Serum miR-373-3p and miR-194-5p Are Associated with Early Tumor Progression during FOLFIRINOX Treatment in Pancreatic Cancer Patients: A Prospective Multicenter Study.

In this study, we explored the predictive value of serum microRNA (miRNA) expression for early tumor progression during FOLFIRINOX chemotherapy and its association with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 132 PDAC patients of all disease stages were included in this study, of whom 25% showed progressive disease during FOLFIRINOX according to the RECIST criteria. MiRNA expression was analyzed in serum collected before the start and after one cycle of chemotherapy. In the discovery cohort (n = 12), a 352-miRNA RT-qPCR panel was used. In the validation cohorts (total n = 120), miRNA expression was detected using individual RT-qPCR miRNA primers. Before the start of FOLFIRINOX, serum miR-373-3p expression was higher in patients with progressive disease compared to patients with disease control after FOLFIRINOX (Log2 fold difference (FD) 0.88, p = 0.006). MiR-194-5p expression after one cycle of FOLFIRINOX was lower in patients with progressive disease (Log2 FD -0.29, p = 0.044). Both miRNAs were predictors of early tumor progression in a multivariable model including disease stage and baseline CA19-9 level (miR-373-3p odds ratio (OR) 3.99, 95% CI 1.10-14.49; miR-194-5p OR 0.91, 95% CI 0.83-0.99). MiR-373-3p and miR-194-5p did not show an association with OS after adjustment for disease stage, baseline CA19-9, and chemotherapy response. In conclusion, high serum miR-373-3p before the start and low serum miR-194-5p after one cycle are associated with early tumor progression during FOLFIRINOX.

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitis and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitis in perforated diverticulitis (NTR2037).

BACKGROUND: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). METHODS/DESIGN: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs. DISCUSSION: The Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis. TRIAL REGISTRATION: Nederlands Trial Register NTR2037.

Current surgical treatment of diverticular disease in The Netherlands.

AIM: To evaluate the development of diagnostic tools, indications for surgery and treatment modalities concerning diverticular disease (DD) in The Netherlands. METHODS: Data were collected from 100 patients who underwent surgery for DD in three Dutch hospitals. All hospitals used the same standardized database. The collected data included patient demographics, patient history, type of surgery and complications. Patients were divided into two groups, one undergoing elective surgery (elective group) and the other undergoing acute surgery (acute group). RESULTS: Two hundred and ninety-nine patients were admitted between 2000 and 2007. One hundred and seventy-eight patients underwent acute surgery and 121 patients received elective operations. The median age of the 121 patients was 69 years (range: 28-94 years), significantly higher in acute patients (P = 0.010). Laparoscopic resection was performed in 31% of elective patients. In the acute setting, 61% underwent a Hartmann procedure. The overall morbidity and mortality were 51% and 10%, and 60% and 16% in the acute group, which were significantly higher than in the elective group (36% and 1%). Only 35% of the temporary ostomies were restored. CONCLUSION: This study gives a picture of current surgical practice for DD in The Netherlands. New developments are implemented in daily practice, resulting in acceptable morbidity and mortality rates.

A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice.

OBJECTIVE: To review the effectiveness of preoperative biliary drainage (PBD) in patients with obstructive jaundice resulting from tumors. SUMMARY BACKGROUND DATA: This was a systematic review, including a meta-analysis, of randomized controlled trials and comparative cohort studies conducted worldwide and published between 1966 and September 2001, classified on methodologic strength and subdivided into level 1 (randomized controlled trials) and level 2 (comparative cohort studies). METHODS: Comparison was made of PBD versus no PBD in jaundiced patients undergoing resection of a tumor. Outcome measures were in-hospital death rate, overall complications resulting from the treatment modality (drainage- and surgery-related complications), and hospital stay. Effect sizes were calculated and combined in meta-analyses. Relative differences (%) were calculated to compare effects on outcome measures. RESULTS: Five randomized controlled studies comprising 302 patients met the inclusion criteria for level 1 studies, and 18 cohort studies comprising 2,853 patients met the criteria for level 2 studies. Meta-analysis of level 1 studies showed no difference in the overall death rate between patients who had PBD and those who had surgery without PBD. The overall complication rate, however, was significantly adversely affected by PBD compared with surgery without PBD. At level 2, there was no difference in the death rate between the two treatment modalities. The overall complication rate, however, was significantly adversely affected by PBD compared with surgery without PBD. If PBD had been without complications, then complications would be in favor of drainage based on level 1 studies, and no difference based on level 2 studies. Further, PBD was not able to reduce the length of postoperative hospital stay compared with surgery without PBD; instead, it prolonged the stay. CONCLUSIONS: This meta-analysis shows that PBD with current standards for patients with obstructive jaundice resulting from tumors carries no benefit and should not be performed routinely. The potential benefit of PBD in terms of postoperative rates of death and complications does not outweigh the disadvantage of the drainage procedure. Only if PBD-related complications could be reduced by 27% and consequently diminish hospital stay could PBD be beneficial. Further randomized controlled trials with improved PBD techniques are necessary.