Antibiotic resistance patterns of bacterial bile cultures during pancreatic surgery-a single center analysis and systematic review.

BACKGROUND: Septic complications after pancreatic surgery are common. However, it remains unclear if and how a shift of the microbiological spectrum affects morbidity. The aim of the present study was to assess the microbiological spectrum and antibiotic resistance patterns and their impact on outcome. METHODS: We conducted a retrospective study including patients undergoing pancreatic surgery at our center between 2005 and 2018. A systematic literature review and descriptive meta-analysis of the published and original data was performed according to the PRISMA guidelines. RESULTS: A total of 318 patients were included in the analysis. Patients with biliary drainage had a significantly higher incidence of bacterobilia (93% vs. 25%) and received preoperative antibiotics (46% vs. 12%). The analyzed bile cultures showed no resistance to piperacillin/tazobactam, fluoroquinolones, or carbapenems. Resistance to cefuroxime was seen in 58% of the samples of patients without biliary drainage (NBD) and 93% of the samples of those with drainage (BD). In general, there was no significant difference in overall postoperative morbidity. However, superficial surgical site infections (SSIs) were significantly more common in the BD group. We included a total of six studies and our own data (1627 patients) in the descriptive meta-analysis. The percentage of positive bile cultures ranged from 53 to 81%. In patients with BD, the most frequent microorganisms were Enterococcus spp. (58%), Klebsiella spp. (29%), and E. coli (27%). Almost all studies demonstrated resistance to first- and second-generation cephalosporins and to third- and fourth-generation cephalosporins for patients with BD. CONCLUSION: A change in perioperative antibiotic strategy according to local resistance patterns, especially after BD, might be useful for patients undergoing pancreatic surgery. Appropriate perioperative antibiotic coverage may help to prevent abdominal infectious complications and especially superficial SSIs.

Pancreatoduodenectomy with or without prophylactic falciform ligament wrap around the hepatic artery for prevention of postpancreatectomy haemorrhage: randomized clinical trial (PANDA trial).

BACKGROUND: Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels. METHODS: In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH. RESULTS: Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively). CONCLUSION: A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy. REGISTRATION NUMBER: NCT02588066 (http://www.clinicaltrials.gov).

More is More? Total Pancreatectomy for Periampullary Cancer as an Alternative in Patients with High-Risk Pancreatic Anastomosis: A Propensity Score-Matched Analysis.

BACKGROUND: Postpancreatectomy morbidity remains significant even in high-volume centers and frequently results in delay or suspension of indicated adjuvant oncological treatment. This study investigated the short-term and long-term outcome after primary total pancreatectomy (PTP) and pylorus-preserving pancreaticoduodenectomy (PPPD) or Whipple procedure, with a special focus on administration of adjuvant therapy and oncological survival. METHODS: Patients who underwent PTP or PPPD/Whipple for periampullary cancer between January 2008 and December 2017 were retrospectively analyzed. Propensity score-matched analysis was performed to compare perioperative and oncological outcomes. Correspondingly, cases of rescue completion pancreatectomy (RCP) were analyzed. RESULTS: In total, 41 PTP and 343 PPPD/Whipple procedures were performed for periampullary cancer. After propensity score matching, morbidity (Clavien-Dindo classification (CDC) ≥ IIIa, 31.7% vs. 24.4%; p = 0.62) and mortality rates (7.3% vs. 2.4%, p = 0.36) were similar in PTP and PPPD/Whipple. Frequency of adjuvant treatment administration (76.5% vs. 78.4%; p = 0.87), overall survival (513 vs. 652 days; p = 0.47), and progression-free survival (456 vs. 454 days; p = 0.95) did not significantly differ. In turn, after RCP, morbidity (CDC ≥ IIIa, 85%) and mortality (40%) were high, and overall survival was poor (median 104 days). Indicated adjuvant therapy was not administered in 77%. CONCLUSIONS: In periampullary cancers, PTP may provide surgical and oncological treatment outcomes comparable with pancreatic head resections and might save patients from RCP. Especially in selected cases with high-risk pancreatic anastomosis or preoperatively impaired glucose tolerance, PTP may provide a safe treatment alternative to pancreatic head resection.

Pelvic exenteration for colorectal and non-colorectal cancer: a comparison of perioperative and oncological outcome.

BACKGROUND: Pelvic exenteration (PE) is the only option for long-term cure of advanced cancer originating from different types of tumor or recurrent disease in the lower pelvis. The aim was to show differences between colorectal and non-colorectal cancer in survival and postoperative morbidity. METHODS: Retrospective data of 63 patients treated with total pelvic exenteration between 2013 and 2018 are reported. Pre-, intra-, and postoperative parameters, survival data, and risk factors for complications were analyzed. RESULTS: A total of 57.2% (n = 37) of the patients had colorectal cancer, 22.3% had gynecological malignancies (vulvar (n = 6) or cervical (n = 8) cancer), 11.1% (n = 7) had anal cancer, and 9.5% had other primary tumors. A total of 30.2% (n = 19) underwent PE for a primary tumor and 69.8% (n = 44) for recurrent cancer. The 30-day in-hospital mortality was 0%. Neoadjuvant treatment was administered to 65.1% (n = 41) of the patients and correlated significantly with postoperative complications (odds ratio 4.441; 95% CI: 1.375-14.342, P > 0.05). R0, R1, R2, and Rx resections were achieved in 65.1%, 19%, 1.6%, and 14.3% of the patients, respectively. In patients undergoing R0 resection, 2-year OS and RFS were 73.2% and 52.4%, respectively. Resection status was a significant risk factor for recurrence-free and overall survival (OS) in univariate analysis. Multivariate analysis revealed age (P = 0.021), ASA ≥ 3 (P = 0.005), high blood loss (P = 0.028), low preoperative hemoglobin level (P < 0.001), nodal positivity (P < 0.001), and surgical complications (P = 0.003) as independent risk factors for OS. CONCLUSION: Pelvic exenteration is a procedure with high morbidity rates but remains the only curative option for advanced or recurrent colorectal and non-colorectal cancer in the pelvis.

Impact of pulmonary embolism on morbidity and mortality in patients undergoing pancreatic surgery.

PURPOSE: Postoperative pulmonary embolism (PE) after pancreatic surgery is a potentially life-threatening complication. However, the magnitude of morbidity and mortality of PE is still uncertain. The present study aims to assess the incidence of PE after pancreatic surgery and analyze its impact on the outcome. METHODS: We conducted a retrospective study including all patients who underwent pancreatic resections between 2005 and 2017. The development of PE was analyzed for a 90-day period following surgery. Risk factors were evaluated using regression models. RESULTS: The study investigated 947 patients undergoing pancreatic surgery. Overall, 26 (2.7%) patients developed PE. The median body mass index (BMI) of patients with PE was significantly higher (28.1 kg/m2 [24.7-31.8] vs. 24.8 kg/m2 [22.4-27.8], p < 0.001). Patients with PE had a significantly increased duration of the operation and more often underwent multivisceral resections. The lowest incidence of PE was found after distal or total pancreatectomy (2%). In median, PE occurred on the fifth postoperative day (interquartile range: 3-9). Increased BMI, duration of operation, and postoperative deep venous thrombosis were found to be multivariate risk factors for the development of PE. Importantly, postoperative complications (53.8% vs. 15.1%, p < 0.001) and the 30-day mortality rate were significantly increased in the PE group (19.2% vs. 3.3%, p < 0.001). CONCLUSIONS: Patients with increased BMI, a history of deep venous thrombosis, and multivisceral resections are a high-risk group for PE after pancreatic surgery. While the absolute incidence and related mortality of PE after pancreatic surgery is low, it is associated with severe sequelae.

Disease duration before surgical resection for chronic pancreatitis impacts long-term outcome.

Many patients with chronic pancreatitis (CP) undergo a step-up approach with interventional procedures as first-line treatment and resection reserved for later stages. The aim of this study was to identify predictive factors for a significant clinical improvement (SCI) after surgical treatment.All patients operated for CP between September 2012 and June 2017 at our center was retrospectively reviewed. A prospective patient survey was conducted to measure patients postoperative outcome. The primary endpoint SCI was defined as stable health status, positive weight development and complete pain relief without routine pain medication. Additionally, risk factors for relaparotomy were analyzed.A total of 89 patients with a median follow-up of 38 months were included. In most cases, a duodenum-preserving pancreatic head resection (n = 48) or pancreatoduodenectomy (n = 28) was performed. SCI was achieved in 65.3% (n = 47) of the patients after the final medium follow-up of 15.0 months (IQR: 7.0-35.0 months), respectively. Patients with a longer mean delay (7.7 vs 4 years) between diagnosis and surgical resection were less likely to achieve SCI (P = .02; OR .88; 95%CI .80-98). An endocrine insufficiency was a negative prognostic factor for SCI (P = .01; OR .15; 95%CI .04-68). In total, 96.2% of the patients had a complete or major postoperative relief with a mean pain intensity reduction from 8.1 to 1.9 on the visual analogue scale.The results support that surgical resection for CP should be considered at early stages. Resection can effectively reduce postoperative pain intensity and improve long-term success.

Prognostic impact of para-aortic lymph node metastases in non-pancreatic periampullary cancer.

BACKGROUND: Resection of the para-aortic lymph node (PALN) group Ln16b1 during pancreatoduodenectomy remains controversial because PALN metastases are associated with a worse prognosis in pancreatic cancer patients. The present study aimed to analyze the impact of PALN metastases on outcome after non-pancreatic periampullary cancer resection. METHODS: One hundred sixty-four patients with non-pancreatic periampullary cancer who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005 and 2016 were retrospectively investigated. The data were supplemented with a systematic literature review on this topic. RESULTS: In 67 cases, the PALNs were clearly assigned and could be histopathologically analyzed. In 10.4% of cases (7/67), tumor-infiltrated PALNs (PALN+) were found. Metastatic PALN+ stage was associated with increased tumor size (P = 0.03) and a positive nodal stage (P < 0.001). The median overall survival (OS) of patients with metastatic PALN and non-metastatic PALN (PALN-) was 24.8 and 29.5 months, respectively. There was no significant difference in the OS of PALN+ and pN1 PALN patients (P = 0.834). Patients who underwent palliative surgical treatment (n = 20) had a lower median OS of 13.6 (95% confidence interval 2.7-24.5) months. Including the systematic literature review, only 23 cases with PALN+ status and associated OS could be identified; the average survival was 19.8 months. CONCLUSION: PALN metastasis reflects advanced tumor growth and lymph node spread; however, it did not limit overall survival in single-center series. The available evidence of the prognostic impact of PALN metastasis is scarce and a recommendation against resection in these cases cannot be given.

Drain Amylase or Lipase for the Detection of POPF-Adding Evidence to an Ongoing Discussion.

： Objectives: A postoperative pancreatic fistula (POPF) is defined as a threefold increase in the amylase concentration in abdominal drains on or after the third postoperative day (POD). However, additional lipase fluid analysis is widely used despite lacking evidence. In this study, drain amylase and lipase levels were compared regarding their value in detecting POPF. Methods: We conducted a retrospective study including all patients who underwent pancreatic resections at our center between 2005 and 2016. Drain fluid analysis was performed from day 2 to 5. Results: 990 patients were included in the analysis. Overall, 333 (34%) patients developed a POPF. The median amylase and lipase concentrations at POD 3 in cases with POPF were 11.55 µmol/(s·L) (≈13 ×-fold increase) and 39 µmol/(s·L) (≈39 ×-fold increase), respectively. Seven patients with subsequent POPF (2%) were missed with amylase analysis on POD 3, but detected using 3-fold lipase analysis. The false-positive rate of lipase was 51/424 = 12%. A cutoff lipase value at POD 3 of > 4.88 yielded a specificity of 94% and a sensitivity of 89% for development of a POPF. Increased body mass index turned out as risk factor for the development of POPF in a multivariable model. Conclusions: Threefold-elevated lipase concentration may be used as an indicator of a POPF. However, the additional detection of POPF using simultaneous lipase analysis is marginal. Therefore, assessment of lipase concentration does not provide added clinical value and only results in extra costs.

Results of portosystemic shunts during extended pancreatic resections.

PURPOSE: Patients with borderline resectable pancreatic cancer are increasingly explored after neoadjuvant treatment protocols. A complete resection, then, frequently includes the resection of the mesentericoportal axis. Portosystemic shunting for advanced tumours with infiltration of the splenic vein or cavernous transformation of the portal vein can enable complete tumour resection and prevent portovenous congestion of the intestine. The aim of this study was to report the results of this technique for selected patients. METHODS: Patients operated for pancreatic cancer at our department between September 2012 and December 2017 using intraoperative portosystemic shunting were included in this retrospective analysis. RESULTS: Some 11 patients with pancreatectomy and simultaneous portosystemic shunting were included. The median age was 65.1 years. A distal splenorenal shunt and a temporary mesocaval shunt were accomplished in 5 and 4 cases, respectively. Two patients were operated using persistent mesocaval shunts (from the coronary, splenic or inferior mesenteric veins). The median operating time was 9.43 h. All but one patient were resected with tumour-negative resection margins; 5 patients had relevant complicated postoperative courses. There was one case of in-hospital mortality but no further 30- or 90-day mortality or graft-associated complications. Five patients were alive after a median follow-up of 24.6 months. The median postoperative survival was 12 months. CONCLUSION: Portosystemic shunting at the time of extended pancreatectomy is technically challenging but feasible and enables complete tumour resection in cases in which standard vascular reconstruction is limited by cavernous transformation or to prevent sinistral portal hypertension with acceptable morbidity in selected cases. Considering the limited overall survival, the potential individual patient benefit needs to be weighed against the considerable morbidity of advanced tumour resections.

Use of Activity Tracking in Major Visceral Surgery-the Enhanced Perioperative Mobilization Trial: a Randomized Controlled Trial.

BACKGROUND: Early mobilization is one essential item within the enhanced recovery after surgery (ERAS) concept, but lacks solid evidence and a standardized assessment. The aim was to monitor and increase the postoperative mobilization of patients after major visceral surgery by providing a continuous step count feedback using activity tracking wristbands. METHODS: The study was designed as a randomized controlled single-center trial (NCT02834338) with two arms (open and laparoscopic surgery). Participants were randomized to either receive feedback of their step counts using an activity tracker wristband or not. The primary study endpoint was the mean step count during the first 5 postoperative days (PODs). RESULTS: A total of 132 patients were randomized. After laparoscopic operations, the average step count during PODs 1-5 was significantly increased by the feedback compared with the control group (P < 0.001); the cumulative step count (9867 versus 6103, P = 0.037) and activity time were also significantly increased. These results could not be confirmed in the open surgery arm. Possible reasons were a higher age and significantly more comorbidities in the open intervention group. Patients who achieved more than the median cumulative step count had a significantly shorter hospital stay and lower morbidity in both arms. The average step count also correlated with the length of hospital stay (R = - 0.341, P < 0.001). CONCLUSION: This study is the first randomized controlled trial investigating the use and feasibility of activity tracking to monitor and enhance postoperative mobilization in abdominal surgery. Our results demonstrate that activity tracking can enhance perioperative mobilization after laparoscopic surgery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02834338.

Pancreatoduodenectomy with or without prophylactic falciform ligament wrap around the gastroduodenal artery stump for prevention of pancreatectomy hemorrhage.

BACKGROUND: The purpose of this study is to evaluate whether wrapping of the pedicled falciform ligamentum flap around the gastroduodenal artery (GDA) stump/hepatic artery can significantly decrease the incidence of erosion hemorrhage after pancreatoduodenectomy (PD). METHODS/DESIGN: This is a randomized controlled multicenter trial involving 400 patients undergoing PD. Patients will be randomized into two groups. The intervention group consists of 200 patients with a prophylactic wrapping of the GDA stump using the pedicled falciform ligament. The control group consists of 200 patients without the wrap. The primary endpoint is the rate of postoperative erosion hemorrhage of the GDA stump or hepatic artery within 3 months. The secondary endpoints are postpancreatectomy hemorrhage stratified according to the texture of the pancreas, postoperative pancreatic fistula (POPF), postoperative rate of therapeutic interventions, morbidity, and mortality. DISCUSSION: Only few retrospective studies investigated the effectiveness of a falciform ligament wrap around the GDA for prevention of erosion hemorrhage. Erosion hemorrhage occurs in up to 6-9% of cases after PD and is most frequently evoked by a POPF. Erosion hemorrhage is associated with a remarkable mortality of over 30%. The rate of hemorrhage after performing the wrap is reported to be low. However, there exist no prospectively controlled data to support its general use. Therefore, the presented randomized controlled trial will provide clinically relevant evidence of the effectiveness of the wrap with statistical significance. TRIAL REGISTRATION: clinicaltrials.gov, NCT02588066 ; Registered on 27 October 2015.

Prognostic Impact of Bacterobilia on Morbidity and Postoperative Management After Pancreatoduodenectomy: A Systematic Review and Meta-analysis.

BACKGROUND: Intraoperative bile analysis during pancreatoduodenectomy (PD) is performed routinely at specialized centers worldwide. However, it remains controversial if and how intraoperative bacterobilia during PD affects morbidity and its management. The aim of the study was a systematic review and meta-analysis of intraoperative bacterobilia and its impact on patient outcome after PD. METHODS: Five relevant outcomes of interest were defined, and a systematic review of the literature with meta-analysis was performed according to the PRISMA guidelines. RESULTS: A total of 28 studies (8523 patients) were included. The median incidence of bacterobilia was 58% (interquartile range 51-67%). The most frequently isolated bacteria were Enterococcus species (51%), Klebsiella species (28%), and Escherichia coli (27%). Preoperative biliary drainage was significantly associated with bacterobilia (86 vs. 25%; RR 3.27; 95% confidence interval (CI) 2.42-4.42; p < 0.001). The incidence of surgical site infections (SSI) was significantly increased in cases with bacterobilia (RR 2.84; 95% CI 2.17-3.73; p < 0.001). Postoperative pancreatic fistula, overall postoperative morbidity, and mortality were not significantly influenced. Identical bacteria in bile and the infectious sources were found in 48% (interquartile range 34-59%) of the cases. CONCLUSIONS: Bacterobilia is detected during almost every second PD and is associated with an increased rate of SSI. The microbiome from intraoperative bile and postoperative infectious sources match in ~50% of patients, providing the option of early administration of calculated antibiotics and the determination of resistance patterns.

Reproducibility of preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula.

BACKGROUND: A postoperative pancreatic fistula (POPF) is the most common and potentially life-threatening surgical complication in pancreatic surgery. One possible pharmacological treatment could be the endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi to prevent POPF. Promising data reported a significantly reduced rate of clinically relevant POPF. We analyzed the effect of BTX injection in our patients undergoing distal pancreatectomy (DP). METHODS: A retrospective analysis of patients undergoing DP was performed. Patients with preoperative endoscopic injection of BTX into the sphincter of Oddi were included. The end points were postoperative outcomes including POPF. BTX patients were compared with a historical cohort and matched in a 1:1 ratio using a propensity score analysis. RESULTS: A total of 19 patients were treated with endoscopic injection of BTX before open (n=8) or laparoscopic (n=11) DP. The median age of the patients was 67 years and the mean body mass index was 25.9 kg/m2. In median, the intervention was performed 1 day (range, 0-14 days) before the operation. There were no intervention-related complications. The incidence of POPF was not statistically different between the two groups: a clinically relevant POPF grade (B/C) occurred in 32% (BTX) and 42% (control; p=0.737). Likewise, there were no significant differences in postoperative drain fluid amylase levels, morbidity, and mortality. CONCLUSION: The present study could not reproduce the published results of a significant lowering of grade B/C POPF. The explanations could be the timing of BTX injection before surgery and the endoscopic technique of BTX injection. However, the conflicting results after BTX injection in two high-volume centers prompt a randomized controlled multicenter trial with trained endoscopists.

Use of activity tracking in major visceral surgery-the Enhanced Perioperative Mobilization (EPM) trial: study protocol for a randomized controlled trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs are aimed at minimizing postoperative stress and accelerating postoperative recovery by implementing multiple perioperative principles. "Early mobilization" is one such principle, but the quality of assessment and monitoring is poor, and evidence of improved outcome is lacking. Activity trackers allow precise monitoring and automatic feedback to the patients to enhance their motivation for early mobilization. The aim of the study is to monitor and increase the postoperative mobilization of patients by giving them continuous automatic feedback in the form of a step count using activity-tracking wristbands. METHODS/DESIGN: Patients undergoing elective open and laparoscopic surgery of the colon, rectum, stomach, pancreas, and liver for any indication will be included. Further inclusion criteria are age between 18 and 75 years, American Society of Anesthesiologists Physical Status class less than IV, and a signed informed consent form. Patients will be stratified into two subgroups, laparoscopic and open surgery, and will be randomized 1:1 for automatic feedback of their step count using an activity tracker wristband. The control group will have no automatic feedback. The sample size (n = 30 patients in each of the four groups, overall n = 120) is calculated on the basis of an assumed difference in step count of 250 steps daily (intervention group versus control group). The primary study endpoint is the average step count during the first 5 postoperative days; secondary endpoints are the percentage of patients in the two groups who master the predefined mobilization (step count) targets, assessment of additional activity data obtained from the devices, assessment of preoperative mobility, length of hospital and intensive care unit stays, number of patients who receive physiotherapy, 30-day mortality, and overall 30-day morbidity. DISCUSSION: Early mobilization is a key element of ERAS. However, enhanced early mobilization is difficult to define, to assess objectively, and to implement in clinical practice. Consequently, there is a discrepancy between ERAS targets and actual practice, especially in patients undergoing major visceral surgery. This study is the first randomized controlled trial investigating the use and feasibility of activity tracking to monitor and enhance postoperative early mobilization. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02834338 . Registered on 15 June 2016.

Falciform ligament wrap for prevention of gastroduodenal artery bleed after pancreatoduodenectomy.

BACKGROUND: The present study aims to assess the effectiveness and current evidence of a pedicled falciform ligament wrap around the gastroduodenal artery stump for prevention of erosion hemorrhage after pancreatoduodenectomy (PD). METHODS: Retrospective data were pooled for meta-analysis. At the own center, patients who underwent PD between 2012 and 2015 were retrospectively analyzed based on the intraoperative performance of the wrap. A systematic literature review and meta-analysis was performed that combined the published and the obtained original data. The following databases were searched: Medline, Embase, Web of Science, and the Cochrane Library. RESULTS: At the own center, a falciform ligament wrap was performed in 39 of 196 PDs (20%). The wrap group contained more ampullary neoplasms, but the pancreatic fistula rate was not significantly different from the nonwrap group (28% versus 32%). In median, erosion hemorrhage occurred after 21.5 d, and it was lethal in 39% of the patients. Its incidence was not significantly lower in the wrap group (incidence: 7.7% versus 9.6% in the nonwrap group). The systematic literature search yielded four retrospective studies with a high risk of bias; only one study was controlled. When the five data sets of published and own cases with a falciform ligament wrap were pooled, the incidence of erosion hemorrhage was 5 of 533 cases (0.9%) compared with 24 of 297 cases (8.1%) without the wrap. CONCLUSIONS: The reported incidence of erosion hemorrhage after the falciform ligament wrap is low, but there are still insufficient controlled data to support its general use.

A Comprehensive MicroRNA Expression Profile of Liver and Lung Metastases of Colorectal Cancer with Their Corresponding Host Tissue and Its Prognostic Impact on Survival.

MicroRNAs are small non-coding RNAs with a length of 18-25 nucleotides. They can regulate tumor invasion and metastasis by changing the expression and translation of their target mRNAs. Their expression is substantially altered in colorectal cancer cells as well as in the adjacent tumor-associated stroma. Both of these compartments have a mutual influence on tumor progression. In the development of metastases, cancer cells initially interact with the host tissue. Therefore, compartment-specific expression signatures of these three locations-tumor, associated stroma, and host tissue-can provide new insights into the complex tumor biology of colorectal cancer. Frozen tissue samples of colorectal liver (n = 25) and lung metastases (n = 24) were laser microdissected to separate tumor cells and the adjacent tumor-associated stroma cells. Additionally, normal lung and liver tissue was collected from the same patients. We performed a microarray analysis in four randomly selected liver metastases and four randomly selected lung metastases, analyzing a total of 939 human miRNAs. miRNAs with a significant change >2-fold between the tumor, tumor stroma, and host tissue were analyzed in all samples using RT-qPCR (11 miRNAs) and correlated with the clinical data. We found a differential expression of several miRNAs between the tumor, the tumor-associated stroma, and the host tissue compartment. When comparing liver and lung metastases, miR-194 showed a 1.5-fold; miR-125, miR-127, and miR-192 showed a 2.5-fold; miR-19 and miR-215 a 3-fold; miR-145, miR-199-3, and miR-429 a 5-fold; miR-21 a 7-fold; and, finally, miR-199-5 a 12.5-fold downregulation in liver metastases compared to lung metastases. Furthermore miR-19, miR-125, miR-127, miR-192, miR-194, miR-199-5, and miR-215 showed a significant upregulation in the normal liver tissue compared to the normal lung tissue. Univariate analysis identified an association of poor survival with the expression of miR-125 (p = 0.05), miR-127 (p = 0.001), miR-145 (p = 0.005), miR-192 (p = 0.015), miR-194 (0.003), miR-199-5 (p = 0.008), miR-215 (p < 0.001), and miR-429 (p = 0.03) in the host liver tissue of the liver metastases. Colorectal liver and lung metastases have a unique miRNA expression profile. miRNA expression in the host tissue of colorectal liver metastases seems to be able to influence tumor progression and survival. These findings can be used in the development of tailored therapies.

Cost-effectiveness comparison of prophylactic octreotide and pasireotide for prevention of fistula after pancreatic surgery.

PURPOSE: Postoperative pancreatic fistula (POPF) is a major determinant of pancreatic surgery outcome, and prevention of POPF is a relevant clinical challenge. The aim of the present study is to compare the cost-effectiveness of octreotide and pasireotide for POPF prophylaxis. METHODS: A systematic literature review and meta-analysis and a retrospective patient cohort provided the data. Cost-effectiveness was calculated by the incremental cost-effectiveness ratio (ICER) and by decision tree modelling of hospital stay duration. RESULTS: Six randomised trials on octreotide (1255 patients) and one trial on pasireotide (300 patients) were included. The median POPF incidence without prophylaxis was 19.6 %. The relative risks for POPF after octreotide or pasireotide prophylaxis were 0.54 or 0.45. Octreotide prophylaxis (21 × 0.1 mg) costs were 249.69 Euro, compared with 728.84 Euro for pasireotide (14 × 0.9 mg) resulting in an ICER of 266.19 Euro for an additional 1.8 % risk reduction with pasireotide. Decision tree modelling revealed no significant reduction of median hospital stay duration if pasireotide was used instead of octreotide. CONCLUSION: Prophylactic octreotide is almost as effective as pasireotide but incurs significantly fewer drug costs per case. However, the data quality is limited, because the effect of octreotide on clinically relevant POPF is unclear. Together with the lack of multicentric data on pasireotide and its effectiveness, a current off-label use of pasireotide does not appear to be justified.

Adherence to ERAS elements in major visceral surgery-an observational pilot study.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs have been introduced increasingly into major visceral surgery. Key elements target on early drain removal and mobilization of the patients; however, reporting of adherence to ERAS protocols has often been insufficiently assessed. The present study aims to prospectively evaluate ERAS compliance after major visceral surgery. METHODS: A prospective pilot study was designed, and 34 patients scheduled for major hepatopancreatic or gastric surgery were followed postoperatively until postoperative day (POD) 10. Analgesia and drain management, diet, mobilization, willingness to exercise, and the use of discharge criteria were accurately assessed within an established ERAS protocol scenario. RESULTS: Thirty-one cases were analyzed that consisted of 54.8 % major pancreatic, 29.0 % hepatic, and 16.1 % gastric resections. The median hospital stay was 12.5 days, and 83.9 % of the patients met the objective criteria before discharge. By POD 4, wound, epidural, and urinary catheters were still in place in 70, 60, and 40 % of the patients, respectively. Fifty percent of the patients ambulated out of bed until POD 2. The cumulative duration of postoperative mobilization per day ranged from 15 to 155 min, and only 40 % of the patients felt comfortable with additional mobilization or physical exercise. CONCLUSIONS: Adherence to ERAS protocols is poorly reported. The results indicate a discrepancy between ERAS targets and actual practice in comorbid patients undergoing major visceral surgery, need for a prompt redefinition of ERAS mobilization targets, need for the improvement of counseling, and need for the implementation of ERAS principles.