Chylous ascites after hepatopancreatobiliary surgery.

BACKGROUND: Postoperative chylous ascites following abdominal surgery is uncommon. It potentially induces malnutrition and immunodeficiency, contributing to increased mortality. In the field of hepatopancreatobiliary (HPB) surgery, no large studies have been conducted that focused on postoperative chylous ascites. The aim of this study was to determine the incidence, risk factors and management of chylous ascites following HPB surgery, with particular emphasis on pancreatic resection. METHODS: Consecutive patients who had HPB surgery between 2000 and 2011 at a single institution were reviewed retrospectively. Chyle leak was defined as 100 ml/day or more of milky, amylase-free peritoneal fluid with a triglyceride concentration of 110 mg/dl or above. Risk factors for chylous ascites associated with pancreatic resection and the clinical efficacy of octreotide in treating chylous ascites were evaluated. RESULTS: Of 2002 consecutive patients who underwent HPB surgery during the study period, 21 (1·0 per cent) developed chylous ascites. Chylous ascites occurred relatively frequently in patients who had a pancreatic resection, such as pancreaticoduodenectomy (3·3 per cent) or distal pancreatectomy (3·8 per cent). Multivariable analysis revealed that manipulation of the para-aortic area (P < 0·001), retroperitoneal invasion (P = 0·031) and early enteral feeding after operation (P < 0·001) were independent risk factors for chylous ascites following pancreatic resection. Octreotide treatment decreased drainage output of chylous ascites on day 1 after initiation of treatment (P = 0·002). CONCLUSION: Chylous ascites is a rare complication following HPB surgery. It is more common after pancreatic resection. Treatment with octreotide combined with total parenteral nutrition is recommended.

Increased circulating cell signalling phosphoproteins in sera are useful for the detection of pancreatic cancer.

BACKGROUND: Intracellular phosphoprotein activation significantly regulates cancer progression. However, the significance of circulating phosphoproteins in the blood remains unknown. We investigated the serum phosphoprotein profile involved in pancreatic cancer (PaCa) by a novel approach that comprehensively measured serum phosphoproteins levels, and clinically applied this method to the detection of PaCa. METHODS: We analysed the serum phosphoproteins that comprised cancer cellular signal pathways by comparing sera from PaCa patients and benign controls including healthy volunteers (HVs) and pancreatitis patients. RESULTS: Hierarchical clustering analysis between PaCa patients and HVs revealed differential pathway-specific profiles. In particular, the components of the extracellular signal-regulated kinase (ERK) signalling pathway were significantly increased in the sera of PaCa patients compared with HVs. The positive rate of p-ERK1/2 (82%) was found to be superior to that of CA19-9 (53%) for early stage PaCa. For the combination of these serum levels, the area under the receiver-operator characteristics curves was showing significant ability to distinguish between the two populations in independent validation set, and between cancer and non-cancer populations in another validation set. CONCLUSION: The comprehensive measurement of serum cell signal phosphoproteins is useful for the detection of PaCa. Further investigations will lead to the implementation of tailor-made molecular-targeted therapeutics.

Significance of repeated resection for recurrent intrahepatic cholangiocarcinoma.

BACKGROUND/AIMS: Management of patients with recurrent intrahepatic cholangiocarcinoma (ICC) following surgical resection is difficult, and surgical resection is rarely indicated. We retrospectively reviewed patients with recurrent intrahepatic cholangiocarcinoma. METHODOLOGY: Between April 1998 and March 2007, 57 consecutive patients with ICC underwent surgical resection. Mode of recurrence and treatment of recurrent tumors, especially surgical resection for these tumors, in patients with cancer recurrence were evaluated. RESULTS: 37 (65%) patients experienced tumor recurrence. Out of these patients, 24 underwent some type of cancer-directed therapy, including 9 patients (24%) for whom surgical resection was attempted: the latter included 4 hepatic resections, 2 pulmonary resections, 2 tumor resections, and 1 gastric resection. For 6 patients with recurrent tumor in the liver or the lung, microscopic complete resection was achieved, while incomplete resection was resulted in the remaining 3 patients. No postoperative mortality was encountered. Among patients with complete resection, 3 are alive without disease 32, 39 and 77 months after the second operation, one has lived with disease for 13 months, and 2 died of disease after 22 and 26 months. No significant difference in overall survival was observed between patients undergoing primary and second surgical resections, calculated from the primary and the second operations, respectively. CONCLUSIONS: Repeated surgical resection for recurrent ICC can be performed with acceptable morbidity, and affords selected patients a chance for long-term survival.

FGF10/FGFR2 signal induces cell migration and invasion in pancreatic cancer.

Pancreatic cancer has one of the highest mortalities among all malignancies and there is an urgent need for new therapy. This might be achieved by resolving the detailed biological mechanism, and in this study we examined how pancreatic cancer cells develop aggressive properties by focusing on signalling through the fibroblast growth factor (FGF)10 and FGF receptor (FGFR)2, which play important roles in pancreatic organogenesis. Immunostaining of pancreatic cancer tissues showed that FGFR2 was expressed in cancer cells, whereas FGF10 was expressed in stromal cells surrounding the cancer cells. Patients with high FGFR2 expression in cancer cells had a shorter survival time compared to those with low FGFR2 expression. Fibroblast growth factor 10 induced cell migration and invasion of CFPAC-1 and AsPC-1 pancreatic cancer cells through interaction with FGFR2-IIIb, a specific isoform of FGFR2. Fibroblast growth factor 10 also induced expression of mRNA for membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor (TGF)-beta1, and increased secretion of TGF-beta1 protein from these cell lines. These data indicate that stromal FGF10 induces migration and invasion in pancreatic cancer cells through interaction with FGFR2, resulting in a poor prognosis. This suggests that FGF10/FGFR2 signalling is a promising target for new molecular therapy against pancreatic cancer.

Poor postoperative blood glucose control increases surgical site infections after surgery for hepato-biliary-pancreatic cancer: a prospective study in a high-volume institute in Japan.

Two hundred and sixty-five consecutive patients awaiting hepato-biliary-pancreatic surgery were prospectively observed for surgical site infections (SSIs). SSI rates differed according to type of hepato-biliary-pancreatic surgery. Multivariate analysis identified enteric anastomoses, poor postoperative blood glucose control and type of cancer as independent risk factors. SSI rates were directly correlated with the degree of hyperglycaemia encountered during the postoperative period. In particular, SSI rates were 5/25 (20%) among patients in whom a blood glucose level of <200mg/dL was maintained by insulin infusion therapy, which was significantly better than the rates of 49/94 (52%) among patients in whom a blood glucose level of <200mg/dL was not maintained despite insulin infusion therapy (P<0.01). It is necessary to maintain postoperative blood glucose levels of <200mg/dL in order to reduce SSI rates.

Effects of LDL-apheresis on serum lipoprotein (a), C4b binding protein, protein C, protein S, and complement components.

The short-term effects of low-density lipoprotein (LDL) apheresis using a dextran sulfate-cellulose (DSC) column equipped with a plasma separator using a polysulfone (PS) membrane filter on the serum total cholesterol, lipoprotein(a) (Lp(a)), C4b binding protein (C4bp), protein C and protein S and complement components levels were examined in a patient with familial hypercholesterolemia (heterozygote, type IIa). PS/DSC-LDL apheresis markedly lowered the total cholesterol by 69.9 +/- 2.9%, serum Lp(a) level by 80.2 +/- 3.4%, and C4bp by 81.1 +/- 2.5% after 8 apheresis sessions. All the above parameters gradually returned to the baseline levels within 10 days. The free protein S level was not significantly changed, while the C4bp/protein S complex level was markedly decreased relative to the decrease in C4bp. The protein C level was moderately reduced by 29%. Almost all serum complements and complement co-factors as well as C4bp were moderately to markedly decreased after LDL apheresis, but returned to the initial levels within a few days. PS/DSC-LDL apheresis effectively eliminated both serum LDL and Lp(a), and did not have an adverse effect on fibrinolysis or complement cascade in the blood.

Cerebrotendinous xanthomatosis: clinical and biochemical evaluation of eight patients and review of the literature.

We present the clinical and laboratory findings of 8 patients with cerebrotendinous xanthomatosis. The clinical features consisted of a combination of bilateral Achilles tendon xanthomas, cataracts, low intelligence, pyramidal signs, cerebellar signs, convulsions, peripheral neuropathy, foot deformity, cardiovascular disease or atherosclerosis, EEG abnormality, and increased CSF protein. Increased cholesterol was present in the serum, CSF and red cell membrane of all 8 patients. The bile of one patient with late age onset of the disease showed an attenuated production of bile acids and bile alcohols. Three of the 7 had obstruction and/or marked narrowing of the coronary arteries. Data on 136 patients reported throughout the world are reviewed.

Experimental simvastatin-induced myopathy in rabbits.

We induced experimental myopathy in rabbits by giving simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. After oral administration of simvastatin (50 mg/kg/day) for 2 weeks, serum CK was elevated in 5 of 7 rabbits; degenerating or necrotic fibers were seen in 3 rabbits. Using electromyography, myotonic discharges were found in the 2 rabbits examined. The combination of myotonic discharges, necrosis and raised serum CK levels suggests that the myopathy was induced by lesions of the muscle surface membrane.

Benefits and limits of hepatic resection for gastric metastases.

BACKGROUND: The significance of hepatic resection for gastric metastases has been controversial. METHODS: Forty consecutive patients undergoing hepatic resection for gastric metastases were reviewed to examine the benefits and the limits of hepatic resection using univariate and multivariate analyses. RESULTS: The overall survival was 27% at 2 years, 18% at 5 years, and 11% at 10 years. Six patients survived more than 5 years. All of the 6 patients underwent anatomical hepatic resection more extensive than segmentectomy, with sufficient resection margin. There were recurrences in 31 patients, and 94% of the recurrences were in the remaining liver. Univariate analysis showed time of hepatic metastases (P = 0.0078) and resection margin (P = 0.024) as significant prognostic factors. Multivariate analysis indicated that only time of hepatic metastases was an independent prognostic factor that influenced survival. CONCLUSIONS: These results suggest that in patients with synchronous metastases we should consider patient selection more strictly, and that in patients with metachronous metastases we should perform anatomical hepatic resection with sufficient resection margin.

Changes in hepatic venous oxygen saturation related to the extent of regeneration after partial hepatectomy in rats.

BACKGROUND: Changes in hepatic oxygen metabolism in relation to the extent of liver regeneration are expected after partial hepatectomy. There are few reports, however, about hepatic oxygen metabolism during liver regeneration. In this study, we evaluated changes in hepatic oxygen metabolism related to the regeneration rate, and the relationship between hepatic venous oxygen saturation (Shvo2) and liver regeneration after partial hepatectomy. METHODS: The work was done using 50% hepatectomized rats with continuous infusion of octreotide for inhibition of liver regeneration or with saline as control. The hepatic hemodynamics, oxygen metabolism, and Shvo2 levels as well as the regenerating liver status were evaluated for 3 days after hepatectomy. RESULTS: Administration of octreotide resulted in a significant reduction of the regenerating liver weight on days 1 and 3 after hepatectomy compared with the control group. Significantly decreased DNA synthesis and proliferating cell nuclear antigen labeling index were also found on day 1. Meanwhile, hepatic oxygen consumption (HVO2) and oxygen extraction ratio were significantly decreased in the octreotide-treated group on day 1. In contrast, the Shvo2 levels in the octreotide-treated group were significantly higher than those in the control group, and were inversely correlated with the HVO2. CONCLUSION: The remnant liver demands an increased amount of oxygen in relation to the extent of regeneration, and changes in the Shvo2 are inversely correlated with the HVo2. Therefore, monitoring the Shvo2 could be useful for estimating liver regeneration after partial hepatectomy.

Blood dolichols in a patient with abetalipoproteinaemia.

Dolichol and dolichyl derivatives have an important function as glycosyl carriers in the assembly of the N-asparaginyl-linked oligosaccharide core region of glycoproteins. Dolichols are synthesized through the cholesterol biosynthesis pathways in all mammalian organs and are present in all tissues, and are also associated with lipoproteins in the blood circulation. However, the origin and metabolic pathway of blood dolichols remain unknown. Abetalipoproteinaemia is a disorder of the secretion of very low-density lipoprotein (VLDL) from the liver and of chylomicrons from the intestine into the blood circulation. Therefore, examination of blood dolichols in this disorder may provide valuable information on their origin and metabolic pathway. Dolichols were exclusively associated with the high-density lipoprotein (HDL) fraction (80.7 +/- 6.3% of total dolichols) in control human blood. Serum from a patient also contained dolichols in the HDL fraction (82.8% of total dolichols). The total amount of dolichols was higher in the patient (207.0 ng/mL) than in the controls (106.2 +/- 22.7 ng/mL, n = 14). The compositions of dolichols were very similar to each other. These results indicated that, at least in the patient with abetalipoproteinaemia, the HDL-associated dolichols were possibly derived from the liver not through other lipoproteins but through dolichol transfer protein, or were possibly taken up and carried by HDL from peripheral tissues.

Management issues regarding hepatic adenomatosis.

Hepatic adenomatosis is a rare disease defined by multiple hepatic adenomas. There is controversy with regard to the optimal treatment for this disease because the potential for intraperitoneal hemorrhage or malignant transformation of the tumors is difficult to estimate. Furthermore, the technical difficulties of complete resection of all adenomas present unique operative challenges. We report experience with two patients and reviewed all reported cases from 1977. We define hepatic adenomatosis as five or more hepatic adenomas not associated with a medical history of glycogen storage disease, anabolic steroid use, or oral contraceptive use. The incidence of hepatic adenomatosis was preponderate among women [20 of 32 patients (63%)]. Thirteen of 32 patients (41%) had intratumoral bleeding, including four patients with intraperitoneal hemorrhage. Ten of 13 patients (77%) with intratumoral bleeding complained of abdominal pain; overall, 19 of 32 patients (59%) had abdominal pain. Twelve patients underwent hepatic resection, 6 patients underwent liver transplantation with no reported mortality, and 14 patients had no surgical treatment. Hepatocellular carcinoma was histologically confirmed in 2 of 32 patients (6%). Larger symptomatic adenomas exposed to liver surface have a bleeding propensity and should be surgically resected. Routine biopsy of other small nodules suspected as adenomas is recommended for definitive diagnosis.

An approach to intrapericardial inferior vena cava through the abdominal cavity, without median sternotomy, for total hepatic vascular exclusion.

In surgical resection for hepatocellular carcinoma with tumor thrombus extending into the inferior vena cava and other malignancies involving the retrohepatic inferior vena cava, the usefulness of total hepatic vascular exclusion has been reported by several authors. Total hepatic vascular exclusion usually consists of clamping at three points; at the infrahepatic inferior vena cava, at the suprahepatic inferior vena cava, and in Pringles' maneuver. Tumor thrombus extending into the inferior vena cava at the intrapericardial level below the right atrium can be resected without the use of cardio-pulmonary bypass. The inferior vena cava at the intrapericardial level has been reported to be usually approached by median sternotomy such as Chevron incision. We herein demonstrate an approach to the intrapericardial inferior vena cava through the abdominal cavity without median sternotomy.

Unilateral hepatic artery reconstruction is unnecessary in biliary tract carcinomas involving lobar hepatic artery: implications of interlobar hepatic artery and its preservation.

BACKGROUND/AIMS: The interruption of hepatic arterial flow when performing a bilioenteric anastomosis has been reported to usually bring about serious postoperative complications, such as anastomotic leakage, hepatic abscess and infarction. We aimed to evaluate the surgical implications of the interlobar hepatic artery when patients with advanced biliary tract carcinomas undergo surgical resection with a bilioenteric anastomosis. METHODOLOGY: In 7 patients with advanced biliary tract carcinomas, the combined resection of the liver (greater than hemihepatectomy in 2 and less than hemihepatectomy in 5), extrahepatic bile duct, hepatic artery (right hepatic artery in 5, right and left hepatic artery in 1, left hepatic artery in 1), and the portal vein was performed in 4 patients. The portal vein was reconstructed in all 4 patients. The hepatic artery was reconstructed in only one patient, with combined resection of both right and left hepatic arteries, but was not reconstructed in 2 other patients, even though they underwent resection greater than hemihepatectomy. RESULTS: The interlobar hepatic artery running into the Glissonian sheath around the hepatic duct confluence could be preserved in 5 patients, as shown by angiography, but could not be preserved in 2 patients who underwent greater than hemihepatectomy. Moderate and transient ischemic liver damage occurred, but no serious postoperative complications were induced in any of the 5 patients in the unilateral hepatic artery preserved group. However, both cases without preservation of the hepatic artery encountered liver failure, liver abscess and leakage of bilioenteric anastomosis, and one patient died of multiple organ failure. CONCLUSIONS: One major lobar branch of the hepatic artery involved by cancer invasion could be safely resected without reconstruction in patients with advanced biliary tract carcinomas when the interlobar hepatic artery running into the Glissonian sheath around the hepatic duct confluence is preserved.

A successful treatment for hepatocellular carcinoma with atrial tumor thrombus.

A 66-year-old man with an advanced hepatocellular carcinoma and tumor thrombus extending into the right atrium was treated by transcatheter arterial infusion of lipiodol and aclarubicin. This brought about a remarkable reduction of the tumor and the disappearance of the right atrial tumor thrombus. The tumor was then radically resected by hepatic posterior segmentectomy with combined resection of the right hepatic vein, where the tumor thrombus remained. He is doing well without any signs of recurrence 22 months after the operation.

[Hepatectomy (parenchyma-preserving) for hilar cholangiocarcinoma].

The aim of this study was to evaluate the results of parenchyma-preserving hepatectomy as surgical treatment for hilar cholangiocarcinoma. Ninety-three resected patients with hilar cholangiocarcinoma were included in this study. The resected patients were stratified into three groups: the extended hepatectomy (EXH) group (n = 66); the parenchyma-preserving hepatectomy (PPH) group (n = 14); and the local resection (LR) group(n = 13). The EXH group underwent hepatectomy more extensive than hemihepatectomy, the PPH group underwent hepatectomy less extensive than hemihepatectomy; and the LR group underwent extrahepatic bile duct resection without hepatic resection. Surgical curability of the PPH and EXH groups was better than that of the LR group. Surgical morbidity was higher in the EXH group(48%) than in the LR group (8%) and the PPH group(14%) (p < 0.01 and p < 0.05, respectively). The survival rates after resection were significantly higher in patients who underwent hepatectomy, including PPH and EXH, than in patients who underwent LR (29% vs 8% at 5 years, respectively, p < 0.05). However, no significant difference in survival was found between the PPH and EXH groups. Univariate and multivariate analysis showed that significant prognostic factors for survival were resected margins, lymph node status, and vascular resection. In conclusion, PPH may be beneficial in highly selected patients based on cancer extent and high-risk patients with liver dysfunction and advanced age.

Clinical findings, status of care, comprehensive quality of life, daily life therapy and treatment at home in patients with Parkinson's disease.

We analyzed patients with Parkinson's disease from various aspects such as clinical findings, the degree of independence in daily life, care environment, quality of life (QOL) and treatment at home. The subjects were 104 in- and outpatients (47 males and 57 females) seen at our hospital. The mean age was 69.85 years in the males and 70.35 years in the females. The disease most frequently developed at the age of 60-69 years and the disease duration was 5 years or more in 52 patients. Rigidity was the most common symptom (91 patients), followed by gait disturbance (n = 87) and tremor (n = 86). Levodopa/carbidopa was the drug most frequently used (77 patients). The number of patients treated by combination drug therapy increased with the duration of disease. Concerning the degree of independence in daily life, assistance was often necessary in bathing, dressing and undressing, toileting and walking. In particular, total assistance was necessary in patients with Hoehn-Yahr stage-IV and V disease. The comprehensive QOL was the lowest in terms of social activities, hobbies and leisure activities, followed in order by work and subjective QOL. QOL decreased in each item with the severity of the disease. Treatment at home was performed for 19 patients, of whom 11 are still being treated by our staff. Treatment at home combined with persons who care for the patient and in cooperation with other welfare resources may improve the patient's QOL. In diseases that require long-term care such as Parkinson's disease, a comprehensive care management system should be established from the aspect of the patient's QOL.