Risk Factors and Outcome of Portal Vein Thrombosis After Laparoscopic and Open Hepatectomy for Primary Liver Cancer: A Single-Center Experience.

BACKGROUND: Post-hepatectomy portal vein thrombosis (PH-PVT) is a severe complication. The risk factors of PH-PVT after laparoscopic and open hepatectomy have not been clarified yet. We aimed to retrospectively investigate the risk factors and outcome of PH-PVT in patients with primary liver cancer. METHODS: We enrolled 622 consecutive patients who underwent hepatectomy in our hospital between January 2006 and August 2016. RESULTS: Of 21 patients (3.4%) with PH-PVT, 7 had grade I; 13, grade II; and 1, grade III. The patients with PH-PVT were significantly older than those without PH-PVT. Of the 413 patients who underwent open hepatectomy, those who underwent a major right hepatectomy (4.1%) had a slightly higher incidence of PH-PVT. Of the 209 patients who underwent laparoscopic hepatectomy, those who underwent a left lateral sectionectomy (21.2%) and major right hepatectomy (16.7%) had high incidence rates of PH-PVT. The treatment was only observation in five patients, medication with an antithrombotic drug in 15 patients, and reoperation in one patient. PH-PVT diminished in 17 patients. Cavernous transformation and/or stenosis of the portal vein developed in three patients. The patient with grade III PH-PVT after open right hemihepatectomy underwent reoperation but died of hepatic failure. CONCLUSION: This study demonstrated that patient age, left lateral sectionectomy were risk factors of PH-PVT. Laparoscopic left lateral sectionectomy and major right hepatectomy might bring about relatively higher risk of PH-PVT. Major right hepatectomy tends to lead to severe PH-PVT. Careful handling of the PV during hepatectomy and early treatment of PH-PVT are necessary.

Impaired expression of innate immunity-related genes in IgG4-related disease: A possible mechanism in the pathogenesis of IgG4-RD.

Background: IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. The pathogenesis of this disease is not clear. Transcriptome analysis was performed to identify genes over- and under-expressed in patients with IgG4-RD.Method: DNA microarray analysis was performed using RNA from peripheral blood mononuclear cells of two patients with IgG4-RD and four healthy individuals. Genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy were identified. Four genes related to innate immunity such as transcobalamin I (TCN1), secretory leukocyte peptidase inhibitor (SLPI), bactericidal/permeability-increasing protein (BPI) and lactotransferrin (LTF) were assessed by real-time PCR in 15 IgG4-RD patients and 13 healthy individuals.Result: DNA microarray analysis identified 30 genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy. Real-time RT-PCR showed that the levels of mRNAs encoding TCNI and SLPI, except for BPI and LTF, were significantly lower in patients with IgG4-RD than in healthy people. The levels of all four mRNAs in patients with IgG4-RD were significantly increased after steroid treatment.Conclusion: These results indicate that reduction in expression of innate immunity-related genes may participate in the pathogenesis of IgG4-RD that steroid treatment may rectify impaired innate immunity as well as acquired immunity.

Current approach to the diagnosis of IgG4-related disease - Combination of comprehensive diagnostic and organ-specific criteria.

IgG4-related disease (IgG4-RD) is a fascinating clinical entity proposed by Japanese investigators, and includes a wide variety of diseases, formerly diagnosed as Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis, retroperitoneal fibrosis, etc. Although all clinicians in every field of medicine may encounter this new disease, a unifying diagnostic criterion has not been established. In 2011, the Japanese IgG4 team, organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan, published comprehensive diagnostic criteria for IgG4-RD. Several problems with these criteria have arisen in clinical practice, however, including the difficulty obtaining biopsy samples from some patients, and the sensitivity and the specificity of techniques used to measure serum IgG4 concentrations. Although serum IgG4 concentration is an important clinical marker for IgG4-RD, its diagnostic utility in differentiating IgG4-RD from other diseases, called IgG4-RD mimickers, remains unclear. This review describes the current optimal approach for the diagnosis of IgG4-RD, based on both comprehensive and organ-specific diagnostic criteria, in patients with diseases such as IgG4-related pancreatitis (AIP), sclerosing cholangitis, and renal, lung and orbital diseases.

Isolation of vascular smooth muscle antigen-reactive CD4(+)αßTh1 clones that induce pulmonary vasculitis in MRL/Mp-Fas(+/+) mice.

Here, we established CD4(+)αßTh1 clones specific for rat vascular smooth muscle antigen (VSMAg) that induced vasculitis lesions in the lungs of MRL/Mp-Fas(+/+) mice following adoptive transfer. Six different T cell clones, MV1b1 (Vß1), MV1b4 (Vß4), MV1b8.3 (Vß8.3), MV1b61 (Vß6), MV1b62 (Vß6), and MV1b63 (Vß6), were isolated from the MV1 T cell line from the regional lymph nodes of immunized MRL/Mp-Fas(+/+) mice; the three (Vß6) clones had unique CDR3 amino acid sequences. Following stimulation with VSMAg-pulsed antigen presenting cells, MV1b61 and MV1b62 failed to secrete interferon-γ and tumor necrosis factor-α, although the other four clones secreted high levels of both cytokines. In adoptive transfer experiments, MV1b61 and MV1b62 did not induce organ involvement including pulmonary vasculitis. In contrast, MV1b1, MV1b4, MV1b8.3, and MV1b63 induced perivascular mononuclear cell infiltration in pulmonary small arteries. These clones may provide useful tools for investigating the underlying mechanisms of vasculitis syndromes and for developing therapeutic strategies.

Deficient leptin signaling ameliorates systemic lupus erythematosus lesions in MRL/Mp-Fas lpr mice.

Leptin is secreted by adipocytes, the placenta, and the stomach. It not only controls appetite through leptin receptors in the hypothalamus, it also regulates immunity. In the current study, we produced leptin-deficient MRL/Mp-Fas(lpr) mice to investigate the potential role of leptin in autoimmunity. C57BL/6J-ob/ob mice were backcrossed with MRL/Mp-Fas(lpr) mice, which develop human systemic lupus erythematosus (SLE)-like lesions. The effects of leptin deficiency on various SLE-like manifestations were investigated in MRL/Mp-Fas(lpr) mice. The regulatory T cell population in the spleen was analyzed by flow cytometry, and the effects of leptin on regulatory T cells and Th17 cells were evaluated in vitro. Compared with leptin-producing MRL/Mp-Fas(lpr) mice, leptin-deficient MRL/Mp-Fas(lpr) mice showed less marked splenomegaly and a particularly low population of CD3(+)CD4(-)CD8(-)B220(+) T cells (lpr cells). Their serum concentrations of Abs to dsDNA were lower, and renal histological changes at age 20 wk were ameliorated. Regulatory T cells were increased in the spleens of leptin-deficient MRL/Mp-Fas(lpr) mice. Leptin suppressed regulatory T cells and enhanced Th17 cells in vitro. In conclusion, blockade of leptin signaling may be of therapeutic benefit in patients with SLE and other autoimmune diseases.

IgG4-related disease and its pathogenesis-cross-talk between innate and acquired immunity.

IgG4-related disease (IgG4-RD) is a novel clinical entity proposed in Japan in the 21th century and is attracting strong attention over the world. The characteristic manifestations of IgG4-RD are increased serum IgG4 concentration and tumefaction by IgG4(+) plasma cells. Although the clinical manifestations in various organs have been established, the pathogenesis of IgG4-RD is still unknown. Recently, many reports of aberrant acquired immunity such as Th2-diminated immune responses have been published. However, many questions still remain, including questions about the pathogenesis of IgG4-RD and the roles of IgG4. In this review, we discuss the pathogenesis of IgG4-RD by focusing on the cross-talk between innate and acquired immunity.

Prognostic value of biomarkers in metastatic colorectal cancer patients.

BACKGROUNDS: The prognostic value of biomarkers in metastatic colorectal cancer (mCRC) patients with liver metastases remains unclear. We assessed the difference of expression of biomarkers between primary tumors and liver metastases treated with chemotherapy in mCRC patients, as well as the prognostic value of these markers. METHODS: Forty-three mCRC patients with liver-limited disease from January 2007-November 2011 were analyzed. They all received resection of primary tumors followed by oxaliplatin-based chemotherapy. After chemotherapy, they all received hepatic resection. Forty-three paired primary and metastatic tumor specimens were collected to measure the messenger RNA expression of six biomarkers by the Danenberg tumor profile method (thymidylate synthase, dihydropyrimidine dehydrogenase [DPD], excision repair cross-complementing gene1, thymidine phosphorylase [TP], folylpolyglutamate synthase, and regenerating islet-derived family, member 4). RESULTS: Thirty-six patients' messenger RNA was used for analysis. All markers showed similar expression between primary and metastatic sites. The low-expression group of Danenberg tumor profile and TP in the primary tumor showed significantly higher overall survival than the high-expression group (P < 0.001 and P = 0.033), but for DPD and TP in liver metastases, there were no significant differences of overall survival between the two groups. The ratios of marker expression in liver metastatic site to that in primary site of DPD and TP were significantly higher in chemo-responders than in non-chemo-responders (P = 0.034 and P = 0.022). CONCLUSIONS: Biomarkers' expressions in liver metastases were similar to those in the primary tumor. DPD and TP in the primary lesion may be a prognostic factor in chemotherapy-naïve mCRC patients with liver-limited disease, but those in liver tumor were not. Further validated analysis to our results would be warranted.

Role of preferential cyclooxygenase-2 inhibition by meloxicam in ischemia/reperfusion injury of the rat liver.

BACKGROUND: Ischemia/reperfusion injury (IRI) is one of the major clinical problems in liver and transplant surgery. Livers subjected to warm ischemia in vivo often show a severe dysfunction and the release of numerous inflammatory cytokines and arachidonic acid metabolites. Cyclooxygenase (COX)-2 is the inducible isoform of an intracellular enzyme that converts arachidonic acid into prostaglandins. The aim of the study was to evaluate the effect of COX-2 inhibition and the role of Kupffer cells in IRI of the liver. METHODS: Male Wistar rats [250- 280 g body weight (BW)] were anesthetized and subjected to 30-min warm ischemia of the liver (Pringle's maneuver) and 60-min reperfusion after median laparotomy. The I/R group received no additional treatment. In the COX-2 inhibitor (COX-2I) group, the animals received 1 mg/kg BW meloxicam prior to operation. Gadolinium chloride (GdCl3) (10 mg/kg BW) was given 24 h prior to operation in the GdCl3 and GdCl3 + COX-2I groups for the selective depletion of Kupffer cells. The GdCl3 + COX-2I group received both GdCl3 and meloxicam treatment prior to operation. Blood and liver samples were obtained at the end of the experiments for further investigations. RESULTS: After 30 min of warm ischemia in vivo, severe hepatocellular damage was observed in the I/R group. These impairments could be significantly prevented by the selective COX-2 inhibition and the depletion of Kupffer cells. Alanine aminotransferase was significantly reduced upon meloxicam and GdCl3 treatment compared to the I/R group: I/R, 3,240 ± 1,262 U/l versus COX-2I, 973 ± 649 U/l, p < 0.001; I/R versus GdCl3, 1,611 ± 600 U/l, p < 0.05, and I/R versus GdCl3 + COX-2I, 1,511 ± 575 U/l, p < 0.01. Plasma levels of tumor necrosis factor alpha (TNF-α) were significantly reduced in the COX-2I treatment group compared to I/R (3.5 ± 1.5 vs. 16.3 ± 11.7 pg/ml, respectively; p < 0.05). Similarly, the amount of TxB2, a marker for COX-2 metabolism, was significantly reduced in the meloxicam treatment groups compared to the I/R group: I/R, 22,500 ± 5,210 pg/ml versus COX-2I, 1,822 ± 938 pg/ml, p < 0.001, and I/R versus GdCl3 + COX-2I, 1,530 ± 907 pg/ml, p < 0.001. All values are given as mean ± SD (n = 6). CONCLUSION: These results suggest that the inhibition of COX-2 suppressed the initiation of an inflammatory cascade by attenuating the release of TNF-α, which is an initiator of the inflammatory reaction in hepatic IRI. Therefore, we conclude that preferential inhibition of COX-2 is a possible therapeutic approach against warm IRI of the liver.

CD4+ T-cell dysfunctions through the impaired lipid rafts ameliorate concanavalin A-induced hepatitis in sphingomyelin synthase 1-knockout mice.

Membrane microdomains consisting of sphingomyelin (SM) and cholesterol appear to be important for signal transduction in T-cell activation. The present study was designed to elucidate the role of membrane SM in vivo and in vitro using sphingomyelin synthase 1 (SMS1) knock out (SMS1(-/-)) mice and Concanavalin A (ConA)-induced hepatitis. After establishing SMS1(-/-) mice, we investigated CD4+ T-cell functions including proliferation, cytokine production and signal transduction in vivo. We also examined severity of hepatitis, cytokine production in serum and liver after ConA injection at a dose of 20 mg kg(-1). CD4+ T cells from SMS1(-/-) mice showed severe deficiency of membrane SM and several profound defects compared with wild-type controls as follows: (i) cellular proliferation and production of IL-2 and IFN-γ by co-cross-linking of CD3 and CD4; (ii) tyrosine phosphorylation of LAT and its association with ZAP-70; (iii) clustering and co-localization of TCR with lipid rafts. Consistent with these impaired CD4+ T-cell functions in vitro, SMS1(-/-) mice showed decreased serum levels of IL-6 and IFN-γ by ConA injection, which renders SMS1(-/-) mice less sensitive to ConA-induced hepatitis. These results indicated that the deficiency of membrane SM caused the CD4+ T-cell dysfunction through impaired lipid raft function contributed to protection of ConA-induced liver injury, suggesting that the membrane SM is critical for full T-cell activation both in vitro and in vivo.

Feasibility and potential benefit of preoperative chemotherapy for colorectal liver metastasis (CLM): a single-centered retrospective study.

PURPOSES: The benefit of neo-adjuvant chemotherapy for liver-limited metastatic colorectal cancer is still controversial. This study defined the resectability regardless of the size and number of liver metastases, and attempted curative hepatic resection in all cases. METHODS: Sixty-four patients that tolerated chemotherapy were diagnosed with CLM (colorectal liver metastases) without extrahepatic metastase from January 2007 to November 2010, and received an oxaliplatin-based regimen. This study assessed the resectability after chemotherapy, and the patients were divided in two groups; the resected and unresected group. Sixteen patients underwent hepatic resection without chemotherapy. RESULTS: Thirty-five patients underwent surgical resection (resected group) and twenty-nine patients were considered unresectable (unresected group). All 35 patients in the resected group safely received oxaliplatin-based chemotherapy safely without serious adverse effects. No serious postoperative complications were observed. The median overall survival (MST) was significantly higher in the resected than in the unresected group (56.93 [95% CI 38.13-75.73] and 25.07 months [95% CI 17.87-32.26], respectively; P < 0.001). The median disease-free survival was 20.2 [95% CI 8.82-31.65] months in the resected group. CONCLUSION: Preoperative chemotherapy for CLM is well tolerated and does not increase postoperative complications. Curative surgery with preoperative chemotherapy has the potential to improve the overall survival in patients with CLM.

[Once-weekly bortezomib plus dexamethasone therapy induced complete response, reducing severe gastrointestinal adverse events for a patient with relapsed multiple myeloma - a case report].

A 74-year-old female with relapsed multiple myeloma was treated with twice-weekly bortezomib plus dexamethasone (BD)therapy, but severe gastrointestinal adverse events(grade 3 paralytic ileus and constipation)developed. After changing to once-weekly BD therapy, ≥ grade 3 gastrointestinal adverse events did not develop, and she was able to continue BD therapy. A complete response and a treatment-free interval ≥ 2 years were obtained by 8 courses of BD therapy. This case report suggests that once-weekly BD therapy may reduce severe gastrointestinal adverse events without decreasing the clinical efficacy for multiple myeloma.

[Primary neurolymphomatosis of the cervical nerve root].

A 74-year-old woman was admitted with muscle weakness and sharp pain in her upper limbs. On (18)FDG-PET, abnormal accumulation was noted on both sides of the brachial plexus at the cervical spinal cord. A diagnosis of primary peripheral nerve neurolymphomatosis was made based on biopsy of the third cervical nerve. Following R-CHOP therapy, the abnormal accumulation of (18)FDG-PET scan disappeared. However, disturbance of consciousness occurred 6 months later and recurrence as multiple brain tumors was detected. Although salvage chemotherapy was performed, the patient died of overwhelming sepsis. Primary peripheral nerve neurolymphomatosis is extremely rare. Early distinct diagnosis using (18)FDG-PET and combination chemotherapy of rituximab and high dose methotrexate may improve the outcome for such patients.

Clinical and prognostic significance of urinary trypsin inhibitor in patients with hepatocellular carcinoma after hepatectomy.

BACKGROUND: Urinary trypsin inhibitor (UTI), produced in the liver, has been considered to suppress inflammation. The production of UTI may decrease after a hepatectomy and thereby increase the incidence of postoperative inflammation. This study investigated whether the changes in the UTI level affected the postoperative course in patients undergoing a hepatectomy for hepatocellular carcinoma (HCC). The prognostic significance of UTI was also analyzed. METHODS: The perioperative plasma UTI was measured in 25 HCC patients who underwent hepatic resection, and the correlation between the kinetics of UTI and clinicopathological factors was investigated. The expression of UTI in the resected specimens was examined by immunohistochemistry in 65 patients. Expression of UTI in the cancer cells were then correlated to both the liver pathology and the clinical outcomes in the corresponding patients. RESULTS: The plasma UTI level greatly decreased on the first postoperative day. This decrease significantly correlated with the resected tumor volume (r (s) = -.530, P = .006), but it had no influence on inflammatory complications. Immunohistochemistry revealed UTI expression in both noncancerous and cancerous lesions. An overexpression of UTI in HCC tissue was found to be an independent prognostic factor for early recurrence (P = .006). CONCLUSIONS: Although UTI plasma levels were noted to decrease after the removal of an HCC tumor, this decrease did not lead to an increase in inflammatory complications. However, overexpression of UTI in cancer was found to be a risk factor for tumor recurrence after resection, suggesting that UTI expression may be a useful prognostic marker.

Molecular basis for reduced estrone sulfate transport and altered modulator sensitivity of transmembrane helix (TM) 6 and TM17 mutants of multidrug resistance protein 1 (ABCC1).

Multidrug resistance protein 1 (MRP1) confers drug resistance and also mediates cellular efflux of many organic anions. MRP1 also transports glutathione (GSH); furthermore, this tripeptide stimulates transport of several substrates, including estrone 3-sulfate. We have previously shown that mutations of Lys(332) in transmembrane helix (TM) 6 and Trp(1246) in TM17 cause different substrate-selective losses in MRP1 transport activity. Here we have extended our characterization of mutants K332L and W1246C to further define the different roles these two residues play in determining the substrate and inhibitor specificity of MRP1. Thus, we have shown that TM17-Trp(1246) is crucial for conferring drug resistance and for binding and transport of methotrexate, estradiol glucuronide, and estrone 3-sulfate, as well as for binding of the tricyclic isoxazole inhibitor N-[3-(9-chloro-3-methyl-4-oxo-4H-isoxazolo-[4,3-c]quinolin-5-yl)-cyclohexylmethyl]-benzamide (LY465803). In contrast, TM6-Lys(332) is important for enabling GSH and GSH-containing compounds to serve as substrates (e.g., leukotriene C(4)) or modulators (e.g., S-decyl-GSH, GSH disulfide) of MRP1 and, further, for enabling GSH (or S-methyl-GSH) to enhance the transport of estrone 3-sulfate and increase the inhibitory potency of LY465803. On the other hand, both mutants are as sensitive as wild-type MRP1 to the non-GSH-containing inhibitors (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl][[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid (MK571), 1-[2-hydroxy-3-propyl-4-[4-(1H-tetrazol-5-yl)butoxy]phenyl]-ethanone (LY171883), and highly potent 6-[4'-carboxyphenylthio]-5[S]-hydroxy-7[E], 11[Z]14[Z]-eicosatetrenoic acid (BAY u9773). Finally, the differing abilities of the cysteinyl leukotriene derivatives leukotriene C(4), D(4), and F(4) to inhibit estradiol glucuronide transport by wild-type and K332L mutant MRP1 provide further evidence that TM6-Lys(332) is involved in the recognition of the gamma-Glu portion of substrates and modulators containing GSH or GSH-like moieties.

P-glycoprotein expression affects 18F-fluorodeoxyglucose accumulation in hepatocellular carcinoma in vivo and in vitro.

18F-fluorodeoxyglucose (FDG) uptake in hepatocellular carcinoma (HCC) is associated with tumor differentiation and expression of P-glycoprotein (P-gp), a drug efflux pump that plays an important role in chemoresistance. The aim of the study was to clarify the factors that affects FDG uptake in HCC in vivo and in vitro. The standardized uptake value (SUV) and the tumor to non-tumor SUV ratio (TNR) for FDG uptake in HCC in vivo was determined by FDG-PET in 28 patients. Expression levels of glucose transporter-1 (GLUT-1), GLUT-2 and type II hexokinase (HK-II) were examined immunohistochemically in resected specimens. The glucose-6-phosphatase (G-6-Pase) activity was determined in tissue homogenates. In vitro, PLC/PRF/5 cells and doxorubicin-resistant PLC/DOR cells were used to examine the effect of P-gp on FDG uptake. The effects of two P-gp inhibitors, verapamil and cepharanthine, on accumulation of FDG were also examined. in vivo, GLUT-1 expression was low in HCCs, but was significantly higher in poorly differentiated HCCs than in moderately differentiated HCCs (P=0.043) and was positively correlated with SUV (r=0.75, P<0.0001) and TNR (r=0.7, P<0.0001). GLUT-2 and HK-II expression and G-6-Pase activity were not correlated with tumor differentiation, SUV or TNR. P-gp was over-expressed in PLC/DOR cells, and accumulation of FDG was significantly higher in PLC/PRF/5 cells than in PLC/DOR cells (P=0.04). Verapamil and cepharanthine restored FDG uptake in PLC/DOR cells, but not in PLC/PRF/5 cells. Collectively, our results show that FDG uptake in HCC is weakly correlated with GLUT-1 expression, and that FDG could be a substrate of P-gp, which may act as an efflux pump to reduce FDG accumulation.

[Very good partial response and long time to progression by short-term bortezomib plus dexamethasone therapy for a patient with relapsed and refractory multiple myeloma-a case report].

A 63-year-old female with relapsed and refractory multiple myeloma, in whom the duration of disease and history of chemotherapy were 15 years and 9 years, respectively, was treated with bortezomib and dexamethasone. A very good partial response and about 500 days to progression were obtained at a total dose of 10.2 mg bortezomib, until the day 4 injection of the second course. Bone pain has completely disappeared. These findings suggested that the therapeutic efficacy of bortezomib may persist over a long period regardless of the duration of chemotherapy. When a favorable response is obtained, but continuous therapy with bortezomib is difficult for reasons such as adverse events (other than refractory to bortezomib), careful observation may be one of the important options.

Influence of coexisting cirrhosis on outcomes after partial hepatic resection for hepatocellular carcinoma fulfilling the Milan criteria: an analysis of 293 patients.

BACKGROUND: For patients with liver cirrhosis and hepatocellular carcinoma (HCC) satisfying the Milan criteria (single tumor < or =5 cm or 2 or 3 tumors < or =3 cm), orthotopic liver transplantation (OLT) is an effective treatment. Nevertheless, it remains controversial whether OLT is the best treatment strategy for patients with resectable HCC. METHODS: This study included 293 HCC patients (both with and without cirrhosis) oncologically satisfying the Milan criteria who underwent primary and curative liver resection between 1990 and 2003. RESULTS: There were 127 noncirrhotic, 129 Child-Pugh A cirrhotic, and 37 Child-Pugh B cirrhotic patients. Five-year survival rates in each population were 81%, 54%, and 28%, respectively. Coexisting cirrhosis, Child-Pugh classification, alpha-fetoprotein value, tumor burden, and vascular invasion by the tumor were identified as significant prognostic factors. Among these factors, coexisting cirrhosis was the most crucial variable by multivariate analysis. During the initial 3 postoperative years, yearly tumor recurrence rate was 22% in cirrhotic patients and 15% in noncirrhotic patients. In cirrhotic patients, the recurrence rate did not decrease even after three years of tumor-free survival post-resection, whereas in noncirrhotic patients the recurrence rate decreased to 9%. Cirrhosis was associated with a higher probability of recurrence exceeding the Milan criteria. CONCLUSIONS: Hepatic resection offers an acceptable survival result for HCC patients fulfilling the Milan criteria. Coexisting cirrhosis is associated with higher mortality and recurrence rate, possibly due to multicentric carcinogenesis which limits the efficacy of hepatic resection.

Challenging Differential Diagnosis of Hypergastremia and Hyperglucagonemia with Chronic Renal Failure: Report of a Case with Multiple Endocrine Neoplasia Type 1.

A 53-year-old woman developed end-stage renal failure during a 15-year clinical course of primary hyperparathyroidism and was referred to our hospital for evaluation of suspected multiple endocrine neoplasia type 1 (MEN1). Genetic testing revealed a novel deletion mutation at codon 467 in exon 10 of the MEN1 gene. Systemic and selective arterial calcium injection (SACI) testing revealed hyperglucagonemia and hypergastrinemia with positive gastrin responses. A pathological examination revealed glucagonoma and a lymph node gastrinoma. The findings in this case indicate the importance of early diagnosis of MEN1 and demonstrate the utility of systemic and SACI testing in renal failure cases.

A Novel Missense Mutation of the MEN1 Gene in a Patient with Multiple Endocrine Neoplasia Type 1 with Glucagonoma and Obesity.

A 35-year-old obese diabetic man presented with recurrent primary hyperparathyroidism during a three-year outpatient follow-up. He was clinically diagnosed with multiple endocrine neoplasia type 1 (MEN1) due to the presence of a pituitary adenoma and multiple glucagonomas. The glucagonomas may have affected his glycemic control. However, he did not demonstrate weight loss, suggesting that the patient's obesity could have obscured the early diagnosis of a glucagonoma. Genetic testing revealed a novel missense mutation at codon 561 in exon 10, resulting in an amino acid substitution from methionine to arginine (M561R) in the MEN1 gene. This mutation appeared to be responsible for the MEN1 pathogenicity.