Liver resection of hepatocellular carcinoma in patients with portal hypertension and multiple tumors.

AIM: Liver resection for hepatocellular carcinoma (HCC) has been recommended only for patients with a single tumor without portal hypertension. We aimed to validate this treatment strategy that is based on by the Barcelona Clinic Liver Cancer staging system. METHODS: Patients undergoing liver resection were divided into two groups: patients with single HCC without portal hypertension (Group 1) and those with at least one factors of portal hypertension and multiple tumors, up to three lesions each ≤3 cm (Group 2). We compared survival and postoperative complications between the two groups. RESULTS: The median overall and recurrence-free survival periods of patients in Group 1 (n = 695) were 8.5 years (95% confidence interval [CI], 6.6-9.0) and 2.4 years (2.2-2.7), respectively, and were significantly longer compared with those of patients in Group 2 (n = 197) (5.6 years [95% CI, 4.8-6.7], P = 0.001, and 1.9 years [1.6-2.1], P < 0.001). On multivariate analysis, the independent factors for overall survival were hepatitis C virus infection (hazard ratio, 1.29 [95% CI, 1.02-1.65], P = 0.032), multiple tumors (1.42 [1.01-1.98], P = 0.040), and vascular invasion (1.66 [1.31-2.10], P < 0.001). Frequency of morbidity (23 [3.3%] patients vs 11 [5.5%] patients, P = 0.143) and mortality (3 [0.4%] patients vs 2 [1.0%] patients, P = 0.305) was not significantly different between the two groups. CONCLUSIONS: Patients with HCC with portal hypertension and/or multiple tumors could be candidates for liver resection due to the safety of the procedure.

Decreased blood loss reduces postoperative complications in resection for hepatocellular carcinoma.

BACKGROUND: The correlation between blood loss and the risk of postoperative complications was unclear in patients undergoing resection of hepatocellular carcinoma (HCC). METHODS: We studied 539 patients who had resection of HCC. Postoperative complications were recorded according to the modified Clavien-Dindo classification. Variables were compared between patients with grade III to V complications and those with no or grade I to II. A spline regression analysis was used to estimate the probability of grade III to V complications. RESULTS: Among variables, blood loss (P = 0.0001), operating time (P = 0.0001), blood transfusion (P = 0.0001), and tumor size (P = 0.02) differed significantly between patients with grade III to V and those with no or I to II. Multivariate analysis revealed that the factor most strongly related to complications was blood loss (odds ratio 1.68; 95% confidence interval [CI] 1.45-1.96, P = 0.0001). Spline regression analysis showed that an increase in blood loss was accompanied by increase in the risk of complication; when the estimated probability of grade III to V complications exceeded 50% (95% CI 30.0-70.0), the corresponding blood loss was 820 ml. CONCLUSION: Decrease in blood loss in resection of HCC is accompanied by reduced risk of complications. Surgeons need to minimize blood loss as less as 820 ml.

Early cancer-related death after resection of hepatocellular carcinoma.

BACKGROUND: Surgeons have attempted to prevent early cancer-related death after resection of hepatocellular carcinoma to identify risk factors associated with early death from hepatocellular carcinoma recurrence after liver resection. METHODS: The study group comprised 350 patients who had undergone liver resection for hepatocellular carcinoma between 1997 and 2007. The preoperative risk factors for early death from intrahepatic recurrence (within 1 year after resection) were evaluated. RESULTS: Fourteen (4%) patients died of intrahepatic recurrence in the first year after resection. Multivariate analyses identified the following risk factors for early cancer-related death: multiple tumors (odds ratio 10.4; 95% confidence interval, 2.42-44.3; P = .002), vascular invasion (odds ratio 10.1; 95% confidence interval 2.07-50; P = .004), serum alpha-fetoprotein level >20 ng/mL (odds ratio 9.52; 95% confidence interval 1.0--84.2; P = .043), and tumor size ≥50 mm (odds ratio 4.80; 95% confidence interval 1.06-21.9; P = .042). Each of these factors was assigned a score of 1 point, and an algorithm was developed to predict the risk of early death. Outcomes did not differ significantly between patients with 3 or 4 points (P = .48) or between those with 1 or 2 points (P = .49). Patients who underwent liver resection could be stratified into the following distinct groups according to the point score and the associated 1-year survival rate and median survival (shown respectively): 0 points, 99%, and not yet; 1 or 2 points, 96%, and 68 months; and 3 or 4 points, 50%, and 12 months) (P < .0001). CONCLUSION: Even if hepatocellular carcinoma is resectable, patients with a score of 3 or 4 points may not be good candidates for liver resection.

The risk factors of fungal infection in living-donor liver transplantations.

PURPOSE: The aim of the study was to retrospectively assess in a Japanese university hospital the risk factors for fungal infections and mortality in living-donor liver transplantations (LDLTs). Although fungal infections are an important complication associated with high mortality in liver transplantation, the risk factors for fungal infections developing after LDLT remain poorly understood. METHODS: Patient records for a total of 156 patients undergoing LDLT over a 6-year period in our institution were retrospectively evaluated. All transplant recipients were routinely observed for fungal infections with close monitoring for febrile episodes and collection and culture of saliva, pharynx, sputum, urine, feces, and drain discharge specimens undertaken. Fungal infection was defined as proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group. Patients with definite or probable infection were diagnosed as having specific invasive fungal infection in this study. Data were reviewed and collated from these patients' records, and multivariate analyses were performed to identify possible risk factors for mortality and the development of fungal infections. RESULTS: Nineteen of 156 patients (12.2%) developed invasive fungal infections, involving Candida spp. (n = 13), Pneumocystis jiroveci (n = 4), and Aspergillus spp. (n = 2). Eight of these 19 patients died, 4 from pneumonia, and 1 each from cerebral hemorrhage, chronic rejection, virus-associated hemophagocytic syndrome, and cancer recurrence. The 5-year survival rate was significantly lower in patients with fungal infections than in those without (53 vs. 90%; p < 0.001). Fungal infection was independently associated with reoperation (odds ratio 6.92, 1.82-26.27, p = 0.004), posttransplant dialysis (5.62, 1.51-20.88, p = 0.009), and bacterial infection (3.94, 1.02-15.26, p = 0.04). CONCLUSION: Independent risk factors of fungal infection after LDLT are reoperation, posttransplant dialysis, and bacterial infection.

Validation of perioperative steroids administration in liver resection: a randomized controlled trial.

OBJECTIVE: We performed a randomized controlled trial to investigate the clinical benefits of perioperative treatment with steroids in patients undergoing liver resection. BACKGROUND: Perioperative steroids are considered to reduce surgical stress, but evidence supporting proposed clinical benefits is largely anecdotal. PATIENTS AND METHODS: The 210 patients scheduled to undergo liver resection were randomly assigned to a steroids group (n = 105) or a control group (n = 105). The steroids group received 500 mg hydrocortisone immediately before hepatic-pedicle clamping, followed by 300 mg hydrocortisone on postoperative day (POD) 1, 200 mg on POD 2, and 100 mg on POD 3. Serum levels of total bilirubin, aminotransferases coagulation factors, and inflammatory-related cytokines, and the clinical course were compared between the 2 groups. The primary end point was the postoperative bilirubin level. RESULTS: All 210 patients underwent radical liver resection with no operative mortality. The median bilirubin level on POD 2 was significantly lower in the steroids group [0.71 mg/dL (0.33-2.17)] than in the control group [1.03 mg/dl (0.39-3.57); P = 0.01]. The postoperative time courses of the bilirubin level (P = 0.01), the interleukin-6 level (P = 0.01) and the C-reactive protein level (P = 0.01) were significantly lower whereas the the prothrombin level (P = 0.01) and interleukin-10 level (P = 0.01) were significantly higher in the steroids group. There was no difference between the groups in the proportion of patients with complications (40% vs 43%; P = 0.66) or the length of the hospital stay (14 days vs 13 days; P = 0.68). CONCLUSIONS: Perioperative treatment with steroids has a positive impact on the liver function of patients who undergo liver resection, without increasing the risk of complications.

Phase I/II study of a fine-powder formulation of cisplatin for transcatheter arterial chemoembolization in hepatocellular carcinoma.

AIM: The clinical feasibility of transcatheter arterial chemoembolization (TACE) with fine-powder cisplatin (CDDP) in patients with hepatocellular carcinoma (HCC) has not been investigated. A phase I/II study was conducted to investigate the safety and tolerability of fine-powder CDDP when it was used with lipiodol and gelatin sponge particles for TACE. METHODS: Fine-powder CDDP emulsified in lipiodol was injected into tumor arteries. Embolization was subsequently performed with gelatin sponge particles. The CDDP dose was started at 45 mg/m(2) (level 1) and increased to 65 mg/m(2) in 10 mg/m(2) increments. RESULTS: Thirteen patients were enrolled in phase I study since no dose limiting toxicity was observed in any patients, even in seven patients at level 3 (65 mg/m(2)), the recommended dose was 65 mg/m(2). The major adverse event was grade 3 thrombocytopenia, which occurred in 8% of patients. The incidence of hematological toxicities was 15% for leukocytopenia, 84% for thrombocytopenia, and 84% for anemia. Increased serum total bilirubin was observed in 54% and increased aspartate aminotransferase or alanine aminotransferase in all patients. All digestive tract symptoms (nausea 77%, anorexia 84%, vomiting 31%) were grade 2 or lower. Total adverse events were grade 3 or higher in 44%. The response rate in 19 patients who received the recommended dose was 21%. CONCLUSIONS: TACE with a fine-powder formulation of CDDP at a dose of 65 mg/m(2) is well tolerated in patients with unresectable HCC.

[Case report of transarterial chemoembolization to lymph node metastasis of hepatocellular carcinoma].

We performed transarterial chemoembolization (TACE) on the 67-year-old man who had hepatectomy for hepatocellular carcinoma with hepatitis C, recurrence in the liver and lymph nodes.The metastasis in lymph node did not show a clear increase until dying, and TACE showed the possibility of one treatment method to the metastasis in lymph node of the hepatocellular carcinoma.

[Chemotherapy and hepatectomy for liver metastasis from colorectal cancer].

Hepatic resection for colorectal liver metastasis remains the only treatment that has curative potential. In half of the patients with recurrences after hepatectomy for liver metastasis, the first site of recurrence is the remnant liver. Furthermore, most patients with recurrence develop metastases. Despite the fact, that adjuvant chemotherapy has been proven very successful in primary colorectal cancer, there is only recent evidence of a benefit after liver surgery. To improve the survival for colorectal liver metastasis, surgery may be combined with adjuvant chemotherapy. In the future, the safety and effectiveness should be determined by clinical trials. The optimal dose, schedule, and combination of oxaliplatin, irinotecan, and fluorouracil plus leucovorin, the presently most effective drugs in colorectal cancer, must be assessed. In this paper, we describe the current status of liver resection and chemotherapy for liver metastasis from colorectal cancer with a review of the literature. Multidisciplinary care and the improved outcomes that are available when we integrate the best of medical and surgical oncology are important.

[A case of advanced sigmoid colon cancer with peritoneal dissemination responding to FOLFOX4 therapy].

A 62-year-old woman complained of thin feces, lower blood and abdominal pain, and she was diagnosed as having bowel obstruction due to sigmoid colon cancer. Abdominal CT showed peritoneal dissemination and ascites on the surface of liver. The serum CEA levels were 663.7 ng/mL. We established a diagnosis of unresectable sigmoid colon cancer accompanied by severe peritoneal dissemination and therefore performed only transverse colostomy in April, 2006. Pathological examination of omental dissemination demonstrated moderately-differentiated adenocarcinoma. FOLFOX4 therapy was started on April, 2006. Primary lesion decrease and release from bowel obstruction after 4 cycles was judged as a partial response. The partial response continued, and the serum CEA decreased 18.5 ng/mL after completion of 16 cycles, but grade 3 neuropathy occurred. We started S-1 as second-line chemotherapy in May, 2007. There was primary lesion re-growth after 4 cycles, so we changed to S-1+CPT-11 therapy. The adverse events were grade 3 neuropathy and leucopenia throughout the course. Chemotherapy is now continued on an outpatient basis, 24 months after the medical treatment started. FOLFOX4 therapy is useful for patients with advanced colon cancer accompanied by peritoneal dissemination.

Hepatic cystic echinococcosis with specific CT findings.

A hepatic central bisegmentectomy was performed on a 36-year-old Iranian man with suspected cystic echinococcosis. Hepatic computed tomography (CT) scan findings showed a large cystic lesion, which included many small round shaped cystic lesions. The diagnosis of hepatic cystic echinococcosis was confirmed during surgery. The aforementioned CT scan findings may be specific findings for cystic echinococcosis, in spite of a low appearance rate.

[A clinical study of therapy for local recurrent rectal cancer].

To evaluate the therapy for local recurrent rectal cancer, we examined clinicopathological characteristics and prognoses of 54 local recurrent rectal cancer patients. The cumulative 5 year survival rate was 20.3%, 3-year survival rate was 74% for a curative surgery group, 21.8% for a non-curative surgery group and 0% for a non surgery group. There were significant differences in the rates of three year survival between the curative surgery group and non surgery group, but there were no differences between the non curative surgery group and non-surgery group. A survival analysis showed that prognoses of patients ew (-) or CEA under 10 ng/ml group were statistically better than the other group. Thirty four patients underwent operation. The mean operation time and the mean blood loss were 334.2 minutes and 1977 ml, respectively. Eighteen patients had some complications associated with the operation. Radiotherapy and chemotherapy did not contribute to improve survival rate, but contribute to improved symptoms. In conclusion, curative surgery is the only therapy for local recurrent rectal cancer to improve survival rates, but there are many complications associated with non curative surgery. We therefore must evaluate the indication of operation carefully.

[Local recurrence of pancreatic cancer successfully treated with gemcitabine].

We report a patient for whom systemic chemotherapy using gemcitabine was effective against local recurrence of pancreatic cancer. A 58-year-old man underwent pancreatoduodenectomy for a pancreatic head cancer. The diagnosis was Stage IVb poorly-differentiated tubular adenocarcinoma, scirrhous type, pT4, PL (+), P0, H0, pN2. However, after 21 months, gastrointestinal bleeding occurred. Gastroscopy and CT examination revealed a mass at the cut-end of the pancreas invading the stomach. The serum CA19-9 level was found to be elevated. Systemic chemotherapy was performed with a regimen of gemcitabine 1,000 mg/m2/week for 2 weeks, followed by a week rest. The recurrent tumor in the stomach disappeared, and the mass at the cut-end of the pancreas became small. The serum CA 19-9 level regained the normal value. Two years after the diagnosis of recurrence, he returned to work, and his chemotherapy is being continued as an outpatient.

Impact of previous multiple portoenterostomies on living donor liver transplantation for biliary atresia.

BACKGROUND/AIMS: The present study examined the impact of portoenterostomy on the morbidity and mortality of patients who later underwent living donor liver transplantation for biliary atresia. METHODOLOGY: Sixty-one consecutive patients from January 1996 to May 2001 were analyzed. They were divided into two groups according to the number of previous portoenterostomies: once (group A, n=26) and twice or more (group B, n=35). Preoperative status, mortality, morbidity, hospital duration and survival were examined and compared between the groups. RESULTS: Preoperative parameters regarding liver function and urgency status were comparable between the groups. The operation duration tended to be longer in group B than in group A (p=0.07). The blood loss and transfusion volumes in group B were greater than those in group A (p=0.03 for both comparisons). Vascular complications tended to be more frequent in group B patients. However, this difference was not significant (12% vs. 29%, p=0.06). The duration of hospitalization was longer in group B (p=0.04). Survival rates were comparable between the groups. CONCLUSIONS: Our surgical results suggest that multiple previous portoenterostomies might have negative short-term effects in patients who undergo living donor liver transplantation for biliary atresia.

Early recurrence of hepatocellular carcinoma after living donor liver transplantation.

Milan criteria are standards for considering the indications of liver transplantation for hepatocellular carcinoma. A 57-year-old man underwent living donor liver transplantation for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. Hepatocellular carcinoma had been treated with percutaneous microwave coagulation therapy and transarterial chemoembolization. Resected specimens revealed a solitary necrotic tumor 5 cm in diameter, which satisfied the Milan criteria. Although the patient survived the operation, he suffered from tumor recurrence in the graft and lung 2 months afterward. Adjuvant chemotherapy had no effect and the patient expired 7 months after transplantation. The present results indicate that a tumor satisfying the Milan criteria does not necessarily guarantee long-term survival after transplantation.

Living-donor liver transplantation in adults: Tokyo University experience.

The objective of this study was to analyze the experience of a single center with living-donor liver transplantation (LDLT) for adult patients. Ninety consecutive LDLT procedures were analyzed. Preoperative status, morbidity, hospital stay duration, and postoperative graft function and survival rates were examined. Donors showed only minimal morbidity and were discharged 15 +/- 6 days after LDLT. Morbidity in the patients included acute rejection (32%), vascular complications (8%), and biliary complications (20%). The mortality rate was 6% and three additional patients experienced late death. The 2-year cumulative survival rate was 92%. The present results suggest that LDLT can be performed with an acceptable outcome in adult patients.

Vein reconstruction in modified right liver graft for living donor liver transplantation.

OBJECTIVE: To report the authors' experience with hepatic vein reconstruction and plasty in living donor liver transplantation for adult patients. SUMMARY BACKGROUND DATA: A right liver graft without the middle hepatic vein (MHV) trunk (modified right liver graft) can cause severe congestion of the right paramedian sector. However, the need for MHV reconstruction has not been fully recognized. METHODS: From June 2000 to December 2001, 30 adult patients received a modified right liver graft. Major MHV tributaries were preserved and reconstructed under the authors' criteria. Plasty of recipient hepatic veins for a wide outflow orifice was performed when necessitated. The regeneration of paramedian and lateral sectors of the grafts was examined by computed tomography 1 and 3 months after the operation. RESULTS: MHV tributaries were reconstructed in 18 grafts. Plasty of recipient hepatic veins was performed in 15 patients. All patients survived the operation. The regeneration of paramedian and lateral sectors was equivalent. CONCLUSIONS: A modified right liver graft can provide satisfactory surgical results if hepatic vein reconstruction and plasty are performed using the present techniques.

Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy.

BACKGROUND/AIMS: We conducted a retrospective cohort study to investigate factors to early and late phase recurrence of hepatocellular carcinoma (HCC). METHODS: The study population consisted of 249 patients including 157 with cirrhosis who underwent hepatectomy for HCC. The endpoint was time-to-recurrence. Using a Cox regression model, factors to early and late phase recurrences were investigated censoring recurrence-free patients at the 2-year time point and in patients without recurrence at 2 years. RESULTS: Actuarial probability of overall recurrence at 1, 3, and 5 years were 0.301, 0.623, and 0.790, respectively, with a median follow-up of 624 days. Early recurrence was observed in 123 out of 249 patients; while late recurrence was found in 61 out of 113 patients. Factors to early recurrence were as follows: non-anatomical resection, presence of microscopic vascular invasion, and serum alpha-fetoprotein level >or=32 ng/ml. Those contributing to late phase recurrence were higher grade of hepatitis activity, multiple tumors, and gross tumor classification. CONCLUSIONS: Variables associated with metastatic recurrence were factors to early phase recurrence; whereas those related with elevated carcinogenesis contributed to late phase recurrence, thus providing an epidemiological evidence that different mechanisms, i.e. metastasis and de novo, are involved in intrahepatic recurrence after hepatectomy for HCC.

Normal splenic volume in adults by computed tomography.

BACKGROUND/AIMS: The purpose of the present study was to examine variations in spleen size in adults. METHODOLOGY: The spleen volume was measured by computed tomography in 150 healthy donors for liver transplantation. The correlations between spleen volume and age, gender, body weight and body surface area were analyzed. RESULTS: The mean volume of the spleen was 112 cm3, ranging from 32 to 209 cm3. The spleen volume significantly correlated with age (R = 0.36, p = 0.0002), but not with body weight or surface area. Gender did not influence the variation in spleen size. CONCLUSIONS: A crude normal range stratified by age should provide useful information in the diagnosis of splenomegaly.