Journal of Gastrointestinal Cancer最新文献

Background: Complete mesocolon excision (CME) and central vascular ligation for right colonic cancers have been developed to improve oncological outcomes. However, it has been linked with a higher risk of morbidity and technical difficulties in operating near major vessels. This study investigated the impact of preoperative surgical planning utilizing CT reconstruction on surgical outcomes in right colectomy with CME.

Methods: This systematic review and meta-analysis followed PRISMA and AMSTAR 2 guidelines. The analysis included clinical trials and observational studies comparing outcomes after preoperative CT scan reconstruction (navigation group) vs. no preoperative CT reconstruction (control group).

Results: Four eligible studies (published between 2013 and 2023) were included, comprising 420 patients (203 in the navigation group and 217 in the control group). Preoperative navigation was associated with significantly lower blood loss (SMD = - 77.50; 95% CI [- 126.77, - 28.22], p = 0.002), shorter operative time (SMD = - 24.44; 95% CI [- 33.33, - 15.55], p < 0.00001), and a higher number of harvested lymph nodes (SMD = 1.39; 95% CI [0.58, 2.20], p = 0.0007). There was no statistically significant difference between the two groups in terms of overall morbidity (OR = 0.82; 95% CI [0.28, 2.40], p = 0.71), intraoperative complications (OR = 1.39; 95% CI [0.37, 5.26], p = 0.63), anastomotic leak (OR = 1.10; 95% CI [0.16, 7.63], p = 0.92), or hospital stay (SMD = - 0.06; 95% CI [- 0.48, 0.37], p = 0.80).

Conclusion: Preoperative navigation using CT reconstruction could help better delineate the complex vascular anatomy of the right colon. It may reduce operative time and increase the yield of harvested lymph nodes.

Background and objective: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Despite advances in treatment, metastatic colorectal cancer (mCRC) remains a significant challenge due to its heterogeneity and resistance to therapy. Regorafenib, a multikinase inhibitor, can inhibit tumor progression through multiple mechanisms, thereby improving patient prognosis. It has emerged as a potential treatment option for mCRC patients who have progressed on standard therapies. This systematic review and meta-analysis aims to evaluate the efficacy and safety of Regorafenib in this patient population, synthesizing data from clinical trials to provide a comprehensive understanding of its role in mCRC treatment.

Methods: A systematic literature search was conducted via the PubMed, Web of Science (WOS), and Embase databases from January 2012 to December 2024. Studies were included if they were randomized controlled trials (RCTs) or clinical trials that reported outcomes of regorafenib treatment in mCRC patients, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Secondary outcomes included the incidence of serious adverse events (SAEs). OS refers to the length of time from the start of treatment until the death of the patient from any cause, while mortality specifically denotes the number of deaths occurring within the study period. Data were extracted by two independent reviewers using a standardized form. The meta-analysis was performed using RevMan 5.0 statistical software.

Results: A total of 5,082 articles were retrieved, and ultimately, 9 eligible studies involving a total of 2,823 patients were included. All 9 included studies reported OS and PFS. In these mCRC patients, the dose of regorafenib was usually 160 mg daily. The meta results indicated that the OS of patients in the regorafenib group was significantly different [MD = 1.33, 95% CI (0.33, 2.33), P = 0.009]. Eight studies reported the ORR of the disease [OR = 1.13, 95% CI (0.73, 1.76), P = 0.57]. Five studies reported the DCR, and the DCR of patients in the regorafenib group was significantly different from that of patients in the control group [OR = 3.45, 95% CI (2.04, 5.84), P < 0.00001]. The incidence of SAEs (> grade 3) was reported in all 9 included studies [OR = 2.48, 95% CI (1.29, 4.73), P = 0.006].

Conclusion: In this systematic review of prospective trials, regorafenib resulted in improved OS with manageable adverse effects for patients with advanced mCRC. Still, considering the safety, future research should focus on investigating the dose optimization of regorafenib, as well as predictive biomarkers for therapeutic efficacy.

Background: The prognosis of esophageal squamous cell carcinoma (ESCC) with obstruction is unclear. This study aimed to analyze clinical outcomes and prognosis of patients with ESCC and obstruction.

Methods: Patients with advanced ESCC were included and divided into obstructive and non-obstructive groups. Clinical outcomes and survival according to treatment were compared between these groups.

Results: Among 353 patients with advanced ESCC, obstruction was present in 105 (29.7%). ESCC with obstruction was more common in the upper thoracic location (23.8% vs. 14.5%, p = 0.036) and had a higher stage (7.6% vs. 32.7%, p < 0.001 in stage 2; 41.0% vs. 24.2%, p = 0.002 in stage 4) than those without obstruction. The median survival time of patients with obstruction was significantly shorter than that of patients without obstruction (7.6 months vs. 20.2 months, p < 0.001). Patients with obstruction had a significantly lower survival rate regardless of treatment. When surgery was performed first on patients with obstruction, the R0 resection rate was significantly lower (33.3% vs. 88.5%, p < 0.001). For patients with obstruction in resectable stages, surgery after neoadjuvant chemoradiotherapy resulted in the best survival (HR: 0.48; 95% CI: 0.15 - 1.49; p = 0.201). When only chemoradiotherapy was performed in resectable stages, clinically complete response rate was significantly lower (35.3% vs. 64.9%, p = 0.035) in the obstructive group.

Conclusion: ESCC with obstruction was at a more advanced stage and had a poor prognosis regardless of treatment. Surgery first or chemoradiotherapy alone is not recommended for these patients. Neoadjuvant chemoradiotherapy prior to surgical resection is recommended for those with ESCC and obstruction at resectable stages.

Background and aims: To investigate gender, racial, ethnic, and regional disparities in first and senior authorship positions in gastroenterology/hepatology-related randomised controlled trials (RCT).

Method: Retrospective bibliometric analysis of PubMed-indexed RCTs published between January 2000 to December 2022 in leading journals with an impact factor of at least five.

Results: 943 RCTs met our inclusion criteria, providing a participant pool of 301 female (15.96%) and 1,585 male (84.04%) authors from 37 countries (70% high-income countries). Despite a significant increase in the proportion of female authors in first and senior authorship positions between 2000 and 2022 (p<0.001), females were grossly underrepresented in both authorship positions, with a male-to-female ratio of 4.45 and 6.37, respectively. The male-to-female ratio was highest among Asian authors (7.79) than among White (4.22), Hispanic (1.44), and Black (1) authors in the first authorship position. In contrast, the male-to-female ratio was similar for Asian (6.2) and White (6.67) authors in the senior authorship position, with a low underlying frequency of Hispanic and Black female authors.

Conclusion: Despite significant improvements in gender, racial and ethnic representation in first and senior authorship of gastroenterology/hepatology-related RCTs published in high-impact journals, progress toward parity remains slow. Targeted interventions to improve author diversity are warranted.

Background: Hepatic angiosarcoma (HA) is a rare malignant vascular neoplasm. Currently, there are no standardized protocols for treating HA. This study aims to understand clinicopathologic analysis, prognostic factors, and treatment outcomes comprehensively.

Methods: The data retrieved from the SEER database was reviewed for hepatic angiosarcoma cases between 2000 and 2021.

Results: A total of 389 patients with hepatic angiosarcoma were identified with a mean age of 63.9 years (SD ± 16). Most patients were male (64%), and per US census data, non-Hispanic Asians or Pacific Islanders were the most common race (17%). In known cases of tumor stage (61%), the most common tumor stage was distant (22%), and most were grade III (18%) tumors. Overall, the 3-year survival rate was 6.7% with a 95% confidence interval (95% CI 0.044-0.100), disease-specific survival at a 1-year survival rate was 4.43% (95% CI 0.023-0.083), and no patients survived by 3 years. The best overall survival rate was the 1-year rate for surgical resection, 18.20% (95% CI 0.075-0.441). Chemotherapy had a 1-year survival rate of 11% (95% CI 0.057-0.211), and radiation therapy had no survival significance (p = 0.2). Multivariate analysis shows age above 70 years (H.R. 1.67 (95% CI 1.181-2.381), p < 0.05), no surgical intervention (H.R. 2.29 (95% CI 1.585-3.336) p < 0.001), and distant stage (H.R. 2.54 (95% CI 1.696-3.805) p < 0.001) are negative prognostic factors, whereas female sex (H.R. 0.68 (95% CI 0.536-0.875) p < 0.05) is a positive prognostic factor.

Conclusion: Increasing age (> 70 years), male sex, and distant stage were found to be strong predictors of poor survival outcomes. Patients had better outcomes when surgical resection and chemotherapy were included in their treatment. These results can provide continued evidence in the future management of patients with hepatic angiosarcoma.

Background: The clinicoradiological staging for esophageal cancer is fraught with variable accuracy, potentially depriving patients who have been understaged of the benefit of neoadjuvant therapy, which has been shown to improve long-term survival in locally advanced malignancies. It is imperative to identify these high-risk tumors for tailored treatment.

Methods: Retrospective analysis of a prospective database of patients undergoing esophagectomy for carcinoma esophagus between 2011 and 2019. Patients with clinicoradiological early-stage esophageal carcinoma (T1/2 and N0), staged with EUS and fluoro-deoxy-glucose positron emission tomography with contrast-enhanced computed tomography (FDG PET-CECT), and undergoing upfront surgery were included. Demographic profile, staging, perioperative outcomes, and follow-up data were extracted from electronic records and analyzed using SPSS 26.0.

Results: During this period, we performed 1496 esophagectomies, of which 68 patients (4.5%) underwent upfront surgery for early-stage tumors. The overall concordance between clinical and surgical staging was 55.8%. The positive predictive value (PPV) of EUS for T1, T2, and N0 was 81.6%, 46.7%, and 82.4%, respectively, with 10.2% and 17% upstaging to T3 and N + , respectively. On multivariate analysis, T2 on EUS and tumors longer than 3.5 cm and having standardized uptake value (SUVmax) > 3.05 on FDG PET were strong predictors of stage migration. The 3-year overall survival (OS) of the entire cohort was 74.2%, while those who were understaged had a worse outcome, with a 3-year survival of 48.2%.

Conclusion: Endoscopic T2 stage, length more than 3.5 cm, and SUVmax more than 3.05 are associated with significant understaging and hence should be considered for neoadjuvant therapy.

Purpose: Neoadjuvant therapy (NT) is increasingly used for gastrointestinal (GI) and hepatopancreatobiliary (HPB) cancers. Risk factors for surgical attrition during NT are poorly understood. A planned secondary analysis of patient-reported outcomes (PROs) from a prospective cohort study of patients undergoing NT was performed to identify factors associated with surgical attrition.

Methods: Adult patients with GI/HPB cancer receiving NT were provided a mobile phone application administering QOL assessments every 30 days and measuring mood/symptoms until NT completion. Univariate and multivariate logistic regression were performed to determine the association between demographic, clinical characteristics, and PROs with surgical attrition (no surgery (NS) versus surgery or watchful waiting (SWW)). Mixed-effects regression models evaluated trends of QOL and symptoms between the cohorts.

Results: Among 104 enrolled patients, mean age was 60.5 ± 11.5 years, 57 (55%) were male, and 95 (91%) were Caucasian. After a mean duration of 3.4 months of NT, 76 (73%) patients underwent SWW, while 28 (27%) did not (NS). Cancer type (HPB vs GI, OR 7.0, CI 2.7-19.3, p < 0.001), comorbidities (OR 1.72, CI 1.0-2.99, p = 0.05), and severe complications during NT (OR 4.2, CI 1.2-15.3, p = 0.03) were associated with NS. There were no differences between longitudinal QOL scores or PROs among patients who underwent SWW versus NS except for the lack of appetite, which was associated with NS (OR 3.6, CI 1.0-12.2, p = 0.04).

Conclusions: Among patients undergoing NT for GI/HPB malignancies, type of cancer, comorbidities, and severe complications during NT were associated with failure to undergo surgery, whereas QOL and PROs were largely not.

Purpose: Interval to surgery following short course radiotherapy (SCRT) for rectal cancer is not standardized. This study investigated pathologic outcomes and survival with varying intervals to surgery.

Methods: Using the National Cancer Database, adults who received SCRT from 2005 to 2020 were grouped by additional neoadjuvant chemotherapy. Outcomes were analyzed for early (within 1 week) and delayed (over 4 weeks) intervals.

Results: Of 1154 patients, 671 received neoadjuvant SCRT and chemotherapy (Group 1: median interval 29 days, 50% delayed) and 483 received SCRT only (Group 2: median interval 9 days, 27% delayed). In Group 1, delay was associated with tumor downstaging (OR 1.61; 95% CI, 1.03-2.51; p = 0.036), decreased lymphovascular invasion (OR 0.53; 95% CI, 0.33-0.85; p = 0.009), and complete pathologic response (OR 2.86; 95% CI, 1.06-7.76; p = 0.039). Delay was associated with decreased tumor deposits in Group 1 (OR 0.46; 95% CI, 0.30-0.71; p < 0.001) and Group 2 (OR 0.37; 95% CI 0.21-0.65; p = 0.001). Survival was not affected.

Conclusion: Delaying surgery following neoadjuvant SCRT results in favorable pathologic outcomes without impacting overall survival, regardless of neoadjuvant chemotherapy.

Purpose: MET amplification (amp) is a driver of acquired resistance to epidermal growth factor receptor (EGFR) antibodies in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC). Savolitinib is an oral small molecule tyrosine kinase inhibitor that has demonstrated anti-tumor activity in MET-driven advanced solid tumors. We report the results of a phase 2 study of savolitinib in patients with mCRC with MET amp detected by circulating cell free (cf)DNA.

Methods: Patients with chemotherapy refractory mCRC and MET amp detected by cfDNA were treated with savolitinib until unacceptable toxicity or disease progression. The primary endpoint was objective response rate. Secondary endpoints were clinical activity and safety.

Results: Five patients were enrolled and treated. Best overall response was stable disease (SD) in two patients, progressive disease (PD) in two patients, and one patient unevaluable for response. The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2. The most common TEAEs included fatigue (n = 3) and nausea (n = 3). There were no grade 4 or 5 TEAEs.

Conclusion: Savolitinib was well tolerated; however, in this small group of biomarker-selected patients, we observed no evidence of anti-tumor activity.

Trial registration: Clinicaltrials.gov Identifier: NCT03592641. Registered on July 17, 2018.

Background: Metastatic colorectal cancer (mCRC) remains a significant clinical challenge. While anti-EGFR inhibitors have improved survival rates, their long-term efficacy is limited by disease progression, which is often associated with the development of acquired resistance mutations. However, some patients may regain sensitivity to anti-EGFR agents after alternative therapies, suggesting a potential benefit for rechallenge strategies. Our study aims to conduct a systematic review and meta-analysis to comprehensively evaluate the efficacy and safety of EGFR rechallenge in patients with mCRC.

Methods: A systematic search of the MEDLINE, EMBASE, and Cochrane databases was conducted between October 28 and December 24, 2023, to identify clinical trials investigating treatment regimens incorporating panitumumab or cetuximab as a rechallenge strategy. Pooled proportions or hazard ratios (HR) were calculated using a random effects model. Inter-study heterogeneity was assessed using the I².

Results: Among the 2105 articles identified through the search, 13 met the predetermined inclusion criteria. Of these, 12 were phase II studies, encompassing 92.3% of the patient population. Cetuximab was administered to 302 patients (75.1%), whereas panitumumab was utilized in 100 patients (24.9%).A pooled analysis of eight studies demonstrated an objective response rate of 20.50% (95% CI 7.94 to 33.07) and a disease control rate of 67.35% (95% CI 58.60 to 76.09). The median progression-free survival was estimated at 3.5 months (95% CI 2.68-6.69), with a median OS of 9.8 months (95% CI 6.71-12.89). Patients exhibiting RAS wild-type status in circulating tumor DNA (ctDNA) analysis derived enhanced benefits from anti-EGFR rechallenge (HR: 0.41; 95% CI 0.28-0.60, I² = 60%). Common grade 3 or higher treatment-related adverse events included neutropenia (22.8%) and rash (14.9%).

Conclusion: This meta-analysis underscores the efficacy and safety of anti-EGFR rechallenge as a promising therapeutic approach for a subset of patients afflicted with mCRC. The observed correlation between wild-type RAS status, as determined through ctDNA analysis, and improved OS signals the prospect of precision oncology in guiding treatment decisions.