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Emicizumab, a factor (F)VIIIa-function mimetic bispecific antibody (BsAb) to FIXa and FX, has become an indispensable treatment for people with hemophilia A (PwHA). Although emicizumab is very potent, long-term outcomes from the clinical studies suggest that a small proportion of PwHA still experiences bleeds. Additionally, non-clinical studies indicate that the maximum cofactor activity of emicizumab is lower than international standard activity (100 IU/dL of FVIII). An increased cofactor activity BsAb would benefit such patients. Here, we report NXT007, a BsAb binding FIXa and FX developed through further engineering of emicizumab. Emicizumab has a common light chain, but through advances in antibody engineering, we were able to create a more potent BsAb with two new non-common light chains. After extensive optimization of the heavy and light chains, the resulting BsAb, NXT007, exerted in vitro thrombin generation (TG) activity in hemophilia A plasma equivalent to 100 IU/dL of FVIII when triggered by tissue factor. NXT007 demonstrated potent hemostatic activity in an acquired hemophilia A model in non-human primates at a much lower dosage than emicizumab, consistent with an around 30-fold dose shift in the in vitro TG activity between NXT007 and emicizumab. Moreover, together with Fc engineering that enhanced FcRn binding and reduced in vivo clearance, we demonstrate that NXT007 could be effective at a much lower dosage with a longer dosing interval compared to emicizumab. These non-clinical results suggest that NXT007 could maintain a non-hemophilic range of coagulation potential in PwHA and provides a rationale for its clinical testing.

The prognosis of gastric cancer patients with positive lavage cytology without gross peritoneal dissemination (P0CY1) is poor. The survival benefit of gastrectomy for these patients has not been established.In this population-based cohort study, we investigated the impact of radical gastrectomy with lymph node dissection for P0CY1 patients. Patients who were diagnosed with Stage IV gastric cancer from 2008 to 2015 in all nine cancer-designated hospitals in a tertiary medical area were listed. Patients who were diagnosed with histologically proven adenocarcinoma in both the primary lesion and lavage cytology during the operation or a diagnostic laparoscopic examination were enrolled. Patients with a gross peritoneal lesion or other metastatic lesions were excluded. The primary outcome was the adjusted hazard ratio (aHR) of gastrectomy for overall survival. We also evaluated the survival time in patients who underwent gastrectomy or chemotherapy in comparison to patients managed without primary surgery or with best supportive care.One hundred patients were enrolled. The aHR (95% confidence interval) of gastrectomy was 0.677 (0.411-1.114, p = 0.125). The median survival time in patients who received gastrectomy (n = 74) was 21.7, while that in patients managed without primary surgery (n = 30) was 20.5 months (p = 0.155). The median survival time in patients who received chemotherapy (n = 76) was 23.0 months, while that in patients managed without chemotherapy was 8.6 months (p 0.001).Gastrectomy was not effective for improving the survival time in patients with P0CY1 gastric cancer. Surgeons should prioritize the performance of chemotherapy over surgery as the initial treatment.

Background There are a few established prognostic factors for stage IV colorectal cancer. Thus, this study aimed to evaluate the impact of histological subtypes on prognosis and metastatic patterns in patients with stage IV colorectal cancer. Methods This was a population-based, multicenter, cohort study. We included consecutive patients diagnosed with stage IV colorectal cancer between 2008 and 2015 at all designated cancer hospitals in Fukushima prefecture, Japan. Patients were classified into two groups according to histological subtypes as follows: poorly differentiated adenocarcinoma (Por), mucinous adenocarcinoma (Muc), or signet-ring cell carcinoma (Sig) and well (Wel) or moderately differentiated adenocarcinoma (Mod). We evaluated the relationship between these histological groups and survival time. After adjusting for other clinical factors, we calculated the hazard ratio for Por/Muc/Sig. Results A total of 1,151 patients were enrolled, and 1,031 and 120 had Wel/Mod and Por/Muc/Sig, respectively. The median overall survival was 19.2 and 11.9 months for Wel/Mod and Por/Muc/Sig, respectively (p < 0.001). The adjusted hazard ratio for Por/Muc/Sig with regard to survival time was 1.42 (95% confidence interval: 1.13–1.77). Por/Muc/Sig had a lower incidence of liver and lung metastases and a higher incidence of peritoneal dissemination and metastasis to rare organs, such as the bone and brain. Conclusions The Por/Muc/Sig histological subtype was an independent prognostic factor for poor prognosis among patients with stage IV colorectal cancer. The histological subtype may be useful for predicting the prognosis of patients with stage IV colorectal cancer and designing the treatment strategy.

Background/aim We investigated the clinical impact of the primary tumor site in stage IV colorectal cancer (CRC). Patients and methods In this statewide multicenter retrospective cohort, patients with stage IV CRC from nine hospital-based cancer registries across the Fukushima Prefecture (2008-2015) were categorized based on three primary tumor sites: right colon cancer (RCC), left colon cancer (LCC), and rectal cancer. Overall survival was assessed using Cox regression analysis. Results A total of 1,211 patients were included. The most common clinical symptom was obstruction in LCC and bleeding in rectal cancer. Liver metastases were multiple and larger in LCC, while lung metastases were multiple in rectal cancer. Compared to LCC, the adjusted hazard ratio (HR) for overall survival was 1.19 [95% confidence interval (CI)=1.01-1.39, p=0.032] in RCC and 1.03 (95% CI=0.86-1.23, p=0.77) in rectal cancer. Conclusion RCC was independently associated with a worse prognosis in stage IV CRC.

Purpose: With the aging of society, the age of patients with gastric cancer (GC) in Japan has been increasing. However, there are few documented outcomes for young patients with stage IV GC. We investigated the clinical characteristics and prognosis of patients with stage IV GC aged under 40 years using a dataset from an integrated population-based cohort study.Methods: We conducted this multicenter population-based cohort study to determine whether earlier onset of GC was a poor prognostic factor. We enrolled patients with metastatic GC aged under 40 years (young group) and those aged between 60 and 75 years (middle-aged group). Patients were histologically diagnosed as having gastric adenocarcinoma. We evaluated the overall survival (OS) of both groups and the hazard ratio (HR) for OS based on age. The adjusted HR with 95% confidence interval (CI) was evaluated using the Cox proportional hazards model after adjusting for confounding factors, including sex, histology, number of metastatic lesions, surgical resection, and chemotherapy.Results: This study enrolled 555 patients. The patients were classified into the young group (n=20) and the middle-aged group (n=535). The median OS values were 5.7 months and 8.8 months in the young and middle-aged groups, respectively (P=0.029). The adjusted HR (95% CI) of the young group was 1.88 (1.17–3.04, P=0.009).Conclusions: Age was an independent prognostic factor in patients with stage IV GC. Further studies investigating the genomic characteristics of GC and exploring more effective chemotherapeutic agents are required.

Objective The prognosis of patients with liver metastases from gastric cancer is determined using tumor size and number of metastases; this is similar to the factors used for the prediction of liver metastases from colorectal cancer. The relationship between the degree of liver metastasis from gastric cancer and prognosis with reference to the classification of liver metastasis from colorectal cancer was investigated. Methods This was a multi-institutional historical cohort study. Among patients with stage IV gastric cancer, who visited the cancer hospitals in Fukushima Prefecture, Japan, between 2008 and 2015, those with simultaneous liver metastasis were included. Abdominal pretreatment computed tomography images were reviewed and classified into H1 (four or less liver metastases with a maximum diameter of ≤5 cm); H2 (other than H1 and H3) or H3 (five or more liver metastases with a maximum diameter of ≥5 cm). The hazard ratio for overall survival according to the H grade (H1, H2 and H3) was calculated using the Cox proportional hazards model. Results A total of 412 patients were analyzed. Patients with H1, H2 and H3 grades were 118, 162 and 141, respectively, and their median survival time was 10.2, 5.7 and 3.1 months, respectively (log-rank P Conclusions The grading system proposed in this study was a simple and easy-to-use prognosis prediction index for patients with liver metastasis from gastric cancer.

It remains unclear whether intensive chemotherapy for Stage IV colorectal cancer (CRC) patients aged 80 years or older is beneficial prognostically. This study aimed to investigate the overall survival of Stage IV CRC patients aged ≥ 80 years receiving intensive chemotherapy. The study design was a population-based, multicenter, historical cohort study. The extracted participants’ data were consecutive patients diagnosed as Stage IV CRC between January 2008 and May 2015 in nine hospitals in Japan. Patients were classified into two groups according to age: aged group (≥ 80 years) and younger group (

A new and exciting imaging technique being applied to thin films, nanocoatings, nanogels, and nanoparticle analysis is ultra-low accelerating voltage or ultra-low-landing-energy scanning electron microscopy (ULVSEM). Instrument conditions in this mode are different than with typical SEM observation or contemporary low accelerating voltage (LVSEM) imaging. Hence, the images appear far different due to reduced beam penetration. The landing energy of the primary electron beam can be much lower than LVSEM, it can be reduced to far below 500 electron volts (eV), even as low as 10 eV. Thus, the electron beam range and penetration are reduced tremendously with some unavoidable loss of spatial resolution. Surface details are enhanced, contrast might favorably change, and secondary electron (SE) edge enhancement or “blooming” contributing to measurement uncertainty is greatly reduced, potentially allowing for more precise and new measurements once this imaging mode is fully characterized and accurately modeled. High-resolution field-emission electron sources, improved lens, detector designs, and sample biasing all contribute to the ability to image at such low electron landing energies. The techniques of ULVSEM are discussed, and an application example is presented.

Aedes albopictus (Skuse) (Diptera: Culicidae) is distributed widely and is common in much of Japan. In Japan, female adults begin to bite in between April and June, except in the southern subtropics where the mosquito has no dormant period. It is difficult to estimate the first Ae. albopictus biting day because it varies annually depending on the location. Over several years, we surveyed the mosquitoes at different locations that covered a range of warmer to cooler areas of Japan. We found an association between the timing of first biting day by Ae. albopictus and spring temperature. In spring months, the strongest correlation was found with mean April temperatures, followed by March. Based on these data, it may, therefore, be possible to apply a simple formula to predict the timing of the first biting day at various geographical locations in Japan. Forecasting maps were created using a simple prediction formula. We found that the first biting day for Ae. albopictus changed depending on early spring temperatures for each year. There was an approximate 20-d difference in first biting day between years with warmer and cooler springs. This prediction model will provide useful insight for planning and practice of Ae. albopictus control programs, targeting larvae and adults, in temperate regions globally., Article, Journal of Medical Entomology.54(6):1519-1524(2017)

SummaryEmicizumab, a humanised bispecific antibody recognising factors (F) IX/IXa and X/Xa, can accelerate FIXa-catalysed FX activation by bridging FIXa and FX in a manner similar to FVIIIa. However, details of the emicizumab–antigen interactions have not been reported so far. In this study, we first showed by surface plasmon resonance analysis that emicizumab bound FIX, FIXa, FX, and FXa with moderate affinities (K D = 1.58, 1.52, 1.85, and 0.978 μM, respectively). We next showed by immunoblotting analysis that emicizumab recognised the antigens’ epidermal growth factor (EGF)-like domains. We then performed K D-based simulation of equilibrium states in plasma for quantitatively predicting the ways that emicizumab would interact with the antigens. The simulation predicted that only a small part of plasma FIX, FX, and emicizumab would form antigen-bridging FIX–emicizumab–FX ternary complex, of which concentration would form a bell-shaped relationship with emicizumab concentration. The bell-shaped concentration dependency was reproduced by plasma thrombin generation assays, suggesting that the plasma concentration of the ternary complex would correlate with emicizumab’s cofactor activity. The simulation also predicted that at 10.0–100 μg/ml of emicizumab–levels shown in a previous study to be clinically effective–the majority of plasma FIX, FX, and emicizumab would exist as monomers. In conclusion, emicizumab binds FIX/FIXa and FX/FXa with micromolar affinities at their EGF-like domains. The K D-based simulation predicted that the antigen-bridging ternary complex formed in circulating plasma would correlate with emicizumab’s cofactor activity, and the majority of FIX and FX would be free and available for other coagulation reactions.Institution where the work was carried out: Research Division, Chugai Pharmaceutical Co., Ltd.Supplementary Material to this article is available online at www.thrombosis-online.com.

Dimensional measurements from secondary electron (SE) images were compared with those from backscattered electron (BSE) and low-loss electron (LLE) images. With the commonly used 50% threshold criterion, the lines consistently appeared larger in the SE images. As the images were acquired simultaneously by an instrument with the capability to operate detectors for both signals at the same time, the differences cannot be explained by the assumption that contamination or drift between images affected the SE, BSE, or LLE images differently. Simulations with JMONSEL, an electron microscope simulator, indicate that the nanometer-scale differences observed on this sample can be explained by the different convolution effects of a beam with finite size on signals with different symmetry (the SE signal’s characteristic peak versus the BSE or LLE signal’s characteristic step). This effect is too small to explain the >100 nm discrepancies that were observed in earlier work on different samples. Additional modeling indicates that those discrepancies can be explained by the much larger sidewall angles of the earlier samples, coupled with the different response of SE versus BSE/LLE profiles to such wall angles.

Objective: Many patients with a chief complaint of chest tightness are examined in medical facilities, and a lack of diagnosis is not uncommon. We have reported that these patients often in...

While antibody engineering improves the properties of therapeutic antibodies, optimization of regions that do not contact antigens has been mainly focused on modifying the effector functions and pharmacokinetics of antibodies. We recently reported an asymmetric anti-FIXa/FX bispecific IgG4 antibody, ACE910, which mimics the cofactor function of FVIII by placing the two factors into spatial proximity for the treatment of hemophilia A. During the optimization process, we found that the activity was significantly affected by IgG subclass and by modifications to the inter-chain disulfide bonds, upper hinge region, elbow hinge region, and Fc glycan, even though these regions were unlikely to come into direct contact with the antigens. Of these non-antigen-contacting regions, the tertiary structure determined by the inter-chain disulfide bonds was found to strongly affect the FVIII-mimetic activity. Interestingly, IgG4-like disulfide bonds between Cys131 in the heavy chain and Cys114 in the light chain, and disulfide bonds between the two heavy chains at the hinge region were indispensable for the high FVIII-mimetic activity. Moreover, proline mutations in the upper hinge region and removal of the Fc glycan enhanced the FVIII-mimetic activity, suggesting that flexibility of the upper hinge region and the Fc portion structure are important for the FVIII-mimetic activity. This study suggests that these non-antigen-contacting regions can be engineered to improve the biological activity of IgG antibodies with functions similar to ACE910, such as placing two antigens into spatial proximity, retargeting effector cells to target cells, or co-ligating two identical or different antigens on the same cell.

Emicizumab is a humanized bispecific antibody that binds simultaneously to factor (F) IXa and FX replacing the cofactor function of FVIIIa. Because emicizumab recognizes FIX/FIXa and FX/FXa, a question may arise whether emicizumab competes with antithrombin (AT) and/or tissue factor pathway inhibitor (TFPI), thereby enhancing overall hemostatic potential by blocking their antihemostatic effects. To address this question, we performed enzymatic assays using purified coagulation factors to confirm whether emicizumab interferes with the action of AT on FIXa or FXa, or with the action of TFPI on FXa. In those assays, we found no interference of emicizumab on the actions of AT and TFPI. We next assessed emicizumab's influences on the anticoagulation actions of AT or TFPI in thrombin generation assays triggered with FXIa or tissue factor (TF) in AT-depleted or TFPI-depleted plasma supplemented with AT or TFPI in vitro. In those assays, we employed anti-FIXa and anti-FX monospecific one-armed antibodies derived from emicizumab instead of emicizumab itself so as to prevent emicizumab's FVIIIa cofactor activity from boosting thrombin generation. Consequently, we found that neither anti-FIXa, anti-FX monospecific antibody, nor the mixture of the two interfered with the anticoagulation actions of AT or TFPI in plasma. Although emicizumab can bind to FIXa and FXa, our results showed no interference of emicizumab with the action of AT or TFPI on FIXa or FXa. This indicates that the presence of emicizumab is irrelevant to the action of AT and TFPI, and thus should not alter the coagulant/anticoagulant balance related to AT and TFPI.

ACE910 is a humanized anti-factor IXa/X bispecific antibody mimicking the function of factor VIII (FVIII). We previously demonstrated in nonhuman primates that a single IV dose of ACE910 exerted hemostatic activity against hemophilic bleeds artificially induced in muscles and subcutis, and that a subcutaneous (SC) dose of ACE910 showed a 3-week half-life and nearly 100% bioavailability, offering support for effective prophylaxis for hemophilia A by user-friendly SC dosing. However, there was no direct evidence that such SC dosing of ACE910 would prevent spontaneous bleeds occurring in daily life. In this study, we newly established a long-term primate model of acquired hemophilia A by multiple IV injections of an anti-primate FVIII neutralizing antibody engineered in mouse-monkey chimeric form to reduce its antigenicity. The monkeys in the control group exhibited various spontaneous bleeding symptoms as well as continuous prolongation of activated partial thromboplastin time; notably, all exhibited joint bleeds, which are a hallmark of hemophilia. Weekly SC doses of ACE910 (initial 3.97 mg/kg followed by 1 mg/kg) significantly prevented these bleeding symptoms; notably, no joint bleeding symptoms were observed. ACE910 is expected to prevent spontaneous bleeds and joint damage in hemophilia A patients even with weekly SC dosing, although appropriate clinical investigation is required.

The Great East Japan Earthquake Disaster (GEJED) struck the northeast region of Honshu, the main island of Japan, on March 11, 2011. This mega-disaster claimed more than 15,000 lives, with approximately 3000 later deaths being disaster related. The GEJED consisted of a mega-earthquake, tsunami, and nuclear accident. Survivors living in temporary shelters might have received insufficient levels of vitamins, with the exception of vitamin B1, which appeared to be overestimated, and excess levels of sodium. However, scientific data collection and surveys following the GEJED were extremely limited. This experience highlights the need to prepare an “emergency nutrition assessment” system for optimal nutrition in future disasters.

SummaryBackground We previously reported that a humanized anti-factor IXa/X bispecific antibody, hBS23, mimics the function of FVIII even in the presence of FVIII inhibitors, and has preventive hemostatic activity against bleeding in an animal model of acquired hemophilia A. After further molecular engineering of hBS23, we recently identified an improved humanized bispecific antibody, ACE910, for clinical investigation. Objectives To elucidate the in vivo hemostatic potency of ACE910 by examining its effect against ongoing bleeds, and to determine its pharmacokinetic parameters for discussion of its potency for prophylactic use. Methods A non-human primate model of acquired hemophilia A was established by injecting anti-primate FVIII neutralizing antibody. When bleeds emerged following an artificial bleed-inducing procedure, either ACE910 or recombinant porcine FVIII (rpoFVIII) was intravenously administered. rpoFVIII was additionally administered twice daily on the following 2 days. Bleeding symptoms were monitored for 3 days. A pharmacokinetic study and multiple-dosing simulations of ACE910 were also performed. Results A single bolus of 1 or 3 mg kg−1 ACE910 showed hemostatic activity comparable to that of 10 U kg−1 (twice daily) rpoFVIII against ongoing bleeds. The determined ACE910 pharmacokinetic parameters included a long half-life (3 weeks) and high subcutaneous bioavailability (nearly 100%). The simulation results based on pharmacokinetic parameters indicated that the above hemostatic level could be maintained with once-weekly subcutaneous administration of ACE910, suggesting the possibility of more effective prophylaxis. Conclusions ACE910 may offer an alternative on-demand treatment option for patients with hemophilia A, as well as user-friendly and aggressive routine supplementation.

We report on a 58-year-old man with an anomalous systemic artery to the basal segments of the left lung. The anomalous systemic artery originated from the descending thoracic aorta, distributed to the basal segments of the left lower lobe, and drained into the normal left inferior pulmonary vein. The pulmonary artery to the basal segments was not recognized. His bronchoscopic findings were normal. He underwent left lower lobectomy with division of the aberrant artery. The patient has remained well without any complications since surgery.

症例は82歳の男性.突然の下腹部痛を主訴に来院した.既往歴は糖尿病,高血圧,慢性心不全,脳梗塞,気管支喘息.来院時は腹部全体に強い自発痛を認めたが筋性防御や反跳痛は認めなかった.腹部CT検査で上腸間膜動脈根部は造影された.肝臓両葉に肝内門脈ガス像を認めた.発症約6時間後に虚血性腸疾患による門脈ガス血症の診断のもと手術施行.上腸間膜動脈根部の拍動は触知出来たがTreitz靱帯より210cm以降の小腸と盲腸から上行結腸にかけての腸管拡張,浮腫および腸間膜の浮腫を認め,これを切除し機能的端々吻合を行った.術後は徐々に軽快し111日目に退院となった.病理診断では腸管粘膜は出血性壊死を認めたが腸間膜動静脈に血栓等特異な所見を認めず, nonoc-clusive mesenteric ischemiaと診断した.本疾患は予後不良と言われているが発症早期に開腹術に踏み切れば一期的手術も可能であると示唆された.

壊死性膵炎は発症早期に重要臓器障害を伴い,後期では過半数に壊死巣の感染が合併し保存的治療は限界で,外科的治療を必要とする.今回,感染性膵壊死に対し後腹膜ドレナージ術を行い14カ月後に胆嚢結石症に腹腔鏡下胆嚢摘出術を施行しえた1例を報告する.症例は48歳,男性.主訴はアルコール多飲後腹痛,当院へ紹介入院.急性膵炎の診断にて保存的加療す.一時軽快するも,その後症状悪化し膵全体の著明な腫大と左腎下極へ炎症波及しCT Grade Vを示した.発症後95日目に感染性膵壊死に対し後腹膜アプローチによるドレナージ術およびnecrosectomyを行った.術後144日目に軽快退院となった. 14カ月後に胆嚢結石症に対し腹腔鏡下胆嚢摘出術が可能であった.感染性膵壊死に対する後腹膜アプローチ術は,直接腹腔内操作が避けられ,その後の腹腔鏡下胆嚢摘出術が可能であり大変有用な方法と思われた.

消化器癌の臍転移はSister Mary Joseph結節の名で知られ比較的稀である.今回われわれは,同時性臍転移を認めた大腸癌の1切除例を経験したので報告する.症例89歳,女性.平成14年12月頃から臍部の痛みを伴う2 cm大の腫瘍に気付き近医を受診した.この時右下腹部に腫瘍を触知し,内視鏡検査にて盲腸癌と診断された.平成15年3月12日右結腸切除術,臍切除を施行した.肝転移,腹膜播腫はなかった.盲腸癌と臍部との連続性はなかった.病理組織学的検査では中分化腺癌の盲腸癌と臍部皮膚転移であった.術後経過は特に問題なく退院となった.臍転移は予後不良な徴候として,原発巣の診断に先行して発見されることがあり臨床的に留意すべきである.

Ablation therapy (MCT and RFA) has been reported to be one of the useful approaches except for hepatic resection in the primary hepatic carcinoma with liver damage.In the present study, hepatic resection with intraoperative ablation therapy was performed on two cases of HCCs and a case of cholangiocarcinoma with liver cirrhosis and HCV positive. Case 1 : A 63-year-old man with liver damage, diabetic nephropathy and diabetic neuropathy underwent left hepatic lateral segmentectomy for large HCC (5 cm) and RFA for small HCC (exceeding 2 cm) in S8. Case 2 : A 62-year-old woman with liver cirrhosis underwent left hepatic lateral segmentectomy for large cholangiocarcinoma (4.5 cm) and MCT for small tumor (2 cm) in S5. Case 3 : A 69-year-old man with liver cirrhosis underwent partial caudate lobectomy of the liver for HCC (3 cm) in S1 and RFA for HCC (exceeding 3 cm) in S4.The efficiency of the coagulation was proven by employing postoperative enhanced computed tomography in all cases. All patients had an uneventful postoperative course.It was suggested that limited hepatic resection with multimodal minimally invasive treatment such as ablation therapy is effective when combined with interstinal therapy for multiple primary hepatic carcinomas with liver damage.

症例は72歳,女性. 2000年10月頃,左腰背部膨隆に気づくも放置.その後徐々に大きくなり,2001年10月1日当科受診した.腹部CTおよびMRI検査にて左上腰ヘルニアと診断した. 2001年11月29日に手術施行し,手術所見では上腰三角部に直径約2cmのヘルニア門を認め,後腹膜脂肪組織が脱出していた.術式は脂肪組織を還納後,周囲組織が脆弱であったためPHS (PROLENE Hernia System ®)を挿入し補強した.術後経過は良好で術後4カ月現在再発を認めていない.上腰ヘルニアは稀な疾患で本邦報告は自験例を含めて39例である.治療は外科的修復が基本であり, tension-freeヘルニア修復術としてmesh-plug法の報告はあるが, PHSを応用した報告は初めてであり有用な方法と考えられた.

腹腔鏡下胆嚢摘出術の術中に落下した結石が原因となり腹腔内膿瘍形成後,胸腔に穿破を認めたため,手術を要した症例を経験したので報告する. 症例は73歳女性.急性胆嚢炎,胆嚢結石症にて腹腔鏡下胆嚢摘出術を施行した.術中に胆嚢損傷で結石が腹腔内に落下したが可及的に回収.術後経過は良好で退院した. 術後9カ月後,右側腹部痛,全身倦怠感,呼吸苦,両下肢の浮腫を主訴に再入院した.右横隔膜下に結石を伴う腹腔内膿瘍を認め,さらに右胸腔内に通じる瘻孔を確認した.以上より全身麻酔下に膿瘍ドレナージ,結石摘出と瘻孔切除術を施行した.経過は良好で現在まで再発は認めていない. 腹腔鏡下胆嚢摘出術における落下結石は稀に本症例のように膿瘍形成,胸腔への瘻孔形成することもあり,落下結石の予防は大切である.僅かな落下結石もできるだけ回収し,術後,長期に観察することが大切と思われる.

By means of PCR-SSCP and direct sequencing, we detected 12 germ-line mutations of hMSH2 or hMLH1 in 37 Japanese hereditary non-polyposis colorectal cancer (HNPCC) kindreds, of whom 15 satisfied the Amsterdam and 22 the Japanese criteria. The germ-line mutation detection rate of hMSH2 was much higher than that of hMLH1 (11/37 vs. 1/37). The total mutation detection rate of hMSH2 and hMLH1 in the Amsterdam criteria group was significantly higher than that in the Japanese criteria group (9/15 vs. 3/22). Furthermore, the mean age of the HNPCC patients in the mutation-positive group was lower than that in the mutation-negative one; the rates of both vertical transmission and multiplicity of tumors in the mutation-positive group were higher than those in the mutation-negative one. In addition, the number of patients with microsatellite instability–positive cancers in the mutation-positive group was higher than that in the mutation-negative one. Our results suggest firstly that the hMSH2 gene plays a much more important role than hMLH1 in the carcinogenesis of Japanese HNPCC patients, secondly that the rate of hMSH2 and hMLH1 mutations is high in the kindreds satisfying the Amsterdam criteria and thirdly that both the clinical phenotypes (early onset, vertical transmission and multiplicity of tumors) and the microsatellite instability status are important for the genetic screening of HNPCC. Int. J. Cancer 82:512–515, 1999. © 1999 Wiley-Liss, Inc.

Thoracoscopic microwave coagulonecrotic therapy (TMCT) has been reported to be one of the useful approaches in the management of hepatocellular carcinoma (HCC) that is located in the subphrenic area of the liver.In the present study, TMCT was performed on a 75-year-old woman with HCCs and liver cirrhosis. On admission, computed tomography revealed low density areas [exceeding 3 cm in Couinaud's segment 8 (S8) and 1 cm in segment 2 (S2)]. TMCT was selected for the HCC in S8 because percutaneous ethanol injection therapy (PEIT) and transcatheter arterial embolization (TAE) were not effective and surgical resection was not possible due to hepatic dysfunction and multicentric carcinogenesis. A thoracoscope was introduced into the thoracic cavity through the 5 th intercostal space on the midaxillary line, and two other trocars were placed in the appropriate intercostal spaces along the anterior and posterior axillary lines. We treated the HCC in S8 with TMCT across the diaphragma using laparoscopic ultrasonography and in S2 with intraoperative PEIT to avoid complications due to its location near Glisson's sheath. The efficiency of the coagulation and ethanol injection was proven by employing postoperative enhanced computed tomography.It was suggested that multimodal minimally invasive treatment such as TMCT is effective when combined with interstinal therapy for multiple HCCs with liver cirrhosis.