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Surgery in elderly patients with esophageal cancer is challenging due to high mortality and limited survival. This study aimed to evaluate the safety and effectiveness of curative esophagectomy in elderly patients with esophageal cancer. This study included 77 and 112 patients with esophageal cancer aged ≥ 70 and 40–64 years, respectively, who underwent R0 esophagectomy between January 1998 and December 2016. Patient characteristics, intraoperative outcomes, postoperative complications, and long-term survival were compared. The proportions of comorbid diseases (85.7% vs. 57.1%; P

Background: The predictive factors for discontinuation of S-1 administration and prognostic factors in elderly patients with pStage II/III gastric cancer receiving S-1 adjuvant chemotherapy remain unclear. Methods: Between January 2004 and December 2016, 80 elderly gastric cancer patients (≥70 years) undergoing curative D2 gastrectomy were enrolled in this study. Predictive factors for completion of S-1 administration over 1 year, adverse events due to S-1 administration, and prognostic factors for overall survival (OS) and relapse-free survival (RFS) were evaluated. Results: Twenty-eight patients (35%) completed 8 courses of S-1. The median relative dose intensity was 82.1% (IQR 31.1–100%). The incidence rates of hematological and nonhematological adverse events were acceptable. Distal gastrectomy was an independent predictive factor for completion of S-1 administration (odds ratio [OR] 0.364; 95% confidence interval [CI] 0.141–0.939; p = 0.037). Higher postoperative neutrophil count/lymphocyte count (N/L) ratio and more advanced stage adversely influenced OS. Multivariate analysis revealed that a higher postoperative N/L ratio and more advanced stage adversely affected RFS. Conclusion: To complete adjuvant S-1 administration to elderly patients with pStage II/III gastric cancer, total gastrectomy should be avoided if possible. A new regimen for elderly gastric cancer patients with higher postoperative N/L ratios and more advanced stage should be established.

Background/aim Prophylactic splenectomy has shown no inferiority for tumors not invading the greater curvature side. Despite this, the clinical impact of prophylactic splenectomy for proximal advanced gastric cancer is not clear. This review aimed to clarify the impact of splenectomy for advanced gastric cancer in the upper third of the stomach. Materials and methods A systematic review and meta-analysis were conducted based on PubMed and EMBASE databases. The following search terms were used: "gastric cancer" OR "splenectomy" OR upper third of the stomach" OR preservation of the spleen. Results Out of 765 articles, 18 studies (combined n=6,341) were included in the analysis. Four randomized controlled trials (RCT) and eight retrospective studies suggested the benefits of spleen-preserving gastrectomy. Six retrospective studies showed no significant benefit of spleen-preserving gastrectomy. Prophylactic splenectomy showed a close association with a higher incidence of postoperative morbidity (pancreatic fistula and anastomotic leakage) with no concomitant improvement in overall survival. Prophylactic splenectomy should not be routinely performed and RCTs are necessary to confirm the impact of splenectomy for cN(+) at the splenic hilum tumors and tumors invading the greater curvature.

Background A drain exchange with the use of a guidewire may be accompanied by serious complications. Case presentation This case involved an 86-year-old man with overlapping cancers of intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma. A left hepatectomy, a left caudal lobectomy (with a medial hepatic vein preservation), an extrahepatic bile duct resection, and a right hepatojejunostomy were performed. The abdominal drain was placed into the hepatectomy side. Bile leakage occurred on the seventh day after the surgery, and the drain was exchanged. Since the bile leakage was still detectable via a computed tomography (CT) scan on the 15th postoperative day, the drain was exchanged again. On the next day, blood had discharged from the drain. A CT scan revealed that the tip of the drain was straying into the right atrium (RA) and the drain was removed from the inferior vena cava (IVC) under general anesthesia. One week later, a fiburin thrombus was observed from the IVC to the RA via the use of transthoracic echocardiography. A right atrial incision, a thrombus removal, and a middle hepatic vein merging section closure surgery were performed. Afterward, the patient’s general condition gradually improved, and he was transferred to the hospital for rehabilitation. Conclusion More careful guidewire operations are necessary at the time of the exchange of the drain to prevent the drain from being placed too close to blood vessels.

AIMS Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. METHODS We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription-polymerase chain reaction (PCR). RESULTS Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P

Background The significance of the dimensional factors (tumor diameter, area and volume) as the prognostic factor has not been precisely evaluated in pT1 gastric cancer. Objectives This study aimed to identify the clinical impact and to confirm the clinical feasibility of the dimensional factors as prognostic factors in pT1 gastric cancer. Methods We analyzed prognostic factors for disease-specific survival (DSS), overall survival (OS) using clinicopathological factors by univariate and multivariate analyses and the pattern of recurrence in 2011 pT1 gastric cancer (mucosal and submucosal cancers) undergoing R0 gastrectomy. The cut-off values of each dimensional factor was decided by the ROC curve. Results Cox proportional hazard regression model showed that older age (≥75) and more advanced pN stage were adverse independent prognostic factors for DSS, and revealed that older age (≥75), greater preoperative co-morbid diseases, proximal and total gastrectomy, operative method and Clavien-Dindo classification (≥grade III) were independent adverse factors for OS. Any dimensional factors were not independent prognostic factors for any survival. Conclusions The dimensional factors do not influence both OS and DSS in pT1 gastric cancer patients and so it is difficult to apply these dimensional factors for conducting therapeutic strategies.

Background Although endoscopic interventions for chronic pancreatitis are highly developed, surgery for severe complicated cases such as the coexistence of bile duct, duodenum, and portal vein stenosis is a challenging issue for surgeons. In such instances, pancreaticoduodenectomy could lead to massive intraoperative bleeding due to severe collateral veins. A surgical drainage procedure, instead of pancreatic resection, may be a reasonable and safer option in such cases, but the literature on a surgical drainage technique to resolve all obstructions of the pancreatic duct, bile duct, and duodenum at once is limited. We devised a new surgical drainage method for such cases with consideration for a possible future second surgery for newly developed pancreatic cancer because chronic pancreatitis is a well-known high-risk factor for pancreatic cancer in the long term. Here, we report this surgical procedure. Case presentation A 55-year-old man was diagnosed with alcoholic chronic pancreatitis 15 years ago. Before surgery, he underwent regular endoscopic pancreatic stenting for pancreatic ductal stenosis for 3 years. Three months before surgery, his duodenal stenosis worsened, and he was referred to our department for surgery. Preoperative imaging revealed pancreatic and bile duct stenosis, duodenal stenosis, and portal vein stenosis. To avoid intraoperative bleeding caused by the development of collateral veins, we performed a triple drainage procedure: longitudinal pancreaticojejunostomy with coring-out of the pancreatic head, hepaticojejunostomy, and gastrojejunostomy. The patient did not develop postoperative complications, and he was discharged from the hospital on postoperative day 14. For 5 years after surgery, no abdominal pain or recurrent pancreatitis was observed. Conclusion Our triple drainage procedure seems effective and minimally invasive for patients complicated with bile duct stenosis, duodenal stenosis, and portal vein stenosis.

Although vascular invasion is an important factor in the progression and treatment of hepatocellular carcinoma (HCC), it remains difficult to determine, on the basis of preoperative imaging alone, whether vascular invasion, especially microvascular invasion, has occurred. The current retrospective study enrolled 292 patients who, between 2004 and 2014, underwent curative hepatectomy as an initial treatment for HCC. The patients were divided between those with (n=70) and those without (n=222) microvascular invasion. Whether tumor-marker-based prediction of microvascular invasion was possible was assessed by comparing the preoperative serum α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II concentrations between two groups of patients. The AFP concentration was significantly higher in patients with microvascular invasion compared with patients without microvascular invasion (P=0.0019). Stepwise logistic regression analysis demonstrated the AFP concentration and the logarithmic conversion ratio of the AFP gradient (log AFP grad) to be useful (P=0.0019; 0.0424) for predicting microvascular invasion. The serum AFP concentration and log AFP grad appear to be clinically useful in predicting microvascular invasion in patients with HCC.

Regorafenib is an oral multikinase inhibitor affecting angiogenesis, oncogenesis, metastasis, and tumor immunity. As a systemic treatment, it has been shown to provide survival benefits in hepatocellular carcinoma (HCC) patients progressing on sorafenib treatment. We report herein a case of HCC with hepatic vein tumor thrombosis protruding into the inferior vena cava (IVC-HVTT) which was successfully treated by surgery following second-line chemotherapy with regorafenib. A 79-year-old man with chronic hepatitis was diagnosed with HCC. Computed tomography revealed a solitary tumor in segments 7 and 8 and an IVC-HVTT from the right hepatic vein. Since IVC-HVTT removal is a difficult procedure, the tumor was diagnosed as unresectable, and administration of sorafenib was started. Five weeks later, the lesion had increased in size by 15.3%; subsequently, regorafenib was given as second-line therapy for 12 months. After shrinkage of the IVC-HVTT, the patient was referred to our hospital for surgery. One month after the cessation of regorafenib, an extended resection of segment 8 and total removal of the IVC-HVTT was successfully performed without using total hepatic vascular exclusion. There were no serious postoperative complications. Additionally, there has been no recurrence for about 2 years since the initial therapy.

The post-operative mortality and morbidity rates associated with living-donor liver transplantation (LDLT) are still relatively high. Several papers have reported the risk factors associated with post-operative infectious complications, but few have analyzed the risk factors with respect to the severity of sepsis. The aim of this study was to clarify the risk factors that affect severe sepsis after LDLT.For 63 LDLT patients at our institute, we compared peri-operative characteristics in 29 patients who developed sepsis after surgery and 34 patients who did not. The sepsis group was further divided into severe sepsis (n = 16) and sepsis (n = 13) subgroups to identify significant peri-operative risk factors.Multivariate analysis identified 3 significant risk factors for post-operative sepsis after LDLT: ABO incompatibility (P = .015), low estimated glomerular filtration rates (90 mL/min/1.73 m(2); P = .074), and low peripheral lymphocyte counts (850/μL; P = .008). Multivariate analysis showed that the only significant risk factor for severe sepsis was a low pre-operative lymphocyte count (850/μL; P = .01). In the 2 sepsis subgroups, the 5- and 10-year survival rates for the severe sepsis subgroup (37.5% and 37.5%) were significantly lower than for the sepsis subgroup (83.3% and 62.5%; P = .05). The lung was the most common site of severe sepsis (n = 8; 50.0%).Patients who developed severe sepsis after LDLT had poor long-term survival, with pre-operative lymphocyte counts 850/μL being the significant risk factor. Pre-operative nutritional intervention and rehabilitation should be considered to improve LDLT outcomes.

A 52-year-old Japanese male underwent ABO-incompatible living donor liver transplantation for acute-on-chronic hepatitis B infection. Fifty-one months later, he became feverish and a cytomegalovirus (CMV) infection was diagnosed. A dramatically high CMV pp65 antigen (C10/C11) load (2,412) was measured, which did not respond to ganciclovir and immune globulin treatment, and increased further to 5,353. The next treatment strategy was the reduction of immunosuppressants, but to simply reduce immunosuppressants can lead to graft loss. Therefore, before using this strategy, responses to alloantigens were evaluated using a carboxyfluorescein-diacetate-succimidyl ester-labeled mixed lymphocyte reaction (CFSE-MLR). Only limited CD4(+) and CD8(+) T-cell proliferation was observed, suggesting the patient was hyporesponsive. After reducing tacrolimus levels from 3-4 ng/mL to

A 72-year-old man underwent total gastrectomy for gastric cancer (por2, T3, N2, Stage IIIA). Eleven courses of postoperative chemotherapy with TS-1 (tegafur/gimeracil/oteracil) were administered. Five months after surgery, the serum carcinoembryonic antigen value was slightly elevated. However, computed tomography did not reveal any metastatic lesions in other organs. Two years after surgery, the patient felt a mass in the left mammary. A 2-cm tumor was palpable in the central portion of the breast. Ultrasonography revealed a hypoechoic tumor, which was Class 3 on aspiration biopsy cytological examination. No mass was detected on positron emission tomography-computed tomography. The mammary gland tumor increased in size to 3 cm, and a core needle biopsy procedure was performed. Histological examination findings revealed breast metastasis of gastric cancer. No other recurrence was found, and radical mastectomy was performed 2 years and 5 months after gastrectomy. Immunohistological analysis of the resected material confirmed breast metastasis of the gastric cancer. Two courses of TS-1 + cisplatin were administered, but this treatment was subsequently terminated because the patient experienced Grade 3 diarrhea and neutropenia. Three years and 1 month after the gastrectomy, the tumor recurred in the pelvic area. Chemotherapy and radiation therapy were performed, but the patient's overall condition became progressively worse, and he died 3 years and 9 months after gastrectomy.

The prognostic factors for patients with colorectal cancer liver metastasis (L-Mets) have not been fully described. Resected specimens were obtained surgically from 1998 to 2008 at our university hospital. We investigated whether the status of two primary lesion cancer stem biomarkers, CD44 and CD133, were maintained in L-Mets and whether these markers were L-Mets prognostic factors. To investigate the CD133 and CD44 status, proliferation, invasiveness, and chemoresistance were examined immunohistochemically by using MIB-1, E-cadherin, and ABC-G2. The CD44-positive rate in primary lesions and L-Mets was 41.4 and 58.7 %, respectively. There was no correlation of CD44 expression between primary lesions and L-Mets (r = 0.250, p = 0.071). The CD133-positive rate in primary lesions and L-Mets was 53.6 and 44.6 %, respectively. There was no correlation of CD133 expression between primary lesions and L-Mets (r = 0.219, p = 0.135). In the CD133-negative group, the MIB-1 index was significantly higher than in the CD133-positive group (61.6 vs. 46.3 %, p = 0.003), and E-cadherin expression was significantly lower in the CD133-negative group compared with the CD133-positive group (29.3 vs. 46.8 %, p = 0.001). Absence of CD133 expression in L-Mets correlated with poor overall survival (p = 0.006), and multivariate regression analysis showed that it was an independent marker for poor survival (hazard ratio 0.320, p = 0.0016). The absence of CD133 expression in L-Mets was an independent marker and a poor prognostic factor, possibly because of increased proliferation and invasiveness.

Background The inflammation-based Glasgow prognostic score (GPS) has been demonstrated to be prognostic for various tumors. We investigated the value of the modified GPS (mGPS) for the prognosis of patients undergoing curative resection for colorectal liver metastases (CRLM). Methods A total of 343 patients were enrolled onto this study. The mGPS was calculated as follows: mGPS-0, C-reactive protein (CRP) ≤10 mg/L; mGPS-1, CRP >10 mg/L and albumin ≥35 g/L; and mGPS-2, CRP >10 mg/L and albumin

Background In the present study, we conducted a multicenter nationwide survey to investigate the effects of preoperative fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Methods From 16 Japanese LT centers, data were collected on 182 recipients with HCC who underwent living donor liver transplantation (LDLT) between February 2005 and November 2013. PET-positive status was defined as increased uptake of FDG in the tumor compared to the surrounding non-tumor liver tissue. The median follow-up after LDLT was 54.5 months (range 1–125 months). Results Postoperative HCC recurrence occurred in 23 patients. Multivariate analysis revealed that exceeding the Milan criteria (MC), alpha-fetoprotein (AFP) level ≥115 ng/ml, and PET-positive status were significant and independent risk factors for recurrence. In the over-MC group, a subgroup of patients with AFP level

Although many studies have concluded that prophylactic drain insertion during elective liver resection offers few advantages, we reassessed the clinical value and appropriate management of drain insertion. We retrospectively studied the clinical value of abdominal drainage in 167 consecutive patients who underwent hepatectomy, focusing on drainage volumes, bilirubin concentrations, drainage fluid bacterial culture results and short-term postoperative outcomes. The results were then validated prospectively in the next 50 consecutive patients to undergo hepatectomy. Most of the patients with morbidities such as biliary fistulas, ascites, fluid collection or duodenal perforation (20/24 or 83 %) were treated using operative drainage tubes, avoiding the use of percutaneous drainage procedures. The values obtained with the formula (drainage fluid bilirubin concentration/serum bilirubin concentration) × drainage fluid volume, were greater on both postoperative days (POD) 2 and 3 (P = 0.03 and P

Tumor downsizing by effective chemotherapy while increasing remnant liver volume by two-stage hepatectomy can expand eligibility for resection of otherwise unresectable liver metastases. However, optimal timing of two-stage hepatectomy with respect to chemotherapy is undetermined.We retrospectively analyzed the effect of timing of two-stage hepatectomy and chemotherapy using data from 95 patients whose colorectal liver metastases initially were considered unresectable.In 21 of 22 (95 %) patients whose first liver resection preceded chemotherapy (Hx-CTx group) and in 39 of 73 (53 %) patients whose chemotherapy preceded surgery (CTx-Hx group), macroscopic complete resection ultimately was achieved (P0.01). Overall and disease-free survivals were comparable between groups. However, overall survival of patients not achieving complete resection in the CTx-Hx group was significantly poorer than that for patients achieving complete resection (P0.01). When the 21 patients with complete resection in the Hx-CTx group were compared to the 39 patients with complete resection in the CTx-Hx group, no difference in overall or disease-free survival was observed (P = 0.12 and P = 0.24, respectively), although poor response to chemotherapy was more frequent in the Hx-CTx group.Optimal timing of hepatectomy and chemotherapy is difficult to specify, but performing the initial resection in a two-stage hepatectomy before chemotherapy may increase likelihood of macroscopic complete resection, even in patients with a poor response to chemotherapy or with limited courses of chemotherapy.

En-bloc liver resection with caudate lobectomy (segmentectomy 1) is the standard procedure for hilar cholangiocarcinoma. Although its surgical mortality has been reduced below 5%, it is still a potentially hazardous operation. Complete tumor resection with negative surgical margins and safe reconstruction of bilio-enteric continuity are two principles of the surgical treatment of hilar cholangiocarcinoma. Surgeons must pay attention to the variation of the hilar structures including portal veins, hepatic arteries, and bile ducts. Three-dimensional imaging is beneficial not only for understanding anatomical variations but also for preoperative simulations. Since the U-point can be identified by both preoperative imaging and intraoperative inspection, it can be used as the landmark for the hepatectomy and the dissection point of the hilar plate. The hanging maneuver might be useful for both hepatic parenchymal dissection and bile duct dissection just right of the U-point. For safe biliary reconstruction, stay sutures in the anterior wall and transanastomotic stents may be helpful.

Purpose We studied the risk factors for postoperative mortality between patients who underwent emergency or elective living-donor liver transplantation (LDLT). Methods Forty-seven patients underwent LDLT in our institute, 16 for emergencies and 31 as elective procedures. The emergency LDLT status was applied to cases in which the time period between referral to our institution and transplantation did not exceed 10 days, and in which liver failure was accompanied by the presence of any degree of hepatic encephalopathy. Results With regard to preoperative factors, age (P = 0.03), the model for end-stage liver disease score (P = 0.001), preoperative tracheal intubation (P = 0.001), ratio between arterial oxygen tension and fractional inspired oxygen (PaO2/FiO2 ratio) (P = 0.03), steroid therapy use (P = 0.001), lymphocyte count (P = 0.02), and cases requiring hemodiafiltration (P = 0.001) differed significantly between the two groups. Postoperative pneumonia occurred more frequently in emergency LDLT patients than in elective LDLT patients (P = 0.006). Invasive pulmonary aspergillosis (IPA) was the main cause of postoperative death in emergency LDLT patients, and, in a univariate analysis, a preoperative status of high serum (1 → 3)-β-d-glucan (>20 pg/ml, P = 0.001), advanced age (>52 years, P = 0.02), and a low PaO2/FiO2 ratio (

BACKGROUND: Although tumor reduction via present-day prehepatectomy chemotherapy can render initially unresectable disease potentially resectable, little is known about the effects of such chemotherapy on liver metastases with known attachment to or invasion of major intrahepatic vessels. We histologically assessed the relationships of liver tumors to major intrahepatic vessels after chemotherapy. METHODS: In 45 patients who underwent chemotherapy and hepatectomy with pretreatment images showing metastases attached to or invading major intrahepatic vessels, 77 metastases showed attachment to or invasion of 96 vessels. RESULTS: Using postchemotherapy imaging, 11 of 77 metastases (14.3%) appeared separated from 12 of 96 major hepatic vessels (12.5%). Among 83 vessels later examined pathologically, 29 showed direct invasion (35%) and 10 showed attachment (12%). Tumors involved another 9 vessels (11%) that were separated surgically from the tumor and preserved during hepatectomy. Tumor attachment that exceeded 25% of vessel circumferences via imaging after chemotherapy was a factor associated with pathological vascular invasion or attachment according to multivariate analysis (relative risk, 8.449; 95% confidence interval, 1.961-36.415; P = .0042). CONCLUSIONS: Liver metastasis attachment to or invasion of major intrahepatic vessels is difficult to eradicate even with otherwise effective chemotherapy. Cancer 2012;. © 2011 American Cancer Society.

症例は46歳男性で，アルコール性慢性膵炎で通院中に膵尾部の仮性嚢胞と，嚢胞内に仮性動脈瘤を認めた．血管造影では仮性動脈瘤内に噴出する動脈波を認めコイリングを行ったが，膵炎の増悪を認めたため膵体尾部切除を施行した．術後徐々に主膵管が拡張し，膵炎症状の再燃がみられたため超音波内視鏡下に尾側拡張膵管のドレナージを試みたが不良であり，食事のたびに膵炎様症状を繰り返したため残膵の尾側拡張膵管と空腸の側々吻合術（Partington手術）を施行した．術後経過は良好で第10病日に軽快退院した．術後約1年5ヶ月経過しているが膵炎症状の再燃を認めず経過は良好である．本症例のように慢性膵炎で膵体尾部切除後の膵炎再燃に対してPartington手術を施行した報告はないが，積極的なドレナージ手術によりQOLの改善が得られると考えられた．

Bile duct strictures remain a major source of morbidity after orthotopic liver transplantation (OLT). Endoscopic management by the conventional methods of biliary dilatation and/or stent placement has been successful, but sometimes severe complications occur, necessitating prolonged therapy. The aim of this study is to clarify the complications of the endoscopic approach for endoscopic dilatation and/or stent placement.Of 46 patients who underwent living-donor liver transplantation, 10 were diagnosed as having anatomic biliary strictures by endoscopic retrograde cholangiopancreatography (ERCP). Two patients developing biliary strictures after deceased-donor liver transplantation were also enrolled in the study. For the purpose of comparison, 302 patients with a total of 550 consecutive ERCP cases (including 115 patients with 250 malignant bile duct strictures) were recruited in this study. Success rate, number of endoscopy sessions, the median procedure time for ERCP, and incidence of complications including post-ERCP pancreatitis were compared in the OLT cases and other cases.The following results were obtained in the OLT cases, malignant stricture cases, and all cases, respectively: mean number of endoscopy sessions was 3.62, 2.17, and 1.94 (P = 0.0216, P 0.0001); post-ERCP pancreatitis occurred in 5 (12.5%), 10 (4.0%), and 19 cases (3.5%) (P = 0.0327, P = 0.0093); and severe pancreatitis occurred in 2 cases of OLT. In a univariate analysis for post-ERCP pancreatitis, OLT was extracted as the only significant risk factor.Endoscopic maneuvering for biliary dilatation and/or stent placement following OLT was associated with a higher risk of post-ERCP pancreatitis than the use of the same technique for the treatment of malignant biliary stricture. Endoscopic treatment after OLT was a significant risk factor for post-ERCP pancreatitis.

Objective: We studied the influence of complete pathologic response of colorectal cancer liver metastases to prehepatectomy chemotherapy on long-term survival after hepatectomy. Summary Background Data: Although complete response seen on imaging may be a useful criterion for evaluating efficacy of chemotherapy, complete clinical response by imaging has shown limited predictive value for complete pathologic response in treating colorectal liver metastases. Methods: We retrospectively analyzed data from 63 patients who received preoperative chemotherapy and underwent hepatectomy. Results: Of 472 liver metastases evaluated, 86 were no more visible from images after chemotherapy. We excluded 14 of these metastasis treated with local ablation. Of the remaining 72 metastasis, 22 (30.6%) were microscopically persistent metastases or recurrences in situ. Liver metastases with complete pathologic response had smaller diameters at diagnosis than others (P < 0.001), and microscopic cancer deposits surrounding macroscopic tumors were less frequent in patients with complete pathologic response than others (P < 0.05). Outcomes were favorable in patients whose liver metastases all showed a complete pathologic response. Even patients with complete pathologic response in only some metastases showed higher overall and disease-free survival rates than pathologic nonresponders (P = 0.001 and P = 0.002, respectively). Presence or absence of metastases showing complete pathologic response was an independent prognostic factor (relative risk, 4.464; P = 0.0099). Conclusions: Little correlation was observed between imaging response of colorectal cancer liver metastases to chemotherapy and pathologic response. Liver surgery should be undertaken even after a complete response by imaging. Outcome after hepatectomy was favorable in patients showing complete pathologic response of least one metastasis.

Although portal vein embolization (PVE) and staged hepatectomy (StHx), as well as prehepatectomy chemotherapy, have improved the resectability rate of patients with multiple bilobar colorectal liver metastases, the impact of prehepatectomy chemotherapy on liver hypertrophy following PVE and/or StHx has remained unclear. Sixty patients who underwent PVE followed by one-stage hepatectomy and StHx with or without PVE were analyzed. Liver hypertrophy following PVE and/or the first hepatectomy of StHx and the clinical course after final hepatectomy was compared between patients with and without prehepatectomy chemotherapy. No difference of volume of the future liver remnant (FLR) before or after the procedure was seen between the chemotherapy group and the nonchemotherapy group. Even in 38 patients who underwent right PVE prior to a planned right hemihepatectomy, the chemotherapy group (n = 14) and the nonchemotherapy group (n = 24) were comparable in terms of volumes of FLR before (P = 0.71) and after (P = 0.29) PVE and posthepatectomy courses. However, the liver hypertrophy ratio for patients showing steatosis in adjacent nonmalignant liver parenchyma, which frequently is induced by chemotherapy, was lower than that for patients without steatosis (P = 0.04). Although prehepatectomy chemotherapy did not impair liver hypertrophy, PVE and/or StHx accompanied by prehepatectomy chemotherapy should be performed with particular care to minimize risk of liver failure after the procedure.

Although heme oxygenase-1 (HO-1) is induced in keratinocytes after UV radiation, HO-1 expression during normal epidermal differentiation has not yet been reported. We showed by real-time PCR, western blotting, and ELISA that HO-1 mRNA and protein expression by cultured normal human keratinocytes was upregulated during epidermal differentiation induced by a high-calcium medium. Immunohistochemical staining and in situ hybridization showed the graduated expression of HO-1 in the upper epidermis, which was accompanied by suprabasal HO-1 mRNA expression, and the accumulation of bilirubin (BR) in the stratum corneum. We examined the activation of nuclear factor E2-related factor 2 (Nrf2), which is a pivotal transcription factor for HO-1 expression, by western blotting and by examining the mRNA expression of Nrf2 target genes, and excluded its role in HO-1 expression in epidermal differentiation. Next, we examined the regulation of HO-1 expression by inflammatory cytokines. IL-4 and IL-22 significantly reduced HO-1 mRNA and protein expression, whereas IL-1beta, IL-17A, and tumor necrosis factor-alpha (TNF-alpha) increased it. Finally, immunohistochemical studies on psoriatic lesional skin showed that HO-1 expression was downregulated in the parakeratotic epidermis, whereas it was retained in the orthokeratotic epidermis. These studies demonstrate that HO-1 is functionally expressed by keratinocytes in parallel with epidermal differentiation and that its expression is independently affected by several cytokines.

Massive arterial hemorrhage is, although unusual, a life-threatening complication of major pancreatobiliary surgery. Records of 351 patients who underwent major surgery for malignant pancreatobiliary disease were reviewed in this series. Thirteen patients (3.7%) experienced massive hemorrhage after surgery. Complete hemostasis by transcatheter arterial embolization (TAE) or re-laparotomy was achieved in five patients and one patient, respectively. However, 7 of 13 cases ended in fatality, which is a 54% mortality rate. Among six survivors, one underwent selective TAE for a pseudoaneurysm of the right hepatic artery (RHA). Three patients underwent TAE proximal to the proper hepatic artery (PHA): hepatic inflow was maintained by successful TAE of the gastroduodenal artery in two and via a well-developed subphrenic artery in one. One patient had TAE of the celiac axis for a pseudoaneurysm of the splenic artery (SPA), and hepatic inflow was maintained by the arcades around the pancreatic head. One patient who experienced a pseudoaneurysm of the RHA after left hemihepatectomy successfully underwent re-laparotomy, ligation of RHA, and creation of an ileocolic arterioportal shunt. In contrast, four of seven patients with fatal outcomes experienced hepatic infarction following TAE proximal to the PHA or injury of the common hepatic artery during angiography. One patient who underwent a major hepatectomy for hilar bile duct cancer had a recurrent hemorrhage after TAE of the gastroduodenal artery and experienced hepatic failure. In the two patients with a pseudoaneurysm of the SPA or the superior mesenteric artery, an emergency re-laparotomy was required to obtain hemostasis because of worsening clinical status. Selective TAE distal to PHA or in the SPA is usually successful. TAE proximal to PHA must be restricted to cases where collateral hepatic blood flow exists. Otherwise or for a pseudoaneurysm of the superior mesenteric artery, endovascular stenting, temporary creation of an ileocolic arterioportal shunt, or vascular reconstruction by re-laparotomy is an alternative.

Background Accumulation of tumor-infiltrating mast cells (MCs) predicts poor survival in several cancers after resection. However, its effect on the prognosis of patients with colorectal liver metastases (CRLM) is not known. Methods Our retrospective study included 135 patients who underwent potentially curative resection for CRLM between 2001 and 2010. Expression of tryptase, MAC387, CD83, and CD31, which are markers for MCs, macrophages, mature dendritic cells, and vascular endothelial cells, respectively, was determined via immunohistochemistry of resected tumor specimens. The relationship between immune cell infiltration and long-term outcome was investigated. Results The median follow-up time was 48.4 months for all patients and 57.5 months for survivors. Overall survival (OS) rates at 1, 3, and 5 years were 91.0, 62.4, and 37.4 %, respectively. Five-year disease-free survival (DFS) and OS rates were 21.6 and 38.1 %, respectively, in patients with high MC infiltration, and 42.6 and 55.6 %, respectively, in patients with low MC infiltration (p

We report a rare case of porcelain gallbladder associated with pancreas divisum (PD). A 60-year-old woman suffered from discomfort in the back of the right side. An abdominal radiograph revealed a calcified spherical mass in the right upper quadrant. Ultrasonography revealed a scattered echo with a posterior acoustic shadow in the gallbladder wall. A plain computed tomography (CT) scan showed flecks of intramural calcification in the wall of the gallbladder. Endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP) showed separate openings for the Santorini and Wirsung ducts. The patient underwent cholecystectomy after porcelain gallbladder and pancreas divisum had been diagnosed. The porcelain gallbladder resulted from a stone impacted in the neck of the gallbladder. Patients with PD should be followed carefully, because gallstones often accompany PD, and porcelain gallbladder may result, as in this patient.

To determine whether or not the Milan criteria (MC) should be used to determine the applicability of liver transplantation (LT) as a first-line treatment for patients with cirrhosis with hepatocellular carcinoma (HCC) who are able to endure hepatectomy.Retrospective analysis of 82 patients with cirrhosis with HCC who were treated by hepatectomy without LT at our institution between 1990 and 2003.Of these 82 patients, 48 met the MC. Proportional hazard regression analyses to determine the independent prognostic factors for postoperative cumulative patient and disease-free survival showed that meeting the MC is the strongest prognostic factor for both patient and disease-free survival. The cumulative patient and disease-free survival rates were 76.7% and 28.9%, respectively, at 5 years in patients who met the MC. The cumulative disease-free survival was markedly inferior to those in previously reported series of LT for HCC who met the MC, but the cumulative patient survival was comparable to those in the previously reported series. A comparison of cumulative postoperative survival between patients who met the MC and fulfilled all five factors listed below and patients who met the MC but did not fulfill any of the five factors demonstrated that the latter patients showed statistically significantly worse postoperative patient survival than the former. The five factors included: Model for End-Stage Liver Disease score10, indocyanine green retention rate at 15 minutes20%, absence of microscopic fibrous capsular invasion and microscopic intrahepatic metastases, and earlier grade (T1 or T2) of American Joint Committee on Cancer tumor classification.The MC should not be used to determine the applicability of LT as a first-line treatment for patients with HCC considered able to endure hepatectomy. However, modifying MC with some clinicopathological factors could satisfy the appropriate criteria for applying LT as a first-line treatment for these patients.

DESIGN: It has recently been shown that deficiency of adrenomedullin (AM), a potent vasodilator peptide, leads to insulin resistance. We studied expression of AM in NIH 3T3-L1 adipocytes and compared it with expression of resistin, an adipocyte-derived peptide hormone that is proposed to cause insulin resistance. Moreover, we studied the effects of tumor necrosis factor-alpha (TNF-alpha), a known mediator of insulin resistance, on the expression of AM and resistin in 3T3-L1 adipocytes. METHODS: 3T3-L1 cells were induced to differentiate to adipocytes by insulin, dexamethasone and 3-isobutyl-1-methylxanthine. Expression of AM mRNA and resistin mRNA was examined by Northern blot analysis. Immunoreactive AM in the medium was measured by RIA. RESULTS: AM mRNA was expressed in preadipocytes, but barely detectable in adipocytes. Immunoreactive AM was detected in the medium of both preadipocytes and adipocytes, with about 2.5 times higher levels found in preadipocytes. In contrast, resistin mRNA was expressed in adipocytes, whereas it was not detected in preadipocytes. Treatment with TNF-alpha increased AM expression in both adipocytes and preadipocytes, whereas it decreased resistin mRNA levels in adipocytes. CONCLUSIONS: The present study has shown that AM expression was down-regulated and resistin expression was up-regulated during adipocyte differentiation of 3T3-L1 cells. TNF-alpha acted as a potent negative regulator of resistin expression and a potent positive regulator of AM expression in adipocytes, raising the possibility that in addition to its known actions in causing insulin resistance, TNF-alpha may also have actions against insulin resistance through AM and resistin.

拡大肝切除後の遷延した高ビリルビン血症に対して, 集学的治療を実施し, 奏効した症例を経験したので報告する. 症例は58歳の男性. 診断はS状結腸癌術後の転移性肝癌でS1, S5以外の全亜区域に転移巣を認めた. これに対し, 2回に分けて肝切除を施行した. 術直後から発熱とビリルビン値の上昇を認め, 肝不全に陥った. 血液培養からMethicillin-resistant Staphylococcus epidermidis, Enterococcus faecalisが検出され, 肝生検にてディッセ腔側の肝細胞索に線維化を認めた. 残肝は, 術後43日で術前体積の96%まで腫大した. 感染が制御された後も, 高ビリルビン血症が依然として持続した. これに対し, 高圧酸素療法, 利胆剤, フェノバール, ステロイド投与を実施し, ビリルビン値が改善した. 感染制御後に使用した利胆剤とステロイドによる肝細胞, 胆管上皮保護作用や, 高圧酸素療法による肝細胞の酸素化作用が有効であった可能性が示唆された.

Portosystemic shunt is a common complication in patients with portal hypertension. Mesenteric varix is one of the collaterals that can cause post-transplant liver dysfunction. In this case report, a 45-year-old woman underwent living relative donor liver transplantation for alcoholic cirrhosis. Although the early postoperative course was uneventful, she was readmitted for treatment of liver hypofunction. Fatty change in the graft liver was confirmed by histopathology of the biopsy specimen. The venous phase of a superior mesenteric angiogram revealed large-caliber mesenteric varices comprising portosystemic venous shunts. Surgery was performed to ligate the shunts. The intraoperative color Doppler ultrasonography showed hepatofugal portal blood flow, which was corrected to hepatopetal blood flow by clamping the shunt vessels. The portal pressure was moderately elevated from 13.6 cm to 21.8 cm H(2)O. Two shunt vessels were ligated and divided. Her liver function returned to nearly normal thereafter. We recommend that descending collaterals be divided during liver transplantation.

We describe here a rare case of hepatoid adenocarcinoma (HAC) of the gallbladder without the production of alpha-fetoprotein (AFP). A 77-year-old man was referred to our division with complaints of general fatigue, loss of appetite, and loss of body weight. A preoperative diagnosis of advanced gallbladder cancer was made, and cholecystectomy with combined resection of two liver subsegments (S4a + S5) and lymph node dissection were performed. Microscopically, the tumor was mainly composed of characteristic cells featuring eosinophilic cytoplasm, enlarged nuclei, and prominent nucleoi, arranged in nests or proliferated in a trabecular pattern. These features were highly suggestive of HAC of the gallbladder, and the tumor cells were negative for AFP immunohistochemical staining. The patient is doing well and has survived for 15 months postoperatively without any recurrence.

We report a case of hepatic mesenchymal hamartoma in an adult; this condition is extremely rare, with only 15 cases having been reported in the English-language literature worldwide. The patient was a 36-year-old woman who was seen at her local hospital for upper abdominal distension. A giant multilocular cystic tumor, which had almost entirely replaced the normal parenchyma of the right lobe of the liver, was diagnosed. She was referred to our hospital, where, with a diagnosis of biliary cystadenoma, the tumor was successfully removed by right hemihepatectomy. After an uneventful postoperative course, the patient was discharged from our hospital. On histological examination, the tumor consisted of numerous cystic lesions without epithelial lining cells; hepatocytes, bile duct, and vascular components, without either lobular structure or atypia, were observed in the pseudocyst wall, leading to a diagnosis of hepatic mesenchymal hamartoma. There have been a few previously reported cases of multifocal hepatic mesenchymal hamartoma reappearing in the remaining liver after hepatectomy, although these cases are considered to be extremely rare. Therefore, periodic follow-up will be necessary for the patient.

Background. In the present study we attempted to evaluate the role of the graft as an alloantigen in induction and maintenance of donor-specific prolongation of allograft survival by short course(s) of FK506 treatment in rat heart transplantation. Materials and methods. In the WKA/Qdj-to-LEW combination group, FK506 (3 mg/kg/day, 7 days, sc) was administered from Day 0 after cardiac transplantation. A second WKA/Qdj cardiac graft was transplanted on Day 14 into the LEW recipient after removal of the first graft on Day 3 or Day 7. In other groups an additional course of FK506 (3 mg/kg/day, 7 days, sc) was given from Day 35. A second WKA/Qdj cardiac graft was transplanted on Day 49 into the LEW recipient after removal of the first graft on Day 7 or Day 28. Results. A short course of FK506 treatment allowed for survival prolongation of a cardiac allograft [mean survival time (MST) = 42.8 days]. Removal of the first graft on Day 7 (MST = 16.4 days) but not on Day 3 (MST = 10.2 days) caused donor-specific prolongation of the second allograft survival, which was significantly shorter than that in the recipient without the graftectomy (MST = 32.8 days). When graftectomy was performed on Day 3, there were immunohistochemically detectable levels of donor class II expressing cells in the recipient spleen on Day 7, indicating that the presence of the graft more effectively induced unresponsiveness than microchimerism alone. The additional course of FK506 treatment on Day 35 maintained graft survival (MST > 90.6 days). Removal of the first graft on Day 7 (MST = 13.5 days) or Day 28 (MST = 24.7 days) did not show significant prolongation of the second allograft survival, whereas significant survival prolongation of the second graft was observed in the recipient without the graftectomy (MST = 38.8 days). However, marked survival prolongation of the second donor-specific allograft in half of the recipients that had received the second course of FK506 treatment after graftectomy on Day 28 indicates that residual donor antigen can function as tolerizing antigen with an FK506 supplement. Conclusions. We concluded that the persistence of a graft more effectively induces and maintains donor-specific unresponsiveness than does the chimeric state of graft-derived cells alone under immunosuppression by FK506 in the rat heart transplantation model.

Regulatory T cells (Tregs) play a role in the immunosuppressive state in pancreatic cancer patients. We aimed to evaluate the changes of immune cells population including Tregs caused by gemcitabine (GEM)-based chemotherapy.Fifty-three patients with pancreatic cancer were enrolled in this study, of which 32 received GEM- based chemotherapy. Blood samples were collected before and at least 2 weeks after the last dose of chemotherapy. The peripheral blood mononuclear cells (PBMCs) were subjected to flow cytometry analysis after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Other lymphocytes and NK cell markers were also measured. The proliferative capacity of PBMCs stimulated with anti-CD3 was analyzed using H(3) thymidine.The percentage and number of Tregs were significantly decreased after chemotherapy (p = 0.032, p = 0.003, respectively). The other immune cells and the proliferative capacity did not change.This study showed that GEM-based chemotherapy produced an immunomodulatory effect via the depletion of Tregs.

This study sought to determine whether a prognostic score is a useful indicator of donor safety using 13 consecutive donors enrolled for liver transplantation. The donor operations were right hepatic lobectomies (n = 10) and left hepatic lobectomies (n = 3). The postoperative maximal level of serum total bilirubin was used to assess the magnitude of surgical stress. Variables such as donor age, percentage of liver resection (PLR), indocyanine green 15-minute retention rate (ICGR15), operative blood loss, operation time, prognostic score and graft weight were evaluated as predictors of the magnitude of surgical stress. The PLR and prognostic score (PS) were calculated according to the following formulae: PLR (%) = 100*Graft weight (g)/standard liver volume of the donor (mL); PS = -84.6 + 0.933*PLR (%) +1.11*ICGR15 (%) +0.999*age (years); Standard liver volume (mL) = 706.2*body surface area (m2) + 2.39. No serious complications occurred after the donor operations. Maximal bilirubin ranged from 1.9 to 10.9 mg/dL. There were no mortalities, although there were two morbidities, bile leakage and prolonged liver dysfunction. Postoperative hyperbilirubinemia was observed in two donors and in one Gilbert's syndrome donor. Linear regression analysis of each variable indicated poor correlations between those variables and maximal bilirubin. However, close correlations were seen between maximal bilirubin and both donor age and PS except for the three patients who showed postoperative hyperbilirubinemia. In these uneventful donors, statistical formulae were obtained as follows: maximal bilirubin (PMB) = 0.271 + 0.056*donor age (correlation coefficient 0.612, P.008), PMB = 1.541 + 0.059*PS (correlation coefficient 0.597, P.009). In conclusion, PS is useful to predict maximal bilirubin and to ensure donor safety.

血清GOT, GPT, γ-GTPを157例の健常例および117例の血液透析施行の慢性腎不全患者を対象として対比検討した. その結果, HBs抗原およびHCV抗体両者陰性の血液透析例において, 健常対照例に比して, GOTおよびGPT活性の有意の低値を認め, γ-GTP活性には差を認めなかった. 透析患者および対照例の両群における交絡因子を除外するために, 年齢および肥満の指標としてのbody mass index (BMI) をマッチさせて検討した結果も同様であり, 透析例において, GOTおよびGPTの明らかな低値を認めた. これらの結果から透析患者においてトランスアミナーゼを肝障害の指標とする際には, 正常域上限値を低く設定する必要があり, HBs抗原およびHCV抗体両者陰性のHD例における平均値 (GOT 11.6±4.6IU/l, GPT 8.8±4.4IU/l) に2倍の標準偏差を加えたもの (GOT 21IU/l, GPT 18IU/l) を正常域上限値とすることが妥当と考えられた.

This study identified risk factors associated with prolonged intubation after living donor liver transplantation (LDLT).Out of 50 patients who underwent LDLT, clinical data were compared between those extubated within 4 days of LDLT (early group; n=20) and those extubated 5 days post-LDLT (delayed group; n=30).Univariate analysis associated the following factors with prolonged intubation: preoperative age48 years (p=0.05), body mass index22 kg/m² (p=0.01), creatinine clearance90 mL/min/1.73 m² (p=0.003), ratio between arterial oxygen tension and fractional inspired oxygen ≤375 (p=0.02) and postoperative changes of body-weight per body surface area ((BW - preoperative BW)/BSA)) on postoperative day (POD) 3 (2.0 kg/m²) (p=0.01). Multivariate analysis showed that creatinine clearance and (BW - preoperative BW)/BSA on POD 3 remained as independent predictive factors (p=0.04 and 0.04, respectively).We should aim for postoperative fluid management such that ((BW - preoperative BW)/BSA) ≤2.0 kg/m² on POD 3, especially in patients with low preoperative levels of creatinine clearance.

Background Although short- and long-term results have been described in previous reports of 2-stage hepatectomy, growth activity in metastases resected at the first versus second hepatectomy has not been compared. Methods We analyzed growth activity of liver metastases from colorectal cancers resected at first and second hepatectomy by real-time reverse-transcription polymerase chain reaction and immunohistochemistry in 21 patients undergoing 2-stage hepatectomy to justify the 2-stage approach. Results Of 24 patients planned to undergo 2-stage hepatectomy for colorectal liver metastases, 21 had completion of both stages. Although maximum tumor size and serum carcinoembryonic antigen before and after the first procedure did not differ, volume of the future liver remnant increased after the first procedure. Ki67 and proliferating cell nuclear antigen positivity rates were comparable between initially and subsequently resected tumors ( P = .09 and P = .83, respectively). Expression of mRNA (relative to glyceraldehyde-3-phosphate dehydrogenase mRNA) in initially versus subsequently resected tumors for cyclin D1 (4.27 ± 1.29 vs 6.52 ± 2.23; P = .90), cyclin E1 (24.18 ± 16.81 vs 10.53 ± 2.28; P = .60), hepatocyte growth factor (3.16 ± 1.42 vs 0.58 ± 0.15; P = .11), basic fibroblast growth factor (5.42 ± 1.54 vs 5.92 ± 3.33; P = .13), epidermal growth factor (19.56 ± 14.76 vs 9.07 ± 4.54; P = .74), and transforming growth factor-α (2.63 ± 1.02 vs 2.07 ± 1.15; P = .29) showed no differences between the 2 time points. Conclusion Two-stage hepatectomy did not seem to induce tumor growth activity or growth factor expression. The 2-stage strategy in combination with effective preoperative chemotherapy is a valuable strategy for colorectal metastases.

A 50-year-old man with primary biliary cirrhosis underwent living-donor liver transplantation (LDLT) using a graft of a left hemiliver with a left caudate lobe and duct-to-duct hepaticocholedochostomy. Postoperative bile leakage necessitated percutaneous drainage 22 days after LDLT. The patient presented to our hospital 205 days after the LDLT with abdominal distension and fever. Computed tomography showed ascites and a diffusely mottled pattern in the graft. The caudate lobe was swollen, and its bile ducts were dilated. The inferior vena cava was forced to the right by the swollen caudate lobe, and the root of the hepatic vein was stretched. The hepatic vein was not contrasted. Endoscopic retrograde cholangiography showed a biliary anastomotic stricture. Based on these findings, we diagnosed a severe outflow block of the hepatic vein and biliary anastomotic stricture. We performed balloon dilation of the biliary anastomosis and implanted a metallic stent in the hepatic vein. Thereafter, his clinical symptoms improved dramatically.

Here we reassess anticipated inability to obtain a microscopically clear surgical margin as an absolute contraindication to surgery for colorectal liver metastases in view of improvements in treatment modalities adjunctive to surgery.We retrospectively analysed 310 patients treated at our institution to estimate the survival benefit from R1 hepatectomy performed to remove liver metastases from colorectal cancer.Considering all 310 patients evaluated, the R1 resection group (positive margin; n = 55) showed a lower disease-free rate (P 0.01) and worse overall survival (P 0.01) than the R0 resection group (negative margin; n = 255). When patients were divided according to initial resectability, similar differences in disease-free rate and overall survival (P = 0.03) between R1 (n = 19) and R0 (n = 182) were observed in patients whose metastases were resectable. However, superior impact of R0 resection (n = 73) compared to R1 resection (n = 36) on disease-free rate (P = 0.44) and overall survival (P = 0.50) was not confirmed in patients with initially unresectable or marginally resectable metastases, especially those with a favourable response to prehepatectomy chemotherapy.A predicted positive surgical margin after resection no longer should be an absolute contraindication to surgery for aggressive or advanced liver metastases.

A 27-year-old Japanese man underwent liver transplantation because of uncompensated cirrhosis due to Dorfman-Chanarin syndrome (DCS). At birth, the patient displayed ichthyosis and liver dysfunction. Moreover, mental retardation appeared and intracytoplasmic vacuoles were observed within peripheral blood neutrophils. A fatty liver was also noticed, leading to the diagnosis of DCS. When he was referred to our hospital, his American Society of Anesthesiologists score was 3. The findings of computed tomography showed liver atrophy, splenomegaly, and ascites. The Child-Pugh score was B, and the Model for End-stage Liver Disease score was 14. The pathophysiology was DCS with uncompensated liver cirrhosis. Therefore, living donor liver transplantation (LDLT) was performed from the patient's brother. The histological appearance of the resected liver revealed macrovesicular steatosis in most hepatocytes with excess fibrous tissue in the portal areas. These findings were compatible with nonalcoholic steatohepatitis. Although the patient's mental retardation and characteristic appearance have not improved, good liver function has been maintained since LDLT. An outpatient protocol liver biopsy performed at 12 months after LDLT did not show recurrence of macrovesicular steatosis.

AIM: To clarify short- and long-term outcomes of combined resection of liver with major vessels in treating colorectal liver metastases. METHODS: Clinicopathologic data were evaluated for 312 patients who underwent 371 liver resections for metastases from colorectal cancer. Twenty-five patients who underwent resection and reconstruction of retrohepatic vena cava, major hepatic veins, or hepatic venous confluence during hepatectomies were compared with other patients, who underwent conventional liver resections. RESULTS: Morbidity was 20% (75/371) and mortality was 0.3% (1/312) in all patients after hepatectomy. Hepatic resection combined with major-vessel resection/reconstruction could be performed with acceptable morbidity (16%) and no mortality. By multivariate analysis, repeat liver resection (relative risk or RR, 5.690; P = 0.0008) was independently associated with resection/reconstruction of major vessels during hepatectomy, as were tumor size exceeding 30 mm (RR, 3.338; P = 0.0292) and prehepatectomy chemotherapy (RR, 3.485; P = 0.0083). When 312 patients who underwent a first liver resection for initial liver metastases were divided into those with conventional resection (n = 296) and those with combined resection of liver and major vessels (n = 16), overall survival and disease-free rates were significantly poorer in the combined resection group than in the conventional resection group (P = 0.02 and P < 0.01, respectively). A similar tendency concerning overall survival was observed for conventional resection (n = 37) vs major-vessel resection combined with liver resection (n = 7) performed as a second resection following liver recurrences (P = 0.09). Combined major-vessel resection at first hepatectomy (not performed; 0.512; P = 0.0394) and histologic major-vessel invasion at a second hepatectomy (negative; 0.057; P = 0.0005) were identified as independent factors affecting survival by multivariate analysis. CONCLUSION: Hepatic resection including major-vessel resection/reconstruction for colorectal liver metastases can be performed with acceptable operative risk. However, such aggressive approaches are beneficial mainly in patients responding to effective prehepatectomy chemotherapy.

A 47-year-old Japanese man was transferred to our hospital because of acute-on-chronic hepatitis B virus infection. On admission, he was suffering from sepsis due to a catheter infection and respiratory failure caused by pulmonary edema and pneumonia, but, as a result of preoperative intensive care, we avoided septic shock. ABO-incompatible liver transplantation (ABO-I-LT) was performed. In accordance with our ABO-I-LT protocol, we administered, rituximab and performed plasma exchange, splenectomy as well as hepatic artery infusion. The patient was discharged 80 days after living donor transplantation (LDLT). However, 136 days after LDLT, he experienced recurrent respiratory failure due to severe pneumonia. At that time, the CD19(+) B-cell count in the peripheral blood flow remained below 1%. We suspected a mixed infection involving Streptococcus pneumonia, Pneumocystis carinii, and fungus. The cause of the complication was overwhelming postsplenectomy infection (OPSI). We started administration of sulfamethoxazole and trimethoprim, ciprofloxacin hydrochloride, and micafungin sodium therapy as well as gamma-globulin. Oxygenation improved gradually; the patient was discharged at 41 days after re-admission. Although this patient survived the OPSI, it was clear that some aspects of the ABO-I-LT protocol should also be altered.

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly. Risk factors include old age, female gender, obesity, smoking, low dietary intakes of antioxidants and increased exposure to the toxic metal cadmium (Cd(2+)). Supplementation with high-dose zinc (80 mg) provides some protection, but the mechanism(s) underlying such protection has not been fully elucidated. The present study had a focus on the human retinal pigment epithelial (RPE) cell line ARPE-19 in an attempt to demonstrate a reduction in intracellular Cd(2+) effect associated with heme oxygenase-1 (HO-1) expression by co-exposure with zinc (Zn(2+)) or manganese (Mn(2+)), which is known to be a more potent inhibitor of Cd(2+) uptake than Zn(2+). Our results indicated that co-exposure of 10 microM Cd(2+) with 5 microM Mn(2+) reduced the intracellular Cd(2+) effect by 50-60%, possibly by limiting the amounts of Cd(2+) entering cells through Mn(2+) transporter protein (ZIP8). A similar reduction in a Cd(2+) effect was achieved by co-exposure with 20 microM Zn(2+) while co-exposure with 5 and 10 microM Zn(2+) ions was ineffective. Mn(2+) ions as low as 2.5 microM were found to cause an increase in HO-1 mRNA expression levels in ARPE-19 cells, demonstrating for the first time that Mn(2+) is an inducer of HO-1. Mn(2+) ions at 1 microM induced HO-1 mRNA expression in the HEK293 human embryonic kidney cells. In contrast, Zn(2+) in 5, 10 or 20 microM concentrations did not induce expression of HO-1 in ARPE-19 cells or any other cells tested. These data suggest the superiority of Mn(2+) over Zn(2+) in preventing Cd(2+) uptake and accumulation in RPE to toxic levels. Further, induction of HO-1 by Mn(2+) could provide RPE with some resistance to enhanced oxidative stress arising from Cd(2+) accumulation in RPE as HO-1 is one of the frontline cellular antioxidant defense mechanisms.

Patients with hepatocellular carcinoma (HCC) who undergo liver resection and transplantation are predicted to have a poor outcome if the disease is associated with vascular invasion. This study aimed to identify preoperative predictors of microvascular invasion in patients with HCCs larger than 5 cm. From May 1992 to October 2005, 231 patients underwent curative hepatic resection for HCC. Of these, 96 patients had HCCs larger than 5 cm. Analysis was limited to patients without macroscopic vascular invasion (n = 65). Multivariate analysis showed that patients with tumors larger than 7 cm and type 2 (single nodular type with extranodular growth) and type 3 (contiguous multinodular type formed by a cluster of small and contiguous nodules) tumors had an increased risk of microscopic vascular invasion. The overall incidence of microscopic vascular invasion was 46.2% (n = 30), but only 12.5% (2/16) in patients with type 1 tumors (single nodular type that is approximately round with a clear demarcation) measuring less than 7 cm. Larger tumors (>7 cm) and type 2 and type 3 tumors are strong predictors of microvascular invasion in patients with HCCs larger than 5 cm.

A 29-year-old man was referred to our hospital with fulminant hepatic failure (FHF) and stage III hepatic coma (somnolence and confusion). Living donor liver transplantation (LDLT) was planned for 2 days after admission to our hospital. However, on the day after admission, he lapsed into stage IV hepatic coma: no right reflexes and no response to pain stimuli. Emergency cranial computed tomography revealed a subarachnoid hemorrhage (SAH), but no aneurysm was seen on magnetic resonance angiography. We speculated that the cause of the SAH may have been bleeding of intracranial veins secondary to coagulopathy and overextension of a vein due to brain edema. We considered that only LDLT could improve the coagulopathy and brain edema. The patient recovered consciousness on postoperative day (POD) 2 and was finally discharged from the hospital without neurological deficit on POD 85. This case suggested that SAH is not a prohibiting factor for LDLT in an FHF patient if the cause of the SAH is venous bleeding.

BACKGROUND: The clinical symptoms, histological findings, and treatments for antibody-mediated rejection (AMR), which is the leading cause of graft loss in adult ABO-incompatible liver transplantation (ABO-I-LT), have rarely been discussed. METHODS: We performed adult living donor ABO-I-LT on six patients. We used anti-CD20 monoclonal antibody combined with plasma exchange preoperatively and intraportal or hepatic-arterial infusion, consisting of prostaglandin E1, corticosteroids, and protease inhibitor postoperatively to prevent AMR. Splenectomy was performed in patients 1, 4, 5 and 6 but not in patients 2 and 3. Weekly liver biopsies were performed after ABO-I-LT. When severe AMR was diagnosed, we performed plasma exchange combined with gamma-globulin bolus infusion (PE+IVIG). RESULTS: In patients 1-3, severe jaundice, rapid decreases in platelet counts, and severe coagulopathy were observed in the early postoperative period. Liver biopsies sampled after the onset of these clinical findings were characterized by severe periportal and lobular hemorrhagic and neutrophil infiltration, suggesting that severe AMR occurred. However, after the initiation of PE+IVIG, AMR was remedied in all three patients. In patients 4-6, severe AMR was not observed. Mild AMR characterized by mild portal hemorrhagic infiltration was observed in patient 4, and moderate AMR characterized by moderate periportal and lobular hemorrhagic infiltration was observed in patient 6. Patients 4-6 did not require PE+IVIG and their clinical course was uneventful. CONCLUSION: Given the experience of these six patients, we consider that AMR may be graded based on liver biopsy findings including hemorrhagic infiltration and neutrophil infiltration, as well as clinical findings. All six patients are currently doing well.