Major hepatectomy with combined vascular resection for perihilar cholangiocarcinoma.

BACKGROUND: Hepatectomy with vascular resection (VR) for perihilar cholangiocarcinoma (PHCC) is a challenging procedure. However, only a few reports on this procedure have been published and its clinical significance has not been fully evaluated. METHODS: Patients undergoing surgical resection for PHCC from 2002-2017 were studied. The surgical outcomes of VR and non-VR groups were compared. RESULTS: Some 238 patients were included. VR was performed in 85 patients. The resected vessels were hepatic artery alone (31 patients), portal vein alone (37 patients) or both (17 patients). The morbidity rates were almost the same in the VR (49.4 per cent) and non-VR (43.8 per cent) groups (P = 0.404). The mortality rates of VR (3.5 per cent) and non-VR (3.3 per cent) were also comparable (P > 0.999). The median survival time (MST) was 45 months in the non-VR group and 36 months in VR group (P = 0.124). Among patients in whom tumour involvement was suspected on preoperative imaging and whose carbohydrate antigen 19-9 (CA19-9) value was 37 U/ml or less, MST in the VR group was significantly longer than that in the non-VR group (50 versus 34 months, P = 0.017). In contrast, when the CA19-9 value was greater than 37 U/ml, MST of the VR and non-VR groups was comparable (28 versus 29 months, P = 0.520). CONCLUSION: Hepatectomy with VR for PHCC can be performed in a highly specialized hepatobiliary centre with equivalent short- and long-term outcomes to hepatectomy without VR.

Utility of remnant liver volume for predicting posthepatectomy liver failure after hepatectomy with extrahepatic bile duct resection.

BACKGROUND: Hepatectomy with extrahepatic bile duct resection is associated with a high risk of posthepatectomy liver failure (PHLF). However, the utility of the remnant liver volume (RLV) in cholangiocarcinoma has not been studied intensively. METHODS: Patients who underwent major hepatectomy with extrahepatic bile duct resection between 2002 and 2018 were reviewed. The RLV was divided by body surface area (BSA) to normalize individual physical differences. Risk factors for clinically relevant PHLF were evaluated with special reference to the RLV/BSA. RESULTS: A total of 289 patients were included. The optimal cut-off value for RLV/BSA was determined to be 300 ml/m2. Thirty-two patients (11.1 per cent) developed PHLF. PHLF was more frequent in patients with an RLV/BSA below 300 ml/m2 than in those with a value of 300 ml/m2 or greater: 19 of 87 (22 per cent) versus 13 of 202 (6.4 per cent) (P < 0.001). In multivariable analysis, RLV/BSA below 300 ml/m2 (P = 0.013), future liver remnant plasma clearance rate of indocyanine green less than 0.075 (P = 0.031), and serum albumin level below 3.5 g/dl (P = 0.015) were identified as independent risk factors for PHLF. Based on these risk factors, patients were classified into three subgroups with low (no factors), moderate (1-2 factors), and high (3 factors) risk of PHLF, with PHLF rates of 1.8, 14.8 and 63 per cent respectively (P < 0.001). CONCLUSION: An RLV/BSA of 300 ml/m2 is a simple predictor of PHLF in patients undergoing hepatectomy with extrahepatic bile duct resection.

The tumor diameter cut-off for predicting microscopic intrahepatic metastasis of hepatocellular carcinoma patients without treatment history differs from that of hepatocellular carcinoma patients with a treatment history.

BACKGROUND AND AIM: Intrahepatic metastasis (IM) of hepatocellular carcinoma (HCC) occurs via vascular invasion; the tumor diameter that affects the risk of micro intra-hepatic metastasis (MIM) should be larger than that which affects the risk of micro vessel invasion (MVI). The aim of the present study was to determine the optimum tumor diameter cut-off value for predicting the presence of MIM in HCC patients without treatment history and HCC patients with a treatment history and to compare these diameters between cases of MVI and MIM. METHODS: This retrospective study included 621 patients without macroscopic vessel invasion or intrahepatic metastasis on preoperative imaging who underwent hepatectomy. The cut-off tumor diameter for predicting the presence of MIM was determined by a receiver operating characteristic curves analysis. RESULTS: The optimum cut-off value for predicting the presence of MIM in HCC patients without treatment history was 43 mm. In contrast, the optimum cut-off value for predicting the presence of MIM in HCC patients with a treatment history was 20 mm. Among 46 HCC patients with MIM without treatment history, there were 20 patients with MIM without MVI who were considered to have potential multi-centric (MC) tumors rather than IM. The cumulative overall survival rates in patients with MIM without MVI (potential MC) was significantly better than that in patients with both MIM and MVI (P = 0.022). CONCLUSIONS: The tumor diameter cut-off value for predicting MIM differed between HCC patients without treatment history and with a treatment history and slightly smaller than those for predicting MVI beyond our expectation.

Prognostic role of the length of tumour-vein contact at the portal-superior mesenteric vein in patients having surgery for pancreatic cancer.

BACKGROUND: The length of tumour-vein contact between the portal-superior mesenteric vein (PV/SMV) and pancreatic head cancer, and its relationship to prognosis in patients undergoing pancreatic surgery, remains controversial. METHODS: Patients diagnosed with pancreatic head cancer who were eligible for pancreatoduodenectomy between October 2002 and December 2016 were analysed. The PV/SMV contact was assessed retrospectively on CT. Using the minimum P value approach based on overall survival after surgery, the optimal cut-off value for tumour-vein contact length was identified. RESULTS: Among 491 patients included, 462 underwent pancreatoduodenectomy for pancreatic head cancer. PV/SMV contact with the tumour was detected on preoperative CT in 248 patients (53·7 per cent). Overall survival of patients with PV/SMV contact exceeding 20 mm was significantly worse than that of patients with a contact length of 20 mm or less (median survival time (MST) 23·3 versus 39·3 months; P = 0·012). Multivariable analysis identified PV/SMV contact longer than 20 mm as an independent predictor of poor survival, whereas PV/SMV contact greater than 180° was not a predictive factor. Among patients with a PV/SMV contact length exceeding 20 mm on pretreatment CT, those receiving neoadjuvant therapy had significantly better overall survival than patients who had upfront surgery (MST not reached versus 21·6 months; P = 0·002). CONCLUSION: The length of PV/SMV contact predicts survival, and may be used to suggest a role for neoadjuvant therapy to improve prognosis.

ANTECEDENTES: El valor pronóstico de la longitud del contacto del tumor de la cabeza pancreática con las venas porta y mesentérica superior (portal-superior mesenteric vein, PV/SMV) en los pacientes sometidos a cirugía pancreática sigue siendo un tema controvertido. MÉTODOS: Se analizaron los pacientes diagnosticados de un cáncer de la cabeza pancreática a los que se realizó una duodenopancreatectomía cefálica entre octubre de 2002 y diciembre de 2016. El contacto tumoral con la PV/SMV se evaluó de forma retrospectiva mediante tomografía computarizada (TC). Se identificó el valor de corte óptimo para la longitud del contacto tumoral con la PV/SMV, utilizando el valor mínimo de la P basado en la supervivencia global (overall survival, OS) después de la cirugía. RESULTADOS: De 491 pacientes incluidos, en 462 pacientes se realizó una duodenopancreatectomía cefálica por cáncer de la cabeza de páncreas. En la TC preoperatoria, se detectó contacto tumoral con la PV/SMV en 248 (53,7%) pacientes. La OS de los pacientes en los que el contacto del tumor con la PV/SMV fue > 20 mm fue significativamente peor que en aquellos cuyo contacto fue ≤ 20 mm (mediana de supervivencia (median survival time, MST) 23,3 versus 39,3 meses; P = 0,012). En un análisis multivariado se identificó el contacto tumoral-PV/SMV > 20 mm como un factor independiente predictor de mala supervivencia, pero el contacto tumor-PV/SMV > 180° no fue un factor pronóstico. En los pacientes en los que el contacto tumor-PV/SMV fue > 20 mm en el TC preoperatorio, la OS en aquellos que recibieron tratamiento neoadyuvante fue significativamente mejor en comparación con los pacientes tratados directamente con cirugía (MST, no alcanzada versus 21,6 meses, P = 0,002). Conclusión La longitud del contacto tumoral con la PV/SMV predice la supervivencia, por lo cual dicha longitud podría jugar un papel en la indicación de tratamiento neoadyuvante para mejorar el pronóstico.

Propensity score-matched comparison of non-anatomical resection and radiofrequency ablation for hepatocellular carcinoma in patients with up to three tumours, each measuring up to 3 cm in diameter.

BACKGROUND: Non-anatomical liver resection (NAR) and radiofrequency ablation (RFA) are treatment options for early-stage hepatocellular carcinoma (HCC). The aim was to compare the outcomes of NAR and RFA for HCC in patients with three or fewer tumour nodules, each measuring not more than 3 cm in maximum diameter. METHODS: Eligible patients undergoing NAR or RFA with curative intent between September 2002 and December 2014 were identified. A propensity score-matching analysis was performed to reduce bias, and outcomes in these patients were analysed. RESULTS: From a total of 199 patients, 1:1 propensity score matching identified 70 matched pairs. Patients having NAR had a longer hospital stay (median 10 days versus 4 days for those who had RFA; P < 0·001) and a higher morbidity rate (24 versus 10 per cent respectively; P = 0·042). Patients who had NAR had slightly better recurrence-free survival but this failed to reach statistical significance in univariable analysis (P = 0·064). There was no significant difference in overall survival between the two groups (P = 0·475). RFA was identified as an independent risk factor for recurrence-free survival (hazard ratio (HR) 1·57; P = 0·041) in multivariable analysis. Local recurrence was significantly more common in patients receiving RFA (23 versus 1 per cent; P < 0·001). CONCLUSION: RFA was an independent risk factor for shorter recurrence-free survival, with a significantly higher local recurrence rate than NAR. Despite these differences, overall survival was not affected.

Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer.

BACKGROUND: Although some retrospective studies have suggested the value of adjuvant therapy, no recommended standard exists in bile duct cancer. The aim of this study was to test the hypothesis that adjuvant gemcitabine chemotherapy would improve survival probability in resected bile duct cancer. METHODS: This was a randomized phase III trial. Patients with resected bile duct cancer were assigned randomly to gemcitabine and observation groups, which were balanced with respect to lymph node status, residual tumour status and tumour location. Gemcitabine was given intravenously at a dose of 1000 mg/m2 , administered on days 1, 8 and 15 every 4 weeks for six cycles. The primary endpoint was overall survival, and secondary endpoints were relapse-free survival, subgroup analysis and toxicity. RESULTS: Some 225 patients were included (117 gemcitabine, 108 observation). Baseline characteristics were well balanced between the gemcitabine and observation groups. There were no significant differences in overall survival (median 62·3 versus 63·8 months respectively; hazard ratio 1·01, 95 per cent c.i. 0·70 to 1·45; P = 0·964) and relapse-free survival (median 36·0 versus 39·9 months; hazard ratio 0·93, 0·66 to 1·32; P = 0·693). There were no survival differences between the two groups in subsets stratified by lymph node status and margin status. Although haematological toxicity occurred frequently in the gemcitabine group, most toxicities were transient, and grade 3/4 non-haematological toxicity was rare. CONCLUSION: The survival probability in patients with resected bile duct cancer was not significantly different between the gemcitabine adjuvant chemotherapy group and the observation group. Registration number: UMIN 000000820 (http://www.umin.ac.jp/).

Impact of Patient Age on the Postoperative Survival in Pancreatic Head Cancer.

BACKGROUND: Some reports have stated that pancreatoduodenectomy for elderly patients have comparable morbidity and mortality to that of young patients. However, the long-term outcomes of these patients have not been fully evaluated, especially for pancreatic head cancer. METHODS: A total of 227 patients who underwent pancreatoduodenectomy for pancreatic head cancer between 2007 and 2014 were included. They were stratified according to age: young (<70 years), elderly (70 to <80 years), and very elderly (≥80 years). The short- and long-term outcomes were evaluated. RESULTS: There were no significant differences in terms of morbidity among the three groups. The median disease-free survival times were 15 months in the young, 11 months in the elderly, and 7 months in the very elderly. The disease-free survival of the young patients was significantly better than that in both the elderly and the very elderly (p = 0.012 and p = 0.016). The median overall survival times were 30 months in the young, 20 months in the elderly, and 14 months in the very elderly. The overall survival of the young patients was significantly better than that in both the elderly and the very elderly (p = 0.007 and p < 0.001). The difference was marginal between the elderly and the very elderly (p = 0.053). Multivariate analysis revealed that lymph node metastasis (p < 0.001), age ≥80 years (p = 0.013), lack of adjuvant chemotherapy (p = 0.003), blood transfusion (p = 0.015), and CA 19-9 ≥300 U/ml (p = 0.040) were significant prognostic factors. CONCLUSIONS: Patient age influenced the survival after pancreatoduodenectomy for pancreatic cancer.

Indications for major hepatectomy and combined procedures for advanced gallbladder cancer.

BACKGROUND: The clinical impact of major hepatectomy for advanced gallbladder cancer is currently unclear. METHODS: Patients who underwent resection for stage II, III or IV gallbladder cancer were enrolled. The surgical outcomes of patients who underwent major hepatectomy were compared with those of patients treated with minor hepatectomy and those with unresectable gallbladder cancer. The clinical impact of major hepatectomy and combined advanced procedures such as portal vein resection or pancreatoduodenectomy for advanced gallbladder cancer were evaluated. RESULTS: A total of 96 patients were enrolled; 29 patients underwent major and 67 had minor hepatectomy. The overall morbidity rate was higher in the major hepatectomy group (55 versus 27 per cent; P = 0·022). There were no deaths after major hepatectomy. Overall survival was better in the major hepatectomy group than in the group of 15 patients with unresectable disease (median survival 17·7 versus 11·4 months; P = 0·003). In a subgroup analysis of the major hepatectomy group, liver metastasis (P = 0·038) and hepatic arterial invasion (P = 0·017) were independently associated with overall survival. Overall survival in patients with liver metastasis (P = 0·572) or hepatic arterial invasion (P = 0·776) was comparable with that in the unresectable group. However, overall survival among patients with lymph node metastasis (P = 0·062) or following portal vein resection (P = 0·054) or pancreatoduodenectomy (P = 0·011) was better than in the unresectable group. CONCLUSION: Major hepatectomy combined with portal vein resection or pancreatoduodenectomy, if necessary, may be considered in the treatment of advanced gallbladder cancer, especially in selected patients without liver metastasis or hepatic arterial invasion.

Neutrophil to lymphocyte ratio as an indicator of the malignant behaviour of hepatocellular carcinoma.

BACKGROUND: The preoperative serum neutrophil to lymphocyte ratio (NLR) has been associated with survival in patients with hepatocellular carcinoma (HCC). However, it is still unclear what the NLR reflects precisely. This study aimed to elucidate the relationship between the NLR and TNM stage, and the role of NLR as a prognostic factor after liver resection for HCC. METHODS: This retrospective study enrolled patients who underwent liver resection as initial treatment for HCC. The best cut-off value of serum NLR was determined, and overall survival was compared among patients grouped according to TNM stage (I, II and III). RESULTS: The best cut-off value for NLR was 2·8. A high preoperative NLR was more frequently associated with poor overall survival than a low preoperative NLR after resection for TNM stage I tumours (5-year survival 45·0 versus 76·4 per cent, P < 0·001), but not stage II (P = 0·283) or stage III (P = 0·155) tumours. Among patients with TNM stage I disease, the proportion of patients with extrahepatic recurrence was greater in the group with a high preoperative NLR than in the low-NLR group (P = 0·006). In multivariable analysis, preoperative NLR was the strongest independent prognostic risk factor for overall survival in TNM stage I (hazard ratio 2·69, 95 per cent c.i. 1·57 to 4·59; P < 0·001). CONCLUSION: Preoperative NLR was an important prognostic factor for TNM stage I HCC after liver resection with curative intent. These results suggest that the NLR may reflect the malignant potential of HCC.

Impact of bacterial contamination of the abdominal cavity during pancreaticoduodenectomy on surgical-site infection.

BACKGROUND: Several risk factors for complications after pancreaticoduodenectomy have been reported. However, the impact of intraoperative bacterial contamination on surgical outcome after pancreaticoduodenectomy has not been examined in depth. METHODS: This retrospective study included patients who underwent pancreaticoduodenectomy and peritoneal lavage using 7000 ml saline between July 2012 and May 2014. The lavage fluid was subjected to bacterial culture examination. The influence of a positive bacterial culture on surgical-site infection (SSI) and postoperative course was evaluated. Risk factors for positive bacterial cultures were also evaluated. RESULTS: Forty-six (21.1 per cent) of 218 enrolled patients had a positive bacterial culture of the lavage fluid. Incisional SSI developed in 26 (57 per cent) of these 46 patients and in 13 (7.6 per cent) of 172 patients with a negative lavage culture (P < 0.001). Organ/space SSI developed in 32 patients with a positive lavage culture (70 per cent) and in 43 of those with a negative culture (25.0 per cent) (P < 0.001). Grade B/C pancreatic fistula was observed in 22 (48 per cent) and 48 (27.9 per cent) respectively of patients with positive and negative lavage cultures (P = 0.010). Postoperative hospital stay was longer in patients with a positive lavage culture (28 days versus 21 days in patients with a negative culture; P = 0.028). Multivariable analysis revealed that internal biliary drainage, combined colectomy and a longer duration of surgery were significant risk factors for positive bacterial culture of the lavage fluid. CONCLUSION: Intraoperative bacterial contamination has an adverse impact on the development of SSI and grade B/C pancreatic fistula following pancreaticoduodenectomy.

A case of synthetic oestrogen-induced autoimmune hepatitis with microvesicular steatosis.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced liver injury (DILI) is a leading cause of acute liver failure in developed countries. Hepatotoxicity is a well-recognized adverse effect associated with synthetic oestrogens, which can cause cholestasis. The current report describes ethinyloestradiol (EE2)-associated highly unusual adverse effects of autoimmune hepatitis (AIH) and microvesicular steatosis (MS). DILI that fulfils the criteria for AIH is referred to as drug-induced autoimmune hepatitis (DIAIH). MS is a potentially severe liver lesion that results from mitochondrial dysfunction. We explore the pathophysiological mechanisms underlying DIAIH and MS. CASE SUMMARY: A 51-year-old woman presented with jaundice, increased liver enzymes and IgG, and positive ANA. She had been taking EE2 for 3 years. Liver biopsy showed prominent interface hepatitis with MS. A drug-lymphocyte stimulation test (DLST) using EE2 was positive. The liver biochemical parameters had normalized after the EE2 discontinuation; however, they exacerbated 5 months post-onset. Repeated liver biopsy showed interface hepatitis with no MS. Considering EE2-induced DIAIH, corticosteroids treatment was initiated. Then, all liver biochemical parameters had normalized, and the corticosteroids were successfully withdrawn. The patient continued to be in complete remission over the next 3 years. WHAT IS NEW AND CONCLUSION: Five remarkable points should be emphasized: (i) a long latency interval, despite the acute presentation; (ii) exacerbation of liver biochemical parameters, even after drug cessation; (iii) the paired liver biopsies indicating continuing inflammation and disappearance of toxic features; (iv) a positive DLST and the absence of fibrosis consistent with DIAIH and not AIH; and (v) a rare histological feature of MS. Intense immunoallergic reactions were likely triggers of MS in the current case. A possibility of DIAIH should be considered in cases of DILI which exhibit overt jaundice, autoantibodies, intense histological inflammation and a long latency period.

A predictive factor of insufficient liver regeneration after preoperative portal vein embolization.

BACKGROUND: Preoperative portal vein embolization (PVE) is performed to enhance the future remnant liver function (FRLF) and volume (FRLV). However, the volume of the nonembolized liver does not increase enough in some patients, which results in an insufficient FRLF. The aim of this study was to evaluate the predictors of insufficient FRLF after PVE for extended hepatectomy. METHODS: This retrospective study included 172 patients (107 patients with cholangiocarcinoma, 40 patients with metastatic liver cancer and 25 patients with hepatocellular carcinoma) who underwent PVE before extended hepatectomy. The total liver function was evaluated by measuring the indocyanine green plasma clearance rate (KICG). Computed tomography volumetry was conducted to evaluate the total liver volume and FRLV. The KICG of the future remnant liver (remK) was calculated using the following formula: KICG × FRLV/total liver volume. The safety margin for hepatectomy was set at remK after PVE (post-PVE remK) ≥ 0.05. RESULTS: One hundred and twenty-three patients with a post-PVE remK level of >0.05 underwent hepatectomy without postoperative liver failure [sufficient liver regeneration (SLR) group], and 9 patients with a post-PVE remK level of <0.05 did not due to insufficient FRLF [insufficient liver regeneration (ILR) group]. In the SLR group, the KICG values did not change after PVE (median, 0.144-0.146, p = 0.523); however, the %FRLV and remK increased significantly (35.0-44.3%, p < 0.001 and 0.0488-0.0610, p < 0001, respectively). In contrast, in the ILR group, the KICG values decreased significantly (0.128-0.108, p = 0.021) and the %FRLV increased marginally (27.4-32.6%, p = 0.051). As a result, the remK did not increase significantly (0.0351-0.0365, p = 0.213). A receiver operating characteristic curve demonstrated an remK value of 0.04 obtained before PVE (pre-PVE remK) to be the optimal cutoff point for defective liver regeneration. The univariate and multivariate analyses revealed that a pre-PVE remK value of <0.04 was a factor for ILR. It was also correlated with postoperative liver failure in the analysis of the patients who underwent hepatectomy. CONCLUSIONS: The patients in the ILR group did not achieve SLR after PVE due to a significant decrease in the KICG and an insufficient increase in %FRLV. A pre-PVE remK value of <0.04 is a useful predictor of insufficient regeneration of the nonembolized liver, even after PVE.

Perineural invasion has a negative impact on survival of patients with gallbladder carcinoma.

BACKGROUND: The clinical significance of perineural invasion of gallbladder carcinoma remains unclear. The aim of this study was to elucidate the incidence and mode of perineural invasion of gallbladder carcinoma and clarify its prognostic significance. METHODS: A clinicopathological study was conducted on 68 patients who underwent attempted curative resection for gallbladder carcinoma. According to the pathological tumour node metastasis (pTNM) classification of the Union Internacional Contra la Cancrum, there were five (7 per cent), nine (13 per cent), 20 (29 per cent) and 34 (50 per cent) patients with pT1, pT2, pT3 and pT4 disease respectively. Twenty patients (29 per cent) had pM1 disease, including involved para-aortic nodes, liver metastases and localized dissemination. RESULTS: The overall incidence of perineural invasion was 71 per cent (48 of 68 patients). Forty-four (96 per cent) of 46 patients with extrahepatic bile duct invasion had perineural invasion. Although several histological factors were associated with perineural invasion, multivariate analysis demonstrated that extrahepatic bile duct invasion was the only significant factor correlated with perineural invasion (odds ratio 99.0, P < 0.001). The perineural invasion index, defined as the ratio of the number of involved nerves to the total number of nerves examined, was significantly higher at the centre than in the proximal and distal parts of the tumour in the 46 patients with extrahepatic bile duct invasion (P < 0.001). The 5-year survival rate for patients with perineural invasion was significantly lower than that for patients with no invasion (7 versus 72 per cent; P < 0.001). Cox proportional hazard analysis identified perineural invasion (relative risk (RR) 5.3, P < 0.001) and lymph node metastasis (RR 2.5, P = 0.008) as significant independent prognostic factors. CONCLUSION: Perineural invasion is common in advanced gallbladder carcinoma and has a significant negative impact on patient survival.

Extensive surgery for carcinoma of the gallbladder.

BACKGROUND: The purpose of this study was to clarify the efficacy of, and define the indications for, extensive surgery for gallbladder carcinoma. METHODS: Between 1979 and 1994, 116 patients with gallbladder carcinoma underwent operation. Radical resection was performed in 80 patients. RESULTS: In 68 patients with stage III or IV disease, extensive resection including extended right hepatectomy (n = 40), pancreaticoduodenectomy (n = 23) and/or portal vein resection (n = 23) was employed to achieve complete tumour excision. The hospital mortality rate was 18 per cent. The postoperative 3- and 5-year survival rates were 44 and 33 per cent respectively in the patients with stage III disease (n = 9), and 24 and 17 per cent respectively in patients with stage IV (M0) disease (n = 29). In contrast, the postoperative survival rate for the 30 patients with stage IV (M1) disease (7 per cent at 3 years and 3 per cent at 5 years) was worse than that for patients with stage III and stage IV (M0) disease (P = 0.009 and P = 0.062 respectively). CONCLUSION: Radical resection should be undertaken for stage III and stage IV (M0) gallbladder cancer. Although portal vein resection and/or pancreaticoduodenectomy did not contribute to long-term survival, better survival was obtained than that for the unresected patients.

Complications of hepatectomy for hilar cholangiocarcinoma.

We retrospectively reviewed postoperative complications in 105 patients with hilar cholangiocarcinoma who underwent hepatectomy at Nagoya University Hospital from January 1990 through March 1999. Of the 105 subjects, 97 (92.4%) underwent resection of two or more Healey's segments of the liver. Combined portal vein resection was performed in 33 (31.4%) patients and pancreatoduodenectomy in 10 (9.5%). Twenty (19.0%) patients had no postoperative complications, another 39 (37.1%) patients had minor complication(s) only, and the remaining 46 (43.8%) developed major complication(s). The morbidity rate reached as high as 81.0%. Major complications required relaparotomy in 11 (10.5%) patients. Of the 46 patients with major complication(s) 36 recovered; the remaining 10 patients died of liver failure with other organ failure(s) or of intraabdominal bleeding 12, 14, 18, 21, 57, 75, 75, 87, 93, or 134 days after surgery. Thus the 30-day mortality was 3.8% and the overall mortality 9.5%. Pleural effusion was the most frequent complication found in 66 (62.9%) patients, followed by wound sepsis in 39 (37.1%), and then liver failure in 29 (27.6%). Liver failure developed in 16.7% of 48 patients with less than 50% liver resection and in 36.8% of 57 patients with 50% or more resection (P < 0.05). Other organ failures, including renal, respiratory, gastrointestinal, and hematologic failures, developed as a sign of multiple organ failure following liver failure in most patients or preceding liver failure in a few patients. None of the six patients with four or more organ failures survived. Hepatectomy for hilar cholangiocarcinoma is risky owing to impaired hepatic functional reserve in jaundiced patients and the technical difficulty associated with hepatobiliary resection. Our goal is to reduce mortality to less than 5% while keeping a high resectability rate (above 80%).

Liver regeneration after major hepatectomy for biliary cancer.

BACKGROUND: The aim of this study was to evaluate serial changes in liver volume after major hepatectomy for biliary cancer and to elucidate clinical factors influencing liver regeneration. METHODS: Serial changes in liver volume were determined, using computed tomography, in 81 patients with biliary cancer who underwent right hepatic lobectomy or more extensive liver resection with or without portal vein resection and/or pancreatoduodenectomy. Possible factors influencing liver regeneration were evaluated by univariate and multivariate analyses. RESULTS: The remnant mean(s.d.) liver volume was 41(8) per cent straight after hepatectomy. This increased rapidly to 59(9) per cent within 2 weeks, then increased more slowly, finally reaching a plateau at 74(12) per cent about 1 year after hepatectomy. The regeneration rate within the first 2 weeks was 16(8) cm3/day and was not related to the extent of posthepatectomy liver dysfunction. On multivariate analysis, the extent of liver resection (P < 0.001), body surface area (P = 0.02), combined portal vein resection (P = 0.024) and preoperative portal vein embolization (P = 0.047) were significantly associated with the liver regeneration rate within the first 2 weeks. In addition, body surface area (P < 0.001) and liver function expressed as plasma clearance rate of indocyanine green (P = 0.01) were significant determinants of final liver volume 1 year after hepatectomy. CONCLUSION: The liver regenerates rapidly in the first 2 weeks after major hepatectomy for biliary cancer. This early regeneration is influenced by four clinical factors. Thereafter, liver regeneration progresses slowly and stops when the liver is three-quarters of its original volume, approximately 6 months to 1 year after hepatectomy.

Hepatocellular carcinoma with biliary tumor thrombi: aggressive operative approach after appropriate preoperative management.

BACKGROUND: The aim of this study was to clarify clinicopathologic characteristics of, and to evaluate an aggressive treatment strategy for, hepatocellular carcinoma with biliary tumor thrombi. METHODS: From 1980 to 1999, a total of 132 patients underwent hepatectomy for hepatocellular carcinoma. Of these, 17 patients had macroscopic biliary tumor thrombi and were retrospectively analyzed. RESULTS: The operative procedures included right hepatic trisegmentectomy (n = 1), right or left hepatic lobectomy (n = 11), and segmentectomy or subsegmentectomy (n = 5). In 13 patients, tumor thrombi extended beyond the hepatic confluence and was treated by thrombectomy through a choledochotomy in 8 patients and extrahepatic bile duct resection and reconstruction in 5 patients. The 3- and 5-year survival rates were 47% and 28%, respectively, with a median survival time of 2.3 years. These survival rates were similar to those achieved in 115 patients without biliary tumor thrombi. In a multivariate analysis, expansive growth type and solitary tumors were independent prognostic variables for favorable outcome after operation, whereas biliary tumor thrombi was not a significant prognostic factor. CONCLUSIONS: Surgery after appropriate preoperative management of hepatocellular carcinoma with biliary tumor thrombi yields results similar to those of patients without biliary involvement. Hepatectomy with thrombectomy through a choledochotomy appears to be as effective as a resection procedure.