Acinar content at pancreatic resection margin is significantly associated with clinically relevant pancreatic fistula after partial pancreatoduodenectomy.

BACKGROUND: This study aimed to evaluate the clinical significance of acinar content at the pancreatic resection margin after partial pancreatoduodenectomy (PD). METHODS: A total of 228 consecutive patients undergoing PD were included for analysis. Resection margins were assessed for acinar, fibrosis, and fat contents by 2 pathologists blinded to the patients' clinical data. Univariate and multivariable analyses of possible predictors for clinically relevant postoperative pancreatic fistula (cr-POPF) were performed. RESULTS: The median acinar, fibrosis, and fat contents were 70% (IQR, 25%-82%), 13% (IQR, 5%-40%), and 15% (IQR, 9.25%-25%), respectively. The rates of cr-POPF were significantly higher in patients with an acinar content of >70% than in patients with an acinar content of ≤70% (26.4% vs 5.5%, respectively; P < .001). In addition, the rates of postoperative hyperamylasemia (POH) were significantly higher in patients with an acinar content of ≥70% than in patients with an acinar content of ≤70% (55.2% vs 13.8%, respectively; P < .001). The median fat content did not differ between patients with and without cr-POPF (13.0% [IQR, 7.5%-20.0%] vs 15.0% [IQR, 10.0%-30.0%], respectively; P = .06). An acinar content of >70% at the pancreatic resection margin (odds ratio [OR], 4.85; 95% CI, 1.61-14.58; P = .005) and a soft pancreatic texture (OR, 2.82; 95% CI, 1.02-7.76; P = .046) were independent predictive factors of cr-POPF in the multivariable analysis. CONCLUSION: An acinar content of ≥70% at the pancreatic resection margin was a significant predictive factor for cr-POPF after PD and was also significantly associated with POH, a precursor of cr-POPF after PD in many cases. Fatty infiltration of the pancreatic resection margin was not associated with cr-POPF.

Serum amylase on postoperative day 1 is superior to serum lipase in predicting clinically relevant pancreatic fistula after partial pancreaticoduodenectomy.

PURPOSE: To compare the predictive value of serum amylase and lipase regarding the occurrence of clinically relevant postoperative pancreatic fistula (cr-POPF) after partial pancreaticoduodenectomy (PD). METHODS: Data from 228 consecutive patients undergoing PD were obtained from a prospective database. Serum amylase and lipase were measured on postoperative days (PODs) 0-2. Receiver-operating characteristics analysis was performed and cutoff values were tested using logistic regression. RESULTS: Serum amylase had a larger area under the curve (AUC) on POD1 (AUC 0.89, p <0.001) than serum lipase. For serum amylase POD 1, a cutoff value of 70 U/l showed sensitivity and specificity of 100% and 70% for the diagnosis of cr-POPF. Serum amylase POD 1 > 70 U/l (OR 9.815, 95% CI 3.683-26.152, p < 0.001), drain amylase POD 1 > 300 U/l (OR 2.777, 95% CI 1.071-7.197, p= 0.036), and a small (≤ 3mm) pancreatic duct diameter (OR 3.705, 95% CI 1.426-9.627, p= 0.007) were significant predictors of cr-POPF in the multivariable analysis. Patients were divided into three risk groups based on serum amylase POD 1 and pancreatic duct diameter. This model had a good performance in discriminating cr-POPF (AUC 0.846, 95% CI 0.793-0.898). The sensitivity, specificity, and negative predictive value for the combination of serum amylase POD 1 <70 U/l and pancreatic duct diameter >3 mm were 100%, 70%, and 100%. CONCLUSION: Serum amylase POD 1 was superior to serum lipase in predicting cr-POPF after PD. The proposed risk prediction model had a sensitivity and negative predictive value of 100%, allowing for early identification of cr-POPF.

Vessel-Sparing Lymphadenectomy Should Be Performed in Small Intestine Neuroendocrine Neoplasms.

INTRODUCTION: The goal of primary tumor resection with lymphadenectomy (PTR) in small intestine neuroendocrine neoplasms (SI-NENs) is to avoid local recurrence while sparing as much of the small bowel as possible, even in the case of extensive mesenteric fibrosis. The results of PTR with retrograde vessel-sparing lymphadenectomy (VS-LA) were compared to those of conventional lymphadenectomy (Con-LA). METHODS: Prospectively collected clinical, surgical and pathological data of consecutive patients with SI-NENs who underwent small bowel resections were retrospectively analyzed regarding the resection technique performed. RESULTS: In a 7-year period, 50 of 102 patients with SI-NENs had only small bowel resections; of those, 25 were VS-LA and 25 were Con-LA. Patients with VS-LA had tendentially more advanced diseases with slightly higher rates of abdominal pain, mesenteric shrinkage and more level III lymph node involvement compared to patients with Con-LA. VS-LA, however, resulted in shorter resected bowel segments (median 40 cm vs. 65 cm, p = 0.007) with similar rates of local R0 resections (72% vs. 84%) and resected lymph nodes (median 13 vs. 13). Postoperative clinically relevant complications occurred in 1 of 25 (4%) in the VS-LA and in 7 of 25 (28%) patients in the Con-LA group (p = 0.02). Three months after surgery, 1 of 25 (4%) patients of the VS-LA group and 10 of 25 (40%) patients in the Con-LA group (p = 0.002) complained about abdominal pain. One of eight patients in the VS-LA group and two of thirteen patients in the Con-LA group who had completely resected stage III disease complained about diarrhea (p = 0.31). CONCLUSION: VS-LA seems to be oncologically safe and should be considered in small bowel resections for SI-NENs.

Indocyanine Green Near-Infrared Fluoroangiography Is a Useful Tool in Reducing the Risk of Anastomotic Leakage Following Left Colectomy.

Purpose: To evaluate whether visualization of the colon perfusion with indocyanine green near-infrared fluoroangiography (ICG-NIFA) reduces the rate of anastomotic leakage (AL) after colorectal anastomosis. Methods: Patients who underwent elective left colectomy, including all procedures involving the sigmoid colon and the rectum with a colorectal or coloanal anastomosis, were retrospectively analyzed for their demographics, operative details, and the rate of AL. Univariate and multivariate analyses were used to compare patients with and without ICG-NIFA-based evaluation. Results: Overall, our study included 132 colorectal resections [70 sigmoid resections and 62 total mesorectal excisions (TMEs)], of which 70 (53%) were performed with and 62 (47%) without ICG-NIFA. Patients' characteristics were similar between both the groups. The majority of the procedures [91 (69%)] were performed by certified colorectal surgeons, while 41 (31%) operations were supervised teaching procedures. In the ICG-NIFA group, bowel perfusion could be visualized by fluorescence (dye) in all 70 cases, and no adverse effects related to the fluorescent dye were observed. Following ICG-NIFA, the transection line was changed in 9 (12.9%) cases. Overall, 10 (7.6%) patients developed AL, 1 (1.4%) in the ICG-NIFA group and 9 (14.5%) in the no-ICG-NIFA group (p = 0.006). The multivariate analysis revealed ICG-NIFA as an independent factor to reduce AL. Conclusion: These results suggest that ICG-NIFA might be a valuable tool to reduce the rate of AL in sigmoid and rectal resections in an educational setting.

Clinical Implications of Postoperative Hyperamylasemia after Partial Pancreaticoduodenectomy.

Introduction: The present study aimed to examine the clinical implications of postoperative hyperamylasemia (POH) after partial pancreaticoduodenectomy (PD). Methods: Data from all consecutive patients undergoing PD were obtained from a prospectively maintained database and reviewed. POH was defined as an elevation of serum pancreatic amylase above the upper limit of normal (53 U/L) on postoperative days 0-2. Clinically relevant POH (cr-POH) was defined as POH in patients with clinically relevant (Clavien-Dindo ≥ III) postoperative complications. Results: POH occurred in 61 of 170 (35.9%) and cr-POH in 24 of 170 (14.1%) patients. Patients with POH had higher rates of clinically relevant postoperative pancreatic fistula (cr-POPF) (44.3 vs. 3.7%, p < 0.001) and clinically relevant postoperative complications than those without POH (39.3 vs. 21.1%, p = 0.001). Patients with cr-POH had higher C-reactive protein (CRP, milligrams per liter) levels on third (257.7 vs. 187.85 mg/L, p = 0.016) and fourth (222.5 vs. 151, p = 0.002) postoperative day (POD) than those with POH alone. Serum procalcitonin (PCT, micrograms per liter) levels on POD 2 (1.2 vs. 0.4 µg/L, p = 0.028) and POD 3 (0.85 vs. 0.4 µg/L, p = 0.001) were also higher in patients with cr-POH. Rates of cr-POPF in patients with cr-POH were higher than in those with POH alone (70.8 vs. 27%, p = 0.001). POH (OR 0.011, 95% CI: 0.001-0.097, p < 0.001) was an independent predictor of cr-POPF in the multivariable analysis. A high-risk pathology, defined as nonadenocarcinoma/nonchronic pancreatitis pathology (OR 0.277, 95% CI: 0.106-0.727, p = 0.009), and a small duct diameter (OR 0.333, 95% CI: 0.139-0.796, p = 0.013) were independent predictors of POH in the multivariable analysis. Conclusion: POH is a frequent, but not always clinically relevant, finding after partial PD. Serum CRP and PCT levels in the early postoperative period can be used to identify patients with cr-POH. POH is an independent risk factor for increased postoperative morbidity, including cr-POPF, after partial PD.

Postoperative morbidity following pancreatic cancer surgery is significantly associated with worse overall patient survival; systematic review and meta-analysis.

BACKROUND: The influence of postoperative morbidity on survival after potentially curative resection for pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: Medline, Web of Science and Cochrane Library were searched for studies reporting survival in patients with and without complications, defined according to the Clavien-Dindo classification, after primary, potentially curative resection for pancreatic cancer followed by adjuvant treatment. Meta-analysis was performed using a random-effects model. RESULTS: Fourteen retrospective cohort studies comprising a total of 7.604 patients with an overall complication rate of 40.8% (n = 3.103 patients) were included. Median overall survival for the entire patient cohort ranged from 15.5 to 24 months. Overall survival in patients with severe postoperative complications ranged from 7.1 to 37.1 months and was significantly worse compared to the overall survival in patients without severe complications ranging from 16.5 to 38.2 months. Postoperative complication rates ranged from 24.3% to 64%, severe (Clavien-Dindo ≥ III) complication rates from 4.2% to 31%. Results sufficient for meta-analysis were reported by ten studies, representing 6.028 patients. Meta-analysis showed reduced overall survival following any complication (summary adjusted HR 1.47; 95% CI 1.23-1.76, p < 0.0001). Hazard of death was 1.5 times higher in patients experiencing severe postoperative complications than in patients without severe complications (summary adjusted HR 1.45; 95% CI 1.13-1.85, p = 0.003). CONCLUSIONS: Postoperative complications after potentially curative resection of PDAC are significantly associated with worse overall patient survival.

Preoperative Bacterobilia Is an Independent Risk Factor of SSIs after Partial PD.

INTRODUCTION: The impact of bacterobilia on postoperative surgical and infectious complications after partial pancreaticoduodenectomy (PD) is still a matter of debate. METHODS: All patients undergoing PD with and without a preoperative biliary drainage (PBD) with complete information regarding microbial bile colonization were included. Logistic regression was applied to assess the influence of bacterobilia on postoperative outcome. RESULTS: One hundred seventy patients were retrospectively analysed. Clinically relevant postoperative complications (Clavien-Dindo ≥ III) occurred in 40 (23.5%) patients, clinically relevant postoperative pancreatic fistulas in 29 (17.1%) patients, and surgical site infections (SSIs) in 16 (9.4%) patients. Thirty-seven of 39 (94.9%) patients with PBD and 33 of 131 (25.2%) patients without PBD had positive bile cultures (p < 0.001). A polymicrobial bile colonization was reported in 9 of 33 (27.3%) patients without PBD and 27 of 37 (73%) patients with PBD (p < 0.001). Resistance to ampicillin-sulbactam was shown in 26 of 37 (70.3%) patients with PBD and 12 of 33 (36.4%) patients without PBD (p = 0.001). PBD (OR 0.015, 95% CI 0.003-0.07, p < 0.001) and male sex (OR 3.286, 95% CI 1.441-7.492, p = 0.005) were independent predictors of bacterobilia in the multivariable analysis. Bacterobilia was the only independent predictor of SSIs in the multivariable analysis (OR 0.143, 95% CI 0.038-0.535, p = 0.004). CONCLUSIONS: Patients with a PBD show significantly higher rates of bacterobilia, polymicrobial bile colonization, and resistance to ampicillin-sulbactam. Bacterobilia is an independent predictor of SSI after PD.

C-reactive protein and drain amylase accurately predict clinically relevant pancreatic fistula after partial pancreaticoduodenectomy.

BACKROUND: C-reactive protein (CRP) and procalcitonin (PCT) have shown to be reliable predictors of inflammatory complications and anastomotic leak after colorectal surgery. Their predictive value after partial pancreaticoduodenectomy (PD) remains unclear. MATERIALS AND METHODS: All consecutive pancreaticoduodenectomies (2009-2018) at our hospital were included. Drain amylase was evaluated on postoperative day (POD) 1, serum CRP and PCT were evaluated on POD 1-3. Receiver-operating characteristics curves were performed and significant cut-off values were tested using logistic regression. RESULTS: Among 188 patients who underwent partial PD, clinically relevant pancreatic fistulas (POPF) occurred in 30 (16%) patients, including 20 (10.6%) with Grade B and 10 (5.3%) patients with Grade C. Postoperative complications (Clavien-Dindo ≥ III) were reported in 46 (24.5%) patients, including Grade IIIa in 16 (8.5%), IIIb in 18 (9.6%), IVa in 3 (1.6%), IVb in 2 (1.1%) and V in 7 (3.7%) patients. Drain amylase on POD 1 showed the largest area under the curve (0.872, p < 0.001), followed by CRP (0.803, p < 0.001) and PCT on POD 3 (0.651, p < 0.011). Drain amylase on POD 1 > 303 U/l (OR 0.045, 95% CI 0.010-0.195, p < 0.001), CRP > 203 mg/l (OR 0.098, 95% CI 0.041-0.235, p < 0.001) and PCT > 0.85 µg/l (OR 0.393, 95%CI 0.178-0.869, p = 0.02) were significant predictors of relevant POPF in the univariate analysis. CRP > 203 mg/l (OR 0.098, 95% CI 0.024-0.403, p = 0.001) and drain amylase > 303 U/l (OR 0.064, 95% CI 0.007-0.554, p = 0.01) remained independent predictors in the multivariable analysis. The combination of drain amylase on POD 1 and CRP on POD 3 had a sensitivity and specificity of 87.4% and 90.9% to predict relevant POPF. CONCLUSION: Drain amylase on POD 1 and CRP on POD 3 can accurately predict clinically relevant POPF after partial pancreaticoduodenectomy. The accuracy of PCT on POD 3 is limited.

The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III trial of the German AIO/CAO-V/CAOGI.

BACKGROUND: Historical data indicate that surgical resection may benefit select patients with metastatic gastric and gastroesophageal junction cancer. However, randomized clinical trials are lacking. The current RENAISSANCE trial addresses the potential benefits of surgical intervention in gastric and gastroesophageal junction cancer with limited metastases. METHODS: This is a prospective, multicenter, randomized, investigator-initiated phase III trial. Previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) receive 4 cycles of FLOT chemotherapy alone or with trastuzumab if Her2+. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will proceed to randomization. The primary endpoint is overall survival; main secondary endpoints are quality of life assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 22 patients have been enrolled. DISCUSSION: If the RENAISSANCE concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, patients with gastric or GEJ cancer and metastases will no longer be considered candidates for surgical intervention. TRIAL REGISTRATION: The article reports of a health care intervention on human participants and is registered on October 12, 2015 under ClinicalTrials.gov Identifier: NCT02578368 ; EudraCT: 2014-002665-30.

Reduced complication rate after modified binding purse-string-mattress sutures pancreatogastrostomy versus duct-to-mucosa pancreaticojejunostomy.

BACKGROUND AND PURPOSE: A 2011 metaanalysis demonstrated no difference in postoperative complications between pancreatogastrostomy and pancreaticojejunostomy after pancreaticoduodenectomy with the limitation of heterogeneity among the analysed studies. The present study compares postoperative complications after duct-to-mucosa pancreaticojejunostomy with a modified binding purse-string-mattress sutures pancreatogastrostomy in a teaching hospital. METHODS: One-hundred consecutive pancreaticoduodenectomies were reconstructed either by pancreaticojejunostomy (n = 50, 2004-2008) or modified pancreatogastrostomy (n = 50, 2008-2011). Prospective patients' data was retrospectively analysed for postoperative complications. MAIN FINDINGS: Complications occurred significantly less after modified pancreatogastrostomy compared to pancreaticojejunostomy (p = 0.016). This was mainly due to a significantly lower rate of pancreatic fistula (p = 0.029), especially a lower rate of clinically relevant B and C fistulas (p = 0.011). In particular, the fistula rate was reduced in patients with a soft, non-fibrotic pancreas (p = 0.0231). Postoperative mortality was also lower after modified pancreatogastrostomy (p = 0.042). Uni- and multivariate analyses revealed a soft, non-fibrotic pancreatic texture (odds ratio 5.4, p = 0.028), a non-dilatated pancreatic duct (p = 0.047) and pancreaticojejunostomy (odds ratio 10.7, p = 0.026) as independent, negative factors for pancreatic fistula. CONCLUSION: In a teaching hospital, modified pancreatogastrostomy seems to be superior to pancreaticojejunostomy regarding pancreatic fistula, especially in patients with a soft, non-fibrotic pancreas and/or a small duct. An ongoing prospective randomised multicentre trial (RECOPANC) might confirm these results.