Meta-analysis of pancreaticojejunostomy versus pancreaticogastrostomy reconstruction after pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy is the primary treatment for periampullary cancer. Associated morbidity is high and often related to pancreatic anastomotic failure. This paper compares rates of pancreatic fistula, morbidity and mortality after pancreaticoduodenectomy in patients having reconstruction by pancreaticogastrostomy with those in patients having reconstruction by pancreaticojejunostomy. METHODS: A meta-analysis was performed of all large cohort and randomized controlled trials carried out since 1990. RESULTS: Eleven articles were identified for inclusion: one prospective randomized trial, two non-randomized prospective trials and eight observational cohort studies. The meta-analysis revealed a higher rate of pancreatic fistula associated with pancreaticojejunostomy reconstruction (relative risk (RR) 2.62 (95 per cent confidence interval (c.i.) 1.91 to 3.60)). A higher overall morbidity rate was also demonstrated in this group (RR 1.43 (95 per cent c.i. 1.26 to 1.61)), as was a higher mortality rate (RR 2.51 (95 per cent c.i. 1.61 to 3.91)). CONCLUSION: Current literature suggests that the safer means of pancreatic reconstruction after pancreaticoduodenectomy is pancreaticogastrostomy, but much of the evidence comes from observational cohort study data.

Care plans for acutely deteriorating COPD: a randomized controlled trial.

INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a frequent reason for admission to hospital and are responsible for the majority of the direct economic costs of treating COPD. AIMS: To test whether an individualized care plan for patients experiencing acute exacerbations of COPD result in reduced health care utilization and improved quality of life for patients. METHODS: Ninety-two patients with confirmed COPD were selected by general practitioners or district nurses, and randomly assigned to care plan or usual care groups. The care plan was developed in collaboration with general practitioners, secondary care specialists, specialist nurses, ambulance service providers and the after hours clinic. Patients were followed for 12 months, and the primary end-points were frequency of use of primary care services and hospital admissions. RESULTS: There was no significant reduction in hospital admissions or improvement in quality of life in the group of patients who used the care plan compared to controls. The care plan group called out the ambulance service more frequently [2.8 (1.3, 4.3) versus 1.1 (0.7, 1.5) calls per 12 months; P = 0.03], and there was a trend towards greater use of oral prednisone [2.3 (1.4, 3.2) versus 1.3 (0.8, 1.8) courses per 12 months; P = 0.06]. CONCLUSION: In contrast to asthma, the provision of individualized self-management plans, whose content was enhanced to provide guidance to carers and health care professionals, did not reduce health care utilization or improve overall quality of life during acute exacerbations of COPD. Other strategies are required.

Gallstone pancreatitis: does discharge and readmission for cholecystectomy affect outcome?

BACKGROUND: Conventional surgical wisdom is that a patient with gallstone pancreatitis should have the gallbladder removed during their initial hospitalization. However, patients are now often discharged to await operating room availability. METHODS: A retrospective review of all cases of gallstone pancreatitis at the Foothills Hospital between 1992 and 1996 was undertaken. Patients with a first attack of mild gallstone pancreatitis were studied. RESULTS: In all, 164 patients were identified: 90 patients were discharged for readmission cholecystectomy (discharged group), and 74 patients had the cholecystectomy before discharge (in-hospital group). Over the 5-year time period the proportion of patients discharged for readmission cholecystectomy increased from 27% to 67% (p<0.01). The total number of days waited for operation was greater in the discharged group versus in-hospital group: 40+/-69 days versus 8+/-10 days respectively (mean+/-SD). There was a trend towards an increased total number of days in hospital in the in-hospital group, 15.5+/-17 days versus 10.7+/-16 days. In the discharged group 20% (18 of 90) of patients experienced an adverse event requiring readmission while awaiting operation. Three had documented recurrent pancreatitis, 10 experienced recurrent pain, and 5 developed acute cholecystitis. There were no deaths in either group. DISCUSSION: Twenty percent of patients with gallstone pancreatitis who are discharged to await operating room time (average wait 40 days) will require readmission for biliary symptoms.

Cystadenomas of the liver: a spectrum of disease.

OBJECTIVES: To describe the wide variation in presentation of cystadenomas of the liver and to delineate useful tests for diagnosis and effective surgical treatment. DESIGN: A case series. SETTING: A university-affiliated hospital. PATIENTS: Four patients (3 women, 1 man) having cystadenoma of the liver, 2 of whom had associated mesenchymal stroma. MAIN OUTCOME MEASURES: Serum and cyst fluid carcinoembryonic antigen (CEA) and CA19-9 levels, type of surgery, morbidity and recurrence rates. RESULTS: Cyst fluid CEA and CA19-9 levels were elevated. One patient had resection, 2 had complete enucleation and 1 had partial enucleation. There were no deaths. Morbidity included 1 wound infection; there were no biliary fistulas. The patient with partial enucleation had a radiologically confirmed recurrence. CONCLUSIONS: Analysis of cyst fluid CEA and CA19-9 is useful for diagnosis; besides hepatic resection, complete enucleation should be considered as a reasonable treatment for patients with this disease.

Cystadenoma of the liver without mesenchymal stroma in a female following hormonal therapy for acne.

BACKGROUND: Liver cystadenomas are relatively rare tumours that can be difficult to diagnose; treatment entails complete surgical extirpation either by either anatomical resection or enucleation. CASE OUTLINE: A 19-year-old woman presented with acute onset of abdominal pain and was found to have a multilocular giant liver cyst.The cyst was percutaneously drained; CEA and CA 19-9 tumour markers were elevated in this cyst fluid: CEA 96 microg/L, CAI9-9 37 550 kU/L. The cyst was completely enucleated and has not recurred. Pathological examination confirmed a cystadenoma without mesenchymal stroma, and tumour oestrogen and progesterone receptors were negative. DISCUSSION: This is the fourth report of a liver cystadenoma without mesenchymal stroma in a female and the first to document elevated cyst fluid tumour markers. This case also illustrates the possible relationship between hormonal therapy and tumour growth.

Non-heart-beating organ donors as a source of kidneys for transplantation: a chart review.

BACKGROUND: Organ transplantation is the treatment of choice for patients with end-stage organ failure, but the supply of organs has not increased to meet demand. This study was undertaken to determine the potential for kidney donation from patients with irremediable brain injuries who do not meet the criteria for brain death and who experience cardiopulmonary arrest after withdrawal of ventilatory support (controlled non-heart-beating organ donors). METHODS: The charts of 209 patients who died during 1995 in the Emergency Department and the intensive care unit at the Foothills Hospital in Calgary were reviewed. The records of patients who met the criteria for controlled non-heart-beating organ donation were studied in detail. The main outcome measure was the time from discontinuation of ventilation until cardiopulmonary arrest. RESULTS: Seventeen potential controlled non-heart-beating organ donors were identified. Their mean age was 62 (standard deviation 19) years. Twelve of the patients (71%) had had a cerebrovascular accident, and more than half (10 [59%]) did not meet the criteria for brain death because one or more brain stem reflexes were present. At the time of withdrawal of ventilatory support, the mean serum creatinine level was 71 (29) mumol/L, mean urine output was 214 (178) mL/h, and 9 (53%) patients were receiving inotropic agents. The mean time from withdrawal of ventilatory support to cardiac arrest was 2.3 (5.0) hours; 13 of the 17 patients died within 1 hour, and all but one died within 6 hours. For the year for which charts were reviewed, 33 potential conventional donors (people whose hearts were beating) were identified, of whom 21 (64%) became donors. On the assumption that 40% of the potential controlled non-heart-beating donors would not in fact have been donors (25% because of family refusal and 15% because of nonviability of the organs), there might have been 10 additional donors, which would have increased the supply of cadaveric kidneys for transplantation by 48%. INTERPRETATION: A significant number of viable kidneys could be retrieved and transplanted if eligibility for kidney donation was extended to include controlled non-heart-beating organ donors.

Mucinous cystadenoma of the appendix in a patient with systemic lupus erythematosus.

A 38-year-old female with systemic lupus erythematosus presented with abdominal pain, diarrhea and iron-deficient anemia. Computed tomogram showed a 2 x 4 cm inhomogeneous lesion of the right adnexa. An unusual mass was identified extending from the appendiceal orifice at colonoscopy, and an 8 cm tubular appendix, apparently prolapsed into the cecum, was identified at celiotomy. An appendectomy with cecectomy was performed. On cut section, mucin was extruded from the lumen of the appendix. A mucinous neoplasm of the appendix with mucinous dissection to the serosal surface was reported at the time of frozen section. No gross ovarian pathology or peritoneal implants were noted. Cystadenoma with associated mucocele formation was verified by permanent histology. Mucocele of the vermiform appendix is a rare condition associated with neoplastic transformation in approximately 75% of all cases. Benign mucinous cystadenoma of the appendix should be differentiated from cystadenocarcinoma by frozen section at the time of celiotomy to ensure appropriate treatment. While systemic lupus erythematosus can lead to cutaneous mucinosis, an association with mucinous cystadenoma of the appendix has not been previously reported. Surveillance for metachronous colonic neoplasms is warranted in patients diagnosed with a mucinous neoplasm of the appendix.

Legislating organ donation: problems with this approach.

The number of organs available for transplantation in Canada is insufficient to meet the demand, so many patients die waiting for surgery. Improving the supply of donor organs by enacting legislation is controversial. Three approaches to legislation have been suggested: required request, mandated choice, and presumed consent. Required-request legislation demands that physicians ask all families of potential donors for permission to retrieve organs. Mandated choice requires all adults to register whether they wish to be organ donors. Presumed consent allows the removal of organs without permission if no choice was registered. These laws are aimed at coercion of physicians, patients and families retrospectively, but their relative success and ethics are questionable. Facilitating the organ donation process may be a better solution.

Percutaneous versus open tracheostomy: a retrospective cohort outcome study.

Percutaneous tracheostomy has been advocated as a faster, safer, and less invasive method of placing tracheostomy tubes in ventilated patients. To compare outcome differences, as measured by complication rates, between percutaneous and open tracheostomy, a retrospective cohort study was performed. All procedures were performed in the intensive care unit of a university-affiliated hospital. The minor complication rates did not differ significantly between percutaneous and open tracheostomy (12/31 vs. 12/29, respectively; p > 0.05), nor did there appear to be a difference in rates of major complications between the two groups (7/31 vs. 5/29; p > 0.05). This study identified a trend towards an increased risk of delayed airway loss in the percutaneous tracheostomy group.

Effects of liver transplantation on bile formation and biliary lipid secretion in the Sprague-Dawley rat.

Altered hepatic secretory function after orthotopic liver transplantation constitutes a major perioperative clinical problem. Cholestasis and cholesterol gallstone formation are among the most frequent complications reported. Such changes in the allograft secretory function can be secondary to many factors like graft injury due to preservation and marked rejection, surgical complications, immunosuppressive therapy, and sepsis. The effects of liver transplantation per se on bile formation and biliary lipid secretion are unknown. The rat model of orthotopic liver transplantation was used to characterize better the true effect of transplantation without the influence of these confounding variables. Twenty-four-hour bile collections were performed on nine transplanted versus nine liver-denervated (sham) rats 4 weeks after surgery, and nine normal Sprague-Dawley rats. The liver allografts showed mild lymphocytic infiltration in portal tracts and the serum alanine transaminase levels were not significantly elevated. Bile flow and the secretion of bile salts and bilirubin under basal conditions were unchanged. Bile salt pool size, synthesis rate, and bile acid composition did not differ among the three groups. However, cholesterol secretion was dramatically reduced (50%) in the transplanted rats and decreased 31% in the liver-denervated rats (P < .001 and .01, respectively), resulting in a more favorable cholesterol saturation index (CSI = 0.29 for transplanted and 0.32 for sham versus 0.45 for normal controls; P < .01). Thus, liver transplantation with its attendant denervation did not impair hepatic secretory function, but rather improved biliary lipid composition despite mild rejection.

The evolution of the concept of brain death.

The definition of death has taken many forms throughout history. Because of advances in critical care and developments in transplantation, a new definition of death has evolved over the past 30 years. The first accounts of brain death were published in 1959, in relative obscurity. They were only considered to be of academic interest. In the mid-1960s, advances in transplantation and the need for viable organs started debate about the use of "brain-dead" patients as organ donors. Conceptual advances by the ad hoc committee of the Harvard medical school and the use of angiography and the electroencephalogram both advanced and confused the issue. Acceptance by the medical community remained divided. During the 1970s, brain-stem death was proposed as the true definition of death by pioneers in the United States and Britain. In the 1980s, the clinical diagnosis of brain-stem death was officially accepted and many of the controversies subsided.

Initial nonfunction in cadaveric renal transplantation.

Patients who receive a kidney transplant that does not function immediately have more complications and decreased graft survival than patients whose allografts function immediately. To determine the causes of initial nonfunction (INF), the authors reviewed 188 consecutive cadaveric kidney transplants performed between 1985 and 1988 at the University Hospital, London, Ont. Data were collected on 16 putative risk factors for INF, which were divided into three categories: donor, recipient and technical. INF was defined as the need for dialysis within 7 days of transplantation. Forty-eight (26%) of the 188 allografts had INF, 6 of which never functioned. Univariate analysis identified five variables associated with increased risk of INF: no donor dopamine use, back-table flush, single-organ retrieval, exchanged kidney and prolonged cold ischemic time. Multivariate analysis, however, identified only three variables associated with INF: cerebrovascular accident as the cause of donor death, no donor dopamine use and single-organ retrieval. The authors recommend (a) low-dose dopamine therapy for all donors and (b) multiorgan retrieval to produce quality kidneys for transplantation.

The effect of cyclosporine and liver autotransplantation on bile flow and composition in dogs.

Following liver transplantation bile formation may be influenced by hepatic denervation and cyclosporine therapy. To better establish any effect of liver transplantation on bile secretion, 6 mongrel dogs were studied: 3 underwent liver denervation by a modified autotransplantation procedure and insertion of a Thomas cannula to create a chronic duodenal fistula; 3 others had cholecystectomy and the duodenal cannula placement without manipulating the liver. One month after surgery, two control studies were done, one week apart. Then oral cyclosporine was given in doses of 5, 15, and 50 mg/kg/day for consecutive 1-week periods each. Twice on each cyclosporine regimen, after 4 and 7 days of therapy, the common duct was cannulated and bile collected for 5 h; animals were awake and fasted. The first 3 h of bile collection established basal conditions; flow was then stimulated with consecutive hour-long taurocholate infusions at 1 and 2 mumol/kg/min. In all dogs, bile flow increased as the cyclosporine dose increased, under both basal and bile salt-stimulated conditions. The increased flow primarily resulted from increased bile salt-independent flow. Cyclosporine had no effect on bile salt, bilirubin, or cholesterol secretion. Phospholipid secretion, however, decreased significantly in a dose-related manner with increasing cyclosporine in the dogs with autotransplanted livers, but not in the nontransplanted dogs. This decrease in phospholipid secretion resulted in a significant increase in the calculated cholesterol saturation of bile. Thus, cyclosporine administered orally is not cholestatic but rather increases bile flow independent of any change in bile salt secretion. Cyclosporine reduced phospholipid secretion in autotransplanted dogs, possibly related to denervation of the liver. The resultant change in biliary composition may pose a risk factor for gallstone formation.

Human orthotopic small intestine transplantation: radiologic assessment.

The authors describe the postoperative anatomy and review the radiologic examinations of five patients who underwent orthotopic small intestine or combined orthotopic liver and small intestine transplantation. Mucosal thickening of the transplanted intestine was demonstrated on the first postoperative contrast material-enhanced images and was due to submucosal edema. This resolved within 2 weeks in the long-term survivors. Bowel peristalsis appeared normal as early as 31 days after transplantation. Contrast-enhanced examinations of the intestine were useful to exclude surgical complications such as anastomotic leaks or strictures, but were insensitive for biopsy-proved cytomegalovirus enteritis or rejection.

Mechanisms of rejection during OKT3 therapy: propagation and characterization of CD3 resistant allospecific cytotoxic T cells from a rejecting liver allograft.

Allograft rejection remains the single largest impediment to success in the field of transplantation. While OKT3 therapy has proven to be a significant advancement, many grafts are still lost. Late treatment, subtherapeutic OKT3 levels, anti-OKT3 antibodies, and OKT3-induced class II antigen expression are possible explanations. To determine the mechanism of OKT3 resistant rejection we propagated and characterized infiltrating T cells from the biopsy of a liver transplant patient who was rejecting while on prophylactic OKT3. The T lymphocytes demonstrated allospecific proliferation and interleukin 2 (IL2) production and showed a high degree of cytolysis of donor splenocytes. CD3 epsilon monoclonal antibodies (Mab) in concentrations up to 100 micrograms/ml did not inhibit lysis. In contrast, T lymphocytes derived from rejecting allografts of patients receiving cyclosporine and prednisone were readily inhibited from killing by CD3 epsilon Mab at doses of 1 microgram/ml. Furthermore, allospecific proliferation and IL2 production were not inhibited in the OKT3-treated patient by the addition of CD3 epsilon MaB. Incomplete modulation of the CD3-TCR complex was noted after a 72-hr incubation with CD3 epsilon Mab. The T cells did demonstrate other intact CD3-mediated functions such as a rise in intracellular calcium and CD3-dependent cytotoxicity. These results should alert clinicians that CD3 resistant cytotoxic T cells can emerge during OKT3 therapy and may cause rejection. Immunotherapy that targets additional cell surface structures may be of benefit.

The importance of class I and class II HLA in cadaveric renal transplantation.

The importance of avoiding mismatches (MM) at Class I and Class II HLA antigens in cyclosporine-treated renal allograft patients is controversial. In order to assess the role of HLA, 200 consecutive cadaveric renal allografts over a 4-year period were analysed. All patients received cyclosporine/predinisone immunosuppression and 75% were induced with ALG. Minimum follow-up period was one year. HLA A, B, DR, DQ, and DRw52/53 typing were available on 77-100% of allografts. A beneficial effect was noted at the HLA A locus. One-year survival was 87.2% in the 0 and 1 HLA A MM group combined vs 73.8% in the 2 HLA A MM group (p less than 0.05). The mean creatinine level at one year was also lower in the 0 plus 1 MM vs 2 MM group: 152.8 mumol/L vs 184.8 mumol/L, respectively (p less than 0.05). Significantly fewer rejection episodes occurred in the 0 and 1 HLA DQ MM group combined vs the 2 MM group. Steroid-resistant rejection episodes (SRRE) were not associated with the number of HLA MM. Patients who had an SRRE had significantly higher mean current and historical peak panel reactive antibodies (PRA) than patients who did not have SRRE. These results indicate that avoiding mismatches at the HLA A locus may improve renal allograft survival, and matching at HLA DQ may predispose patients to a more quiescent post-transplant course. The degree of preoperative sensitization may be an important etiologic factor in SRRE.

The effect of cyclosporine A on bile secretion in dogs.

Cyclosporine A is reported to cause cholestasis, but the evidence is confounded by anesthesia and surgery used in acute experiments. To better investigate the effect of cyclosporine on the liver, bile output was directly measured in three cholecystectomized dogs by cannulating the common duct through a chronic duodenal fistula. Control studies were done 1 month after surgery. Cyclosporine in oral doses of 5, 15, and 50 mg.kg-1.d-1 was then given for consecutive 1-week periods. Twice during each study period, bile output was measured for 5 h in fasted, awake animals: 3 h to establish basal conditions, followed by 2 h of taurocholate infusions at 1 and then 2 mumols.kg-1.min-1. Under basal conditions, bile flow rose with each dose of cyclosporine, increasing 63, 127, and 179% above control with cyclosporine 5, 15, and 50 mg.kg-1,d-1, respectively. Bile flow increased similarly during taurocholic acid stimulation. Cyclosporine had no effect on bile salt or bilirubin secretion. In this chronic dog model isolated from other causes of cholestasis, cyclosporine did not induce cholestasis but rather caused a dose-related choleresis without any change in bile salt secretion.