Journal of Gastrointestinal Cancer最新文献

Background: Intrahepatic cholangiocarcinoma is a biliary neoplasm usually showing a dismal prognosis. In early stages, surgical resection is the best treatment option, significantly increasing the overall survival. This approach is also recommended in the case of relapsing disease. In this study, we report the case of a patient affected by intrahepatic cholangiocarcinoma with multiple relapses and still alive for over 18 years. We also provide a systematic review regarding long-survivor (> 60 months) of intrahepatic cholangiocarcinoma.

Case presentation: A 41-year-old woman with no pathological history was diagnosed with localized intrahepatic cholangiocarcinoma and surgically treated with left hepatectomy. After the first intervention, the patients underwent three further surgical resections because of locoregional recurrences. Histologically, there were some significant similarities among all neoplasms, including the tubule-glandular architecture, but also morphological heterogeneity. The tumor immune microenvironment remained stable across the different lesions. The molecular analysis with next-generation sequencing demonstrated that all neoplasms shared the same genomic profile, including NBN and NOTCH3 mutations and chromosomes 1 and 3 alterations.

Conclusions: This case study highlights the essential role of a stringent follow-up after resection of intrahepatic cholangiocarcinoma for detecting early relapsing tumors. Moreover, it shows the importance of the molecular characterization of multiple tumors for understanding their real nature. The accurate study of long-surviving patients highlights the features that are critical for outcome improvement.

Background: Our study aims to determine the predictors and patterns of relapses after curative colorectal liver metastasis (CRLM) resection.

Methods: A single-centre, retrospective study of CRLM patients operated between 2010 and 2022 was performed. The site of first recurrence was either hepatic (marginal (≤ 1 cm) or extramarginal), extrahepatic, or both. Factors that predicted relapse patterns and overall survival were determined by multivariable Cox regression analysis with backward elimination of variables.

Results: The study consisted of 258 patients, with a similar proportion of synchronous (144; 56%) and metachronous(114; 43%) metastasis. At a 43-month median follow-up, 156 patients (60.4%) developed recurrences with 33 (21.1%) in the liver, 62(24.03%) extra-hepatic recurrences, and 58 (22.48%) having both. Isolated marginal liver relapses were seen in seven (9.89%) liver recurrence patients. The median overall and relapse-free survivals were 38 months (30-54) and 13 months (11-16), respectively. The 3-year liver-relapse-free survival was 54.4% (44.9-60.6). Size of liver metastases > 5 cm (HR 2.06 (1.34-3.17), involved surgical margins (HR 2.16 (1.27-3.68)), and adjuvant chemotherapy (HR 1.89 (1.07-3.35)) were predictors of hepatic recurrences. Node positivity of primary (HR 1.61 (1.02-2.56)), presence of baseline extra-hepatic metastases (HR 0.30 (0.18-0.51)), size of liver metastases > 5 cm (HR 2.02 (1.37-2.99)), poorly differentiated histology (HR 2.25 (1.28-3.49)), presence of LVI (HR 2.25 (1.28-3.94)), and adjuvant chemotherapy (HR 2.15 (1.28-3.61)) were predictors of extra-hepatic recurrences.

Conclusion: The study found majority relapses occurred at extrahepatic sites whilst isolated marginal recurrences were few. The consistent predictors of recurrence were size and inability to deliver adjuvant therapy. A tailored adjuvant therapy might improve outcomes after liver metastasectomy in colorectal cancers.

Purpose: The clinical effectiveness of triple chemotherapy consisting of gemcitabine, cisplatin plus either S-1 (GCS), durvalumab (DGC), or pembrolizumab (PGC) as first-line treatment for advanced biliary tract cancer (BTC) has been reported. However, their comparative cost-effectiveness is unclear. We conducted a model-based cost-effectiveness analysis from the perspective of Japanese healthcare payer.

Methods: A 10-year partitioned survival model was constructed by comparing the time-dependent hazards of the KHBO1401-MITSUBA, TOPAZ-1, and KEYNOTE-966 trials. The cost and utility came from previously published reports. Quality-adjusted life years (QALY) were used to measure the effects on health. Costs for direct medical care were taken into account. There was a one-way analysis and a probability sensitivity analysis. A willingness-to-pay threshold of 7.5 million yen (57,034 USD) per QALY was defined.

Results: The incremental costs per QALY for GCS, DGC, and PGC in the base case study were 3,779,374 JPY (28,740 USD), 86,058,056 JPY (65,4434 USD), and 28,982,059 JPY (220,396 USD), respectively. No parameter had an influence beyond the threshold in a one-way sensitivity analysis. A probabilistic sensitivity analysis revealed that the probability of GCS, DGC, and PGC being cost-effective at the threshold was 85.6%, 0%, and 0%, respectively.

Conclusion: Given the current circumstances, it is probable that triple therapy utilizing GCS will emerge as a plausible and efficient primary chemotherapy strategy for patients with advanced BTC in the Japanese healthcare system, as opposed to DGC and PGC.

Purpose: As long-term survival improves after allogeneic hematopoietic stem cell transplantation (HSCT), the risk for secondary solid cancers, including colon cancer, also increases. However, the pathogenesis of secondary solid cancers in post-HSCT patients remains unclear. This study aimed to investigate the involvement of local immunity in colon carcinogenesis in post-HSCT patients by assessing the infiltrating T cells in colon adenomas as premalignant lesions of colon cancer in adenoma-carcinoma sequence.

Methods: Colon adenoma samples obtained from 19 post-HSCT patients and 57 non-HSCT participants were analyzed via immunohistochemistry. Double staining of CD4/T-bet, CD4/GATA3, and CD4/FoxP3 was performed for evaluation of helper T-cell lineages (Th1, Th2, and regulatory T cells, respectively) and CD8 staining for CD8⁺ T cells.

Results: There were no significant between-group differences in the number of infiltrating CD4⁺ T cells and CD8⁺ T cells in adenomas. However, the number of both CD4⁺/T-bet⁺ and CD4⁺/GATA3⁺ T cells was significantly lower in the post-HSCT adenomas than in the non-HSCT adenomas (P = 0.0171 and 0.0009, respectively), whereas no significant differences were found in the number of CD4⁺/FoxP3⁺ cells.

Conclusion: Although the number of infiltrating CD4⁺ and CD8⁺ T cells, and even Treg cell counts, is sufficiently recovered post-HSCT, CD4⁺ T-cell dysfunction due to suppressed activation and differentiation in colon adenomas might be involved in colon carcinogenesis in post-HSCT patients. Elucidating the pathogenesis will contribute to the development of effective screening and prevention programs for secondary colon cancer in post-HSCT patients.

Objective: Immunotherapy-based regimens (IMT) versus cytotoxic chemotherapy (CHT) improved overall survival (OS) of patients with unresectable or metastatic esophageal squamous cell carcinoma (mESCC), but the role of prognostic variables is unclear. The study aims to explore the interaction of prognostic factors with survival after IMT or CHT.

Methods: A systematic review was performed to select trials comparing IMT and CHT regimens in mESCC patients. A meta-analysis of upfront IMT + CHT vs. CHT trials evaluated the overall effect size and heterogeneity between studies. In view of the expected differences between chemotherapy and immunotherapy on the survival curve, to better explore the effect of any prognostic variables on OS, before and after progression, the treatment arms were evaluated as independent cohorts, and ten baseline variables were extracted and assessed by linear regression.

Results: Fourteen trials were identified. Seven studies compared upfront CHT + IMT vs. CHT documenting longer OS for CHT + IMT (HR 0.69, CI 0.65-0.72), without heterogeneity (Q = 1.43, p value = 0.968) or differences in the most represented subgroups. Twenty-nine study cohorts were selected from the 14 trials. Median OS and PPS, but not PFS, were significantly increased after IMT compared with CHT. The analysis of baseline variables after CHT documented a favorable prognostic effect for advanced age (β = 0.768, p value = 0.016), involvement of 0-1 metastasis sites (β = 0.943, p value = 0.005), and absence of previous radiation therapy (β =  - 0.939, p value = 0.006), while none of them influenced prognosis after IMT.

Conclusion: The introduction of upfront IMT prolonged mESCC patients OS, mostly improving the outcomes of young patients, with multiple metastasis sites and without previous radiotherapy.

Background and objective: Metronomic capecitabine has been found to be useful in several types of cancers such as pancreatic cancer, breast cancer, gastrointestinal cancers, nasopharyngeal carcinoma, and metastatic colorectal cancer. This unique systematic literature review and meta-analysis was undertaken to assess the effectiveness and safety of metronomic capecitabine as a treatment regimen for hepatocellular carcinoma.

Method: A systematic search of major databases was performed. Eight studies that dealt with the use of metronomic capecitabine for hepatocellular carcinoma (HCC) were selected, seven were non-randomized control trials (n-RCTs), and one was a randomized control trial (RCT). Meta-analysis of these studies was performed using Review Manager v5.3 and STATA 15.1 software. The pooled prevalence of overall survival (OS), progression-free survival (PFS), overall response rate (ORR), grade 1-2 adverse events (grade 1-2 AEs), grade 3-4 adverse events (grade 3-4 AEs) was determined, including publication bias and sensitivity analysis.

Result: Eight studies met the inclusion criteria, combining the pooled data of 476 patients from safety and efficacy studies. The pooled prevalence of disease control rate (DCR) and overall response rate (ORR) achieved with metronomic capecitabine was 36% (95% CI 32-41) and 7% (95% CI 5-9) respectively. The median progression-free survival (PFS) and median overall survival (OS) were 3.57 months (95% CI 3.29-3.85) and 11.75 months (95% CI 10.56-12.95) respectively. The incidence of grade 3-4 adverse events (grade 3-4 AEs) and grade 1-2 adverse events (grade 1-2 AEs) was 38% (95% CI 32-44) and 73% (95% CI 67-79) respectively.

Conclusion: This meta-analysis highlights metronomic capecitabine as a potential treatment for hepatocellular carcinoma (HCC) in the advanced stage. However, effective management of capecitabine's side effects is essential.

Purpose: Outcomes of unresectable biliary tract cancer (BTC) with varying extents of liver involvement remain unclear. We evaluated characteristics and outcomes of BTC patients with liver metastases who underwent chemotherapy.

Methods: We retrospectively reviewed consecutive BTC patients with synchronous or metachronous intrahepatic metastases who started first-line chemotherapy at our institution between January 2016 and December 2021.

Results: Ninety-six patients were included, of which 57 only had liver metastases and 39 had multiorgan involvement. The liver only group had longer median overall survival (OS) (11.8 vs. 7.4 months, P = 0.006) and median progression-free survival (PFS) (4.1 vs. 2.7 months, P = 0.035) than the multiorgan group. Patients with oligometastases (defined as no more than three liver metastases) achieved longer OS than those with polymetastases (four or more liver metastases) in the entire cohort. Within the liver only group, there were no significant differences in OS or PFS between the oligometastasis and polymetastasis groups. Patients who underwent subsequent surgery had significantly longer median OS than those who did not (44.4 vs. 7.7 months, P < 0.001). Age ≥ 75 years, liver-only metastasis, modified Glasgow prognostic score ≥ 1 carcinoembryonic antigen ≥ 5 μg/L, and subsequent surgery were independent predictors of OS. Liver oligometastasis was only a significant predictor of longer OS in univariate Cox analysis.

Conclusions: Outcomes in BTC patients with metastases limited to the liver, particularly those with oligometastasis, were more favorable than those with multiorgan metastases. Selected cases, generally with liver oligometastases, may achieve prolonged OS through subsequent surgery.

Purpose: With advances in chemotherapy, conversion surgery is often performed for initially unresectable colorectal cancer liver metastasis (CLM). However, unexpected posthepatectomy liver failure (PHLF) is sometimes associated with chemotherapy-associated liver injuries following long-term chemotherapy. We aimed to identify predictive factors for PHLF after conversion surgery for initially unresectable CLM.

Methods: We retrospectively identified 774 consecutive patients who underwent initial liver resections for histologically confirmed CLMs between 2010 and 2019 at our institute. We enrolled 107 patients with initially unresectable CLMs. Clinicopathological characteristics were evaluated to determine their association with PHLF. Logistic regression analysis was performed to analyze the predictors of PHLF.

Results: Among the 107 patients, PHLF occurred in 15 cases (14%). Multivariate analysis revealed that splenomegaly during preoperative chemotherapy (> 135%) was an independent risk factor for PHLF (P = 0.002; odds ratio 14.30; 95% confidence interval 2.69-76.08). In the analysis limited to the splenomegaly group, lower platelet counts, increased blood loss and operative times, and large liver resection areas (> 100 cm²) were significant risk factors for PHLF (P = 0.018, 0.043, 0.020, and 0.024, respectively). Among them, a liver resection area > 100 cm² can be calculated preoperatively and correlate with a complex hepatectomy.

Conclusion: These findings could help predict PHLF after conversion surgery and induction chemotherapy for initially unresectable CLMs. Careful decisions, including detailed procedures and timing of hepatectomy, should be made before conversion hepatectomy in patients who develop splenomegaly after induction chemotherapy and require complex hepatectomies with a large liver resection area.

Purpose: FOLFOXIRI is a standard treatment for unresectable colorectal cancer (CRC) liver metastases. However, limited data exists on its safety and effectiveness in low-to-middle-income countries (LMICs). This prospective study addresses this gap in a Vietnamese LMIC setting.

Methods: We enrolled 92 patients with unresectable CRC liver metastases between 2022 and 2023. All patients received FOLFOXIRI every 2 weeks, with routine G-CSF prophylaxis to prevent neutropenia. A multidisciplinary team (MDT) assessed diagnoses and treatment responses. Outcomes were R0/R1 resection rate, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs), and recurrence-free survival (RFS) for surgical patients.

Results: The median patient age was 56 years, with a male predominance (70.7%). The primary tumors were located in the left colon (42.4%), rectum (37%), and right colon (20.7%). Thirty-two patients (34.8%) experienced severe (grade 3 or higher) AEs, with thrombocytopenia (13.1%) and anemia (9.8%) being the most frequent. Most patients (72/87, 82.9%) achieved a partial response. The ORR and DCR were 85.1% and 95.4%, respectively. Fifty-seven patients (62%) achieved resectability, and 54 (58.7%) underwent radical surgery. The R0/R1 resection rate was 88.9%. The median PFS and OS for all patients were 13 and 22 months, respectively. The median RFS of surgical patients was 14 months.

Conclusions: FOLFOXIRI improves the response rates, R0/R1 resection rates, and survivals for patients with CRC liver metastases. Future research is necessary to improve the prognosis of patients while minimizing toxicities.

Trial registration: NCT05362825 dated 5 May 2022.

Background: Tumor deposits (TDs) are known to have a poor prognosis independent of lymph node (LN) involvement and are considered equivalent to LN metastases in the latest staging system. In stage III colon cancer (CC), high-risk patients (pT4 or pN2) receive 6 months of adjuvant chemotherapy, while low-risk patients (pT1-3 and N1) are recommended either 3 or 6 months of CAPOX or 6 months of FOLFOX therapy. However, the optimal chemotherapy duration for low-risk patients classified as pN1c remains unknown. The aim of this study is to investigate the impact of adjuvant chemotherapy duration (3 months vs. 6 months) on survival in patients with low-risk stage III CC either in pN1a-b and pN1c patient groups.

Methods: We retrospectively analyzed patients with stage III CC who underwent surgery at a tertiary center between January 2014 and May 2024. Demographic and pathological data of patients were retrospectively collected. The primary outcome was disease-free survival (DFS).

Results: A total of 142 patients were included. Among the patients, 116 were pT1-3N1a-b and 26 were pT1-3N1c. Local (23.1% vs. 1.7%, P < 0.001) and overall (38.5% vs 14.6%, P = 0.011) recurrences were significantly higher in the pN1c group. Univariate and multivariate analyses revealed no significant impact of adjuvant chemotherapy duration on DFS in the pN1a-b group (P = 0.359), whereas in the pN1c group, 3-month chemotherapy resulted in significantly shorter DFS (P = 0.044) in univariate analysis.

Conclusion: Our study indicates that shorter duration of adjuvant chemotherapy is associated with worse survival and 6-month chemotherapy is recommended for patients with pT1-3 and N1c disease.