Search

Background FOLFIRINOX (FFX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have recently been available for treating pancreatic ductal adenocarcinoma (PDAC). We investigated trends in characteristics, treatment and outcomes of unselected patients with unresectable PDAC in real-life practice in Japan. Methods We retrospectively reviewed the medical records of 1085 patients diagnosed as having unresectable or recurrent PDAC in multiple centers in the Hokuriku area between January 2009 and July 2015. Results The incidence of pathologically proven PDAC had increased from 18.7% in 2009 to 56.2% in 2015. Oncological therapy was administered to 779 patients (71.8%): chemotherapy (n = 675), chemo-radiotherapy (n = 92) or radiotherapy (n = 12); the remaining patients were treated with best supportive care. Of 100 patients diagnosed in 2009, 62.0% received GEM as first-line chemotherapy; whereas 30.7% of the 75 patients diagnosed in 2015 received FFX, 25.3% GnP, 22.7% GEM and 17.3% S-1. The objective response rates of patients treated with FFX, GnP and GEM were 14.9%, 35.0% and 5.5%, respectively and the OS 10.3, 9.9 and 7.5 months after FFX, GnP and GEM, respectively. Grade 3 or greater any hematological toxicity occurred in 70.2%, 70.0% and 18.8% of the patients treated with FFX, GnP and GEM, respectively. The reasons for treatment discontinuation were adverse events in 9.8%, 26.7% and 24.1% of the patients treated with FFX, GnP and GEM, respectively. Conclusion Chemotherapeutic protocols changed dramatically between 2009 and 2015. Continuous collection and analysis for our cohort with longer follow-up provides useful information about treatment selection and prediction of outcome.

Background and aim Relapse and diabetes mellitus (DM) are major problems for the prognosis of autoimmune pancreatitis (AIP). We examined the prognosis of type 1 AIP after corticosteroid therapy (CST)-induced remission in terms of relapse and DM. Methods The study enrolled 82 patients diagnosed with type 1 AIP who achieved remission with CST. We retrospectively evaluated the relapse rate in terms of the administration period of CST, clinical factors associated with relapse, and the temporal change in glucose tolerance. Results During follow-up, 32 patients (39.0%) experienced relapse. There was no significant clinical factor that could predict relapse before beginning CST. AIP patients who ceased CST within 2 or 3 years experienced significantly earlier relapse than those who had the continuance of CST (p = 0.050 or p = 0.020). Of the 37 DM patients, 15 patients (40.5%) had pre-existing DM, 17 (45.9%) showed new-onset DM, and 5 (13.5%) developed CST-induced DM. Patients with new-onset DM were significantly more likely to show improvement (p = 0.008) than those with pre-existing DM. Conclusions It was difficult to predict relapse of AIP based on clinical parameters before beginning CST. Relapse was likely to occur within 3 years after the beginning of CST and maintenance of CST for at least 3 years reduced the risk of relapse. The early initiation of CST for AIP with impaired glucose tolerance is desirable because pre-existing DM is refractory to CST.

金沢大学医薬保健研究域医学系, We report the case of an 80-year-old female suffering from pancreatic cancer who developed severe non-alcoholic steatohepatitis (NASH) resulting in fatal hepatic failure after anti-cancer chemotherapy with gemcitabine. Hepatic encephalopathy appeared 1 year after the chemotherapy, and the patient developed progressive liver failure and eventually died. Radiological examination showed severe fatty liver. Histopathological examination of a liver needle necropsy showed almost panlobular macrovesicular fatty change. Ballooning degeneration and necrosis of hepatocytes accompanying neutrophil infiltration, Mallory bodies, and a few bile plugs were found in zone 3. Marked perivenular and pericellular/perisinusoidal fibrosis and extensive bridging fibrosis were also found. Together, these findings indicated steatohepatitis at a precirrhotic stage. Because the patient had no history of drinking in excess, we made a diagnosis of NASH, in particular, chemotherapy-associated steatohepatitis (CASH). Gemcitabine is a pyrimidine nucleoside antimetabolite with anti-cancer activity. A few reports have mentioned fatal hepatotoxicity caused by gemcitabine, but, to our knowledge, this is the first report of steatohepatitis, possibly associated with gemcitabine. Physicians treating patients with this drug should be aware of the possibility of steatohepatitis. © Springer 2010.

CAP, a multiple-drug combination therapy using cyclophosphamide (750 mg/m2), adriamycin (20-30 mg/m2) and cisplatin (50-75 mg/m2), was applied to 69 cases of epithelial ovarian cancer. The results of this therapy were compared with those of FAM (involving 5-fluorouracil, cyclophosphamide and mitomycin C) in 47 cases of the same cancer, retrospectively. The 5-year survival rate was 61.6% for cases treated with CAP and 56.3% for cases treated with FAM. All 9 patients at stage Ia treated with CAP are free of disease, however, 3 patients out of 13 at stage Ia treated with FAM experienced a recurrence of the disease and died. In stage III and IV cases with detectable lesions, a response was observed in 61.3% (19/31) treated with CAP and in 10.5% (2/19) treated with FAM.

Aim: To describe the extremely rare case of an adenomyoma of the papilla of Vater. Case Report: A 42-year-old woman was hospitalized for epigastralgia and high fever. The clinical presentation and endoscopic, biochemical, and radiologic findings led to the diagnostic impression of a dysfunction of the papilla of Vater. The patient was treated successfully by laparotomy and duodenotomy, incorporating cholangiomanometry and cholangiography. Intraoperative frozen-section examination of a transduodenal papillectomy specimen led to the diagnosis of adenomyomatosis of the papilla. The patient is doing well 38 months postoperatively. Conclusion: Such a combined approach to intraoperative diagnosis was important to avoid excessive surgery for a benign periampullary disease.

We investigated the expression of the drug resistance-related genes, multidrug resistance gene 1 (MDR1), multidrug resistance associated protein gene (MRP), and the DNA topoisomerase IIalpha, DNA topoisomerase IIbeta, and glutathione-S-transferase pi gene (GST-pi) in three human hepatoma cell lines (HepG 2, HuH 7, SK-Hep-1) with or without drug treatment with interferon-alpha (IFN-alpha) and cisplatin (CDDP), by a reverse transcription-polymerase chain reaction (RT-PCR) method and a competitive PCR method. The signals of the MDR1, MRP, topoisomerase IIalpha, and topoisomerase IIbeta genes in HepG2 were weakened when IFN-alpha was added to CDDP. In SK-Hep-1, the administration of CDDP alone increased the signals of MDR1 while the addition of IFN-alpha decreased the signals, and the signals of GST-pi were decreased by IFN-alpha plus CDDP. In summary, our results concerning the expression of drug resistance-related genes in three human hepatoma cell lines demonstrate that IFN-alpha may modulate the mechanism of resistance to CDDP in liver cancer.

A 22-year-old woman developed sudden hepatic encephalopathy and severe intestinal bleeding. She was diagnosed with acute fatty liver and hypersensitivity vasculitis and was successfully treated with whole plasma exchange, methylprednisolone pulse therapy, and transcatheter arterial embolization. Twenty-seven months later, she began complaining of lower abdominal fullness, tenderness, and nausea and vomiting. Histologic examination showed that she had developed gastrointestinal and renal amyloidosis with intestinal pseudoobstruction and proteinuria. The immunohistochemical study of the stomach, rectum, and kidney with anti-amyloid A fluorescent antibody showed that the systemic amyloid deposit was secondary to her underlying disease. This is the first report of amyloidosis occurring secondary to hypersensitivity vasculitis.

症例は35歳男性.1965年より露光部に紅斑・浮腫が出現し,1987年,赤血球中プロトポルフィジン(PP)の高値より造血性プロトポルフィリン症(EPP)と診断された.1994年,肝障害にて当科入院.入院時の血液生化学検査で,AST 63IU/l, ALT 92IU/l, γGTP 303IU/lの肝障害と赤血球中PP値の増加(7,606μg/l)を認めた.肝組織像では小葉構造は乱れ,一部に再生結節が認められた.偏光顕微鏡で重屈折性を示す,褐色色業沈着を肝細胞,Kupffer細胞に認め,以上よりEPPによる早期肝硬変と診断した.ケノデオキシコール酸900mg/日の投与により,ALTは30IU/lと正常化し,γGTP 63IU/l,赤血球中PP5, 748μg/lと低下した.EPPにおいては時に肝不全を呈することがあり,早期診断と肝機能の厳重な経過観察が必要である.本例ではケノデオキシコール酸療法が赤血球中PPの低下と肝機能の改善に有効であったと考えられた.

輸血後C型肝炎の遷延化に対する長期インターフェロン(IFN)療法が関与したと思われる甲状腺機能亢進症を発症した1例を経験した.症例は49歳,男性.胃潰瘍からの大量出血に対して1,440mlの輸血を受け,輸血40日後に輸血後肝炎を発症.肝炎発症時,抗マイクロゾーム抗体は陽性であったが,甲状腺機能は正常状態であった.遷延化傾向を認めた肝炎に対し,組み換え型IFNα総計474×106単位を12ヵ月間,皮下投与した.IFN投与終了9ヵ月後より手指振戦が出現,2ヵ月間で10kgの体重減少を認め,また,血中甲状腺ホルモンの上昇を認め甲状腺機能亢進症と診断した.IFN治療開始後,甲状腺刺激抗体,TSH受容体抗体および抗核抗体は新たに陽性化,抗マイクロゾーム抗体に抗体価の上昇を認めた.長期IFN療法に関連し,自己抗体が陽性化し自己免疫疾患としてのGraves病を発症した1例と考えられ,今後IFN療法に際して留意すべき問題点と考え報告した.

Esophago-gastric varices of 22 patients were studied using a newly developed method of endoscopic ultrasonography (EUS). During the observation, the esophagus was filled with de-aerated water, and reflux of the water was prevented using a balloon placed 7 cm proximal to the tip of the endoscope. Thirteen of 22 patients received endoscopic sclerotherapy (EIS) for their esophago-gastric varices, and sequential changes of the varices were observed mith EUS. The EUS method demonstrated esophago-gastric varices as singular, or a bundle of low-echoic luminal structures, and extramural collateral vessels were also observed. Therefore, it was possible to evaluate the residual blood flow after EIS by the EUS findings. Sequential changes of the treated varices were observed as follows: (1) formation of a thrombus in the varices, (2) thickening of variceal wall, and (3) disappearance of luminal structures. Small luminal structures in the extramural space of the lower esophagus, dilated paraesophageal veins, were detected in 6 of 13 patients with EIS. The recurrence rate was smaller and the remission period was longer in these 6 patients than those in patients without these luminal structures. Our new EUS method has been shown to be useful not only for the morphological evaluation of varices, but also for the assessment of the effect of EIS.

無症候性原発性胆汁性肝硬変(a-PBC) 31例を対象として,その自然経過とursodeoxy-cholic acid (UDCA)投与後の経過について,項目別にスコア化した組織変化を含め臨床病理学的に検討した.3～94ヵ月(平均32ヵ月)の自然経過では血液生化学的に有意な変動はみられず,症候性への移行を31例中4例(12.9%)に認め,うち1例では診断後94ヵ月後に肝不全にて死亡した.一方,UDCA (600mg/日)を投与した16例では,3ヵ月後よう肝胆道系酵素,IgM値の有意な減少が認められた.組織所見については,UDCA非投与期では胆管炎のスコアのみが低下したが,UDCA投与期では胆汁うっ滞,胆管炎,線維化,グ鞘炎の各スコアにいずれも有意の改善が認められた.以上より,一部のa-PBCは緩徐ながら進行性で,s-PBCへの移行が認められた.一方,UDCA療法は血液生化学的,組織学的に有意の改善をもたらしたことから,a-PBCに対する有効な治療法である可能性が示唆された.

We reviewed the clinical features and clinical course of patients with duct-narrowing chronic pancreatitis who were negative for immunoserologic test results (n = 16) in comparison with the findings for serological test-positive patients (n = 20) in order to determine an adequate treatment for those who had typical morphology of autoimmune pancreatitis in the absence of immunoserologic abnormality. No significant differences were found between the two groups of patients in clinical profiles including associated autoimmune-related diseases, pancreatic histology, and response to steroid therapy. Of the seronegative patients, eight who showed an improvement in narrowing of the main pancreatic duct with steroid therapy and three who did no show an improvement or who relapsed after surgical resection without this therapy had stenosis of the common bile duct with increased levels of serum hepatobiliary enzymes, except for two patients with affected sites limited to the body or tail of the gland. For the remaining five patients, who showed an improvement in pancreatic duct changes or long-term remission after surgery without steroid administration, normal biochemistry test results for liver functions were obtained, with no abnormal cholangiographic findings in the three patients examined. Duct-narrowing chronic pancreatitis without immunoserologic abnormality overlaps in clinical features with that fulfilling the immunoserologic criteria for a diagnosis of autoimmune pancreatitis. In particular, the disease with bile duct involvement should be treated clinically as autoimmune pancreatitis, for which steroid therapy is recommended, even if an autoimmune mechanism is not demonstrated serologically.

Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis, and the development of new therapeutic strategies is necessary. Here we report the efficacy of combination chemotherapy in our biochemical modulation. Synergistic effects of interferon-alpha-2b on 5-fluorouracil or cisplatin were demonstrated in Huh7 cells. The efficacy of methotrexate-5-fluorouracil, cisplatin, and interferon-alpha-2b combination therapy was demonstrated in 34 patients with HCC complicated by major portal vein thrombosis. Among the 29 patients eligible for the study, there were 3 complete responders and 10 partial responders with an overall response rate of 45%. The 2-year survival of the 34 patients was 15%, and the median survival of complete and partial responders was 11 months. There was severe transient hematological toxicity. Eight patients suffered from renal insufficiency, and 4 of them underwent hemodialysis. Although a control study is clearly necessary, our combination therapy induced a good response in the patients with advanced HCC. On the basis of our results, intensive chemotherapy should be attempted in advanced HCC complicated by major portal vein invasion.

Recent advances in the treatment of hepatocellular carcinoma (HCC) have changed the importance of bone metastasis during the follow up of such patients. In the present study, we investigated risk factors for bone metastasis after treatment for HCC.Two hundred and two patients with HCC were diagnosed as free of bone metastasis by technecium 99m-methylene diphosphonate bone scintigraphy and were followed prospectively after treatment of the primary lesions (follow-up period 2-146 months; median 20 months). We statistically analyzed the risk factors for bone metastasis using the clinical characteristics at the time of first treatment.Multiple tumors (P0.005), main tumor size5 cm in diameter (P0.005), the presence of distant metastasis (P0.005), elevation of serum alpha-fetoprotein (100 ng/mL; P0.05), chemotherapy (P0.05) and insufficient therapeutic response (P0.0005) were identified as risk factors for bone metastasis by univariate analyses. Insufficient therapeutic response and main tumor size5 cm in diameter (both P0.05) were identified as independent predisposing factors for bone metastasis.Complete necrosis of primary HCC during the first treatment is important to prevent subsequent bone metastasis.

Forty-three patients with hepatocellular carcinomas (HCCs) who had undergone subsegmental transcatheter arterial embolization (sTAE) as initial treatment were studied retrospectively to evaluate the prognosis, recurrence, and effect of sTAE on liver function. Frequent recurrences were observed (disease-free survival rates were 51.2% at 1 year and 7.7% at 3 years), and in the recurrent nodules, 66.4% were distant recurrences. No significant difference was observed in the periods of distant recurrence compared with local recurrence, and also in the periods of distant recurrence with and without local recurrence, implying that strict control of the primary lesion did not prevent distant recurrence. Concerning the effect of sTAE on liver function, ALT and LDH were significantly elevated and albumin was significantly reduced after sTAE (p = 0.002, > 0.0001, and = 0.0009, respectively). But 4 weeks after sTAE, all these levels recovered to their previous values. Moreover transient hepatic reserve reduction after sTAE did not affect the prognosis. In conclusion, for HCCs with such levels of recurrence, strict follow-up and repeat treatments with minimum damage to the hepatic reserve are essential. sTAE is an appropriate and reasonable treatment for such HCCs because of low levels of damage to the hepatic reserve and the possibility of repeat operations. Using sTAE as the main treatment against HCC, survival rates of more than 70% at 3 years were achieved.