Chun Yeung

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.

External Drainage of Pancreatic Duct With a Stent to Reduce Leakage Rate of Pancreaticojejunostomy After Pancreaticoduodenectomy: A Prospective Randomized Trial

Objective:Pancreatic fistula is a leading cause of morbidity and mortality after pancreaticoduodenectomy. External drainage of pancreatic duct with a stent has been shown to reduce pancreatic fistula rate of pancreaticojejunostomy in a few retrospective or prospective nonrandomized studies, but no randomized controlled trial has been reported thus far. This single-center prospective randomized trial compared the results of pancreaticoduodenectomy with external drainage stent versus no stent for pancreaticojejunal anastomosis. Methods:A total of 120 patients undergoing pancreaticoduodenectomy with end-to-side pancreaticojejunal anastomosis were randomized to have either an external stent inserted across the anastomosis to drain the pancreatic duct (n = 60) or no stent (n = 60). Duct-to-mucosa anastomosis was performed in all cases. Results:The 2 groups were comparable in demographic data, underlying pathologies, pancreatic consistency, and duct diameter. Stented group had a significantly lower pancreatic fistula rate compared with nonstented group (6.7% vs. 20%, P = 0.032). Radiologic or surgical intervention for pancreatic fistula was required in 1 patient in the stented group and 4 patients in the nonstented group. There were no significant differences in overall morbidity (31.7% vs. 38.3%, P = 0.444) and hospital mortality (1.7% vs. 5%, P = 0.309). Two patients in the nonstented group and none in the stented group died of pancreatic fistula. Hospital stay was significantly shorter in the stented group (mean 17 vs. 23 days, P = 0.039). On multivariate analysis, no stenting and pancreatic duct diameter <3 mm were significant risk factors of pancreatic fistula. Conclusion:External drainage of pancreatic duct with a stent reduced leakage rate of pancreaticojejunostomy after pancreaticoduodenectomy.

Continuous Improvement of Survival Outcomes of Resection of Hepatocellular Carcinoma: A 20-Year Experience

Objective:To investigate the trend of the posthepatectomy survival outcomes of hepatocellular carcinoma (HCC) patients by analysis of a prospective cohort of 1198 patients over a 20-year period. Background:The hospital mortality rate of hepatectomy for HCC has improved but the long-term survival rate remains unsatisfactory. We reported an improvement of survival results 10 years ago. It was not known whether there has been further improvement of results in recent years. Methods:The patients were categorized into two 10-year periods: period 1, before 1999 (group 1, n = 390) and period 2, after 1999 (group 2, n = 808). Patients in group 2 were managed according to a modified protocol and technique established in previous years. Results:The patients in group 2 were older and had a higher incidence of comorbid illness and cirrhosis. They had a lower hospital mortality rate (3.1% vs 6.2%, P = 0.012) and longer 5-year overall survival (54.8% vs 42.1%, P < 0.001) and disease-free survival rates (34.8% vs 24%, P = 0.0024). An improvement in the overall survival rate was observed in patients with cirrhosis, those undergoing major hepatectomy, and those with tumors of tumor-node-metastasis stages II, IIIA, and IVA. A significant increase in the survival rates was also seen in patients whose tumors were considered transplantable by the Milan criteria (72.5% vs 62.7%, P = 0.0237). Multivariate analysis showed a significantly more favorable patient survival for hepatectomy in period 2. Conclusions:A continuous improvement of survival outcomes after hepatectomy for HCC was achieved in the past 20 years even in patients with advanced diseases. Hepatectomy remains the treatment of choice for resectable HCC in a predominantly hepatitis B virus-based Asian population.

Extended Hepatic Resection for Hepatocellular Carcinoma in Patients with Cirrhosis: Is It Justified?

ObjectiveTo evaluate the perioperative outcomes and long-term survival of extended hepatic resection for hepatocellular carcinoma (HCC) in patients with cirrhosis. Summary Background DataHepatic resection is a well-established treatment for HCC in cirrhotic patients with preserved liver function and limited disease. However, the role of extended hepatic resection (more than four segments) for HCC in cirrhotic patients has not been elucidated. MethodsBetween 1993 and 2000, 45 consecutive patients with histologically confirmed cirrhosis underwent right or left extended hepatectomy for HCC (group A). Perioperative outcomes and long-term survival of these patients were compared with 161 patients with HCC and cirrhosis who underwent hepatic resection of a lesser extent in the same period (group B). All clinicopathologic and follow-up data were collected prospectively. ResultsGroup A patients had significantly higher intraoperative blood loss, longer operation time, and longer hospital stay than group B. However, the two groups were similar in overall morbidity and hospital mortality. There were no significant differences in the incidence of liver failure or other complications. The resection margin width was similar between the two groups. Despite significantly larger tumor size in group A compared with group B, long-term survival was comparable between the two groups. ConclusionsExtended hepatic resection for HCC can be performed in selected cirrhotic patients with acceptable morbidity, mortality, and long-term survival that are comparable to those of lesser hepatic resection. Extended hepatectomy for large HCC extending from one lobe to the other or central HCC critically related to the hepatic veins is justifiable in cirrhotic patients with preserved liver function and adequate liver remnant.

Prophylactic effect of somatostatin on post-ERCP pancreatitis : a randomized controlled trial

BACKGROUND Somatostatin is a potent inhibitor of pancreatic secretion and has been studied for its prophylactic effect on post-ERCP pancreatitis. However, results of previous trials have been inconclusive. METHODS A prospective double-blind controlled study was performed to evaluate the effectiveness of somatostatin in preventing post-ERCP pancreatitis. Post-ERCP enzyme elevation, abdominal pain and pancreatitis were evaluated and compared between 109 patients randomized to receive somatostatin infusion and 111 patients randomized to receive normal saline infusion (placebo); both started 30 minutes before ERCP and continued for 12 hours. RESULTS Post-ERCP elevation of serum amylase and lipase levels at 6 and 24 hours after ERCP was less frequent in the group given somatostatin but not statistically significant. There was a tendency toward lower mean serum amylase and lipase levels at 24 hours in patients given somatostatin, although the difference was not statistically significant either. Eight patients given somatostatin (7%) and 18 patients given placebo (16%) had significant abdominal pain after ERCP requiring analgesia (p = 0.04). The frequency of clinical pancreatitis was significantly lower in patients given somatostatin (3%) than in those given placebo (10%) (p = 0.03). CONCLUSIONS Prophylactic treatment with somatostatin reduced the frequency of post-ERCP pancreatitis.

Pancreaticoduodenectomy with en bloc portal vein resection for pancreatic carcinoma with suspected portal vein involvement.

Pancreaticoduodenectomy combined with portal vein resection is increasingly accepted as a viable treatment option for pancreatic carcinoma with suspected involvement of the portal vein.However, its clinical benefit remains controversial. This study evaluated the outcomes of pancreaticoduodenectomy with portal vein resection for pancreatic carcinoma in a group of Chinese patients operated on by a specialized team in a center with a low case volume of pancreatic cancer. The perioperative and long-term outcomes of 12 patients with portal vein resection for suspected involvement of the portal vein and 38 patients who underwent pancreaticoduodenectomy without portal vein resection during the same period were compared. In the former group, eight patients underwent segmental resection, and four patients underwent wedge resection of the portal vein. There were no significant differences in operative blood loss (median 0.8 vs. 0.8 liter, p = 0.313), hospital mortality (0% vs. 2.6%, p = 1.000), or operative morbidity (41.7% vs. 42.1%, p = 0.979) between the two groups. Patients who required portal vein resection had higher frequencies of microscopic lymphatic permeation (58.3% vs. 18.4%, p = 0.023) and vascular invasion (50.0% vs. 15.8%, p = 0.025). Long-term survival was comparable between patients with portal vein resection and those without it (median 19.5 vs. 20.7 months, p = 0.769). These findings suggest that pancreaticoduodenectomy combined with portal vein resection can be performed safely by a specialized team in a center with a low case volume of pancreatic carcinoma and that it may offer survival benefit in patients with suspected portal vein involvement.

Outcome after partial hepatectomy for hepatocellular cancer within the Milan criteria.

There is a trend to offer liver transplantation to patients with hepatocellular carcinoma (HCC) with tumour status within the Milan criteria but with preserved liver function. This study aimed to evaluate the outcome of such patients following partial hepatectomy as primary treatment.

Proteomic expression signature distinguishes cancerous and nonmalignant tissues in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive liver cancer but clinically validated biomarkers that can predict natural history of malignant progression are lacking. The present study explored the proteome-wide patterns of HCC to identify biomarker signature that could distinguish cancerous and nonmalignant liver tissues. A retrospective cohort of 80 HBV-associated HCC was included and both the tumor and adjacent nontumor tissues were subjected to proteome-wide expression profiling by 2-DE method. The subjects were randomly divided into the training (n = 55) and validation (n = 25) subsets, and the data analyzed by classification-and-regression tree algorithm. Protein markers were characterized by MALDI-ToF/MS and confirmed by immunohistochemistry, Western blotting and qPCR assays. Proteomic expression signature composed of six biomarkers (haptoglobin, cytochrome b5, progesterone receptor membrane component 1, heat shock 27 kDa protein 1, lysosomal proteinase cathepsin B, keratin I) was developed as a classifier model for predicting HCC. We further evaluated the model using both leave-one-out procedure and independent validation, and the overall sensitivity and specificity for HCC both are 92.5%, respectively. Clinical correlation analysis revealed that these biomarkers were significantly associated with serum AFP, total protein levels and the Ishaks score. The described model using biomarker signatures could accurately distinguish HCC from nonmalignant tissues, which may also provide hints on how normal hepatocytes are transformed to malignant state during tumor progression.

Predictive Genes in Adjacent Normal Tissue Are Preferentially Altered by sCNV during Tumorigenesis in Liver Cancer and May Rate Limiting

Background In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ∼250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types.

Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis.

Aim:  To assess the efficacy and safety of percutaneous transhepatic cholecystostomy (PTC) in treatment for acute cholecystitis in high surgical risk patients.