Multicenter prospective trial of total gastrectomy versus proximal gastrectomy for upper third cT1 gastric cancer.

BACKGROUND: The appropriate surgical procedure for patients with upper third early gastric cancer is controversial. We compared total gastrectomy (TG) with proximal gastrectomy (PG) in this patient population. METHODS: A multicenter, non-randomized trial was conducted, with patients treated with PG or TG. We compared short- and long-term outcomes between these procedures. RESULTS: Between 2009 and 2014, we enrolled 254 patients from 22 institutions; data from 252 were included in the analysis. These 252 patients were assigned to either the PG (n = 159) or TG (n = 93) group. Percentage of body weight loss (%BWL) at 1 year after surgery, i.e., the primary endpoint, in the PG group was significantly less than that of the TG group (- 12.8% versus - 16.9%; p = 0.0001). For short-term outcomes, operation time was significantly shorter for PG than TG (252 min versus 303 min; p < 0.0001), but there were no group-dependent differences in blood loss and postoperative complications. For long-term outcomes, incidence of reflux esophagitis in the PG group was significantly higher than that of the TG group (14.5% versus 5.4%; p = 0.02), while there were no differences in the incidence of anastomotic stenosis between the two (5.7% versus 5.4%; p = 0.92). Overall patient survival rates were similar between the two groups (3-year survival rates: 96% versus 92% in the PG and TG groups, respectively; p = 0.49). CONCLUSIONS: Patients who underwent PG were better able to control weight loss without worsening the prognosis, relative to those in the TG group. Optimization of a reconstruction method to reduce reflux in PG patients will be important.

Functional characterization of recombinant snake venom rhodocytin: rhodocytin mutant blocks CLEC-2/podoplanin-dependent platelet aggregation and lung metastasis.

Essentials We generated recombinant rhodocytin that could aggregate platelets via CLEC-2. Recombinant wild-type rhodocytin formed heterooctamer with four α- and ß-subunits. Asp 4 in α-subunit of rhodocytin was required for binding to CLEC-2. Inhibitory mutant of rhodocytin blocked podoplanin-dependent hematogenous metastasis. SUMMARY: Background Rhodocytin, a disulfide-linked heterodimeric C-type lectin from Calloselasma rhodostoma consisting of α-subunits and ß-subunits, induces platelet aggregation through C-type lectin-like receptor 2 (CLEC-2). CLEC-2 is a physiological binding partner of podoplanin (PDPN), which is expressed on some tumor cell types, and is involved in tumor cell-induced platelet aggregation and tumor metastasis. Thus, modified rhodocytin may be a possible source of anti-CLEC-2 drugs for both antiplatelet and antimetastasis therapy. However, its molecular function has not been well characterized, because of the lack of recombinant rhodocytin that induces platelet aggregation. Objective To produce recombinant rhodocytin, in order to verify its function with mutagenesis, and to develop an anti-CLEC-2 drug based on the findings. Methods We used Chinese hamster ovary cells to express recombinant rhodocytin (wild-type [WT] and mutant), which was analyzed for induction/inhibition of platelet aggregation with light transmission aggregometry, the formation of multimers with blue native PAGE, and binding to CLEC-2 with flow cytometry. Finally, we investigated whether mutant rhodocytin could suppress PDPN-induced metastasis in an experimental lung metastasis mouse model. Results Functional WT] rhodocytin (αWTßWT) was obtained by coexpression of both subunits. Asp4 in α-subunits of rhodocytin was required for CLEC-2 binding. αWTßWT formed a heterooctamer similarly to native rhodocytin. Moreover, an inhibitory mutant of rhodocytin (αWTßK53A/R56A), forming a heterotetramer, bound to CLEC-2 without inducing platelet aggregation, and blocked CLEC-2-PDPN interaction-dependent platelet aggregation and experimental lung metastasis. Conclusion These findings provide molecular characterization information on rhodocytin, and suggest that mutant rhodocytin could be used as a therapeutic agent to target CLEC-2.

Outflow Reconstruction Using Cryopreserved Homologous Venous Grafts in Living Donor Liver Transplantation.

OBJECTIVES: The techniques and outcomes of outflow reconstruction in living donor liver transplantation (LDLT) using cryopreserved homologous veins at the University of Tokyo Hospital are presented. METHODS: We performed 540 LDLTs from January 1996 to March 2015. Graft types included right liver graft (n = 262), left liver graft (n = 196), left lateral sector graft (n = 53), and posterior sector graft (n = 28). We routinely use cryopreserved homologous vein grafts for the hepatic vein reconstructions to secure the large outflow of the graft. In addition to the presentation of our techniques, the cases with symptomatic outflow obstruction and the treatments were also investigated. RESULTS: The 1-, 3-, and 5-year graft survival rates were 90.6%, 86.1%, and 83.5%, respectively. The incidence of severe complications (Clavien-Dindo grade IIIb and more) was 38%. The overall incidence of outflow obstruction requiring invasive treatment was 1.9% (10/540), including 3 left liver grafts (1.5%, 3/196) and 7 right liver grafts (2.7%, 7/262). Regarding the patency of the reconstructed veins, the left hepatic vein, middle hepatic vein, and right hepatic vein achieved nearly 100% patency. On the contrary, venous tributaries such as V5, V8, and inferior right hepatic vein were frequently occluded in the postoperative course. CONCLUSIONS: Outflow reconstruction is a key for the successful LDLT. Cryopreserved homologous vein graft is useful for the promising hepatic vein reconstruction.

Multicenter randomized phase II study of cisplatin and fluorouracil plus docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as preoperative chemotherapy for resectable esophageal squamous cell carcinoma (OGSG1003).

BACKGROUND: This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC. PATIENTS AND METHODS: Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat. RESULTS: Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33-0.83, P = 0.0057) and 78.6% versus 65.4% (P = 0.08), respectively. CONCLUSION: Compared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).

C-type lectin-like receptor 2 promotes hematogenous tumor metastasis and prothrombotic state in tumor-bearing mice.

Essentials The role of C-type lectin-like receptor-2 (CLEC-2) in cancer progression is unclear. CLEC-2-depleted mouse model is generated by using a rat anti-mouse CLEC-2 monoclonal antibody. CLEC-2 depletion inhibits hematogenous tumor metastasis of podoplanin-expressing B16F10 cells. CLEC-2 depletion prolongs cancer survival by suppressing thrombosis and inflammation. SUMMARY: Background C-type lectin-like receptor 2 (CLEC-2) is a platelet activation receptor of sialoglycoprotein podoplanin, which is expressed on the surface of certain types of tumor cells. CLEC-2-podoplanin interactions facilitate hematogenous tumor metastasis. However, direct evidence of the role of CLEC-2 in hematogenous metastasis and cancer progression is lacking. Objective and methods We generated immunological CLEC-2-depleted mice by using anti-mouse CLEC-2 monoclonal antibody 2A2B10 and investigated whether CLEC-2 promoted hematogenous tumor metastasis and tumor growth and exacerbated the prognosis of mice bearing podoplanin-expressing B16F10 melanoma cells. Results Our results showed that hematogenous metastasis was significantly inhibited in CLEC-2-depleted mice. B16F10 cells co-cultured with wild-type platelets, but not with CLEC-2-deficient platelets, showed increased proliferation. However, B16F10 cell proliferation was not inhibited in CLEC-2-depleted mice. Histological analysis showed that thrombus formation in tumor vessels was significantly inhibited and functional vessel density was significantly increased in CLEC-2-depleted mice. These data suggest that CLEC-2 deficiency may inhibit thrombus formation in tumor vessels and increase the density of functional vessels, thus improving oxygen and nutrient supply to tumors, indirectly promoting tumor proliferation. Furthermore, the overall survival of CLEC-2-depleted mice was significantly prolonged, which may be due to the suppression of thrombus formation in the lungs and subsequent inhibition of systemic inflammation and cachexia. Conclusions These data provide a rationale for the targeted inhibition of CLEC-2 as a new strategy for preventing hematogenous tumor metastasis and for inhibiting cancer-related thromboembolism.

Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer.

BACKGROUND: Survivin and monoamine oxidase A (MAOA) levels are elevated in prostate cancer (PCa) compared to normal prostate glands. However, the relationship between survivin and MAOA in PCa is unclear. METHODS: We examined MAOA expression in the prostate lobes of a conditional PTEN-deficient mouse model mirroring human PCa, with or without survivin knockout. We also silenced one gene at a time and examined the expression of the other. We further evaluated the combination of MAOA inhibitors and survivin suppressants on the growth, viability, migration and invasion of PCa cells. RESULTS: Survivin and MAOA levels are both increased in clinical PCa tissues and significantly associated with patients' survival. Survivin depletion delayed MAOA increase during PCa progression, and silencing MAOA decreased survivin expression. The combination of MAOA inhibitors and the survivin suppressants (YM155 and SC144) showed significant synergy on the inhibition of PCa cell growth, migration and invasion with concomitant decrease in survivin and MMP-9 levels. CONCLUSIONS: There is a positive feedback loop between survivin and MAOA expression in PCa. Considering that survivin suppressants and MAOA inhibitors are currently available in clinical trials and clinical use, their synergistic effects in PCa support a rapid translation of this combination to clinical practice.

Relationship between serotonin transporter occupancies and analgesic effects of AS1069562, the (+)-isomer of indeloxazine, and duloxetine in reserpine-induced myalgia rats.

Serotonin (5-HT) and norepinephrine (NE) have been implicated in the mediation of endogenous analgesic mechanisms via the descending inhibitory pain pathway in the brain, and dysfunction in both the 5-HT and NE systems has been suggested as an etiology of fibromyalgia (FM). Given that 5-HT reuptake inhibition in the brain appears to be associated with pain reduction, this mechanism might exert an analgesic effect also on pain associated with FM. In this case, it would be of interest to investigate the correlation of 5-HT transporter (SERT) occupancy with in vivo analgesic effect on pain associated with FM. Here, we investigated the relationship between SERT occupancies and the analgesic effects of AS1069562, the (+)-isomer of indeloxazine, and duloxetine, which are both 5-HT and NE reuptake inhibitors (SNRIs), on muscular pain in reserpine-induced myalgia (RIM) rats, an animal model of FM-like chronic pain. We also investigated the SERT occupancy level necessary for AS1069562 and duloxetine to exert analgesic effects on muscular pain. AS1069562 and duloxetine attenuated muscular hyperalgesia in RIM rats, representing the first findings to be reported regarding the analgesic effect of AS1069562 on pain associated with FM. SERT occupancy levels of AS1069562 and duloxetine increased in both dose- and plasma and brain concentration-dependent manners. SERT occupancy levels of AS1069562 and duloxetine were significantly correlated with efficacy on muscular pain thresholds in RIM rats. This finding concerning the precise correlation of SERT occupancy with in vivo analgesic effect on pain associated with FM is reported here for the first time. SERT occupancy level above 70% was necessary for AS1069562 and duloxetine to exert significant analgesic effects on muscular pain. These results suggest that SERT occupancy level is useful in determining appropriate analgesic doses of AS1069562 and duloxetine for treating pain symptoms in FM patients.

The real impact of telaprevir dosage on the antiviral and side effects of telaprevir, pegylated interferon and ribavirin therapy for chronic hepatitis C patients with HCV genotype 1.

Triple therapy with telaprevir, pegylated interferon and ribavirin has been reported to improve antiviral efficacy but have potentially severe adverse effects in patients with chronic hepatitis C. To avoid the severe effects of telaprevir, lowering the dose has been suggested. However, impact of dosage changes on antiviral and adverse effects remains unclear. One hundred and sixty-six Japanese patients with HCV genotype 1 were treated with triple therapy. The drug exposure of each medication was calculated by averaging the dose actually taken. The overall SVR rate was 82%. The telaprevir discontinuation rate was 26%. The factors associated with discontinuation were an older age (≥65 y.o.) and a higher average dose during treatment. The telaprevir discontinuation rates were 42%, 25% and 14% in patients at ≥35, 25-35 and <25 mg/kg/day of telaprevir and 58% in older patients at ≥35 mg/kg/day of TVR. The factors associated with SVR were treatment-naïve, relapse to previous treatment, higher average telaprevir dose during treatment and completion of treatment. The SVR rate was higher, at 91%, in patients at 25-35 mg/kg/day of telaprevir than the 71% and 78% observed in those at <25 and ≥35 mg/kg/day of drug. In Japanese patients, a mean telaprevir dose of 25-35 mg/kg/day during treatment can augment its efficacy in triple therapy for patients with HCV genotype 1.

Risk factors for hepatocellular carcinoma in hepatitis C patients with normal alanine aminotransferase treated with pegylated interferon and ribavirin.

Pegylated interferon (Peg-IFN) plus ribavirin combination therapy is effective in patients with hepatitis C virus (HCV) infection and normal alanine aminotransferase levels (NALT). However, it remains unclear whether the risk of hepatocellular carcinoma (HCC) incidence is actually reduced in virological responders. In this study, HCC incidence was examined for 809 patients with NALT (ALT ≤ 40 IU/mL) treated with Peg-IFN alpha-2b and ribavirin for a mean observation period of 36.2 ± 16.5 months. The risk factors for HCC incidence were analysed by Kaplan-Meier method and Cox proportional hazards model. On multivariate analysis among NALT patients, the risk of HCC incidence was significantly reduced in patients with sustained virological response (SVR) or relapse compared with those showing nonresponse (NR) (SVR vs NR, hazard ratio (HR): 0.16, P = 0.009, relapse vs NR, HR: 0.11, P = 0.037). Other risk factors were older age (≥65 years vs <60 years, HR: 6.0, P = 0.032, 60-64 vs <60 years, HR: 3.2, P = 0.212) and male gender (HR: 3.9, P = 0.031). Among 176 patients with PNALT (ALT ≤ 30 IU/mL), only one patient developed HCC and no significant risk factors associated with HCC development were found. In conclusion, antiviral therapy for NALT patients with HCV infection can lower the HCC incidence in responders, particularly for aged and male patients. The indication of antiviral therapy for PNALT (ALT ≤ 30 IU/mL) patients should be carefully determined.

Differences in the locations and modes of labral tearing between dysplastic hips and those with femoroacetabular impingement.

We investigated differences in the location and mode of labral tears between dysplastic hips and hips with femoroacetabular impingement (FAI). We also investigated the relationship between labral tear and adjacent cartilage damage. We retrospectively studied 72 symptomatic hips (in 68 patients: 19 men and 49 women) with radiological evidence of dysplasia or FAI on high-resolution CT arthrography. The incidence and location of labral tears and modes of tear associated with the base of the labrum (Mode 1) or body of the labrum (Mode 2) were compared among FAI, mildly dysplastic and severely dysplastic hips. The locations predominantly involved with labral tears were different in FAI and mild dysplastic hips (anterior and anterosuperior zones) and in severely dysplastic hips (anterosuperior and superior zones) around the acetabulum. Significant differences were observed in the prevalence of Mode 1 versus Mode 2 tears in FAI hips (72% (n = 13) vs 28% (n = 5)) and severe dysplastic hips (25% (n = 2) vs 75% (n = 6)). The frequency of cartilage damage adjacent to Mode 1 tears was significantly higher (42% (n = 14)) than that adjacent to Mode 2 tears (14% (n = 3)). Hip pathology is significantly related to the locations and modes of labral tears. Mode 1 tears may be a risk factor for the development of adjacent acetabular cartilage damage.

Influence of medial meniscectomy on stress distribution of the femoral cartilage in porcine knees: a 3D reconstructed T2 mapping study.

OBJECTIVE: Previous studies have shown that meniscectomy results in an increase of local load transmission and may cause degeneration of the knee cartilage. Using 3D reconstructed T2 mapping, we examined the influence on the femoral cartilage under loading after medial meniscectomy. DESIGN: Ten porcine knees were imaged using a pressure device and a 3.0-T magnetic resonance imaging (MRI) system. Consecutive sagittal T2 maps were obtained in neutral alignment with and without compression, and under compression at 10° varus alignment. After medial meniscectomy, the aforementioned MRI was repeated. Cartilage T2 before and after meniscectomy under each condition were compared at the 12 regions of interest (ROIs) defined on the 3D weight-bearing area of the femoral cartilage. RESULTS: Before meniscectomy, large decreases in T2 under neutral compression were mainly seen at the anterior and central ROIs of the medial cartilage, which shifted to the posterior ROIs after meniscectomy. There were significant differences in decrease in T2 ratio with loading before and after meniscectomy (9.8%/4.3% at the anterior zone, 4.0%/11.4% at the posterior zone, P < 0.05). By applying varus compression, a more remarkable decrease in the cartilage T2 in posterior ROIs after meniscectomy was achieved. (Before/after meniscectomy: 8.7%/2.5% at the anterior zone, 7.2%/18.7% at the posterior zone, P < 0.05). CONCLUSIONS: Assuming a decrease in T2 with loading correlated with the applied pressure, a deficiency of the medial meniscus resulted in a shift of the primary area with a maximal decrease of cartilage T2 with loading posteriorly in the porcine knee joint, presumably reflecting the intraarticular environment of load transmission.

Standardization of perioperative management on hepato-biliary-pancreatic surgery.

Japan-China Joint Medical Workshop (2012) on standardization of perioperative management on hepato-biliary-pancreatic surgery was held by the Center for Medical Standards Research, IRCA-BSSA Group in Japan on April 15-16, 2012. Experts in the fields of surgery, anesthesia, pharmacy, and public health from 21 health institutions from Japan and China presented their research achievements and shared their medical experience of perioperative management on hepato-biliary-pancreatic surgery, which should facilitate building of guidelines for hepatocellular carcinoma and be expected to promote standardized management of liver cancer in Asia.

Preemptive antiviral treatment for hepatitis C virus after living donor liver transplantation.

BACKGROUND: Recurrence following liver transplantation for hepatitis C virus (HCV), which is universal, affects long-term outcomes. Treatment with interferon (IFN) and ribavirin (RBV), the only widely available options at this time, have been faced with low tolerability and overall unsatisfactory results in deceased donor liver transplantation (DDLT). However, its place after living donor liver transplantation (LDLT) remains a matter of debate. Since most LDLT cases are performed in a planned manner at a lower Model for End-stage Liver Disease (MELD) score compared to DDLT, we have aggressively applied preemptive INF/RBV in our series. PATIENTS AND METHODS: We studied 122 adult recipients who underwent LDLT for HCV-related end-stage liver disease. The preemptive IFN/RBV protocol initiated treatment promptly after improvement in the patient's general condition with a low-dose IFN alpha2b and RBV (400 mg/d) followed by a gradual increase in the INFalpha2b dosage. Finally, we applied pegylated IFN (1.5 ug/kg/wk) and RBV (800 mg/d). The treatment was continued for 12 months after serum HCV-RNA became negative, which was defined as the end-of-treatment response (ETR). The response was considered to be a sustained viral response (SVR) if there were negative serologic results without antiviral treatment for another 6 months. Splenectomy was performed at the time of LDLT to improve tolerability to INF/RBV. The median age of the patients was 55 yrs (range = 23-66), with male dominance (87 males and 35 females). Median MELD score was 14 (range = 6-48). The series included 72 patients with hepatocellular carcinomas, and six with HIV coinfections. In 98 cases, HCV genotype was 1b. RESULTS: Overall survival at 5 years was 79%. Cumulative response rates under the protocol were ETR 56% and SVR 44% at 5 years. CONCLUSIONS: Preemptive IFN/RBV therapy after LDLT for HCV is feasible with acceptable outcomes.

Three-dimensional patterns of early acetabular cartilage damage in hip dysplasia; a high-resolutional CT arthrography study.

OBJECTIVE: The purpose of this study was to examine the three-dimensional (3D) progression patterns of early acetabular cartilage damage in hip dysplasia using high-resolutional computed tomography (CT) arthrography. DESIGN: Thirty-two dysplastic hips of 26 Japanese symptomatic females including 21 hips in pre-stage of osteoarthritis (Kellgren-Lawrence (K-L) grade 0; mean patient age, 32.0 years) and 11 hips in early stage of osteoarthritis (K-L grade 1 or 2; mean patient age, 32.8 years) were examined. Isotropic high-resolutional CT arthrography with an image resolution of 0.5 mm in any orthogonal direction was performed. A 3D acetabular cartilage model was generated and we evaluated distribution of cartilage thickness in 12 zones after dividing the weight-bearing area of the hip joint in radial and lateral/medial directions. RESULTS: In pre-stage of osteoarthritis, significant differences in cartilage thickness were observed between the lateral and medial zones in all radial regions, most prominently in the antero-superior region. In early stage of osteoarthritis, no significant differences in cartilage thickness were observed, except in the most posterior region. The lateral-medial (LM) ratio was defined as cartilage thickness in the lateral zone divided by that in the medial zone, and hips with the LM ratio in the antero-superior region of <1.4 had significantly more extensive involvement of labral tears than hips with the LM ratio of ≥1.4. CONCLUSIONS: In hip dysplasia, acetabular cartilage damage was probably occurred in the antero-superior lateral area. The LM ratio may be a sensitive index to quantify early cartilage damage associated with extent of labral disorders.

Model for end-stage liver disease and model for end-stage liver disease-Na scores predict both before-listing and wait-list mortality.

BACKGROUND: Due to the organ shortage, many patients die without transplantation, even before completing an evaluation for candidacy. We analyzed outcomes after patient referral and factors associated with mortality both before and after listing for cadaveric donor liver transplantation. METHODS: We analyzed 132 consecutive patients who were evaluated for candidacy for cadaveric donor liver transplantation between 2003 and 2010. RESULTS: The study included 69 men and 63 women of median age 49 years (range, 1-65). Etiologies of diseases were acute hepatic failure (n=19), liver cirrhosis due to hepatitis B or C (n=36), primary biliary cirrhosis (n=19), nonviral cirrhosis (n=14), hepatocellular carcinoma (n=13), or other causes (n=31). After evaluation for candidacy, we listed 68 (52%), subjects whereas 24 (18%) died before listing. Factors affecting death before listing were the levels of albumin (P<.001), bilirubin (P<.001), sodium (P<.001), international normalized ratio (INR; P<.001), Model for End-stage Liver Disease (MELD) score (P<.001), MELD-Na score (P<.001), and Child-Pugh-Turcotte (CPT) score (P<.001). Based on multivariate Cox regression analysis, MELD score (hazard ratio [HR] 1.201, P=.017), MELD-Na score (HR 1.244, P=.014), CPT score (HR 1.468, P=.033), and INR (HR 0.491, P=.027) were independently associated with death before listing. Among 68 listed candidates, 11 (16%) underwent transplantation, whereas 29 (43%) died without transplantation. Based on multivariate Cox regression analysis, MELD score (HR 1.102, P=.001), MELD-Na score (HR 1.128, P=.001), and CPT score (HR 1.282, P=.038) independently predicted wait-list mortality. All 11 patients who underwent cadaveric liver transplantation were alive at 29 months (range, 1-55) after transplantation. CONCLUSIONS: Patients with a higher MELD, higher MELD-Na, and higher CPT score at referral were at greater risk for death without transplantation, especially before listing. Evaluation for transplantation candidacy is a time-consuming process. Therefore, earlier referral is mandatory to achieve successful listing for transplantation.

Resection of the second portion of the duodenum sacrificing the minor papilla but preserving the pancreas for a recurrent duodenal adenocarcinoma: report of a case.

Duodenal adenocarcinoma is a relatively rare malignancy and pancreaticoduodenectomy would be a standard procedure to achieve curative resection. We report a case of resection of the 2nd portion of the duodenum with nodal dissection preserving the pancreas. The patient was a 75-year-old man with right-sided paresis suffering from early cancer in the 2nd portion of the duodenum. Despite 3 times of endoscopic mucosal resections, mucosal local recurrence was found. The depth of the tumour involvement continued to be limited within the mucosal layer. We performed segmental duodenal resection with nodal dissection sacrificing the minor papilla, while preserving the pancreas and the major papilla. The pathological diagnosis was primary intramucosal adenocarcinoma; the surgical margin was negative for cancer and there was no nodal metastasis. This procedure can be an alternative to pancreaticoduodenectomy in patients with earlystage adenocarcinoma in the 2nd portion of the duodenum when the major papilla can be spared, especially in high-risk patients.

Phase II trial of preoperative S-1 plus cisplatin followed by surgery for initially unresectable locally advanced gastric cancer.

BACKGROUND: The aim of this study was to evaluate the efficacy and feasibility of preoperative chemotherapy with S-1 plus cisplatin in patients with initially unresectable locally advanced gastric cancer. METHODS: We enrolled patients with initially unresectable locally advanced gastric cancer because of severe lymph node metastases or invasion of adjacent structures. Preoperative chemotherapy consisted of S-1 at 80 mg/m(2) divided in two daily doses for 21 days and cisplatin at 60 mg/m(2) intravenously on day 8, repeated every 35 days. If a tumor decreased in size, patients received 1 or 2 more courses. Surgery involved radical resection with D2 lymphadenectomy. RESULTS: Between December 2000 and December 2007, 27 patients were enrolled on the study. No CR was obtained, but PR was seen in 17 cases, and the response rate was 63.0%. Thirteen patients (48.1%) had R0 resections. There were no treatment related deaths. The median overall survival time (MST) and the 3-year overall survival (OS) of all patients were 31.4 months and 31.0%, respectively. Among the 13 patients who underwent curative resection, the median disease-free survival (DFS) and the 3-year DFS were 17.4 months and 23.1%, respectively. The MST and the 3-year OS were 50.1 months and 53.8%, respectively. The most common site of initial recurrence after the R0 resection was the para-aortic lymph nodes. CONCLUSIONS: Preoperative S-1 plus cisplatin can be safely delivered to patients undergoing radical gastrectomy. This regimen is promising as neoadjuvant chemotherapy for resectable gastric cancer. For initially unresectable locally advanced gastric cancer, new trials using more effective regimens along with extended lymph node dissection are necessary.

Reduced risk of hepatocellular carcinoma after interferon therapy in aged patients with chronic hepatitis C is limited to sustained virological responders.

This study was undertaken to investigate the effect of interferon (IFN) monotherapy on the risk of hepatocellular carcinoma (HCC) in aged-patients with chronic hepatitis C. Seven hundred and twenty-five patients with histologically proven chronic hepatitis C were enrolled in this retrospective cohort study; 531 received IFN monotherapy for 6 months between 1992 and 1995, and 157 were collected as a historical control. The effect of IFN therapy on the development of HCC was compared between the patients with chronic hepatitis C under 60 years old (non-aged group, n = 531) and those 60 and over (aged group, n = 194). A stepwise Cox proportional-hazards regression analysis in the non-aged group revealed that IFN therapy (risk ratio 0.52, 95% CI 0.33-0.81, P = 0.004), older age (P = 0.001), and higher histological stage (P < 0.001) were independent factors associated with the development of HCC. In the aged-group, only higher histological stage (P = 0.002) and male gender (P = 0.011), but not IFN therapy (risk ratio 0.77, 95% CI 0.42-1.40, P = 0.386), were identified as independent risk factors for HCC, although HCC was significantly reduced when sustained virological response (SVR) was obtained (risk ratio 0.23, 95% CI 0.08-0.64, P = 0.005). In conclusion, inhibitory effect of IFN on development of HCC in the patients with chronic hepatitis C aged 60 and over was limited to the patients achieving SVR when treated with 6 months-IFN monotherapy.

[Myxoid type of malignant fibrous histiocytoma in the anterior mediastinum; report of a case].

A 58-year-old man was admitted to our hospital complaining of right chest pain. Chest X-ray and chest computed tomography (CT) disclosed a 9 cm mass in the right anterior mediastinum. The tumor demonstrated low signal intensity on T1-weighted images, and high signal intensity on T2-weighted images. It showed delayed enhancement on dynamic magnetic resonance (MR). The operation was performed and the tumor including the infiltrated pericardium and upper and middle lobe of right lung was resected. Histologically, the tumor showed a multinodular proliferation of spindle-shaped or polygonal tumor cells with abundant myxoid background. The histopathological diagnosis of the tumor was myxoid malignant fibrous histiocytoma (MFH). This is a case report of primary myxoid MFH in the anterior mediastinum. The case is rare in its primary site, but it is typical in CT and MR findings.