Chung Mau Lo

Early treatment of acute biliary pancreatitis by endoscopic papillotomy

BACKGROUND Most patients with acute biliary pancreatitis have stones in the biliary tract or ampulla of Vater. Because these stones may be passed spontaneously soon after a patient is admitted to the hospital, the importance of early operative removal is not known. We tested the hypothesis that endoscopic papillotomy within 24 hours of admission decreased the incidence of complications in patients with acute biliary pancreatitis. METHODS We studied 195 patients with acute pancreatitis who were randomly assigned to one of two groups: 97 patients underwent within 24 hours after admission emergency endoscopic retrograde cholangiopancreatography (ERCP) followed by endoscopic papillotomy for ampullary and common-bile-duct stones, and 98 patients received initial conservative treatment and selective ERCP with or without endoscopic papillotomy only if their condition deteriorated. RESULTS One hundred twenty-seven patients ultimately proved to have biliary stones. Emergency ERCP with or without endoscopic papillotomy resulted in a reduction in biliary sepsis as compared with conservative treatment (0 of 97 patients vs. 12 of 98 patients, P = 0.001). The decrease in biliary sepsis occurred both in patients predicted to have mild pancreatitis (0 of 56 patients in the group that received emergency ERCP vs. 4 of 58 patients in the conservative-treatment group, P = 0.14) and in patients predicted to have severe pancreatitis (0 of 41 patients vs. 8 of 40 patients, P = 0.008). In all patients who had unrelenting biliary sepsis, persistent ampullary or common-bile-duct stones were identified. There were no major differences in the incidence of local complications (10 patients in the group that received emergency ERCP vs. 12 patients in the conservative-treatment group) or systemic complications (10 patients vs. 14 patients) of acute pancreatitis between the two groups, but the hospital mortality rate was slightly lower in the group undergoing emergency ERCP with or without endoscopic papillotomy (5 patients vs. 9 patients, P = 0.4). CONCLUSIONS Emergency ERCP with or without endoscopic papillotomy is indicated in the treatment of patients with acute pancreatitis.

Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths.

OBJECTIVE The authors report on the surgical techniques and protocol for perioperative care that have yielded a zero hospital mortality rate in 110 consecutive patients undergoing hepatectomy for hepatocellular carcinoma (HCC). The hepatectomy results are analyzed with the aim of further reducing the postoperative morbidity rate. SUMMARY BACKGROUND DATA In recent years, hepatectomy has been performed with a mortality rate of <10% in patients with HCC, but a zero hospital mortality rate in a large patient series has never been reported. At Queen Mary Hospital, Hong Kong, the surgical techniques and perioperative management in hepatectomy for HCC have evolved yearly into a final standardized protocol that reduced the hospital mortality rate from 28% in 1989 to 0% in 1996 and 1997. METHODS Surgical techniques were designed to reduce intraoperative blood loss, blood transfusion, and ischemic injury to the liver remnant in hepatectomy. Postoperative care was focused on preservation and promotion of liver function by providing adequate tissue oxygenation and immediate postoperative nutritional support that consisted of branched-chain amino acid-enriched solution, low-dose dextrose, medium-chain triglycerides, and phosphate. The pre-, intra-, and postoperative data were collected prospectively and analyzed each year to assess the influence of the evolving surgical techniques and perioperative care on outcome. RESULTS Of 330 patients undergoing hepatectomy for HCC, underlying cirrhosis and chronic hepatitis were present in 161 (49%) and 108 (33%) patients, respectively. There were no significant changes in the patient characteristics throughout the 9-year period, but there were significant reductions in intraoperative blood loss and blood transfusion requirements. From 1994 to 1997, the median blood transfusion requirement was 0 ml, and 64% of the patients did not require a blood transfusion. The postoperative morbidity rate remained the same throughout the study period. Complications in the patients operated on during 1996 and 1997 were primarily wound infections; the potentially fatal complications seen in the early years, such as subphrenic sepsis, biliary leakage, and hepatic coma, were absent. By univariate analysis, the volume of blood loss, volume of blood transfusions, and operation time were correlated positively with postoperative morbidity rates in 1996 and 1997. Stepwise logistic regression analysis revealed that the operation time was the only parameter that correlated significantly with the postoperative morbidity rate. CONCLUSION With appropriate surgical techniques and perioperative management to preserve function of the liver remnant, hepatectomy for HCC can be performed without hospital deaths. To improve surgical outcome further, strategies to reduce the operation time are being investigated.

MicroRNA Expression, Survival, and Response to Interferon in Liver Cancer

BACKGROUND Hepatocellular carcinoma is a common and aggressive cancer that occurs mainly in men. We examined microRNA expression patterns, survival, and response to interferon alfa in both men and women with the disease. METHODS We analyzed three independent cohorts that included a total of 455 patients with hepatocellular carcinoma who had undergone radical tumor resection between 1999 and 2003. MicroRNA-expression profiling was performed in a cohort of 241 patients with hepatocellular carcinoma to identify tumor-related microRNAs and determine their association with survival in men and women. In addition, to validate our findings, we used quantitative reverse-transcriptase-polymerase-chain-reaction assays to measure microRNAs and assess their association with survival and response to therapy with interferon alfa in 214 patients from two independent, prospective, randomized, controlled trials of adjuvant interferon therapy. RESULTS In patients with hepatocellular carcinoma, the expression of miR-26a and miR-26b in nontumor liver tissue was higher in women than in men. Tumors had reduced levels of miR-26 expression, as compared with paired noncancerous tissues, which indicated that the level of miR-26 expression was also associated with hepatocellular carcinoma. Moreover, tumors with reduced miR-26 expression had a distinct transcriptomic pattern, and analyses of gene networks revealed that activation of signaling pathways between nuclear factor kappaB and interleukin-6 might play a role in tumor development. Patients whose tumors had low miR-26 expression had shorter overall survival but a better response to interferon therapy than did patients whose tumors had high expression of the microRNA. CONCLUSIONS The expression patterns of microRNAs in liver tissue differ between men and women with hepatocellular carcinoma. The miR-26 expression status of such patients is associated with survival and response to adjuvant therapy with interferon alfa.

Long-Term Survival and Pattern of Recurrence After Resection of Small Hepatocellular Carcinoma in Patients With Preserved Liver Function: Implications for a Strategy of Salvage Transplantation

ObjectiveTo evaluate the survival results and pattern of recurrence after resection of potentially transplantable small hepatocellular carcinomas (HCC) in patients with preserved liver function, with special reference to the implications for a strategy of salvage transplantation. Summary Background DataPrimary resection followed by transplantation for recurrence or deterioration of liver function has been recently suggested as a rational strategy for patients with HCC 5 cm or smaller and preserved liver function. However, there are no published data on transplantability after HCC recurrence or long-term deterioration of liver function after resection of small HCC in Child-Pugh class A patients. Such data are critical in determining the feasibility of salvage transplantation. MethodsFrom a prospective database of 473 patients with resection of HCC between 1989 and 1999, 135 patients age 65 years or younger had Child-Pugh class A chronic liver disease (chronic hepatitis or cirrhosis) and transplantable small HCC (solitary ≤5 cm or two or three tumors ≤3 cm). Survival results were analyzed and the pattern of recurrence was examined for eligibility for salvage transplantation based on the same criteria as those of primary transplantation for HCC. ResultsOverall survival rates at 1, 3, 5, and 10 years were 90%, 76%, 70%, and 35%, respectively, and the corresponding disease-free survival rates were 74%, 50%, 36%, and 22%. Cirrhosis and oligonodular tumors were predictive of worse disease-free survival. Patients with concomitant oligonodular tumors and cirrhosis had a 5-year overall survival rate of 48% and a disease-free survival rate of 0%, which were significantly worse compared with other subgroups. At a median follow-up of 48 months, 67 patients had recurrence and 53 (79%) of them were considered eligible for salvage transplantation. Decompensation from Child-Pugh class A to B or C without recurrence occurred in only six patients. ConclusionsFor Child-Pugh class A patients with small HCC, hepatic resection is a reasonable first-line treatment associated with a favorable 5-year overall survival rate. A considerable proportion of patients may survive without recurrence for 5 or even 10 years; among those with recurrence, the majority may be eligible for salvage transplantation. These data suggest that primary resection and salvage transplantation may be a feasible and rational strategy for patients with small HCC and preserved liver function. Primary transplantation may be a preferable option for the subset of patients with oligonodular tumors in cirrhotic liver in view of the poor survival results after resection.

Improving Perioperative Outcome Expands the Role of Hepatectomy in Management of Benign and Malignant Hepatobiliary Diseases: Analysis of 1222 Consecutive Patients From a Prospective Database

Objective:To assess the trends in perioperative outcome of hepatectomy for hepatobiliary diseases. Methods:Data of 1222 consecutive patients who underwent hepatectomy for hepatobiliary diseases from July 1989 to June 2003 in a tertiary institution were collected prospectively. Perioperative outcome of patients in the first (group I) and second (group II) halves of this period was compared. Factors associated with morbidity and mortality were analyzed. Results:Diagnoses included hepatocellular carcinoma (n = 734), other liver cancers (n = 257), extrahepatic biliary malignancies (n = 43), hepatolithiasis (n = 101), benign liver tumors (n = 61), and other diseases (n = 26). The majority of patients (61.8%) underwent major hepatectomy of ≥3 segments. The overall hospital mortality and morbidity were 4.9% and 32.4%, respectively. The number of hepatectomies increased from 402 in group I to 820 in group II, partly as a result of more liberal patient selection. Group II had more elderly patients (P = 0.006), more patients with comorbid illnesses (P = 0.001), and significantly worse liver function. Nonetheless, group II had lower blood loss (median 750 versus 1450 mL, P < 0.001), perioperative transfusion (17.3% versus 67.7%, P < 0.001), morbidity (30.0% versus 37.3%, P = 0.012), and hospital mortality (3.7% versus 7.5%, P = 0.004). On multivariate analysis, hypoalbuminemia, thrombocytopenia, elevated serum creatinine, major hepatic resection, and transfusion were the significant predictors of hospital mortality, whereas concomitant extrahepatic procedure, thrombocytopenia, and transfusion were the predictors of morbidity. Conclusions:Perioperative outcome has improved despite extending the indication of hepatectomy to more high-risk patients. The role of hepatectomy in the management of hepatobiliary diseases can be expanded. Reduced perioperative transfusion is the main contributory factor for improved outcome.

Adult-to-adult Living Donor Liver Transplantation Using Extended Right Lobe Grafts

OBJECTIVE The authors report their experience with living donor liver transplantation (LDLT) using extended right lobe grafts for adult patients under high-urgency situations. SUMMARY BACKGROUND DATA The efficacy of LDLT in the treatment of children has been established. The major limitation of adult-to-adult LDLT is the adequacy of the graft size. A left lobe graft from a relatively small volunteer donor will not meet the metabolic demand of a larger recipient. METHODS From May 1996 to November 1996, seven LDLTs, using extended right lobe grafts, were performed under high-urgency situations. All recipients were in intensive care units before transplantation with five having acute renal failure, three on mechanical ventilation, and all with hepatic encephalopathy. The median body weight for the donors and recipients was 58 kg (range, 41-84 kg) and 65 kg (range, 53-90 kg), respectively. The body weights of four donors were less than those of the corresponding recipients, and the lowest donor-to-recipient body weight ratio was 0.62:1. The extended right lobe graft was chosen because the left lobe volume was <40% of the ideal liver mass of the recipient. RESULTS Median blood loss for the donors was 900 mL (range, 700-1600 mL) and hospital stay was 19 days (range, 8-22 days). Homologous blood transfusion was not required. Two donors had complications (one incisional hernia and one bile duct stricture) requiring reoperation after discharge. All were well with normal liver function 5 to 10 months after surgery. The graft weight ranged from 490 g to 1140 g. All grafts showed immediate function with normalization of prothrombin time and recovery of conscious state of the recipients. There was no vascular complication, but six recipients required reoperation. One recipient died of systemic candidiasis 16 days after transplantation and 6 (86%) were alive with the original graft at a median follow-up of 6.5 months (range, 5-10 months). CONCLUSIONS When performed by a team with experience in hepatectomy and transplantation, LDLT, using an extended right lobe graft, can achieve superior results. The technique extends the success of LDLT from pediatric recipients to adult recipients and opens a new donor pool for adults to receive a timely graft of adequate function.

Improving Survival Results After Resection of Hepatocellular Carcinoma: A Prospective Study of 377 Patients Over 10 Years

ObjectiveTo investigate whether the survival results after resection of hepatocellular carcinoma (HCC) have improved within the past decade by an analysis of a prospective cohort of patients over a 10-year period. Summary Background DataThe surgical death rate after resection of HCC has greatly improved in recent years, but the long-term prognosis remains unsatisfactory. It remains unknown whether the survival results after resection of HCC have improved within the past decade. MethodsThe clinicopathologic and follow-up data of 377 patients who underwent curative resection of HCC between January 1989 and January 1999 were prospectively collected. These patients were categorized according to two time periods: before 1994 (group 1, n = 136) and after 1994 (group 2, n = 241). The two groups were compared for clinicopathologic data and survival results. The prognostic factors for disease-free survival were further analyzed to identify the factors that might have led to improved survival outcomes. ResultsThe overall and disease-free survival results were significantly better in group 2 compared with group 1. Patients in group 2 had significantly higher proportions of subclinical presentation, small tumors, and tumors of early pTNM stage. There were also significantly lower frequencies of histologic margin involvement, less intraoperative blood loss, and a lower transfusion rate in group 2. By multivariate analysis, early pTNM stage, subclinical HCC, and no perioperative transfusion were independent favorable prognostic factors for disease-free survival. ConclusionsSignificant improvement of overall and disease-free survival results after resection of HCC has been achieved within the past decade as a result of advances in the diagnosis and surgical management of HCC. Earlier diagnosis of HCC by better imaging modalities, increased detection of subclinical HCC by screening of high-risk patients, and a reduced perioperative transfusion rate were identified as the major contributory factors for the improved outcomes.

Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors.

OBJECTIVE This study aimed to evaluate the long-term results of treatment and prognostic factors in patients with intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA Recent studies have demonstrated the usefulness of re-resection, transarterial oily chemoembolization (TOCE), or percutaneous ethanol injection therapy (PEIT) in selected patients with intrahepatic recurrent HCC. The overall results of a treatment strategy combining these modalities have not been fully evaluated, and the prognostic factors determining survival in these patients remain to be clarified. METHODS Two hundred and forty-four patients who underwent curative resection for HCC were followed for intrahepatic recurrence, which was treated aggressively with a strategy including different modalities. Survival results after recurrence and from initial hepatectomy were analyzed, and prognostic factors were determined by univariate and multivariate analysis using 27 clinicopathologic variables. RESULTS One hundred and five patients (43%) with intrahepatic recurrence were treated with re-resection (11), TOCE (71), PEIT (6), systemic chemotherapy (8) or conservatively (9). The overall 1-year, 3-year, and 5-year survival rates from the time of recurrence were 65.5%, 34.9%, and 19.7%, respectively, and from the time of initial hepatectomy were 78.4%, 47.2%, and 30.9%, respectively. The re-resection group had the best survival, followed by the TOCE group. Multivariate analysis revealed Childs B or C grading, serum albumin < or = 40 g/l, multiple recurrent tumors, recurrence < or = 1 year after hepatectomy, and concurrent extrahepatic recurrence to be independent adverse prognostic factors. CONCLUSIONS Aggressive treatment with a multimodality strategy could result in prolonged survival in patients with intrahepatic recurrence after curative resection for HCC. Prognosis was determined by the liver function status, interval to recurrence, number of recurrent tumors, any concurrent extrahepatic recurrence, and type of treatment.

Endoscopic Biliary Drainage for Severe Acute Cholangitis

Abstract Background. Emergency surgery for patients with severe acute cholangitis due to choledocholithiasis is associated with substantial morbidity and mortality. Because recent results suggested that emergency endoscopic drainage could improve the outcome of such patients, we undertook a prospective study to determine the role of this procedure as initial treatment. Methods. During a 43-month period, 82 patients with severe acute cholangitis due to choledocholithiasis were randomly assigned to undergo surgical decompression of the biliary tract (41 patients) or endoscopic biliary drainage (41 patients), followed by definitive treatment. Hospital mortality was analyzed with respect to the use of endoscopic biliary drainage and other clinical and laboratory findings. Prognostic determinants were studied by linear discriminant analysis. Results. Complications related to biliary tract decompression and subsequent definitive treatment developed in 14 patients treated with endoscopic biliary drainage and 27 ...

Prospective randomized study of early versus delayed laparoscopic cholecystectomy for acute cholecystitis.

OBJECTIVE A prospective randomized study was undertaken to compare early with delayed laparoscopic cholecystectomy for acute cholecystitis. SUMMARY BACKGROUND DATA Laparoscopic cholecystectomy for acute cholecystitis is associated with high complication and conversion rates. It is not known whether there is a role for initial conservative treatment followed by interval elective operation. METHOD During a 26-month period, 99 patients with a clinical diagnosis of acute cholecystitis were randomly assigned to early laparoscopic cholecystectomy within 72 hours of admission (early group, n = 49) or delayed interval surgery after initial medical treatment (delayed group, n = 50). Thirteen patients (four in the early group and nine in the delayed group) were excluded because of refusal of operation (n = 6), misdiagnosis (n = 5), contraindication for surgery (n = 1), or loss to follow-up (n = 1). RESULTS Eight of 41 patients in the delayed group underwent urgent operation at a median of 63 hours (range, 32 to 140 hours) after admission because of spreading peritonitis (n = 3) and persistent fever (n = 5). Although the delayed group required less frequent modifications in operative technique and a shorter operative time, there was a tendency toward a higher conversion rate (23% vs. 11%; p = 0.174) and complication rate (29% vs. 13%; p = 0.07). For 38 patients with symptoms exceeding 72 hours before admission, the conversion rate remained high after delayed surgery (30% vs. 17%; p = 0.454). In addition, delayed laparoscopic cholecystectomy prolonged the total hospital stay (11 days vs. 6 days; p < 0.001) and recuperation period (19 days vs. 12 days; p < 0.001). CONCLUSIONS Initial conservative treatment followed by delayed interval surgery cannot reduce the morbidity and conversion rate of laparoscopic cholecystectomy for acute cholecystitis. Early operation within 72 hours of admission has both medical and socioeconomic benefits and is the preferred approach for patients managed by surgeons with adequate experience in laparoscopic cholecystectomy.