Cancer-associated venous thrombosis in the surgical setting.

OBJECTIVE: Cancer patients are at a relatively high risk of venous thromboembolism (VTE), and this has implications for surgical outcome. DATA SOURCE: English literature search including the keywords cancer, surgery and VTE was undertaken to review the risk, etiology, prevention and treatment of VTE in surgical oncology patients. DATA SYNTHESIS: Malignant disease is highlighted as an important risk factor for VTE with an odds ratio of 6.5. The risk factors include higher age, previous VTE, advanced cancer, length of operation and immobility. CONCLUSIONS: Use of in-hospital thromboprophylaxis with low-molecular-weight heparin (LMWH) or low dose unfractionated heparin with graded stockings has been validated both in terms of safety and efficacy and should be considered for all patients. Subcutaneous LMWH has replaced unfractionated heparin for the initial treatment of VTE. The use of long-term LMWH instead of oral anticoagulants can substantially reduce the risk of recurrent VTE without increased bleeding. Recently, results of few trials have shown that LMWH may improve patient survival.

Correlation between preoperative biliary drainage, bile duct contamination, and postoperative outcomes for pancreatic surgery.

BACKGROUND: Although previously examined, the potential relationship between preoperative biliary drainage (PBD), intraoperative bile culture (IBC), and postoperative morbidity and mortality rate for pancreatic surgery remains unclear. METHODS: Two hundred twenty patients underwent operation for either benign pancreatic disease or malignant periampullary and pancreatic neoplasms, consisting of pylorus-preserving proximal pancreatoduodenectomy (n = 180), biliary bypass (n = 31), and total pancreatectomy (n = 9). An intraoperative bile specimen was prospectively collected immediately after division of the bile duct and sent for bacteriologic evaluation for both aerobic and anaerobic microorganisms. Morbidity and mortality rates were evaluated. RESULTS: Of 220 patients evaluated, 113 patients (51.4%) had a positive IBC. Factors associated with a positive IBC were age >70 years (odds ratio [OR], 5.9;95% confidence interval, [CI]: 1.6-22.1; P = .007), history of coronary artery disease (OR, 0.08; 95% CI, 0.01-0.5; P = .007), diagnosis of neoplasia (OR, 0.3; 95% CI, 0.1-0.9; P =. 03), and PBD (OR, 0.1; 95% CI, 0.06-0.2; P = .0001). Infectious complications (OR, 1.8; 95% CI, 1-3; P = .03), and wound infection (OR, 2.8; 95% CI,1.4-5.3; P = .002) were greater in patients with positive IBC. CONCLUSIONS: PBD predisposes to a positive IBC. Patients with a positive IBC have a clinically important increased risk of developing both infectious complications and wound infection after pancreatic surgery.

Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS).

PURPOSE: In experimental systems, interference with coagulation can affect tumor biology. Furthermore, it has been suggested that low molecular weight heparin therapy may prolong survival in patients with cancer. The primary aim of this study was to assess survival at 1 year of patients with advanced cancer. PATIENTS AND METHODS: Patients with advanced malignancy (N = 385) were randomly assigned to receive either a once-daily subcutaneous injection of dalteparin (5,000 IU), a low molecular weight heparin, or placebo for 1 year. RESULTS: The Kaplan-Meier survival estimates at 1, 2, and 3 years after randomization for patients receiving dalteparin were 46%, 27%, and 21%, respectively, compared with 41%, 18%, and 12%, respectively, for patients receiving placebo (P =.19). In an analysis not specified a priori, survival was examined in a subgroup of patients (dalteparin, n = 55; and placebo, n = 47) who had a better prognosis and who were alive 17 months after randomization. In these patients, Kaplan-Meier survival estimates at 2 and 3 years from randomization were significantly improved for patients receiving dalteparin versus placebo (78% v 55% and 60% v 36%, respectively, P =.03). The rates of symptomatic venous thromboembolism were 2.4% and 3.3% for dalteparin and placebo, respectively, with bleeding rates of 4.7% and 2.7%, respectively. CONCLUSION: Dalteparin administration did not significantly improve 1-year survival rates in patients with advanced malignancy. However, the observed improved survival in a subgroup of patients with a better prognosis suggests a potential modifying effect of dalteparin on tumor biology.

Adenosine preconditioning attenuates hepatic reperfusion injury in the rat by preventing the down-regulation of endothelial nitric oxide synthase.

BACKGROUND: Previous work has suggested that in the liver, adenosine preconditioning is mediated by nitric oxide. Whether the endothelial isoform of nitric oxide synthase plays a part in this mechanism has however not yet been investigated. METHODS: Wistar rats were used (6 in each group)--Groups: (1) sham, (2) ischemia-reperfusion, (3) adenosine + ischemia-reperfusion, (4) endothelial isoform inhibitor + adenosine + ischemia-reperfusion. RESULTS: Using immunohistochemistry, this study has revealed a decrease in the expression of endothelial nitric oxide synthase following hepatic ischemia-reperfusion. This was prevented by adenosine pre-treatment. When an inhibitor of endothelial nitric oxide synthase was administered prior to adenosine pre-treatment, pre-conditioning did not occur despite normal expression of endothelial nitric oxide synthase. CONCLUSIONS: These findings suggest that adenosine attenuates hepatic injury by preventing the downregulation of endothelial nitric oxide synthase that occurs during ischemia-reperfusion.

Differential nitric oxide synthase expression during hepatic ischemia-reperfusion.

BACKGROUND: In recent years the important role of nitric oxide in hepatic ischemia-reperfusion injury has been increasingly recognised. The prevailing consensus is that reperfusion injury may be partly the result of decreased production of nitric oxide from endothelial nitric oxide synthase and excessive production of nitric oxide from the inducible isoform. We therefore undertook this study to characterize the expression of different nitric oxide synthase isoforms during hepatic reperfusion. METHODS: Male Wistar rats (n = 6) were subjected to 45 minutes of partial hepatic ischemia (left lateral and median lobes) followed by 6 hours of reperfusion. Control animals (n = 6) were subjected to sham laparotomy. The expression of endothelial and inducible nitric oxide synthase was examined using immunohistochemistry and Western blotting. Liver sections were also stained with nitrotyrosine antibody, a specific marker of protein damage induced by peroxynitrite (a highly reactive free radical formed from nitric oxide). RESULTS: Liver sections from all the control animals showed normal expression of the endothelial isoform and no expression of inducible nitric oxide synthase. Livers from all the animals subjected to hepatic ischemia showed decreased expression of endothelial nitric oxide synthase, and all but one animal from this group showed expression of the inducible isoform both in inflammatory cells and in hepatocytes. Western blotting confirmed these findings. Staining with the antinitrotyrosine antibody was also confined to five liver sections from animals subjected to hepatic ischemia. CONCLUSIONS: During the reperfusion period after hepatic ischemia, endothelial nitric oxide synthase is downregulated while inducible nitric oxide synthase is expressed in both hepatocytes and inflammatory cells. The presence of nitrotyrosine in livers subjected to hepatic ischemia-reperfusion suggests that the expression of inducible nitric oxide synthase plays an important role in mediating reperfusion injury in this model.

Differential expression of pulmonary nitric oxide synthase isoforms after intestinal ischemia-reperfusion.

BACKGROUND/AIMS: Nitric oxide has been implicated in both attenuating and aggravating ischemia-reperfusion injury in most organs. This study aimed to investigate the role of nitric oxide produced by the two principal isoforms of nitric oxide synthase in the lung during post-ischemic reperfusion of the intestine. METHODOLOGY: Rats were randomized into four groups of 6 animals: Group A: laparotomy and superior mesenteric artery dissection without occlusion and maintenance for 2 h (control group at 2 h). Group B: laparatomy and superior mesenteric artery occlusion for 30 min and reperfusion of the intestine for 2 h (ischemia-reperfusion group at 2 h). Group C: control animals at 6 h. Group D: ischemia-reperfusion animals at 6 h. Arterial blood pressure was monitored throughout the procedure. Animals were euthanazed at the end of the experiment, and lungs were harvested for histological assessment of injury and for immunohistochemical examination of nitric oxide synthase isoforms and nitrotyrosine. RESULTS: In all animals subjected to intestinal ischemia a period of systemic hypotension occurred immediately upon reperfusion. Histological evidence of lung injury was limited to those animals subjected to an intestinal reperfusion insult. Compared to control animals, pulmonary endothelial nitric oxide synthase expression was diminished at 2 h (p = 0.002), while expression of inducible nitric oxide synthase (p = 0.002) and nitrotyrosine (p = 0.02) was increased at 6 h. CONCLUSIONS: Following intestinal ischemia-reperfusion, early pulmonary damage is associated with decreased endothelial nitric oxide synthase expression in the lung. Expression of inducible nitric oxide synthase occurs during the later stages of reperfusion; this leads to overproduction of nitric oxide with consequent nitrosylation of protein tyrosine residues and thus aggravated pulmonary injury.

T-tube jejunostomy feeding after pancreatic surgery: a safe adjunct.

OBJECTIVE: Patients with pancreatic disease are often malnourished because of biliary and gastric outlet obstruction or the catabolic response to sepsis or cancer. In this study, we reviewed our experience of providing enteral nutrition through a T-tube jejunostomy in these patients. METHODS: The records of a consecutive series of 36 patients who had undergone pancreatic operations during the last 4 years were reviewed. Data were collected on preoperative nutritional status and postoperative feeding. RESULTS: All patients had partially hydrolysed feeds administered through a T-tube jejunostomy, placed during pylorus-preserving proximal pancreatoduodenectomy (21 patients), Whipple's procedure (4), debridement of pancreatic necrosis (3), palliative bypass (2), distal pancreatectomy (2), cyst-jejunostomy (3) or accessory sphincteroplasty (1). Tube feeding was employed for a mean of 18 days. There were no related deaths. Eight patients had complications directly attributable to the tube, including blockage (4), dislodgement (2), pericatheter leakage (2) and peritonitis (1). Twenty patients had complications related to feeds that included transient diarrhoea (13), abdominal distension (8), nausea or vomiting (6) and pain (6). Consequently, nitrogen and energy needs were completely fulfilled in only 19 patients. CONCLUSION: Despite many minor shortcomings, jejunostomy tube feeding appears to be a safe adjunct to pancreatic surgery.

Supergastrinoma: simultaneous peptic ulceration of esophagus, stomach, and small intestine.

Synchronous involvement of the esophagus, stomach, and small intestine by peptic ulceration has not been previously described in the Zollinger-Ellison syndrome. Two patients presented with abdominal pain, diarrhea, weight loss, and dysphagia while on acid suppressants. Fasting hypergastrinemia was confirmed. Endoscopy revealed peptic stricture of the esophagus with ulcerations in the stomach, duodenum, and jejunum. Imaging showed a mass in the head of pancreas. The first patient underwent distal esophagectomy, total gastrectomy, and resection of the head of pancreas for a pancreatic primary. Resection of the third and fourth parts of the duodenum and proximal jejunum was undertaken in the second patient with a duodenal primary. Malignant gastrinoma was confirmed histologically. "Supergastrinoma" describes a tumor causing synchronous peptic ulceration and/or stricture extending from the esophagus to the jejunum. Operative management entails customized resection of the areas irretrievably damaged by the ulceration together with the tumor.

Management of delayed postoperative hemorrhage after pancreaticoduodenectomy: a meta-analysis.

OBJECTIVE: To determine whether interventional radiology (IR) or laparotomy (LAP) is the best management of delayed postoperative hemorrhage (DPH) after pancreaticoduodenectomy. Data Source We undertook an electronic search of MEDLINE and selected for analysis only original articles published between January 1, 1990, and December 31, 2007. STUDY SELECTION: Two of us independently selected studies reporting on clinical presentation and incidence of postoperative DPH and the following outcomes: complete hemostasis, morbidity, and mortality. DATA EXTRACTION: Two of us independently performed data extraction. Data were entered and analyzed by means of dedicated software from The Cochrane Collaboration. A random-effects meta-analytical technique was used for analysis. DATA SYNTHESIS: One hundred sixty-three cases of DPH after pancreaticoduodenectomy were identified from the literature. The incidence of DPH after pancreaticoduodenectomy was 3.9%. Seventy-seven patients (47.2%) underwent LAP; 73 (44.8%), IR; and 13 (8%), conservative treatment. On meta-analysis comparing LAP vs IR for DPH, no significant difference was found between the 2 treatment options for complete hemostasis (73% vs 76%; P = .23), mortality (43% vs 20%; P = .14), or morbidity (77% vs 35%; P = .06). CONCLUSIONS: This meta-analysis, although based on data from small case series, is unable to demonstrate any significant difference between LAP and IR in the management of DPH after pancreaticoduodenectomy. The management of this life-threatening complication is difficult, and the appropriate treatment pathway ultimately will be decided by the clinical status of the patient and the institution preference.

Pancreaticoduodenectomy for periampullary malignancies: the effect of bile colonization on the postoperative outcome.

OBJECTIVES: The presence of bacteria in the bile of patients undergoing biliary tract surgery has been proposed as associated to an increased incidence of postoperative complications. The present study was designed to determine whether colonization of the bile has an adverse effect in terms of postoperative infectious or noninfectious complications and mortality in a homogenous population of patients suffering from periampullary region malignancies, who all underwent resectional (curative) procedures. MATERIALS AND METHODS: Between January 1997 and December 2002, 115 patients (n = 115) suffering from periampullary region malignancies underwent resectional procedures. Fifty-two of the above patients were referred having undergone preoperative internal biliary drainage. During the operation, bile was routinely isolated from the common bile duct and was sent for culture and sensitivity. Based on the bile culture results, the patients were divided in sterile and colonized group and were retrospectively compared in terms of postoperative outcome and mortality. RESULTS: Of the 115 bile cultures, 67 were colonized with bacteria and 48 were sterile. Postoperatively, 40 patients developed 35 noninfectious and 21 infectious complications. Univariate analysis did not disclose statistically significant differences in overall, noninfectious or infectious morbidity and mortality between the two groups of patients. Although not statistically significant, a higher incidence (22 vs 10%) of postoperative leaks in the colonized group of patients was noticed. Multiple regression analysis disclosed that colonized bile was independently related to the advanced age, preoperative biliary drainage presence, elevated preoperative serum bilirubin levels and low preoperative serum albumin levels but did not predispose to an increased postoperative morbidity, mortality, or reoperation rate. CONCLUSION: The present study did not conclude in any statistically significant differences in the postoperative infectious and noninfectious morbidity as well as mortality, between colonized and sterile groups of patients who underwent resectional procedures for malignancies of the periampullary region. Although internal biliary drainage introduces microorganisms into the biliary tree, this colonization does not increase the risk of either infectious or noninfectious complications or postoperative death. Thus, the likelihood of bacterobilia should not contraindicate the procedure in selected cases.

Long-term results of distal pancreatectomy for chronic pancreatitis in 90 patients.

OBJECTIVE: To determine the indications for distal pancreatectomy for chronic pancreatitis and to evaluate the risks, functional loss, and outcome of the procedure. SUMMARY BACKGROUND DATA: Chronic pancreatitis is generally associated with continued pain, parenchymal and ductal hypertension. and progressive pancreatic dysfunction, and it is a cause of premature death in patients who receive conservative treatment. Good results have recently been reported by the authors and others for resection of the pancreatic head in this disease, but distal pancreatectomy is a less popular option attended by variable success rates. It remains a logical approach for patients with predominantly left-sided pancreatic disease, however. METHODS: A personal series of 90 patients undergoing distal pancreatectomy for chronic pancreatitis over the last 20 years has been reviewed, with a mean postoperative follow-up of 34 months (range 1-247). Pancreatic function was measured before and after operation in many patients. RESULTS: Forty-eight of 84 patients available for follow-up had a successful outcome in terms of zero or minimal, intermittent pain. There was one perioperative death, but complications developed in 29 patients, with six early reexplorations. Morbidity was unaffected by associated splenectomy or right-to-left dissection. Late mortality rate over the follow-up period was 10%; most of these late deaths occurred because of failure to abstain from alcohol. Preoperative exocrine function was abnormal in two thirds of those tested and was unchanged at follow-up. Diabetic curves were seen in 10% of patients preoperatively, while there was an additional diabetic morbidity rate of 23% related to the procedure and late onset of diabetes (median duration 27 months) in another 23%. Diabetic onset was related to percentage parenchymal resection as well as splenectomy. Outcome was not clearly dependent on the etiology of pancreatitis or on disease characteristics as assessed by preoperative imaging. However, patients with pseudocyst disease alone did better than other groups. Twenty-one of 36 patients who failed to respond to distal pancreatectomy required further intervention, including completion pancreatectomy, neurolysis, and sphincteroplasty. Thirteen of these 21 patients achieved long-term pain relief after their second procedure. CONCLUSIONS: Distal pancreatectomy for chronic pancreatitis from any etiology can be performed with low mortality and a good outcome in terms of pain relief and return to work in approximately 60% of patients. Little effect is seen on exocrine function of the pancreas, but there is a diabetic risk of 46% over 2 years. Pseudocyst disease is associated with the best outcome, but other manifestations of this disease, including strictures, calcification, and limited concomitant disease in the head of the pancreas, can still be associated with a good outcome.