• Ampulla of Vater
• Biliary tract neoplasms
• Chemotherapy
• Survival

• Humans
• Ampulla of Vater/pathology
• Male
• Middle Aged
• Female
• Palliative Care/methods
• Retrospective Studies
• Adenocarcinoma/drug therapy
• Adenocarcinoma/mortality
• Adenocarcinoma/pathology
• Common Bile Duct Neoplasms/drug therapy
• Common Bile Duct Neoplasms/mortality
• Common Bile Duct Neoplasms/pathology
• Aged
• Deoxycytidine/analogs & derivatives
• Deoxycytidine/administration & dosage
• Deoxycytidine/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Gemcitabine
• Oxaliplatin/therapeutic use
• Oxaliplatin/administration & dosage
• Cisplatin/administration & dosage
• Cisplatin/therapeutic use
• Capecitabine/administration & dosage
• Capecitabine/therapeutic use
• Treatment Outcome
• Progression-Free Survival

• Korean Society of Gastrointestinal Cancer Research

• Humans
• Palliative Care/methods
• Adenocarcinoma/drug therapy
• Ampulla of Vater
• Common Bile Duct Neoplasms/drug therapy
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use

• Ampullary adenocarcinoma
• Ampullary adenoma
• Ampullectomy
• Papillectomy
• Recurrence

• Humans
• Female
• Male
• Ampulla of Vater/surgery
• Ampulla of Vater/pathology
• Retrospective Studies
• Adenoma/surgery
• Adenoma/pathology
• Endoscopy, Gastrointestinal
• Adenocarcinoma/surgery
• Pancreatic Neoplasms/surgery
• Liver Neoplasms/pathology
• Common Bile Duct Neoplasms/surgery
• Neoplasm Recurrence, Local/surgery
• Duodenal Neoplasms/surgery
• Treatment Outcome

• T32DK007038 NIDDK NIH HHS
• T32DK007038 NIDDK NIH HHS

• Ampulla of vater
• Carbohydrate antigen 19-9
• Carcinoembryonic antigen
• Carcinoma
• Pancreatoduodenectomy
• peri-ampullary

• Humans
• Retrospective Studies
• Ampulla of Vater/surgery
• Ampulla of Vater/pathology
• Prognosis
• Adenocarcinoma/pathology
• Common Bile Duct Neoplasms/surgery
• Common Bile Duct Neoplasms/pathology
• Pancreatic Neoplasms/pathology

• Adenocarcinoma
• Ampulla of Vater
• Chemotherapy
• Radiotherapy

• Humans
• Ampulla of Vater/pathology
• Ampulla of Vater/surgery
• Adenocarcinoma/diagnosis
• Adenocarcinoma/drug therapy
• Adenocarcinoma/pathology
• Pancreatic Neoplasms/pathology
• Common Bile Duct Neoplasms/diagnosis
• Common Bile Duct Neoplasms/surgery
• Common Bile Duct Neoplasms/pathology
• Duodenal Neoplasms/pathology

• CDX2
• CK20
• CK7
• ampullary adenocarcinomas (AAC)
• clinical behaviours
• clinical management
• immuno-histochemistry
• molecular markers
• subtypes

• biliary tract cancers
• extrahepatic cholangiocarcinoma
• gallbladder cancer
• hilar cholangiocarcinoma
• immunotherapy
• intrahepatic cholangiocarcinoma
• targeted therapy

• DNA damage
• cancer therapeutics
• mutations

• Humans
• BRCA1 Protein/genetics
• DNA Damage
• DNA Repair/genetics
• Mutation
• Neoplasms/genetics
• BRCA2 Protein/genetics

• NRF-2022R1A2C1091563 National Research Foundation of Korea
• NRF- 2019M3E5D3073092 National Research Foundation of Korea
• NRF- 2019R1A5A8083404 National Research Foundation of Korea

• Ampulla of vater cancer
• Intestinal type
• Pancreatobiliary type

• Case-control study
• Colorectal neoplasia
• Sporadic ampullary tumor
• Whole-exome sequencing

Immunohistochemical analysis of mismatch repair (MMR) protein expression is widely used to identify tumors with a deficient MMR (dMMR). MMR proteins (MLH1/PMS2 and MSH2/MSH6) work as functional heterodimers, which usually leads to the loss of expression in only one functional MMR heterodimer. Recently, there have been studies showing the simultaneous loss of immunoexpression in proteins of both heterodimers. Yet, this phenomenon has been rarely investigated. In this study, we retrospectively considered cases of different digestive system cancers (gastric cancer, ampullary cancer, small bowel cancer, colorectal cancer), which were immunohistochemically tested for dMMR within a 4-year period at our university hospital (n=352). Of the 103 cases showing dMMR, 5 cases (1.4% of all, 5.1% of dMMR cases) showed a concurrent loss of MLH1, PMS2 and MSH6 immunoexpression, whereas in the other 98 dMMR cases only one MMR heterodimer was affected. MLH1^-/PMS2^-/MSH6^- cancer cases almost arose throughout the entire digestive tract: from the gastric antrum to the left colic flexur. To provide a comprehensive molecular characterization of this MLH1^-/PMS2^-/MSH6^- immunophenotype, tumors were analyzed for microsatellite instability, MLH1 promotor hypermethylation and BRAF exon 15 status. Furthermore, we performed next-generation sequencing focusing on genes related to DNA repair. Here, we could detect pathogenic germline variants as well as multiple sporadic mutations in different genes involved in MMR and homologous recombination repair (HRR) respectively. The affected MMR/HRR-related genes were: ATM, BARD1, BRCA1, CDK12, CHEK1, CHEK2, FANCA, MLH1, MSH6, PALB2, TP53. Considering the biologic function of HRR/MMR proteins as potential drug targets and the low frequency of most of these mutations in digestive system cancers in general, their common occurrence in our MLH1^-/PMS2^-/MSH6^- cases seems to be even more noteworthy, highlighting the need for recognition, awareness and further investigation of this unusual IHC staining pattern.

Recent studies have reported that immune checkpoint inhibitors are effective against various defective mismatch repair (dMMR)/microsatellite instability-high (MSI-H) cancers. A limited number of reports are available on the frequency of dMMR/MSI-H carcinoma in biliary tract cancer (BTC), describing its clinicopathological characteristics and prognosis. The latter carcinoma is also associated with Lynch syndrome (LS). The present study was performed to investigate the frequency of patients with dMMR/MSI-H in BTC and the clinical characteristics of BTC with dMMR/MSI-H in a single institution in Japan. A total of 116 patients with BTC who underwent curative surgical resection at Kagawa University Hospital between January 2008 and December 2017 were included. The protein expression levels of the mismatch repair (MMR) genes [mutL homolog 1 (MLH1), mismatch repair endonuclease PMS2 (PMS2), MutS homolog (MSH)2 and MSH6] were assessed by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded tissue specimens. Subsequently, MSI testing was performed on patients who exhibited loss of MMR protein expression. Loss of expression of one or more proteins was detected in five cases (4.3%). Loss of MLH1/PMS2 expression was observed in one case of intrahepatic cholangiocarcinoma, whereas loss of PMS2 expression was noted in one case of perihilar cholangiocarcinoma. Loss of MSH2/MSH6 and MSH6 expression was noted in two cases of distal cholangiocarcinoma and loss of PMS2 expression in one case of ampullary carcinoma. Out of the five patients, two demonstrated MSI-H. Microsatellite stability was observed in two cases and for one case, no data were available. Two MSI-H cases were patients with loss of expression of MLH1/PMS2 and MSH2/MSH6. None of the five patients exhibited a past medical history or family history of suspected LS. The frequency of dMMR in BTC was ~5%, which was similar to that reported by similar studies performed in other countries. In the present study, IHC appeared to be more useful than MSI testing for detecting MMR abnormalities with regards to the detection rate. Furthermore, there may only be a limited number of patients with BTCs who are likely to benefit from the therapeutic effects of treatment with immune checkpoint inhibitors.

• Lynch syndrome
• biliary tract cancer
• defective mismatch repair
• immunohistochemistry
• microsatellite instability-high

Periampullary carcinoma refers to a malignant tumor within 2 cm of the duodenal ampulla. Primary ampullary carcinoma is very rare, accounting for only 0.2% of malignant gastrointestinal tumors. The small intestine accounts for 75% of the length of the gastrointestinal tract, and primary tumors in the small intestine account for only 2% of all gastrointestinal tumors. Here, we report the case of a duodenal ampullary tumor with malignant transformation of parapapillary polyps. The patient had both a primary ampullary tumor and high-grade intraepithelial neoplasia of juxtapapillary adenomatous duodenal polyps.

• Periampullary carcinoma
• adenomatous polyp
• duodenum
• high-grade neoplasia
• malignant transformation
• tubular adenoma

• Heterogeneity
• IFN-γ signaling
• Immunotherapy
• Microsatellite instability
• Tumor-infiltrating lymphocytes

• Animals
• Humans
• Immunotherapy/methods
• Interferon-gamma/genetics
• Interferon-gamma/immunology
• Lymphocytes, Tumor-Infiltrating/immunology
• Lymphocytes, Tumor-Infiltrating/metabolism
• Lymphocytes, Tumor-Infiltrating/pathology
• Microsatellite Instability
• Neoplasms/genetics
• Neoplasms/immunology
• Neoplasms/pathology
• Neoplasms/therapy

• National Key R & D Program of China
• National Natural Science Foundation of China

• Adjuvant chemotherapy
• Ampullary carcinoma
• Chemoradiation
• Molecular testing

• adenocarcinoma
• adenoma
• ampullary tumors
• endoscopic papillectomy
• transduodenal ampullectomy

• Biliary tract carcinoma
• Prognosis
• Survival
• Tumor budding

• Bile Duct Neoplasms/pathology
• Biliary Tract Neoplasms/pathology
• Carcinoma/pathology
• Cholangiocarcinoma/pathology
• Gallbladder Neoplasms/pathology
• Humans
• Lymph Nodes/pathology
• Neoplasm Invasiveness
• Neoplasm Staging
• Prognosis
• Proportional Hazards Models
• Survival Rate

• DNA mismatch repair
• biliary tract cancer
• microsatellite instability
• tertiary lymphoid structures
• tumor infiltrating lymphocytes

The wider use of gastrointestinal endoscopic procedures has led to an increased detection of small intestinal preneoplastic and neoplastic epithelial lesions, most of which are identified in the duodenum and ampullary region. Like their malignant counterparts, small intestinal glandular precursor lesions, which include adenomas and hamartomas, may arise sporadically or be associated with hereditary tumor syndromes, such as familial adenomatous polyposis, MUTYH-associated polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and Cowden syndrome. In addition, dysplastic, preinvasive lesions have been observed adjacent to small bowel adenocarcinomas complicating immune-related disorders, such as celiac or Crohn’s disease. Adenomatous lesions may exhibit an intestinal-type, gastric-type, or, very rarely, serrated differentiation, related to different molecular pathogenetic mechanisms. Finally, in the background of multiple endocrine neoplasia 1 syndrome, precursor neuroendocrine growths have been described. In this review we offer a comprehensive description on the histo-molecular features of the main histotypes of small bowel epithelial precursors lesions, including: (i) sporadic adenomas (intestinal-type and gastric-type; non-ampullary and ampullary); (ii) syndromic adenomas; (iii) small bowel dysplasia in celiac and Crohn’s disease; (iv) serrated lesions; (v) hamartomatous lesions; and (vi) neuroendocrine precursor lesions.

• APC
• Crohn’s disease
• GNAS
• adenoma
• ampulla
• celiac disease
• hamartoma
• neuroendocrine
• polyposis
• small intestine

• Animals
• Humans
• Intestinal Neoplasms/metabolism
• Intestinal Neoplasms/pathology
• Intestine, Small/metabolism
• Intestine, Small/pathology

• Adenocarcinoma
• Adjuvant therapy
• Genome
• Subtype
• Vater carcinoma

• checkpoint
• gastrointestinal cancer
• microsatellite instability

Microsatellite instability (MSI) is a hallmark of Lynch syndrome (LS)-related tumors but is not specific, as most of MSI/mismatch repair-deficient (dMMR) tumors are sporadic. Therefore, the identification of MSI/dMMR requires additional diagnostic tools to identify LS. In this review, we address the hallmarks of LS and present recent advances in diagnostic and screening strategies to identify LS patients. We also discuss the pitfalls associated with current strategies, which should be taken into account in order to improve the diagnosis of LS.

Microsatellite instability (MSI) is a hallmark of Lynch syndrome (LS)-related tumors but is not specific to it, as approximately 80% of MSI/mismatch repair-deficient (dMMR) tumors are sporadic. Methods leading to the diagnosis of LS have considerably evolved in recent years and so have tumoral tests for LS screening and for the discrimination of LS-related to MSI-sporadic tumors. In this review, we address the hallmarks of LS, including the clinical, histopathological, and molecular features. We present recent advances in diagnostic and screening strategies to identify LS patients. We also discuss the pitfalls associated with the current strategies, which should be taken into account to improve the diagnosis of LS and avoid inappropriate clinical management.

• BRAF mutation
• Lynch syndrome
• MLH1 promoter methylation
• microsatellite instability
• mismatch repair genes

• Lynch syndrome
• mismatch repair deficiency
• screening

• 15934 Cancer Research UK
• G0100496 Medical Research Council
• C569/A24991 Cancer Research UK

• Adenocarcinoma/epidemiology
• Adenocarcinoma/surgery
• Ampulla of Vater/surgery
• Carcinoma, Signet Ring Cell/epidemiology
• Carcinoma, Signet Ring Cell/surgery
• Common Bile Duct Neoplasms/epidemiology
• Common Bile Duct Neoplasms/surgery
• Duodenal Neoplasms
• Female
• Humans
• Male
• United States/epidemiology

DNA damage repair (DDR) pathways are essential to ensure the accurate transmission of genetic material. However, different endogenous and exogenous factors challenge genomic integrity. Mechanisms involved in the alterations of DDR pathways mainly include genetic inactivation and epigenetic mechanisms. The development and progression of carcinomas are closely associated with DDR pathway aberrations, including the epigenetic silencing of gene O6-alkylguanine-DNA methyltransferase (MGMT); deficiencies of mismatch repair (MMR) genes, including MutL homolog 1 (MLH1), MutS protein homologue (MSH)-2 (MSH2), MSH6, and PMS1 homolog 2; the mismatch repair system component (PMS2); and mutations of homologous recombination repair (HRR) genes, such as the breast cancer susceptibility gene 1/2 (BRCA1/2). Understanding the underlying mechanisms and the correlations between alterations to DDR pathways and cancer could improve the efficacy of antitumor therapies. Emerging evidence suggests that survival is higher in patients with DDR-deficient tumors than in those with DDR-proficient tumors. Thus, DDR alterations play a predictive and prognostic role in anticancer therapies. Theoretical studies on the co-administration of DDR inhibitors and other anticancer therapies, including chemotherapy, radiotherapy, immunotherapy, endocrine therapy, and epigenetic drugs, hold promise for cancer treatments. In this review, we focus on the basic mechanisms, characteristics, current applications, and combination strategies of DDR pathways in the anticancer field.

• Anticancer therapy
• DNA damage repair pathway (DDR pathway)
• DNA repair
• cancer
• immunotherapy

• K08 CA237871 NCI NIH HHS

• Biomarkers
• gastrointestinal diseases
• immunotherapy
• neoplasms

The role of adjuvant chemotherapy (CT) or combination chemoradiation (CRT) remains uncertain for ampullary carcinoma (AC). In this analysis, we reviewed our institution’s experience with early-stage AC.

AC patients who had definitive surgical intervention at the University of Alabama, Birmingham, between 2005 and 2015, were identified. Clinicopathologic factors and disease statuses were obtained from chart review. The univariate Cox proportional hazard model was conducted for evaluating the parameters associated with overall survival (OS). Kaplan-Meier method and log-rank method were used to compare the time-to-events. We estimated the survival for the patients who had definitive surgery (pancreaticoduodenectomy (PD) or ampullectomy), and followed them up with assessing the influence of adjuvant treatment (chemoradiotherapy or CT) alone on the survival in the early-stage (stage I/II) AC.

A total of 63 patients had definitive surgery. The median OS and progression-free survival (PFS) for all the patients who had definitive surgery were 40.5 months and 28 months, respectively. Adjuvant treatment was administered in 60% of patients with early-stage (stage I/II) AC (CT 36% and CRT 24%), while 22% were on surveillance post surgery. The pathological stage ≥ 2, Lymph node (LN) metastasis, peri-nodal extension (PNE) and peri-pancreatic extension (PPE) were found to be the determinants for poor OS and PFS by univariate analysis. Multiple Cox regression of these variables showed a significant influence of PPE and pathological staging on the OS and PFS, respectively. In the early-stage AC with no high-risk features, adjuvant therapy did not improve the survival over surgery alone (40.5 vs. 51.7 months, P = 0.93). The addition of radiation to CT did not yield improved outcome in early-stage cancers. For CRT and CT, OS was 22.8 versus 65.7 months (P = 0.3975), and PFS was 25.3 versus 65.7 months (P = 0.4699).

In the early-stage AC, adjuvant therapy may not improve the outcome in the short term but may benefit over a long period. It should be considered, especially in patients with adverse risk factors. Radiation therapy may not be useful in managing AC in the adjuvant setting.

• Adjuvant treatment
• Adverse factors for ampullary cancer
• Ampullary cancer
• Cancer of ampulla of Vater
• Early-stage ampullary cancer
• Peri-ampullary cancer
• Post-operative management of ampullary cancer

• ampullary carcinoma
• medullary carcinoma
• mismatch repair
• programmed cell death-ligand 1
• tumor-infiltrating inflammation

• Ampullary adenocarcinoma and its sub-types
• CDX2
• Pancreatic adenocarcinoma
• Pancreatic intraepithelial neoplasia (pan-IN)

• Adenocarcinoma/classification
• Adenocarcinoma/pathology
• Aged
• Aged, 80 and over
• Ampulla of Vater/pathology
• Carcinoma, Pancreatic Ductal/classification
• Carcinoma, Pancreatic Ductal/pathology
• Female
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms/classification
• Pancreatic Neoplasms/pathology
• Retrospective Studies
• Pancreatic Neoplasms

• adjuvant chemotherapy
• ampullary carcinoma
• immunohistologic subtype

• Adjuvant treatment
• Lymphnode ratio
• Periampullary carcinoma
• Prognostic factors

Background: Periampullary neoplasms can be challenging to work up and diagnose preoperatively. Herein, we report the case of a patient whose preoperative workup failed to detect a malignancy, yet, underwent a pylorus-preserving pancreaticoduodenectomy (PPPD) with intraoperative pancreatic ductoscopy (IPD) and was ultimately found to have an ampullary adenocarcinoma.

Presentation: A 78-year-old woman presented with 4 weeks of nausea, weight loss, jaundice, and light-colored stools. She underwent outpatient diagnostic studies, including magnetic resonance cholangiopancreatography, endoscopic ultrasound, and endoscopic retrograde cholangiopancreatography with pancreatic duct (PD) stenting and papillotomy. These revealed common bile duct dilatation measuring 2 cm, PD dilatation measuring 7 mm, a 17 mm cyst in the head of the pancreas, and a firm nodule noted between the biliary and pancreatic orifices. Cytologic and pathologic analyses were initially nondiagnostic. A repeat ampullary biopsy was negative for dysplasia and malignancy. A computed tomography scan was then performed and showed cystic pancreatic lesions with pancreatic ductal dilation. Suspicion remained high for periampullary tumor or a main duct intraductal papillary mucinous neoplasm, and the patient underwent a PPPD with IPD and tolerated the procedure well. Her final specimen pathology revealed well-to-moderately differentiated ampullary adenocarcinoma, pancreaticobiliary type with positive nodal disease.

Conclusions: Given the relatively poor prognosis of patients with node-positive pancreaticobiliary-type ampullary adenocarcinoma, clinical suspicion should remain high for malignancy in patients with lesions located in the periampullary region and a negative preoperative workup, as aggressive treatment approaches are warranted to maximize their chance for survival.

• intraoperative pancreatic ductoscopy
• periampullary neoplasm
• pylorus-preserving pancreaticoduodenectomy

Ampullary Carcinoma arises from a histologically heterogeneous region where three different epithelia converge. Even though Ampullary Carcinoma has a superior prognosis compared to pancreatic and biliary ductal neoplasms, at least half of the patients turn up at an advanced stage that limits the treatment prospects. In addition to surgery for early-stage disease, several studies have shown that chemoradiotherapy confers additional benefits in the management of Ampullary Carcinoma. Analogously, chemotherapy plays a crucial role in treating advanced Ampullary Carcinoma with distant metastasis/recurrences. Although, stage of the disease, lymph node status, and histo-morphology are three critical prognostic variables, recently much attention is being placed on the genetic landscape of Ampullary Carcinoma. In this review, we have discussed various studies describing the role of chemoradiation and chemotherapy in the treatment of early and advanced stage Ampullary Carcinoma. Also, we have summarized the molecular landscape of Ampullary Carcinoma and the novel therapeutic strategies which could possibly target the genetic alterations involving the tumor cells.

• Ampullary carcinoma
• chemoradiation
• chemotherapy
• molecular landscape

The use of immunohistochemistry (IHC) as a companion diagnostic is an increasingly important part of the case workup by pathologists and is often central to clinical decision making. New predictive molecular markers are constantly sought for to improve treatment stratification parallel to drug development. Unfortunately, official biomarker guidelines lag behind, and pathologists are often left hesitating when medical oncologists request off-labelled biomarker testing. We performed a literature review of five commonly requested off-label IHC predictive biomarkers in gastrointestinal tract (GIT) malignancies: HER2, mismatch repair (MMR), PD-L1, BRAF V600E and ROS1. We found that HER2 amplification is rare and poorly associated to IHC overexpression in extracolonic and extragastric GIT cancers; however in KRAS wild type colorectal cancers, which fail conventional treatment, HER2 IHC may be useful and should be considered. For MMR testing, more evidence is needed to recommend reflex testing in GIT cancers for treatment purposes. MMR testing should not be discouraged in patients considered for second line checkpoint inhibitor therapy. With the exception of gastric tumors, PD-L1 IHC is a weak predictor of checkpoint inhibitor response in the GIT and should be replaced by MMR in this context. BRAF inhibitors showed activity in BRAF V600E mutated cholangiocarcinomas and pancreatic carcinomas in non-first line settings. ROS1 translocation is extremely rare and poorly correlated to ROS1 IHC expression in the GIT; currently there is no role for ROS1 IHC testing in GIT cancers. Overall, the predictive biomarker literature has grown exponentially, and official guidelines need to be updated more regularly to support pathologists’ testing decisions.

• BRAF V600E
• Gastrointestinal tract cancer
• HER2
• Immunohistochemistry
• MMR
• PD-L1
• Predictive biomarkers
• ROS1

• Ampullary cancer
• Biliary obstruction
• Pancreaticoduodenectomy

• Anorectal
• Immune checkpoint blockade
• Microsatellite instability
• Squamous cell carcinoma

• Adjuvant chemotherapy
• Gastric cancer
• Immune-checkpoint inhibitors
• Microsatellite instability
• Molecular stratification
• Predictive and prognostic value

• Antibodies, Monoclonal/therapeutic use
• Antineoplastic Agents/therapeutic use
• DNA Repair/genetics
• Humans
• Microsatellite Instability
• Microsatellite Repeats/genetics
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology
• Tumor Microenvironment

• 18052 Cancer Research UK

• immunotherapy
• gastrointestinal
• neoplasms

• Antineoplastic Agents, Immunological/therapeutic use
• Biomarkers, Tumor/analysis
• Clinical Trials as Topic
• Gastrointestinal Neoplasms/therapy
• Humans
• Immunotherapy/methods

• Cancer immunotherapy
• Immune checkpoint blockade
• Microsatellite instability
• Mismatch repair
• Tumor mutation burden

Periampullary adenocarcinomas, including pancreatic cancer, are a heterogeneous group of tumors with poor prognosis, where classification into intestinal type (I-type) or pancreatobiliary type (PB-type) is a relevant prognostic factor. The clinical significance of deficient mismatch repair (dMMR) in periampullary adenocarcinoma is comparatively unexplored. Herein, we examined the associations of MMR immunophenotype with long-term survival in patients with resected periampullary adenocarcinoma, with particular reference to morphology and adjuvant treatment response.

MMR protein expression was assessed by immunohistochemistry on tissue microarrays with primary tumors from a retrospective cohort of 175 patients with periampullary adenocarcinoma treated with pancreaticoduodenectomy during 2001–2011 in Malmö and Lund University Hospitals, Sweden. Cox proportional hazards models were applied to calculate hazard ratios (HR) and 95% confidence intervals (CI).

After a mean follow-up of 46.5 (1.9–185.1) months, 35 patients (20.3%) were alive, 24 with I-type and 11 with PB-type tumors. MMR protein expression could be evaluated in 172 cases, in which dMMR was denoted in 20 (11.6%) cases, 13/63 (20.6%) in I-type and 7/109 (6.4%) in PB-type tumors. dMMR was associated with a significantly prolonged overall survival in the entire cohort (HR = 0.28, 95% CI 0.13–0.57), and in I-type tumors (HR = 0.20, 95% CI 0.06–0.68), however not independent of conventional prognostic factors. In PB-type tumors, dMMR was not prognostic, but there was a significant negative interaction between dMMR and adjuvant treatment (p_interaction = 0.015).

dMMR is more frequent in I-type compared to PB-type periampullary adenocarcinoma, and is a prognostic factor for long-term survival only in the former. The finding of the small number of PB-type tumors with dMMR potentially lacking benefit from adjuvant chemotherapy is however noteworthy and merits further validation.

The online version of this article (10.1186/s12967-018-1444-4) contains supplementary material, which is available to authorized users.

• Adjuvant therapy
• Immunohistochemistry
• MMR
• Periampullary adenocarcinoma
• TMA

• Outcomes
• Pancreaticoduodenectomy
• Resection
• SEER
• Survival

• gastrointestinal cancer
• hypermutation
• immune checkpoint inhibitor
• microsatellite instability
• precision medicine

• R01 CA160688 NCI NIH HHS