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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjsurg.2008.05.007 Byline: Kosuke Suda, Masayuki Ohtsuka, Satoshi Ambiru, Fumio Kimura, Hiroaki Shimizu, Hiroyuki Yoshidome, Masaru Miyazaki Keywords: Biliary tract malignancies; Extended hepatectomy; Postoperative hyperbilirubinemia; Remnant liver volume/entire liver volume ratio; Indocyanine green retention rate at 15 minutes Abstract: Postoperative hepatic insufficiency is a critical complication after extended hepatic resection in patients with biliary tract malignancies, the majority of whom suffer from obstructive jaundice. The aim of this study was to assess clinical parameters linked to this type of liver dysfunction. Author Affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8670, Japan Article History: Received 31 January 2008; Revised 12 May 2008

Intraductal papillary neoplasms of the bile duct (IPNB) have been recently proposed as the biliary counterpart of intraductal papillary mucinous neoplasms of the pancreas (IPMN-P). However, in contrast to IPMN-P, IPNB include a considerable number of the tumors without macroscopically visible mucin secretion. Here we report the similarities and differences between IPNB with and without macroscopically visible mucin secretion (IPNB-M and IPNB-NM). Surgically resected 27 consecutive cases with IPNB were divided into IPNB-M (n=10) and IPNB-NM (n=17), and their clinicopathologic features were examined. Clinically, both tumors were similar. Pathologically, the most frequent histopathologic types were pancreatobiliary in IPNB-NM and intestinal in IPNB-M. Various degrees of cytoarchitectural atypia within the same tumor were exhibited in 8 IPNB-M, but only 3 in IPNB-NM. Although the tumor size was similar, 9 IPNB-NM were invasive carcinoma, whereas all but 1 IPNB-M with carcinoma were in situ or minimally invasive. Immunohistochemically, positive MUC2 expression was significantly more frequent in IPNB-M than in IPNB-NM, whereas MUC1 tended to be more frequently expressed in IPNB-NM compared with IPNB-M. Among IPNB-NM with positive MUC1 expression, 3 had negative MUC2 and MUC5AC expressions. These tumors showed a tubulopapillary growth with uniform degree of cytoarchitectural atypia. All IPNB-M were negative for p53, and the frequency of positive p53 protein in IPNB-NM was at the middle level of that in IPNB-M and nonpapillary cholangiocarcinoma. In conclusion, IPNB-M showed striking similarities to IPMN-P, but IPNB-NM contained heterogeneous disease groups.

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.

Gastroenteropancreatic neuroendocrine tumors are uncommon and their tumor biology has not been well elucidated to date. Currently the WHO classification is widely used for the diagnosis and distinction of this tumor entity, which is sometimes cumbersome. Although neuroendocrine tumor markers do exist (ie chromograninA, synaptopyhsin, etc), sensitive and specific markers that accurately predict tumor growth and tumor behavior are still absent. In the present study, we assessed the expression of transcription factors (NeuroD and mASH1) essential for the normal fetal neuronal development in 33 gastroenteropancreatic neuroendocrine tumor patients (12 well-differentiated neuroendocrine tumors, 7 well-differentiated neuroendocrine carcinomas, and 14 poorly differentiated neuroendocrine carcinomas). NeuroD was less expressed in poorly differentiated neuroendocrine carcinoma (small-cell type) compared to well-differentiated neuroendocrine tumor (carcinoid) by reverse transcription–polymerase chain reaction. Immunohistochemical staining revealed that mASH1 was highly (sensitivity of 71%) and specifically (specificity of 95%) expressed in poorly differentiated neuroendocrine carcinoma. High NeuroD expression was seen in all well-differentiated neuroendocrine carcinoma and tumor (carcinoid) patients. Low NeuroD expression was seen in 36% (5 of 14) of poorly differentiated neuroendocrine carcinoma patients, which was associated with significant shorter overall survival. The expression pattern of these transcription factors may represent the biological and pathophysiological difference of gastroenteropancreatic neuroendocrine tumors and may become a new marker for the distinction of gastroenteropancreatic neuroendocrine tumors.

Endoglin, a component of the transforming growth factor receptor expressed in embryonic vascular endothelial cells, is expressed in vascular endothelial cells in several types of cancer tissues and is involved in tumor angiogenesis. The aim of this study was to analyze the expression pattern of endoglin in pancreatic cancer and assess the involvement of this molecule in cancer progression.

Heterogeneous biological characteristics of hepatocellular carcinoma may be attributed to the cellular origin of the tumor. Patients with hepatocellular carcinoma probably derived from hepatic progenitor cells had early tumor recurrence after surgical resection or liver transplantation, suggesting that these tumors have aggressive characteristics. Ezrin, a member of the ERM (ezrin-radixin-moesin) cytoskeleton-associated protein family, is highly expressed in several types of human cancers and correlations between its immunoreactivity and patient outcome have been shown. In this study, ezrin expression, as well as cytokeratin19 and cytokeratin 7 expression, which are regarded as progenitor cell/ductular markers were immunohistochemically assessed in cases of hepatocellular carcinoma. In normal livers, ezrin expression was not found in any cell types, whereas cytokeratin 7 and cytokeratin 19 were exclusively stained in bile duct cells. In contrast, in livers with chronic hepatitis or cirrhosis, positive ezrin expression was observed in ductular reactions with strong intensity and intermediate hepatobiliary cells with various intensity. Of 77 cases of hepatocellular carcinoma, 28 (36%) had positive ezrin expression, 32 (42%) had cytokeratin 7 expression, and 11 (14%) had cytokeratin 19 expression. Ezrin expression in hepatocellular carcinoma was significantly associated with cytokeratin 19 expression, but not with cytokeratin 7 expression. Patients with ezrin-positive hepatocellular carcinoma had a significantly higher prevalence of elevated serum α-fetoprotein. Patients with immunohistochemical ezrin-positive hepatocellular carcinoma demonstrated significantly shorter recurrence-free and overall survival compared to patients with ezrin-negative hepatocellular carcinoma. Multivariate analysis revealed positive ezrin expression and multiple tumors to be independently associated with early recurrence in patients with hepatocellular carcinoma after curative surgical resection. These results suggested that hepatocellular carcinoma with ezrin expression might be at least partly derived from hepatic progenitor cells. Measurement of ezrin expression might be used to identify patients with an increased risk of early recurrence.Modern Pathology (2008) 21, 847–855; doi:10.1038/modpathol.2008.59; published online 18 April 2008

Cytokines and chemokines potentially modulate postoperative immune response. Association of circulating cytokines and chemokines with postoperative infectious complications after pancreaticoduodenectomy was evaluated.

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.

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.

Background/Purpose. The aim of this report was to assess the outcome of aggressive surgical treatment for intrahepatic cholangiocarcinoma. Methods. From 1984 to 2001, we encountered 64 patients with intrahepatic cholangiocarcinoma. Of the 64 patients, 50 patients who underwent surgical resection with macroscopically curative objectives (78%) were reviewed for surgical procedures and outcomes. Results. Hemi- or more extensive hepatectomy was required for surgical resection in 40 patients (80%). Overall hospital morbidity and mortality rates were 50% and 8%, respectively. Curative resection with pathological free margins was achieved in 34 patients (68%). The 1-, 3-, and 5-year patient survival and tumor-free survival rates were 61.6%, 37.6%, and 22.5%; and 55%, 11%, and 11%, respectively. Among the macroscopic types, all 9 patients with intraductal growth type are alive 11–75 months after surgery. Survival rates among patients who had undergone curative resection were significantly better than those in patients who had undergone noncurative resection, even when patients with the intraductal growth type were excluded. Nodal status did not affect patient survival. Conclusions. Although the overall survival rate after surgical resection remains unsatisfactory, long-term survival is possible through extended surgical resection with pathological free margins. Patients with the intraductal growth type of intrahepatic cholangiocarcinoma might have the best chance of being cured by surgical treatment.

The precise mechanisms leading to polymorphonuclear neutrophil (PMN) recruitment and activation in the extended cold-preserved liver after transplantation are not yet fully understood.

Abstract: We describe herein an extremely unusual case of a gastrointestinal stromal tumor (GIST) of the lesser omentum. A 45-year-old man was admitted to our hospital with an intra-abdominal mass that was subsequently misdiagnosed as a submucosal tumor of the stomach. The tumor arose from the lesser omentum and was removed without difficulty. Histologically, the tumor was composed of spindle–shaped cells with an interlacing bundle pattern, and immunohistochemical examination showed that it was positive for myeloid stem cell antigen (CD34), but negative for HHF35 and S-100 protein. These findings were consistent with a GIST lacking myogenic features and neural attributes. The patient had an uneventful postoperative course, and was free of recurrence when last seen 11 months after his operation.

Abstract: A 58-year-old man who underwent a potentially curative resection of cancer of the sigmoid colon at another hospital was subsequently followed up at our hospital. A lateral segmentectomy was per-formed for a solitary hepatic metastasis, and partial resection of right S1 was later carried out for a pulmonary metastasis. Another pulmonary metastasis was found 6 years after his third operation and to minimize the area to be resected, bronchial arterial infusion chemotherapy was performed twice. A 51% reduction in the size of the tumor was achieved, so a right upper lobectomy and wedge resection of the bronchus were performed. The patient remains alive 14 years after the initial resection of colonic cancer. This case is considered noteworthy because it demonstrates the potential effectiveness of local adjuvant chemotherapy and the possibility of extended survival in a patient who has undergone resection of both hepatic and pulmonary metastases from colonic cancer.

Molar excess enthalpies were measured for 1-methyl-2-pyrrolidinone mixed with various pure alcohols and with aqueous alcohols at a low mole fraction of 1-methyl-2-pyrrolidinone at 298°K, using a LKB flow microcalorimeter. Enthalpies of transfer of 1-methyl-2-pyrrolidinone from water to the aqueous alcohol mixtures are estimated from the molar excess enthalpies. The results are discussed from the point of view of the effect of 1-methyl-2-pyrrolidinone on the structure of aqueous alcohol solutions.

Enthalpies of mixing of some a,?-alkanediol monoalkyl ether(ADAE)+heptane systems were measured at 298 K, and limiting partial molar excess enthalpies of ADAE at infinite dilution, x?0limHE/x(1-x), were estimated. The ADAE used were CH3O(CH2)nOH (n=2, 3, 4), C2H5O(CH2)nOH (n=2, 3), C3H7O(CH2)nOH (n=2, 3), and C4H9O(CH2)2OH. The values of x?0limHE/x(1-x), obtained were compared with those of normal alcohols, and discussed in the light of the intramolecular hydrogen bond contained in ADAE. The enthalpic contribution due to the intramolecular hydrogen bond in ADAE is estimated to be about 10 kJ mol-1.

Abstract: The hepatic capacity for acute phase protein synthesis after partial hepatectomy in the elderly patients was prospectively studied. Forty-one patients who consecutively underwent a partial hepatectomy were grouped according to age of greater or less than 70 years; 12 were in the older group and 29 in the younger. The changes in the levels of serum interleukin-6,α 1-antitrypsin,α 1-acid glycoprotein, haptoglobin, and plasma fibrinogen were measured after surgery. The postoperative changes in standard liver function tests were also measured. The incidence of postoperative infected complications was 25% in the older group and 7% in the younger (P=0.28). Although postoperative levels of serum interleukin-6 were similar between the two groups, those of serumα 1-antitrypsin,α 1-antitrypsin glycoprotein, and haptoglobin were significantly lower in the elderly (P<0.05). Postoperative levels of serumα 1-antitrypsin and plasma fibrinogen showed an increase of about 30% compared with the preoperative values (P<0.05) in the younger group, but no significant increasein the older. Postoperative deterioration of serum albumin levels and hepaplastin test values was also significantly more severe in the older group (P<0.05). We conclude that in the older patients, a reduction of acute phase protein synthesis occurs after partial hepatectomy as a result of a global deterioration of liver function, and may render patients liable to infection.

We report the case of a 44-year-old woman who presented with a reducible painless swelling in her left buttock. The mass was preoperatively diagnosed as a sciatic hernia by herniography, which showed the peritoneal sac through the sciatic foramen, and by enterography, intravenous pyelography, and cystography, which demonstrated that the small intestine and urinary bladder had herniated into the sac. The diagnosis and management of this patient are described, followed by a review of the literature on sciatic hernias.