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Low concentrations of albumin in serum and long gastric emptying times have been returned to normal in dogs by salt and water restriction, or a high protein intake. We aimed to determine the effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection in human beings. We randomly allocated ten patients to receive postoperative intravenous fluids in accordance present hospital practice (⩾3 L water and 154 mmol sodium per day) and ten to receive a restricted intake (⩽2 L water and 77 mmol sodium per day). All patients had no disease other than colonic cancer. The primary endpoint was solid and liquid-phase gastric emptying time, measured by dual isotope radionuclide scintigraphy on the fourth postoperative day. Secondary endpoints included time to first bowel movement and length of postoperative hospital stay. Analysis was by intention to treat. Median solid and liquid phase gastric emptying times (T50) on the fourth postoperative day were significantly longer in the standard group than in the restricted group (175 vs 72·5 min, difference 56 [95% CI 12–132], p=0·028; and vs 73·5 min, 52 [9–95], p=0·017, respectively). Median passage of flatus was 1 day later (4 vs 3 days, 2 [1–2], p=0·001); median passage of stool 2·5 days later (6·5 vs 4 days, 3 [2–4], p=0·001); and median postoperative hospital stay 3 days longer (9 vs 6 days, 3 [1–8], p=0·001) in the standard group than in the restricted group. One patient in the restricted group developed hypokalaemia, whereas seven patients in the standard group had side-effects or complications (p=0·01). Positive salt and water balance sufficient to cause a 3 kg weight gain after surgery delays return of gastrointestinal function and prolongs hospital stay in patients undergoing elective colonic resection.

Restoration of blood flow to an acutely ischemic lower limb may, paradoxically, result in systemic complications and unexpected mortality. We investigated the effect of acute ischemia-perfusion of the lower limb on cytokine production and end organ function. Plasma concentrations of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) were determined in five groups of male Wistar rats: control, 3 hours of bilateral hind limb ischemia alone, and 3 hours of bilateral hind limb ischemia followed by 1 hour, 2 hours, or 3 hours of reperfusion, respectively. In a second experiment, the effect of lower limb ischemia-reperfusion on remote organs (lung, liver, and kidney) was assessed biochemically and histologically. There was a significant increase in plasma concentrations of TNF-a in plasma of animals subjected to 3 hours of bilateral hind limb ischemia followed by 1 hour of reperfusion, 40.1 +/- 4.4 pg/ml, when compared with controls, 22.6 +/- 4.4 pg/ml, or animals in the ischemia-alone group, 16.3 +/- 5.2 (p <0.05). Plasma concentration of IL-6 increased progressively and significantly in animals subjected to bilateral hind limb ischemia followed by 1 hour of reperfusion, 720 +/- 107 pg/ml; 2 hours of reperfusion, 1987 +/- 489 pg/ml; or 3 hours of reperfusion, 6284 +/- 1244 (p <0.0001), compared with controls, 104 +/- 43 pg/ml; or animals in the ischemia-alone group, 140 +/- 55 pg/ml. In the study comparing portal and systemic concentrations of IL-6, systemic concentrations of IL-6, 967 +/- 184 pg/ml were significantly higher than those in the portal circulation 577 +/- 127 pg/ml (p <0.05). There was a significant increase in plasma concentrations of urea, creatinine, aspartate transaminase, alanine transaminase, and lactic dehydrogenase in reperfused animals compared with controls (p <0.001). Morbidity and mortality following reperfusion of the acutely ischemic limb may be a manifestation of multiple organ dysfunction caused by a systemic inflammatory response triggered by reperfusion of the ischemic extremities.

Background We aimed to study outcome in patients with an open abdomen in whom the abdominal vacuum-assisted closure system (V.A.C. ® Therapy ™ ) was used to provide temporary cover and achieve wound closure. Methods All patients in whom V.A.C. Therapy was used to manage laparotomy wounds between February 2006 and May 2007 at a University Teaching Hospital were followed up prospectively until successful completion or stoppage of V.A.C. Therapy. Results Of the 51 consecutive patients (33 male), V.A.C. Therapy was used to manage a laparostomy in 10 patients and abdominal wound dehiscence in 41. Median (IQR) duration of V.A.C. Therapy was 17 (7–26) days. Wound healing was achieved in 31 (61%) patients, four of whom had additional surgery to assist wound closure. The rest healed by secondary intention. Treatment was withdrawn due to therapy-related complications in nine patients and due to medical or logistical reasons in seven. Four patients died while on therapy. While most V.A.C. Therapy-related problems were minor, two patients developed enteric fistulae that necessitated surgical repair. At a median (IQR) follow-up of 8 (4–13) months, 18 patients had stable cutaneous coverage with no incisional hernia, 12 developed an incisional hernia, 9 were lost to follow-up, and 12 died. Conclusions V.A.C. Therapy is a useful adjunct in the management of the open abdomen and should be considered in the treatment of this problem. Restoration of cutaneous and fascial integrity of the abdominal wall, the risk of fistulisation, and the cost-effectiveness of this therapy require further evaluation.

Patients with chronic pancreatitis (CP) typically suffer intractable abdominal pain that is resistant to most analgesic strategies. Recent research indicates that the pain of CP may be in part due to oxygen free radical induced pancreatic damage. Using a randomized, double-blind, placebo-controlled crossover trial, we evaluated the efficacy of a combined antioxidant preparation in the management of CP. Patients with confirmed chronic pancreatitis (N = 36) were randomized to receive treatment with either Antox, which contains the antioxidants selenium, betacarotene, L-methionine, and vitamins C and E, or placebo for 10 weeks. Each group of patients then switched to receive the alternative treatment for a further 10 weeks. Markers of antioxidant status were measured by blood sampling, whereas quality of life and pain were assessed using the SF-36 questionnaire. Nineteen patients completed the full 20 weeks of treatment. Treatment with Antox was associated with significant improvements in quality of life in terms of pain (+17 antioxidant vs. −7 placebo), physical (+9 vs. −3) and social functioning (+8 vs. −7), and general health perception (+10 vs. −3). We conclude that treatment with antioxidants may improve quality of life and reduce pain in patients suffering from chronic pancreatitis.

Background T-tube drainage used to be standard practice after surgical choledocholithotomy, but there is now a tendency in some centers to close the common bile duct (CBD) primarily. This study was designed to review the complications associated with T-tube drainage after CBD exploration and to determine whether primary closure of the bile duct reduces postoperative morbidity. Methods A retrospective audit was performed on patients undergoing CBD exploration between July 1997 and March 2007, who were identified from the theatre database of one teaching hospital. Intraoperative findings and postoperative complications were recorded from the clinical notes. Results During the study period, 158 patients (97 women; median age 65 (range, 25–90) years) underwent CBD exploration. A T-tube was inserted in 91 patients (group I) and the CBD was closed primarily in 67 (group II). One or more biliary complications occurred in 26 patients (16.5%): 20 (22.0%) in group I and 6 (8.9%) in group II ( p  = 0.03). In group I, 15 had a biliary leak (3 needed reoperation), 2 had accidental slippage of the tube, 2 an entrapped T-tube, and 1 a retained stone. In group II, six patients had biliary leakage, two of whom were re-explored. Six patients in group I also had peritubal infection, necessitating the use of antibiotics. There were three deaths: two in group I (1 T–tube-related) and 1 in group II ( p  = 1, not significant). Conclusion There is a lower biliary complication rate associated with primary closure of the CBD than after T-tube drainage.

Background Elevated serum concentrations of M2-pyruvate kinase (M2-PK) correlate with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but the expression of M2-PK in formalin-fixed pancreatic tissue is unknown. We aimed to characterise the immunohistochemical expression of M2-PK in archived specimens of pancreaticobiliary and duodenal cancers, premalignant lesions, chronic pancreatitis, and normal pancreas. Methods Immunohistochemical staining was performed with mouse anti-M2-PK monoclonal antibody (clone DF-4) at an optimal dilution of 1:25 on tissue microarrays constructed from formalin-fixed paraffin-embedded pancreatic tissue of 126 consecutive patients undergoing pancreatic resections between June 2001 and June 2006. 104 underwent resection for cancer and 22 for chronic pancreatitis. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. A further 11 premalignant pancreaticobiliary and duodenal lesions were studied. M2-PK expression was quantified with the immunohistochemical score (IHS; Range 0-12). Results Benign non-ductal tissue in chronic pancreatitis and normal pancreas showed variable expression of M2-PK (IHS = 1 in 25%, IHS = 2-3 in 40%, IHS>3 in 40%). Benign pancreatic ductal epithelium, all primary pancreaticobiliary and duodenal premalignant lesions and cancers (and lymph node metastasis) showed complete lack of expression (IHS = 0). Conclusion Complete lack of M2-PK expression was observed in benign pancreatic ducts, premalignant lesions and cancer. M2-PK is present only in benign non-ductal epithelium in normal pancreas and peri-tumoural tissue.

Background Mitochondrial membrane complexes (MMCs) are key mediators of cellular oxidative phosphorylation, and inhibiting them could lead to cell death. No published data are available on the relative abundance of MMCs in different periampullary cancers. Therefore, we studied the expression profile of MMCs I, III, IV and V in periampullary cancers, reactive pancreatitis, normal pancreas and chronic pancreatitis. Methods This was a retrospective study on tissue microarrays constructed from formalin-fixed paraffin-embedded tissue from 126 consecutive patients (cancer = 104, chronic pancreatitis = 22) undergoing pancreatic resections between June 2001 and June 2006. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. Results MMCs I, III, IV and V were highly expressed (p < 0.05) in all primary periampullary cancers compared with metastatic lymph nodes and adjacent benign pancreas. MMCs III, IV and V were highly expressed in all cancers regardless of type compared with chronic pancreatitis (p < 0.05). Higher expression of MMCs I and V was associated with better survival and may, in part, relate to lower expression of these MMCs in poorly differentiated tumours compared with well and moderately differentiated tumours. Conclusions Differential expression of MMCs III, IV and V in primary periampullary cancers compared with adjacent benign periampullary tissue and chronic pancreatitis is a novel finding, which may render them attractive anticancer targets.

Background Morphometry [nuclear Ki-67 labelling, mitotic activity index (MI), and volume-corrected mitotic index (M/V)] for periampullary cancers using tissue microarrays has not been performed previously. The purpose of the study was to assess these indices on tissue microarray (TMA) sections constructed from patients with periampullary cancers and study their association with clinicopathological variables. Methods Immunohistochemical staining for Ki-67 was performed on formalin-fixed pancreatic TMA sections. Expression of Ki-67 was assessed as the percentage of cancer cell nuclei expressing MIB1, MI as the mean percentage of Ki-67 from 10 random high-power fields, and M/V was calculated after standardizing MI for connective tissue volume and microscope parameters in the tumor using established protocols. Results Patients ≥70 years with periampullary cancers had higher Ki-67 expression (>15) compared with patients <70 years of age (χ 2  = 3.9, P  = 0.047). Ki-67 expression was higher in tumors ≥2 cm (χ 2  = 4.9, P  = 0.028) compared with smaller tumors. Higher MI (>15) was clearly associated with worsening histological grade (χ 2  = 9.2, P  = 0.010). The median survival for tumors of the pancreaticobiliary subtype (pancreatic ductal adenocarcinoma and cholangiocarcinoma) was 43 months in the group with an M/V score of <20, compared with 18 months for the group with a score ≥20 ( P  = 0.001). There was no statistically significant difference in survival, based on M/V score, for tumors of the intestinal subtype (ampullary and duodenal adenocarcinoma). Conclusions In periampullary cancers, Ki-67 and MI are proliferative indices predictive of tumor behavior. M/V was predictive of survival in tumors of the pancreaticobiliary subtype.

Background: Necrotising pancreatitis is a challenging problem for the surgeon, as it is associated with considerable morbidity and mortality. The indications, timing of surgical intervention and type of procedure continue to be debated in an effort to improve the outcome of this devastating disease process. Methods: A retrospective analysis of early and long-term results in a series of 44 consecutive patients (34 men, 10 women, median age 46.5, range 13–74 years) who underwent necrosectomy for severe necrotising pancreatitis. In 16 patients necrosectomy and primary abdominal closure with drains was performed, 14 patients had planned staged necrosectomy and delayed abdominal closure with drains, and in 14 patients necrosectomy with open laparostomy was undertaken. Results: There were 8 deaths (18%) and 14 cases (32%) of significant hospital morbidity (fistula 10, pseudocyst 2, renal failure 2). Variables which correlated with mortality were: high APACHE II score, acute renal failure requiring dialysis, and requirement for surgical intervention at an early stage (within the first two weeks). A total of 28 late complications occurred in 21 of the surviving patients (endocrine pancreatic insufficiency 10, exocrine pancreatic insufficiency 2, pseudocyst 2, chronic renal failure 2, incisional hernia 10, recurrent pancreatitis 1, and chronic pain 1). Conclusions: Low mortality can be achieved in patients with severe necrotizing pancreatitis with aggressive surgical intervention and careful perioperative management. Long-term morbidity remains high, and emphasises the need for prolonged follow-up.

Background Mitochondrial membrane complexes (MMCs) are key mediators of cellular oxidative phosphorylation, and inhibiting them could lead to cell death. No published data are available on the relative abundance of MMCs in different periampullary cancers. Therefore, we studied the expression profile of MMCs I, III, IV and V in periampullary cancers, reactive pancreatitis, normal pancreas and chronic pancreatitis. Methods This was a retrospective study on tissue microarrays constructed from formalin-fixed paraffin-embedded tissue from 126 consecutive patients (cancer = 104, chronic pancreatitis = 22) undergoing pancreatic resections between June 2001 and June 2006. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. Results MMCs I, III, IV and V were highly expressed (p [less than] 0.05) in all primary periampullary cancers compared with metastatic lymph nodes and adjacent benign pancreas. MMCs III, IV and V were highly expressed in all cancers regardless of type compared with chronic pancreatitis (p [less than] 0.05). Higher expression of MMCs I and V was associated with better survival and may, in part, relate to lower expression of these MMCs in poorly differentiated tumours compared with well and moderately differentiated tumours. Conclusions Differential expression of MMCs III, IV and V in primary periampullary cancers compared with adjacent benign periampullary tissue and chronic pancreatitis is a novel finding, which may render them attractive anticancer targets.