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In Japan, nivolumab administration is the standard treatment for patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) who are refractory or intolerant to fluoropyrimidines and platinum-based chemotherapy. We determined if inflammatory prognostic factors are useful in patients with ESCC treated with nivolumab monotherapy.The clinical data of patients with ESCC treated with nivolumab monotherapy as the second- or later-line treatment were retrospectively analyzed. Neutrophil/lymphocyte, platelet/lymphocyte, and C-reactive protein/albumin ratios (CAR); prognostic index; and prognostic nutritional index were investigated. Cut-off values for each factor were determined according to overall survival using time-dependent receiver operating characteristic curves.During January 2017-June 2021, 93 consecutive patients with ESCC were enrolled from five institutions (median age, 70 years; male, 77%). With a median follow-up period of 9.1 (range, 1.0-34.7) months, the median overall and progression-free survival were 12.8 (95% confidence interval [CI], 9.0-16.6) and 4.0 (95% CI, 2.6-5.4) months, respectively. Of five inflammatory prognostic factors, the cut-off value for CAR was 0.62; prognosis was significantly longer in those with CAR 0.62 (hazard ratio, 0.39; 95% CI, 0.22-0.67; p = 0.001).Inflammatory prognostic factors were useful in predicting prognosis for ESCC patients pretreated with nivolumab, especially for those with CAR 0.62, suggesting that CAR adequately reflects prognosis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancers worldwide, with a poor prognosis. Owing to the difficulty of early diagnosis, the aim of this study was to isolate biomarkers from extracellular vesicles (EVs) that can lead to early diagnosis.EVs in the culture supernatant were isolated from a pancreatic cancer cell line (PK-1) and expanded by using two-dimensional gel electrophoresis, and protein identification from each spot was performed by using matrix-assisted laser desorption ionization mass spectrometry. The identified proteins were classified and compared with previously reported results for EVs from murine pancreatic cancer PAN02 cells, and their expression specificity was examined using PDAC cell lines and patient-derived PDAC tissues. In addition, the significance of selected biomarker(s) was examined based on the changes in biomarkers in the blood EVs of PDAC patients after surgery.We found that the ITGA6A splice variant was predominantly expressed in several pancreatic cancer cell lines and blood EVs from patients with PDAC, whereas the ITGA6B splice variant was predominantly expressed in EVs from the blood of normal volunteers. In the expression pattern of ITGA6 in EVs from blood samples of two PDAC patients before and after resection surgery, the expression of ITGA6A in EVs significantly decreased after surgery and increased several months before clinical recurrence. Furthermore, the increased expression of ITGA6A in EVs occurred much earlier than that of CA19-9.Determination of ITGA6A expression in blood EVs in PDAC patients could be a useful blood marker for the early diagnosis of PDAC recurrence.

Although nanoliposomal irinotecan combined with 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) has been used to treat first-line resistant unresectable pancreatic cancer, the efficacy and safety data among the elderly remain limited. We retrospectively analyzed clinical outcomes among elderly patients. Patients treated with nal-IRI+5-FU/LV were assigned to the elderly (≥75 years) and non-elderly (

Preoperative chemotherapy is efficacious in several cancers. However, it is not an established treatment for locally advanced colon cancer, particularly cases with microsatellite instability-high (MSI-H)/deficient mismatch repair. Herein, we report a case of pathological complete response of MSI-H clinical T4b ascending colon cancer to preoperative treatment with pembrolizumab. A 78-year-old man was diagnosed with ascending colon cancer that invaded into the iliacus muscle and enlarged regional lymph nodes. The tumor was classified as T4bN1bM0 stage IIIC according to the 8th Union for International Cancer Control guidelines, with MSI-H status. Based on our initial diagnosis, this tumor could not be resected completely. Thus, the patient underwent preoperative therapy with CAPOX (capecitabine and oxaliplatin combination) plus bevacizumab. After 4 cycles of preoperative CAPOX/bevacizumab, we observed tumor reduction corresponding to a partial response based on the Response Evaluation Criteria in Solid Tumors criteria. Nevertheless, tumor invasion of the iliacus muscle persisted. Since oxaliplatin-induced peripheral sensory neuropathy was observed, we discontinued treatment with oxaliplatin and changed the regimen to pembrolizumab in anticipation of the therapeutic effect of this immune checkpoint inhibitor against MSI-H tumors. After 2 cycles of therapy with pembrolizumab (200 mg/body on day 1 every 3 weeks), there was drastic tumor regression. In addition, computed tomography indicated that all lymph node metastases had disappeared. Therefore, the patient underwent laparoscopic right hemicolectomy with D3 lymph node dissection. Analysis of the resected specimen showed pathological complete response.

Background RAS/BRAFV600E mutations are the most remarkable oncogenic driver mutations in colorectal cancer (CRC) and play an important role in treatment selection. No data are available regarding the clinical and prognostic features of patients with detailed RAS/BRAFV600E-mutant metastatic CRC (mCRC) in Japan. Methods A total of 152 chemotherapy-naïve patients with mCRC were included in this study between August 2018 and July 2019. Tumor samples were collected, and RAS/BRAFV600E status was investigated. RAS/BRAFV600E status was examined using a MEBGEN RASKET-B kit and polymerase chain reaction reverse sequence-specific oligonucleotide method. Results RAS/BRAFV600E mutations were detected in 54% of cases (KRAS codon 12, 26%; KRAS codon 13, 17%; KRAS non-Exon2, 5%; NRAS, 5%; and BRAFV600E, 7%). BRAFV600E-mutant CRC mainly existed in the right colon, whereas KRAS non-Exon2 and NRAS-mutant CRC was predominantly present in the left colon. KRAS non-Exon2 and NRAS-mutant CRC were associated with shorter survival time than RAS wild-type CRC (hazard ratio [HR], 2.26; 95% confidence interval [CI], 0.64–8.03; p = 0.19; HR, 2.42; 95% CI, 0.68–8.61; p = 0.16) and significantly shorter overall survival than KRAS Exon2-mutant CRC (HR, 3.88; 95% CI, 0.92–16.3; p = 0.04; HR, 4.80; 95% CI, 1.14–20.2; p = 0.02). Conclusions In our multicenter study, the findings elucidated the clinical and prognostic features of patients with detailed RAS/BRAFV600E-mutant mCRC in Japan.

Background: Trifluridine/tipiracil (FTD/TPI) is an oral chemotherapy comprising a thymidine-based nucleoside analog and a thymidine phosphorylase inhibitor. The FTD/TPI versus placebo in patients with heavily pretreated metastatic gastric cancer trial showed that FTD/TPI is effective with manageable toxicity in these patients. However, data on the effect of FTD/TPI on patients with advanced gastric cancer (AGC) having ascites are limited.Methods: We retrospectively collected and analyzed the clinicopathologic data of patients with AGC who had received FTD/TPI monotherapy in our institutions from September 2019 to July 2021.Results: A total of 53 patients were included in this study. The median age was 70 (range, 37‒85) years, 39 patients were men, the numbers of patients with Eastern Cooperative Oncology Group performance status scores 0, 1, and 2 were 10, 39, and 4, respectively, and 27 patients had diffuse-type histology. A total of 29 patients had ascites, among whom 14 had massive ascites. The response rate and disease control rate (DCR) were 2% and 35%, respectively. The median progression-free survival was 2.4 months and median overall survival (OS) was 5.8 months. Patients with ascites exhibited significantly shorter OS (8.6 vs. 4.7 months, P=0.0291) than those without ascites, and DCR (54% vs. 18%, P=0.0055) was significantly worse in patients with ascites. There was no significant difference in the frequency of occurrence of adverse events of grade 3 or higher between patients with and without ascites.Conclusion: FTD/TPI has a moderate, although inadequate, effect on patients with AGC having ascites.

Trastuzumab deruxtecan (T-DXd) has shown promising efficacy against HER2-positive advanced gastric cancer (AGC). However, data on its real-world efficacy in AGC patients are insufficient, and the predictive marker of T-DXd is unclear. In this multi-center retrospective study, we collected clinical information of 18 patients with HER2-positive AGC who received T-DXd after intolerant or refractory responses to at least two prior regimens and analyzed predictive factors. The median age was 71 years (range: 51–85), 13 men were included, and ECOG performance status (PS): 0/1/2/3 was 9/6/2/1. A total of 11 patients (61%) received prior immune checkpoint inhibitors (ICIs), 14 patients were HER2 3+, and 4 patients were HER2 2+/FISH positive. The median trastuzumab (Tmab)-free interval was 7.7 months (range: 2.8–28.6). The overall response rate was 41%, and the disease control rate was 76%. Median progression-free survival (PFS) was 3.9 months (95% CI: 2.6–6.5), and median overall survival (OS) was 6.1 months (95% CI: 3.7–9.4). PFS (6.5 vs. 2.9 months, p = 0.0292) and OS (9.2 vs. 3.7 months, p = 0.0819) were longer in patients who received prior ICIs than in those who had not. PFS (6.5 vs. 3.4 months, p = 0.0249) and OS (9.4 vs. 5.7 months, p = 0.0426) were longer in patients with an 8 month or longer Tmab-free interval. In patients with ascites, PFS (6.5 vs. 2.75 months, p = 0.0139) and OS (9.4 vs. 3.9 months, p = 0.0460) were shorter. T-DXd showed promising efficacy in HER2-positive AGC patients in a real-world setting. Pre-administration of ICIs and a sufficient Tmab-free interval may be predictive factors of T-DXd efficacy.

Background: Brain metastases (BM) occur in 20%-50% of patients (pts) with HER2-positive (HER2+) metastatic breast cancer (MBC), and their presence is a poor prognostic factor. Leptomeningeal carcinomatosis (LMC) occurs in 12%–43% of pts with MBC. Therapeutic options for BC pts with BM and/or LMC are limited. Results of the DESTINY-Breast01 and DESTINY-Breast03 studies have shown the clinical benefit of trastuzumab deruxtecan (T-DXd) in HER2+ MBC pts with stable BM; however, the study populations were small and did not include pts with active BM (untreated or progressive) and/or LMC. This data gap is addressed in the present study. Methods: ROSET-BM (UMIN000044995) is a multicenter, retrospective chart review study of pts who received T-DXd for HER2+ MBC with BM and LMC between May 25, 2020, and April 30, 2021, in a standard-of-care setting. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Additionally, in the pts with brain imaging data, intracranial (IC)-ORR and IC-PFS were evaluated by independent radiologists to provide central review according to RECIST v1.1. Active BM were determined by independent central review (ICR). Pts whose baseline and pre-baseline brain imaging data were compared and confirmed increased tumor size, or pts with new lesions were classified as active BM. LMC was determined by ICR using brain imaging. Results: In the study period, 62 sites participated, enrolling 113 pts with HER2+ MBC and BM were treated with T-DXd. After exclusion of data from 9 who did not meet the criteria for inclusion, 104 pts were included in the analysis. In the 104 pts, 70.2% (n=73) were active BM, 16.3% (n=17) were active BM with LMC, 5.8% (n=6) were stable BM, 1.9% (n=2) were only LMC, and 5.8% (n=6) were not classified. Symptomatic BM were observed in 30.8% (n=32). Median number of prior lines of therapy was 4 (range, 1–15). Median duration of follow up from first T-DXd treatment was 11.2 months. ORR assessed by investigator was 55.7% (complete response [CR], 5.2%) in all pts, 51.7% (CR, 6.9%) in symptomatic BM pts (n=29), and 57.4% (CR, 4.4%) in asymptomatic BM pts (n=68). Among all pts, median PFS was 16.1 months (95%CI, 12.0–n/a), and median OS was not reached (OS at 1 year was 74.9%). In the 19 pts with LMC, 1-year PFS and OS were 60.7% (95%CI, 34.5–79.1) and 87.1% (95%CI, 57.3–96.6), respectively (neither reached the median). Of the 89 pts with brain lesion imaging data (at both baseline and follow-up), IC-ORR was 62.7% (CR, 0.0%). IC-PD was observed in 5.9% (n=3) of pts. Median IC-PFS was 16.1 months (95%CI, 12.2–n/a). In all pts, the most common event and adverse event leading to discontinuation of T-DXd were PD (27 pts, 26.0%) and interstitial lung disease (19 pts,18.3%), respectively. Conclusion: The results of this retrospective chart review show that T-DXd has promising efficacy in HER2+ MBC pts with active BM and LMC. This study was funded by Daiichi Sankyo Co., Ltd. Citation Format: Takashi Yamanaka, Naoki Niikura, Hironori Nomura, Hiroki Kusama, Mitsugu Yamamoto, Kazuo Matsuura, Kenichi Inoue, Sachiko Takahara, Shosuke Kita, Miki Yamaguchi, Tomoyuki Aruga, Nobuhiro Shibata, Akihiko Shimomura, Yuri Ozaki, Kazuhiro Shiraishi, Shuji Sakai, Yoko Kiga, Tadahiro Izutani, Kazuhito Shiosakai, Junji Tsurutani. Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: A multicenter retrospective study (ROSET-BM study) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD7-01.

Background: Intraperitoneal chemotherapy using paclitaxel (i.p.-PTX) is expected to be a new therapeutic strategy for patients with pancreatic ductal adenocarcinoma (PDAC) and peritoneal dissemination. We evaluated the survival benefit of i.p.-PTX compared with standard systemic chemotherapy. Methods: Clinical data of 101 consecutive PDAC patients with peritoneal dissemination between 2007 and 2018 were analyzed. All patients were determined to have no other sites of distant organ metastasis to the lung, bone, or liver on contrast-enhanced CT imaging. Patients underwent staging laparoscopy or open laparotomy to confirm pathological evidence of peritoneal dissemination, and to exclude occult liver metastasis. Survival curves were estimated using the Kaplan–Meier method, and differences were compared using the log-rank test. Results: Forty-three patients were treated with i.p.-PTX (i.p.-PTX group) and forty-nine patients received standard systemic chemotherapy (Ctrl group). Nine patients did not receive any treatment (BSC group). The median survival time (MST) in the i.p.-PTX group was significantly longer than that in the Ctrl group (17.9 months vs. 10.2 months, p = 0.006). Negative peritoneal washing cytology was observed in 24 out of 43 patients in the i.p.-PTX group. The i.p.-PTX group tended to have a higher proportion of clinical responses than the Ctrl group (30% vs. 18%, p = 0.183). Conversion surgery was performed in 10 patients in the i.p.-PTX group and 2 patients in the Ctrl group after confirming disappearance of peritoneal dissemination with staging laparoscopy or open laparotomy (p = 0.005). The MST in patients who underwent surgical resection was significantly longer than that in patients who did not (27.4 months vs. 11.3 months; p < 0.0001). Conclusion: i.p.-PTX therapy provided improved survival in PDAC patients with peritoneal dissemination, and conversion surgery enhanced it in patients with favorable responses to chemotherapy. i.p.-PTX might become one of the treatment options to PDAC patients with peritoneal dissemination.

Medication support applications(apps)have been introduced to support oral anti-cancer drug management for outpatients with gastrointestinal cancer. It has been suggested that remote support using medication support apps contributes to improving the quality of life through adverse event management as well as medication management. However, it was evident that elderly patients could not install the apps due to barriers related to the network environments and device operations and medical problems such as information management and securing human resources.

733 Background: MONSTAR-SCREEN prospectively assessed the gut microbiota of 2000 patients (pts) with advanced solid cancer at 31 Japanese institutions. Here, we report the interim analysis results of the correlation between gut microbiota and the efficacy of first-line chemotherapy in pts with unresectable pancreatic cancer (PC) and bile tract cancer (BTC). Methods: We analyzed unresectable 205 PC and 83 BTC pts with clinical data as data cut-off on April 30, 2021, and 16S ribosome analysis results of stool samples. Among PC pts, 133 and 40 were treated with GnP (gemcitabine (GEM) plus nab-paclitaxel) and FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin), respectively. Among BTC pts, 32 and 33 were treated with GC (GEM plus cisplatin) and GCS (GEM, cisplatin, plus S-1), respectively. Pts with an above-median overall survival (OS) were defined as long-term survivors (LTS), and those with below-median OS and OS events were defined as short-term survivors (STS). We compared the alpha diversity index (ADI) of LTS and STS, and identified potential microbial biomarkers of LTS, STS, responders, and non-responders to first-line chemotherapy according to RECIST version 1.1, by linear discriminant analysis effect size (LEfSe). In each cohort, the top three microbiota with linear discriminant analysis scores of ≥ 3.0 were considered significant. Results: The median OS of PC and BTC pts was 13.5 and 15.9 months, respectively. In PC pts, no significant difference was noted in the ADI between LTS (n=20) and STS (n=40). In BTC pts, the ADI of LTS (n=10) was significantly higher than that of STS (n=20) in the Shannon index. LEfSe analysis in PC pts revealed that Burkholderiales and Sutterellaceae were predominant in LTS, while Lactobacillaceae was, in STS. In PC pts, Brachyspiraceae and Erysipelotrichales were predominant in responders (n=67), while Enterococcaceae and Lactobacillaceae were, in non-responders (n=137). In BTC pts, Peptostreptococcaceae, Fusobacteriaceae, and Clostridiaceae in LTS; Cardiobacteriaceae, Prevotellaceae, and Actinobacteriota in responders (n=24); and Bacilli in non-responders (n=59) were overrepresented. Conclusions: This interim analysis identified potential biomarkers of the gut microbiota that may contribute to the prognosis and efficacy of chemotherapy in pts with unresectable PC and BTC. The results of this analysis will be validated in the primary analysis.

Summary We report a case of rapid pleural effusion after discontinuation of lenvatinib. A 73-year-old woman was diagnosed with poorly differentiated thyroid cancer with right pleural metastasis. Weekly paclitaxel treatment was performed for 18 weeks, but it was not effective. Oral administration of lenvatinib, a multi-target tyrosine kinase inhibitor, reduced the size of cervical and thoracic tumors and lowered serum thyroglobulin levels. Lenvatinib was discontinued on day 28 because of Grade 2 thrombocytopenia and Grade 3 petechiae. Seven days after discontinuation of lenvatinib, the patient was hospitalized because of dyspnea and right pleural effusion. Pleural effusion rapidly improved with drainage and re-initiation of lenvatinib and did not recur. Anorexia caused by lenvatinib led to undernutrition, which resulted in death 13 months after initiation of lenvatinib. Autopsy revealed extensive necrosis with primary and metastatic lesions, suggesting that the patient responded to lenvatinib. Physicians should be aware of the possibility of flare-up in patients with thyroid cancer treated with lenvatinib. Learning points: Autopsy findings revealed that lenvatinib was efficacious in treating poorly differentiated thyroid cancer without primary lesion resection. Flare-up phenomenon may occur in thyroid cancer treated with lenvatinib. Attention should be paid to flare-up phenomenon within a few days of discontinuing lenvatinib.

今回われわれは極めて稀な男性副乳癌の1症例を経験したので報告する．症例は58歳，男性．2006年より右腋窩に母指頭大の腫瘤を自覚し，2008年初旬より増大傾向となった．同年9月に皮膚科を受診し，副乳癌が疑われ，当科に紹介された．CTでは右腋窩に内部が一部不均一に造影される5.5×3.5×4.0cmの腫瘍を認めた．FDG-PET/CTでも腫瘍のみに異常集積を認め，他部位からの悪性腫瘍のリンパ節・遠隔転移は否定的であった．生検ではER，PgR陽性の腺癌の像を認めた．手術は腋窩郭清を伴う腫瘤切除術を施行し，遺残なく切除可能で，周囲のリンパ節への転移は認めなかった．摘出標本では腫瘍周囲に固有乳腺と連続しない乳腺組織の存在を確認し，免疫組織化学染色ではER，PgR，gross cystic disease fluid protein-15（GCDFP-15）陽性，CK7，CK20，CEA，p63は陰性であり，副乳癌と診断した．術後補助療法としてTamoxifenを継続し，術後28カ月の現在，無再発生存中である．

In order to investigate the influence of the tempering temperature on a S-N characteristic in very high cycle fatigue regime, cantilever-type rotary bending fatigue tests up to 109 cycles were performed in air at room temperature using hour-glass shaped specimens heat treated at four kinds of tempering temperature in low-alloy steel, JIS SNCM439. Specimens tempered at low temperature of 433K and 573K showed a step-wise S-N curve, and were ruptured by internal fracture mode at high cycle fatigue regime above 106cycles. On the other hand, surface fracture mode only appeared on the specimens tempered at high temperature of 773K and 893K, and the fatigue limit existed clearly. Granular bright facet (GBF) area was observed in the vicinity of a non-metallic inclusion which was origin of an internal fracture. Properties of the GBF area were verified from the experimental facts that the roughness of the GBF area was larger than that outside the GBF in a fish-eye, the size and the distribution of convex particles on the GBF area were same as those of spherical carbide particles in the matrix, and a high density of carbon was detected on the GBF area by EPMA. It was suggested that a decohesion of spherical carbide from the matrix for the formation of the GBF area was affected by the size of the carbide which became large with decreasing the tempering temperature.

It is widely accepted that antimicrobial prophylaxis is useful for the prevention of surgical wound infection, especially in colorectal surgery. While many reports support the finding that the first dose should be administered immediately before surgery, there is less evidence concerning the ideal timing for the second dose. The purpose of this study is to examine the significance of intraoperative repeated dosing. A surgical series of 131 patients with primary colorectal cancer was retrospectively analyzed for 14 parameters, including the protocols of antimicrobial administration to determine the clinical risk factors for surgical wound infection. The overall surgical wound infection rate of the 131 patients was 16.0% (21/131). When the operation finished within 4 h after the first dose (n = 29), wound infection was observed in only one patient (3.4%). In a prolonged operation exceeding 4 h after the first dose, the surgical wound infection rates were 8.5% and 26.5%, respectively, for those with (n = 47) and without (n = 49) intraoperative repeated dosing, which were significantly different based on both a univariate analysis (P = 0.031) and a multivariate analysis (P = 0.0079). Intraoperative repeated antimicrobial dosing is therefore recommended to prevent the surgical wound infection for prolonged colorectal surgery.

子宮留膿腫は高齢女性に多くみられる疾患で, まれに腹腔内に穿破し腹膜炎を起こすことがある. 今回, 我々は急性腹症により発症し, 保存的に改善した子宮留膿腫による直腸子宮瘻の1例を経験したので報告する. 症例は61歳の女性で, 2003年5月, 下腹部痛・嘔吐が出現した. 来院時は下腹部に筋性防御がみられ, CTでは直腸と子宮が交通している所見がみられた. 大腸内視鏡では直腸に径2cmの瘻孔を認め, 瘻孔からは子宮内腔が観察され, 子宮留膿腫の直腸穿破と診断した. 発症から約1か月後の大腸内視鏡・注腸検査で瘻孔は縮小傾向にあり, CTでは肥大した子宮の内腔にair densityと液体成分の貯留を認めた. 子宮頸管の癒着による閉鎖がみられたため, 頸管拡張術を施行し経過観察したところ, 症状の再燃はみられなかった. 子宮留膿腫による直腸子宮瘻は適切なドレナージで保存的に閉鎖が期待できるが, 慢性化する可能性もあり, 慎重な経過観察が必要である.

PURPOSE: CA19-9 is often used in combination with carcinoembryonic antigen to manage patients with colorectal cancer, even though there is insufficient evidence to support this use of CA19-9. Carcinoembryonic antigen, by contrast, has been regarded as a better indicator of poor prognosis and recurrence. The purpose of this study is to clarify whether CA19-9 is, in fact, a useful marker in the management of colorectal cancer patients by comparing it with carcinoembryonic antigen. METHODS: A retrospective investigation was done for a consecutive series of 155 patients with colorectal adenocarcinoma who underwent potentially curative surgery between 1995 and 1999. Excluded were patients with postoperative assays performed less than three times for either carcinoembryonic antigen or CA19-9 and those who had developed secondary cancers. Data from 118 patients were analyzed in terms of prediction of prognosis and detection of recurrences. RESULTS: The sensitivities of preoperative CA19-9 and carcinoembryonic antigen were 29.8 percent and 45.3 percent, respectively. In the univariate analysis of preoperative carcinoembryonic antigen and CA19-9 assays in 114 patients, high carcinoembryonic antigen level was significantly associated with poor prognosis (P = 0.0090 by log-rank test). We could not find a significant association between preoperative CA19-9 abnormality and survival (P = 0.12). Multivariate analysis of preoperative factors indicated significance in TNM stage (P = 0.0094) and tumor location (P = 0.036) but in neither carcinoembryonic antigen (P = 0.061) nor CA19-9 (P = 0.22). Among 40 patients with recurrences, postoperative elevations of tumor markers were seen in 19 cases for CA19-9 and in 37 for carcinoembryonic antigen throughout the follow-up periods. Sensitivity, specificity, positive predictive value, and negative predictive value were 0.48, 0.88, 0.68, and 0.77, respectively, for CA19-9, and 0.93, 0.88, 0.80, and 0.96, respectively, for carcinoembryonic antigen. In patients with recurrences, the initial postoperative elevation of tumor markers was seen earlier than the detection of recurrence in 68.4 percent of those with CA19-9 elevation and in 67.6 percent of those with carcinoembryonic antigen elevation. There was only one patient with recurrence who had CA19-9 elevation without carcinoembryonic antigen elevation, while 19 recurrent patients had carcinoembryonic antigen elevation without CA19-9 elevation. Multivariate analysis showed a significant risk of carcinoembryonic antigen elevation against recurrence with an odds ratio of 32.0 (P < 0.0001), in contrast to an insignificant association of CA19-9 elevation (P = 0.23). CONCLUSION: We could not find clinical significance to support the use of CA19-9 to predict the prognosis and detect recurrence of colorectal cancer. Because of this, we do not recommend routine use of CA19-9 in staging and surveillance of colorectal cancer patients.

進行胃癌を伴った食道破裂の1例を経験した.症例は57歳男性.昼食後に嘔吐し,急激に右胸部痛,上腹部痛が出現し,発症から約4時間後に当院救急外来を受診した.胸腹部所見,胸部単純レントゲン,胸腹部CT,食道造影により胸部下部食道破裂,幽門狭窄と診断し緊急手術となった.上腹部正中切開による経食道裂孔アプローチにて一期的単純縫合閉鎖術,有茎大網被覆術,縦隔ドレナージ術,胃空腸バイパス術を施行した.胃癌による幽門狭窄のうえ,出血が催吐因子となって発症した,と考えられた.胃癌に伴った食道破裂は自験例を含め本邦9例目であったが,同時に診断されたのは5例であった.また進行胃癌に伴ったものは4例であった.食道破裂は早期診断,治療をしないと死亡率が高く,併存疾患がある場合の診断はより困難である.まず食道破裂の存在を念頭におき,催吐因子として併存疾患の検索も重要であると考えられた.

In 19 surgically treated patients with sleep-disordered breathing for whom electroencephalograms could be recorded before and after surgery, and in 10 patients who suffered from daytime lethargy as assessed using the Epworth Sleepiness Scale (ESS) score, correlations between the stages of sleep before surgery and the ESS score and apnea-hypopnea index (AHI) were evaluated, and changes in AHI and the stages of sleep after surgery were examined. Neither the preoperative severity of AHI nor the ESS score showed an association with the stages of sleep. The improvement in the quality of sleep tended to be greater as the percentage improvement in the ESS score increased.

Although general experience has suggested that the lateral sleeping position is the most effective for patients with sleep-related respiratory disorders, few studies have demonstrated this observation using controlled conditions and objective indicators. The aim of the present study was to investigate the sleeping position of 200 patients with sleep-related respiratory disorders, including some in whom obesity played a role. The apnea-hypopnea index (AHI) improved when patients moved from the supine to the lateral position, but the improvement was only slight in patients with a high AHI or a tendency to obesity. These findings suggest that advising patients to sleep in the lateral position will only be effective for those with a moderate to low AHI, or a minimal tendency to obesity.

OBJECTIVE: We assess the usefulness of microwave hepatic tumor coagulation therapy with balloon occlusion of segmental hepatic blood flow for eight recurrent metastatic hepatic tumors in seven patients. CONCLUSION: Limited early experience with microwave hepatic tumor coagulation therapy and segmental hepatic blood flow occlusion has been positive, suggesting that further clinical evaluation is warranted.

Two cases of obstructive sleep apnea (OSAS) caused by primary hypothyroidism are reported.The first patient was a 66-year-old man who complained of sleep apnea with an apnea/hypopnea index (AHI) of 50.8 per night as assessed by all night monitoring. Hypothyroidism was subsegently suspected when he showed delayed recovery from general anesthesia following surgery involving UPPP (uvulo-palato-pharyngoplasty). Hypothyroidism was diagnosed on the basis of blood tests. His snoring and apnea improved after 2 months of levothyroxine sodium administration and the AuI changed from 50.8 to 13.0.The second patient was a 73-year-old man with an AHI of 41.3 per night as assessed by all night monitoring. Hypothyroidism was diagnosed on the basis of blood tests and was suspected because of his slow speech. He was similarly treated with levothyroxine sodium. The AHI did not decrease after treatment for 4 months. His desaturation time (the rate of O2 saturation less than 90%) improved however, from 56.6 to 31.9, and the symptoms of hypothyroidism also recovered markedly. In both patients, elevated creatine phosphokinase (CPK), dull facial expression, peripheral edema, and slow speech were recognized and these were suggestive of hypothyroidism. The type of sleep apnea was mainly obstructive in both patients.

The following six parameters were studied in 119 patients who responded to a questionnairebased long-term survey of 208 adults who had undergone surgery for obstructive sleep apnea syndrome in the previous 8 years: 1) snoring, 2) sleep apnea, 3) daytime sleepiness, 4) nocturnal arousal, 5) malaise, and 6) quality of sleep.The patients were divided into a markedly or moderately improved group (group A) and a slightly improved or unchanged group (group B) based on improvement of the apnea-hypopnea index (AHI) after surgery.In group A, improvement of snoring, sleep apnea, daytime sleepiness, and quality of sleep tended to decrease over the long term.In group B, improvement of these four symptoms was more marked than improvement of the AHI in the early postoperative period (1 year after surgery), with a significant difference between the two. The same pattern was also apparent in the long-term results.There was no major difference between the improvement of nocturnal awakening or malaise and improvement of the AHI over either the short or long term in groups A or B.

結腸癌の肝転移に対して4回の肝切除を施行し, 8年間生存中の症例を経験したので報告する. 症例は56歳の男性で, 1990年5月, 閉塞性イレウスのため緊急手術をうけた. 術中に横行結腸癌および転移性肝癌と診断され, 結腸右半切除と肝部分切除が行われた. 組織学的にはいずれも中分化型腺癌であった. 1年6か月後にCTスキャンにより外側区域の転移巣が発見され, 2回目の肝切除 (外側区域切除) が行われた. さらに4年後, CTスキャンによりS4とS8に2個の転移巣が発見され, 3回目の肝切除が行われた. その3年後にはS5に4cmの転移巣が発見され, 4回目の肝切除が行われ, いずれの組織診断も中分化型腺癌であった. 患者は初回手術より8年経過した現在, 元気に生存中である. 大腸癌肝転移に対する再肝切除の臨床評価はいまだ明らかでない. この症例経過は選択された症例に対する再肝切除の有効性を示すものである.

A 65-year-old man was diagnosed as having hepatocellular carcinoma (HCC) with liver cirrohosis classified clinical stage, which caused by hepatitis C virus. Abdominal contrast CT showed HCC in the diameter of 2 cm located Segment 4. Laparoscopic microwave coagulation therapy under hepatic blood flow occlusion using clamp was performed. We applied the coagulation time for 10 minutes with an output of 80 watts for 60 seconds at a time. After 2 months the hepatic tumor was completely enclosed within the coagulation area and no recurrence was showed for 14 months after procedure. We have reported that the coagulation areas with the hepatic blood flow occlusion was about twice as big as that without blocking the hepatic blood flow. This suggested that a 3 cm hepatic tumor can be controled by this method. We proposed that laparoscopic microwave coagulation therapy under hepatic blood flow occlusion should be selected for HCC of small size or middle-size hepatic tumor and high risk patients.

The possible use of percutaneous microwave tumor coagulator (PMCT) by using CT for local tumor recurrence of rectal cancer was studied in this paper. Preliminary study was performed using adult Landrace pig and we applied the coagulation time for 3 minutes. The CT guided PMCT was performed for patient with local abdomino-perineal excision. The tumor in the pelvic space were observed on CT images. With patient in the prone position on the CT table, a 14-gauge needle was used to penetrate the tumor under epidural and local anesthesia.PMCT was performed with an output of 60 watts for 60 seconds at a time. Effects of the PMCT were evaluated by CT images obtained three months after the therapy, there was no evidence of growth for the tumor on the CT images. Clinical symptoms disappered soon after the therapy, and no major complication was observed.Results of this study suggests that the CT guided PMCT therapy may be useful for local recurrence of rectal cancer.

Using the bovine liver and experimental deep electrodes, we investigated the coagulation effect in ischemic livers in an attempt to increase the range of coagulation of the deep electrodes. The hepatic blood flow was obstructed by blocking the hepatic artery (A), the portal vein (P), or both the hepatic artery and portal vein (AP), and for comparison, coagulation was performed without blocking the hepatic blood flow (C) in control animals. Two electrodes were used for microwave coagulation ; a 1.6-mm shell-type deep electrode (shell-type), and a 3-mm experimental electrode (30 NL). After coagulation, each sample was fixed in 10% formalin and sliced for histological examination. There was a brown boundary area between the coagulated and non-coagulated areas.When the hepatic blood flow was not blocked and coagulation was performed using the shell-type deep electrode at 60W for 2 minutes, a brown boundary area of 1 to 3 mm was seen. The internal diameter of the coagulated area was 23 × 11 mm, and its external diameter including the brown boundary area was 26 × 16 mm. When the hepatic artery or the portal vein was blocked to obstruct the hepatic blood flow, the internal diameter of the coagulated area was 51 × 20 mm, and its external diameter was 56 × 34 mm. Furthermore, on using the 30 NL electrode was used for coagulation at 60W for 2 minutes, the maximum internal and external diameters of the coagulated areas were 25 × 16 and 34 × 27 mm, respectively, when the hepatic blood flow was not blocked (C), 27 × 19 and 35 × 29 mm, respectively, when the hepatic artery was blocked (A), 24 × 21 and 35 × 34 mm, respectively, when the portal vein was blocked (P), and 27 × 26 and 68 × 50 mm, respectively, when the hepatic artery and portal vein were blocked (AP). This indicated that the brown boundary area increased when the portal vein was blocked, and when the hepatic artery and portal vein were blocked, the diameter of the coagulated areas was about twice as big as that without blocking the hepatic blood flow. HE-staining of the cross sections of boundary areas showed shrunken nuclei and intercellular hemorrhagic changes. This suggested that a 3-cm hepatic tumor can be controlled by a single microwave coagulation inserting the experimental electrode into the center of the tumor while blocking the hepatic blood flow.

Objective: 55 patients diagnosed as having obstructive sleep apnea syndrome (OSAS) underwent uvulopalatopharyngoplasty (UPPP). The effects of surgery were studied based on the findings of endoscopic examination under drug-induced sleep and AHI measurements performed before and after the operation. Changes in airway form during sleep were observed, and the usefulness of upper airway endoscopy in the diagnosis and surgical treatment of OSAS was studied.Methods: The site of airway obstruction during sleep induced by intravenous injection of 10mg of diazepam was classified into five types, and changes in AHI and the site of airway obstruction were compared before and after surgery.Results: The postoperative improvement rate was 73.5% in the soft palate type of obstruction, 75.6% in the tonsillar type, 52.3% in the full-circumference palatal type and 32.3% in the mixed type. Surgical treatment by UPPP had an excellent or good effect on the soft palate and tonsillar types. However, many patients with the ful1-circumference palatal type and the mixed type showed less improvement compared with the soft palate and tonsillar type.Conclusion: In the full-circumference palatal type and the mixed type, improvement can be expected following operations which include surgical treatment of the posterior pharyngeal wall or the lateral funiculus, or midline laser glossectomy.

In the present study, we subjected 65 patients to overnight monitoring and continuous nocturnal blood pressure measurement in order to assess the influence of sleep apnea on the circulatory system. Thirty-one patients were compared before and after surgery. The severity of sleep apnea was classified by Apnea Hypopnea Index (AHI), the duration of exposure to low-level oxygen (calculated as the desaturation time: DT), and increment of blood pressure. Before surgery, a significant correlation was noted between the DT and blood pressure changes. Therefore, this index was considered useful for assessing the influence of sleep apnea on nocturnal blood pressure. After surgery, improvement of AHI was greater than 50% in 19/31 patients (61.3%), and this result was almost the same as described in the literature. The improvements in DT and BP change were greater than 50% in 21/31 (67.7%) and 14/31 (45.2%), respectively. With regard to severity before surgery, AHI was > or = 50 and DT was > or = 40% in 10 and 18 patients, respectively. Nineteen patients had BP changes > or = 40 mmHg. After surgery, 1,5, and 2, patients, respectively, still showed these values. Thus, a beneficial effect of surgery was demonstrated.

Obstructive Sleep Apnea Syndrome (OSAS) is children is commonly caused by upper airway obstruction, such as that caused by adeno-tonsillar hypertrophy. We report a rare case of SAS due to a nasopharyngeal tumor. The patient was a 10-year-old boy who complained of snoring and sleep apnea. The tumor was found in the nasopharynx and mesopharyngeal space. We diagnosed this case as OSAS by overnight sleep study (Apnea Hypopnea Index: AHI = 19.67). The tumor was removed under general anesthesia. Histopathology revealed features of nasopharyngeal angiofibroma. After removal of the tumor, his symptoms resolved completely. A follow-up overnight sleep study confirmed resolution of OSAS. At the last follow up, conducted 17 months after the operation there were no signs of tumor recurrence.

According to the obstructive site, the different types of obstructive-type sleep-disordered breathing are classified as the soft palate type, palatine tonsil type, soft palate and depressed lingual root type, depressed lingual root type and epiglottis type. In this study, we conducted dynamic MRI examinations of the oral, pharyngeal and lingual root sites in patients with obstructive sleep-disordered breathing, and studied the usefulness of MRI as a diagnostic tool for the examination of such obstructive sites.

We statistically investigated the total PTR resource record (RR) based DNS query request packet traffic from the Internet to the top domain DNS server in a university campus network through January 1st to December 31st, 2011. The obtained results are: (1) We found twelve host search (HS) attacks in the scores for detection method using the calculated Euclidean distances between the observed IP address and the last observed IP address in the DNS query keywords by employing both threshold ranges of 1.0-2.0 (consecutive) and 150.2-210.4 (random). However, we found nineteen HS attacks in the scores using the calculated cosine distance between the DNS query IP addresses (threshold ranges of 0.75-0.83 and 0.9-1.0). (3) In the newly found HS attacks, we observed that the source IP addresses of the HS attack DNS query packets are distributed. Therefore, it can be concluded that the cosine distance based detection technology has a possibility to detect the source IP address-distributed host search attack.

長期生存中の胃平滑筋肉腫肝転移の2例を経験した. 症例1は70歳の男性で, 噴門側胃切除後1年7か月目に肝転移を認め, 肝部分切除および門脈内注入化学療法を施行した. 肝切除後3年5か月無再発生存中である. 症例2は51歳の男性で, 術後の残胃に発生した平滑筋肉腫例である. 残胃全摘後2年8か月目に肝に転移を認めた. 肝動脈塞栓術を計3回施行し, 腫瘍の縮小は認めなかったものの, 肝転移の診断より4年10か月生存中である. 胃平滑筋肉腫の肝転移の予後は不良といわれているが, いずれの2症例も長期生存を得ている. また本邦における肝切除術16例の術後平均生存期間は19. 1か月であり, これらの中にも2年以上の長期生存例が5例認められた. 胃平滑筋肉腫の肝転移に対しては, 適応があれば肝切除術を施行し, 適応のないものに対しては肝動脈塞栓術を反復施行して延命効果を期待すべきであると思われた.

盲腸からS状結腸におよぶ広範囲の壊死型虚血性大腸炎を経験した.症例は59歳の女性で, 腹痛・嘔吐を主訴に入院した.翌日腹膜炎症状が出現し, 緊急開腹術を施行した.盲腸からS状結腸まで連続性壊死に陥っており, 壊死型虚血性大腸炎の診断のもと, 結腸亜全摘・回腸人工肛門およびS状結腸痩造設術を施行し, 救命しえた.本邦における壊死型虚血性大腸炎49例の集計では, 年齢34～90歳 (平均年齢70.2歳) で60歳代から80歳代に多く, 性差はほとんど認められなかった.好発部位は下行結腸・S状結腸であり, この範囲で半数以上を占める.予後不明11例を除く38例の死亡率は44.7%で, そのうち切除施行例36例においても死亡率は41.7%と予後不良である.唯一の治療法は病変部の切除であるが, この際切除断端粘膜面を観察しつつ十分広範囲に切除する必要がある.