Columbia: Medical Oncology (Davies), BC Cancer Agency-Centre for the Southern Interior, Kelowna; Medical Oncology (Gill, Kennecke, Lim, Mcghie), BC Cancer Agency, University of BC, Vancouver; Radiation Oncology (Lund), BC Cancer Agency-Fraser Valley Cancer Centre, Fraser Valley; Surgical Oncology (Mcffadden), BC Cancer Agency, Vancouver
| | - V Gordon
- Manitoba: Medical Oncology (Gordon, Krahn, Wong), Cancer Care Manitoba, University of Manitoba, Winnipeg; Surgery (Hebbard, Park), University of Manitoba, Winnipeg
| | - P Hebbard
- Manitoba: Medical Oncology (Gordon, Krahn, Wong), Cancer Care Manitoba, University of Manitoba, Winnipeg; Surgery (Hebbard, Park), University of Manitoba, Winnipeg
| | - E Jones
- Saskatchewan: Medical Oncology (Ahmed, Sami) and Radiation Oncology (Le), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Pathology (Jones), University of Saskatchewan, Regina; Surgery (Luo), Diagnostic Radiology (Rashidi), and Interventional Radiology (Tan), University of Saskatchewan, Saskatoon
| | - H Kennecke
- British Columbia: Medical Oncology (Davies), BC Cancer Agency-Centre for the Southern Interior, Kelowna; Medical Oncology (Gill, Kennecke, Lim, Mcghie), BC Cancer Agency, University of BC, Vancouver; Radiation Oncology (Lund), BC Cancer Agency-Fraser Valley Cancer Centre, Fraser Valley; Surgical Oncology (Mcffadden), BC Cancer Agency, Vancouver
| | - S Koski
- Alberta: Department of Surgery (Bathe, Buie), University of Calgary, Calgary; Radiation Oncology (Doll) and Medical Oncology (Dowden), Tom Baker Cancer Centre, University of Calgary, Calgary; Medical Oncology (Koski, Mulder), Cross Cancer Centre, University of Alberta, Edmonton
| | - M Krahn
- Manitoba: Medical Oncology (Gordon, Krahn, Wong), Cancer Care Manitoba, University of Manitoba, Winnipeg; Surgery (Hebbard, Park), University of Manitoba, Winnipeg
| | - D Le
- Saskatchewan: Medical Oncology (Ahmed, Sami) and Radiation Oncology (Le), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Pathology (Jones), University of Saskatchewan, Regina; Surgery (Luo), Diagnostic Radiology (Rashidi), and Interventional Radiology (Tan), University of Saskatchewan, Saskatoon
| | - H Lim
- British Columbia: Medical Oncology (Davies), BC Cancer Agency-Centre for the Southern Interior, Kelowna; Medical Oncology (Gill, Kennecke, Lim, Mcghie), BC Cancer Agency, University of BC, Vancouver; Radiation Oncology (Lund), BC Cancer Agency-Fraser Valley Cancer Centre, Fraser Valley; Surgical Oncology (Mcffadden), BC Cancer Agency, Vancouver
| | - C Lund
- British Columbia: Medical Oncology (Davies), BC Cancer Agency-Centre for the Southern Interior, Kelowna; Medical Oncology (Gill, Kennecke, Lim, Mcghie), BC Cancer Agency, University of BC, Vancouver; Radiation Oncology (Lund), BC Cancer Agency-Fraser Valley Cancer Centre, Fraser Valley; Surgical Oncology (Mcffadden), BC Cancer Agency, Vancouver
| | - Y Luo
- Saskatchewan: Medical Oncology (Ahmed, Sami) and Radiation Oncology (Le), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Pathology (Jones), University of Saskatchewan, Regina; Surgery (Luo), Diagnostic Radiology (Rashidi), and Interventional Radiology (Tan), University of Saskatchewan, Saskatoon
| | - A Mcffadden
- British Columbia: Medical Oncology (Davies), BC Cancer Agency-Centre for the Southern Interior, Kelowna; Medical Oncology (Gill, Kennecke, Lim, Mcghie), BC Cancer Agency, University of BC, Vancouver; Radiation Oncology (Lund), BC Cancer Agency-Fraser Valley Cancer Centre, Fraser Valley; Surgical Oncology (Mcffadden), BC Cancer Agency, Vancouver
| | - J Mcghie
- British Columbia: Medical Oncology (Davies), BC Cancer Agency-Centre for the Southern Interior, Kelowna; Medical Oncology (Gill, Kennecke, Lim, Mcghie), BC Cancer Agency, University of BC, Vancouver; Radiation Oncology (Lund), BC Cancer Agency-Fraser Valley Cancer Centre, Fraser Valley; Surgical Oncology (Mcffadden), BC Cancer Agency, Vancouver
| | - K Mulder
- Alberta: Department of Surgery (Bathe, Buie), University of Calgary, Calgary; Radiation Oncology (Doll) and Medical Oncology (Dowden), Tom Baker Cancer Centre, University of Calgary, Calgary; Medical Oncology (Koski, Mulder), Cross Cancer Centre, University of Alberta, Edmonton
| | - J Park
- Manitoba: Medical Oncology (Gordon, Krahn, Wong), Cancer Care Manitoba, University of Manitoba, Winnipeg; Surgery (Hebbard, Park), University of Manitoba, Winnipeg
| | - F Rashidi
- Saskatchewan: Medical Oncology (Ahmed, Sami) and Radiation Oncology (Le), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Pathology (Jones), University of Saskatchewan, Regina; Surgery (Luo), Diagnostic Radiology (Rashidi), and Interventional Radiology (Tan), University of Saskatchewan, Saskatoon
| | - A Sami
- Saskatchewan: Medical Oncology (Ahmed, Sami) and Radiation Oncology (Le), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Pathology (Jones), University of Saskatchewan, Regina; Surgery (Luo), Diagnostic Radiology (Rashidi), and Interventional Radiology (Tan), University of Saskatchewan, Saskatoon
| | - K T Tan
- Saskatchewan: Medical Oncology (Ahmed, Sami) and Radiation Oncology (Le), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon; Pathology (Jones), University of Saskatchewan, Regina; Surgery (Luo), Diagnostic Radiology (Rashidi), and Interventional Radiology (Tan), University of Saskatchewan, Saskatoon
| | - R Wong
- Manitoba: Medical Oncology (Gordon, Krahn, Wong), Cancer Care Manitoba, University of Manitoba, Winnipeg; Surgery (Hebbard, Park), University of Manitoba, Winnipeg
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Piso P, Arnold D, Glockzin G. Challenges in the multidisciplinary management of stage IV colon and rectal cancer. Expert Rev Gastroenterol Hepatol 2015; 9:317-26. [PMID: 25192718 DOI: 10.1586/17474124.2015.957273] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Colorectal metastases still represent a challenge to all oncologists despite progresses achieved by improved resectability, systemic chemotherapy and targeted therapies. In particular in patients with oligo-metastases, the role of surgical resections has been redefined. Resection is the most effective treatment method for liver metastases performed with curative intent; however, primary rate of resectability is low. Several methods to increase resectability have been developed: conversion chemotherapy, portal vein embolization, two-stage resections, vascular reconstruction of the liver veins, combination of resection and intraoperative ablation. Liver resections can be performed at present with low mortality. Patients with isolated peritoneal metastases, no extra-abdominal disease, low volume tumor and complete surgical cytoreduction do benefit from surgery and hyperthermic intraperitoneal chemotherapy. Several national guidelines recommend multimodality treatment for highly selected patients. The management of stage IV colorectal cancer includes several disciplines with focus on resection. A multidisciplinary evaluation of all patients is of crucial importance to define the treatment sequence and individual strategies for each patient.
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Affiliation(s)
- Pompiliu Piso
- Department for General- and Visceral Surgery, Hospital Barmherzige Brueder, Pruefeninger Str. 86, 93049 Regensburg Germany
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Fazeli MS, Keramati MR. Rectal cancer: a review. Med J Islam Repub Iran 2015; 29:171. [PMID: 26034724 PMCID: PMC4431429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 12/24/2014] [Indexed: 11/22/2022] Open
Abstract
Rectal cancer is the second most common cancer in large intestine. The prevalence and the number of young patients diagnosed with rectal cancer have made it as one of the major health problems in the world. With regard to the improved access to and use of modern screening tools, a number of new cases are diagnosed each year. Considering the location of the rectum and its adjacent organs, management and treatment of rectal tumor is different from tumors located in other parts of the gastrointestinal tract or even the colon. In this article, we will review the current updates on rectal cancer including epidemiology, risk factors, clinical presentations, screening, and staging. Diagnostic methods and latest treatment modalities and approaches will also be discussed in detail.
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Affiliation(s)
- Mohammad Sadegh Fazeli
- 1 Associate Professor of Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mohammad Reza Keramati
- 2 Assistant Professor of Surgery, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran.
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Brooke-Smith M, Figueras J, Ullah S, Rees M, Vauthey JN, Hugh TJ, Garden OJ, Fan ST, Crawford M, Makuuchi M, Yokoyama Y, Büchler M, Weitz J, Padbury R. Prospective evaluation of the International Study Group for Liver Surgery definition of bile leak after a liver resection and the role of routine operative drainage: an international multicentre study. HPB (Oxford) 2015; 17:46-51. [PMID: 25059275 PMCID: PMC4266440 DOI: 10.1111/hpb.12322] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2014] [Accepted: 06/04/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND The International Study Group for Liver Surgery (ISGLS) proposed a definition for bile leak after liver surgery. A multicentre international prospective study was designed to evaluate this definition. METHODS Data collected prospectively from 949 consecutive patients on specific datasheets from 11 international centres were collated centrally. RESULTS Bile leak occurred in 69 (7.3%) of patients, with 31 (3.3%), 32 (3.4%) and 6 (0.6%) classified as grade A, B and C, respectively. The grading system of severity correlated with the Dindo complication classification system (P < 0.001). Hospital length of stay was increased when bile leak occurred, from a median of 7 to 15 days (P < 0.001), as was intensive care stay (P < 0.001), and both correlated with increased severity grading of bile leak (P < 0.001). 96% of bile leaks occurred in patients with intra-operative drains. Drain placement did not prevent subsequent intervention in the bile leak group with a 5-15 times greater risk of intervention required in this group (P < 0.001). CONCLUSION The ISGLS definition of bile leak after liver surgery appears robust and intra-operative drain usage did not prevent the need for subsequent drain placement.
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Affiliation(s)
- Mark Brooke-Smith
- Flinders Medical CentreBedford Park, SA, Australia,Flinders University of South AustraliaBedford Park, SA, Australia,Correspondence, Mark Brooke-Smith, Department of Surgery and Specialty Services, Flinders Medical Centre, Bedford Park, SA 5065, Australia. Tel: +61 8 8204 4253. Fax: +61 8 8204 5843. E-mail:
| | | | - Shahid Ullah
- Flinders Medical CentreBedford Park, SA, Australia,Flinders University of South AustraliaBedford Park, SA, Australia
| | | | | | | | | | | | | | | | | | - Marcus Büchler
- Department of Surgery, Technische Universität DresdenDresden, Germany
| | - Juergen Weitz
- Department of Surgery, Technische Universität DresdenDresden, Germany
| | - Robert Padbury
- Flinders Medical CentreBedford Park, SA, Australia,Flinders University of South AustraliaBedford Park, SA, Australia
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Montalti R, Tomassini F, Laurent S, Smeets P, De Man M, Geboes K, Libbrecht LJ, Troisi RI. Impact of surgical margins on overall and recurrence-free survival in parenchymal-sparing laparoscopic liver resections of colorectal metastases. Surg Endosc 2014; 29:2736-47. [PMID: 25427420 DOI: 10.1007/s00464-014-3999-3] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2014] [Accepted: 11/07/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND The relationship between the width of surgical margins and local and distant recurrence of colorectal liver metastases (CRLM) remain controversial. We analyzed the impact of surgical margins in laparoscopic liver resections (LLR) for CRLM, using the parenchymal-sparing approach on overall (OS) and recurrence-free survival (RFS). METHODS From January 2005 to October 2012, 114 first LLR for CRLM were performed and retrospectively analyzed. The ultrasonic aspirator was used for parenchyma division. R1 margins were defined when the tissue width was <1 mm. RESULTS After a mean follow-up of 30.9 ± 1.71 months, OS was 97.1-73.9-58.9% and the RFS 64.2-35.2-31% at 1-3-5 years, respectively. The major resection rate was 7%. The median margin width was 3 (0-40) mm, and R1 resection was recorded in 14 (12.3%) cases. Twenty-two patients (33.3%) with hepatic recurrence underwent a repeat hepatectomy. R1 margins were significantly related to lower RFS survival (p = 0.038) but did not affect OS. Multivariate analysis showed that lesions located in postero-superior segments (HR = 2.4, 95% CI 1.24-4.61, p = 0.009) as well as blood loss (HR = 3.2, 95% CI 1.23-7.99, p = 0.012) were independent risk factors for tumor recurrence. The carcinoembryonic antigen level >10 mcg/L affected OS (HR = 4.2 95% CI 2.02-16.9, p = 0.001), and the resection of more than two tumors was significantly associated with R1 margins (HR = 9.32, 95% CI 1.14-32.5, p = 0.037). DISCUSSION Laparoscopic parenchymal-sparing surgery of CRLM does not compromise the oncological outcome, allowing a higher percentage of repeat hepatectomy. R1 margins are a risk factor for tumor recurrence but not for overall survival. The presence of multiple lesions is the only independent risk factor of R1 margins and also the major disadvantage of this technique.
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Affiliation(s)
- Roberto Montalti
- Department of General & Hepato-Biliary Surgery, Liver Transplantation Service, Ghent University Hospital and Medical School, De Pintelaan 185, 2K12 IC, 9000, Ghent, Belgium
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Kelly M, Spolverato G, Lê G, Mavros M, Doyle F, Pawlik T, Winter D. Synchronous colorectal liver metastasis: A network meta-analysis review comparing classical, combined, and liver-first surgical strategies. J Surg Oncol 2014; 111:341-51. [DOI: 10.1002/jso.23819] [Citation(s) in RCA: 104] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Accepted: 09/07/2014] [Indexed: 12/12/2022]
Affiliation(s)
- M.E. Kelly
- Department of Surgery; St Vincent's University Hospital; Dublin Ireland
| | - G. Spolverato
- Department of Surgery; Johns Hopkins; Baltimore Maryland
| | - G.N. Lê
- Department of Surgery; St Vincent's University Hospital; Dublin Ireland
| | - M.N. Mavros
- Department of Surgery; Johns Hopkins; Baltimore Maryland
| | - F. Doyle
- Division of Population Health Sciences; Royal College of Surgeons Ireland; Dublin Ireland
| | - T.M. Pawlik
- Department of Surgery; Johns Hopkins; Baltimore Maryland
| | - D.C. Winter
- Department of Surgery; St Vincent's University Hospital; Dublin Ireland
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