Risk Factors and Management of Bile Leakage after Hepatic Resection

The aim of this study was to identify the perioperative risk factors for postoperative bile leakage after hepatic resection and to propose a treatment strategy for such leakage when it does occur. Between 1992 and 2000 a total of 313 hepatic resections without choledocojejunal anastomosis were performed at our institute. Risk factors related to bile leakage were identified with univariate analysis, and strategies were evaluated in relation to the findings of postoperative fistulography. Postoperative bile leakage developed in 17 patients (5.4%). Univariate analysis identified high risk factors as advanced age, a wide surface area of the incision (bile leakage group versus no bile leakage group: 102.1 vs. 66.4 cm², p < 0.05), and exposure of Glissons sheath at the cut surface (e.g., central bisegmentectomy, S4, S8 subsegmentectomy). Groupings of patients by their postoperative fistulography results showed that patients with involvement of the proximal bile duct were slower to heal than those with no demonstrable bile duct involvement. The one patient whose fistulogram demonstrated peripheral bile duct involvement had uncontrollable leakage and required reoperation. Hepatectomies with a wide surface area and those that expose the major Glissons sheath present serious risk factors for bile leakage. When the fistulogram shows proximal bile duct involvement, endoscopic nasobiliary tube drainage is necessary; when the fistulogram shows peripheral bile duct involvement, reoperation is needed.     

Surgical Anatomy of Hepatic Hilum with Special Reference of the Plate System and Extrahepatic Duct

Background When resecting hilar cholangiocarcinoma, the surgeon cannot visualize the hilar vessels through thick connective tissue known as the plate system. Little has been reported regarding the anatomical relationship between the plate system and the extrahepatic bile duct. Methods Twenty-five formalin-fixed cadaveric livers were dissected carefully and 7 were sectioned sagittally. The extent, composition, and distribution of the extrahepatic bile ducts within the system were investigated. The length between the confluence of the hepatic duct and the branch point of the segmental duct (level I) and the length between the branch point of the segmental duct and the segmental Glisson’s pedicle (level II) were measured. Results The plate system—composed of the hilar, cystic, Arantian, and umbilical regions—was easily separated from the hepatic parenchyma. Histologically, dense connective tissue with abundant capillaries, lymphatic vessels, and neural fibers were noted. Level I of B1pcp and B4a measured 13.0 and 14.7 mm, respectively. Level II measured 8.6 and 17.3 mm, respectively. Conclusions The bile ducts in the plate system correspond to the extrahepatic bile ducts and their lengths are variable for every segment. Knowing the lengths of the resectable extrahepatic bile ducts is useful for deciding which segment should be resected according to the cancerous invasion.     

First pass metabolism and in vitro metabolism of a new orally active dopamine prodrug, N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine in dogs.

To elucidate the first pass metabolism of the dopamine prodrug N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine (TA-870) in the small intestine and liver of dogs, the blood and plasma concentrations of unchanged TA-870 and metabolites in the gastroduodenal vein, portal vein, hepatic vein, and abdominal aorta were measured by HPLC after intraduodenal administration of TA-870. In addition, an in vitro metabolic study of TA-870 was carried out using liver, small intestinal wall, and blood homogenates of dogs. The order of maximal concentration (Cmax 0-30 min) in gastroduodenal blood or plasma was unchanged TA-870 greater than deethoxycarbonylated TA-870 (DEC-TA-870) greater than conjugated dopamine greater than free dopamine (DA) greater than free homovanillic acid (HVA) greater than free 3,4-dihydroxyphenylacetic acid (DOPAC). This result showed that the main pathway of metabolism in the small intestine is catechol ester hydrolysis and minor pathways are amido hydrolysis, oxidative deamination, and catechol 3-O-methylation. The order of Cmax in the hepatic vein and abdominal aorta was conjugated DA greater than free DEC-TA-870 greater than free HVA greater than free DA greater than free DOPAC greater than conjugated DOPAC greater than unchanged TA-870. The main metabolic pathways in the liver were hydrolyses of ester and amido-linkage of TA-870 and conjugation of DA. In the in vitro studies, the main metabolites of TA-870 in liver, small intestinal wall, and blood homogenates were DEC-TA-870, 3- or 4-mono-deethoxycarbonylated TA-870, DA, and an unknown compound.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical or experimental use of an anticancer drug-oil suspension and its characteristics

The anticancer agent, Nimustine, which is a derivative of Nimustine hydrochloride (Sankyo CC, Ltd), was suspended in an oil, Lipiodol, using an ultrasonic suspender and used in experimental animals and human subjects with malignant tumor. The use of Lipiodol facilitates the fluoroscopic demonstration of the site into which the suspension has been injected. The Nimustine-Lipiodol suspension was almost stable in room air over 7 days and diffusion of suspended Nimustine into saline in vitro was still noted 4 weeks later. Remarkable regression of tumor size was observed when the Nimustine-Lipiodol suspension was locally injected into the lesion of Lewis lung cancer subcutaneously inoculated into mice. Moreover, a marked regression of tumor size and improvement of CEA level in serum were also obtained when arterial injection of the Nimustine-Lipiodol suspension was carried out in patients with metastatic liver cancer. Therefore, local or arterial injection of Nimustine-Lipiodol suspension is considered to be effective as a method of cancer targeting therapy.     

Non‐uniformity in the regional pattern of Lewy pathology in brains of dementia with Lewy bodies

We examined the regional pattern of Lewy pathology in brains of dementia with Lewy bodies (DLB) to clarify whether Lewy pathology uniformly progresses or not. Thirty‐five autopsied DLB cases were examined using α‐synuclein‐immunohistochemistry, and the regional degree of Lewy pathology in the brainstem, diencephalon and cerebral cortex was quantitatively evaluated. Consequently, we found that the regional pattern of Lewy pathology differed according to the pathological subtype, and was divided into three types: type 1 showed a brainstem‐predominant pattern, type 2 was almost equal for the brainstem and cerebral cortex, and type 3 showed a cerebral cortex‐predominant pattern. The limbic type/pure and common forms were mainly composed of type 1, whereas the neocortical type/common and Alzheimer's disease (AD) forms were mainly composed of type 3. These findings suggest the possibility that Lewy pathology of the limbic type/pure and common forms mainly progresses from the brainstem to the cerebrum, whereas that of the neocortical type/common and AD forms mainly progresses from the cerebrum to the brainstem. Cases with type 1 Lewy pathology mainly developed parkinsonism, whereas those with type 3 Lewy pathology mainly developed dementia. This corresponded to most of the limbic type/pure and common forms which developed parkinsonism, whereas most of the neocortical type/common and AD forms developed dementia. Type 1 cases may thus be clinically diagnosed as having Parkinson's disease (PD) with dementia. These findings suggest that PD has clinico‐pathological continuity with DLB, and that the regional pattern of Lewy pathology is not uniform.     

Left ventricular assist device implantation after plasma exchange for heparin-induced thrombocytopenia

Treating a patient with heparin-induced thrombocytopenia can be challenging particularly when the patient requires urgent cardiac surgery that uses heparin for anticoagulation. We herein report a case of a 61-year-old man with idiopathic dilated cardiomyopathy associated with heparin-induced thrombocytopenia and who underwent plasma exchange to remove heparin-induced thrombocytopenia antibodies before undergoing left ventricular assist device implantation. The surgery was performed using cardiopulmonary bypass and unfractionated heparin.     

Contrast-enhanced sonography of pancreatic ductal carcinoma using agent detection imaging

Purpose The aim of this study was to evaluate the enhancement behavior of pancreatic ductal carcinoma by contrast-enhanced sonography with agent detection imaging (ADI), and to clarify the origin of microbubble signals by comparisons with histological findings of resected specimens. Methods The subjects were 21 patients with resectable pancreatic carcinoma. The final histological diagnosis was tubular adenocarcinoma in 20 cases, and anaplastic carcinoma in one case. Ultrasound examinations were performed using an Acuson Sequoia 512 series system, and the contrast agent (Levovist) was injected intravenously in doses of 7 ml (300 mg/ml). The ADI signals (in the tumor) were recorded continuously for 30 s after an injection of Levovist (vascular image) and then obtained intermittently (30 s time-intervals) until the signal had diminished in pancreatic tissue (perfusion image). Results Contrast enhancement of the tumor was observed in 71.4% of subjects on the vascular image and 76.3% of subjects on the perfusion image. Enhancement patterns on the vascular image were classified into three types: VI-1 (linear enhancement), VI-2 (spotty enhancement), and VI-3 (no enhancement). VI-1, VI-2, and VI-3 were seen in 9 (42.8%), 6 (28.6%), and 6 (28.6%) of the 21 cases, respectively. Enhancement patterns on the perfusion image were classified into four types: PI-1 (diffuse uneven enhancement), PI-2 (spotty enhancement), PI-3 (peripheral enhancement), and PI-4 (negative enhancement). The incidence of PI-1, PI-2, PI-3, and PI-4 was 4.8%, 42.9%, 28.6%, and 23.8%, respectively. With respect to resectable cases, these enhancement patterns were compared with histological findings, i.e., the distribution of blood vessels in the tumor, remaining pancreatic tissues in the tumor, differentiation of types of adenocarcinoma, volume of stroma, and invasion types of carcinoma. The enhanced patterns consequently corresponded to either the distribution of the blood vessels or the remaining pancreatic tissues in the tumor. Conclusion This study indicated that pancreatic ductal carcinoma is frequently enhanced by microbubbles, and the signals seem to originate from fine blood vessels and the remaining pancreatic tissues in the tumor.     

Pathogenesis in ABO incompatible liver transplantation: a clinicohistological evaluation of four patients

Takeda K, Tanaka K, Morioka D, Kumamoto T, Endo I, Togo S, Shimada H. Pathogenesis in ABO incompatible liver transplantation: a clinicohistological evaluation of four patients.
Clin Transplant 2010: 24: 747–751. © 2009 John Wiley & Sons A/S. Abstract: The aim of this study was to clarify the pathogenesis of antibody‐mediated rejection (AMR) of ABO‐incompatible liver transplantation (ABO‐I‐LT). We investigated, within one month of surgery, the clinical courses of 10 patients who received ABO‐I‐LT. We encountered four cases of AMR, which were classified into two groups according to the stage of the AMR: early (within the first 14 postoperative days [PODs]) or late (after the 14th POD). There were three patients in the early stage, and one patient in the late stage. Three early‐stage AMR patients had both hyperbilirubinemia and thrombocytopenia within one month after LDLT, but the one late‐stage AMR patient had neither. On liver biopsy, hemorrhagic infiltration was seen more frequently in the early‐stage AMR patients than in the patient with late‐stage AMR. Plasma exchange combined with a large amount of gamma‐globulin bolus infusion therapy was effective in the three early‐stage patients, but the late‐stage AMR was controlled by antibiotic treatment. This study showed that the early‐stage AMR resulted from the antigen‐antibody reaction of ABO‐blood‐group antigens, while the late‐stage AMR may have been caused by an infection.     

Evidence for depletion of CASP5 Ala90Thr heterozygous genotype in aged subjects

Our previous studies, which included genotyping of multiple coding apoptotic gene polymorphisms, unexpectedly demonstrated a depletion of heterozygous CASP5 Ala90Thr (rs507879, c.268 G > A) genotypes in elderly subjects. Present investigation was aimed to validate this trend. An analysis of 510 subjects aged 75–103 years revealed 205 (40%) CASP5 Ala90Thr heterozygotes as compared to 254 (50%) expected from the minor allele frequency 0.470 (p = 0.000014). This deviation was not observed in 549 middle-aged (18–50 years) controls (270 (49%) heterozygotes observed vs. 274 (50%) expected; minor allele frequency 0.475; p = 0.743). Unfavorable significance of CASP5 heterozygous genotype may be explained by the role of the caspase-5 in inflammation-related processes. Almost all prior gene-longevity association studies focused on discrimination between “good” and “bad” gene variants. Here we present a distinct situation, where the combination of alternative alleles (i.e., heterozygosity) appears to be unfavorable as compared to the homozygous carriership of either gene variant.     

Prognostic Factors After Resection of Pancreatic Cancer

Objectives  The purpose of this study was to identify important prognostic factors related to the status of a pancreatic tumor, its treatment, and the patient’s general condition. Methods  Between April 1992 and December 2006, 140 patients underwent a pancreatic resection for invasive ductal carcinoma. Prognostic factors were defined by univariate and multivariate analyses. Results  The study included 103 tumors in the head of the pancreas and 37 tumors in the body or tail. The median survival time and the actuarial 5-year survival rate for all patients were 14.5 months and 12.3%, respectively. Using the significant prognostic factors identified by univariate analysis, multivariate analysis revealed that a preoperative serum CA19-9 concentration >100 U/ml (HR = 1.84, p = 0.0074), a tumor size >3 cm (HR = 1.74, p = 0.0235), venous involvement (HR = 2.39, p = 0.0006), a transfusion requirement of ≥1000 ml (HR = 2.23, p = 0.0006), and a serum albumin concentration on 1 postoperative month (1POM) < 3 g/dl (HR = 2.40, p = 0.0009) were significant adverse prognostic factors. The presence of hypoalbuminemia on 1POM significantly correlated with a longer surgical procedure (p = 0.0041), extended nerve plexus resection around the superior mesenteric artery (p = 0.0456), and a longer postoperative hospital stay (p = 0.0063). Conclusion  To improve long-term survival, preserving the patient’s general condition by performing a curative resection with a short operation time and minimal blood loss should be the most important principle in the surgical treatment of pancreatic cancer.