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Background Poor preoperative nutritional and immunological status are major risk factors for postoperative complications in patients with various malignancies. Lower preoperative prognostic nutrition index (PNI) is associated with higher rates of postoperative complications and poorer prognosis in those patients. The aim of this study was to analyze the predictive value of the PNI for post-hepatectomy complications in patients with hepatocellular carcinoma (HCC), and evaluate its utility in the surgical procedure. Methods This retrospective study included 510 patients who underwent open hepatectomies for HCC. The predictive value of the preoperative nutritional and immunological status for postoperative complications was assessed using the PNI. Postoperative complications were defined as grade II or higher per the Clavien-Dindo classification. Postoperative complication rates were compared according to surgical procedure (major hepatectomy vs minor hepatectomy). Results Patients with postoperative complications had significantly lower PNIs than those without (43.1 ± 5.5 vs 47.0 ± 5.7, P < 0.001). In the multivariate analysis, low preoperative PNI (< 45) was an independent risk factor for postoperative complications after hepatectomy (hazard ratio, 3.85). When patients were classified per their PNI (high vs low) and extent of surgical procedures (major vs minor), there were more complications among patients with low PNI than those with high PNI, regardless of the extent of surgical procedures. Specifically, the group of patients with low PNI who underwent major hepatectomy had significantly higher rates of postoperative complications than the other groups. Conclusions Adding the resection range to the PNI is useful for predicting the postoperative morbidities of hepatectomy patients.

Background: The Tokyo Guidelines 2018 recommend a bailout procedure consisting of fundus-first cholecystectomy, subtotal cholecystectomy, or open conversion to prevent serious complications in cases of difficult laparoscopic cholecystectomy (LC).Methods: The hospital records of patients with acute cholecystitis who underwent LC from October 2014 to April 2019 were retrospectively analyzed. The clinical data were compared between the standard and bailout groups. A subgroup analysis was performed to compare the fundus-first and subtotal cholecystectomy techniques versus open conversion.Results: In total, 160 of 416 Japanese patients who underwent LC were diagnosed with acute cholecystitis. Standard LC was performed in 125 (78%) patients, and a bailout procedure was performed in 35 (22%). The duration from onset to surgery was significantly longer (P = 0.04) and the C-reactive protein (CRP) concentration was significantly higher (P = 0.001) in the bailout than standard group. The surgical outcomes were worse in the bailout group. In the multivariate analysis, a high CRP concentration at diagnosis was an independent predictor of bailout (P = 0.004). In the subgroup analysis, the open group had a significantly longer duration from onset to surgery (P = 0.04) and a significantly higher incidence of preoperative drainage (P = 0.002). With respect to surgical outcomes, the open group had significantly greater blood loss (P = 0.02) and longer hospital stays (P = 0.002). Conclusion: A high CRP concentration is a risk factor for a bailout procedure. Early LC should be performed for patients with acute cholecystitis and a high CRP concentration.

This study was designed to assess the tolerability, efficacy, and safety of tri-weekly irinotecan plus S-1 (IRIS) and weekly cetuximab in patients with metastatic colorectal cancer (mCRC). The main eligibility criteria were RAS wild-type mCRC with no prior chemotherapy. S-1 was given orally at a dose of 40 mg/m2 (40–60 mg) twice for 2 weeks, followed by a 1-week rest. Irinotecan was given on day 1 of each cycle at a dose of 150 mg/m2. Cetuximab was administered on days 1 (400 mg/m2), 8 (250 mg/m2), and 15 (250 mg/m2), and then once weekly (250 mg/m2) thereafter. A standard 3 + 3 phase I dose de-escalation design was used to determine the maximum tolerated dose and the recommended dose (RD) of irinotecan. The primary end point of the Phase II study was overall response rate (ORR). Between December 2014 and September 2017, 4 and 54 patients were enrolled in phase I and phase II studies, respectively. No dose-limiting toxicity was observed in the phase I study, and the RD of irinotecan was 150 mg/m2. In the phase II study, the ORR was 56.9% (90% confidence interval 44.4%–68.7%). The safety profile revealed that the most common grade 3/4 adverse events were neutropenia (31.4%), appetite loss (27.5%), hypokalemia (11.8%), and diarrhea (11.8%). Grade 3/4 hand–foot skin syndrome occurred in nine patients (9.8%). This study showed that the efficacy and safety of IRIS combined with cetuximab were comparable to those for other first-line treatments. This regimen is a good candidate for first-line treatment of RAS wild-type mCRC.

Case report A 75-year-old man who underwent nivolumab as the third-line chemotherapy for advanced gastric cancer had chylous ascites (CA) after the primary tumor shrank remarkably. Total parenteral nutrition and subcutaneous octreotide were initiated, and CA disappeared. Nivolumab was continued for a total of 23 courses. Computed tomography showed lymph node swelling; however, staging laparoscopy showed that peritoneal metastasis had disappeared. Therefore, conversion surgery and distal gastrectomy with D1+ dissection were performed. Results The pathological diagnosis was type IV, poorly differentiated adenocarcinoma (por2) with signet ring cells, ypT2 (muscularis propria), without lymphatic or venous invasion, and no involvement of the proximal and distal margins. After the operation, no recurrence was observed over 7 months with no adjuvant chemotherapy. Conclusion Nivolumab has the potential to lead to R0 resection for patients with peritoneal carcinomatosis gastric cancer. To our knowledge, this is the first report of successful conversion surgery after nivolumab-related chylous ascites.

Background Decompression sickness (DCS) induced by extravascular and intravascular gas bubbles during decompression can present with varying manifestations, such as joint pain, numbness, cutaneous symptoms, and cardiopulmonary dysfunction. However, mesenteric venous thrombosis (MVT) is a rare complication of DCS. To the best of our knowledge, only a few cases have been reported, and surgical cases of MVT secondary to DCS have not yet been reported. Case presentation A 59-year-old man who was a fisherman and recreational diver dived to a depth of 100 feet. After diving, he noted abdominal and postcervical pain and visited a community hospital. Computed tomography (CT) revealed a large amount of intravenous gas, so he was diagnosed with DCS. He was then transferred to a previous hospital, where hyperbaric oxygen therapy (HBOT) was performed. HBOT reduced the amount of venous gas, but his abdominal pain worsened, so he was transferred to our hospital. CT showed pneumatosis cystoides intestinalis. Because of the possibility of intestinal necrosis, a laparoscopic examination was performed, which revealed necrosis of the transverse colon. We therefore performed a transverse colon resection. He was discharged 36 days after the surgery and followed an uneventful postoperative course. Conclusions DCS is likely to cause MVT. If intestinal necrosis is suspected, a laparoscopic examination may be useful for determining the diagnosis and treatment. MVT should be included as a differential diagnosis of abdominal pain that persists after HBOT.

This study was designed to evaluate the efficacy and toxicity of XELIRI plus bevacizumab for the treatment of Japanese patients with unresectable or recurrent colorectal cancer (CRC). This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated unresectable or recurrent CRC, presence of measurable lesions, ≥20 years of age, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELIRI (irinotecan 200 mg/m2 on day 1 plus capecitabine 800 mg/m2 b.i.d. on days 1–14) every 3 weeks. The primary endpoint was the objective tumor response rate. A total of 36 patients were enrolled in this study from July 2011 to September 2012. One patient did not fulfill the eligibility criteria and one patient withdrew their consent before the start of the treatment protocol. The confirmed objective response rate was 58.8% (95% CI 35.1–70.2%). The median progression-free survival was 9.6 months (95% CI 5.1–11.1 months) and the median overall survival was 23.1 months (95% CI 11.3–36.7 months). The grade ≥3 adverse events that were frequently encountered in this study were neutropenia (31.4%), leukopenia (22.9%), diarrhea (22.9%), anemia (20.0%), anorexia (20.0%) and febrile neutropenia (17.2%). The frequency of grade 3/4 adverse events, such as neutropenia and leukopenia, was much higher in patients with a UGT1A1 polymorphism. A first-line therapy comprising XELIRI plus bevacizumab yielded a promising response rate. However, careful attention should be given to adverse clinical events in Japanese patients receiving treatment with unresectable or recurrent CRC.

Introduction Laparoscopic bariatric surgery has gradually spread in Japan since it was introduced in 2000. In 2005, we introduced laparoscopic adjustable gastric banding (LAGB) with the LAP-BAND system into Japan. Here, we evaluate our intermediate-term results with the LAP-BAND system. Methods Between August 2005 and June 2010, 27 Japanese patients with morbid obesity (BMI ≥ 35 kg/m2) underwent LAGB with the LAP-BAND system in our institution. Our patients' average weight was 111 kg and BMI was 41 kg/m2. All LAGB procedures were performed through the pars flaccida pathway with band fixation using gastric-to-gastric sutures. The average follow-up period was 48 months. Results All procedures were completed laparoscopically. One early complication (sudden cardiac arrest due to postoperative bleeding) and three late complications (port trouble, megaesophagus, and band slippage) were experienced, and reoperations were performed in three of the patients. Weight loss and percentage of excess weight loss on average were 26 kg and 53% after 3 years and 22 kg and 53% after 6 years, respectively. In line with this good weight loss, comorbidities, especially those of type 2 diabetes and metabolic syndrome were frequently resolved or improved. Conclusion LAGB with the LAP-BAND system appears to be beneficial in obese Japanese patients.

These authors suggest that the best timing of laparoscopic cholecystectomy for acute cholecystitis in Japan may be within 24 hours of the onset of the disease., Background and Objectives: In patients with acute cholecystitis who cannot undergo early laparoscopic cholecystectomy (within 72 hours), 6 weeks to 12 weeks after onset is widely considered the optimal timing for delayed laparoscopic cholecystectomy. However, there has been no clear consensus about it. We aimed to determine optimal timing for delayed laparoscopic cholecystectomy for acute cholecystitis. Methods: Medical records of 100 patients who underwent standard laparoscopic cholecystectomy were reviewed retrospectively. Patients were divided into group 1, patients undergoing laparoscopic cholecystectomy within 72 hours of onset; group 2, between 4 days to 14 days; group 3, between 3 weeks to 6 weeks; group 4, >6 weeks. Results: No significant differences existed between groups in conversion rate to open surgery, operation time, blood loss, or postoperative morbidity, and hospital stay. However, total hospital stay in groups 1 and 2 was significantly shorter than that in groups 3 and 4 (P

We present a case of long-term survival in a patient with inferior vena cava tumor thrombus (IVCTT) and extrahepatic metastasis after resection for spontaneous ruptured hepatocellular carcinoma (HCC). The patient was a 73-year-old Japanese man previously diagnosed with chronic hepatitis B. He was referred to our emergency room and diagnosed with spontaneous ruptured HCC. The patient was immediately treated with transcatheter arterial embolization, and we then performed second-stage hepatic resection 50 days later. Although des-gamma-carboxy prothrombin was reduced to a normal level after hepatectomy, it gradually increased and computed tomography showed a disseminated tumor in the diaphragm near S2 of the liver with IVCTT and right atrium tumor thrombus. Recurrent HCC was treated with monthly transcatheter arterial infusion chemotherapy (TAI) and conformal radiotherapy (RT) of 40 Gy. After TAI and RT procedures, the disseminated tumor and IVCTT completely disappeared. Four years after TAI and RT procedures, the tumors were well controlled with no local recurrence. About 6-7 years after spontaneous ruptured HCC, lung metastasis and spleen metastasis were detected and resected, respectively. The patient is still alive and doing well over 7 years after spontaneous ruptured HCC.

793 Background: We have reported the effectiveness of neoadjuvant radiotherapy (RT) combined with S-1 in terms of compliance and pathologic response for locally advanced rectal cancer. In the present study, we aimed to evaluate the safety and efficacy of laparoscopic surgery for locally advanced rectal cancer following neoadjuvant RT combined with S-1 in comparison with open surgery. Methods: Two multicenter prospective phase II trials were conducted (UMIN003396, UMIN003398). A total of 63 patients with locally advanced rectal cancer classified as T3-4, N0-3, and M0 were enrolled, and neoadjuvant RT combined with S-1 and total mesorectal excision with D3 lymphadenectomy was performed. Of these, 57 patients were analyzed and divided into a laparoscopic group (LAP, n = 43) and open group (OP, n = 14). We evaluated the short- and long-term outcomes of laparoscopic surgery compared with open surgery by univariate and multivariate analyses. Results: In the patient background, there were no significant differences between the two groups except that cases with T3 and N0 were significantly higher in the LAP compared with the OP. In the operative findings, operation time was longer (mean 447 min vs. 352 min, p = 0.007) and blood loss was lesser (median 220 ml vs. 485 ml, p = 0.033) in the LAP than those in the OP. Although there were no significant differences observed in the incidence of perioperative and late complications between the two groups, reoperation within 30 days was significantly less in the LAP compared with the OP (1 case vs. 5 cases, p = 0.0004). In the multivariate analysis, a distance of the tumor from anal verge within 3 cm was the independent risk factor for reoperation within 30 days. Furthermore, estimated 5-year disease-free survival (LAP 72 % vs. OP 73 %, p = 0.945) and 5-year overall survival (LAP 76 % vs. 75 %, p = 0.836) didn’t significantly differ between the two groups in the Kaplan–Meier curve. Conclusions: The findings of this study demonstrated that laparoscopic surgery for locally advanced rectal cancer following neoadjuvant RT combined with S-1 could be an optional procedure in terms of short- and long-term outcomes. Clinical trial information: UMIN000003396, UMIN000003398.

Introduction: We evaluated the safety and efficacy of laparoscopic sleeve gastrectomy (LSG) in Japanese patients with morbid obesity. Materials and Methods: Between June 2006 and March 2009, seven morbidly obese Japanese patients (four women, three men; mean age 36±12 years; mean body mass index (BMI) 51±3 kg/m2) underwent LSG at our institute. The inclusion criteria were morbid obesity (BMI>35 kg/m2), the presence of obesity-related disorders, and failure to lose weight while using other medical therapies for at least 6 months. The criteria also included contraindications for laparoscopic adjustable gastric banding or super-obesity (BMI>50 kg/m2). LSG was carried out using endoscopic linear staplers from the greater curvature of the antrum 6–7 cm proximal to the pyloric ring to the angle of His alongside a 32-Fr endoscope or a 45-Fr overtube of the endoscope. Results: In all of the patients, LSG was successfully performed without open conversion. There were no serious postoperative complications and there was no mortality. The mean weight loss and percent excess weight loss after LSG were 33±8 kg and 47±16% at 6 months, and then 44±16 kg and 63±30% at 12 months. Due to the weight loss, the resolution and improvement rates of comorbidities in the five patients followed up for >3 months were 100% and 100% in type 2 diabetes, 67% and 100% in hypertension, 60% and 100% in dyslipidemia, and 100% and 100% in metabolic syndrome. Discussion: Although further long-term studies are necessary with regard to weight maintenance, LSG is a feasible and safe treatment for Japanese patients with morbid obesity.

Laparoscopic hepatectomy was initially reported in 1992. However, the reported experiences are scarce, and this operation has not been a standard procedure until now. The aims of this study were to assess our results of laparoscopy-assisted left lateral hepatectomy for hepatocellular carcinoma (HCC) and to compare them with those of open conventional procedures.From 1984 to 2002, left lateral hepatectomy for HCC less than 5 cm in diameter was carried out in 21 patients. Ten patients received a laparoscopy-assisted procedure, and remaining 11 patients received an open procedure.There were no significant differences in the operation time, blood loss, resected liver weight, and resection margin between the 2 groups. The total time that analgesics were given, body temperature on postoperative day 1, weight loss on postoperative day 7, and postoperative hospital stay in the laparoscopic group were significantly better than in the conventional group. With regard to the long-term prognosis, there were no differences in patient survival or disease-free survival rates between the 2 groups.Laparoscopy-assisted left lateral hepatectomy for HCC is superior to the conventional open surgery in terms of its short-term results and does not cause the long-term survival to deteriorate. Therefore, laparoscopic hepatectomy may be an alternative choice for treatment of HCC.

Aims Hepatic resection is the most effective therapy for hepatocellular carcinoma (HCC); however, intrahepatic recurrence is common. Predictors of survival after intrahepatic recurrence have not been fully investigated. To clarify the prognosis and choice of treatment of intrahepatic recurrence after hepatic resection, we conducted a comparative retrospective analysis of 147 patients with HCC who underwent hepatic resection. Methods We retrospectively examined the relations between clinicopathologic factors, including the number of recurrent intrahepatic tumors and long-term prognosis after recurrence in 147 HCC patients who underwent resection. We also examined long-term survival after recurrence based on treatment types and recurrence pattern. Results Patients with multiple tumors ( n = 83) showed less tumor differentiation, more frequent portal invasion, a higher alpha-fetoprotein level, and larger tumors than did patients with solitary tumor ( n = 64). In the solitary tumor group, local ablation therapy and repeat hepatic resection were performed in 25 and 10, respectively. In the multiple tumor group, 59 were treated by transarterial chemoembolization. Multivariate analysis showed intraoperative blood transfusion and multiple tumors to be independent risk factors for poor cancer-related survival after recurrence. By subset analysis based on treatment types and recurrence pattern, survival after recurrence was significantly better in patients treated by local ablation therapy than those treated by other therapies in both solitary and multiple tumor groups. Conclusions For patients with solitary recurrence, a good prognosis is predicted. Local ablation therapy is a best candidate for treatment of solitary and multiple intrahepatic recurrences after hepatic resection.

A 45-year-old woman with previously diagnosed chronic type adult T-cell leukemia (ATL) presented with abdominal discomfort and red eruptions on her arms and legs. Anemia, thrombocytopenia, hypercalcemia, and splenomegaly indicated progression to acute-type ATL. Combined chemotherapy resulted in normalization of the serum calcium level and improvement in her symptoms. However, the severe anemia and thrombocytopenia persisted, necessitating transfusions of red blood cells (RBC) and platelets three times a week. We performed splenectomy in an attempt to reduce the total volume of malignant cells and improve the hypersplenism. After the operation, the RBC and platelet counts increased gradually, and the transfusions were stopped on postoperative day (POD) 3. Splenectomy should be considered as an optional treatment for hypersplenism caused by ATL when hypersplenism cannot be controlled by chemotherapy in patients without a high surgical risk.

We introduced intragastric balloon placement in Japan and evaluated the initial data. Between December 2004 and March 2008, intragastric balloons [BioEnterics® Intragastric Balloon (BIB®) system] were placed in 21 Japanese patients with obesity [six women, 15 men; mean age 40 ± 9 years; mean body mass index (BMI) 40 ± 9 kg/m2]. The inclusion criteria were morbid obesity (BMI ≥ 35 kg/m2), the presence of obesity-related disorders, and failure with conventional treatments for at least 6 months. The balloon was routinely removed under endoscopy after 5 months. No serious complications occurred, but in two of the 21 patients (9.5%), early removal (within 1 week) of the balloon was required due to continuous abdominal discomfort. Two other patients (9.5%) could not control their eating behavior and were considered unresponsive to the treatment, and their balloons were also removed before 5 months. Seventeen of the 21 patients (81%) finished the treatment, and the average weight loss and percent excess weight loss (%EWL) at the time the balloons were removed were 12 ± 5 kg and 27 ± 9%, respectively. Eight patients were followed for 1 year without intervention of consecutive bariatric surgery, and at that time, four of these patients had kept more than 20% of %EWL. The other patients regained their weight in the first year. Intragastric balloon placement is a safe and effective procedure in obese Japanese patients, and about half of the patients will maintain their weight loss after the balloon is removed.

Metastasis of cancer to the spleen or small intestine is rare. We encountered a case of hepatocellular carcinoma (HCC) with splenic and jejunal metastases. A 60-year-old man was referred to us in February 2005 with a diagnosis of splenic tumor. Since 2001, he had been treated repeatedly for HCC with liver cirrhosis due to hepatitis C virus infection; partial liver resection, transcatheter arterial chemo-embolization, and radiofrequency ablation therapy had been performed. In October 2004, he had undergone partial pulmonary resection due to metastasis of HCC to the lung. The splenic tumor, which was detected by computed tomography, seemed to be a metastasis of HCC. Splenectomy was performed for the splenic tumor, and a jejunal tumor was discovered and also resected. Both the splenic and jejunal tumors were diagnosed pathologically as metastases from the HCC. After repeated treatment for HCC, metastases can appear in various organs; thus, careful observation is necessary during follow-up.

Aims CD4 + CD25 + forkhead box P3 (FOXP3) + T reg accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (T reg ), we conducted a retrospective study on 164 patients with hepatocellular carcinoma (HCC) who underwent curative hepatic resection. Methods We investigated the number of tumor-infiltrating FOXP3 + T reg in formalin-fixed HCC specimens. The number of FOXP3 + T reg for each case was calculated as the total number of positive cells per 10 high-power fields (HPF) on light microscopy. Long-term survival rate after resection according to the number of FOXP3 + T reg was accessed by univariate and multivariate analyses. Results The mean and median numbers of tumor-infiltrating T reg were 29.0 and 14 per 10 HPF for FOXP3 + T reg . The number of FOXP3 + T reg was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high T reg counts (≥14, n =84) than in those with low T reg counts ( n =80) (13.6% vs. 25.7% at 5 years; P =0.02). By multivariate analysis, the high T reg counts, presence of portal vein invasion, and elevation of preoperative aspartate aminotransferase level were independent predictive factors of tumor recurrence. Conclusions The high number of tumor-infiltrating T reg is an independent predictive factor of tumor recurrence after hepatic resection for HCC.

はじめに: 我々が我が国に導入した腹腔鏡下調節性胃バンディング術 (laparoscopic adjustable gastric banding; 以下, LAGB) の体重減少効果と肥満関連健康障害に対する改善効果について検討したので報告する. 方法: 2005年8月からの2年間に21例の内科治療無効の肥満症例にLAGBを施行した. 平均年齢38歳, BMI 44kg/m2であり, 肥満関連健康障害を平均3.1疾患有していた. LAGBは全例, Pars flaccida法で行い, バンドの逸脱予防のために胃-胃縫合を3～5針行った. 結果 LAGBの周術期に1例も合併症を認めず, 術後の平均在院期間は平均3.4日であった. LAGB後の平均体重減少は12か月25kg, 18か月29kgであり, 過剰体重減少率は12か月41%, 18か月49%であった. 良好な体重減少により, 高血圧91%, 高脂血症94%, 糖尿病100%と高率に改善した. 考察: LAGBは安全性と有効性を兼ね備えた術式であり, 今後我が国においても普及していくものと思われた.

Although extrahepatic metastasis occurs rarely after hepatic resection for hepatocellular carcinoma (HCC), the prognosis of these patients is extremely poor. Predictors of extrahepatic metastasis have not been fully investigated.To identify predictors of extrahepatic metastasis after resection, we retrospectively investigated 77 patients with HCC tumors50 mm in diameter who underwent hepatic resection. We investigated correlations between postoperative extrahepatic metastasis and clinicopathologic factors as well as extrahepatic metastasis-free survival rate by log rank test and predictors of extrahepatic metastasis by univariate and multivariate logistic regression models.Hepatitis B surface antigen (HBs-Ag) was found in 25 (32.5%) of 77 patients, and extrahepatic metastasis occurred in 26 (33.8%). Patients with extrahepatic metastasis showed better liver function and a high occurrence of HBs-Ag positivity than those without. The 5-year extrahepatic metastasis-free survival rate was worse in patients with HBs-Ag positivity, larger tumors (or = 70 mm), higher alfa-fetoprotein level (or = 300 ng/mL), and lower indocyanine green retention rate at 15 minutes (ICGR15) (15%) than in those without. By univariate logistic regression analysis, HBs-Ag positivity, larger HCC tumor (or = 70 mm), lower ICGR15 (15%), and lower preoperative lymphocyte count (1000/mm3) were predictors of extrahepatic metastasis (P.1). By multivariate analysis, HBs-Ag positivity was an independent predictor of postoperative extrahepatic metastasis (P = .04).In patients positive for HBs-Ag, radiologic examination of extrahepatic organs should be performed as a part of the postoperative surveillance. Hepatitis B virus infection may promote establishment of extrahepatic metastasis.

Splenopneumopexy, which was developed in Japan, has been recognized as an effective surgical procedure in patients with Budd-Chiari syndrome. We report the case of a 72-year-old woman with Budd-Chiari syndrome and prominent hepatic encephalopathy. She was treated by splenopneumopexy 19 years previously at our institute. Recently, during a follow-up visit, she experienced disorientation and unconsciousness. Flapping tremor was also recognized, and electroencephalography demonstrated a triphasic wave. In computed tomography and angiography imagings, the inferior vena cava was obstructed and the portopulmonary shunt placed by splenopneumopexy was remarkably dilated. There were no other major collaterals of the portal venous system. These findings showed that the hepatic encephalopathy was caused by the change in the portopulmonary shunt. Because hepatic encephalopathy can appear after splenopneumopexy, long-term follow-up may be necessary in patients with Budd-Chiari syndrome who are treated by splenopneumopexy.

Proteinase-activated receptor-2 (PAR-2), which is a G protein-coupled receptor, is activated in inflammatory processes and cell proliferation. We previously demonstrated that an anti-PAR-2 antibody suppresses proliferation of human pancreatic cells in vitro. However, there have been no studies of PAR-2 signaling pathways in vivo. The aim of this study was to determine whether blockade of PAR-2 by RNA interference influences pancreatic tumor growth. We originally constructed small interfering RNAs (siRNAs) targeting human PAR-2, and performed cell proliferation assays of Panc1 human pancreatic cancer cell line with these siRNAs. Intratumoral treatment with these PAR-2 siRNAs and atelocollagen was also performed in a xenograft model with nude mice and Panc1 cells. siRNAs against human PAR-2 inhibited proliferation of Panc1 cells, whereas control scramble siRNAs had no effect on proliferation. The PAR-2 siRNAs dramatically suppressed tumor growth in the xenograft model. PAR-2-specific siRNA inhibited growth of human pancreatic cancer cells both in vitro and in vivo. Blockade of PAR-2 signaling by siRNA may be a novel strategy to treat pancreatic cancer.

Background: Portal hypertensive gastropathy is an abnormal circulatory state in gastric mucosa with vascular dilatation due to portal hypertension. The aim of the present study was to evaluate expression of endothelin receptors and their roles in the portal hypertensive gastric mucosa. Methods: Portal hypertensive rats were generated by staged portal vein occlusion. Expression of endothelin-A receptor and endothelin-B receptor mRNA was examined by reverse transcriptase–polymerase chain reaction, and protein were examined by immunohistochemistry. The changes of mucosal microcirculation by endothelin receptor antagonists were measured with in vivo microscope. Results: Expression of endothelin-A receptor mRNA was increased significantly in portal hypertensive rats in comparison with sham-operated control rats (P < 0.05). There was no significant difference between the two groups in endothelin-B receptor mRNA expression. Vessels of the gastric mucosa were dilated, and intravessel blood flow was increased significantly in the portal hypertensive group (P < 0.05). Diameters of mucosal vessels and blood flow were increased significantly by endothelin-A receptor antagonist (BQ-485) in the portal hypertensive rats. Endothelin-B receptor antagonist (IRL-1038) had no significant effect on mucosal microcirculation. Conclusion: These data suggest that increased expression of endothelin-A receptor in the portal hypertensive gastric mucosa may be related to the regulation of gastric microcirculation.

Background/Aims: The effectiveness of 5-fluorouracil (5-FU) treatment is influenced by the activities of pyrimidine catabolic enzymes. The aim of this study was to investigate whether interferon (IFN)-α influences expression of 5-FU catabolic or target-related enzymes in human hepatoma cells. Methods: HepG2 cells were treated with 0, 0.15, 1.5, 15, and 150 ng/ml of consensus interferon (C-IFN). Expression of mRNAs encoding dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase, and thymidylate synthase was examined by reverse transcription-polymerase chain reaction before and after C-IFN treatment. To determine the effect of pretreatment with C-IFN on 5-FU+C-IFN combination therapy, we performed WST-1 cell proliferation assays. Results: A significant reduction in the level of DPD mRNA was observed when HepG2 cells were pretreated with C-IFN (P

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan catabolic enzyme that is widely distributed in various tissues. In peripheral blood mononuclear cells (PBMCs), production of IDO by macrophages or dendritic cells has been reported to inhibit T-cell activation and proliferation. In the present study, we have determined that other phenotypes of PBMCs also express IDO. In cultures of PBMCs, IDO was found predominantly in monocyte by immunohistochemistry. Reverse transcriptase polymerase chain reaction analysis showed that IDO mRNA was expressed in T lymphocytes, B lymphocytes and natural killer (NK) cells and that expression was increased upon activation with interferon-gamma. The cytotoxicity of NK cells against K562 and HepG2 cells was reduced by IDO inhibitor. These results suggest that IDO in NK cells is essential for NK cells to generate killing activity against cancer cells.

Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolizing enzyme, is induced under various pathological conditions, including viral and bacterial infection, allograft rejection, cerebral ischemia, and tumor growth. We have previously reported that the expression of IDO mRNA was increased in some clinical cases of hepatocellular carcinoma in which the recurrence-free survival rate in these IDO-positive patients was significantly higher than that in patients without IDO mRNA induction in tumors. Additionally, IDO expressed in tumors was localized not to the tumor cells but instead to tumor-infiltrating cells by immunohistochemistry. In this study, in order to elucidate the mechanisms underlying anti-tumor effect of IDO, we investigated whether IDO inhibitor (1-methyl-dl-tryptophan, 1MT) affects the growth of subcutaneous B16 tumors in mice. Subsequently, the activity of natural killer (NK) cells was investigated under the conditions of inhibited IDO activity in vivo and in vitro. IDO mRNA expression of B16 cells, B16 subcutaneous tumor, sprenocytes of mice, and human NK cells were studied by reverse transcription-polymerase chain reaction. B16 subcutaneous tumor growth with or without IDO inhibition was observed and cytotoxic activity of NK cells were investigated under the conditions of inhibited IDO activity in vivo and in vitro. IDO mRNA was expressed in B16 subcutaneous tumor, splenocytes of tumor bearing mice, co-cultured splenocytes with B16, and human NK cells. On day 14, after injection of B16 melanoma cells, the sizes of tumors in IDO-inhibited mice were significantly larger than those in control mice. The cytotoxic activity of mice NK cells was reduced by IDO inhibition in vivo. In vitro inhibition of IDO, NK activity was reduced in dose-dependent manner of 1MT. In conclusion, these results indicated that IDO plays an important role in anti-tumor immunity by regulating cytotoxic activity of NK cells.

This report describes three patients who underwent a pylorus-preserving pancreaticoduodenectomy (PpPD) and received maintenance hemodialysis due to chronic renal failure. The three cases were diagnosed to have bile duct cancer, intraductal papillary mucinous neoplasm, and carcinoma of the ampulla of Vater, respectively. They underwent chronic hemodialysis for 7.7 years. They all underwent a PpPD with lymph node dissection. The mean operation time was 373 min and mean blood loss was 647 ml. During the postoperative courses, hemodialysis was restarted on postoperative day 1 in all three cases. In the three patients, only minor complications were experienced and these were treated conservatively. The mean postoperative hospital stay was 48 days. Two patients are still alive 135 and 21 months after the operation, respectively, but the other patient died of another disease 21 months after the PpPD. A PpPD may therefore be safe and feasible even in patients receiving chronic hemodialysis.

Laparoscopic bariatric surgery has gradually spread in Japan since it was introduced in 2000. In 2005, we introduced laparoscopic adjustable gastric banding (LAGB) with the LAP-BAND system into Japan. Here, we evaluate our intermediate-term results with the LAP-BAND system.Between August 2005 and June 2010, 27 Japanese patients with morbid obesity (BMI ≥ 35 kg/m(2) ) underwent LAGB with the LAP-BAND system in our institution. Our patients' average weight was 111 kg and BMI was 41 kg/m(2) . All LAGB procedures were performed through the pars flaccida pathway with band fixation using gastric-to-gastric sutures. The average follow-up period was 48 months.All procedures were completed laparoscopically. One early complication (sudden cardiac arrest due to postoperative bleeding) and three late complications (port trouble, megaesophagus, and band slippage) were experienced, and reoperations were performed in three of the patients. Weight loss and percentage of excess weight loss on average were 26 kg and 53% after 3 years and 22 kg and 53% after 6 years, respectively. In line with this good weight loss, comorbidities, especially those of type 2 diabetes and metabolic syndrome were frequently resolved or improved.LAGB with the LAP-BAND system appears to be beneficial in obese Japanese patients.

Idiopathic portal hypertension (IPH) is considered to be closely related to portal vein thrombosis (PVT). The aim of this study was to clarify the incidence, clinical characteristics, and outcomes of PVT in patients with IPH after splenectomy. We investigated the rates, clinical characteristics, and outcomes of PVT in 18 patients who underwent splenectomy for IPH, during a mean follow-up period of 152 ± 83 months. Seven of the 18 patients (39%) experienced gastrointestinal bleeding, which was from the varices in 4. Eight patients (44%) had PVT, and the mean interval until its detection after splenectomy was 22 ± 41 months. The cumulative gastrointestinal bleeding rates 5, 10, and 15 years after surgery were 24%, 31%, and 41%, respectively. The cumulative survival rates 5, 10, and 15 years after surgery were 94%, 74%, and 65%, respectively. There were no significant differences in the cumulative gastrointestinal bleeding and survival rates between patients with and those without PVT. Despite the high incidence of PVT in IPH patients postsplenectomy, it may not be related to their gastrointestinal bleeding or prognosis.

During recent years, obesity has emerged as a major public health problem in the world. It is generally agreed that non-surgical therapies do not solve the problem of morbid obesity (BMIor =35 kg/m). Therefore, bariatric surgery has been frequently performed for treatments of morbid obesity in American and European countries. In 2008, more than 340,000 bariatric surgical operations (or =90% laparoscopically) were done, and the typical procedures were laparoscopic Roux-en-Y gastric bypass, adjustable gastric banding and sleeve gastrectomy. Bariatric surgery certainly reduces weight and improves comorbidities and survival in morbidly obese patients. Recently, several bariatric procedures have been also introduced into Japan, and their excellent results in Japanese patients have been already reported.

Obstructive jaundice is common symptom of carcinoma of the ampulla of Vater. In the present study we evaluated association between preoperative jaundice and prognosis and possible indication of the minimal surgery.Clinicopathological features of 50 patients who underwent curative resection were examined retrospectively and statistically analyzed.Thirty-two of the 50 patients (64%) had preoperative jaundice, and these patients had poorer survival compared with these without jaundice (5 year survival 57.2% vs. 100%, p0.01). Preoperative jaundice, serum carbohydrate antigen 19-9 level, pancreatic invasion, lymphatic invasion, venous invasion, perineural invasion, duodenal invasion, margin status, lymph node metastasis, and T stage were shown to be significant prognostic factors. In the 18 patients without preoperative jaundice, lymphatic invasion was significantly related to lymph node metastasis. In addition, 12 of the 14 patients without jaundice and lymphatic invasion were diagnosed as T1N0 (stage IA) disease, and all the tumors were papillary or well-differentiated adenocarcinoma.Preoperative jaundice may reflect advanced-stage in case of ampullary cancer. Radical surgery may not be necessary in patients without preoperative jaundice if the tumor is diagnosed as a papillary or well-differentiated adenocarcinoma without lymphatic invasion.

OBJECTIVES It is important to identify useful tumor markers for the prediction of postoperative outcomes in patients with pancreatic carcinoma (PC). METHODS A retrospective study was performed in 87 patients who underwent surgical resection for PC. Preoperative levels of tumor markers such as carbohydrate antigen 19-9 (CA19-9) and duke pancreatic monoclonal antigen type 2 (DUPAN-2) were estimated and analyzed in relation to disease-specific survival (DSS). RESULTS The CA19-9 level did not correlate with the DUPAN-2 level (R=-0.057). Prognosis correlated with CA19-9 levels, and patients with 185 U/mL or lower CA19-9 level showed significantly better DSS than patients with 186-U/mL or higher CA19-9 level (P=0.015). Patients with 151- to 800-U/mL DUPAN-2 level showed significantly worse DSS than patients with 801-U/mL or higher DUPAN-2 level (P=0.0023), so the prognosis was reversely related to the DUPAN-2 level. Patients with increased levels of both CA19-9 and DUPAN-2 showed significantly worse DSS than the patients without elevated levels (P

Background and Aims: Portal hypertensive (PHT) gastropathy results in an increased susceptibility to damage. Adaptive cytoprotection against ethanol-induced damage is impaired in the gastric mucosa of rats with portal hypertension. Excessive nitric oxide (NO) production occurs in portal hypertension and is mediated in part via heat-shock protein (Hsp)90 production. The aim of this study was to investigate the relation between adaptive cytoprotection after exposure to ethanol and gastric expression of Hsp90 in PHT rats. Methods: Portal hypertension was induced in rats by staged portal vein occlusion. Adaptive cytoprotection to 70% ethanol was evaluated by assessing the injury index of the gastric mucosa with or without pretreatment with 10% ethanol. Expression of Hsp90 mRNA was evaluated by real-time polymerase chain reaction, and expression of Hsp90 protein was evaluated by western blotting. The effect of Hsp90 inhibition in PHT rats was evaluated by administration of geldanamycin. Results: Gastric Hsp90 mRNA expression in PHT rats was significantly less than that in sham-operated (SO) controls. However, after 10% ethanol pretreatment, Hsp90 mRNA expression was significantly greater in PHT rats than in SO controls. In PHT rats, gastric Hsp90 protein expression after 10% ethanol pretreatment was significantly greater than that without the pretreatment. However, the pretreatment had no effect on the injury index compared to SO rats. Administration of geldanamycin prior to 10% ethanol pretreatment significantly decreased the injury index in response to 70% ethanol in the PHT rats. Conclusions: These results show that 10% ethanol pretreatment markedly increases gastric Hsp90 expression in PHT rats. Excessive production of Hsp90 may contribute impaired adaptive cytoprotection.

Laparoscopic cholecystectomy is being performed with increasing frequency worldwide. This has led to more frequent discovery of incidental gallbladder cancer (IGBC) and in turn to the need for an independent prognostic factor for stages T1b–T3 gallbladder cancer so that is can be determined clinically which cases of IGBC are indicated for additional radical resection (ARR). A retrospective study was conducted that included 72 patients who underwent macroscopically curative surgical resection (R0, R1) at our center for stages T1b–T3 GBC. Survival analysis was performed, and the usefulness of ARR was analyzed in 15 patients with IGBC. Univariate analysis of disease-specific survival showed stage T3, histologic grade II–IV, lymphatic invasion, vessel invasion, perineural invasion, lymph node metastasis, and a positive resection margin to be factors indicative of poor prognosis. Independent predictors of poor disease-specific survival were stage T3 (hazard ratio, 2.33 [95% CI, 1.10–4.95]), lymphatic invasion (5.97 [1.29–27.6]), and a positive resection margin (3.17 [1.51–6.63]). Among the 15 IGBC patients, 4 of 5 patients without lymphatic invasion were cured, 2 of whom underwent cholecystectomy alone; 4 of 10 patients with lymphatic invasion did not undergo ARR, and the cancer recurred in all 4 patients; the other 6 patients underwent ARR, and 4 of them were cured by reoperation. Lymphatic invasion well reflects the malignant phenotype of stages T1b–T3 GBC. We advocate ARR for IGBC patients with lymphatic invasion.

We have introduced intragastric balloon placement (IGB) and laparoscopic adjustable gastric banding (LAGB) into Japan since 2004. We performed IGB in 23 morbidly obese patients with 40 +/- 9 kg/m2 (BMI). When the balloon were removed after 5 months, the averaged weight loss and percent excess weight loss (%EWL) were 12 kg and 27%, respectively. Twenty-seven patients with 45 +/- 9 kg/m2 underwent LAGB in our institute, and after 12 and 24 months, the average weight loss were 25 kg and 35 kg, and %EWL were 40% and 54%. There was no serious complication after both the treatments. IGB and LAGB are safe and effective treatments for Japanease patients with morbid obesity.

Aims The morbidity rate of hepatic resection for hepatocellular carcinoma (HCC) remains high. To clarify predictors and the prognostic significance of operative complications in patients with HCC, we conducted a comparative retrospective analysis of 291 patients with HCC who underwent hepatic resection. Methods Operative complications included hyperbilirubinemia, ascites, hemorrhage, respiratory and cardiovascular diseases, bile leakage and abscess formation, renal failure, wound infection, and pleural effusion. Predictors of operative complications and their prognostic value for long-term survival were studied by univariate and multivariate analyses. Results Mortality and morbidity rates were 7.2% and 42.6%. The main operative complications were ascites ( n = 30), intraabdominal abscess ( n = 25), hyperbilirubinemia ( n = 19), wound infection ( n = 16), pleural effusion ( n = 10) and intraabdominal hemorrhage ( n = 9). By a multivariate logistic regression model, Child–Pugh class B and increased operative blood loss (≥1200 ml) were independent predictors of postoperative complications. Among 243 patients without operative death, the 5-year overall survival rate was significantly lower in patients with operative complications (34.3%) than in those without these complications (48.7%). By the multivariate Cox proportional hazards model, the presence of operative complications was an independent predictor of poor overall survival as well as presence of portal invasion. Conclusions Child–Pugh class B and operative blood loss ≥1200 ml were independent predictors of complications after hepatic resection for HCC. Long-term survival is poorer in patients with postoperative complications. Decreasing operative blood loss may result in fewer postoperative complications and better long-term survival of HCC patients.

Although hepatocellular carcinoma (HCC) is a common tumor, direct invasion of the gastrointestinal tract by HCC is uncommon. Recently, we encountered two cases of HCC with direct invasion to the colon. The first patient was a 79-year-old man who underwent transarterial chemo-embolization (TACE) for HCC 1.5 years prior to admission to our hospital. Computed tomography (CT) showed a 7.5-cm liver tumor directly invading the transverse colon. Partial resection of the liver and transverse colon was performed. The patient survived 6 mo after surgery, but died of recurrent HCC. The second patient was a 69-year-old man who underwent TACE and ablation for HCC 2 years and 7 months prior to being admitted to our hospital for melena and abdominal distension. CT revealed a 6-cm liver tumor with direct invasion to the colon. The patient underwent partial resection of the liver and right hemicolectomy. The patient recovered from the surgery. But, unfortunately, he died of liver failure due to liver cirrhosis one month later. Although the prognosis of HCC that has invaded the colon is generally poor due to the advanced stage of the disease, surgical resection may be a favorable treatment option in patients with a good general condition.

There is accumulating agreement that bariatric surgery is currently the most efficacious and enduring treatment for clinically severe obesity, and as a result, the number of bariatric surgeries performed worldwide has increased in recent years. Although the function of visceral fat has gradually become clear, the effect of visceral fat resection is still unknown. The aim of this study was to clarify the additional effect of visceral fat resection in an obese rat model of gastric banding.Forty male Zucker fatty rats were divided into four groups: the control group, visceral fat resection group, gastric banding group, and gastric banding with visceral fat resection group. They were followed for 8 weeks after surgery, and their body weight change, cumulative food intake, metabolic parameters, and adipocytokines were measured.The gastric banding rats either with or without visceral fat resection showed significant decreases in weight gain, cumulative food intake, and levels of metabolic parameters compared to the control rats. There were no significant differences in weight gain and cumulative food intake between gastric banding with and without visceral fat resection. However, gastric banding with visceral fat resection resulted in lower plasma levels of free fatty acid and TNF-alpha compared to gastric banding alone, and expression of adiponectin mRNA in the adipose tissue was significantly decreased with the addition of visceral fat resection compared with banding alone. There were no significant differences in any parameters between controls and rats receiving visceral fat resection alone.Visceral fat resection may improve adipocytokines and free fatty acid in an obese rat model of gastric banding. However, further studies are necessary before the procedure can be considered an option on bariatric surgery.

Hepatic resection for hepatocellular carcinoma (HCC) in cirrhotic patients with esophageal varices (EV) is often avoided because of poor liver function reserve. Outcomes of resection in such cases have not been fully investigated. We conducted a retrospective study of 134 cirrhotic patients (Child–Pugh class A or B) who underwent hepatic resection for HCC, comparing short- and long-term outcomes in patients with EV (n = 31) to those in patients without EV (n = 103). Patients with EV had higher tumor differentiation, fewer instances of portal invasion, lower liver function reserve, and more limited resections than did patients without EV. Of 31 patients with EV, four died of postoperative complication, and nine of liver failure, seven of HCC, two of ruptured EV, and two of other causes. Median survival time for patients who died of liver failure was 59 months. Mortality and morbidity rates after hepatic resection did not differ between patients with and without EV. The 5-year overall survival rate was significantly higher in patients with EV (70.1%) than in those without EV (47.5%, P = 0.045) but did not differ between patients without portal invasion with and without EV (P = 0.55). Presence of EV was not an independent predictor for survival. Short- and long-term outcomes of hepatic resection in HCC patients with and without EV are similar. Limited hepatic resection for early-stage tumor is an option for Child–Pugh class A or B patients with EV.

Systemic chemotherapy has not seen widespread use in the treatment for hepatocellular carcinoma (HCC). Recently, it was reported that combination treatment of 5-fluorouracil (5-FU) and interferon (IFN)-alpha was effective for non-resectable HCC. The effect of 5-FU treatment is influenced by the activities of pyrimidine catabolic enzymes. The aim of this study was to investigate which IFN-alphais most effective in combination therapy via downregulation of dihydropyrimidine dehydrogenase (DPD).Cell proliferation assay in human hepatoma cells (HepG 2) was performed using 5-FU and/or various IFNs-alpha (C-IFN, Intron A, OIF). At the same time,DPD mRNA levels were quantified by real-time polymerase chain reaction.5-FU alone but not all the IFNs showed anti-cancer effects, and the combination of each IFN +5-FU had a greater anti-cancer effect than 5-FU alone. C-IFN +5-FU most effectively prevented cancer cell proliferation (p0.05). Also, the combination of C-IFN +5-FU most downregulated DPD mRNA expression.The combination of each IFN-alpha +5-FU showed anti-cancer effects for HCC via downregulation of DPD. C-IFN may be most effective in the combination therapy of IFN-alpha +5-FU for HCC.

Prognostic values of leukocyte subset counts in peripheral blood of cancer patients have not yet been fully investigated. We retrospectively examined the relation between preoperative absolute counts of peripheral blood leukocyte subsets and clinicopathologic factors and long-term prognosis in 97 patients with liver metastasis from colorectal cancer who underwent hepatic resection. Median preoperative peripheral blood leukocyte subset counts were as follows: neutrophils 3148/mm3; lymphocytes 1574/mm3; monocytes 380/mm3. Univariate analysis indicated significantly worse 5-year cancer-related survival for patients with a peripheral blood monocyte count >300/mm3 (67.5%) than for patients with a count ≤300/mm3 (36.8%). Multivariate analysis showed a preoperative peripheral blood monocyte count >300/mm3 and preoperative CEA level (>10 ng/ml) to be independent predictive factors for cancer-related survival after hepatic resection. The preoperative peripheral monocyte count correlated positively with white blood cell and neutrophil counts, but not with the tumor number, interval between colorectal and hepatic surgery, or preoperative serum CEA level. Our findings indicate that a preoperative absolute peripheral blood monocyte count >300/mm3 is an independent predictive factor for cancer-related survival of patients with colorectal liver metastasis who have undergone hepatic resection.

Adenomyomatous hyperplasia is most commonly found in the stomach, gallbladder, duodenum, and jejunum, while it is rarely found in the extrahepatic bile duct. A 62-year-old woman was referred to our institution with a diagnosis of common bile duct (CBD) stenosis which had been detected by endoscopic retrograde cholangiopancreatography (ERCP). Abdominal computed tomography with contrast medium revealed a thickening of the wall of the lower CBD, and this lesion was weakly enhanced by contrast medium in the arterial phase. ERCP revealed a 15-mm-long stenosis of the lower CBD, but no malignant cells were detected by either bile cytology or brush cytology. Because CBD cancer could not be ruled out, pylorus-preserving pancreatoduodenectomy was performed. Histopathologically, multiple hyperplastic glands without cellular atypia were present in the lower CBD wall. An immunohistochemical study showed fibroblasts with positive staining for alpha-smooth muscle actin surrounding the glands. The lesion was diagnosed to be adenomyomatous hyperplasia of the CBD. When a diagnosis of adenomyomatous hyperplasia of the CBD is difficult to make both preoperatively and intraoperatively, then a radical surgical procedure, such as a pancreatoduodenectomy, may be an effective treatment alternative.

The effect of perioperative blood transfusion on the survival of hepatocellular carcinoma (HCC) has not been fully investigated. To clarify the prognostic value of intraoperative allogenic blood transfusion, we conducted a comparative retrospective analysis of 224 patients with HCC who underwent hepatic resection.We compared clinicopathologic background and survival after hepatic resection between patients who received intraoperative blood transfusion (n=101) and those who did not (n=123).Patients with blood transfusion had a larger tumor and more frequent vascular invasion than those without blood transfusion. The 5-year cancer-related survival rate after hepatic resection, but not the disease-free survival rate, was significantly lower in patients who underwent blood transfusion than in those who did not (38.3% vs. 66.7%, P0.01). Multivariate analysis showed intraoperative blood transfusion (P=0.02), microscopic portal invasion (P0.01), and preoperative serum alpha-fetoprotein elevation (P=0.03) to be independent risk factors for poor outcome after hepatic resection. The negative effect of blood transfusion on postoperative survival was observed only in patients with a tumor larger than 50mm in diameter. The absolute peripheral blood lymphocyte count on postoperative day 1 was significantly lower in patients who underwent blood transfusion (880/mm(3)) than in those who did not (1081/mm(3)) (P0.01).Our data suggest that intraoperative blood transfusion results in immunosuppression in the early postoperative period, allowing for progression of residual HCC after resection. Therefore, intraoperative allogenic blood transfusion should be avoided in patients with resectable HCC, particularly in those with a large tumor.

The effectiveness of 5-fluorouracil (5-FU) treatment is influenced by the activities of pyrimidine catabolic enzymes. The aim of this study was to investigate whether interferon (IFN)-alpha influences expression of 5-FU catabolic or target-related enzymes in human hepatoma cells.HepG2 cells were treated with 0, 0.15, 1.5, 15, and 150 ng/ml of consensus interferon (C-IFN). Expression of mRNAs encoding dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase, and thymidylate synthase was examined by reverse transcription-polymerase chain reaction before and after C-IFN treatment. To determine the effect of pretreatment with C-IFN on 5-FU+C-IFN combination therapy, we performed WST-1 cell proliferation assays.A significant reduction in the level of DPD mRNA was observed when HepG2 cells were pretreated with C-IFN (P0.05). This reduction occurred in a time-dependent manner. Cell proliferation was reduced most significantly when HepG2 cells were treated with 5-FU and C-IFN. Furthermore, when cells were pretreated with C-IFN for 3 days, the anti-proliferative effect of 5-FU+C-IFN combination therapy was augmented significantly (P0.05).C-IFN likely improves the anti-tumor effect of 5-FU via downregulation of DPD enzyme in hepatoma cells. Pretreatment with C-IFN may increase the anti-cancer effect of 5-FU+C-IFN combination therapy.

BACKGROUND Intrahepatic disease recurrence is observed frequently after locoregional therapies for patients with hepatocellular carcinoma (HCC). However, the indication for locoregional therapy is still unclear. To clarify the indication for locoregional therapy for small HCC tumors, the authors measured the distance of microsatellites from the main tumor and analyzed the relation between this distance and clinicopathologic factors. METHODS The authors retrospectively analyzed 100 patients with small HCC tumors (≤ 5 cm in dimension) treated by curative hepatectomy. A microsatellite was defined as invasion into the portal vein or intrahepatic metastasis, and the distance from the main tumor to the most distant microsatellite was determined under light microscopy. The current study investigated the relation between microsatellite distance (0 mm if none present, ≤ 5 mm, and > 5 mm) and clinicopathologic factors, as well as overall and disease-free survival rates after hepatectomy. RESULTS Of the 100 patients, 46 had microsatellites with a mean distance of 9.9 mm (median, 5.0 mm). Of the clinicopathologic factors investigated, tumor grade and preoperative α-fetoprotein level significantly correlated with the presence of a microsatellite. Tumor size and distance to the microsatellite were significantly correlated. All but 1 tumor associated with a microsatellite distance > 5 mm was a high-grade tumor > 25 mm in greatest dimension. The overall survival rate of patients with a microsatellite distance of > 5 mm was lower than that of patients with a microsatellite distance < 5 mm. CONCLUSIONS Locoregional therapy, including limited resection and ablation therapies, was appropriate for patients with low-grade HCC tumors or with tumors < 25 mm in diameter. Cancer 2005. © 2004 American Cancer Society.

Surgical resection is not always feasible for patients with hepatocellular carcinoma. We used microwave coagulation therapy (MCT) as an alternative to resection and evaluated its efficacy.Twenty-four patients with unresectable hepatocellular carcinoma underwent microwave coagulation therapy by laparotomy (n=18), laparoscopy (n=4), or thoracoscopy (n=2) because of advanced liver cirrhosis and/or intrahepatic metastases. One nodule was treated in 11 patients, 2 nodules were treated in 7, 3 nodules were treated in 3, 6 nodules were treated in 1, and 7 nodules were treated in 2. Tumor size ranged from 10 to 50 mm. Liver function was analyzed at the time of initial MCT and at treatment for recurrence. Patient outcomes were studied.Two patients died postoperatively after initial MCT. Other patients showed rapid recovery without hepatic dysfunction. Liver function just before MCT was equivalent to that measured just before treatment for recurrence. One patient developed local recurrence at the margin of the treated tumor. Recurrent nodules in different segments were detected in 15 patients. Transcatheter arterial embolization was performed in 13 recurrences, percutaneous ethanol injection therapy was performed in 1 recurrence, and MCT was performed in 1 recurrence. The 3-year cancer-free survival rate was 9.9%, and the 3-year cumulative survival rate was 83.9%.Because MCT is indicated for hepatocellular carcinoma patients with advanced liver cirrhosis, intrahepatic recurrences are frequent. Since, liver function is preserved after MCT, however, locoregional therapy can be selected when intrahepatic recurrence is detected, thus improving patient survival rate.