The safety, feasibility and oncological outcomes of laparoscopic completion total gastrectomy for remnant gastric cancer: a prospective study with 3-year follow-up (FUGES-004 study).

BACKGROUND: The efficacy of laparoscopic completion total gastrectomy (LCTG) for remnant gastric cancer (RGC) remains controversial. METHODS: The primary outcome was postoperative morbidity within 30 days after surgery. Secondary outcomes included 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence. Inverse probability treatment weighted (IPTW) was used to balance the baseline between LCTG and OCTG. RESULTS: Final analysis included 46 patients with RGC who underwent LCTG at the FJMUUH between June 2016 and June 2020. The historical control group comprised of 160 patients who underwent open completion total gastrectomy (OCTG) in the six tertiary teaching hospitals from CRGC-01 study. After IPTW, no significant difference was observed between the LCTG and OCTG groups in terms of incidence (LCTG vs. OCTG: 28.0% vs. 35.0%, P=0.379) or severity of complications within 30 days after surgery. Compared with OCTG, LCTG resulted in better short-term outcomes and faster postoperative recovery. However, the textbook outcome rate was comparable between the two groups (45.9% vs. 32.8%, P=0.107). Additionally, the 3-year DFS and 3-year OS of LCTG were comparable to those of OCTG (DFS: log-rank P=0.173; OS: log-rank P=0.319). No significant differences in recurrence type, mean recurrence time, or 3-year cumulative hazard of recurrence were observed between the two groups (all P>0.05). Subgroup analyses and concurrent comparisons demonstrated similar trends. CONCLUSIONS: This prospective study suggested that LCTG was non-inferior to OCTG in both short- and long-term outcomes. In experienced centers, LCTG may be considered as a viable treatment option for RGC.

Optimal postoperative surveillance strategies for cancer survivors with gastric neuroendocrine carcinoma based on individual risk: a multicenter real-world cohort study.

BACKGROUND: The best follow-up strategy for cancer survivors after treatment should balance the effectiveness and cost of disease detection while detecting recurrence as early as possible. Due to the low incidence of gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma [G-(MA)NEC], high-level evidence-based follow-up strategies is limited. Currently, there is a lack of consensus among clinical practice guidelines regarding the appropriate follow-up strategies for patients with resectable G-(MA)NEC. MATERIALS AND METHODS: The study included patients diagnosed with G-(MA)NEC from 21 centers in China. The random forest survival model simulated the monthly probability of recurrence to establish an optimal surveillance schedule maximizing the power of detecting recurrence at each follow-up. The power and cost-effectiveness were compared with the National Comprehensive Cancer Network, European Neuroendocrine Tumor Society, and European Society for Medical Oncology Guidelines. RESULTS: A total of 801 patients with G-(MA)NEC were included. The patients were stratified into four distinct risk groups utilizing the modified TNM staging system. The study cohort comprised 106 (13.2%), 120 (15.0%), 379 (47.3%), and 196 cases (24.5%) for modified groups IIA, IIB, IIIA, and IIIB, respectively. Based on the monthly probability of disease recurrence, the authors established four distinct follow-up strategies for each risk group. The total number of follow-ups 5 years after surgery in the four groups was 12, 12, 13, and 13 times, respectively. The risk-based follow-up strategies demonstrated improved detection efficiency compared to existing clinical guidelines. Further Markov decision-analytic models verified that the risk-based follow-up strategies were better and more cost-effective than the control strategy recommended by the guidelines. CONCLUSIONS: This study developed four different monitoring strategies based on individualized risks for patients with G-(MA)NEC, which may improve the detection power at each visit and were more economical, effective. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending follow-up strategies for G-(MA)NEC.

Effect of sarcopenia on short- and long-term outcomes in patients with gastric neuroendocrine neoplasms after radical gastrectomy: results from a large, two-institution series.

BACKGROUND: The relationship between sarcopenia and the prognoses of patients with gastric neuroendocrine neoplasms (g-NENs) is unclear. This study was designed to explore the effects of sarcopenia on short-term and long-term outcomes of patients with g-NENs after radical gastrectomy. METHODS: This study retrospectively collected data from 138 patients with g-NENs after radical gastrectomy. The skeletal muscle index (SMI) diagnostic threshold for sarcopenia was determined using X-tile software. Cox regression analyses were performed to determine the independent risk factors for 3-year overall survival (OS) and 3-year recurrence-free survival (RFS). RESULTS: In this study, 59 patients (42.8%) were diagnosed with sarcopenia. Among patients in the sarcopenia group and nonsarcopenia group, the incidences of total postoperative complications were 33.9 and 30.4%, incidences of serious postoperative complications were 0 and 3.7%, incidences of postoperative surgical complications were 13.6 and 15.2%, and incidences of postoperative systemic complications were 20.3 and 15.2%, respectively (all p > 0.05). The 3-year OS and RFS rates were significantly worse in the sarcopenia group than in the nonsarcopenia group (OS: 42.37% vs 65.82%, p = 0.004; RFS: 52.54% vs 68.35%, p = 0.036). The multivariate analysis revealed a relation between sarcopenia and the long-term prognoses of patients with g-NENs. A stratified analysis based on the pathological type revealed that the Kaplan-Meier curve was only significantly different in patients with gastric mixed adenoneuroendocrine carcinoma (gMANEC) (OS: 40.00% vs 71.79%, p = 0.007; RFS: 51.43% vs 74.36%, p = 0.026); furthermore, the multivariate analysis identified sarcopenia as an independent risk factor for patients with gMANEC (p < 0.05). CONCLUSIONS: Sarcopenia is not related to the short-term prognoses of patients with g-NENs. Sarcopenia is an independent risk factor for patients with gMANEC after radical surgery.

The factors related to failure of Enhanced Recovery after Surgery (ERAS) in colon cancer surgery.

PURPOSE: Enhanced Recovery after Surgery has been proven effective for patients with gastrointestinal cancer. But radical enhanced recovery could also lead to adverse clinical outcomes. Compared with reports on the estimation of successful implementation of enhanced recovery, studies on risk factors of enhanced recovery failure are still lacking. METHODS: A retrospective analysis was carried out on 102 patients in ERAS who underwent elective colon cancer surgery. This study included 102 patients with colon cancer between 2015 and 2019, defining enhanced recovery failure as postoperative length of stay over 10 days, stay in ICU over 24 h after surgery, reoperation, death, or unplanned readmission within 30 days after surgery. Univariate and multivariate analyses were performed to explore potential risk factors of failure. RESULTS: Aged ≥ 75, open operation, number of drainage tube over 1, re-urethral catheterization, and Clavien-Dindo grade over 2 were associated with ERAS failure, according to univariate analysis. Multivariate analysis showed that age ≥ 75 [OR 7.231; P = 0.009]; open operation (OR 3.599; P = 0.021); and number of drainage tube over 1 (OR 3.202; P = 0.020) were independent risk factors for ERAS failure. CONCLUSIONS: We found age ≥ 75, open operation, and number of drainage tube over 1 are independent risk factors associated with ERAS failure after colon cancer surgery.

Failure of enhanced recovery after surgery in laparoscopic colorectal surgery: a systematic review.

PURPOSE: Enhanced recovery after surgery programs has been applied extensively in laparoscopic colorectal surgery. However, several studies have found that some patients fail from ERAS programs. It is important to identify these patients so that remedial action can be taken in a timely manner. The aim of this study was to perform a systematic review of ERAS failure and related risk factors following laparoscopic colorectal surgery. METHODS: A literature search of the PubMed, EMBASE, OVID, and Cochrane databases was performed. The search strategy involved terms related to ERAS, failure, and colorectal surgery. The main outcomes were definitions of ERAS failure and related risk factors. RESULTS: Seven studies including 1463 patients were analyzed. The definition of ERAS failure was mostly associated with a prolonged postoperative length-of-stay (poLOS). Twenty-four kinds of identified risk factors were divided into three parts, the operative part, the pathophysiological part, and the ERAS elements, of which operative factors including more intraoperative blood loss and longer operative duration were the most frequently identified. CONCLUSIONS: ERAS failure was mostly related to a prolonged poLOS, and operative factors were the most frequently identified risk factors for ERAS failure following laparoscopic colorectal surgery. These findings will help physicians to take remedial action in a timely manner. Nonetheless, high-quality randomized controlled trials following a standardized framework for evaluating ERAS programs are needed in the future.

Comparison of Single-Incision and Conventional Laparoscopic Sleeve Gastrectomy for Morbid Obesity: a Meta-Analysis.

BACKGROUND: Single-incision laparoscopic sleeve gastrectomy (SILSG) has been proposed as an alternative to conventional laparoscopic sleeve gastrectomy (CLSG) in obese patients. This study aims to compare the surgical outcomes of these two techniques. METHODS: A meta-analysis of existing literature obtained through a systematic literature search in the PubMed, EMBASE, and Cochrane Library CENTRAL databases from 2009 to 2019 was conducted. RESULTS: Eleven articles including 1168 patients were analyzed. Patients in the SILSG group reported greater satisfaction with cosmetic scar outcomes than those in the CLSG group (SMD = 2.47, 95% CI = 1.10 to 3.83, P = 0.00). There was no significant difference between the SILSG group and the CLSG group regarding operative time, intraoperative estimated blood loss, conversion rate, intraoperative complications, length of hospital stay, postoperative analgesia, postoperative complications, excess weight loss (EWL), and improvements in comorbidities (P > 0.05). CONCLUSIONS: Compared to CLSG, SILSG resulted in improved cosmetic satisfaction and showed no disadvantages in terms of surgical outcomes; thus, SILSG can serve as an alternative to CLSG for obese patients. Nonetheless, high-quality randomized controlled trials (RCTs) with large study populations and long follow-up periods are needed.

Conditional survival and recurrence of remnant gastric cancer after surgical resection: A multi-institutional study.

The present study was designed to evaluate the dynamic survival and recurrence of remnant gastric cancer (RGC) after radical resection and to provide a reference for the development of personalized follow-up strategies. A total of 298 patients were analyzed for their 3-year conditional overall survival (COS3), 3-year conditional disease-specific survival (CDSS3), corresponding recurrence and pattern changes, and associated risk factors. The 5-year overall survival (OS) and the 5-year disease-specific survival (DSS) of the entire cohort were 41.2% and 45.8%, respectively. The COS3 and CDDS3 of RGC patients who survived for 5 years were 84.0% and 89.8%, respectively. The conditional survival in patients with unfavorable prognostic characteristics showed greater growth over time than in those with favorable prognostic characteristics (eg, COS3, ≥T3: 46.4%-83.0%, Δ36.6% vs ≤T2: 82.4%-85.7%, Δ3.3%; P < 0.001). Most recurrences (93.5%) occurred in the first 3 years after surgery. The American Joint Committee on Cancer (AJCC) stage was the only factor that affected recurrence. Time-dependent Cox regression showed that for both OS and DSS, after 4 years of survival, the common prognostic factors that were initially judged lost their ability to predict survival (P > 0.05). Time-dependent logistic regression analysis showed that the AJCC stage independently affected recurrence within 2 years after surgery (P < 0.05). A postoperative follow-up model was developed for RGC patients. In conclusion, patients with RGC usually have a high likelihood of death or recurrence within 3 years after radical surgery. We developed a postoperative follow-up model for RGC patients of different stages, which may affect the design of future clinical trials.

A novel prognosis prediction model after completion gastrectomy for remnant gastric cancer: Development and validation using international multicenter databases.

BACKGROUND: Examined lymph node counts of remnant gastric cancer patients are often insufficient, and the prognostic ability of tumor-node-metastasis staging is therefore limited. This study aimed to create a simple and universally applicable prediction model for RGC patients after completion of gastrectomy. METHODS: A 5-year overall survival prediction model for remnant gastric cancer patients was developed using a test dataset of 148 consecutive patients. Model coefficients were obtained based on the Cox analysis of clinicopathological factors. Prognostic performance was assessed with the concordance index (C-index) and decision curve analysis. For internal validation, the bootstrap method and calibration assessment were used. The model was validated using 2 external cohorts from China (First Affiliated Hospital of Fujian Medical University, n = 46) and the United States (Mayo Clinic, n = 20). RESULTS: Depth of tumor invasion, number of metastatic lymph nodes, distant metastasis, and operative time were independent prognostic factors. Our model's C-index (0.761) showed better discriminatory power than that of the eighth tumor-node-metastasis staging system (0.714, P = .001). The model calibration was accurate at predicting 5-year survival. Decision curve analysis showed that the model had a greater benefit, and the results were also confirmed by bootstrap internal validation. In external validation, the C-index and decision curve analysis showed good prognostic performances in patient datasets from 2 participating institutions. Moreover, we verified the reliability of the model in an analysis of patients with different examined lymph node counts (>15 or ≤15). CONCLUSION: Utilizing clinically practical information, we developed a universally applicable prediction model for accurately determining the 5-year overall survival of remnant gastric cancer patients after completion of gastrectomy. Our predictive model outperformed tumor-node-metastasis staging in diverse international datasets regardless of examined lymph node counts.

Development and External Validation of Web-Based Models to Predict the Prognosis of Remnant Gastric Cancer after Surgery: A Multicenter Study.

BACKGROUND: Remnant gastric cancer (RGC) is a rare malignant tumor with poor prognosis. There is no universally accepted prognostic model for RGC. METHODS: We analyzed data for 253 RGC patients who underwent radical gastrectomy from 6 centers. The prognosis prediction performances of the AJCC7th and AJCC8th TNM staging systems and the TRM staging system for RGC patients were evaluated. Web-based prediction models based on independent prognostic factors were developed to predict the survival of the RGC patients. External validation was performed using a cohort of 49 Chinese patients. RESULTS: The predictive abilities of the AJCC8th and TRM staging systems were no better than those of the AJCC7th staging system (c-index: AJCC7th vs. AJCC8th vs. TRM, 0.743 vs. 0.732 vs. 0.744; P>0.05). Within each staging system, the survival of the two adjacent stages was not well discriminated (P>0.05). Multivariate analysis showed that age, tumor size, T stage, and N stage were independent prognostic factors. Based on the above variables, we developed 3 web-based prediction models, which were superior to the AJCC7th staging system in their discriminatory ability (c-index), predictive homogeneity (likelihood ratio chi-square), predictive accuracy (AIC, BIC), and model stability (time-dependent ROC curves). External validation showed predictable accuracies of 0.780, 0.822, and 0.700, respectively, in predicting overall survival, disease-specific survival, and disease-free survival. CONCLUSIONS: The AJCC TNM staging system and the TRM staging system did not enable good distinction among the RGC patients. We have developed and validated visual web-based prediction models that are superior to these staging systems.

A modified subclassification to evaluate the survival of patients with N3 gastric cancer: an international database study.

BACKGROUND: The eighth TNM classification for gastric cancer categorizes N3 as N3a and N3b in the final pathologic stage. The cutoff for N3a/N3b is defined as 15 metastatic lymph nodes, but the rationale for this cutoff remains unclear. This study aimed to determine the optimal N3a/N3b cutoff and evaluate its prognostic significance. METHODS: An international database was constructed by combining data from patients with N3 gastric cancer and complete five-year follow-up data from the Surveillance, Epidemiology, and End Results program database (n = 1833) and the Fujian Medical University Union Hospital database (n = 920) (total n = 2753). A log-rank test was performed to determine the optimal N3a/N3b cutoff, and its prognostic significance was confirmed in a two-step multivariate analysis and compared to that of the eighth TNM. RESULTS: A cut-point analysis performed at each metastatic lymph node number identified the greatest survival difference between N3a and N3b at 13 metastatic lymph nodes (χ2 = 157.671, P = 3.65 × 10- 36). In patients with 14-15 metastatic lymph nodes, prognoses were significantly worse than those in patients with 7-13 metastatic lymph nodes (P < 0.001) but similar to those in patients with > 15 metastatic lymph nodes (P = 0.078). Therefore, patients with 14-15 metastatic lymph nodes were incorporated into a modified N3b classification. In the two-step multivariate analysis, the eighth N3 classification fell out of the model, while the modified N3 classification remained intact (HR 1.51, P < 0.001). Further analyses demonstrated that the modified TNM classification had superior homogeneity, discriminatory ability, and gradient monotonicity compared to the eighth TNM classification. CONCLUSIONS: For improved prognostic stratification, we recommend adjusting the cutoff for subclassification of N3 gastric cancer to 13 metastatic lymph nodes.

Multiple gene mutations in patients with type 2 autoimmune pancreatitis and its clinical features.

BACKGROUND: It is now clear that there are two histological types (type 1 and type 2) of autoimmune pancreatitis (AI P). The histological substance of type 1 AI P is known as lymphoplasmacytic sclerosing pancreatitis (LPSP) or traditional AIP, and type 2 AIP is characterized by distinct histology called idiopathic duct centric pancreatitis (IDCP). Serum IgG4 increase is considered as a marker for type 1 AI P. Far less is known about type 2 and it lacks predicting markers, so it easily leads to missed diagnosis and misdiagnosis. THE AIM OF THIS STUDY: The aim of this study was to describe multi-gene mutations in patients with type 2 AI P and its clinical features. MATERIAL AND METHODS: Three unrelated patients with type 2 AI P, 10 cases with type 1 AIP, 15 cases with other chronic pancreatitis and 120 healthy individuals were studied. The mutations and polymorphisms of 6 genes involved in chronic pancreatitis or pancreatic cancer - PRSS1, SPINK1, CFTR, MEN1, PKHD1, and mitochondrial DNA - were sequenced. Information of clinical data was collected by personal interview using a structured questionnaire. RESULTS: Novel mutations were found in the genes encoding for MEN1 (p.546 Ala > The) and PKHD1 (c. 233586 A > G and c. 316713 C > T) from patients with type 2 AIP. What is more, the serum TCR (T cell receptor) level is relatively higher in patients with type 2 AIP than in patients with type 1 AIP and other chronic pancreatitis or normal controls. Weight loss was the major manifestation and no patients had extrapancreatic involvement in type 2 AIP. CONCLUSIONS: Type 2 AIP may occur with multi-gene mutations. For screening purposes, it is more reasonable to evaluate TCR levels in serum.

PRSS1_p.Leu81Met mutation results in autoimmune pancreatitis.

AIM: To describe protease serine 1 (PRSS1) gene mutations in patients with autoimmune pancreatitis (AIP) and the clinical features of AIP. METHODS: Fourteen patients with AIP, 56 with other chronic pancreatitis, 254 with pancreatic cancer and 120 normal controls were studied. The mutations and polymorphisms of four genes involved with pancreatitis or pancreatic cancer, PRSS1, SPINK1, CFTR and MEN1, were sequenced. The pathogenic mechanism of AIP was investigated by comparing the wild-type expression system with the p.81Leu→Met mutant expression system. RESULTS: Two novel mutations (p.81Leu→Met and p.91Ala→Ala) were found in PRSS1 gene from four patients with AIP. PRSS1_p.81Leu→Met mutation led to a trypsin display reduction (76.2%) combined with phenyl agarose (Ca(2+) induced failure). Moreover, the ratio of trypsin/amylase in patients with AIP was higher than in the patients with pancreatic cancer and other pancreatitis. A large number of lymphocytes and plasma cells were found in the bile ducts accompanied by hyperplasia of myofibroblasts. CONCLUSION: Autoimmune pancreatitis may be related to PRSS1 gene mutations.

[A prospective randomized controlled trial of Sapylin combined with chemotherapy for advanced colon cancer following radical operation].

OBJECTIVE: To evaluate the effect of Sapylin combined with intraperitoneal and systemic chemotherapy for advanced colon cancer following radical operation on local recurrence, hepatic metastasis, and overall survival rate. METHODS: From Jan. 2004 to Dec. 2005,132 patients with stage II or III colon carcinoma after radical operation were randomly divided into two groups: Sapylin combined with chemotherapy(Sapylin) group and the control group. Toxic reaction, local recurrence, hepatic metastasis, and overall survival rate between two groups were compared. RESULTS: Both groups successfully completed the trial. There was no significant difference in toxic reaction between two groups, the recurrence and hepatic metastasis rate in Sapylin group were lower than those in the control group(9/60, 15.0% vs. 22/72, 30.6%; 11/60,18.3% vs. 22/72, 34.7%, respectively), which were statistically significant (P<0.05 respectively). The 3- year survival rate in Sapylin group was higher than that in control group(73.3% vs. 54.2%), which was statistically significant (P<0.05). CONCLUSION: Sapylin combined with intraperitoneal and systemic chemotherapy can effectively decrease local recurrence and hepatic metastasis,and improve the survival in patients with advanced colon cancer following radical operation.

Addition of hepatectomy decreases liver recurrence and leads to long survival in hilar cholangiocarcinoma.

AIM: To evaluate hepatic recurrence and prognostic factors for survival in patients with surgically resected hilar cholangiocarcinoma in a single institution over the last 13 years. METHODS: From 1994 to 2007, all patients with hilar cholangiocarcinoma referred to a surgical clinic were evaluated. Demographic data, tumor characteristics, and outcome were analyzed retrospectively. Outcome was compared in patients who underwent additional liver resection with resection of the tumor. RESULTS: Of the 69 patients submitted to laparotomy for tumor resection, curative resection (R(0) resection) was performed in 40 patients, and palliative resection in 29. Thirty-one patients had only duct resection, and 38 patients had combined duct resection with liver resection including 34 total or part caudate lobes. Curative rates with the combined hepatectomy were significantly improved compared with those without additional hepatectomy (27/38 vs 13/31; chi2 = 5.94, P < 0.05). Concomitant liver resection was associated with a decreased incidence of initial recurrence in liver one year after surgery (11/38 vs 23/31; chi2 = 13.98, P < 0.01). The 3-year survival rate after R(0) resection was 30.7% and was 10.5% for palliative resection. R(0) resection improved the 3-year survival rate (30.7% vs 10.5%; chi2 = 12.47, P < 0.01). CONCLUSION: Hepatectomy, especially including the caudate lobe combined with bile duct resection should be considered standard treatment to cure hilar cholangiocarcinoma.

Antisense RhoC gene suppresses proliferation and invasion capacity of human QBC939 cholangiocarcinoma cells.

BACKGROUND: Cholangiocarcinoma is a highly aggressive, fatal malignancy, which is resistant to all current therapeutic approaches. The recent elevation in the incidence of cholangiocarcinoma has highlighted the need for novel approaches targeting the molecular basis of its invasiveness. Previously we reconstructed a RhoC antisense eukaryotic expression vector and transfected it into a cholangiocarcinoma cell line (QBC939) by the lipofectamine method. This study was undertaken to determine the effect of the antisense RhoC gene on the proliferation and invasion capacity of QBC939. METHODS: Antisense RhoC cDNA was transfected into QBC939 with lipofectin 2000. The cell growth curve was constructed to determine the proliferation rate of cells; flow cytometry was used to analyze cell cycle changes of the tumor cells; and a Boyden chamber was used to assess the invasive ability of the cells before and after gene transfection. RESULTS: After the antisense RhoC cDNA was transfected, the number of colonies formed was significantly lower than that in the other two groups (54+/-8 vs. 91+/-11 vs. 90+/-9, P<0. 05) so was the number of the cells which crossed to the lower surface of the matrigel-coater filters (36+/-6 vs. 96+/-12 vs. 95+/-7, P<0.05). There was also a higher percentage of transfected cells in G1 phase than in the other two groups (52.5% vs. 43.4% vs. 43.7%). CONCLUSION: The antisense RhoC gene can suppress the capacities of proliferation and invasion in a cholangiocarcinoma cell line in vitro.