Robert Padbury

Living donor liver transplantation—Adult donor outcomes: A systematic review

The objective of this study was to evaluate the safety and efficacy of adult‐to‐adult living donor liver transplantation, specifically donor outcomes. A systematic review, with searches of the literature up to January 2004, was undertaken. Two hundred and fourteen studies provided information on donor outcomes. The majority of these were case series studies, although there were also studies comparing living donor liver transplantation with deceased donor liver transplantation. Both underreporting and duplicate reporting is likely to have occurred, and so caution is required in interpretation of these results. Overall reported donor mortality was 12 to 13 in about 6,000 procedures (0.2%) (117 studies). Mortality for right lobe donors to adult recipients is estimated to be 2 to 8 out of 3,800 (0.23 to 0.5%). The donor morbidity rate ranged from 0% to 100% with a median of 16% (131 studies). Biliary complications and infections were the most commonly reported donor morbidities. Nearly all donors had returned to normal function by 3 to 6 months (18 studies). In conclusion, there are small, but real, risks for living liver donors. Due to the short history of adult‐to‐adult living donor liver transplantation, the long‐term risks for donors are unknown. Liver Transpl 12:24–30, 2006.

Laparoscopic cholecystectomy for acute inflammation of the gallbladder.

OBJECTIVE The aim of this study was to prospectively assess the results of laparoscopic cholecystectomy in patients with acute inflammation of the gallbladder. SUMMARY BACKGROUND DATA Laparoscopic cholecystectomy has become the standard treatment for symptomatic gallbladder disease. Its role in the surgical treatment of acute cholecystitis has not been defined, although a number of recent reports suggest that there should be few contraindications to an initial laparoscopic approach. METHODS All patients presenting with symptomatic cholelithiasis from October 1990 until June 1992 were evaluated at laparoscopy with intention of proceeding to a laparoscopic cholecystectomy. The gross appearance of the gallbladder was categorized as acute inflammation, chronic inflammation, or no inflammation. Ninety-eight (23.4%) of 418 patients had acute inflammation of the gallbladder: 55 were edematous, 10 were gangrenous, 15 had a mucocele, and 18 had an empyema. RESULTS The authors assessed outcome in these patients. The frequency of conversion to an open operation was 33.7% for acute inflammation, 21.7% for chronic inflammation (p < 0.05), and 4% for no inflammation (p < 0.001). The conversion rate was highest for empyema (83.3%) and gangrenous cholecystitis (50%), while the conversion rate for edematous cholecystitis was 21.8% and for acute inflammation with a mucocele it was 7%. The median operation time for successful laparoscopic cholecystectomy for acute inflammation was 105 minutes, which was longer than that with no inflammation (90 minutes). However, the incidence of complications was not different from that for chronic or no inflammation. The median postoperative stay for patients with acute gallbladder inflammation was 2 days for successful laparoscopic cholecystectomy and 7 days for patients converted to an open operation. CONCLUSIONS Laparoscopic cholecystectomy for acute inflammation of the gallbladder is safe and is associated with a significantly shorter postoperative stay compared to open surgery. A greater number of patients required conversion to open operation compared to those with no obvious inflammation. Conversion to open operation was most frequent for empyema and gangrenous cholecystitis, suggesting that once this diagnosis is made, excessive time should not be spent in laparoscopic trial dissection before converting to an open operation.

Prospective randomized comparison of open versus laparoscopic appendectomy in men.

Abstract. A prospective, randomized trial was performed to compare open appendectomy with laparoscopic appendectomy in men with a clinical diagnosis of acute appendicitis. Sixty-four patients with a median age of 25 years (range 18–84 years) were randomized to open appendectomy (n = 31) or laparoscopic (n = 33) appendectomy. Of the 64 men, 56 (87.5%) had appendicitis (27 open, 29 laparoscopic procedures). The mean operating times were 50.6 ± 3.7 minutes (± SEM) for open and 58.9 ± 4.0 minutes for laparoscopic appendectomy (p = 0.13). Five (15%) patients randomized to laparoscopic appendectomy had an open operation. The mean postoperative hospital stay was significantly longer for open appendectomy (3.8 ± 0.4 days) than for laparoscopic appendectomy (2.9 ± 0.3 days) (t = 2.05,df = 62,p = 0.045). The complication rate after open appendectomy (25.8%) was not significantly different from that after laparoscopic appendectomy (12.1%). There was a single postoperative death due to a pulmonary embolus in the laparoscopic group and a single death due to cardiac and renal failure in the open group. The mean time to return to normal activities was significantly longer following open appendectomy (19.7 ± 2.4 days) than after laparoscopic appendectomy (10.4 ± 0.9 days), (t = 3.75,df = 49,p = 0.001). In conclusion, laparoscopic appendectomy in men has significant advantages in terms of a more rapid recovery compared to open appendectomy. There were no significant disadvantages to laparoscopic appendectomy compared to open appendectomy.

TG13 surgical management of acute cholecystitis

BackgroundLaparoscopic cholecystectomy is now accepted as a surgical procedure for acute cholecystitis when it is performed by an expert surgeon. There are several lines of strong evidence, such as randomized controlled trials (RCTs) and meta-analyses, supporting the introduction of laparoscopic cholecystectomy for patients with acute cholecystitis. The updated Tokyo Guidelines 2013 (TG13) describe the surgical treatment for acute cholecystitis according to the grade of severity, the timing, and the procedure used for cholecystitis in a question-and-answer format using the evidence concerning surgical management of acute cholecystitis.Methods and materialsForty-eight publications were selected for a careful examination of their full texts, and the types of surgical management of acute cholecystitis were investigated using this evidence. The items concerning the surgical management of acute cholecystitis were the optimal surgical treatment for acute cholecystitis according to the grade of severity, optimal timing for the cholecystectomy, surgical procedure used for cholecystectomy, optimal timing of the conversion of cholecystectomy from laparoscopic to open surgery, and the complications of laparoscopic cholecystectomy.ResultsThere were eight RCTs and four meta-analyses concerning the optimal timing of the cholecystectomy. Consequently, it was found that cholecystectomy is preferable early after admission. There were three RCTs and two meta-analyses concerning the surgical procedure, which concluded that laparoscopic cholecystectomy is preferable to open procedures. Literature concerning the surgical treatment according to the grade of severity could not be quoted, because there have been no publications on this topic. Therefore, the treatment was determined based on the general opinions of professionals.ConclusionSurgical management of acute cholecystitis in the updated TG13 is fundamentally the same as in the Tokyo Guidelines 2007 (TG07), and the concept of a critical view of safety and the existence of extreme vasculobiliary injury are added in the text to call the surgeon’s attention to the need to reduce the incidence of bile duct injury.Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.

Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines.

Diagnostic and therapeutic strategies for acute biliary inflammation/infection (acute cholangitis and acute cholecystitis), according to severity grade, have not yet been established in the world. Therefore we formulated flowcharts for the management of acute biliary inflammation/infection in accordance with severity grade. For mild (grade I) acute cholangitis, medical treatment may be sufficient/appropriate. For moderate (grade II) acute cholangitis, early biliary drainage should be performed. For severe (grade III) acute cholangitis, appropriate organ support such as ventilatory/circulatory management is required. After hemodynamic stabilization is achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. For patients with acute cholangitis of any grade of severity, treatment for the underlying etiology, including endoscopic, percutaneous, or surgical treatment should be performed after the patient’s general condition has improved. For patients with mild (grade I) cholecystitis, early laparoscopic cholecystectomy is the preferred treatment. For patients with moderate (grade II) acute cholecystitis, early laparoscopic or open cholecystectomy is preferred. In patients with extensive local inflammation, elective cholecystectomy is recommended after initial management with percutaneous gallbladder drainage and/or cholecystostomy. For the patient with severe (grade III) acute cholecystitis, multiorgan support is a critical part of management. Biliary peritonitis due to perforation of the gallbladder is an indication for urgent cholecystectomy and/or drainage. Delayed elective cholecystectomy may be performed after initial treatment with gallbladder drainage and improvement of the patient’s general medical condition.

Steroid withdrawal from long-term immunosuppression in liver allograft recipients.

Corticosteroids were withdrawn from the immunosuppressive regimen of 168/197 (85%) of liver transplant patients who survived for more than three months. In 14, steroids were restarted for reasons other than rejection. The remaining 154 patients were evaluated for the occurrence of rejection and graft loss. Risk factors for the development of rejection after steroid withdrawal were assessed. There were 13 episodes of rejection in 12 (7.8%) grafts; 7 (4.5%) experienced acute cellular rejection, and 6 (3.9%) developed chronic ductopenic rejection. All cases of acute rejection resolved with high-dose steroids. Graft and patient loss due to chronic rejection was 3 (1.9%) and 2 (1.3%), respectively. Chronic rejection resolved in 1 patient, 1 was successfully retransplanted, and in the other 2 the principal cause of death was recurrent tumor. None of the risk factors examined (primary indication for transplant, severity of previous acute rejection, use of OKT3, retransplantation, ABO blood group donor/recipient match, CMV infection, and CsA mono versus CsA and AZA double therapy) were associated with the development of chronic rejection poststeroid withdrawal. The prevalence of side effects, after steroid withdrawal, was low; 66% of patients never required antihypertensive medication; 14% experienced a significant septic episode, and only 4 died with sepsis as the major factor. There were no fungal sepsis and no new cases of diabetes. Withdrawal of corticosteroids after 3 months can be successfully achieved in the majority of liver allograft recipients and is associated with a low rate of rejection, graft loss, and complications attributable to immunosuppressive medication.

Acute liver allograft rejection--is treatment always necessary?

A group of 195 consecutive adult patients who received a primary orthotopic liver allograft were reviewed retrospectively to analyze the incidence of rejection, the response to antirejection therapy, and the impact of acute rejection on the development of ductopenic rejection. The diagnosis of acute rejection (AR) was based on a combination of clinical and histological criteria, and 69.7% of the patients had at least one episode of acute rejection. Only 6.7% of the patients failed to respond to steroids and were treated with OKT3. Four (2.3%) patients developed acute vanishing bile duct syndrome (within 60 days) and 6 (3.5%) patients developed chronic rejection. Eight patients who spontaneously recovered from AR without additional immunosuppression are described in detail. In addition to histological damage, all developed

Projections of nerve cells from the duodenum to the sphincter of Oddi and gallbladder of the Australian possum

BACKGROUND This study investigated the existence of direct neural connections between the duodenum and the biliary tract in the Australian possum. METHODS Retrogradely transported neuronal dyes, Fast Blue and Dil, were injected into the wall of the gallbladder and the sphincter of Oddi. The duodenum, biliary tract, and sympathetic and sensory ganglia were examined for the presence of labeled cell bodies. RESULTS Two to 3 weeks after gallbladder injection, labeled nerve cell bodies were found in the myenteric plexus of the proximal duodenum but were rare in the duodenum distal to the sphincter of Oddi. No neurons were found in the submucous plexus. Labeled nerve cells were also found in the sphincter of Oddi. After injection of the sphincter, labeled neurons were in both the submucous and myenteric plexuses of the duodenum, on either side. Approximately one third of labeled myenteric neurons were immunoreactive for enkephalin. Labeled cell bodies were also in the coeliaco-mesenteric, nodose, and dorsal root ganglia after both gallbladder and sphincter injection. After a myotomy on the proximal duodenum, no neurons were labeled on the pyloric side of the lesion by subsequent sphincter injection of dye. CONCLUSIONS Direct neural pathways connect the duodenum with the gallbladder and the sphincter of Oddi, and the sphincter with the gallbladder; this implies that enteric nerve circuits participate in coordinating duodenal and biliary functions.

Donor Mannose-Binding Lectin Deficiency Increases the Likelihood of Clinically Significant Infection after Liver Transplantation

BACKGROUND Mannose-binding lectin (MBL) is an important mediator of innate immunity and is synthesized primarily by the liver. Low MBL levels are common, are due primarily to polymorphisms in the gene encoding MBL (MBL2), and are associated with an increased risk of infection, particularly when immunity is compromised. We report a large, retrospective study that examined the association between MBL status and clinically significant infection following orthotopic liver transplantation. METHODS One hundred two donor-recipient orthotopic liver transplantation pairs were studied. Five polymorphisms in the promoter and coding regions of MBL2 were examined. MBL levels were measured, using the mannan-binding and C4-deposition assays, in serum samples obtained before and after transplantation. Associations between MBL status, as assessed by serum MBL levels and MBL2 genotype, and time to first clinically significant infection (CSI) after transplantation were examined in survival analysis with consideration of competing risks. RESULTS The median duration of follow-up after orthotopic liver transplantation was 4 years. Thirty-six percent of recipients developed CSI after transplantation. The presence of MBL2 coding mutations in the donor was significantly associated with CSI in the recipient; the cumulative incidence function of infection was 55% in recipients of deficient livers, compared with 32% for recipients of wild-type livers (P = .002). Infection was not associated with recipient MBL2 genotype. Low MBL levels after orthotopic liver transplantation levels (mannan-binding <1 microg/mL or C4 deposition <0.2 C4 U/microL) were also associated with CSI (cumulative incidence function, 52% vs. 20%, P = .003; and cumulative incidence function, 54% vs. 24%, P = .007, respectively). In multivariate analysis, mutation in the MBL2 coding region of the donor (hazard ratio, 2.8; P = .005) and the use of cytomegalovirus prophylaxis (hazard ratio, 2.6; P = .005) were independently associated with CSI. CONCLUSIONS Recipients of MBL-deficient livers have almost a 3-fold greater likelihood of developing CSI and may benefit from MBL replacement.

Predicting patient survival after pancreaticoduodenectomy for malignancy: histopathological criteria based on perineural infiltration and lymphovascular invasion

BACKGROUND Accurate and simple prognostic criteria based on histopathology following pancreaticoduodenectomy would be helpful in assessing prognosis and considering and evaluating adjuvant therapy. This study analysed the histological parameters influencing outcome following pancreaticoduodenectomy for periampullary malignancy. METHODS A total of 110 pancreaticoduodenectomies were performed from 1998 to 2008. The median age of patients was 69 years (range 20-89 years). The median follow-up was 4.9 years. Of the procedures, 87% (96) were performed for malignancies and the remainder (n= 14) for benign aetiologies. Of the 96 malignancies, 60 were pancreatic adenocarcinoma and the rest were ampullary (14), cholangio (9), duodenal (9) carcinomas and others. Statistical analysis was performed using log-rank and Cox regression multivariate analyses. RESULTS Patients who underwent resection had 1-, 3- and 5-year survival rates of 70%, 46% and 41%, respectively. The 1-, 3- and 5-year survival rates for periampullary cancers other than pancreatic adenocarcinoma were 83%, 69% and 61%, respectively; those for pancreatic adenocarcinoma were 62%, 31% and 27%, respectively (P < 0.003). Poor tumour differentiation (P < 0.02), tumour size >3 cm (P < 0.04), margin <or=2 mm (P < 0.02), nodal involvement (P < 0.003), perineural infiltration (P < 0.0001) and lymphovascular invasion (P < 0.002) were associated with poorer prognosis. In a multivariate analysis, histologically identified perineural infiltration (P < 0.03) and lymphovascular invasion (P= 0.05) were significant factors influencing outcome. Five-year survival was 77% in patients negative for both factors and 15% in patients positive for both (P < 0.0001). In the pancreatic adenocarcinoma subgroup, patients who were negative for both factors had a 5-year survival of 71%, whereas those who were positive for both had a 5-year survival of 16% (P < 0.02). CONCLUSIONS The presence of perineural infiltration and lymphovascular invasion on histopathology is highly significant in predicting 5-year outcomes after pancreaticoduodenectomy for periampullary and pancreatic malignancies.