The primary treatment for gastric cancer (GC) is surgical resection, particularly for locally advanced cases. While laparoscopic gastrectomy (LG) has shown short- and long-term benefits, robotic gastrectomy (RG) offers enhanced precision and may lead to better outcomes, especially in advanced-stage disease.

This retrospective study analyzed data from 1538 patients with pathological Stage I-III GC who underwent RG or LG between 2014 and 2021. Propensity score matching created 466 matched pairs. Perioperative outcomes, 3 year overall survival (OS), 3 year recurrence-free survival (RFS), and recurrence patterns were compared between RG and LG.

RG demonstrated significantly shorter operative time (235.5 vs. 242.5 min, p = 0.001), less blood loss (19.1 vs. 33.4 ml, p < 0.001), and shorter hospital stay (7.9 vs. 9.7 days, p < 0.001). Overall complications did not differ significantly (p = 0.183), but RG had lower rates of anastomotic leakage (p = 0.045) and pancreatic fistula (p = 0.024). No significant differences in OS were observed in the overall cohort or by stage. Similarly, RFS showed no significant differences in the overall cohort (3 year RFS: RG 86.81% vs. LG 83.04%, p = 0.1347). By stage, no differences were found in stage I or II, but in stage III, RG showed better 3 year RFS (67.52% vs. 52.97%, p = 0.0424). RG also had lower recurrence rates (9.0% vs. 14.8%, p = 0.0061), with fewer liver (p = 0.0069) and lymph node metastases (p = 0.0223).

RG demonstrated superior short-term outcomes and comparable three-year OS to laparoscopic gastrectomy, with improved three-year RFS and reduced recurrence in Stage III, likely facilitated by earlier adjuvant chemotherapy initiation.

Gastric cancer (GC) is a highly heterogeneous and complex malignancy, often characterized by tumor stemness and immune evasion mechanisms, which contribute to a poor response to neoadjuvant chemotherapy (NAC) and treatment resistance. In this study, we performed a comprehensive analysis using single-cell and multi-omics approaches on 375 GC samples from The Cancer Genome Atlas database, along with 141 clinical samples from patients who underwent NAC. We identified key gene modules associated with stemness and immune traits, and developed a novel stem cell-immune risk score. This score effectively distinguished responders from non-responders to chemotherapy, and was significantly associated with overall survival. Through multi-omics analysis, we further elucidated the role of phospholysine phosphohistidine inorganic pyrophosphatase (LHPP) in the tumor immune microenvironment. Our findings showed that high LHPP expression was closely linked to the increased infiltration of antitumor immune cells, such as CD8+ T cells, and significantly suppressed the development of stemness characteristics in GC. Additionally, single-cell sequencing data revealed that tumor epithelial cells with low LHPP expression exhibited heightened stemness and demonstrated the strongest communication with CD8+-exhausted T cells. We also observed that LHPP inhibited stemness and chemotherapy resistance in GC cells by regulating the phosphorylation of GSK-3β. In conclusion, LHPP plays a critical regulatory role in the stemness features and tumor immune microenvironment of GC, presenting a promising biomarker and potential therapeutic target for personalized treatment of GC.

This study aimed to clarify the significance of the relative dose intensity (RDI) of S-1 adjuvant chemotherapy (ACT) after gastrectomy in elderly patients with stage II/III gastric cancer (GC) and to determine whether the cachexia index (CXI) correlates with RDI.

We enrolled 76 patients with stage II/III GC, aged > 70 years. The overall survival (OS) and disease-specific survival (DSS) of participants in the surgery alone, S-1 ACT completion (RDI ≥ 58%), and S-1 ACT non-completion (RDI < 58%) groups were compared. In addition, the clinicopathological determinants of RDI were examined.

The S-1 ACT completion group had better OS and DSS, while the prognoses of patients in the surgery alone and S-1 ACT non-completion groups did not differ significantly. S-1 ACT non-completion or surgery alone was identified as an independent poor prognostic factor for OS and DSS. Furthermore, a multivariate analysis revealed that a high preoperative CXI (≥ 75.5 for males and ≥ 79.4 for females) was an independent predictor of success in achieving an RDI ≥ 58%.

A higher preoperative CXI can result in a higher RDI and improve the prognosis of elderly patients with stage II/III GC who underwent S-1 ACT.

Examined lymph node (ELN) count is a critical factor affecting the number of metastatic lymph nodes (MLNs). The impact of the ELN number on survival and staging remains unclear.

This study included 4,291 stage N3 GC patients from the SEER database (training cohort) and 567 stage N3 GC patients from the FAHZZU database (validation cohort). The optimal ELN count and stage migration were investigated, and a modified TNM (mTNM) staging system including the ELN count was proposed. LASSO regression and random forest analyses were used to screen and evaluate the variables associated with survival, and an mTNM-based nomogram was constructed. The performance of the mTNM staging system and mTNM-based nomogram were compared with that of the 8th edition of the TNM staging system.

The optimal threshold of the ELN count was identified as 21. An insufficient number of ELNs (≤ 21) was associated with poorer survival outcomes and led to stage migration in all N3 patients. A new mTNM staging system was proposed, integrating the ELN count into the TNM staging system (8th edition). LASSO regression analysis revealed that age, tumor size, adjuvant chemotherapy, adjuvant radiotherapy, and the mTNM system were associated with overall survival (OS) outcomes, and random forest analysis revealed that the mTNM system was the most important variable for predicting survival. An mTNM-based nomogram was constructed to predict 1-, 3-, and 5-year OS rates. Compared with the TNM staging system (8th edition), the mTNM staging system and mTNM-based nomogram showed superior prognosis discriminative ability, better predictive accuracy, and greater net improvement in survival outcomes.

The optimal ELN count for N3 GC patients was 21. The mTNM staging system and mTNM-based nomogram showed superior discriminative ability, predictive accuracy, and greater net benefit for OS outcomes.

The present study investigated the impact of lifestyle behaviors and body mass index (BMI) on late recurrence, gastric remnant cancer (GRC), and long-term survival after curative gastrectomy.

This retrospective study utilized data from the Korean National Health Insurance claims database. Among 71,014 patients with gastric cancer who underwent curative gastrectomy between January 2009 and December 2012, 23,359 remained cancer-free for five years. Of these, 7,735 patients with health examination data within 2 years before surgery and 5 years after surgery were analyzed for lifestyle behaviors, including smoking, alcohol consumption, and physical activity. Multivariable analysis was used to evaluate the independent effects of these factors and changes in BMI on late recurrence, GRC, and long-term survival.

Late recurrence or GRC occurred among 628 patients (8.1%). Older age (≥60 years) and total gastrectomy were identified as risk factors. Although lifestyle behaviors and BMI changes did not directly affect recurrence, they significantly affected mortality. In the total gastrectomy group, current underweight status (hazard ratio [HR], 1.586) was associated with increased mortality. Among the partial gastrectomy group, continued smoking (HR, 1.366) and current underweight status (HR, 1.915) increased mortality risk. Conversely, regular physical activity (starting: HR, 0.674; continuing: HR, 0.699) and postoperative overweight or obesity (BMI >25 kg/m²) (HR, 0.713) were associated with reduced mortality. Changes in alcohol consumption showed inconsistent effects between the partial and total gastrectomy groups.

The long-term survival of post-gastrectomy patients improved with smoking cessation, regular physical activity, and maintenance of body weight.

The C-Reactive Protein (CRP)-Albumin-Lymphocyte (CALLY) index is an established immuno-nutritional scoring system. We screened relevant literature from the major databases up until May, 2024, and extracted the data for analysis. A total of 2829 gastric cancer (GC) patients from six studies were included in this meta-analysis, the results of which revealed that the CALLY index was an independent prognostic factor for OS and RFS in both univariate analyses and multivariate analyses, and that a high CALLY index was a favorable prognostic factor. Moreover, GC patients in the high CALLY index group seemed to have better 5-year OS and 5-year RFS than those in the low CALLY index group. There was a higher proportion of patients with T1 status in the high CALLY index group than in the low CALLY index group. However, the opposite results were found in the analyses of lymph node metastasis positivity, lymph-vascular invasion positivity, postoperative complications, differentiated histological type, anastomotic leakage, and adjuvant chemotherapy. The present meta-analysis concluded that the CALLY index was a simple and useful independent prognostic biomarker for GC patients after gastrectomy.

Gastric cancers are silent malignancies that are typically diagnosed at advanced stages. Similarly, patients with prostate cancer can have an asymptomatic presentation despite widespread metastasis. The insidious nature of both malignancies highlights the importance of implementing appropriate screening protocols for early detection, prompt treatment, and better patient outcomes.

A 66-year-old man presented with unintentional weight loss and early satiety for 3 months and was found to have gastric adenocarcinoma after diagnostic testing. Further imaging demonstrated prostate enlargement and diffuse bony involvement, culminating in the diagnosis of a second primary tumor, prostate adenocarcinoma. A workup of gastric adenocarcinoma revealed metastasis to aortic-pulmonary (level 5) lymph nodes. Gastric outlet obstruction was treated with open gastrojejunostomy. Metastatic prostate cancer was treated with hormonal therapy.

Double primary tumors are rare occurrences and patient care should be optimized using an interdisciplinary care team. Treatment aims to mitigate disease progression, and is influenced by tumor type, anatomical location, and criteria for resectability.

Both gastric and prostate cancer pose significant challenges in both diagnosis and treatment, largely due to its often-asymptomatic nature in early stages and the complexity of its progression.

We investigated the safety and efficacy of laparoscopic gastrectomy (LG) in patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy (NAC).

This study included 247 consecutive patients with advanced gastric cancer who underwent NAC followed by gastrectomy between 2007 and 2017 at one of six institutions. The patients were divided into the open gastrectomy (OG) and LG groups. The short- and long-term outcomes in both groups were investigated after propensity score matching.

After propensity score matching, 72 pairs of patients were selected. The baseline characteristics were not significantly different after matching. Compared with the OG group, the LG group had a significantly longer operative time (360 vs. 305 min, P = 0.002) and less intraoperative blood loss (271 vs. 652 mL, P < 0.001). The LG group had more harvested lymph nodes than the OG group (57.4 vs. 45.1, P < 0.001). The frequency of Clavien-Dindo grade ≥ 2 postoperative complications was not significantly different (26% vs. 22%, P = 0.698). The interval between surgery and postoperative chemotherapy was significantly shorter in the LG group (48.7 vs. 68.6 days, P = 0.048). The 5-year overall survival rates in the OG and LG groups were 54.4% and 53.5%, respectively. The overall survival was similar between the two groups (P = 0.773). No significant differences were observed between the two groups in terms of the type of recurrence, including lymph node, hematogenous, and peritoneal recurrences (P = 1.000, P = 1.000, and P = 0.686, respectively).

Based on both short- and long-term results, LG is a potential therapeutic option for patients with gastric cancer who undergo NAC.

Whether adjuvant chemotherapy should be different for patients with stage II and III gastric cancer is unknown.

We retrospectively analyzed the effects of adjuvant chemotherapy on the outcomes of 140 and 256 patients with stage II and III gastric cancer, respectively, between January 2008 and December 2018. Chemotherapies were stratified as fluoropyrimidine plus platinum versus fluoropyrimidine alone, tegafur/gimeracil/octeracil (S-1)-containing versus non-S-1-containing regimens, and S-1 plus cisplatin versus S-1 alone.

The median age of patients was 67.0 (range 24.6-98.8) years. With a median follow-up of 105 months, recurrence occurred in 32 (22.9%) and 130 (50.8%) patients with stage II and III disease, respectively. Adjuvant chemotherapy was administered as fluoropyrimidine monotherapy to 68 (48.6%) and 73 (28.5%) patients, fluoropyrimidine plus platinum to 9 (6.4%) and 104 (40.6%) patients, and none to 63 (45.0%) and 79 (30.9%) patients with stage II and III gastric cancer, respectively. Doublet chemotherapy was associated with longer disease-free survival (DFS) (26.5 vs. 15.2 months, P = 0.001) and overall survival (OS) (41.2 vs. 22.0 months, P < 0.001) than fluoropyrimidine monotherapy for stage IIIB-IIIC disease. Furthermore, S-1-containing regimens prolonged DFS (57.4 vs. 21.9 months, P = 0.044) and OS (81.4 vs. 28.6 months, P = 0.023) compared with non-S-1-containing chemotherapy in stage III disease.

Although fluoropyrimidine monotherapy is feasible for stage II-IIIA disease, doublet chemotherapy is significantly associated with longer survival than monotherapy for stage IIIB-IIIC disease. S-1-containing regimens might lead to longer survival than non-S-1-containing chemotherapy in stage III gastric cancer.

Large type 3 (≥ 8 cm) and type 4 gastric cancers (GCs) have poor prognoses and necessitate multidisciplinary treatment. A multi-institutional phase II study (OGSG1902) was conducted to assess the efficacy and safety of neoadjuvant chemotherapy (NAC) with docetaxel, oxaliplatin, and S-1 (DOS) in these patients.

Patients with large type 3 or type 4 GC without distant metastasis, except for positive peritoneal cytology (CY), were enrolled. Patients received three courses of neoadjuvant DOS therapy (docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 on day 1 via intravenous infusion, and S-1 80 mg/m2 orally for 14 days, repeated every 3 weeks) followed by gastrectomy. After R0 resection, adjuvant docetaxel/S-1 therapy was administered for 1 year.

From October 2019 to February 2022, 48 patients were enrolled. NAC was completed in 91.7% of patients. The R0 resection rate was 89.6%. The pathological response rate (Grade 1b-3) was 66.7%. Among patients with measurable lesions, the response rate was 50.0%. The CY-negative conversion rate was 80.0%, and the protocol completion rate was 45.8%. Grade 3 or 4 adverse events during NAC, including neutropenia and appetite loss, occurred in 37.5% of patients. Major postoperative complications (Clavien-Dindo Grade IIIa or higher) were observed in 2.1% of patients.

NAC with DOS for large type 3 or type 4 GC followed by gastrectomy demonstrated promising efficacy, high pathological response rates, and an acceptable toxicity profile. Further evaluation of long-term survival outcomes is ongoing.

As adjuvant chemotherapy for stage III gastric cancer, the phase III (JACCRO GC-07) trial showed that docetaxel plus S-1 (DS) was superior to S-1 in terms of recurrence-free and overall survival. However, whether adding docetaxel to S-1 in the adjuvant setting affects survival after recurrence remains unclear. The optimal treatment strategy for patients who develop recurrence during or after DS has also been controversial.

We used results from JACCRO GC-07 to investigate post-recurrence survival (PRS) in patients who developed recurrence during or after completing adjuvant chemotherapy. PRS was compared between adjuvant groups and among post-recurrence chemotherapeutic regimens.

During 5 years of follow-up after surgery, 161 of 441 patients in the DS group and 216 of 452 patients in the S-1 group developed recurrence, with median PRS of 12.6 and 11.4 months, respectively (hazard ratio [HR] 0.98, 95 % confidence interval [CI] 0.79-1.22; p = 0.84). Among patients with recurrence, 115 patients in the DS group and 165 patients in the S-1 group received chemotherapy, and median PRS was 14.5 and 13.7 months, respectively (HR 1.04, 95 %CI 0.81-1.34; p = 0.76). Platinum-based chemotherapy resulted in longer PRS than non-platinum chemotherapy, regardless of the adjuvant chemotherapeutic regimen or time of recurrence.

PRS was similar between patients who received adjuvant chemotherapy with DS or with S-1 alone. PRS was also similar between groups of patients who received chemotherapy after recurrence. Platinum-based chemotherapy might be the optimal treatment for patients who develop recurrence after completing adjuvant DS, regardless of the time of recurrence.

This study aimed to investigate the safety of gastrectomy for gastric cancer in oldest-old patients aged ≥ 85 years.

This study retrospectively analyzed the patients aged ≥ 85 years who diagnosed with gastric cancer between 2008 and 2022. The study patients were divided into three groups: a surgery group, an endoscopic submucosal dissection (ESD) group, and a non-surgery and non-ESD group (n = 64, 57, and 152). Surgical outcomes and 3-year overall and recurrence-free survival (OS and RFS) were investigated.

In the surgery group, the study cohort comprised 30 males and 34 females with a median age of 87 years. Distal, proximal, and total gastrectomy (DG, PG, and TG) were performed in 54, 1, and 9 patients, respectively. There were 27, 16, 17, and 4 patients with pStage I, II, III, and IV, respectively. Thirty-day morbidity with Clavien-Dindo grade ≥ 3 and 30-day mortality were 12.5% and 3.1%, respectively. Kaplan-Meier curves for the 3-year OS and RFS demonstrated that survival curves worsened with increasing pStage (p = 0.005 and p < 0.001, respectively). In multivariate analyses for the 3-year OS and RFS, TG and pStage ≥ III were independent risk factors (p = 0.028 and 0.011 in OS, p = 0.021 and 0.001 in RFS). In comparisons of 3-year OSs among the three groups in each cStage, survivals in the surgery group were consistently better than those in the non-surgery and non-ESD group in cStages I to III (p < 0.001, 0.001, and < 0.001 in cStage I, II, and III, respectively).

Our findings suggest that the radical gastrectomy for gastric cancer can be performed safely and has a chance to improve survival even in the oldest-old patients aged ≥ 85 years.

Based on the phase 3 PRODIGY study, neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) have emerged as a viable treatment option for Asian patients with resectable locally advanced gastric cancer (LAGC). This phase 2 study evaluated the efficacy and safety of combining neoadjuvant durvalumab with DOS, followed by surgery and adjuvant durvalumab plus S-1 chemotherapy, for resectable LAGC.

Patients with LAGC with cT2/3N+or cT4Nany tumors were enrolled in this study. Patients with proficient mismatch repair protein (pMMR) tumors received three cycles of neoadjuvant durvalumab plus DOS, administered every 3 weeks, followed by surgery and adjuvant S-1 plus durvalumab (main study arm). The primary endpoints were the rate of pathologic complete regression (pCR) and safety. An exploratory arm evaluated patients with deficient mismatch repair protein (dMMR) tumors, who received three cycles of neoadjuvant durvalumab and tremelimumab, followed by surgery and adjuvant durvalumab.

In the main study arm, 50 pMMR patients were enrolled, and received at least one dose of neoadjuvant treatment. The median age was 63 years, with 72.0% being men. 18 and 32 patients presented with clinical stage II and III tumors, respectively. 49 (98.0%) underwent surgery, with 45 achieving R0 resection. A pCR rate of 30.0% was observed, meeting the prespecified primary efficacy endpoint. With a median follow-up of 21.8 months, the 3-year progression-free survival and overall survival rates were 69.9% and 88.1%, respectively. 10% of patients experienced predefined unacceptable severe toxicities, including febrile neutropenia (n=3) and persistent G4 neutropenia (n=2) lasting more than 7 days, thereby meeting the primary safety endpoint. Nine patients with dMMR tumors were enrolled in the exploratory arm. All nine underwent surgery, with a pCR rate of 22.2%.

This study met its primary efficacy and safety endpoints. The combination of neoadjuvant durvalumab plus DOS, followed by surgery and adjuvant durvalumab plus S-1 chemotherapy, warrants further investigation in a phase 3 trial for Asian patients with LAGC.

04221555.

Transmembrane protease serine 4 (TMPRSS4) is a member of the type II transmembrane serine protease family known to be upregulated in many malignancies. We previously showed that TMPRSS4 may be a prognostic biomarker and therapeutic target for gastric cancer (GC), especially in stage III. In this retrospective study conducted at 10 institutions, all 325 patients underwent R0 resection involving D2 lymph node dissection. TMPRSS4 expression was examined using immunohistochemical analysis. TMPRSS4 expression was upregulated in 44.9% of participants. The 5-year overall survival (OS) of the TMPRSS4-positive group was significantly lower than that of the TMPRSS4-negative group (62.4% vs. 76.4%, respectively; p = 0.0149). Univariate analysis revealed that TMPRSS4 upregulation, tumor size, deeper tumor invasion, lymph node metastasis (N), lymphatic invasion, and tumor stage were significant prognostic factors for OS. Multivariate analysis revealed that N and TMPRSS4 upregulation were significant prognostic factors for OS. The 5-year OS rate was examined in two patient groups: the group with the receiver operating characteristic curve cut-off value ≥ 45% for TS-1 (cancer drug formulation) oral dosage and the group with TS-1 dosage cut-off value < 45%. For the patients in the TS-1 dosage ≥ 45% group, there were significant differences in OS between the TMPRSS4-positive and -negative groups (p = 0.0284): the 5-year OS rates of TMPRSS4-positive and -negative groups were 65.2% and 79.2%, respectively. Our findings suggest that TMPRSS4 overexpression is a useful biomarker for GC, and that an anti-TMPRSS4 antibody may have potential as a novel therapeutic agent.

To report the latest systematic review and meta-analysis of randomized controlled trials (RCT) to compare perioperative versus adjuvant chemotherapy for resectable gastric cancer.

We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April, 2024 for RCT which compared perioperative versus adjuvant chemotherapy for resectable gastric cancer. Outcomes measured were overall survival (OS) and progression-free survival (PFS).

5 RCTs including 2,735 patients were included for meta-analysis. Meta-analysis revealed a significant longer PFS in the neoadjuvant chemotherapy (NAC) group (HR: 0.77; 95% CI: 0.69, 0.85; P<0.00001) compared with adjuvant chemotherapy (AC) group. Subgroup analysis found that there was still a significant superiority of NAC in female (HR: 0.53; 95% CI: 0.40, 0.70; P<0.0001) and cN+ (HR: 0.77; 95% CI: 0.67, 0.89; P=0.0005) patients, while the superiority disappeared in male (HR: 0.87; 95% CI: 0.74, 1.01; P=0.07) and cN- patients (HR: 0.91; 95% CI: 0.46, 1.78; P=0.77). In addition, meta-analysis observed a trend towards improved OS with NAC (HR: 0.86; 95% CI: 0.70, 1.07; P = 0.17), and sensitivity analysis demonstrated instability in OS.

NAC can significantly prolong PFS in patients with resectable gastric cancer compared to AC, and the benefit is more significant in women and cN+ patients. Besides, our analysis indicated that NAC has a potential to improve OS compared with AC.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024546165.

The recommended treatment for gastric cancer with positive peritoneal cytology (CY1) is primary surgery and S-1 chemotherapy, with 5-year overall survival rates of 24.6%-30.2% reported in previous studies. However, it is unclear whether this strategy is applicable in cases of Type 4 or large Type 3 tumors, which have malignant characteristics and are considered to have different chemosensitivities.

The present study examined the survival of patients who were diagnosed with gastric cancer with CY1, without any other macroscopic distant metastasis, who underwent primary gastrectomy with D2 or more lymph node resection, achieved curative resection except for CY1-positive, and received S-1 postoperative chemotherapy between 2000 and 2017. Patients were divided into the S group (Type 4 or large Type 3 GC) and C group (common GC types).

Among the 352 patients who underwent gastrectomy with CY1, 40 patients were analyzed as the S group and 28 patients as the C group in this study. Both groups were similar in age and ASA-PS, but the S group had more female patients and larger tumors. The median duration of S-1 chemotherapy was 273 days in the S group and 358.5 days in the C group, with similar 1-year continuation rates. The median overall survival of these patients was 24.1 months in the S group and 45.6 months in the C group, with a 5-year survival rate of 23.7% in the S group and 22.0% in the C group. There was no significant difference. Recurrence occurred in 35 patients in the S group and 20 in the C group, with peritoneal metastasis as the most common recurrence site in both groups.

Primary surgery and S-1 chemotherapy could be considered a viable treatment option, even for Type 4 or large Type 3 gastric cancer with CY1.

Gemcitabine/cisplatin (GemCis) was the long-standing first-line treatment for advanced biliary tract cancers (BTCs). Following positive results from the TOPAZ-01 and KEYNOTE-966 trials, immune checkpoint inhibitors (ICIs) combined with chemotherapy are now the standard of care. We aim to compare the efficacy of first-line therapies for advanced BTCs.

Our systematic review included studies from five databases focusing on English-language articles published between January 2010 and June 2024. We included randomized clinical trials (RCTs) that featured GemCis in a treatment arm for treatment-naive adults with advanced BTCs. The primary endpoints were overall survival (OS) and progression-free survival. We conducted a one-stage meta-analysis using reconstructed survival data, Cox-based models, and restricted mean survival time (RMST).

After screening 8,797 studies, 17 RCTs were selected, involving a total of 4,584 patients. Of these, 2,140 (46.7%) received GemCis. The majority (68.9%) were diagnosed with intrahepatic or extrahepatic cholangiocarcinoma, and 80% had metastatic disease at the time of treatment. The pooled median OS in the GemCis group was 11.6 months (95% CI 11.3-12.2 months). GemCis plus pembrolizumab (hazard ratio [HR] 0.99, 95% CI 0.98-0.99; p <0.001), GemCis plus durvalumab (HR 0.98, 95% CI 0.97-0.99; p = 0.015), GemCis plus S-1 (HR 0.97 95% CI 0.95-0.99; p <0.001), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.98-0.99; p <0.001) demonstrated superior OS compared with GemCis alone. These combinations also showed increases in RMST by +1.1, +2.5, +2.8, and +2.1 months, respectively. In terms of progression-free survival, GemCis with ICIs (HR 0.91, 95% CI 0.78-0.94; p <0.001), GemCis plus S-1 (HR 0.98, 95% CI 0.96-0.99; p = 0.003), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.97-0.99; p <0.001) also demonstrated superiority, with corresponding RMST increases of +0.7, +1.9, and +2.5 months, respectively.

Despite incremental advancements, a breakthrough in advanced BTC treatment remains elusive. Further improvements in treatment efficacy may require biomarker identification to optimize combinational therapies for better patient selection.

This study analyzed recent RCTs, including KEYNOTE-966, TOPAZ-1, NIFE, and SWOG 1815, involving 4,584 patients with advanced biliary tract cancer. A meta-analysis of 17 treatment arms, using reconstructed survival data, confirmed the modest survival benefit of GemCis plus ICIs, supporting its guideline adoption. The findings, however, highlight the need for biomarker identification and better patient selection.

In resectable gastric/gastroesophageal junction adenocarcinoma, microsatellite instability-high (MSI-H) confers improved survival, but limited benefit from chemotherapy. Immunotherapy may eliminate the need for chemotherapy or surgery.

INFINITY is a multicenter, multicohort phase II trial (NCT04817826) investigating in cohort 1 the activity and safety of tremelimumab + durvalumab (T300/D) as neoadjuvant treatment of mismatch repair deficient/MSI-H, resectable gastric/gastroesophageal junction adenocarcinoma. Primary endpoint was pathologic complete response (pCR) rate; Secondary endpoints: progression-free survival (PFS), overall survival (OS), quality of life, and translational analyses. In cohort 2, the activity and safety of T300/D was explored as definitive treatment in patients achieving clinical complete response (cCR). Primary endpoint was 2-year cCR rate, and secondary endpoints were PFS, OS, quality of life, gastrectomy-free survival and translational analyses.

In cohort 1, 18 patients were recruited and 15 evaluable. pCR and major pathologic response-pCR were 60% and 80%, respectively. Since pCR rate in T4 tumors was 17%, this subgroup of patients was excluded from enrollment in cohort 2. At 28.1 months median follow-up, 24-month gastric cancer-specific PFS and OS rates were 85% and 92%, respectively. In cohort 2, 18 patients were enrolled and 17 assessable, and 13 had cCR and started non-operative management. At 11.5 months median follow-up, one patient had local regrowth and underwent salvage surgery; 12-month gastrectomy-free survival was 64.2%.

The INFINITY study provided promising activity results of a chemo-free T300/D combination regimen as preoperative treatment in mismatch repair deficient/MSI gastric/gastroesophageal junction adenocarcinoma and the first available feasibility results of a non-operative management strategy in this disease setting, worthy of further validation in larger cohorts.

Identifying the most effective postoperative surveillance interval in patients with gastric cancer (GC) remains challenging. To elucidate a logical and effective surveillance schedule, we analyzed GC recurrence risk trends after gastrectomy using the hazard function.

We retrospectively reviewed the medical records of 2503 patients who underwent curative GC resection between 2000 and 2018. We examined recurrence risk over time and the influence of clinicopathological variables on it.

Overall, GC recurred in 291 patients (11.6%) over a median of 64.6 months. Recurrence risk was highest at approximately 11-months postoperatively (hazard rate [HR]: 0.0045), decreasing to half the peak at approximately 39-months postoperatively. Patients with Stage I GC maintained a low risk. In Stage II patients, the risk peaked at 16-months postoperatively (HR: 0.006) and gradually declined thereafter. Stage III patients had the highest risk at 11 months postoperatively (HR: 0.019), plateauing at 40 months.

We demonstrated significant cancer stage-dependent differences in postsurgical GC recurrence risk by using the hazard function. Reductions in surveillance intensity might be acceptable according to the individual risk of recurrence.

The long term survival of patients undergoing curative resection for gastric cancer remains poor owing to high recurrence rates. The use of adjuvant chemotherapy in node positive gastric cancer to prolong survival and prevent recurrence is widely accepted. However, the role for adjuvant chemotherapy in node negative gastric cancer is less clear, particularly in the era of neoadjuvant chemotherapy.

To determine the association of adjuvant chemotherapy with survival in patients undergoing pathologically node negative gastric cancer resection, following neoadjuvant chemotherapy.

We examined a national cancer database containing patients who had undergone neoadjuvant chemotherapy and pathologically node negative curative gastrectomy. We divided these patients into those who had undergone adjuvant chemotherapy versus those who had not. Using a propensity score matched analysis, we analyzed the survival of these patients between the 2 groups.

5309 patients who had undergone curative gastrectomy were identified from the database and 806 of these patients were given adjuvant chemotherapy. Following propensity score matched analysis, patients who had been given adjuvant chemotherapy had an increased median survival of 150 vs 125 months (5-year 68 % vs 62 %, p < 0.001).

There is a small, but statistically significant survival benefit for adjuvant chemotherapy in patients with node negative gastric cancer who had undergone neoadjuvant chemotherapy. Further studies are required to examine the role of adjuvant chemotherapy in this subset of patients.

Lymphadenectomy (LND) is a crucial component of the curative surgical treatment of gastric cancer (GC). The LND serves to both accurately stage the disease and offer therapeutic benefits. At the time of "curative-intent" gastrectomy, D2 LND is the optimal treatment for patients with locally advanced GC due to its survival benefits and acceptable morbidity. Mastery of the technical aspects of LND, especially D2, requires significant training, adequate case volume, and expertise. This review discusses key aspects of D2 LND, including its status as the standard treatment for locally advanced GC, definition and anatomic borders, technical details, and controversial topics such as splenic hilar dissection and omentectomy. The application of indocyanine green (ICG) fluorescence imaging to elucidate the drainage patterns of GC and to facilitate lymph node (LN) identification is briefly reviewed. Finally, GC standardization and centralization, including surgical treatment, are discussed.

The nationwide registry of the Japanese Gastric Cancer Association contains data related to the efficacy of adjuvant chemotherapy and prognostic factors across this patient population; elderly patients with advanced resectable gastric cancer are especially prevalent. Here, we analyzed data from 34,931 patients, who were treated between 2011 and 2013 at 421 hospitals in Japan. Although adjuvant chemotherapy was effective overall, 75 years or older elderly patients had a worse prognosis compared to younger patients. The most administered adjuvant chemotherapy was S-1 monotherapy. Adjuvant S-1 monotherapy was also effective for patients with pT1N2, pT1N3, and pT3N0 stage II tumors, as well as patients with other stage II and III malignancies. Independent prognostic factors for poor overall and relapse-free survival in patients at both stage II and stage III were age 75 or older, male, preoperative Eastern Cooperative Oncology Group performance status (ECOG-PS) 1 or more, preoperative renal dysfunction, undifferentiated adenocarcinoma, undergoing total gastrectomy, open laparotomy, no adjuvant chemotherapy, D1 lymphadenectomy, residual tumor R1 or R2, and Clavien-Dindo classification grade II or higher. Age 75 or older, renal dysfunction, ECOG-PS 1 and total gastrectomy were also significant risk factors for postoperative complications and lower compliance with adjuvant chemotherapy. Our analysis also revealed that adjuvant chemotherapy after resection of cancer of gastric remnant and postoperative chemotherapy against CY1 gastric cancer were also effective. We conclude that adjuvant chemotherapy is effective for all stage II and III patients including age 75 or older gastric cancer patients, in addition to distal gastrectomy, proximal gastrectomy, and pylorus-preserving surgery to avoid total gastrectomy may improve surgical outcomes and quality of life for elderly patients.

This review addresses the current treatment paradigm and new advancements in the management of microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) esophagogastric cancer (EGC).

While chemotherapy and surgery remain the cornerstone of EGC treatment, MSI-H/dMMR tumors harbor high tumor mutational burden and represent a subset of patients who benefit from immune checkpoint inhibitors (ICI). ICI has been incorporated in the front line setting with and without chemotherapy for advanced disease. Recently, ICI has been studied in the perioperative setting for resectable disease. Though perioperative ICI results in improved response rates, it is not yet clear whether this translates to a survival benefit. Despite high response rates with ICI in this patient population, many do not respond to therapy, representing a major challenge in treatment. Preclinical studies have highlighted potential mechanisms of resistance which will guide drug development and clinical trials.

Gastric cancer is prevalent worldwide and is a leading cause of cancer-related death. Patients with GC often present at advanced stages at diagnosis. Patients with locally advanced diseases experience poor survival rates with surgery alone. Multimodality therapy, including peri-operative therapy and adjuvant therapy, has improved outcomes. However, there is no consensus on the optimal treatment approach. Molecular characteristics of GC may help guide treatment choices and studies are currently underway to evaluate other treatment modalities including immunotherapy and targeted therapy.

Elderly patients with advanced gastric cancer have poor prognoses. This study aims to develop a prediction model for long-term survival after radical surgery and to identify patients who may benefit from chemotherapy.

Data from 555 elderly patients with advanced gastric cancer admitted to two medical centers from 2009 to 2018 were retrospectively analyzed. Sarcopenia was combined with the Controlling Nutritional Status (CONUT) score to create a modified nutritional index (mCONUT). Cox regression analyses were used to develop a novel nomogram prediction model (mCNS) that combined mCONUT, pN, and tumor size, and its performance was further verified both internally and externally.

Multivariate Cox analysis revealed that tumor size, pN, and mCONUT were independent prognostic risk factors for overall survival (OS). The mCNS model showed good fit and high predictive value (AUC: training set 0.711; validation set 0.707), outperforming the pTNM model (p < 0.05). To further investigate the association between the model and adjuvant chemotherapy, we categorized the model into two risk groups: a high-risk group and a low-risk group. Further analysis revealed that, in the low-risk group, the OS and recurrence-free survival(RFS) for patients receiving adjuvant chemotherapy was significantly better than that of those who did not receive chemotherapy (p = 0.047,p = 0.019). In the high-risk group, this result was not observed (p = 0.120, p = 0.053).

The mCNS model has high predictive value in predicting long-term survival of elderly patients with advanced gastric cancer. Patients with mCNS-L were able to benefit from chemotherapy after laparoscopic radical gastrectomy.

Body weight loss after surgery for gastric cancer is related to S-1 compliance and it also affects the prognosis. However, it is unclear whether the preoperative skeletal muscle mass affects S-1 completion for gastric cancer. We investigated the impact of preoperative skeletal muscle mass loss on the completion of S-1 adjuvant chemotherapy for gastric cancer.

We retrospectively analyzed data from 53 patients who underwent curative gastrectomy followed by adjuvant S-1 monotherapy for pStage II-III gastric cancer between 2012 and 2021 at our hospital. The psoas muscle mass index (PMI) was used as the index for preoperative skeletal muscle mass.

Thirty-six patients completed S-1 treatment and 17 discontinued treatment. The patients who completed S-1 treatment had a longer overall survival than those who discontinued treatment (log-rank test, p = 0.043). According to a univariate analysis, the patients in the discontinuation group had a significantly lower preoperative body mass index (< 22.9 kg/m2, p = 0.005) and a higher rate of adverse events (grade 2 or higher, p < 0.001) than those in the completion group. According to a multivariate analysis, preoperative PMI (HR 3.563, p = 0.030) was an independent predictive factor for S-1 completion.

Preoperative skeletal muscle loss might therefore prevent the completion of adjuvant chemotherapy S-1 in patients with gastric cancer.

Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant tumor of the liver and gallbladder, which is usually diagnosed at an advanced stage and the opportunity for surgery is lost. Therefore, conversion therapy is important to convert the iCCA into a resectable state. In recent years, the conversion protocol of immuno-chemotherapy has been applied for advanced liver cancer. However, little has been reported about iCCA conversion therapy. The aim of this report is to present the results of conversion therapy with Gemcitabine plus S-1 (GS) combined with PD-1 inhibitors (Zimberelimab) in a 74-year-old female IIIB iCCA patient. After 6 cycles of conversion therapy, enhanced CT showed that the patient's tumor had shrunk to nearly half its original size, making radical resection possible. Postoperative pathology showed a complete pathological response. This provides a new way to convert advanced iCCA into resectable state.

Neoadjuvant chemotherapy followed by surgery (NAC-S) is the standard therapy for locally advanced esophageal squamous cell carcinoma (ESCC) in Japan.

The aim of this phase II trial was to assess the efficacy and safety of the addition of adjuvant S-1 after R0 resection in ESCC patients who received NAC-S.

Key eligibility criteria included clinical stage IB-III (without T4 disease) ESCC, age 20-75 years, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients received adjuvant therapy with four cycles of S-1 (80 mg/m2/day) administered orally for 4 weeks of 6-week cycles. The primary endpoint was 3 year relapse-free survival (RFS). If the lower confidence limit for 3 year RFS was >50%, we judged that the primary endpoint of this study was met.

A total of 52 patients were enrolled between January 2016 and January 2019. Two patients were excluded from analysis; five patients were determined to have R1 or R2 resection, and seven patients did not receive adjuvant S-1. The 3-year RFS and overall survival rates in the intention-to-treat population were 72.3% (90% confidence interval [CI] 59.9-81.5) and 85.0% (90% CI 73.9-91.6), indicating that the primary endpoint was met. Grade ≥3 adverse events with an incidence ≥10% included neutropenia (13.2%), anorexia (13.2%), and diarrhea (10.5%). There were no treatment-related deaths.

Adjuvant S-1 after NAC-S showed promising efficacy with a manageable safety profile for patients with resectable ESCC and warrants further evaluation in larger studies.

Adjuvant chemotherapy offers survival benefit to patients with gastric cancer. Only 50-65% of patients who undergo neoadjuvant chemotherapy and gastrectomy are able to receive adjuvant therapy. It is optimal to start adjuvant therapy within 8 weeks after gastrectomy. We compared the rate of return to intended oncologic therapy (RIOT) between minimally invasive gastrectomy (MIG) and open gastrectomy (OG).

Retrospectively, we analyzed patients who underwent gastrectomy within a multi-hospital university-based health system (2019-2022). Data on patient demographics, comorbid conditions, operative approach, and postoperative outcomes were assessed with univariate analysis and multivariable analysis (MVA) to determine the association with RIOT.

Among 87 eligible patients, 33 underwent MIG and 54 underwent OG. There were no differences in demographics, performance status, comorbid conditions, or type of gastrectomy between the two groups. MIG patients were significantly more likely to RIOT compared with OG patients (87.9% vs. 63%, p = 0.003), with 73.1% of MIG patients starting adjuvant therapy within 8 weeks compared with 53.1% of OG patients. Factors associated with higher odds of RIOT included MIG and age <65 years, while major postoperative complications (Clavien-Dindo grade ≥IIIa) was associated with lower odds of RIOT. On MVA, MIG was independently associated with higher odds of RIOT compared with OG (odds ratio 6.05, 95% confidence interval 1.47-24.78, p = 0.008).

The minimally invasive approach may benefit patients undergoing gastrectomy, irrespective of the extent of gastric resection for adenocarcinoma. MIG is associated with a higher likelihood of (1) RIOT and (2) starting adjuvant therapy within the optimal time period after gastrectomy.

It is essential to ensure optimal adherence to adjuvant chemotherapy regimens following gastric cancer surgery. However, treatment intensity for S-1 as adjuvant chemotherapy has not as yet been compared between minimally invasive (MI) and open (Open) surgery.

We retrospectively compared dose modification of adjuvant S-1 between MI and Open surgery in patients undergoing R0 gastrectomy for gastric or esophago-gastric junction cancer at the Cancer Institute Hospital Tokyo, Japan, during the period from 2012 to 2022, and receiving S-1 for pStage II or S-1 plus docetaxel for pStage III as adjuvant chemotherapy. Propensity score matching (PSM) was conducted to adjust for possible confounders.

In total, 323 patients were initially included. After PSM, 158 patients remained, 79 in each group. The adjuvant chemotherapy completion rates were similar in the two groups. However, the proportion of patients who required S-1 dose reduction was significantly lower in the MI than in the Open group (43.0% vs. 65.8%, p = 0.004). In addition, the MI group had significantly fewer patients requiring suspension of S-1 than the Open group (46.8% vs. 64.6%, p = 0.025). Moreover, the frequency of adverse events of grade ≥ 3 was significantly lower in the MI than in the Open group (17.7% vs. 31.7%, p = 0.042).

In adjuvant chemotherapy for gastric cancer, minimally invasive surgery may offer better treatment intensity for oral S-1 administration than open surgery.

The prognosis remains poor for stage III gastric cancer, and neoadjuvant chemotherapy is increasingly used to improve outcomes. Accurate diagnosis prior to treatment is essential to develop appropriate treatment strategies for poor prognosis subgroups. This study aims to enhance the accuracy of pre-treatment gastric cancer diagnosis using a biological approach centered on circulating circular RNA (circRNA).

We conducted a comprehensive analysis of circRNA expression profiles using two Gene Expression Omnibus datasets to identify circRNA candidates associated with stage III gastric cancer. Subsequently, we validated these circRNA biomarkers in two independent clinical cohorts comprising a total of 174 patients with gastric cancer and non-disease controls through real-time polymerase chain reaction (PCR).

Genome-wide circRNA analysis identified a panel of four biomarkers capable of diagnosing pathologically confirmed stage III (pStage III) gastric cancer. In a training cohort (n = 83), a clinically applicable panel of four circRNAs was developed (AUC 0.81), which was successfully validated in an independent clinical cohort (n = 82; AUC 0.76). To assess clinical utility, we combined clinical imaging (cStage) with the circRNA panel. Among those initially diagnosed as cStage III but later confirmed as pStage I/II, 86% were accurately diagnosed using the molecular biological approach with circRNAs.

We have developed a circRNA-based non-invasive liquid biopsy that can improve the diagnostic performance of pStage III gastric cancer before treatment. Our circRNA model could provide a sophisticated and personalized approach to assist in treatment planning for patients with advanced gastric cancer.

Patients aged >80-years-old with gastric cancer are commonly excluded from clinical trials, and no consensus exists regarding surgical indications and outcomes in older patients. In this study, we analyzed the post-gastrectomy long-term survival and etiologies of mortality in older patients with gastric cancer.

Patients aged >80-years-old with pathological stages I-III primary gastric cancer who undergone radical gastrectomies, between May 2006 and March 2017, were included in the study. Eligible patients were categorized into 3 age cohorts: <85-, 85-90-, and >90-years-old. The primary outcome was the overall survival. The etiologies of mortalities were compared. Survival curves were compared using the log-rank test. Prognostic factors were identified by multivariate analysis, using the Cox proportional hazards regression model.

The median follow-up duration was 59 months. Of the 353 patients, 269 (76.2%), 71 (20.1%), and 13 (3.7%) were categorized into the <85-, 85-90-, >90-years-old age cohorts, respectively. Older patients had a poorer overall survival (p = 0.003) and statistically significant difference in the other-cause survival (p < 0.001). The multivariate analysis revealed that age was not an independent prognostic factor for overall or cancer-specific survival. However, an age >90-years-old was an independent prognostic factor for the other-cause survival.

In patients aged >80-years-old with gastric cancer who had undergone gastrectomies, mortalities from other diseases increased with age; while mortalities from gastric cancer did not. An age of ≥90-years-old was an independent prognostic factor for mortalities from other diseases.