Hyperbaric oxygen therapy for the treatment of postoperative paralytic ileus and adhesive intestinal obstruction associated with abdominal surgery: experience with 626 patients

BACKGROUND/AIMS: The results of hyperbaric oxygen (HBO) therapy for treatment of postoperative paralytic ileus and adhesive intestinal obstruction associated with abdominal surgery are unknown. METHODOLOGY: A retrospective review of postoperative paralytic ileus and adhesive intestinal obstruction associated with abdominal surgery in 626 patients required 758 admissions who underwent HBO therapy was undertaken to examine the efficacy of HBO therapy. RESULTS: The overall resolution rates for patients receiving HBO therapy in cases of postoperative paralytic ileus and adhesive intestinal obstruction were 92% and 85%, respectively. Among patients who were more than 75 years old, the therapies resolved 35 (97%) of 36 cases of postoperative paralytic ileus and 42 (81%) of 52 cases of adhesive intestinal obstruction, which was comparable to the results for patients less than 75 years old. The mortality rate was 1.2% overall. Complications related to HBO therapy occurred in 3.8% of the admissions, and most of them were not serious. CONCLUSIONS: These results suggest that HBO therapy might deserve further assessment for use in management of postoperative paralytic ileus and adhesive intestinal obstruction as a new modality. HBO therapy is safe and non-invasive, and may be useful in the elderly patients, since mortality was relatively low in this series.     

Familial facioscapulohumeral muscular dystrophy: phenotypic diversity and genetic abnormality

We report two cases showing facioscapulohumeral muscular dystrophy (FSHD) with phenotypic diversity but the same genetic abnormality detected by a p13E-11 probe. The proband, a 26-year-old woman, showed an early onset, tortuosity of retinal arterioles and respiratory failure. The 53-year-old mother of the proband had limb-girdle (L-G) type muscular weakness with very mild facial involvement. Muscle biopsy showed perivascular cell infiltration in both patients. These cases suggest that the phenotypic diversity ranges from L-G type weakness to severe respiratory failure in FSHD family.     

Aggressive surgical resection for hepatocellular carcinoma with tumor thrombus extending to inferior vena cava and synchronous pulmonary metastasis

We describe a 66-year-old man having hepatocellular carcinoma with tumor thrombus extending into the inferior vena cava and synchronous pulmonary metastasis. He was referred to Chiba University Hospital on May, 2000, complaining of emaciation. Radiological findings showed a huge hepatocellular carcinoma in the entire right lobe and tumor thrombus extended into the intrapericardial inferior vena cava. He also had a solitary pulmonary metastasis in the left pulmonary lobe (stage IVB). Right hemihepatomy was performed under total hepatic vascular exclusion without cardiopulmonary bypass, and tumor thrombus was completely removed. Thoracoscopic wedge resection of pulmonary metastasis was also performed. The patient had an uneventful postoperative course. Histopathological examination revealed that the tumor was moderately differentiated hepatocellular carcinoma The patient is still alive after 26 months with pulmonary recurrence, but without hepatic recurrence. To our knowledge, there has been no reported case of resection for both hepatocellular carcinoma invading the inferior vena cava and synchronous pulmonary metastasis. In conclusion, aggressive surgical resection for advanced hepatocellular carcinoma concomitant with pulmonary resection may bring about better prognosis in highly selected patients.     

Decreased cell-mediated immune status in colorectal cancer patients with hepatic metastasis

BACKGROUND/AIMS: Depression of cell-mediated immunity frequently accompanies solid tumor malignancy, and appears to be worsened as the disease progresses. In this study, we investigated cell-mediated immune status in colorectal cancer patients. METHODOLOGY: Interleukin-2 (IL-2) productivity by phytohemagglutinin (PHA)-stimulated non-adherent peripheral blood mononuclear cells (PBMC), and prostaglandin E2 (PGE2) productivity by LPS-stimulated adherent PBMC were investigated in colorectal cancer patients with hepatic metastasis (n=20) and without hepatic metastasis (n=20), and in non-malignant disease controls (n=20). Percentages of peripheral blood T-cell subsets and NK activity were also investigated. RESULTS: In the colorectal cancer patients with hepatic metastasis IL-2 productivity was significantly decreased, compared with the controls. However, the percentages of T-cell subsets and NK activity were not significantly different among the groups. Meanwhile, PGE2 productivity in the patients with hepatic metastasis was significantly increased, compared with the other groups, and was significantly correlated with the hepatic tumor load. CONCLUSIONS: Tumor-bearing state, especially metastasis to the liver, may influence immune status of the patient. For evaluating cellular immunity status, cytokine productivity by activated lymphocytes and monocytes may be a more sensitive marker rather than other conventional immunological parameters, and may also provide useful information for immune intervention in the treatment of patients from this point of view.     

Does prolonged biliary obstructive jaundice sensitize the liver to endotoxemia?

Biliary obstructive jaundice (OJ) is an important clinical consideration concerning high bacteremic risk. Hepatocyte apoptosis is one of the causes of cholestatic liver injury. The aim of the current study was to examine the precise pathway and time course of hepatocyte apoptosis during OJ with LPS administration and to determine if OJ sensitizes the liver to endotoxemia. Male C57BL/6 mice were subjected to bile duct ligation and division and were administered with LPS at 3 (OJ3) or 14 (OJ14) days after surgery. Fas ligand expression, poly (adenosine diphosphate-ribose) polymerase p85 fragment immunohistochemistry, activation of caspases 3, 8, and 9, serum alanine aminotransferase levels, and hepatic adenosine triphosphate (ATP) contents were examined. Survival after LPS administration in male C57BL/6 or gld/gld (Fas ligand-deficient) mice was determined. The expression of Fas ligand increased during OJ. After LPS administration, the expression of cleaved caspases 3 and 8 increased in Sham3, Sham14, OJ3, and OJ14 mice, and it significantly increased in OJ14 compared with other mice. Poly (adenosine diphosphate-ribose) polymerase p85 immunohistochemistry showed significant hepatocyte apoptosis after LPS administration in OJ14 mice relative to OJ3. In OJ14 with LPS administration, ATP contents significantly decreased and alanine aminotransferase levels increased. Hepatocyte apoptosis was decreased in gld/gld OJ14 mice compared with C57BL/6 OJ14. All C57BL/6 OJ14 mice with LPS died, but survival in gld/gld OJ14 significantly ameliorated. In prolonged OJ with LPS administration, hepatocyte apoptosis depending on Fas ligand expression significantly increased in association with a decrease in ATP contents, thus resulting in liver necrapoptosis.     

Right hepatectomy combined with retrohepatic caval resection,using a left renal vein patch graft for advanced cholangiocarcinoma

Combined resection of the inferior vena cava for hepatobiliary malignancies remains a technical challenge. We successfully resected an intrahepatic cholangiocarcinoma involving the retrohepatic vena cava, and reconstructed the caval defect using a left renal vein patch graft. The patient was a 79-year-old man. Preoperative ultrasonography and computed tomography revealed that the tumor was located in the right lobe of the liver and was about 6?cm in diameter. Arteriogram revealed encasement of the right arterial and portal branches. Magnetic resonance imaging scan revealed that the tumor involved the retrohepatic vena cava. The patient underwent a right hepatectomy combined with resection of the retrohepatic vena cava. The resected portion of the caval wall was 3.6?cm long and 2.7?cm wide. The caval defect was reconstructed using a left renal vein patch graft of a rhomboid shape, which was made by oblique incision of the vein graft. The postoperative course was uneventful. Postoperative cavogram showed adequate patency of the reconstructed retrohepatic vena cava. The patient was disease-free 22 months after surgery. In conclusion, major liver resection combined with caval resection and reconstruction can be performed safely. Furthermore, a left renal vein graft can provide a flexible patch according to the form and size of the caval defect.     

Establishment of gemcitabine-resistant human pancreatic cancer cells and effect of brefeldin-a on the resistant cell line

To date, no therapy has been found to which pancreatic cancer responds with the exception of surgical resection in early stages. Recently, gemcitabine has become the standard of care for chemotherapy in those patients with advanced disease. Most pancreatic tumors however, develop resistance to gemcitabine. The aim of this study is to clarify the mechanism of resistance to gemcitabine in human pancreatic cells. Using a cell selection method, a human pancreatic cancer cell line resistant to gemcitabine was established. Cellular proliferation and viability were determined by MTT assay. The cell line with acquired resistance was also found to have cross resistance to fluorouracil. Brefeldin-A (BFA) has been used as a tool for studies of intracellular protein traffic, rather than as an anticancer drug. BFA displays the same effects on wild type cells and those with acquired resistance. Gemcitabine combined with BFA in low doses is significantly more effective than gemcitabine alone against MIA PaCa-2 cell line. Our data suggest that the gemcitabine-resistant and 5-FU-resistant pathways may partially overlap each other. In short, BFA may be used as a modulator of gemcitabine.     

Obstructive jaundice impairs hepatic sinusoidal endothelial cell function and renders liver susceptible to hepatic ischemia/reperfusion

BACKGROUND/AIMS: Obstructive jaundice is associated with increased surgical morbidity and mortality. While parenchymal injury has been defined in obstructive jaundice, the pathogenesis of hepatic sinusoidal endothelial cell injury in obstructive jaundice is unclear. The aims of this study were to investigate hepatic sinusoidal endothelial cell injury in obstructive jaundice by determining serum hyaluronic acid levels, purine nucleoside phosphorylase/alanine aminotransferase ratios, and hyaluronic acid elimination rate, and also to determine whether hepatic parenchymal cell injury in obstructive jaundice is induced more than in normal liver after hepatic ischemia/reperfusion. METHODS: Male Wistar rats underwent ligation and division of the common bile duct (obstructive jaundice group) or sham operation (Sham group). Serum hyaluronic acid levels and purine nucleoside phosphorylase/alanine aminotransferase ratios in both groups were examined at intervals up to 21 days after surgery. Hepatic blood flow, permeability, neutrophil accumulation, and hyaluronic acid elimination rates in both groups were measured 14 days after surgery. Changes in serum hyaluronic acid and alanine aminotransferase concentrations were determined after 15 min of hepatic ischemia followed by reperfusion. RESULTS: Serum hyaluronic acid levels remained elevated after bile duct ligation. Hepatic sinusoidal endothelial cell swelling was observed by electron microscopy, and hepatic permeability was increased 14 days after bile duct ligation in association with neutrophil accumulation. Hepatic blood flow in obstructive jaundice remained unchanged, but hyaluronic acid elimination capacity was less than that in the Sham group. After hepatic reperfusion, the disappearance rate of serum hyaluronic acid in obstructive jaundice was lower, and serum alanine aminotransferase levels were higher than those in the Sham group. CONCLUSIONS: Our findings suggest that obstructive jaundice impairs sinusoidal endothelial cells and that sinusoidal endothelial cell damage in association with sinusoidal deterioration during obstructive jaundice renders liver susceptible to ischemia/reperfusion relative to normal liver.     

Hepatocyte growth factor promotes liver regeneration and protein synthesis after hepatectomy in cirrhotic rats

BACKGROUND/AIMS: Hepatocyte growth factor, a potent mitogen for hepatocytes has been reported to be a hepatrophic factor in normal livers. In this study, the effect of exogenous hepatocyte growth factor on liver regeneration in cirrhotic rats was investigated, in vitro and in vivo. METHODOLOGY: Liver cirrhosis was induced by intraperitoneal injections of an emulsion, carbon tetrachloride and olive oil, twice weekly for 10 weeks. In vitro, various amounts of exogenous hepatocyte growth factor; 0, 0.5, 1, 2.5, 5, and 10 ng/mL; were added to the hepatocytes isolated using in situ perfusion method. In vivo, partial hepatectomy (Hx), according to the procedure described by Higgins and Anderson, was performed on cirrhotic rats. Saline solution (control group) or 3 micrograms/kg of exogenous hepatocyte growth factor (HGF group) was then injected through the tail vein at intervals 12 hours after Hx. RESULTS: In vitro, DNA synthesis in hepatocytes obtained from cirrhotic livers increased following exogenous hepatocyte growth factor in dose-dependent fashion. In vivo, the labeling index of 5-bromo-2'-deoxyuridine at 24 hours after Hx was markedly increased by exogenous hepatocyte growth factor (control, 10.0 +/- 3.1%; hepatocyte growth factor, 25.8 +/- 9.8%; P < 0.01). Furthermore, serum albumin at 24 and 72 hours and a normotest at 24 hours after Hx, were significantly higher in the HGF group than in the control group. CONCLUSIONS: These results indicate that exogenous hepatocyte growth factor may promote DNA synthesis and protein synthesis during liver regeneration after Hx with cirrhosis.