Neoadjuvant Immunotherapy With Ipilimumab Plus Nivolumab in Mismatch Repair Deficient/Microsatellite Instability-High Colorectal Cancer: A Preliminary Report of Case Series.

BACKGROUND: Although ipilimumab plus nivolumab have significantly improved the survival of metastatic colorectal cancer (CRC) with mismatch repair deficient (dMMR) /microsatellite instability-high (MSI-H), the data on neoadjuvant setting is limited. PATIENTS AND METHODS: We enrolled 11 patients with advanced dMMR/MSI-H CRC. 10 patients were locally advanced and 1 was metastatic. Ten patients were treated with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg), and 1 patient was treated with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg) with 2 cycles. All the patients underwent surgery after immunotherapy. The aim of the study was to evaluate the safety and short-term efficacy of this strategy. RESULTS: Pathologic responses were observed in 11/11 (100%) dMMR/MSI-H tumors, with 9/11 (81.8%) achieving complete responses. Among these 9 cases with complete responses, 1 achieved a radiological noncomplete response after treatment with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg), so another cycle of treatment with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg) was administered, followed by surgery. The postoperative pathological evaluation was a complete response. Seven patients (63.6%) developed grade I/II adverse events. No patients developed grade III/IV adverse events or postoperative complications. CONCLUSION: Neoadjuvant immunotherapy with ipilimumab plus nivolumab induced tumor regression with a major clinical and pathological response in advanced dMMR/MSI-H CRC. Notably, patients do not achieve a complete response to neoadjuvant immunotherapy, additional neoadjuvant immunotherapy may offer benefits. Further research is needed to assess the long-term efficacy of this strategy.

Long-term survival outcomes of laparoscopic versus open gastrectomy for gastric cancer: a systematic review and meta-analysis.

Many meta-analyses have confirmed the technical feasibility and favorable short-term surgical outcomes of laparoscopic gastrectomy (LG) for gastric cancer patients, but the long-term survival outcome of LG remains controversial compared with open gastrectomy (OG). This study aimed to compare the 5-year overall survival (OS), recurrence, and gastric cancer-related death of LG with OG among gastric cancer patients. PubMed was searched to February 2014. The resectable gastric cancer patients who underwent curative LG or OG were eligible. The studies that compared 5-year OS, recurrence, or gastric cancer-related death in the LG and OG groups were included. A meta-analysis, meta-regression, sensitivity analysis, subgroup analysis, and stage-specific analysis were performed to estimate the survival outcome between the two groups and identify the potential confounders. Quality assessment was based on a tailored comparability scoring system. Twenty-three studies with 7336 patients were included. The score of comparability between two groups and the extent of lymphadenectomy were two independent confounders. Based on the well-balanced studies, the 5-year OS (OR = 1.07, 95% CI 0.90-1.28, P = 0.45), recurrence (OR = 0.83, 95% CI 0.68-1.02, P = 0.08), and gastric cancer-related death (OR = 0.86, 95% CI 0.65-1.13, P = 0.28) rates were comparable in LG and OG. Several subsets such as the publication year, study region, sample size, gastrectomy pattern, extent of lymphadenectomy, number of nodes harvested, and proportion of T1-2 or N0-1 did not influence the estimates, if they were well balanced. Particularly, the stage-specific estimates obtained comparable results between the two groups. Randomized controlled trials comparing LG with OG remain sparse to assess their long-term survival outcomes. The major contributions of this systematic review compared with other meta-analyses are a comprehensive collection of available long-term survival outcomes within a much larger number of observations and a more precise consideration of confounders. Current knowledge indicates that the long-term survival outcome of laparoscopic gastric cancer surgery is comparable to that of open surgery among early or advanced stage gastric cancer patients, and LG is acceptable with regard to oncologic safety.

Can K-ras gene mutation be utilized as prognostic biomarker for colorectal cancer patients receiving chemotherapy? A meta-analysis and systematic review.

INTRODUCTION: K-ras gene mutations were common in colorectal patients, but their relationship with prognosis was unclear. OBJECTIVE: Verify prognostic differences between patient with and without mutant K-ras genes by reviewing the published evidence. METHOD: Systematic reviews and data bases were searched for cohort/case-control studies of prognosis of colorectal cancer patients with detected K-ras mutations versus those without mutant K-ras genes, both of whom received chemotherapy. Number of patients, regimens of chemotherapy, and short-term or long-term survival rate (disease-free or overall) were extracted. Quality of studies was also evaluated. PRINCIPAL FINDINGS: 7 studies of comparisons with a control group were identified. No association between K-ras gene status with neither short-term disease free-survival (OR=1.01, 95% CI, 0.73-1.38, P=0.97) nor overall survival (OR=1.06, 95% CI, 0.82-1.36, P=0.66) in CRC patients who received chemotherapy was indicated. Comparison of long-term survival between two groups also indicated no significant difference after heterogeneity was eliminated (OR=1.09, 95% CI, 0.85-1.40, P=0.49). CONCLUSIONS: K-ras gene mutations may not be a prognostic index for colorectal cancer patients who received chemotherapy.

Laparoendoscopic single-site versus traditional laparoscopic surgery in patients with cholecystectomy: a meta-analysis.

OBJECTIVES: To evaluate the primary outcomes of traditional laparoscopic cholecystectomy (TLC) compared with laparoendoscopic single-site cholecystectomy (LESSC). SUBJECTS AND METHODS: Randomized controlled trials (RCTs) comparing TLC with LESSC were included by a systematic literature research. The inclusion and extraction of the data were completed by two authors independently. Meta-analysis was performed using Review Manager version 5.1.4 software. The clinical outcomes were evaluated by odds ratio (OR) and standard mean difference (SMD) according to the different types of data. Sensitivity and heterogeneity analyses were used to account for rationality of pooling data and sources of heterogeneity. RESULTS: Seven RCTs involving 611 patients met the predefined inclusion criteria. The cosmetic score of the LESSC group was significantly higher at 1 week (SMD = 0.48; 95% confidence intervals [CI] 0.24, 0.73; P = .0001), 2 weeks (SMD = 0.87; 95% CI 0.61, 1.13; P < .00001), and 1 month (SMD = 0.88; 95% CI 0.62, 1.44; P<.00001) postoperatively. However, LESSC showed a lesser physical quality of life (PQOL) score at 3 days (SMD = -0.28; 95% CI -0.52, -0.44; P = .02), 1 week (SMD = -0.31; 95% CI -0.55, 0.06; P = .01), and 2 weeks (SMD = -0.30; 95% CI -0.55, -0.05; P = .02) postoperatively. There was no significant difference between the two groups in operating time, perioperative complication, intraoperative blood loss, postoperative hospital stay, Visual Analog Scale pain score, and PQOL on 1 day, 5 days, and 1 month postoperatively. CONCLUSION: LESSC is associated with a higher cosmetic score and a lesser short-term PQOL score compared with TLC.

Duodenal intussusception due to a giant neuroendocrine carcinoma in a patient with Peutz-Jeghers syndrome: case report and systematic review.

Duodenal intussusception is a rare entity. To date, only a few cases have been reported in the literature. In this report, a case of duodenal intussusception due to an unusual tumor was presented and the clinical features of this entity were discussed. A 42-year-old man with Peutz-Jeghers syndrome presented with epigastric pain, vomiting, and severe anemia. Computed tomography scan revealed synchronous duodenojejunal and jejunojejunal intussusceptions. An emergency laparotomy revealed a polypoid mass originating from the lateral wall of the descending duodenum with intussusception of the distal duodenum. Histological examination demonstrated a poorly differentiated neuroendocrine carcinoma with muscularis infiltration, vascular invasion, and a Ki-67 index of 20%. A comprehensive literature search revealed 44 English reports that provided adequate descriptions of an additional 47 such cases. Clinical presentation was usually chronic and nonspecific. Diagnostic modalities included ultrasonography, upper gastrointestinal series, computed tomography, and endoscopy. Five patients were due to a non-neoplastic lesion; however, the other 43 patients were secondary to a tumor, benign in 35 cases and malignant in eight cases. Only one patient was treated by endoscopic polypectomy, whereas the remaining underwent open surgeries. Duodenal intussusception is a challenging condition due to its rarity and nonspecific presentation. It should be considered in the differential diagnosis of gastric outlet obstruction, upper gastrointestinal bleeding, pancreatitis, and obstructive jaundice.

Chaiqin Chengqi Decoction decreases IL-6 levels in patients with acute pancreatitis.

OBJECTIVE: In this paper, we investigated the effect of the traditional Chinese medicine Chaiqin Chengqi Decoction (CQCQD) on serum cytokines in acute pancreatitis (AP) patients. METHODS: Peripheral blood samples from 107 AP patients were collected within the first 48 h of AP onset and on the 10th day of CQCQD treatment. Control samples were collected from 20 healthy individuals. Serum proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and anti-inflammatory cytokines IL-10 and IL-1ß receptor antagonist (IL-1ra) were examined using the Luminex 100 system. RESULTS: Within the first 48 h of AP onset, IL-6 and IL-1ra levels in severe AP (SAP) patients were significantly higher than those in mild AP (MAP) patients, but IL-10 levels in SAP patients were significantly lower than those in MAP patients. Proinflammatory cytokine IL-6 was significantly decreased after CQCQD treatment (P<0.05), especially in SAP patients (n=25 of 36, P<0.05). The hospitalization time of SAP patients was shortened significantly when serum IL-6 decreased after CQCQD treatment (P<0.05). CONCLUSIONS: CQCQD decreased proinflammatory cytokine IL-6 levels in AP patients.