Laparoscopic versus open distal pancreatectomy-a propensity score-matched analysis from the German StuDoQ|Pancreas registry.

PURPOSE: The aim of this study was to assess intraoperative, postoperative, and oncologic outcome in patients undergoing laparoscopic distal pancreatectomy (LDP) versus open distal pancreatectomy (ODP) for benign and malignant lesions of the pancreas. METHODS: Data from patients undergoing distal pancreatic resection were extracted from the StuDoQ|Pancreas registry of the German Society for General and Visceral Surgery. After propensity score case matching, groups of LDP and ODP were compared regarding demography, comorbidities, operative details, histopathology, and perioperative outcome. RESULTS: At the time of data extraction, the StuDoQ|Pancreas registry included over 3000 pancreatic resections from over 50 surgical departments in Germany. Data from 353 patients undergoing ODP (n = 254) or LDP (n = 99) from September 2013 to February 2016 at 29 institutions were included in the analysis. Baseline data showed a strong selection bias in LDP patients, which disappeared after 1:1 propensity score matching. A comparison of the matched groups disclosed a significantly longer operation time, higher rate of spleen preservation, more grade A pancreatic fistula, shorter hospital stay, and increased readmissions for LDP. In the small group of patients operated for pancreatic cancer, a lower lymph node yield with a lower lymph node ratio was apparent in LDP. CONCLUSIONS: LDP needed more time but potential advantages include increased spleen preservation and shorter hospital stay, as well as a trend for less transfusion, ventilation, and mortality. LDP for pancreatic cancer was performed rarely and will need critical evaluation in the future. Data from a prospective randomized registry trial is needed to confirm these results.

Hybrid minimally invasive esophagectomy vs. open esophagectomy: a matched case analysis in 120 patients.

PURPOSE: In esophageal surgery, total minimally invasive techniques compete with hybrid and robot-assisted procedures. The benefit of the individual techniques for the patient remains vague. At our institution, the hybrid minimally invasive laparoscopic-thoracotomic esophagectomy (HMIE) has been routinely applied since 2013. We conducted this retrospective study to analyze the perioperative outcome. METHODS: Since 2013, 60 patients were operated in HMIE technique for esophageal cancer. Each of these patients was paired according to the criteria of gender, BMI, age, tumor histology, pulmonary preexisting conditions, and a history of smoking with a patient treated by open esophagectomy (OE). Perioperative parameters were extracted from our prospectively maintained database and compared among the groups. RESULTS: The HMIE and OE groups were homogeneous in terms of patient- and tumor-related data. There was no difference in lymph nodes harvested (22 vs. 20, p = 0.459) and R0-resection rate (95 vs. 93%, p = 0.500). The operation time for the HMIE was significantly shorter (329 vs. 407 min, p < 0.001). There was no difference between the groups with respect to surgical complications (37 vs. 37%, p = 0.575), but the patients undergoing hybrid technique showed more delayed gastric emptying (23 vs. 10%, p = 0.042). Pulmonary morbidity was significantly reduced after HMIE (20 vs. 42%, p = 0.009). This affected both the occurrence of pneumonia and pleural effusions. The difference in the overall complication rate was not significant (50 vs. 60%, p = 0.179), but life-threatening complications (Clavien/Dindo 4/5) were less frequent (2 vs. 12%, p = 0.031). Overall, there was significantly less need for transfusion after HMIE (18 vs. 50%, p < 0.001), and hospital (and IMC) stay was significantly shorter (14 (6) vs. 18 (7) days, p = 0.002 (0.003)). The multivariate analysis confirms the surgical procedure as an independent risk factor for the development of pulmonary complications (OR 3.2, p = 0.011). Furthermore, preexisting pulmonary conditions were identified as a risk factor (OR 3.6, p = 0.006). CONCLUSION: Our retrospective analysis shows that reduction of postoperative pulmonary morbidity, perioperative blood loss, and shortening of hospital stay can be achieved by HMIE. The procedure is safe, and the rate of surgical complications and oncological radicality is comparable to the conventional procedure.

Characterization of various cell lines from different ampullary cancer subtypes and cancer associated fibroblast-mediated responses.

BACKGROUND: Ampullary cancer is a relatively rare form of cancer and usually treated by pancreatoduodenectomy, followed by adjuvant therapy. The intestinal subtype is associated with markedly improved prognosis after resection. At present, only few cell lines are available for in vitro studies of ampullary cancer and they have not been collectively characterized. METHODS: We characterize five ampullary cancer cell lines by subtype maker expression, epithelial-mesenchymal transition (EMT) features, growth and invasion, drug sensitivity and response to cancer-associated fibroblast conditioned medium (CAF-CM). RESULTS: On the basis of EMT features, subtype marker expression, growth, invasion and drug sensitivity three types of cell lines could be distinguished: mesenchymal-like, pancreatobiliary-like and intestinal-like. Heterogeneous effects from the cell lines in response to CAF-CM, such as different growth rates, induction of EMT markers as well as suppression of intestinal differentiation markers were observed. In addition, proteomic analysis showed a clear difference in intestinal-like cell line from other cell lines. CONCLUSION: Most of the available AMPAC cell lines seem to reflect a poorly differentiated pancreatobiliary or mesenchymal-like phenotype, which is consistent to their origin. We suggest that the most appropriate cell line model for intestinal-like AMPAC is the SNU869, while others seem to reflect aggressive AMPAC subtypes.

Detailed analysis of epithelial-mesenchymal transition and tumor budding identifies predictors of long-term survival in pancreatic ductal adenocarcinoma.

BACKGROUND AND AIM: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive biology and poor prognosis even after resection. Long-term survival is very rare and cannot be reliably predicted. Experimental data suggest an important role of epithelial-mesenchymal transition (EMT) in invasion and metastasis of PDAC. Tumor budding is regarded as the morphological correlate of local invasion and cancer cell dissemination. The aim of this study was to evaluate the biological and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head. METHODS: Patients were identified from a prospectively maintained database, and baseline, operative, histopathological, and follow-up data were extracted. Serial tissue slices stained for Pan-Cytokeratin served for analysis of tumor budding, and E-Cadherin, Beta-Catenin, and Vimentin staining for analysis of EMT. Baseline, operative, standard pathology, and immunohistochemical parameters were evaluated for prediction of long-term survival (≥ 30 months) in uni- and multivariate analysis. RESULTS: Intra- and intertumoral patterns of EMT marker expression and tumor budding provide evidence of partial EMT induction at the tumor-host interface. Lymph node ratio and E-Cadherin expression in tumor buds were independent predictors of long-term survival in multivariate analysis. CONCLUSIONS: Detailed immunohistochemical assessment confirms a relationship between EMT and tumor budding at the tumor-host interface. A small group of patients with favorable prognosis can be identified by combined assessment of lymph node ratio and EMT in tumor buds.

The degree of local inflammatory response after colonic resection depends on the surgical approach: an observational study in 61 patients.

BACKGROUND: Clinical data indicate that laparoscopic surgery reduces postoperative inflammatory response and benefits patient recovery. Little is known about the mechanisms involved in reduced systemic and local inflammation and the contribution of reduced trauma to the abdominal wall and the parietal peritoneum. METHODS: Included were 61 patients, who underwent elective colorectal resection without intraabdominal complications; 17 received a completely laparoscopic, 13 a laparoscopically- assisted procedure and 31 open surgery. Local inflammatory response was quantified by measurement of intraperitoneal leukocytes and IL-6 levels during the first 4 days after surgery. RESULTS: There was no statistical difference between the groups in systemic inflammatory parameters and intraperitoneal leukocytes. Intraperitoneal interleukin-6 was significantly lower in the laparoscopic group than in the laparoscopically-assisted and open group on postoperative day 1 (26.16 versus 43.25 versus 40.83 ng/ml; p = 0.001). No difference between the groups was recorded on POD 2-4. Intraperitoneal interleukin-6 showed a correlation with duration of hospital stay on POD 1 (0.233, p = 0.036), but not on POD 2-4. Patients who developed a surgical wound infection showed higher levels of intraperitoneal interleukin-6 on postoperative day 2-4 (POD 2: 42.56 versus 30.02 ng/ml, p = 0.03), POD 3: 36.52 versus 23.62 ng/ml, p = 0.06 and POD 4: 34.43 versus 19.99 ng/ml, p = 0.046). Extraabdominal infections had no impact. CONCLUSION: The analysis shows an attenuated intraperitoneal inflammatory response on POD 1 in completely laparoscopically-operated patients, associated with a quicker recovery. This effect cannot be observed in patients, who underwent a laparoscopically-assisted or open procedure. Factors inflicting additional trauma to the abdominal wall and parietal peritoneum promote the intraperitoneal inflammation process.

Multimodal treatment of locally advanced esophageal adenocarcinoma: which regimen should we choose? Outcome analysis of perioperative chemotherapy versus neoadjuvant chemoradiation in 105 patients.

BACKGROUND: The study was done to compare treatment and long-term outcomes of neoadjuvant chemoradiation (neoCRT) and perioperative chemotherapy (periCTX) in patients with surgically treated esophageal adenocarcinoma. METHODS: An analysis of 105 patients with esophageal adenocarcinoma undergoing neoCRT (n = 58) or periCTX (n = 47) and esophagectomy between 2000 and 2012 was carried out. RESULTS: The overall median survival was 5.97 years. Postoperative morbidity and in-hospital mortality occurred in 74%/7% of the patients the neoCRT group and in 53%/0% of the patients in the periCTX group (P = 0.03/P = 0.08). Total or subtotal histological tumor response after neoadjuvant treatment and esophagectomy was found in 59% after neoCRT and 30% after periCTX (P < 0.01). Three- and five-year survival rates were 52%/45% for neoCRT and 68%/63% for periCTX (P = 0.05). PeriCTX was identified as an independent predictor of survival (RR2.6; 95% CI 1.3-5.1; P < 0.01). CONCLUSION: A higher rate of histologic response to neoCRT compared to histologic response following the preoperative cycles of periCTX does not translate to a benefit in overall survival. PeriCTX offers a decreased incidence of treatment-related morbidity and mortality and at least equal results in terms of survival compared to neoCRT in patients with locally advanced esophageal adenocarcinoma.

Impact of intraoperative temperature and humidity on healing of intestinal anastomoses.

PURPOSE: Clinical data indicate that laparoscopic surgery has a beneficial effect on intestinal wound healing and is associated with a lower incidence of anastomotic leakage. This observation is based on weak evidence, and little is known about the impact of intraoperative parameters during laparoscopic surgery, e.g., temperature and humidity. METHODS: A small-bowel anastomosis was formed in rats inside an incubator, in an environment of stable humidity and temperature. Three groups of ten Wistar rats were operated: a control group (G1) in an open surgical environment and two groups (G2 and G3) in the incubator at a humidity of 60 % and a temperature of 30 and 37 °C (G2 and G3, respectively). After 4 days, bursting pressure and hydroxyproline concentration of the anastomosis were analyzed. The tissue was histologically examined. Serum levels of C-reactive-protein (CRP) were measured. RESULTS: No significant changes were seen in the evaluation of anastomotic stability. Bursting pressure was very similar among the groups. Hydroxyproline concentration in G3 (36.3 µg/g) was lower by trend (p = 0.072) than in G1 (51.7 µg/g) and G2 (46.4 µg/g). The histological evaluation showed similar results regarding necrosis, inflammatory cells, edema, and epithelization for all groups. G3 (2.56) showed a distinctly worse score for submucosal bridging (p = 0.061) than G1 (1.68). A highly significant increase (p = 0.008) in CRP was detected in G3 (598.96 ng/ml) compared to G1 (439.49 ng/ml) and G2 (460 ng/ml). CONCLUSION: A combination of high temperature and humidity during surgery induces an increased systemic inflammatory response and seems to be attenuating the early regeneration process in the anastomotic tissue.

Covered self-expanding stent treatment for anastomotic leakage: outcomes in esophagogastric and esophagojejunal anastomoses.

BACKGROUND: Anastomotic leakage of esophagogastric and esophagojejunal anastomoses is a severe complication after esophagectomy and gastrectomy associated with a high mortality. We conducted this non-randomized observational study to evaluate the outcomes and clinical effectiveness of covered self-expanding stents (CSESs) in treating esophageal anastomotic leakage. METHODS: From 2002 to 2013, consecutive patients with anastomotic leakage after esophagogastrostomy or esophagojejunostomy who received CSESs were analyzed concerning leakage characteristics, leakage sealing rate, success and failure rates of CSES treatment, stent-related complications, and mortality. RESULTS: In 35 patients, anastomotic leakage originating from 5 cervical esophagogastrostomies, 6 thoracic esophagogastrostomies, 12 mediastinal esophagojejunostomies and 12 abdominal esophagojejunostomies were treated with 48 CSESs (16 fully CSES, 32 partially CSES). Of 35 patients, 24 received one stent, 9 received two consecutive stents, and 2 received three consecutive stents. Stent-related complications occurred in 71 % of patients (25/35). The most frequent complications were leakage persistence (44 %) and stent dislocation (19 %). Sealing of the anastomotic leakage was achieved in 24 (69 %) patients after a median (range) stenting time of 19 (1-78) days. Sealing rates differed significantly with 20 % (cervical esophagogastrostomies), 50 % (thoracic esophagogastrostomies), 92 % (mediastinal esophagojejunostomies) and 67 % (abdominal esophagojejunostomies) of patients (p = 0.023). Moreover, clinical success rates differed among these groups (60 vs. 67 vs. 92 vs. 58 %; p = 0.247). Clinical failure of stent treatment was more likely to be recognized in early postoperative leakage (median postoperative day 3 vs. 8; p = 0.098) compared with successful treatment, whereas no difference for clinical success rates was found comparing leakage ≤ 10 versus >10 mm (68 vs. 64 %; p = 0.479). CONCLUSION: CSESs are an effective treatment for anastomotic leakage in patients with esophagogastrostomies and esophagojejunostomies. Best results can be achieved in patients with anastomotic leakages following mediastinal esophagojejunostomy, and in leakages occurring after the very early postoperative phase.

Hybrid laparoscopic versus open pylorus-preserving pancreatoduodenectomy: retrospective matched case comparison in 80 patients.

PURPOSE: We compared the outcome of hybrid laparoscopic pylorus-preserving pancreatoduodenectomy (lapPPPD) and open PPPD (oPPPD) in a retrospective case-matched study. METHODS: Patients operated from 2010 to 2013 by lapPPPD were matched 1:1 for age, sex, histopathology, American Society of Anesthesiologists category and body mass index to oPPPD patients operated from 1996 to 2013. RESULTS: Patients eligible for lapPPPD are a risk group due to a high rate of soft pancreata. Complication rate and mortality were comparable to oPPPD. There was a significantly reduced transfusion requirement and a trend towards shorter operation time, less delayed gastric emptying, and reduced hospital stay. The main reason for conversion was portal venous tumor adhesion. Patient selection changed and operation time and hospital stay decreased with the surgeons' experience. CONCLUSION: In selected patients, a hybrid laparoscopic technique of pancreatoduodenectomy is feasible with complication rates comparable to the open procedure. There seem to be advantages in terms of transfusion requirement, operation time, and hospital stay.

Intestinal-type of differentiation predicts favourable overall survival: confirmatory clinicopathological analysis of 198 periampullary adenocarcinomas of pancreatic, biliary, ampullary and duodenal origin.

BACKGROUND: Periampullary adenocarcinomas comprise pancreatic, distal bile duct, ampullary and duodenal adenocarcinoma. The epithelia of these anatomical structures share a common embryologic origin from the foregut. With steadily increasing numbers of pancreatoduodenectomies over the last decades, pathologists, surgeons and oncologists are more often confronted with the diagnosis of "other than pancreatic" periampullary cancers. The intestinal subtype of ampullary cancer has been shown to correlate with better prognosis. METHODS: Histological subtype and immunohistochemical staining pattern for CK7, CK20 and CDX2 were assessed for n = 198 cases of pancreatic ductal, distal bile duct, ampullary and duodenal adenocarcinoma with clinical follow-up. Routine pathological parameters were included in survival analysis performed with SPSS 20. RESULTS: In univariate analysis, intestinal subtype was associated with better survival in ampullary, pancreatic ductal and duodenal adenocarcinoma. The intestinal type of pancreatic ductal adenocarcinoma was not associated with intraductal papillary mucinous neoplasm and could not be reliably diagnosed by immunohistochemical staining pattern alone. Intestinal differentiation and lymph node ratio, but not tumor location were independent predictors of survival when all significant predictor variables from univariate analysis (grade, TNM stage, presence of precursor lesions, surgical margin status, perineural, vascular and lymphatic vessel invasion, CK7 and CDX2 staining pattern) were included in a Cox proportional hazards model. CONCLUSIONS: Intestinal type differentiation and lymph node ratio but not tumor location are independent prognostic factors in pooled analysis of periampullary adenocarcinomas. We conclude that differentiation is more important than tumor location for prognostic stratification in periampullary adenocarcinomas.

One hundred consecutive kidney transplantations with simultaneous ipsilateral nephrectomy in patients with autosomal dominant polycystic kidney disease.

PURPOSE: Surgical management of autosomal dominant polycystic kidney disease (ADPKD) in patients awaiting renal transplantation is a challenging task. METHODS: From 1998 to 2009, a total of 100 consecutive renal transplantations with simultaneous unilateral nephrectomy were performed in 59 men and 41 women with ADPKD and end-stage renal failure. About 38% received kidney allografts from living donors. The ipsilateral polycystic kidney was removed at the time of renal transplantation. Immunosuppressive therapy was not modified. Cold ischaemia time was 155 (38-204 min) versus 910 min (95-2760 min) for living versus deceased donor transplantation. Mean weight of removed kidneys was 2002 g (414-8850 g). Mean follow-up was 3.0 years (0.8-10.0 years). RESULTS: Overall patient and graft survival were 97 and 96% at 1 year and 93 and 80% at 5 years, respectively. Serum creatinine at current follow-up was 1.49 (0.8-2.8) mg/dL. Surgical complications, which might be associated with simultaneous nephrectomy requiring re-operation, occurred in 12% (lymphocele 4%, hernia 4%, post-operative haematoma or bleeding 4%). None of the patients died peri-operatively. CONCLUSION: Renal transplantation with simultaneous unilateral nephrectomy in ADPKD is a reasonable procedure for patients suffering from massively enlarged native kidneys.

Total laparoscopic partial pancreatoduodenectomy and reconstruction via laparoscopic pancreatogastrostomy.

INTRODUCTION: Minimally invasive surgery has conquered almost all niches of abdominal surgery. Even though some surgeons have shown equal lymph node ratio and oncologic radicality for laparoscopic surgery of pancreatic cancer, oncologic surgeons still take reasonably conservative views of the use of minimally invasive techniques for the treatment of pancreatic cancer, especially if located in the head of the pancreas. Laparoscopic abdominal approaches on the other hand have a potential advantage of better visualization, decreased postoperative pain, decreased use of analgetics, and shorter hospital stay. We demonstrate in this technical surgical report the first description of a total laparoscopic pancreatoduodenectomy and reconstruction via laparoscopic pancreatogastrostomy in a 74-year-old female patient with a periampullary tumor. DISCUSSION: After pylorus-preserving pancreatoduodenectomy by superior mesenteric artery, first approach including standard lymphadenectomy, the reconstruction involved total laparoscopic end-to-side running-suture hepaticojejunostomy, double-layer running-suture antecolic pylorojejunostomy to the first jejunal loop, and pancreatogastrostomy via posterior gastrotomy secured by two anchoring and purse-string sutures.

Neutrophil granulocyte derived MMP-9 is a VEGF independent functional component of the angiogenic switch in pancreatic ductal adenocarcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) that is secreted by tumor cells plays a key role in angiogenesis. Matrix metalloproteinase 9 (MMP-9) is produced by inflammatory cells, such as stromal granulocytes (PMN), remodels the extracellular matrix and is known to promote angiogenesis indirectly by interacting with VEGF. The aim of this study was to determine the role of PMN-derived MMP-9, its interaction with VEGF, and the efficacy of anti-angiogenic therapy targeting MMP-9 with oral Doxycycline and VEGF with Bevacizumab in pancreatic cancer (PDAC). METHODOLOGY/PRINCIPAL FINDINGS: Inhibitors to MMP-9 (Doxycycline) and VEGF (Bevacizumab) were used alone or in combination in an in vitro angiogenesis assay to test their effect on angiogenesis caused by MMP-9, VEGF, PMN and PDAC cells. In an in vivo model of xenografted PDAC, treatment effects after 14 days under monotherapy with oral Doxycycline or Bevacizumab and a combination of both were evaluated. In vitro, PMN-derived MMP-9 had a direct and strong proangiogenic effect that was independent and additive to PDAC-derived VEGF. Complete inhibition of angiogenesis required the inhibition of VEGF and MMP-9. In vivo, co-localization of MMP-9, PMN and vasculature was observed. MMP inhibition with oral Doxycycline alone resulted in a significant decrease in PDAC growth and mean vascular density comparable to VEGF inhibition alone. CONCLUSIONS/SIGNIFICANCE: PMN derived MMP-9 acts as a potent, direct and VEGF independent angiogenic factor in the context of PDAC. MMP-9 inhibition is as effective as VEGF inhibition. Targeting MMP-9 in addition to VEGF is therefore likely to be important for successful anti-angiogenic treatment in pancreatic cancer.

Risk factors and complications following percutaneous endoscopic gastrostomy: a case series of 1041 patients.

BACKGROUND: Most studies exclude patients with severe coagulation disorders or those taking anticoagulants when evaluating the outcomes of percutaneous endoscopic gastrostomy (PEG). OBJECTIVE: To investigate complications and risk factors of PEG in a large clinical series including patients undergoing antiplatelet and anticoagulant therapy. METHODS: During a six-year period, 1057 patients referred for PEG placement were prospectively audited for clinical outcome. Exclusion criteria and follow-up care were defined. Complications were defined as minor or severe. Uni- and multivariate analyses were used to evaluate 14 risk factors. No standardized antibiotic prophylaxis was given. RESULTS: A total of 1041 patients (66% male, 34% female) with the following conditions underwent PEG: neurogenic dysphagia (n=450), cancer (n=385) and others (n=206). No anticoagulants were administered to 351 patients, thrombosis prophylaxis was given to 348 while full therapeutic anticoagulation was received by 313. No increased bleeding risk was associated with patients who had above-normal international normalized ratio values (OR 0.79 [95% CI 0.08 to 7.64]; P=1.00). The total infection rate was 20.5% in patients with malignant disease, and 5.5% in those with nonmalignant disease. Severe complications occurred in 19 patients (bleeding 0.5%, peritonitis 1.3%). Cirrhosis (OR 2.91 [95% CI 1.31 to 6.54]; P=0.008), cancer (OR 2.34 [95% CI 1.33 to 4.12]; P=0.003) and radiation therapy (OR 2.34 [95% CI 1.35 to 4.05]; P=0.002) were significant predictors of post-PEG infection. The 30-day mortality rate was 5.8%. There were no procedure-related deaths. CONCLUSIONS: Cancer, cirrhosis and radiation therapy were predictors of infection. Post-PEG bleeding and other complications were rare events. Collectively, the data suggested that patients taking concurrent anticoagulants had no elevated risk of post-PEG bleeding.

Colloid vs. crystalloid infusions in gastrointestinal surgery and their different impact on the healing of intestinal anastomoses.

BACKGROUND: The aim of this study was to investigate if colloid infusions have different effects on intestinal anastomotic healing when compared to crystalloid infusions depending on the amount of the administered volume. MATERIALS AND METHODS: Twenty-eight Wistar rats were randomly assigned to four groups receiving different amounts of either a crystalloid (Cry) or a colloid (Col) infusion solution. Animals with volume restriction (Cry (-) or Col (-)) were treated with a low and animals with volume overcharge (Cry (+) or Col (+)) with a high flow rate. All animals received an infusion for a 60-min period, while an end-to-end small bowel anastomosis was performed. At reoperation, the anastomotic bursting pressure (millimeters of mercury) was measured, as well as anastomotic hydroxyproline concentration. The presence of bowel wall edema was assessed histologically. RESULTS: Median bursting pressures were comparable in the Col (-) [118 mm Hg (range 113-170)], the Cry (-) [118 mm Hg (78-139)], and the Col (+) [97 mm Hg (65-152)] group. A significantly lower median bursting pressure was found in animals with crystalloid volume overload Cry (+) [73 mm Hg (60-101)]. Corresponding results were found for hydroxyproline concentration. Histology revealed submucosal edema in Cry (+) animals. CONCLUSIONS: In case of a fixed, high-volume load, colloids seem to have benefits on intestinal anastomotic healing when compared to crystalloid infusions.

A simple scoring system based on clinical factors related to pancreatic texture predicts postoperative pancreatic fistula preoperatively.

BACKGROUND: Postoperative pancreatic fistula (POPF) is regarded as the most serious complication of pancreatic surgery. The preoperative risk stratification of patients by simple means is of interest in perioperative clinical management. METHODS: Based on prospective data, we performed a risk factor analysis for POPF after pancreatoduodenectomy in 62 patients operated between 2006 and 2008 with special focus on clinical parameters that might serve to predict POPF. A predictive score was developed and validated in an independent second dataset of 279 patients operated between 2001 and 2010. RESULTS: Several pre- and intraoperative factors, as well as underlying pathology, showed significant univariate correlation with rate of POPF. Multivariate analysis (binary logistic regression) disclosed soft pancreatic texture (odds ratio [OR] 10.80, 95% confidence interval [CI] 1.80-62.20) and history of weight loss (OR 0.15, 95% CI 0.04-0.66) to be the only independent preoperative clinical factors influencing POPF rate. The subjective assessment of pancreatic hardness by the surgeon correlated highly with objective assessment of pancreatic fibrosis by the pathologist (r = -0.68, P < 0.001, two-tailed Spearman's rank correlation). A simple risk score based on preoperatively available clinical parameters was able to stratify patients correctly into three risk groups and was independently validated. CONCLUSIONS: Preoperative stratification of patients regarding risk for POPF by simple clinical parameters is feasible. Pancreatic texture, as evaluated intraoperatively by the surgeon, is the strongest single predictive factor of POPF. The findings of the study may have important implications for perioperative risk assessment and patient care, as well as for the choice of anastomotic techniques.

Impact of different crystalloid volume regimes on intestinal anastomotic stability.

BACKGROUND: Anastomotic insufficiency still remains an unsolved problem in digestive surgery. Little clinical data, regarding the impact of perioperative volume management exist, which suggest lower complication rates in intestinal surgery under restrictive volume regimens. The aim of our study was to investigate the effect of the extent of intraoperative fluid administration with crystalloids on the stability of intestinal anastomoses. MATERIAL AND METHODS: Twenty-one rats were randomly assigned to 3 experimental groups (n = 7 rats/group): control group CO (9 mL kg h crystalloid infusion), volume restriction group V (-) (3 mL kg h), and animals with volume overload V (+) (36 mL kg h). After midline incision, all animals received the corresponding infusion for a 30-minute period. Infusion was continued for further 30 minutes whereas an end-to-end small bowel anastomosis was performed 15 cm proximal to the Bauhin valve with 8 nonabsorbable interrupted inverting sutures. At reoperation on the 4th postoperative day, the anastomotic segment was dissected and the bursting pressure [mmHg] was measured. As a second parameter for the quality of anastomotic healing, hydroxyproline concentration was examined with a spectrophotometric method [microg/g dry tissue]. Histologically, structural changes of the anastomotic segments were assessed by 2 pathologists. Data are given as mean +/- SEM. RESULTS: Anastomotic insufficiency was not seen in all animals. Bursting pressure of CO animals was 102 +/- 8 mmHg. Bursting pressure was lowest in V (+) with high volume exposure at 77 +/- 6 mmHg and significantly lower than V (-) (112 +/- 9 mmHg; P = 0.01) whereas the difference compared with the CO group did not reach significant values. Hydroxyproline concentration in V (+) (64.4 microg/g dry tissue +/- 7.7) was significantly lower compared with V (-) (91.7 microg/g dry tissue +/- 9.1) animals (P < 0.05). In all animals with volume overload a marked submucosal edema was found. CONCLUSION: We could demonstrate for the first time in a systematic investigation, that the quantity of crystalloid infusion, applied intraoperatively, has a significant impact on functional (bursting pressure) and structural (hydroxyproline) stability of intestinal anastomoses in the early postoperative period. Because the stability and quality of an intestinal anastomosis have an impact on insufficiency rates, it should be noted that volume overload may have deleterious effects on anastomotic healing and postoperative complications in digestive surgery, possibly because of a marked bowel wall edema.

The inflammatory pancreatic head mass: significant differences in the anatomic pathology of German and American patients with chronic pancreatitis determine very different surgical strategies.

BACKGROUND: The indications for surgery and the surgical strategy selected for chronic pancreatitis (CP) vary widely, perhaps because of unaccounted characteristics of different patient populations such as the "inflammatory mass" in the head of the pancreas, commonly described in Europe but not in America. METHODS: We compared the pancreatic morphology, anatomic complications, indications leading to intervention, and the operation performed in 93 consecutive patients with CP operated upon either at a German (n = 48) or an American (n = 45) center specializing in pancreatic surgery. Pretreatment computed tomography/magnetic resonance imaging scans were reevaluated by 2 independent radiologists, especially to measure the anterior-posterior diameter of the pancreatic head (the inflammatory mass). RESULTS: The prevalence of endocrine and exocrine insufficiency was not significantly different. The median diameter of the pancreatic head mass was significantly larger in the German group (4.5 vs. 2.6 cm, P < 0.001). Inflammatory mass-dependent symptoms [gastric outlet obstruction (9/48 vs. 1/45; P = 0.02) and hemorrhage (7/48 vs. 0/45; P = 0.013)] were more frequent in the German group. Bile duct stenosis (19/48 vs. 11/43; P = 0.18) and suspicion of malignancy (5/48 vs. 11/43; P = 0.10) were comparable, whereas chronic pain (15/48 vs. 28/43; P = 0.001) was a more frequent indication for surgery in the US group. Splenic or portal vein thrombosis was found only in the German group. The duration of nonoperative therapy was significantly longer in the German group (median 56 vs. 26 months; P = 0.02). In the US group, a pancreatoduodenectomy with antrectomy was performed in most (89%) cases, whereas in the German group a duodenum-preserving head resection was preferred in more than half (25/47) of the cases (P < 0.001). CONCLUSIONS: Symptoms, duration of conservative therapy, and selection of surgical treatment all differed significantly between German and American patients with CP. These differences seem to be dependent upon surprising but unexplained disparities in the pathologic pancreatic anatomy between the 2 populations.

Long-term results after intraoperative radiation therapy for gastric cancer.

PURPOSE: We retrospectively analyzed the impact of intraoperative radiation therapy (IORT) on long-term survival in patients with resectable gastric cancer. METHODS AND MATERIALS: From 1991 to 2001, a total of 84 patients with gastric neoplasms underwent gastectomy or subtotal resection with IORT (23 Gy, 6-15 MeV; IORT-positive [IORT(+)] group). Patients with a history of additional neoadjuvant chemotherapy, histologically confirmed R1 or R2 resection, or reoperation with curative intention after local recurrence were excluded from further analysis. The remaining 61 patients were retrospectively matched with 61 patients without IORT (IORT-negative [IORT(-)] group) for Union Internationale Contre le Cancer (UICC) stage, patient age, histologic grading, extent of surgery, and level of lymph node dissection. Subgroups included postoperative UICC Stages I (n = 31), II (n = 11), III (n = 14), and IV (n = 5). RESULTS: Mean follow-up was 4.8 years in the IORT(+) group and 5.0 years in the IORT(-) group. The overall 5-year patient survival rate was 58% in the IORT(+) group vs. 59% in the IORT(-) group (p = 0.99). Subgroup analysis showed no impact of IORT on 5-year patient survival for those with UICC Stages I/II (76% vs. 80%; p = 0.87) and III/IV (21% vs. 14%, IORT(+) vs. IORT(-) group; p = 0.30). Perioperative mortality rates were 4.9% and 4.9% in the IORT(+) vs. IORT(-) group. Total surgical complications were more common in the IORT(+) than IORT(-) group (44.3% vs. 19.7%; p < 0.05). The locoregional tumor recurrence rate was 9.8% in the IORT(+) group. CONCLUSIONS: Use of IORT was associated with low locoregional tumor recurrence, but had no benefit on long-term survival while significantly increasing surgical morbidity in patients with curable gastric cancer.

Targeting vascular endothelial growth factor pathway offers new possibilities to counteract microvascular disturbances during ischemia/reperfusion of the pancreas.

BACKGROUND: It is of crucial importance to explore new therapeutic strategies capable of combating or even preventing pancreatic graft failure after transplantation caused by ischemia reperfusion damage. So far, the role of the hypoxia induced mediator vascular endothelial growth factor (VEGF) upon pancreatic microcirculation has not been described. Therefore the aim of this study was to investigate its influence, using the novel tyrosinekinase inhibitor PTK787/ZK222584 (PTK/ZK), upon functional capillary density (FCD), leukocyte-endothelium interaction (LEI), and macromolecular permeability (P) of normal and postischemic pancreas tissue. METHODS: Sprague-Dawley rats were anesthetized and randomly assigned to five groups (n=7/group): (a) sham, (b) ischemia/reperfusion (I/R) control, (c) I/R and PTK/ZK treatment, (d) VEGF-superfusion, (e) VEGF-superfusion and PTK/ZK-treatment. A recently established method of digital dynamic intravital epifluorescence microscopy was used for evaluating the effective microvascular permeability together with FCD and LEI. RESULTS: Comparison between sham vs. I/R shows a significant upregulation of VEGF-expression followed by deterioration of microcirculation with decreased FCD, increased P and LEI. Treatment with PTK/ZK resulted in a significant decrease of P under conditions of superfusion with VEGF as well as I/R compared to corresponding groups without treatment. CONCLUSION: VEGF plays a crucial causative role involving an increase in permeability in normal as well as in postischemic pancreatitis via tyrosinkinase receptors. VEGF seems to be partly accountable for a deterioration of FCD and an upregulation of LEI via VEGF-tyrosinekinase receptor independent mechanisms. VEGF might be a promising potential therapeutic target in order to minimize edema formation caused by I/R and pancreatitis in pancreas transplantation.