Clinical relevant pancreatic fistula after pancreatoduodenectomy: when negative amylase levels tell the truth.

Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940-0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81-0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five.

The role of abdominal drainage in pancreatic resection - A multicenter validation study for early drain removal.

BACKGROUND: Abdominal drainage and the timing of drain removal in patients undergoing pancreatic resection are under debate. Early drain removal after pancreatic resection has been reported to be safe with a low risk for clinical relevant postoperative pancreatic fistula (CR-POPF) when drain amylase on POD1 is < 5000U/L. The aim of this study was to validate this algorithm in a large national cohort. METHODS: Patients registered in the Dutch Pancreatic Cancer Audit (2014-2016) who underwent pancreatoduodenectomy, distal pancreatectomy or enucleation were analysed. Data on post-operative drain amylase levels, drain removal, postoperative pancreatic fistulae were collected. Univariate and multivariate analysis using a logistic regression model were performed. The primary outcome measure was grade B/C pancreatic fistula (CR-POPF). RESULTS: Among 1402 included patients, 433 patients with a drain fluid amylase level of <5000U/L on POD1, 7% developed a CR-POPF. For patients with an amylase level >5000U/L the CR-POPF rate was 28%. When using a cut-off point of 2000U/L or 1000U/L during POD1-3, the CR-POPF rates were 6% and 5% respectively. For patients with an amylase level of >2000U/L and >1000UL during POD 1-3 the CR-POPF rates were 26% and 22% respectively (n = 223). Drain removal on POD4 or thereafter was associated with more complications (p = 0.004). Drain amylase level was shown to be the most statistically significant predicting factor for CR-POPF (Wald = 49.7; p < 0.001). CONCLUSION: Our data support early drain removal after pancreatic resection. However, a cut-off of 5000U/L drain amylase on POD1 was associated with a relatively high CR-POPF rate of 7%. A cut-off point of 1000U/L during POD1-3 resulted in 5% CR-POPF and might be a safer alternative.

Multicentre randomized clinical trial of inspiratory muscle training versus usual care before surgery for oesophageal cancer.

BACKGROUND: Up to 40 per cent of patients undergoing oesophagectomy develop pneumonia. The aim of this study was to assess whether preoperative inspiratory muscle training (IMT) reduces the rate of pneumonia after oesophagectomy. METHODS: Patients with oesophageal cancer were randomized to a home-based IMT programme before surgery or usual care. IMT included the use of a flow-resistive inspiratory loading device, and patients were instructed to train twice a day at high intensity (more than 60 per cent of maximum inspiratory muscle strength) for 2 weeks or longer until surgery. The primary outcome was postoperative pneumonia; secondary outcomes were inspiratory muscle function, lung function, postoperative complications, duration of mechanical ventilation, length of hospital stay and physical functioning. RESULTS: Postoperative pneumonia was diagnosed in 47 (39·2 per cent) of 120 patients in the IMT group and in 43 (35·5 per cent) of 121 patients in the control group (relative risk 1·10, 95 per cent c.i. 0·79 to 1·53; P = 0·561). There was no statistically significant difference in postoperative outcomes between the groups. Mean(s.d.) maximal inspiratory muscle strength increased from 76·2(26·4) to 89·0(29·4) cmH2 O (P < 0·001) in the intervention group and from 74·0(30·2) to 80·0(30·1) cmH2 O in the control group (P < 0·001). Preoperative inspiratory muscle endurance increased from 4 min 14 s to 7 min 17 s in the intervention group (P < 0·001) and from 4 min 20 s to 5 min 5 s in the control group (P = 0·007). The increases were highest in the intervention group (P < 0·050). CONCLUSION: Despite an increase in preoperative inspiratory muscle function, home-based preoperative IMT did not lead to a decreased rate of pneumonia after oesophagectomy. Registration number: NCT01893008 (https://www.clinicaltrials.gov).

Role of omentectomy as part of radical surgery for gastric cancer.

BACKGROUND: A complete omentectomy is recommended as part of radical (sub)total gastrectomy for gastric cancer, but there is little evidence to suggest any survival benefit. The aim of this study was to evaluate the incidence of, and risk factors for, metastases in the greater omentum in patients undergoing gastrectomy for gastric cancer. METHODS: This was a multicentre prospective cohort study (OMEGA trial) of consecutive patients with gastric cancer undergoing (sub)total gastrectomy with complete en bloc omentectomy and modified D2 lymphadenectomy. After resection, the omentum was separated from the gastrectomy specimen distal to the gastroepiploic vessels and sent separately for pathological examination. The primary endpoint was the presence of metastases in the greater omentum. RESULTS: Of 100 included patients, five (5·0 per cent) had metastases in the greater omentum. Pathology results showed advanced tumours in all five (pT4b N1 M1, pT4b N2 M1, ypT4a N1 M1, ypT3 N2 M0, ypT3 N3 M0). The resection was microscopically non-radical at the proximal (3) or distal (2) resection margin in all of these patients. Metastases in the greater omentum correlated significantly with a microscopically non-radical resection, tumour expansion in the oesophagus or duodenum, linitis plastica or a proximal gastric tumour with diameter of at least 5 cm, stage III-IV disease and (y)pM1 category. CONCLUSION: In resectable gastric cancer, the incidence of metastases in the greater omentum is low, and when present associated with advanced disease and non-radical features. Thus, omentectomy as part of a radical gastrectomy may be omitted. REGISTRATION NUMBER: NCT02050659 ( http://www.clinicaltrials.gov).

Minimally invasive intrathoracic anastomosis after Ivor Lewis esophagectomy for cancer: a review of transoral or transthoracic use of staplers.

BACKGROUND: Minimally invasive Ivor Lewis esophagectomy is one of the approaches used worldwide for treating esophageal cancer. Optimization of this approach and especially identifying the ideal intrathoracic anastomosis technique is needed. To date, different types of anastomosis have been described. A literature search on the current techniques and approaches for intrathoracic anastomosis was held. The studies were evaluated on leakage and stenosis rate of the anastomosis. METHODS: The PubMed electronic database was used for comprehensive literature search by two independent reviewers. RESULTS: Twelve studies were included in this review. The most frequent applied technique was the stapled anastomosis. Stapled anastomoses can be divided into a transthoracic or a transoral introduction. This stapled approach can be performed with a circular or linear stapler. The reported anastomotic leakage rate ranges from 0 to 10%. The reported anastomotic stenosis rate ranges from 0 to 27.5%. CONCLUSIONS: This review has found no important differences between the two most frequently used stapled anastomoses: the transoral introduction of the anvil and the transthoracic. Clinical trials are needed to compare different methods to improve the quality of the intrathoracic anastomosis after esophagectomy.

Systematic approach of postoperative gastric conduit complications after esophageal resection.

Complications after esophagectomy related to ischemia of the graft are dreaded. Prompt assessment of the situation is essential. The series presented describes our experience regarding the evaluation of gastric tube complications. A score is presented classifying flexible endoscopy and CT-scan findings. A retrospective analysis from the charts of 47 consecutive patients who underwent esophagectomy for cancer was conducted. Patients who underwent upper endoscopy during admittance were entered in this study. Findings on flexible endoscopy and CT scan were systematic scored. According to the findings, different attitudes were taken. Between January 2006 and December 2007, 47 patients underwent esophagectomy for cancer. Eleven (23%) out of 47 patients were suspected to have complications related to the viability of the anastomosis. Median period to deterioration was 5 days. In 3 (27%) patients, stent placement was the only intervention necessary. In 2 (18%) patients, stent placement was combined with drainage of abscesses in the upper mediastinum. Five (46%) patients required a new right thoracotomy, with drainage of mediastinal abscesses and empyema. In 2 patients a limited resection and a new cervical anastomosis with a stent was created. Mean intensive care admission and hospital admittance was 30.2 days and 67.9 days, respectively. Two patients (18%) died during hospital admittance. All cervical anastomosis required postoperative dilatation. No complications related to the use of flexible endoscopy were seen. An aggressive policy is adopted in patients deteriorating following esophagectomy. CT-scanning of the thorax and a flexible endoscopy of the gastric conduit should always be performed. Direct therapy should be adopted without delay.

Influence of circumferential resection margin on prognosis in distal esophageal and gastroesophageal cancer approached through the transhiatal route.

We studied the influence of circumferential resection margin (CRM) involvement on survival in patients with malignancies of the distal esophagus and gastroesophageal junction. One hundred ten consecutive patients undergoing a laparoscopic or open transhiatal esophagectomy for malignancy of the distal 5 cm of the esophagus, or a Siewert I gastroesophageal junction tumor were analyzed, retrospectively. Only patients with potentially resectable tumors were included. CRM status was defined as clear or involved (microscopic tumor within 1 mm of the resection margin). Statistical analysis was done by means of univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard model. One hundred ten patients were analyzed. Sixty patients underwent open transhiatal esophagectomy, and 50 patients underwent laparoscopic transhiatal esophagectomy. There were 6 (5%) T(1), 18 (16%) T(2), and 86 (89%) T(3) tumors. CRM was clear in 68 (62%) patients and involved in 42 (38%) patients. Median survival in these groups was 50 vs. 20 months (P = 0.000). Since CRM involvement was only seen in T(3) tumors, this group was analyzed in detail. Median survival in the T(3)CRM(-) and T(3)CRM(+) group was 33 vs. 19 months (P = 0.004). For T(3)N(0) tumors, median survival in CRM(-) and CRM(+) was 40 and 22 months, respectively (P = 0.036). Median survival for T(3)N(1) tumors in CRM(-) and CRM(+) was 22 and 13 months, respectively (P = 0.049). Involvement of the circumferential resection margin was found to be an independent prognostic factor on survival in our study. It predicts a poor prognosis in patients with potentially resectable malignancies of the distal 5 cm of the esophagus and Siewert I adenocarcinomas of the gastro esophageal junction.

Immunological consequences of laparoscopic versus open transhiatal resection for malignancies of the distal esophagus and gastroesophageal junction.

BACKGROUND/AIM: Surgery remains the only curative therapy for esophageal cancer. The objective of the current study was to evaluate the impact of laparoscopic transhiatal esophagectomy versus open transhiatal esophagectomy on both inflammatory and immunological responses. METHODS: Seventeen patients undergoing laparoscopic or open surgery were included in the study. The postoperative inflammatory response was assessed by measuring WBC count and CRP, IL-6, IL-8, soluble TNF I and II receptor, and elastase levels. The postoperative immune function was assessed by measuring the monocyte HLA-DR expression. LPS-binding protein (LBP) and bactericidal/permeability-increasing protein (BPI) were measured to evaluate bacterial translocation. RESULTS: The IL-6 level increased significantly more in the patients who received open surgery as compared with the laparoscopic group. Both LBP and BPI increased predominantly in the laparoscopic group as compared with the group who received open surgery. No difference was found in HLA-DR expression between the two groups. CONCLUSION: Although both laparoscopic and conventional esophageal resections result in an activation of the inflammatory response, this study suggests that this response could be less pronounced after the laparoscopic approach. However, in the laparoscopic group higher LBP and BPI levels were seen, suggesting an increased endotoxemia. We postulate that the persistently elevated abdominal pressure results in a loss of mucosal barrier function, resulting in bacterial translocation. The cellular acidification of the cells of the peritoneum induced by CO(2) insufflation, however, blunts the expected inflammatory response.