[A Case of Chemotherapy with Low-Dose Paclitaxel and Bevacizumab for Elderly Recurrent Breast Cancer Patient].

An 86-year-old woman underwent mastectomy with sentinel lymph node biopsy for cStage ⅡA breast cancer. The subtype of tumor was triple negative breast cancer. Pulmonary metastasis was found 1 month after surgery. Chemotherapy was done because of her good performance status(PS)and her hope. Administration of S-1 produced SD status of tumor for 8 months. However, NCC-ST-439 was increased and tumor size was enlarged. Therefore, the second line of chemotherapy by low-dose- biweekly paclitaxel and bevacizumab was planned because of her high age and good PS. Thereafter, tumor maker levels dramatically decreased and lung metastasis turned to be small. This therapy had been continued without any severe adverse events for 9 months. Unfortunately, this therapy was failed because of proteinuria, but pulmonary metastasis kept favorable efficacy during administration. Biweekly low-dose paclitaxel and bevacizumab therapy can be safe and effective therapy even for elderly patient with recurrent and metastatic breast cancer.

P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma.

Cancer vaccine therapy is one of the most attractive therapies as a new treatment procedure for pancreatic adenocarcinoma. Recent technical advances have enabled the identification of cytotoxic T lymphocyte (CTL) epitopes in various tumor-associated antigens (TAAs). However, little is known about which TAA and its epitope are the most immunogenic and useful for a cancer vaccine for pancreatic adenocarcinoma. We examined the expression of 17 kinds of TAA in 9 pancreatic cancer cell lines and 12 pancreatic cancer tissues. CTL responses to 23 epitopes derived from these TAAs were analyzed using enzyme-linked immunospot (ELISPOT), CTL, and tetramer assays in 41 patients, and factors affecting the immune responses were investigated. All TAAs were frequently expressed in pancreatic adenocarcinoma cells, except for adenocarcinoma antigens recognized by T cells 1, melanoma-associated antigen (MAGE)-A1, and MAGE-A3. Among the epitopes recognized by CTLs in more than two patients in the ELISPOT assay, 6 epitopes derived from 5 TAAs, namely, MAGE-A3, p53, human telomerase reverse transcriptase (hTERT), Wilms tumor (WT)-1, and vascular endothelial growth factor receptor (VEGFR)2, could induce specific CTLs that showed cytotoxicity against pancreatic cancer cell lines. The frequency of lymphocyte subsets correlated well with TAA-specific immune response. Overall survival was significantly longer in patients with TAA-specific CTL responses than in those without. P53, hTERT, WT-1, and VEGFR2 were shown to be attractive targets for immunotherapy in patients with pancreatic adenocarcinoma, and the induction of TAA-specific CTLs may improve the prognosis of these patients.

Immunoglobulin G4-related periaortitis complicated by aortic rupture and aortoduodenal fistula after endovascular AAA repair.

PURPOSE: To report a rare and complicated case of immunoglobulin (Ig) G4-related periaortitis involving both the aortic wall and the retroperitoneum without aneurysmal formation. CASE REPORT: A 79-year-old man with IgG4-related periaortitis suffered aortic rupture despite a normal caliber aorta after 6 months of steroid therapy (20 mg/d). Endovascular repair with an aortic cuff sealed the rupture. Steroid therapy was halted 2 weeks later due to infection. Four months later, a biopsy during esophagogastroduodenoscopy to investigate gastrointestinal bleeding suggested a relapse of IgG4-RD in the duodenum. Subsequent aortoduodenal fistula formation proved fatal. Generally, IgG4-related periaortitis does not result in such complications due to the absence of aneurysm formation and a thick aortic wall. CONCLUSIONS: Our report highlights a rare case of IgG4-related periaortitis where complications resulted following steroid therapy and surgical intervention, emphasizing the difficulties in dealing with IgG4-related cardiovascular lesions.

Surgical resection of brain and adrenal gland metastases from gastric cancer: a case report and literature review.

The prognosis of recurrent gastric cancer is generally poor, and aggressive surgical treatment is rarely performed. Herein, we present the case of a patient who underwent resection of cerebellar and adrenal gland metastases from gastric cancer. The patient was treated for gastric cancer with distal gastrectomy at 23 years and for remnant gastric cancer with completion gastrectomy at 48 years. At 59 years old, she experienced vertigo and nausea and was diagnosed with cerebellar and left adrenal gland tumours. First, the cerebellar tumours were resected and diagnosed as metastases of gastric cancer. After 1 month, the adrenal gland tumour was resected and diagnosed as metastatic. She underwent whole-brain radiotherapy and subsequent chemotherapy with S-1. One year after the surgery, the patient died of meningitis carcinomatosa. There are few reports on long-term survival after the resection of brain metastases. Herein, we report our experience along with a review of the literature.

Management of postoperative hemorrhage associated with factor VIII inhibitor: report of a case.

This report presents a case that was successfully treated for acquired factor VIII inhibitor after extensive visceral surgery. A 71-year-old male who underwent surgery for bile duct cancer had active bleeding in the abdominal drainage tube on postoperative day (POD) 5, and prolonged activated partial thromboplastin time (aPTT) was detected (83.1 s) on POD 7. An extensive coagulation work-up revealed factor VIII deficiency (1 %), and a diagnosis of an acquired factor VIII deficiency was established when a factor VIII inhibitor of 8 Bethesda units was demonstrated. The patient was treated with activated prothrombin complex concentrate (aPCCs) and bloody discharge was stopped within 3 days. Inhibitor elimination was started using prednisolone on POD 20; rituximab, was administered on POD 74 and 81. Factor VIII inhibitor had disappeared by POD 124, and factor VIII (72 %) and aPTT recovered to 45.9 s. This case report demonstrated the efficacy of aPCCs and rituximab in the treatment of acquired hemophilia associated with visceral surgery.

Surgeons have hesitated early cholecystectomy because of cardiovascular comorbidities during adoption of guidelines.

The introduction of the guidelines has resulted in an increase of laparoscopic surgeries performed, but the rate of early surgery was still low. Here, the initial effect of the introduction of the guideline was confirmed in single center, and factors disturbing early cholecystectomy were analyzed. This study included 141 patients who were treated for acute cholecystitis from January 2010 to October 2014 at Kanazawa Medical Center. Each patient was assigned into a group according to when they received treatment. Patients in Group A were treated before the Tokyo Guidelines were introduced (n = 48 cases), those in Group B were treated after the introduction of the guidelines (93 cases). After the introduction of the guidelines, early laparoscopic cholecystectomy was significantly increased (P < 0.001), however, the rate of early operations was still 38.7% only. There are many cases with cardiovascular disease in delayed group, the prevalence had reached 50% as compared with early group of 24% (P < 0.01). Approximately 25% of patients continued antiplatelet or anticoagulant therapy. In the early days of guidelines introduction, the factor which most disturbed early surgery was the coexistence of cardiovascular disease. These contents could be described in the next revision of the guidelines.

Small intestinal metastasis from intrahepatic cholangiocarcinoma: report of a case.

Metastasis of the small intestine that derives from a primary hepatic neoplasm is rare. We encountered a case of intrahepatic cholangiocarcinoma (ICC) with jejunal metastasis after resection of a primary lesion. A 61-year-old male patient was referred to us with a diagnosis of liver tumors. Partial hepatectomy was performed, and the pathological diagnosis was ICC. Seventeen months after surgery, the patient was found to have a mass in the jejunum and lymph node swelling by positron emission tomography-computed tomography. The jejunal tumor was preoperatively diagnosed as a metastasis of ICC from a biopsy specimen obtained by double balloon endoscopy, and the tumor was resected. The patient received systemic chemotherapy but succumbed with ICC recurrence 46 months after the primary surgery. To the best of our knowledge, this case is the first report of jejunal recurrence of ICC. In addition, this report suggests the usefulness of double balloon endoscopy to make the correct diagnosis of the jejunal tumor.

[En bloc resection including the superior mesenteric artery and vein of locally advanced pancreatic carcinomas].

Curative resection has been shown to be one of the key factors affecting the survival of patients with carcinomas of the head of the pancreas. However, local recurrence is very common, and Esposito and colleagues stated that: "Most pancreatic cancer resections are R1 resections." In 2002, we developed a new method for en bloc resection of the pancreatic head including the superior mesenteric artery (SMA) and vein (SMV) for pancreatic head carcinoma with portomesenteric invasion, called "augmented regional pancreatoduodenectomy (ARPD)." The technical and general eligibility criteria for ARPD are: 1) presumed achievement of R0 status; 2) tumor infiltration proximal to the SMV and SMA; and 3) tumor respecting the hepatic artery, splenic artery, and celiac trunk and neither hepatic nor paraaortic nodal metastasis. Between 2002 and 2010, 17 patients underwent ARPD in our institution. Postoperative death occurred in 2 patients. One death occurred after full-dose radiotherapy and the other after rupture of an aortic aneurysm. The surgical margins (R0) were histologically negative in 14 patients (82%). The overall 5-year survival probabilities were 24% in R0. Three patients survived more than 5 years. The ARPD procedure has advantages in obtaining sufficient margins at the uncinate and posterior site in patients with pancreatic head carcinoma.

A Case of Duodenal Neuroendocrine Tumor Accompanied by Gastrointestinal Stromal Tumors in Type 1 Neurofibromatosis Complicated by Life-Threatening Vascular Lesions.

BACKGROUND Type 1 neurofibromatosis (NF1) is known to be associated with not only neurogenic tumors but also gastrointestinal (GI) neoplasms. However, there are few reports on vascular lesions and the incidence is unknown. CASE REPORT We report here the case of a 45-year-old woman with a history of NF1 referred to our hospital for the purpose of detailed examination for positive fecal occult blood test. On the basis of the investigation reports, she was diagnosed with a neuroendocrine tumor (NET)-G1. We planned a subtotal stomach-preserving pancreaticoduodenectomy. The abdominal structures, including the vascular system, were abnormally fragile, and it was very difficult to achieve satisfactory hemostasis. The total amount of intraoperative blood loss was 7580 mL. Fulminant intra-abdominal bleeding occurred on postoperative day (POD) 3. Urgent angiography showed a rupture of the gastroduodenal artery. Transarterial embolization was performed, but the patient died of multiorgan failure on POD5. On histological examination, neurofibroma cells proliferating into the surrounding blood vessels were seen; moreover, immunohistochemistry staining with S-100 antibody showed positive neurofibroma cells surrounding the vascular wall. The pathological diagnosis was duodenal NET-G1 with multinodal involvement. CONCLUSIONS This case is a rare presentation of a NET with multiple gastrointestinal stromal tumors associated with NF1, which led to a fatal outcome due to the extreme fragility of the vessel walls. Since patients with NF1 might have vulnerable vessel walls, adequate surgical preparation for major surgical treatment is necessary.

A case of midgut volvulus related to adult intestinal malrotation found with weight loss after streptococcus infection: A case report and literature review.

INTRODUCTION AND IMPORTANCE: The incidence of intestinal malrotation is 1 in 6000 births, and 90% of cases occur within the first year of life. Adult cases are rare, with a reported incidence of 0.2%-0.5% of all cases. The significance of reporting this case is to recognize that some adult-onset cases require surgery even in the absence of intestinal necrosis. CASE PRESENTATION: A 36-year-old man was infected with streptococcus and treated with antibiotics. He developed appetite loss and his weight decreased 12 kg in 4 months. His abdomen was flat and soft with no tenderness. A computed tomography scan showed that the horizontal duodenal leg was not anchored to the retroperitoneum. Rotation of the mesentery, which was wrapped around the superior mesenteric artery in a clockwise direction, was observed, suggesting midgut volvulus. We performed emergency surgery and Ladd's procedure. CLINICAL DISCUSSION: A previous study reported that the most common symptom in the chronic course of intestinal malrotation was abdominal pain in 41.2% of cases, and weight loss was observed in only 2.6% of patients. The high degree of intestinal adhesion suggests that repeated torsion and release and the development of collateral vessels may have contributed to the asymptomatic course. CONCLUSION: Adult-onset intestinal malrotation should be considered as a differential diagnosis in the presence of weight loss and gastrointestinal symptoms. The timing of surgery is still controversial. In chronic cases, severe adhesion might be expected and laparoscopic surgery should be considered carefully.

Pancreatic acinar cell carcinoma with extension into the main pancreatic duct: a case report.

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare exocrine malignant tumor. Its widespread intraductal extension into the main pancreatic duct (MPD) is also rare. CASE PRESENTATION: We report the case of a 71-year-old man with PACC with MPD extension. The patient was assessed with laboratory and radiographic investigations that facilitated a preoperative diagnosis. Endoscopic ultrasonography (EUS) and dynamic thin-slice multi-detector row computed tomography (MDCT) were useful for determining the resection line of the pancreas. EUS-guided fine needle aspiration (EUS-FNA) was also helpful in determining the tumor biology and treatment strategy. Distal pancreatectomy was performed. The MPD was occupied by the tumor 35 mm downstream and 5 mm upstream. Histopathologically, the pancreatic tail tumor extended continuously into the MPD. The tumor was solid with cells showing eosinophilic and granular cytoplasm, indicating the diagnosis of PACC. This is an interesting case of PACC with intraductal extension into the MPD. We discuss the possible mechanisms of tumor extension in this rare case together with a review of the literature. CONCLUSIONS: We describe a rare pancreatic acinar cell carcinoma that could be adequately treated using preoperative precise imaging and histopathological evaluations. When an intraductal tumor extension in the MPD is encountered, the diagnosis of a rare pancreatic tumor should be considered, as in our case.

Imaging features and pathological evaluation by EUS-FNA enable conservative management in patient of lymphoepithelial cyst of the pancreas: a case report.

Pancreatic lymphoepithelial cysts (LECs) are rare cystic lesions filled with a keratinous substance and lined by squamous epithelium with underlying lymphoid tissue. Because pancreatic LECs are entirely benign, correct preoperative diagnosis is important to avoid unnecessary surgery. However, the imaging features of pancreatic LECs are not specific and preoperative diagnosis has proven difficult. A pancreatic mass was incidentally detected through abdominal ultrasonography in a 63-year-old male presenting without any symptoms. Computed tomography showed an exophytic cystic lesion in the pancreatic head. The lesion had heterogeneous high signal intensity with partial low intensity on T2-weighted magnetic resonance imaging (MRI) and high signal intensity on diffusion MRI. Endoscopic ultrasound (EUS) examination showed an encapsulated cystic lesion with relatively homogenous and highly echoic contents. EUS-guided fine-needle aspiration (EUS-FNA) revealed caseous appearance and rare fragments of apparently benign squamous epithelium on a background of keratinous debris, cyst contents, and scattered lymphocytes. We diagnosed a pancreatic LEC and opted for conservative management without surgery. Pathological evaluation based on images obtained through EUS-FNA showed macro- and microscopic features that were critical to determining the management strategy. In conclusion, the imaging and pathological features of pancreatic LECs can inform preoperative diagnosis, which may enable conservative management.

MDCT findings of extrapancreatic nerve plexus invasion by pancreas head carcinoma: correlation with en bloc pathological specimens and diagnostic accuracy.

OBJECTIVE: To elucidate the multi-detector row computed tomography (MDCT) findings of extrapancreatic nerve plexus (PLX) invasion by pancreas head carcinoma (PhC) by "point-by-point" correlation with en bloc pathological specimens and to assess their diagnostic accuracy. METHODS: Each pathological section of PhC and adjusted double oblique multiplanar reconstruction MDCT images were correlated in 554 sections from 37 patients. The diagnostic accuracy of the MDCT patterns derived was assessed by blind reading. RESULTS: PLX invasion with fibrosis showed mass or strand shape (85.6%) or coarse reticula (13.3%). The CT findings were divided into fine reticular and linear, coarse reticular, mass and strand, and nodular patterns. PLX invasion was revealed pathologically in 92% of the regions of investigation showing the mass and strand pattern and 63% of the coarse reticular pattern (all continuous with PhC), and they were highly suggestive of PLX invasion by PhC on MDCT images (p < 0.001). Sensitivity, specificity, accuracy, and positive and negative predictive values of these MDCT findings in the diagnosis of PLX invasion were 100% (25/25), 83.3% (10/12), 94.6% (35/37), 92.6% (25/27) and 100% (10/10), respectively. CONCLUSION: The mass and strand pattern and the coarse reticular pattern continuous with PhC on MDCT images were highly suggestive of PLX invasion by PhC.

Gross appearance of the ampullary tumor predicts lymph node metastasis and outcome.

BACKGROUND/AIMS: Patterns of lymph node involvement in carcinoma of the papilla of Vater (CPV) have not been studied in detail to date, and factors associated with lymphatic metastases and surgical outcome of this disease remain to be determined. METHODS: Lymph node involvement and surgical outcome of 51 CPV patients were evaluated by extended lymphadenectomy specimens. RESULTS: Lymph nodes with high metastatic potential were posterosuperior pancreaticoduodenal nodes (group 13a, 18%), posterior-inferior pancreaticoduodenal nodes (group 13b, 22%), and nodes around the superior mesenteric artery (group 14, 18%). Gross appearance of the primary tumor and depth of tumor invasion correlated with lymph node involvement (p < 0.05, respectively). A correlation with positivity was also found in groups 13 and 14. Disease-specific survival correlated with the gross appearance of the primary tumor and nodal involvement. However, there was no relationship between survival and the level of nodal involvement. Multivariate analysis indicated that the gross appearance of the tumor was the only significant independent predictor of a poor outcome. CONCLUSIONS: Gross appearance of the tumor is the most important prognosticator of lymph node metastases in CPV. Nodal dissection around the superior mesenteric artery may improve survival except in patients without invasion of the sphincter of Oddi. Pylorus-preserving pancreaticoduodenectomy is the treatment of choice.

Transectional gastrectomy: an old but renewed concept for early gastric cancer.

Segmental resection of the stomach was first described at the end of the 19th century by Mikulicz, who devised it to preserve the pylorus when performing gastric ulcer surgery. Although this technique was abandoned because of delayed gastric emptying, in 1967 Maki et al. developed a new improved concept of segmental gastrectomy: pylorus-preserving gastrectomy (PPG). The dramatic decrease in the occurrence of gastric ulcers limited the opportunity to perform these operations; however, PPG was then used for treating early gastric cancer, the incidence of which has increased remarkably over the last two decades. From the viewpoint of surgical oncology, a rationale to justify reducing the range of lymphadenectomy is required for preserving the curability. Therefore, we devised a new technique of transectional gastrectomy using sentinel node navigation for early gastric cancer located in the middle third of the stomach. The results of a questionnaire about postoperative symptoms and endoscopic assessment indicated the superiority of transectional gastrectomy over conventional distal gastrectomy. Future confirmation of the sentinel node concept through a multi-institutional validation study conducted by the Japanese Society of Sentinel Node Navigation Surgery would lead to widespread adoption of transectional gastrectomy.

[The role of renin-angiotensin system independent angiotensin II production in progression and fibrosis of intrahepatic cholangiocarcinoma].

Angiotensin II (Ang II) plays an important role in stromal fibrosis and tumor progression in cancer tissues. Now we investigated the role of Ang II in the cross-interaction between intrahepatic cholangiocarcinoma (ICC) cells and hepatic stellate cells (HSCs). The concentrations of Ang II in ICC tissues were significantly higher than those of hepatocellular carcinoma and normal liver. The expression of Ang II type 1 receptor (AT-1) in ICC specimens, two ICC cell lines, and HSC cell line, LI-90 was demonstrated by immunostain and Western blot. The proliferative activity of ICC cells and HSCs added Ang II dose-dependently increased and telmisartan inhibited the proliferative effects in MTT assay. HSCs added Ang II showed a higher expression of α-smooth muscle actin (α-SMA) compared with control cells. Telmisartan also inhibited the activation of HSCs added Ang II. Ang II in ICC tissues may play a pivotal role in tumor growth and stromal fibrosis and Ang II receptor blocker will be a potential therapy in cancer tissue expressing AT-1.

Tumor deposits are encountered in advanced colorectal cancer and other adenocarcinomas: an expanded classification with implications for colorectal cancer staging system including a unifying concept of in-transit metastases.

The seventh edition of the TNM Classification of Malignant Tumors is due to be published soon. In the current version dating back to 2002, tumor deposits, which are metastatic lesions commonly encountered in the routine histopathological examination of advanced colorectal cancer specimens, are classified according to their shape with different implications for staging. So distinguished, these lesions are considered either as metastatic lymph nodes (N category) or as vascular invasions (T category). We recently proposed a more comprehensive classification approach that also includes the M category. Relying on two of our independent recent studies, we aim here to provide suggestions for a novel classification of tumor deposits with diverse implications for TNM staging system of colorectal cancer. Furthermore, we show that tumor deposits are not limited to colorectal cancer, but they are common to different adenocarcinoma types.

Local angiotensin II-generation in human gastric cancer: correlation with tumor progression through the activation of ERK1/2, NF-kappaB and survivin.

Angiotensin II is a main effector peptide in renin-angiotensin system, acting as a growth promoter via angiotensin II type 1 (AT1) receptor. The present study examined intrinsic angiotensin II generating system in gastric cancer and potential roles of angiotensin II in cellular proliferation and survival. The expression of AT1 receptor was examined in gastric cancer cell lines and tissues. In addition, we measured angiotensin II concentration in tissues from twenty gastric cancer and corresponding normal region using the florisil method. In vitro, we investigated the potential roles of angiotensin II in cellular proliferation and cell survival in cultured human gastric cancer cell line. The effects of AT1 receptor blocker candesartan were evaluated in a mouse model of peritoneal carcinomatosis. AT1 receptor protein was expressed in gastric cancer cell lines and tissues. Angiotensin II concentration in tumor region (1447+/-624 pg/g wet) was significantly higher than those of normal region (775+/-320 pg/g wet) (p<0.05). Angiotensin II stimulates the cell proliferation in the AT1 receptor-positive OCUM2MD3 gastric cancer cell line and this proliferative effect of angiotensin II was inhibited by a specific AT1 receptor antagonist, candesartan. We also confirmed the angiotensin II stimulated ERK1/2, nuclear transcript factor-kappaB (NF-kappaB) and surviving activation, which are central molecules of cellular proliferation and survival in OCUM2MD3 cells. Candesartan significantly prolonged survival time in a mouse model of peritoneal carcinomatosis compared with control group (p=0.0.197, log-rank test). Our data provide in vivo evidence of intrinsic angiotensin II generating system in gastric cancer and indicate locally formed angiotensin II is involved in cellular proliferation and survival.

Selective lymphadenectomy of para-aortic lymph nodes for advanced gastric cancer.

The Japanese randomized trial comparing standard D2 with D2 plus additional para-aortic lymph node (PAN) dissection for advanced gastric cancer (JCOG study 9501) did not demonstrate any difference in survival between the two groups. It is unknown whether there is any prognostic benefit in dissection for subgroups of PAN. Non-inferiority in survival of the patients with PAN metastasis to the patients having n2 metastasis was examined according to the subgroup of PANs and the tumor location. The survival curve of n2 patients (n=131) were retrospectively compared with that of patients with PAN metastasis (n=55) and also compared with that of patients with metastasis to subgroup of PANs by the location of primary tumor (regions U, M and L). Expectedly, the prognosis of the n2 patients is significantly better than that of the patients with PAN metastasis, but there was no difference in the survival times between the n2 (+) group and the a2-lat (+) or the b1-int (+) group, suggesting that the a2-lat or the b1-int dissection matched the D2 dissection. Furthermore, the importance in dissection of the a2-lat and the b1-int was investigated according to the primary tumor location. The patients with metastasis to a2-lat in the region U, a2-lat and b1-int in the region M and b1-int in the region L demonstrated prognostic non-inferiority to the patients having n2 metastasis. Selective lymphadenectomy of subgroups of PANs in which metastases are highly suspected according to the tumor location is one of treatment strategies to advanced gastric cancer.

Effect of porto-systemic shunting on NOS expression after extended hepatectomy in rats.

AIM: Several surgical procedures have been developed for reducing portal vein pressure to prevent postoperative liver injury. Nitric oxide synthase expression (NOS) induced by elevation of portal vein pressure is thought to play an important role in liver regeneration, but the details are not well understood. METHODS: Rats in the control group and in the subcutaneous splenic transposition (SST) group underwent 90% partial hepatectomy. Survival and portal vein pressure were analyzed. The serum IL-6 and TNF-alpha levels were measured by enzyme-linked immunosorbent assay (ELISA). Hepatocyte proliferation and apoptosis 12 hours after hepatectomy were analyzed immunohistochemically. The protein and messenger RNA expression of inducible and endothelial NOS were analyzed using Western blotting and quantitative reverse transcriptase polymerase chain reaction, respectively. RESULTS: The survival rate of the SST group was significantly higher. Portal vein pressure, TNF-alpha level and the apoptotic index were significantly lower in the SST group. Twelve hours after surgery, liver inducible NOS (iNOS) protein expression was significantly lower in the SST group. However, protein expression of endothelial NOS was not significantly different between the groups. CONCLUSION: Inducible NOS expression after extended hepatectomy is related to the effects of porto-systemic shunting on the splanchnic circulation. Also, iNOS induction and concomitant nitric oxide generation appear to participate in the cytotoxicity of excessive portal pressure after extended hepatectomy.