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Objective: To elucidate the diagnostic accuracy of macroscopic and histopathological diagnoses of molar pregnancy as compared with cytogenetic diagnosis as the gold standard., Study Design: Patients were recruited for the molecular diagnostic study of suspected molar pregnancy at Chiba University Hospital between 2007 and 2011. Gynecologists performed macroscopic diagnoses immediately after the evacuation. Pathological diagnoses were then made by pathologists in routine bases without performing p57Kip2 immunostaining. Molecular cytogenetic diagnosis was performed via short tandem repeat (STR) polymorphism analysis. Androgenetic, biparental triploid, and biparental diploid villous tissues determined on STR polymorphism analysis were classified as complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), and abortion, respectively., Results: A total of 86 patients were enrolled. The number of CHMs, PHMs, and abortions on cytogenetic diagnoses were 64, 9, and 13, respectively. The concordance rate between macroscopic and cytogenetic diagnoses was 85% (CHM: 56, PHM: 4, and abortions: 13). The concordance rate between histopathological and cytogenetic diagnoses was 87% (CHM: 59, PHM: 5, and abortions: 10). The complete agreement rate among the 3 categories was 78% (CHM: 55, PHM: 3, and abortions: 10)., Conclusion: Neither macroscopic nor histopathological diagnoses were perfect, but both were quite accurate in a single trophoblastic center.

Adenocarcinomas exhibiting gastric differentiation represent a recently described and uncommon subtype of non-human papillomavirus (HPV)-related cervical adenocarcinoma. They comprise a spectrum from a well-differentiated variant (adenoma malignum/mucinous variant of minimal deviation adenocarcinoma) to a more poorly differentiated overtly malignant form, generally referred to as gastric-type adenocarcinoma. Rarely, such tumors have also been described as primary vaginal neoplasms. Gastric-type adenocarcinomas exhibit considerable morphologic overlap with adenocarcinomas originating outside the female genital tract, especially mucinous adenocarcinomas arising in the pancreas and biliary tract. Moreover, they often metastasize to unusual sites, such as the ovary and peritoneum/omentum, where they can be mistaken for metastatic adenocarcinomas from other, nongynecologic sites. There is little information regarding the immunophenotype of gastric-type adenocarcinomas, and knowledge of this is important to aid in the distinction from other adenocarcinomas. In this study, we undertook a detailed immunohistochemical analysis of a large series of cervical (n=45) and vaginal (n=2) gastric-type adenocarcinomas. Markers included were cytokeratin (CK)7, CK20, CDX2, carcinoembryonic antigen, CA125, CA19.9, p16, estrogen receptor, progesterone receptor, MUC6, PAX8, PAX2, p53, hepatocyte nuclear factor 1 beta, carbonic anhydrase IX, human epidermal receptor 2 (HER2), and mismatch repair (MMR) proteins. All markers were classified as negative, focal (<50% of tumor cells positive), or diffuse (≥50% tumor cells positive) except for p53 (classified as "wild-type" or "mutation-type"), HER2 (scored using the College of American Pathologists guidelines for gastric carcinomas), and MMR proteins (categorized as retained or lost). There was positive staining with CK7 (47/47-45 diffuse, 2 focal), MUC6 (17/21-6 diffuse, 11 focal), carcinoembryonic antigen (25/31-12 diffuse, 13 focal), carbonic anhydrase IX (20/24-8 diffuse, 12 focal), PAX8 (32/47-20 diffuse, 12 focal), CA125 (36/45-5 diffuse, 31 focal), CA19.9 (11/11-8 diffuse, 3 focal), hepatocyte nuclear factor 1 beta (13/14-12 diffuse, 1 focal), CDX2 (24/47-4 diffuse, 20 focal), CK20 (23/47-6 diffuse, 17 focal), and p16 (18/47-4 diffuse, 14 focal). Most cases were negative with estrogen receptor (29/31), progesterone receptor (10/11), PAX2 (18/19), and HER2 (25/26). p53 showed "wild-type" and "mutation-type" staining in 27 of 46 and 19 of 46 cases, respectively. MMR protein expression was retained in 19 of 20 cases with loss of MSH6 staining in 1 patient with Lynch syndrome. Molecular studies for HPV were undertaken in 2 tumors, which exhibited diffuse "block-type" immunoreactivity with p16, and both were negative. This is the first detailed immunohistochemical study of a large series of gastric-type adenocarcinomas of the lower female genital tract. Our results indicate immunophenotypic overlap with pancreaticobiliary adenocarcinomas but suggest that PAX8 immunoreactivity may be especially useful in distinguishing gastric-type adenocarcinomas from pancreaticobiliary and other nongynecologic adenocarcinomas, which are usually negative. Diffuse "block-type" p16 immunoreactivity in a cervical adenocarcinoma is not necessarily indicative of a high-risk HPV-associated tumor.

The awkward movements and postures associated with childcare activities can lead to musculoskeletal symptoms in the neck and shoulders. "Dakko" is a method for carrying a child in Japan, and recently it has been reported to cause shoulder stiffness. To our knowledge, the relationship between childcare activities and the physical load on the neck and shoulders is poorly understood. The present study aims to clarify the muscle load on the neck and shoulder region through dakko simulations. First, the association between dakko movements and trapezius muscle activity is clarified by image and electromyogram analyses. Based on this clarification, the distributions and intensity of the muscle load from repetitive dakko movements are clarified using myogenic potential topography. During dakko movements, trapezius muscle activity was observed when lifting up and setting down the child, but not when holding the child. For the repetitive movements, myogenic electrical potentials were observed in the trapezius region after movement load, and individual characteristics of participants were revealed in both the load distributions and the recovery process. Repetitive dakko movements likely induced sustained muscle tonus in the trapezius, which may be a factor related to shoulder stiffness.

Objective: To characterize clinical features of polymyositis/dermatomyositis (PM/DM) patients with different anti-aminoacyl transfer RNA synthetase (ARS) antibodies and their association with anti-Ro52., Methods: Autoantibodies in sera from 97 Japanese patients (36 PM, 56 DM, and 5 clinically amyopathic DM), who satisfied Bohan and Peter or modified Sontheimer's criteria, were characterized by immunoprecipitation and enzyme-linked immunosorbent assay. Clinical information was from medical records. Features associated with different anti-ARS and anti-Ro52 antibodies were analyzed., Results: The prevalence of anti-ARS was similar to other studies (Jo-1, 22%; EJ, 4%; OJ, 1%; PL-12, 1%), except for a high prevalence of anti-PL-7 (12%), which allowed us to characterize patients carrying this specificity. Serum creatine kinase >3000 IU/l was less common in anti-PL-7-positive patients (57%) than anti-Jo-1-positive patients (18%) (p = 0.0328) and was not found in anti-EJ-positive individuals. Interstitial lung disease was common in anti-ARS-positive patients (97%) (p < 0.0001 vs. 48% in anti-ARS-negative). Anti-Ro52 antibodies were frequently detected with anti-ARS (59%) (57% in anti-Jo-1, 67% in anti-PL-7) (vs. 21% in anti-ARS-negative, p < 0.0002). Anti-Ro52 was associated with overlap syndrome (26%) (vs. 7% in anti-Ro52-negative, p = 0.0119)., Conclusions: Patients with different anti-ARS in combination with anti-Ro52 appear to be associated with distinctive clinical subsets.

Cells respond to the environment and alter gene expression. Recent studies have revealed the social aspects of bacterial life, such as biofilm formation. Biofilm formation is largely affected by the environment, and the mechanisms by which the gene expression of individual cells affects biofilm development have attracted interest. Environmental factors determine the cell's decision to form or leave a biofilm. In addition, the biofilm structure largely depends on the environment, implying that biofilms are shaped to adapt to local conditions. Second messengers such as cAMP and c-di-GMP are key factors that link environmental factors with gene regulation. Cell-to-cell communication is also an important factor in shaping the biofilm. In this short review, we will introduce the basics of biofilm formation and further discuss environmental factors that shape biofilm formation. Finally, the state-of-the-art tools that allow us investigate biofilms under various conditions are discussed.

Aims: The carcinogenesis of ovarian clear cell carcinoma (CCC) has been hypothesized to comprise two different pathways: an adenofibroma-carcinoma sequence and an endometriosis-carcinoma sequence. However, the difference in the genetic basis of these two pathways remains unclear. Recent studies have suggested that an ARID1A mutation and the loss of the corresponding protein, BAF250a, are frequent events in CCC. Herein, we investigated the difference in the loss of BAF250a expression in adenofibroma-related CCC and endometriosis-related CCC., Methods and Results: In total, 93 cases of surgically treated CCC were evaluated. The presence of adenofibroma and endometriosis associated with carcinoma was determined by reviewing haematoxylin and eosin-stained slides for each case. BAF250a expression in carcinoma was examined immunohistochemically. The loss of BAF250a expression was detected in carcinomas in 50 of 93 (54%) cases, including five of 18 (28%) with adenofibroma alone, 30 of 45 (67%) with endometriosis alone, eight of 18 (44%) with both conditions and seven of 12 (58%) with neither condition. The loss of BAF250a expression was significantly less frequent in CCC cases with adenofibroma than in cases with endometriosis (P = 0.01, Fisher's exact test)., Conclusions: The action of ARID1A in carcinogenesis differs between adenofibroma-related CCC and endometriosis-related CCC., (© 2015 John Wiley & Sons Ltd.)

Background: The feasibility of gastrectomy with standard lymphadenectomy for patients over 85 years of age is not known. This study investigated short- and long-term outcomes and the tolerability of gastrectomy with standard lymphadenectomy for patients over 85 years with gastric cancer., Methods: Altogether, 77 patients aged over 85 years underwent gastrectomy with lymphadenectomy for gastric cancer at the Cancer Institute Hospital, Japan from May 2000 to February 2012. Postoperative short-term outcomes and survivals were analyzed retrospectively. Standard lymphadenectomy was defined according to the Japanese Gastric Cancer Association guidelines. Lymphadenectomy without splenectomy during total gastrectomy was called "reduced" lymphadenectomy., Results: Distal gastrectomy was performed in 51 patients, total gastrectomy in 20, remnant total gastrectomy in 5, and proximal gastrectomy in 1 patient. Gastrectomy with standard lymphadenectomy was initially planned for 50 (64.9 %) patients and completed in 42 (54.5 %) patients. The other 8 patients underwent reduced lymphadenectomy because they required R1 or R2 resection. There were no deaths. The morbidity rate was 55.8 % overall and 54.8 % with standard lymphadenectomy. The most frequent complication was intestinal hypoperistalsis (29.9 %). The mean postoperative hospital stay was 19 days (range 10-70 days). The median overall survival time was 46.8 months., Conclusion: Coupled with comprehensive postoperative medical care due to the relative high morbidity risk, gastrectomy with standard lymphadenectomy for gastric cancer may be acceptable for relatively healthy patients over 85 years of age. Decisions to reduce the extent of lymphadenectomy during gastrectomy should not be based on advanced age alone.

Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of 3 institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (1 Li-Fraumeni, 1 Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II to IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least 1 site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 mo); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease-specific survival at 5 years was 42% for GAS versus 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon.

Background: Chrysotile had been used in asbestos textile workshops in Southeast China but a clear relation to mesothelioma is lacking., Methods: All patients diagnosed with mesothelioma from 2003 to 2010 at Yuyao People's Hospital were re-evaluated by multiple expert pathologists with immunohistochemistry and asbestos exposure data were collected., Results: Of 43 patients with a mesothelioma diagnosis, 19 peritoneal and nine pleural cases were finally diagnosed as mesothelioma. All were females, and the mean age of the patients with peritoneal or pleural mesothelioma was 52.4 and 58.2 years, respectively. All these cases had a history of domestic or occupational exposure to chrysotile. Two-thirds of the patients were from two adjoining towns with multiple small asbestos textile workshops. Contamination of tremolite was estimated to be less than 0.3%., Conclusions: This is a report of mesothelioma in women exposed to chrysotile asbestos at home and at work, with an over-representation of peritoneal mesothelioma., (© 2015 Wiley Periodicals, Inc.)

Pregnancy of unknown location is defined as empty endometrial cavity despite positive pregnancy test, and often develops as overt intrauterine or ectopic pregnancy. The pathophysiology of persistent pregnancy of unknown location, however, which involves continuous low serum human chorionic gonadotropin without any visible implantation site, is unknown. We report a case of left tubal pregnancy associated with additional conception in the contralateral tube. Left tubal pregnancy was suspected in a 40-year-old nulligravid woman after two embryo transfers following in vitro fertilization. Laparoscopic bilateral salpingectomy was performed for bilateral hydrosalpinx. Products from an additional conception were identified in the right tube. Short tandem repeat analysis using genomic DNA from resected specimens indicated two conceptions of different origin. The extra conception identified on microscopy may indicate one pathogenesis of persistent pregnancy of unknown location. Salpingectomy of the contralateral tube with hydrosalpinx is an option to prevent persistent occult pregnancy., (© 2015 Japan Society of Obstetrics and Gynecology.)

Accurate distinction of clear cell carcinoma (CCC) from endometrioid carcinoma (EC) has important clinical implications, but, not infrequently, EC demonstrates clear cell change (EC-CC), mimicking CCC. We examined whether a panel of immunomarkers can help distinguish between these tumors. Sixty-four CCCs (40 ovarian and 24 uterine), 34 ECs (21 ovarian and 13 uterine), and 34 EC-CCs (6 ovarian and 28 uterine) were stained for HNF1β, BAF250a, Napsin A, ER, and PR. Intensity and extent of immunoreactivity was assessed. Fifty-seven of 64 (89%) CCCs, 14/34 (41%) EC-CCs, and 16/34 (47%) ECs expressed HNF1β, and 56/64 (88%) CCCs, 4/34 (12%) EC-CCs, and 1/34 (3%) ECs stained for Napsin A. Most CCCs demonstrated at least moderate and diffuse staining for both markers, whereas only focal and weak expression was identified in most EC-CC/EC. Compared to HNF1β, Napsin A showed increased specificity (93.0% vs. 55.9%, P<0.0001) and similar sensitivity (87.5% vs. 89.1%) in distinguishing CCC from EC-CC/EC. Thirteen of 64 (20%) CCCs, 6/34 (18%) EC-CCs, and 2/34 (6%) ECs showed loss of BAF250a. ER was expressed by 10/64 (16%) CCCs, 30/34 (88%) EC-CCs, and 33/34 (97%) ECs, whereas PR positivity was identified in 9/64 (14%) CCCs, 26/34 (77%) EC-CCs, and 33/34 (97%) ECs. The majority of EC and EC-CC demonstrated diffuse staining for ER/PR, whereas most CCCs showed very focal positivity. There is a statistically significant difference in HNF1β, Napsin A, ER, and PR immunoexpression between CCC and EC/EC-CC, with Napsin A being a more specific marker for CCC than HNF1β. Overall, the immunoprofile of EC-CC is more comparable to that of EC than CCC. The use of a panel of immunostains can help distinguish EC-CC from CCC.

Background: To achieve optimal cytoreduction for advanced-stage ovarian cancer, modified posterior exenteration is the most frequently performed bowel surgery. We assessed the extents of tumor spreading in the rectosigmoid wall and pelvic side wall in modified posterior exenteration specimens during primary debulking surgery (PDS) and interval debulking surgery (IDS) following neoadjuvant chemotherapy, and compared the validity of selecting this surgical procedure in the patients undergoing PDS with that in the patients undergoing IDS., Methods: Clinicopathological data from consecutive patients who had undergone a modified posterior exenteration for primary ovarian, tubal, and peritoneal cancer at our institution between April 2008 and March 2013 was retrospectively reviewed., Results: A total of 75 patients (38 in PDS and 37 in IDS) were included in this study. Tumor involvement of the rectosigmoid was histopathologically confirmed in 65% of the specimens. Though the extent of tumor spreading in the rectosigmoid was deeper in PDS than in IDS, the frequency of tumor involvement of the rectosigmoid in patients who had undergone modified posterior exenteration during PDS was equivalent to that in the IDS group. Lateral tumor spreading to the side wall(s) was histopathologically confirmed in 53% of the patients in whom a pelvic side wall resection had been performed., Conclusions: During both PDS and IDS for ovarian cancer presenting with tumor involvement of the cul-de-sac, close inspection and palpation by gynecologic oncologists may enable the extent of tumor spreading in the pelvis to be estimated, enabling valid decisions as to whether an en bloc resection of the pelvic tumors together with the rectosigmoid and the pelvic side wall might or might not be appropriate.

Napsin A is a reliable marker for pulmonary adenocarcinoma and is expressed in a subset of ovarian clear cell carcinomas (O-CCCs), endometrial (EM) CCCs, and endometrioid carcinomas (EC). We investigated napsin A levels in O-CCC and EM-CCC and compared these with levels in other nonmucinous ovarian carcinomas and EM-EC, respectively. Napsin A, thyroid transcription factor (TTF)-1, paired box (PAX) 8, and cancer antigen (CA) 125 expression was evaluated in 111 ovarian and uterine carcinoma cases (22 O-CCC, 15 EM-CCC, 13 ovarian EC (O-EC), 39 high-grade serous carcinoma [HGSC], and 22 EM-EC) using immunohistochemistry. Napsin A immunoreactivity was observed in 21 (95.5%) of 22 O-CCC and 10 (66.7%) of 15 EM-CCC cases but was rare in O-EC and EM-EC (7.7% and 4.5%) and undetectable in HGSC cases. Thyroid transcription factor 1 was not expressed in O-CCC but was detected in 1 (6.7%) of 15 EM-CCC, 3 (23.1%) of 13 O-EC, 2 (5.1%) of 39 HGSC, and 1 (4.5%) of 22 EM-EC cases. All 111 cases examined were positive for PAX8, whereas 3 (20.0%) of 15 of EM-CCC and 1 (4.5%) of 22 EM-EC cases were negative for CA125. There were no napsin A/TTF-1 double-positive cases, except for 1 EM-CCC, in which cells had a focal expression pattern. All napsin A- and/or TTF-1-positive cases expressed PAX8 and CA125. In conclusion, napsin A is frequently expressed in O-CCC and EM-CCC, rarely in O-EC and EM-EC, and never in HGSC cases. These findings confirm the importance of using a panel of antibodies that includes napsin A, TTF-1, and PAX8 when evaluating metastatic carcinomas of unknown origin, particularly when gynecologic and pulmonary adenocarcinomas are included in the differential diagnosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The diagnosis of primary immune thrombocytopenia (ITP) is based on differential diagnosis. Although the measurement of percentages of reticulated platelets (RP%) by flow cytometry is useful as a supportive diagnostic test, this method is nonetheless a time-consuming, laboratory-based assay. To identify alternative assays that are useful in daily practice, we compared three methods in parallel, IPF% measured by XE-2100 [IPF% (XE), Sysmex Corp.], IPF% measured by new XN-1000 [IPF% (XN)], and RP%. We examined 47 patients with primary ITP, 28 patients with aplastic thrombocytopenia (18 aplastic anemia and 10 chemotherapy-induced thrombocytopenia) and 80 healthy controls. In a selected experiment, we examined 16 patients with paroxysmal nocturnal hemoglobinuria (PNH) to examine the effect of hemolysis. As compared with IPF% (XE), IPF% (XN) showed better within-run reproducibility. The sensitivity and specificity for the diagnosis of ITP were 83.0 and 75.0 % for IPF% (XE), 85.1 and 89.3 % for IPF% (XN), and 93.6 and 89.3 % for RP%, respectively. Examination of PNH patients revealed that hemolysis and/or red blood cell fragments interfered with IPF% (XE) values, but not with IFP % (XN) values. Our results suggest that IPF% measured by XN-1000 may be of comparable value with RP% as a supportive diagnostic test for ITP.

Many bacteria convert bicyclic compounds, such as indole and naphthalene, to oxidized compounds, including hydroxyindoles and naphthols. Pseudomonas aeruginosa, a ubiquitous bacterium that inhabits diverse environments, shows pathogenicity against animals, plants, and other microorganisms, and increasing evidence has shown that several bicyclic compounds alter the virulence-related phenotypes of P. aeruginosa. Here, we revealed that hydroxyindoles (4- and 5-hydroxyindoles) and naphthalene derivatives bearing hydroxyl groups specifically inhibit swarming motility but have minor effects on other motilities, including swimming and twitching, in P. aeruginosa. Further analyses using 1-naphthol showed that this effect is also associated with clinically isolated hyperswarming P. aeruginosa cells. Swarming motility is associated with the dispersion of cells from biofilms, and the addition of 1-naphthol maintained biofilm biomass without cell dispersion. We showed that this 1-naphthol-dependent swarming inhibition is independent of changes of rhamnolipid production and the intracellular level of signaling molecule cyclic-di-GMP (c-di-GMP). Transcriptome analyses revealed that 1-naphthol increases gene expression associated with multidrug efflux and represses gene expression associated with aerotaxis and with pyochelin, flagellar, and pilus synthesis. In the present study, we showed that several bicyclic compounds bearing hydroxyl groups inhibit the swarming motility of P. aeruginosa, and these results provide new insight into the chemical structures that inhibit the specific phenotypes of P. aeruginosa., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Introduction: The feasibility, safety, and improved quality of postoperative life following laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG) with a hand-sewn anastomosis via a mini-laparotomy for early gastric cancer (EGC) have been previously established. Here we describe the surgical procedure of totally laparoscopic pylorus-preserving gastrectomy (TLPPG) using an intracorporeal delta-shaped anastomosis technique, and the short-term surgical outcomes of 60 patients with EGC in the middle stomach are reported., Methods: After lymphadenectomy and mobilization of the stomach, intraoperative gastroscopy was performed in order to verify the location of the tumor, and then the distal and proximal transecting lines were established, 5 cm from the pyloric ring and just proximal to Demel's line, respectively. Following transection of the stomach, a delta-shaped intracorporeal gastrogastrostomy was made with linear staplers., Results: There were no intraoperative complications or conversions to open surgery. Mean operation time and blood loss were 259 min and 28 mL, respectively. Twelve patients (20.0%) experienced postoperative complications classified as grade II using the Clavien-Dindo classification, with the most frequent complication being gastric stasis (6 cases, 10.0 %). The incidence of severe complications classified as grade III or above was 1.7%; only one patient required reoperation and intensive care due to postoperative intraabdominal bleeding and subsequent multiple organ failure., Conclusion: TLPPG with an intracorporeal delta-shaped anastomosis was found to be a safe procedure, although it tended to require a longer operating time than the well-established LAPPG with a hand-sewn gastrogastrostomy.

Neonatal alloimmune thrombocytopenia (NAIT) is induced by maternal alloantibodies raised against fetal platelet antigens inherited from the paternal parent. In contrast to Caucasians, in Asians, predominantly in Japanese, most frequently detected antibodies in NAIT are anti-HPA-4b and anti-HPA-5b. In some NAIT cases multiple alloantibodies are detected. In such cases it is very difficult to determine which antibody is the dominant antibody in NAIT. In this case report, we describe a NAIT case (first sibling) with severe thrombocytopenia and cephalhematoma in the presence of both anti-HPA-4b and anti-HPA-5b antibodies in the maternal serum. We carefully examined titers of anti-HPA antibodies during the subsequent pregnancy with HPA-4b-positive and HPA-5b-negative fetus determined by amniocentesis at gestational week 16. We administered IVIG (1 g/kg/w) to the mother from gestational week 32 to 35. The mother subsequently delivered a second sibling with normal platelet count by cesarean section. Although we could not completely rule out the involvement of anti-HPA-4b, our findings suggested that anti-HPA-5b was implicated in the NAIT in the first sibling.

Background: Metformin, an antidiabetic drug, decreases the incidence of various cancers in diabetic patients. Metformin-induced inhibition of cancer cell proliferation has been confirmed in vitro but not in humans. Because endometrial cancer is associated with insulin resistance, the authors investigated whether a diabetes-therapeutic metformin dose inhibits cancer cell growth in patients with endometrial cancer., Methods: A dose of metaformin was administered (1500-2250 mg/day) to 31 patients with endometrial cancer preoperatively for 4 to 6 weeks. Cell proliferation was assessed in patient tissues using immunohistochemical and Western blot analyses and DNA synthesis was measured in serum using a thymidine uptake assay. All statistical tests were 2-sided. P values of < .05 were considered statistically significant., Results: Preoperative metformin treatment decreased DNA synthesis in sera and significantly reduced the Ki-67 (mean proportional decrease, 44.2%; 95% confidence interval [95% CI], 35.4-53.0 [P < .001]) and topoisomerase IIα (mean proportional decrease, 36.4%; 95% CI, 26.7-46.0 [P < .001]) labeling indices. Levels of phospho-ribosomal protein S6 and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) were found to be significantly decreased and phospho-adenosine monophosphate-activated protein kinase and p27 levels were significantly increased. Preoperative metformin use caused significant decreases in circulating factors, including insulin, glucose, insulin-like growth factor 1, and leptin. DNA synthesis-stimulating activity in patient sera was significantly decreased during metformin administration., Conclusions: An antidiabetic dose of metformin inhibited endometrial cancer cell growth in vivo, an effect likely due to its effect on humoral factor(s). This translational study provides considerable rationale to initiate large clinical trials., (© 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Surgical resection with a free margin is the gold standard treatment for these lesions., Objective: The aim of this study was to evaluate the feasibility of performing laparoscopic resection for gastric GIST from the viewpoint of operative and long-term oncological outcomes., Methods: Between 2005 and 2011, a total of 78 consecutive patients undergoing laparoscopic resection of gastric GISTs were enrolled in a retrospective single-center study. Patient and tumor characteristics, surgical procedures, risk classification, postoperative complications, mortality, recurrence, and survival time were collected from a database, and the descriptive statistics were estimated., Results: Patients (N = 78; 32 males and 46 females) with a median age of 63 years (range 31-82) were evaluated. The tumors were located at the cardia (10.3%), upper stomach (59.0%), middle stomach (23.1), and lower stomach (7.7%). The mean size of the tumors was 34.7 ± 12.1 mm. The laparoscopic procedures included wedge resection (92.3%), such as laparoscopy and endoscopy cooperative surgery (51.3%), and gastrectomy (7.7%). All cases exhibited a pathologically negative margin. The mean operative time was 147.5 ± 63.8 min, and the mean estimated amount of blood loss was 17.8 ± 47.9 ml. The mean length of hospitalization was 9.4 ± 12.8 days. The incidence of perioperative complications higher than grade III was 2.6%, including two cases of anastomotic leakage. Regarding risk classification, low, intermediate and high were observed in 61, 6, and 11 cases, respectively. During a mean follow-up period of 45.3 ± 18.5 months, one patient experienced local recurrence in the omentum. Meanwhile, four patients died due to other diseases; all other patients survived., Conclusions: Adequate oncologic resection was achieved in all cases. Laparoscopic surgery is a feasible option for gastric GISTs <5 cm.

Risk-reducing salpingo-oophorectomy for reducing future cancer risk in women with hereditary breast and ovarian cancer syndrome is rarely performed in Japan; therefore, the cancer preventive effect of risk-reducing salpingo-oophorectomy for hereditary breast and ovarian cancer syndrome among the Japanese population remains unclear. Here, we report the first case of serous tubal intraepithelial carcinoma identified through a risk-reducing salpingo-oophorectomy in a Japanese woman with hereditary breast and ovarian cancer syndrome and who had a deleterious germline mutation of E1214X in BRCA1, but not a BRCA2 mutation. A pre-operative examination revealed multiple uterine leiomyomas but no adnexal mass. Robotic-assisted bilateral salpingo-oophorectomy together with hysterectomy was performed. A pathological examination identified serous tubal intraepithelial carcinoma in the right fallopian tube with no dissemination. Serous tubal intraepithelial carcinoma is implicated as an origin of invasive cancer of the fallopian tube with peritoneal dissemination; prophylactic salpingo-oophorectomy is currently the only method to identify this occult cancer. Our case demonstrated that risk-reducing salpingo-oophorectomy can detect occult cancers, including serous tubal intraepithelial carcinoma, thereby preventing future cancer development in the Japanese hereditary breast and ovarian cancer syndrome population., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

It has been established that nuclear pseudostratification of the neural epithelium in vertebral embryos is caused by interkinetic nuclear migration, a cell cycle-dependent regulation of nuclear movement, during which the G2/M-phase nuclei move apically before returning basally in the G1/S phase. Here we demonstrate the cell cycle-related nuclear location characteristic of interkinetic nuclear migration in human neoplastic and non-neoplastic pseudostratified glands. Immunohistochemical analysis with phosphohistone H3 (a G2/M-phase marker) and Ki67 was performed on fetal tissues, proliferative-phase endometrium (5 cases), and colonic adenomas (12 cases). In all cases, G2/M nuclei were significantly located apically, whereas Ki67-positive nuclei were widely distributed along the basal-apical axis. In the proliferating zone of the normal colon mucosa, elongated nuclei in the G2/M phase were occasionally found on the apical side of the cells. These results suggest that the interkinetic nuclear migration occurs in association with cell proliferation in both neoplastic and non-neoplastic glands.

Background/aims: The Japanese National Hospital Organization evidence-based medicine (EBM) Study group for Adverse effects of Corticosteroid therapy (J-NHOSAC) is a Japanese hospital-based cohort study investigating the safety of the initial use of glucocorticoids (GCs) in patients with newly diagnosed autoimmune diseases. Using the J-NHOSAC registry, the purpose of this observational study is to analyse the rates, characteristics and associated risk factors of intracellular infections in patients with newly diagnosed autoimmune diseases who were initially treated with GCs., Methodology/principal Findings: A total 604 patients with newly diagnosed autoimmune diseases treated with GCs were enrolled in this registry between April 2007 and March 2009. Cox proportional-hazards regression was used to determine independent risk factors for serious intracellular infections with covariates including sex, age, co-morbidity, laboratory data, use of immunosuppressants and dose of GCs. Survival was analysed according to the Kaplan-Meier method and was assessed by the log-rank test. There were 127 serious infections, including 43 intracellular infections, during 1105.8 patient-years of follow-up. The 43 serious intracellular infections resulted in 8 deaths. After adjustment for covariates, diabetes (Odds ratio [OR]: 2.5, 95% confidence interval [95% CI] 1.1-5.9), lymphocytopenia (≦1000/μl, OR: 2.5, 95% CI 1.2-5.2) and use of high-dose (≧30 mg/day) GCs (OR: 2.4, 95% CI 1.1-5.3) increased the risk of intracellular infections. Survival curves showed lower intracellular infection-free survival rate in patients with diabetes, lymphocytopaenia and high-dose GCs treatments., Conclusions/significance: Patients with newly diagnosed autoimmune diseases were at high risk of developing intracellular infection during initial treatment with GCs. Our findings provide background data on the risk of intracellular infections of patients with autoimmune diseases. Clinicians showed remain vigilant for intracellular infections in patients with autoimmune diseases who are treated with GCs.

Glucocorticoid (GC) therapy is associated with the risk of life-threatening adverse events in patients with autoimmune disease. To determine accurately the incidence and predictors of GC-related adverse events during initial GC treatment, we conducted a cohort study. Patients with autoimmune disease who were initially treated with GCs in Japan National Hospital Organization (NHO) hospitals were enrolled. Cox proportional hazard regression was used to determine the independent risks for GC-related serious adverse events and mortality. Survival was analyzed according to the Kaplan-Meier method and was assessed with the log-rank test.The 604 patients had a total follow-up of 1105.8 person-years (mean, 1.9 year per patient). One hundred thirty-six patients had at least 1 infection with objective confirmation, and 71 patients had serious infections. Twenty-two cardiovascular events, 55 cases of diabetes, 30 fractures, 23 steroid psychosis events, and 4 avascular bone necrosis events occurred during the follow-up period. The incidence of serious infections was 114.8 (95% confidence interval, 95.7-136.6) per 1000 person-years. After adjustment for covariates, the following independent risk factors for serious infection were found: elderly age (hazard ratio [HR], 1.25/10-yr age increment; p = 0.016), presence of interstitial lung disease (HR, 2.01; p = 0.011), high-dose GC use (≥29.9 mg/d) (HR, 1.71; p = 0.047), and low performance status (Karnofsky score, HR, 0.98/1-score increment; p = 0.002). During the follow-up period, 73 patients died, 35 of whom died of infection. Similarly, elderly age, the presence of interstitial lung disease, and high-dose GC use were found to be significant independent risk factors for mortality. The incidence of serious and life-threatening infection was higher in patients with autoimmune disease who were initially treated with GCs. Although the primary diseases are important confounding factors, elderly age, male sex, the presence of interstitial lung diseases, high-dose GCs, and low performance status were shown to be risk factors for serious infection and mortality.

The aim of this study was to determine the impact of prognostic factors in primary fallopian tube carcinoma (PFTC). All cases of PFTC diagnosed between 1990 and 2010 were retrieved from the files of 6 academic centers. The cases were staged according to a modification of the International Federation of Obstetrics and Gynecology staging system proposed by Alvarado-Cabrero et al (Gynecol Oncol 1999; 72: 367-379). One hundred twenty-seven PFTC cases were identified. The mean age of the patients was 64.2 years. Stage distribution was as follows: 72 (57%), stage I; 19 (15%), stage II; 28 (22%), stage III; and 8 (6.2%), stage IV. Depth of infiltration of the tubal wall was an independent prognostic factor in stage I cases (P < .001). Carcinomas located in the fimbriated end even without invasion had a worse prognosis than did carcinomas involving the tubal portion of the organ. The presence of vascular space invasion correlated with the depth of tubal wall invasion (P = .001) and the presence of lymph node metastases (P = .003). Tumor grade significantly correlated with survival (P < .0001), but histologic type was of marginal significance and only if it was grouped as nonserous/non-clear cell vs serous/clear cell (P = .04). The depth of invasion of the tubal wall and the presence of carcinoma in the fimbriated end even without invasion are important prognostic indicators. The modified International Federation of Obstetrics and Gynecology staging system should be used on a routine basis in all carcinomas of the fallopian tube., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Bacteria participate in social behaviors by communicating with each other and forming surface-associated biofilms. In Pseudomonas aeruginosa, such social behaviors are affected greatly by the environment. Although P. aeruginosa survive under anaerobic conditions, previous studies indicate that quorum sensing is attenuated under such conditions, and that this leads to decreased activity of extracellular virulence factors as compared to aerobic conditions. Hence it has come into question whether P. aeruginosa are virulent under anaerobic conditions. Here, we compared various phenotypes between PAO1 and clinical isolates under anaerobic conditions. Our data revealed that when grown anaerobically, growth and cell morphology greatly differed among the strains. One of the clinical isolates produced comparable amounts of quorum-sensing signaling molecules and extracellular virulence factors under aerobic and anaerobic conditions, while the other strains showed low production under anaerobic conditions. Biofilm formation also exhibited strain-dependent variations, suggesting that there are several mechanisms that lead to biofilm formation under anaerobic conditions. Taken together, these results indicate that the impact of anaerobiosis on the social interactions of P. aeruginosa is strain dependent, and suggest that multiple regulatory mechanisms are involved in the regulation of quorum sensing and biofilm formation under anaerobic conditions.

Granulocytic sarcoma is a rare disease that is rarely curable with conventional chemotherapy. This report describes a case of a patient with bulky granulocytic sarcoma of the retroperitoneum who was treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation without administering granulocyte colony-stimulating factor before stem cell collection. According to bone marrow assessment and imaging studies, the patient remained in complete remission at 5 years after transplantation. This case suggests that high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation is a therapeutic option for granulocytic sarcoma.

We report a gastric cancer patient with positive peritoneal lavage cytology (CY1) who achieved 20-month progression free survival by S-1 monotherapy. An 82-year-old male patient who underwent distal gastrectomy with residual disease for type 4 scirrhous gastric cancer manifesting pyloric stenosis, direct invasion to the pancreas, and CY1. He received S-1 monotherapy postoperatively. His ECOG performance status (PS) was 0. The initial treatment schedule was 100mg/day, twice daily for 4 weeks with a 2-week rest, repeated every 6 weeks. Grade 2 thrombocytopenia at the end of the 5th course of treatment required discontinuation of one course of treatment, and subsequent treatment was continued with a dose reduction to 80mg/day. Afterwards, although treatment was temporarily postponed for 2 weeks, the dose modification enabled him to receive S-1 for 20 months, leading to a relative dose intensity of 81%. There was no evidence of disease progression. The most severe adverse events were transient grade 3 neutropenia as well as leukocytopenia, anemia, and thrombocytopenia, grade 2 each, without gastrointestinal toxicities. His PS was not deteriorated. Although survivalrates of CY1 gastric cancer patients are still poor, our case suggests that S-1 monotherapy is effective against CY1, even for patients aged over 80, if the relative dose intensity is maintained by comprehensive patient management and appropriate dose modification.

We present the case of a 43-year-old man diagnosed with HLA-B39-positive spondyloarthritis who developed cutaneous lesions consistent with cutaneous polyarteritis nodosa (CPN). Previous studies indicated an elevated incidence of HLA-B39 in HLA-B27-negative Japanese patients with spondyloarthritis. This case suggested that CPN may also occur in association with forms of HLA-B39-positive spondyloarthritis. The rarity of this association is emphasized. Therapy with corticosteroid and methotrexate improved both the cutaneous lesions and the clinical symptoms of spondyloarthritis.

Aim: CD147 is a membrane glycoprotein that is expressed in various cancer cells and is involved in tumor invasion and metastasis by inducing stromal fibroblastic cells to produce matrix metalloproteinases. This study was carried out to evaluate the correlation between CD147 expression and various clinicopathologic parameters, including histological grade and prognosis in a small sample set of human ovarian cancer patients., Material and Methods: Paraffin-embedded surgical tissue samples from 25 patients with ovarian serous and endometrioid adenocarcinoma were stained with anti-CD147 antibody (monoclonal antibody 12C3: MoAb 12C3) for immunohistochemical analysis., Results: CD147 protein was expressed in 84.0% (21 of 25 cases) of cancerous lesions, but not in normal lesions. CD147 expression by ovarian cancer cells was inversely correlated with overall survival. There was no correlation between CD147 expression and histological grade., Conclusions: These results suggest that measurement of CD147 expression may enhance the understanding of the pathophysiology of epithelial ovarian cancer., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Choriocarcinoma is a highly malignant tumor of trophoblastic origin. Most cases occur in association with preceding gestational events. However, on very rare occasions, nongestational choriocarcinoma arises from germ cell or trophoblastic differentiation in different types of carcinoma. This article reports the case of a 58-year-old woman with primary nongestational choriocarcinoma of the uterus that developed 19 years after her final pregnancy and 4 years after menopause. A total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. Histopathological examination showed choriocarcinoma of the uterus without components of other germ cell tumors. Karyotype analysis of the tumor cells demonstrated XX. We confirmed its nongestational origin by DNA polymorphism analysis at 15 short tandem repeat loci. After surgery, the patient was given four courses of combination chemotherapy. She is still alive and there has been no evidence of recurrence 3 years after surgery.

In this experiment, we evaluated the effects of strong static magnetic fields (SMF) on the orientation of myotubes formed from a mouse-derived myoblast cell line, C2C12. Myogenic differentiation of C2C12 cells was conducted under exposure to SMF at a magnetic flux density of 0-10 T and a magnetic gradient of 0-41.7 T/m. Exposure to SMF at 10 T led to significant formation of oriented myotubes. Under the high magnetic field gradient and a high value of the product of the magnetic flux density and magnetic field gradient, myotube orientation increased as the myogenic differentiation period increased. At the 3 T exposure position, where there was a moderate magnetic flux density and moderate magnetic field gradient, myotube orientation was not observed. We demonstrated that SMF induced the formation of oriented myotubes depending on the magnetic flux density, and that a high magnetic field gradient and a high value of the product of the magnetic flux density and magnetic field gradient induced the formation of oriented myotubes 6 days after myogenic differentiation. We did not detect any effect of the static magnetic fields on myogenic differentiation or cell number. To the best of our knowledge, this is the first report to demonstrate that myotubes orient to each other under a SMF without affecting the cell number and myogenic differentiation., (Copyright © 2011 Wiley Periodicals, Inc.)

Systemic chemotherapy is the treatment recommended for prolonged survival in cases of metastatic gastric cancer. There have been a number of clinical reports of surgical resection of liver metastasis in selected patients with gastric cancer. Here, we report on a case of treatment of far advanced gastric cancer with synchronous multiple liver metastases with prompt S-1 in combination with fractional cisplatin sandwiched between twostage surgery. Metastases including peritoneal dissemination and extensive lymph node involvement were absent so it was feasible to completely remove all of the macroscopic liver metastases. Each step of the chemotherapy progressed satisfactorily and histological examination after the hepatectomy yielded a pathologically complete response of liver metastases from the gastric cancer. This strategy provides a promising treatment for far advanced gastric cancer with a limited number of synchronous liver metastases. The referral to surgical oncology is a crucial step for the documentation of pathological complete response.

We report a case of sex cord tumor with annular tubules featuring a giant multilocular cyst, grossly similar to cystadenoma, in the ovary of an 8.5 year old girl. Estrogen-related symptoms, including precocious puberty and irregular uterine bleeding, immediately improved after tumor resection., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: To clarify the preoperative differential diagnosis and management of minimal deviation adenocarcinoma (MDA) and lobular endocervical glandular hyperplasia (LEGH), a multicenter study was performed., Methods: A total of 112 patients who underwent conization or a hysterectomy for suspected MDA were collected from 24 hospitals. The pathological diagnosis in each case was determined by a central pathological review board. The diagnostic significance of clinicopathologic findings including results of magnetic resonance imaging (MRI), Papanicolaou (Pap) smears, and testing for gastric mucin was analyzed., Results: The central pathological review identified 37 cases of Nabothian cyst or tunnel cluster, 54 cases of LEGH, 6 cases of MDA, 11 cases of adenocarcinoma, and 4 cases of benign disease. Lobular endocervical glandular hyperplasia was often associated with adenocarcinoma in situ, MDA, and mucinous adenocarcinoma. Three MDA patients had a recurrence, whereas none of LEGH patients had a recurrence irrespective of the type of surgery. On MRI, LEGH appeared as a characteristic multicystic lesion with an inner solid component, whereas MDA showed a predominantly solid pattern. A Pap smear or gastric mucin alone had limited diagnostic power. However, a combination of these findings is useful; that is, a cystic structure with inner solid components on MRI associated with mild glandular atypia and gastric mucin strongly suggested LEGH (24/26, 92%). A solid structure with atypical glandular cells was indicative of MDA or adenocarcinoma (5/5, 100%)., Conclusions: The combination of MRI, Pap smears, and gastric mucin will improve the accuracy of the preoperative diagnosis of MDA and LEGH. Patients suspected of having LEGH may need to be treated with less aggressive methods.

Background: Endocervical adenocarcinomas of the usual type are etiologically related to infection with oncogenic human papillomaviruses (HPVs). These tumors are typically diffusely positive for p16 and carcinoembryonic antigen (CEA) immunostains. The goal of our study was to determine the HPV status and immunohistochemical profiles of unusual histologic subtypes of endocervical adenocarcinoma., Methods: The study consisted of a total of 26 cases of unusual subtypes including clear cell carcinoma (CCC, n=9), gastric-type adenocarcinoma (GAS, n=11), minimal deviation adenocarcinoma (MDA, n=3), mesonephric adenocarcinoma (MSN, n=1), serous adenocarcinoma (SER, n=1), and malignant mixed Müllerian tumor (n=1). In addition, 5 cases of usual-type endocervical adenocarcinoma (UEA) were included in the study as a control group. The cases were tested for HPV using SPF-10 PCR and LiPA assays, and immunostained for p16, HIK1083, hepatocyte nuclear factor 1-β, p53, CEA, estrogen receptor (ER), and progesterone receptor (PR)., Results: HPV DNA was not detected in any of the unusual adenocarcinoma subtypes, with the exception of a single case of SER in which HPV16 was detected. p16 positivity did not correlate with HPV status, as 42% of HPV-negative tumors showed patchy/diffuse p16 overexpression; however, p16 positivity was uncommon in GAS/MDA. HIK1083 positivity was limited to GAS and MDA, indicating relative specificity for tumors with gastric mucin expression. Hepatocyte nuclear factor 1-β was positive in the majority of CCCs and also in other tumor variants and in some UEA as well, indicating a lack of specificity for clear cell differentiation. CEA was consistently negative in CCCs and in a single MSN, but positive in GAS, MDA, SER, and UEA, suggesting that it may serve as a negative marker of clear cell differentiation. p53 was diffusely positive in almost half of the GAS cases, whereas UEA showed mostly negative staining and other variants showed focal staining. PR was negative in all variant cases and in all UEA. ER expression, although mostly negative, showed focal staining in a few variant cases and UEA., Conclusions: Unusual variants of endocervical adenocarcinoma are not related to HPV infection, with only rare exceptions, and p16 overexpression in non-UEA does not correlate with HPV status. Negative staining for PR and ER may serve as a general marker of endocervical neoplasia. GAS/MDA may be differentiated from all other adenocarcinomas with either positive HIK1083 stain or negative/focal p16 stain. Positive CEA stain differentiates GAS/MDA from CCC and negative PR and ER stains differentiate GAS/MDA from benign endocervical glands. CCC may be distinguished from all other adenocarcinomas, except MSN, with a negative CEA stain. Strong and diffuse p53 positivity in SER may be useful in differentiation from UEA. MSN may be identified with negative CEA, ER, and PR stains.

The radical treatment of gastric cancer is complete resection of the tumor by surgery. For advanced gastric cancer, a multidisciplinary approach has been attempted to improve patient prognosis. Potentially resectable and curable advanced gastric cancer is treated with routine surgery, followed by postoperative adjuvant chemotherapy. For highly advanced gastric cancer, extended radical surgery or preoperative adjuvant chemotherapy have been attempted. Laparoscopic gastrectomy for advanced gastric cancer has not been widely used because of the difficult surgical technique involved, but enhanced magnification in the surgical field is expected to improve the accuracy of the lymph node dissection procedure. In future, the significance of currently available treatments should be investigated. The key treatment for advanced gastric cancer at present is surgery.

The increasing use of mobile phones has aroused public concern regarding the potential health risks of radiofrequency (RF) fields. We investigated the effects of exposure to RF fields (2.45 GHz, continuous wave) at specific absorption rate (SAR) of 1, 5, and 10 W/kg for 1, 4, and 24 h on gene expression in a normal human glial cell line, SVGp12, using DNA microarray. Microarray analysis revealed 23 assigned gene spots and 5 non-assigned gene spots as prospective altered gene spots. Twenty-two genes out of the 23 assigned gene spots were further analyzed by reverse transcription-polymerase chain reaction to validate the results of microarray, and no significant alterations in gene expression were observed. Under the experimental conditions used in this study, we found no evidence that exposure to RF fields affected gene expression in SVGp12 cells.

We report a 30-year-old man with severe obesity hypoventilation syndrome (OHVS) complicated by right-sided heart failure. Polysomnography revealed severe obstructive sleep apnea with apnea-hypopnea index (AHI) 70.4/h and gradual decrease in minimum oxygen saturation (SpO 2 ) from 86% before sleep to 36% during sleep. Cardiac output (CO) was suppressed from 3.9 L/min before sleep to 2.5 L/min during sleep. Noninvasive positive pressure ventilation (NPPV) treatment drastically restored CO to the level before sleep, and improved AHI to 9.4/h and minimum SpO 2 to 87%. NPPV may provide rapid and powerful symptom relief in patients with OHVS complicated with right sided heart failure.

A subset of endocervical-type mucinous adenocarcinomas (ACs) of the uterine cervix exhibit a gastric phenotype and morphology, as reported in cases of minimal deviation AC in which the presence of human papillomavirus (HPV) has been rarely detected. To investigate the HPV-independent pathway of carcinogenesis in cases of gastric-type AC, we investigated the common high-risk HPV (hr-HPV) status in 52 nonsquamous cell carcinomas, using a PCR-based typing method and immunohistochemistry of p16INK4a (a cyclin-dependent kinase inhibitor that is overexpressed in both cancerous and precancerous cervical tissue, making it an ideal biomarker for cervical cancer cases). Using novel morphological criteria, seven of 52 (13.5%) carcinomas were designated as gastric-type ACs, all of which were negative for both hr-HPV DNA and p16INK4a. Nongastric-type ACs were frequently positive for both hr-HPV DNA (90%, 28/31) and p16INK4a (94%, 29/31) with adenosquamous and neuroendocrine carcinomas demonstrating the presence of hr-HPV DNA in 86% (6/7) and 83% (5/6) of cases, respectively. In these two types of carcinoma, 86% (6/7) and 100% (6/6) were positive for p16INK4a, respectively. Our data suggests that gastric-type AC appears to represent an oncogenic hr-HPV-independent neoplasm and therefore is a potential pitfall of HPV DNA testing and vaccination.

We report a mitochondrial (MT) scoring system related to response to platinum treatment in ovarian cancer (OC). Ultra-thin sections of surgical specimens of primary tumors prepared from 41 OC patients were examined by electron microscopy. The ovarian carcinoma cell line 2008 and its platinum-resistant variant C13 were used as controls. Seven independent MT features, including MT diameter, pattern of cresta structure, electron density, MT distribution, pattern of distribution, ovoid ratio and MT architecture, were examined. Each of the seven parameters was assigned a point score of 0-2 and was summed up with a total score of 14. Clinical response and in vitro sensitivity to platinum, taxane, irinotecan and doxorubicin were evaluated. Clinical information was available for 37 of the 41 cases. Twenty-four cases were stage III and, histologically, 16 serous, 6 endometrioid and 6 clear cell carcinoma were included. All of the patients underwent surgery followed by 6 cycles of taxane and platinum chemotherapy. Fifteen patients exhibited a response, while 22 were resistant to treatment. The total MT score was 5.13±1.13 (mean ± SE) in the 15 responsive cases and 11.41±0.43 in the 22 resistant cases (P<0.001). Receptor operative characteristic (ROC) analysis revealed that the resistant total 'cut-off' score was ≥10 points (P<0.05; AUC=0.86) with 95.5% sensitivity and 80.0% specificity. The MT scoring system correlated well with response to drugs, with the exception of doxorubicin. The progression-free survival (PFS) curves showed an absolute difference in the 6-month PFS of 10% (83 vs. 73%) and in the 12-month PFS of 21% (80 vs. 59%), in favor of patients with low MT scores. This MT scoring system correlates very closely with clinical response as well as cellular sensitivity to chemotherapy, resulting in an association with PFS.

Background/aims: The anastomosis performed during laparoscopy-assisted pylorus-preserving gastrectomy (PPG) is usually handsewn; however, the technique is sometimes difficult because it is done through a small incision and the level of skill of each operator may vary. The present study describes a triangulating stapling technique used during an anastomosis in laparoscopy-assisted pylorus-preserving gastrectomy., Method: The 80-mm stapler was used 3 times for the triangulating stapling technique. The posterior walls, including the stay sutures, were joined by firing the stapler, and the anterior stomach ends were stapled in an everting fashion using two firings of the stapler. Both the anterior staple lines should overlap in the middle. Patient demographics and the operative data were examined., Results: The triangulating stapling technique was performed during laparoscopy-assisted PPG in 9 patients. The median time for the anastomosis during laparoscopy-assisted PPG using the triangulating stapling technique was 19.0 min (16.0-31.0). Postoperative complications, including gastric stasis and anastomotic failure, were not found in any of the present patients., Conclusion: The triangulating stapling technique using a linear stapler is a safe and reliable technique to perform and can be easily conducted in a short time. We therefore consider it a useful anastomosis method for laparoscopy-assisted pylorus-preserving gastrectomy, even by unskilled surgeons., (Copyright © 2010 S. Karger AG, Basel.)

We report 2 cases of serum sickness after rituximab infusion. Case 1 is a patient with Waldenström's macroglobulinemia, and case 2 is a patient with marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type and Sjögren's syndrome. Both patients had polyclonal hypergammaglobulinemia, were treated with rituximab monotherapy, developed serum sickness between 9 and 17 days after the first rituximab infusion, developed fever and arthralgia, and improved soon after corticosteroid treatment. Serum sickness after rituximab treatment for hematological malignancies is very rare as far as we know. We identified three risk factors of serum sickness after rituximab infusion from previous reports and our cases; administration of rituximab alone, the existence of Sjögren's syndrome, and polyclonal hypergammaglobulinemia.

Apart from typical yolk sac tumors, ovarian tumors with elevated alfa-fetoprotein (AFP) are uncommon and the differential diagnosis needs to consider the hepatoid pattern of a yolk sac tumor, hepatocellular carcinoma metastatic to the ovary, hepatoid carcinoma, and other epithelial ovarian tumors. We report here an AFP-producing ovarian tumor with uncertain pathological diagnosis, which was extremely responsive to chemotherapy. A 59-year-old Japanese woman presented with lower abdominal distension and was found to have a left ovarian mass on pelvic examination and magnetic resonance imaging (MRI) scan. Laboratory tests showed serum AFP, 73 687 ng/ml; carbohydrate antigen 125 (CA125), 1599 U/ml; and carcinoembryonic antigen (CEA), 13.9 ng/ml. Total hysterectomy with bilateral salpingo-oophorectomy, partial omentectomy, and low anterior resection of the rectum was performed, without any residual macroscopic tumor. Microscopically, the tumor was characterized by a hepatoid carcinomatous component composed of solid sheets of large eosinophilic cells with pleomorphic nuclei. The pathological stage was pT2N0M0. Tumor cells were diffusely immunoreactive for AFP and cytokeratin (CAM5.2), but monoclonal CEA and CA19-9 were focally positive in the cytoplasm, while CA125 was negative. The patient was treated postoperatively with three cycles of chemotherapy consisting of bleomycin, etoposide, and cisplatin; with this regimen, serum AFP decreased to 16 ng/ml from 12 600 ng/ml just before the initiation of chemotherapy. The patient received secondary cytoreductive surgery of systemic lymphadenectomy, which revealed no evidence of residual tumor.

Purpose: The aim of this study is to evaluate the effects of intermediate frequency (IF) fields generated by induction heating (IH) cooktops from the perspective of cellular genotoxicity and stress responses., Materials and Methods: We evaluated the effects of exposure to 23 kHz magnetic fields at 6.05 mT(rms) for 2 h on cellular genotoxicity and stress responses in vitro. The maximum output power in most IH cooktops is at this frequency. The magnetic flux density is approximately 1000 times higher than the reference level in the International Commission on Non-ionising Radiation Protection (ICNIRP) guidelines. For assessment of genotoxicity, we studied cell growth, comet assay, micronucleus formation and hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutation. Heat shock protein (Hsp) 27, 70, 105 and phosphorylated Hsp27 were evaluated as indicators of the stress responses., Results: We did not detect any effects of the IF magnetic fields on cell growth, comet assay, micronucleus formation, HPRT gene mutation, expression of phosphorylated Hsp27, or nuclear translocation of Hsp27, 70 or 105., Conclusions: Our results indicate that exposure to an IF magnetic field at 6.05 mT(rms) for 2 h does not cause detectable cellular genotoxicity, and does not induce detectable cellular stress.

We developed mitochondrial (MT) scoring system based on MT ultrastructural findings in association with response to chemotherapy in ovarian cancer (OC). Ultrathin sections of MT prepared from 28 OC patients before chemotherapy were examined by electron microscopy. Platinum-sensitive ovarian carcinoma cell line 2008 and its resistant variant C13 were used as control cells. Seven independent MT features including, diameter, pattern of cresta structure, electron density, distribution-density and -pattern, ratio of minimal/maximal diameter and MT architecture were examined and were assigned a score between 0 and 2. Twenty-eight cases were primary advanced OC, including 4 recurrent cases. Nine cases were chemosensitive while 19 were resistant. Univariate and multivariate analysis in each factor showed good correlation to chemosensitivity for 2 factors of electron density, distribution pattern. Total score of these 2 factors in 9 sensitive cells was 1.44+/-0.41 (M +/- SE) and was 3.58+/-0.18 in 19 resistant cells (P<0.001). Receptor operative characteristics (ROC) analysis revealed that total 'cut-off' score was 3 point (P<0.05; AUC=0.84). In conclusion, this MT scoring system was excellently correlated to response regardless of histopathologic findings and this strongly suggests that the system is deemed to be of great value as biomarker for the chemosensitivity in OC.