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Objective: / To apply the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system to all patients who underwent trachelectomy in our previous study and to update the oncologic and obstetric results. / Methods: / We retrospectively reviewed the medical records of patients in whom abdominal trachelectomy was attempted between June 2005 and September 2021. The FIGO 2018 staging system for cervical cancer was applied to all patients. / Results: / Abdominal trachelectomy was attempted for 265 patients. Trachelectomy was converted to hysterectomy in 35 patients, and trachelectomy was completed successfully in 230 (conversion rate: 13%). Applying the FIGO 2018 staging system, 40% of the patients who underwent radical trachelectomy had stage IA tumors. Among 71 patients who had tumors measuring ≥2 cm, 8 patients were classified as stage IA1 and 14 as stage IA2. Overall recurrence and mortality rates were 2.2% and 1.3%, respectively. One hundred twelve patients attempted to conceive after trachelectomy; 69 pregnancies were achieved in 46 patients (pregnancy rate: 41%). Twenty-three pregnancies ended in first-trimester miscarriage, and 41 infants were delivered between gestational weeks 23 and 37; 16 were deliveries at term (39%) and 25 were premature deliveries (61%). / Conclusion: / This study suggested that patients judged to be ineligible for trachelectomy and patients receiving overtreatment will continue to appear using the current standard eligibility criteria. With the revisions to the FIGO 2018 staging system, the preoperative eligibility criteria for trachelectomy, which were based on the FIGO 2009 staging system and tumor size, should be changed.

Background Pancreatic trauma is a rare condition with a wide presentation, ranging from hematoma or laceration without main pancreatic duct involvement, to massive destruction of the pancreatic head. The optimal diagnosis of pancreatic trauma and its management approaches are still under debate. The East Association of Surgery for Trauma (EAST) guidelines recommend operative management for high-grade pancreatic trauma; however, several reports have reported successful outcomes with nonoperative management (NOM) for grade III/IV pancreatic injuries. Herein, we report a case of grade IV pancreatic injury that was nonoperatively managed through endoscopic and percutaneous drainage. Case presentation A 47-year-old Japanese man was stabbed in the back with a knife; upon blood examination, both serum amylase and lipase levels were within normal limits. Contrast-enhanced computed tomography (CT) showed extravasation of the contrast medium around the pancreatic head and a hematoma behind the pancreas. Abdominal arterial angiography revealed a pseudo aneurysm in the inferior pancreatoduodenal artery, as well as extravasation of the contrast medium in that artery; coil embolization was thus performed. On day 12, CT revealed a wedge-shaped, low-density area in the pancreatic head, as well as consecutive pseudocysts behind the pancreas; thereafter, percutaneous drainage was performed via the stab wound. On day 22, contrast radiography through the percutaneous drain revealed the proximal and distal parts of the main pancreatic duct. The injury was thus diagnosed as a grade IV pancreatic injury based on the American Association for the Surgery of Trauma guidelines. On day 26, an endoscopic nasopancreatic drainage tube was inserted across the disruption; on day 38, contrast-enhanced CT showed a marked reduction in the fluid collection. Finally, on day 61, the patient was discharged. Conclusions Although the EAST guidelines recommend operative treatment for high-grade pancreatic trauma, NOM with appropriate drainage by endoscopic and/or percutaneous approaches may be a promising treatment for grade III or IV trauma.

Simple Summary For 657 cases of segment or less repeat liver resection with results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery, the indicators were compared before and after surgery. There were 268 open repeat after open and 224 cases laparoscopic repeat after laparoscopic liver resection. The background factors and liver functional indicators before and after surgery, and the changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Though laparoscopic group had poorer performance status and liver function, changes of the values and overall survivals were similar between both groups. Plasma levels of albumin and bilirubin and ALBI score could be the liver functional indicators for liver functional deterioration after liver resection. The laparoscopic group with poorer conditions showed a similar deterioration of liver function and overall survival to the open group. Whether albumin and bilirubin levels, platelet counts, ALBI, and ALPlat scores could be useful for the assessment of permanent liver functional deterioration after repeat liver resection was examined, and the deterioration after laparoscopic procedure was evaluated. For 657 patients with liver resection of segment or less in whom results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery could be retrieved, liver functional indicators were compared before and after surgery. There were 268 patients who underwent open repeat after previous open liver resection, and 224 patients who underwent laparoscopic repeat after laparoscopic liver resection. The background factors, liver functional indicators before and after surgery and their changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Laparoscopic group had poorer preoperative performance status and liver function. Changes of liver functional values before and after surgery and overall survivals were similar between laparoscopic and open groups. Plasma levels of albumin and bilirubin and ALBI score could be the indicators for permanent liver functional deterioration after liver resection. Laparoscopic group with poorer conditions showed the similar deterioration of liver function and overall survivals to open group.

Simple Summary Less morbidity is considered among the advantages of laparoscopic liver resection for HCC patients. However, our previous international, multi-institutional study of laparoscopic repeat liver resection (LRLR) failed to prove it. We hypothesize that these results may be since the study included complex cases performed during the procedure’s developing stage. To examine it, subgroup analysis based on propensity score were performed, defining the proximity of the tumors to major vessels as the complexity. A propensity score matching earned 115 each patient of LRLR and open repeat liver resection (ORLR) without the proximity to major vessels, and the outcomes were compared. With comparable operation time and long-term outcome, less blood loss and less morbidity were shown in LRLR group than ORLR. Even in its worldwide developing stage, LRLR for HCC patients could be beneficial in blood loss and morbidity for the patients with less complexity in surgery. Abstract Less morbidity is considered among the advantages of laparoscopic liver resection (LLR) for HCC patients. However, our previous international, multi-institutional, propensity score-based study of emerging laparoscopic repeat liver resection (LRLR) failed to prove this advantage. We hypothesize that these results may be since the study included complex LRLR cases performed during the procedure’s developing stage. To examine it, subgroup analysis based on propensity score were performed, defining the proximity of the tumors to major vessels as the indicator of complex cases. Among 1582 LRLR cases from 42 international high-volume liver surgery centers, 620 cases without the proximity to major vessels (more than 1 cm far from both first–second branches of Glissonian pedicles and major hepatic veins) were selected for this subgroup analysis. A propensity score matching (PSM) analysis was performed based on their patient characteristics, preoperative liver function, tumor characteristics and surgical procedures. One hundred and fifteen of each patient groups of LRLR and open repeat liver resection (ORLR) were earned, and the outcomes were compared. Backgrounds were well-balanced between LRLR and ORLR groups after matching. With comparable operation time and long-term outcome, less blood loss (283.3±823.0 vs. 603.5±664.9 mL, p = 0.001) and less morbidity (8.7 vs. 18.3 %, p = 0.034) were shown in LRLR group than ORLR. Even in its worldwide developing stage, LRLR for HCC patients could be beneficial in blood loss and morbidity for the patients with less complexity in surgery.

Gα13, a heterotrimeric G-protein of the Gα12/13 subfamily, is associated with aggressive phenotypes in various human cancers. However, the mechanisms by which Gα13 promotes cancer progression have not been fully elucidated. Here, we demonstrate that the activation of Gα13 induces epithelial-mesenchymal transition in ovarian cancer (OvCa) cells through down-regulation of large tumor suppressor kinase (LATS) 1, a critical component of the Hippo signaling pathway. A synthetic biology approach using a mutant GPCR and chimeric G-protein revealed that Gα13-regulated phosphorylation of LATS1 at serine 909 within its activation loop induced recruitment of the itchy E3 ubiquitin protein ligase to trigger LATS1 degradation. Our findings uncover novel mechanisms through which Gα13 activation induces dysregulation of the Hippo signaling pathway, which leads to aggressive cancer phenotypes, and thereby identify a potential target for preventing the metastatic spread of OvCa.-Yagi, H., Onoyama, I., Asanoma, K., Hori, E., Yasunaga, M., Kodama, K., Kijima, M., Ohgami, T., Kaneki, E., Okugawa, K., Yahata, H., Kato, K. Gα13-mediated LATS1 down-regulation contributes to epithelial-mesenchymal transition in ovarian cancer.

Background/aim The aim of this study was to examine the clinicopathological features of pancreatic adenosquamous carcinoma (PASC). Patients and methods Our study included seven patients who underwent resection of PASC. Results PASC is characterized by large tumors and strong infiltration into the major blood vessels and other organs, forcing many patients to undergo extended resections. In addition, all patients experienced liver metastasis recurrence following surgery, with a very poor prognosis. Histopathologically, a poorly differentiated sarcomatous component existed in all patients in addition to an adenocarcinoma component and squamous carcinoma component. Although P40 staining for the sarcomatous component was positive along with squamous carcinoma, E-cadherin expression disappeared while vimentin was expressed. It has been suggested that it is highly likely that these sarcomatous components are derived from squamous carcinoma and have an impact on prognosis. Conclusion The sarcomatous component may be related to the biological malignancy of PASC.

Background/aim The aim of this study was to investigate the effects of preoperative chemotherapy on the healthy, metastasis-free part of the liver in colorectal cancer patients with liver metastasis, and the relationship between chemotherapy and postoperative complications. Patients and methods Our study included 90 cases of colorectal cancer liver metastasis resected after preoperative chemotherapy. The patients were divided into three groups according to the received chemotherapy regimen: 20 cases received mFOLFOX6, 54 cases a combination of mFOLFOX6 with bevacizumab, and 16 cases a combination of mFOLFOX6 and cetuximab or panitumumab. Results The mean numbers of sinusoidal injuries for each chemotherapy type were compared. The group treated with the combination of mFOLFOX6 and bevacizumab showed a lower extent of sinusoidal injury relative to other groups; this intergroup difference became increasingly remarkable as the number of chemotherapy cycles increased. Complications of various extents were found in all three groups, but no significant differences were observed between the three groups. Conclusion In cases where preoperative chemotherapy was extended over a long period, combined use of bevacizumab was thought to be effective because of stabilization of disturbed liver hemodynamics resulting from sinusoidal injury suppression effects, allowing effective distribution of anti-cancer agents to tumors.

Ageing of the uterine endometrium is a critical factor that affects reproductive success, but the mechanisms associated with uterine ageing are unclear. In this study, we conducted a qualitative examination of age-related changes in endometrial tissues and identified candidate genes as markers for uterine ageing. Gene expression patterns were assessed by two RNA-sequencing experiments using uterine tissues from wild type (WT) C57BL/6 mice. Gene expression data obtained by RNA-sequencing were validated by real-time PCR. Genes expressing the pro-inflammatory cytokines Il17rb and chemokines Cxcl12 and Cxcl14 showed differential expression between aged WT mice and a group of mice composed of 5- and 8-week-old WT (young) animals. Protein expression levels of the above-mentioned genes and of IL8, which functions downstream of IL17RB, were analysed by quantitative immunohistochemistry of unaffected human endometrium tissue samples from patients in their 20s and 40s (10 cases each). In the secretory phase samples, 3,3ʹ- diaminobenzidine staining intensities of IL17RB, CXCL12 and CXCL14 for patients in their 40s were significantly higher than that for patients in their 20s, as detected by a Mann–hitney U test. These results suggest that these genes are candidate markers for endometrial ageing and for prediction of age-related infertility, although confirmation of these findings is needed in larger studies involving fertile and infertile women.

Highlights • This report shows very rare cases of small cell carcinoma of the ovary, hypercalcemic type and pulmonary type. • Their chemo sensitivity is quite different. These two cases followed opposite clinical courses. • The first case (SCOHT) progressed rapidly, and showed resistance to chemotherapy and radiotherapy. • The second case (SCOPT) showed sensitivity to chemotherapy and radiotherapy although recurrence was repeated.

Background/aim Intraductal papillary mucinous neoplasm (IPMN) has a variety of histological and morphological appearances. Matrix metalloproteinases (MMPs) have been considered to be associated with tumor progression or poor prognosis. The aim of this study was to elucidate the molecular basis of IPMN variation in different types of lesions. Materials and methods The expression of MMP-1,2,7,9 in 51 cases of IPMN were investigated. The MMP score was calculated as the sum of the score of staining distribution and the score of the intensity staining. Results MMP scores were correlated with histological grade, histological subtype, and type of invasion. MMP high expression groups (MMP score ≥5) had worse prognosis than low-expression groups. Conclusion MMP expression varied between different types of IPMN, a result supporting differences in molecular basis of malignancies. These considerations may be helpful for optimal management or treatment according to various types of IPMN.

Background/aim Neoplastic spindle cells (NSCs) are believed to play a role in cancer invasion and metastasis, as well as in poor prognosis. The clinicopathological characteristics and prognostic relevance of NSCs was investigated in gallbladder cancer. Materials and methods Specimens were obtained from 62 patients with gallbladder cancer who underwent surgery. The emergence of NSCs and their correlation with clinicopathological factors, prognosis, and EMT markers was evaluated. Results The NSC grade correlated with tumor size, preoperative CA19-9, surgical margin, the degree of differentiation, the depth of invasion, lymph node metastasis, lymphatic invasion, vascular invasion, and perineural invasion. Multivariate analysis of overall survival showed that NSCs were an independent prognostic factor. A correlation between NSCs and EMT was also suggested. Conclusion NSCs are an independent prognostic factor for patients with postoperative gallbladder cancer, which also suggests a correlation between NSCs and EMT.

BHLHE40 and BHLHE41 (BHLHE40/41) are basic helix-loop-helix type transcription factors involved in multiple cell activities including epithelial-to-mesenchymal transition (EMT). However, the expression mechanism of BHLHE40/41 in EMT remains unclear. In the present study, we showed that the expression levels of BHLHE40/41 were negatively correlated with those of the microRNA (MIR) 130 family in endometrial cancer (EC) specimens. Our in vitro assays indicated that the expression of BHLHE40/41 was suppressed directly by the MIR130 family in a 3'-untranslated region-mediated manner. In EC cells, the MIR130 family promoted EMT and tumor cell invasion by suppressing the expression of BHLHE40/41. We identified the critical promoter region of the MIR301B-MIR130B cluster for its basal transcription by the transcription factor, SP1. We also found that BHLHE40/41 suppressed the expression of MIR301B and MIR130B, and we identified a binding site in the promoter region for BHLHE40/41. This study is the first to report that BHLHE40/41 and the MIR301B-MIR130B cluster suppressed each other to regulate EMT and invasion of EC cells. We propose that BHLHE40/41 and the MIR130 family are excellent markers to predict the progression of EC cases, and that molecular therapy targeting the MIR130 family-BHLHE40/41 axis may effectively control EC extension.

Objective: For oncologic safety, vaginal radical trachelectomy is generally performed only in patients with cervical cancers smaller than 2 cm. However, because inclusion criteria for abdominal trachelectomy are controversial, we evaluated the safety of abdominal trachelectomy for cervical cancers ≥2 cm. / Methods: We began performing abdominal trachelectomies at our institution in 2005, primarily for squamous cell carcinoma ≤3 cm or adenocarcinoma/adenosquamous carcinoma ≤2 cm. If a positive sentinel lymph node or cervical margin was diagnosed intraoperatively by frozen section, the trachelectomy was converted to a hysterectomy. Medical records of these patients were reviewed retrospectively. Patients who had undergone simple abdominal trachelectomy were excluded from this study. / Results: We attempted trachelectomy in 212 patients. Among the 135 patients with tumors

T2 (tumor invades perimuscular connective tissue; no extension beyond serosa or into liver) gallbladder cancer has generally been treated by S4aS5 subsegmentectomy (S4aS5 HR). We investigated the therapeutic effect of full-thickness cholecystectomy (FC) and gallbladder bed resection (GBR), in terms of tumor location and resection margin (distance from the tumor). At our department we employ the following protocol to determine the extent of resection needed to achieve R0 status: (1) A tumor located in the gallbladder fundus (Gf) or body (Gb) and only on the free peritoneal side was classified as P-type, for which full-thickness cholecystectomy and regional lymph node dissection were performed. (2) A tumor located in Gf or Gb and in contact with the liver bed was classified as H-type, for which gallbladder bed resection and regional lymph node dissection were performed. (3) A tumor located in the gallbladder neck (Gn) was classified as N-type, for which gallbladder bed resection, bile duct resection, and regional lymph node dissection were performed. Twenty-two patients admitted to our department between January 2000 and December 2014 with pT2gallbladder cancers were included in our study. Surgical procedures performed were compared with those specified in our protocol, and patients in whom the extent of resection was greater than that specified in our strategy were evaluated clinicopathologically and in terms of recurrence and the prognosis. Six (27.2%), 7 (31.8%), and 9 (40.9%) patients underwent limited, standard, and extended surgery, respectively. Ten (66.7%) of 15 patients with tumors close to the liver bed underwent cholecystectomy or extended surgery, 7 (85.7%) of 8 patients with tumors close to the bile duct underwent bile duct resection, and 16 (72.7%) of 22 patients underwent regional lymph node dissection. Recurrence at the bile duct resection margin, para-aortic lymph node metastasis, and hepatic metastasis occurred in 2, 1, and 3 patients, respectively. The 3-year survival rates (for patients including those dying of noncancer causes) were 50, 100, and 75% after limited, standard, and extended surgery, respectively. There was a significant difference in the survival rate of patients who underwent standard or extended surgery (P=0.0273). Favorable results were obtained in T2 gallbladder cancer patients without performing S4aS5 subsegmentectomy. Depending on the tumor location, neither full-thickness cholecystectomy nor gallbladder bed resection appeared to pose problems regarding recurrence or prognosis. In conclusion, surgical treatment based on our protocol, which aims to achieve the condition of R0, may result in a sufficient therapeutic effect.

Objectives The purpose of this study was to assess the correlations among the maximum standardized uptake value (SUVmax) on 18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT); the expressions of glucose transporter 1 (GLUT-1), glucose transporter 3, and epidermal growth factor receptor (EGFR); as well as prognosis in patients with invasive ductal carcinoma of the pancreas. Methods A total of 41 patients with surgically resected and histologically proven invasive ductal carcinoma of the pancreas who underwent preoperative FDG-PET/CT were assessed. The SUVmax at the primary tumor site was measured by FDG-PET/CT, and immunohistochemical staining of tumor sections was performed for GLUT-1, glucose transporter 3, and EGFR. Results Higher FDG uptake (SUVmax, >3.40) and GLUT-1 expression were significantly associated with shorter overall survival (P < 0.05). The SUVmax was not found to be significantly correlated with clinicopathological characteristics such as TNM classification, lymph node metastasis, and tumor differentiation. The EGFR expression was significantly correlated with the SUVmax (P = 0.024). Conclusions Higher FDG uptake and GLUT-1 expression in invasive ductal carcinoma of the pancreas seems to be an important prognostic factor. In addition, the EGFR expression was significantly correlated with the SUVmax.

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplastic diseases, associated with a remarkably poor prognosis. However, the molecular mechanisms underlying the development of PDAC remain elusive. The aim of this study was to identify genes whose expressions are correlated with a poor prognosis in PDAC patients, and to unravel the mechanisms underlying the involvement of these genes in the development of the cancer. Methods Global gene expression profiling was conducted in 39 specimens obtained from Japanese patients with PDAC to identify genes whose expressions were correlated with a shorter overall survival. The effect of gene silencing or overexpression of ARHGEF15 in pancreatic cancer cell lines was examined by introducing siRNAs of ARHGEF15 or the ARHGEF15 expression vector. After assessing the effect of ARHGEF15 deregulation on the Rho-family proteins by pull-down assay, wound healing, transwell and cell viability assays were carried out to investigate the cellular phenotypes caused by the perturbation. Results The global mRNA expression profiling revealed that overexpression of ARHGEF15, a Rho-specific GEF, was significantly associated with a poor prognosis in patients with PDAC. We also found that the depletion of ARHGEF15 by RNA interference in pancreatic cancer cell lines downregulated the activities of molecules of the Rho signaling pathway, including RhoA, Cdc42 and Rac1. Then, we also showed that ARHGEF15 silencing significantly reduced the motility and viability of the cells, while its overexpression resulted in the development of the opposite phenotype in multiple pancreatic cancer cell lines. Conclusion These data suggest that upregulation of ARHGEF15 contributes to the development of aggressive PDAC by increasing the growth and motility of the pancreatic cancer cells, thereby worsening the prognosis of these patients. Therefore, ARHGEF15 could serve as a novel therapeutic target in patients with PDAC. Electronic supplementary material The online version of this article (doi:10.1186/s12943-016-0516-4) contains supplementary material, which is available to authorized users.

症例は58歳,女性.下痢と食思不振のため精査,腹部CTにて後腹膜腫瘍を指摘された.腫瘍マーカーは,いずれも正常範囲であった.種々の画像診断の結果,十二指腸後壁より発生したGISTを疑われ手術の方針となった.実際の開腹所見で,腫瘍は膵後面の膵実質から膵外へ発育していたため,膵実質を一部腫瘍に付ける形で腫瘍切除術を行った.病理組織学所見で,腫瘍部は小型で核小体の出現・クロマチン増量を示す異型細胞が,策状・リボン状配列を呈しながら増殖し,免疫染色では,シナプトフィジン・クロモグラニン陽性,グリメリウス・c-kit・CD34陰性であった.ホルモン関連は,ガストリン陽性,グルカゴン・インスリン.ソマトスタチン陰性であった.この結果より膵内分泌腫瘍(ガストリノーマ)と診断された.後日判明した内分泌検査の結果,血中ガストリンが2,400pg/mlと高値を示していた.現在は外来通院にて経過観察中である.

We report 2 patients with acute cholecystitis for which percutaneous transhepatic gallbladder aspiration (PTGBA) was useful. In Case 1, the patient was a 75-year-old woman who experienced a sudden onset of back pain and upper abdominal pain at night. Abdominal ultrasound (US) showed enlargement of the gallbladder with thickening of the wall, a sonolucent layer, and a stone in the neck of the gallbladder, which led to a diagnosis of acute cholecystitis. Magnetic resonance imaging (MRI) demonstrated thickening of the gallbladder wall and 2 areas of low-intensity signal. The pain and fever persisted, for which we performed PTGBA, aspirating about 113 ml of infected bile. Subsequently, the pain and fever subsided, and abdominal US revealed a reduction in the enlargement of the gallbladder with the persistence of thickening of the wall. On the eighth day after PTGBA, open abdominal cholecystectomy was performed. In Case 2, the patient was a 56-year-old woman who had right hypochondriac pain after supper. The pain gradually increased in severity. Abdominal US showed enlargement of the gallbladder with a thickened wall, a sonolucent layer, and a gallstone in the neck of the gallbladder, which led to a diagnosis of acute cholecystitis. Magnetic resonance cholangiopancreatography (MRCP) showed enlargement of the gallbladder with no abnormalities in the common bile duct. After admission to hospital, the pain and fever persisted, for which we performed PTGBA, aspirating about 50 ml of infected bile. Subsequently, the pain and fever vanished. Abdominal US revealed a reduction in the enlargement of the gallbladder with the persistence of thickening of the wall. On the seventh day after PTGBA, laparoscopic cholecystectomy was performed. PTGBA seems useful for early alleviation of the symptoms of acute cholecystitis because of low invasiveness and ease of performance.

We report a case of gallbladder cancer associated with pancreaticobiliary maljunction. The patient was a 60-year-old woman who consulted a local doctor because of discomfort in the right hypochondriac region. Abdominal ultrasonography (US) showed a gallbladder abnormality, and she was referred to Kurume University Hospital, where she was hospitalized for further study and surgery. Abdominal US revealed a sessile tumor with an irregular surface in the fundus of the gallbladder. The internal echo of the tumor was nonhomogeneous, and the structure of the gallbladder wall was partly torn. The common bile duct and the left intrahepatic bile duct were dilated. Abdominal computed tomography (CT) showed an elevated lesion with the same degree of imaging effect as that of the liver on the peritoneal side of the fundus of the gallbladder. The structure of the gallbladder was preserved, and the gallbladder was well demarcated from the surrounding tissue. No hepatic or lymph node metastases were noted. Endoscopic retrograde cholangiopancreatography (ERCP) visualized the pancreaticobiliary maljunction where the pancreatic duct joined the bile duct, entering an approximately 2-cm-long common channel. Dilatation of the common bile duct and intrahepatic bile ducts was observed and diagnosed as the IV-A type according to the Toya classification. Abdominal angiography in the arterial phase showed dilatation of the cystic artery and hyperplasia of vessels but no apparent encasement. In the venous phase, a deep-staining tumor was observed. From the above findings, we made a diagnosis of gallbladder cancer complicating pancreaticobiliary maljunction, and performed an operation. Since intraoperative US showed that the outermost layer of the gallbladder was in part ill-demarcated, we diagnosed the depth of penetration as ss, and performed cholecystectomy and bile duct resection and hepatic resection (S4a and S5), and lymphnode dissection (D2; dissection of groups 1 and 2 lymphnodes). The resected specimen grossly showed a papillomatous lesion with a cauliflower-like surface. The histopathologic diagnosis was papillary adenocarcinoma, depth ss, stage II. Tumor cells proliferated in a papillomatous pattern and were mostly confined to the muscular coat but partly infiltrated into the subserosal coat. In the diagnosis of pancreaticobiliary maljunction, it is crucial to consider complicating gallbladder cancer.

A61-year-old woman was seen at the hospital because she noticed a left breast mass. A well movable tumor was palpable in the C area of left breast. Ultrasonography revealed a 12×9×8mm demarcated iow-echoic region with slightly heterogeneous inside. Mammography visualized a partially irregular image in the left berast. Needle aspiration biopsy cytology disclosed nucleoli as well as relatively numerous cells, indicating class III. Under local anesthesia, an excisional biopsy was perfor-med. Aa a result of histopathological exploration, ductal carcinoma was diagnosed and a radical operation was performed. Despite the pathological diagnosis of ductal carcinoma, the tumor cells were positive for S-100 protein and HHF-35 and vascular infiltrating was revealed. The definite diagnosis of malignant adenomyoepithelioma was made. In the diagnosis of the disease, histopathological and electron microscopic findings are helpful. Adenomyoepithelioma manifesting malgnant features is so rare that only two cases have been reported in Japan.

This study evaluated in vitro assay for chemosensitivity test using a collagen-gel droplet embedded culture drug sensitivity test (CD-DST) for colorectal cancer. CD-DST was performed in 24 patients with Dukes B, C colorectal cancer. Primary cultures of tumor cell samples from 87.5% (21124) patients with colorectal cancer were successful. The efficacy rates assessed by CD-DST of five anticancer drugs evaluated were : 60.4% for adriamycin, 58.9% for etoposide, 56.7% for cisplatin, 53.4% for 5-fluorouracil, for 31.1% for mitomycin C, and 9.5% for vindesine. The present study demonstrated the clinical usefulness of CD-DST in evaluating the response to chemotherapy in colorectal cancer.

A prospective study was carried out to analyze the clinical and functional results of transsacral rectopexy with a DEXON mesh in the elderly or poor risk patients with complete rectal prolapse. Six patients with complete rectal prolapse were operated from 1994 to 1996. All patients could be traced for examination with anorectal manometry and defecography. None of the patients had recurrence for the longest three years. In postoperative clinical symptoms, fecal incontinence score recovered from the preoperative mean score of 3.8 to the postoperative 1.2 and constipation was improved in 4 out of 5 cases (80.0%). Straining anorectal angle (S-ARA) by defecography improved from the preoperative value of 120.6 +/- 6.9 degrees to the postoperative value of 98.5 +/- 3.5 degrees (p < 0.05) and the perineal descent (PD) improved from the preoperative value of 16.2 +/- 2.5 cm to the postoperative value 8.1 +/- 1.3 cm (p < 0.05). Maximal resting pressure (MRP) increased from the preoperative value of 20.5 +/- 3.7 cmH2O to the postoperative value of 40.5 +/- 4.8 cmH2O (p < 0.05). Transsacral rectopexy with DEXON mesh for complete rectal prolapse is useful as this technique is simple to conduct, can be applied to the elderly or poor risk patients, replaces rectal prolapse, improves defecation troubles and recovers fecal incontinence.

Clinical aspects of laparoscopy combined total colectomy (LTC) (n = 10) and open total colectomy (OTC) (n = 29) with ileorectal anastomosis for familial adenomatous polyposis and ulcerative colitis are compared in a retrospective study. The mean operative time was 282 (range, 169 to 420) minutes in the LTC group and 274 (range, 139 to 570) minutes in the OTC group. The mean volume of operative blood loss was 321 (range, 52 to 728) ml and 471 (range, 48 to 1040) ml for the LTC and OTC groups, respectively. Nasogastoric tube could be removed after POD 1.2 vs. 5.8 (p0.05), the mean time to passage of stool was 1.9 (range, 1 to 3) vs. 5.2 (range, 3 to 7) days (p0.01), and in the LTC group watery stool was soon made solidification after POD 23.4 vs. 84.1 (p0.01). Laparoscopy combined total colectomy may prove to have one-stage restorative total colectomy without a temporary ileostomy due to early solidification of watery stool and more benefits than conventional open surgery.

Improvement of functional outcome after proctocolectomy for ulcerative colitis and familial adenomatous polyposis was compared between transanal ileal pouch-anal anastomosis (T-IAA group, n = 29) and double-stapled ileal pouch-anal anastomosis (DS-IAA group, n = 8). Clinical functions were evaluated using a functional scoring system, and physiologic functions by anorectal manometry after one year postoperatively. Although in the T-IAA group 4 of the 29 patients (13.8%) displayed partial incontinence (9 points), all of 8 patients in the DS-IAA group showed good results referring to continence (10 points). The maximum resting pressure was 44.3 +/- 5.2 cmH2O in the T-IAA group vs. 56.6 +/- 5.8 cmH2O in the DS-IAA group, and postoperatively the maximum squeezing pressure was 96.8 +/- 9.2 cmH2O in the T-IAA group vs. 106.3 +/- 8.1 cmH2O in the DS-IAA group. There was a significant difference of maximum resting pressure and no significant difference of maximum squeezing pressure between the two groups. The length of the high pressure zone in the anal canal was significantly shorter in patients of the T-IAA group (2.1 +/- 0.8 cm) than in those of the DS-IAA group (3.5 +/- 1.1 cm) (p0.05). The DS-IAA is associated with excellent objective physiologic and subjective functional results. This reflects the sacrifice of the internal anal sphincter 1.5 cm cephalad necessary to effect this anastomosis at a mean of 1.4 cm from the dentate line.

Splenectomy may be a treatment option in hepatocellular carcinoma (HCC) and cirrhosis when there is no potential donor for liver transplantation. We retrospectively investigated the long-term outcome of splenectomy on survival in advanced cirrhotic patients with HCC and thrombocytopenia. Between 1999 and 2009, 46 cirrhotic patients with thrombocytopenia (Child-Pugh class B or C) who underwent splenectomy for the simultaneous or secondary treatment of HCC at our institute were evaluated. The 1-, 3-, and 5-year survival rates were 93.5, 76.0, and 37.9%, respectively. Splenectomy resulted in a significant reduction in mean portal venous pressure from 21.2 to 16.8 mmHg and improvements in liver function tests such as total bilirubin, prothrombin time, platelet count, Child-Pugh score for 3 years, and albumin for 2 years. The mean frequency of treatment for HCC recurrence after surgery was 3.0 times (range 1-11). Seven patients out of 16 scheduled for Interferon (IFN) therapy after surgery achieved a sustained virological response (SVR). Multivariate analysis identified SVR after IFN therapy as an independent significant prognostic factor (Hazard ratio 0.18, 95%CI 0.03-0.65, P=0.006). Postoperative complications including liver failure (n=1), portal thrombosis (n=7), ascites (n=5), and bacterial infections (n=4) were observed in 14 patients (30%). Splenectomy can be a feasible supportive therapy for the continuation of anticancer therapy and completion of IFN therapy based on improvements in liver function and thrombocytopenia with minimum complications in patients with HCC and advanced cirrhosis with no potential donor.

Most patients with Asherman's syndrome present with infertility and menstrual problems. In this retrospective clinical study, we analyzed patients with Asherman's syndrome who underwent hysteroscopic adhesiolysis to examine their associated symptoms, disease etiologies, and fertility outcomes.Twenty-seven patients with Asherman's syndrome that were diagnosed using hysteroscopy were recruited. The chief complaints were infertility, hypomenorrhea, and amenorrhea. Each case of Asherman's syndrome was classified according to the American Fertility Society classification. Hysteroscopic adhesiolysis was performed in all cases and concomitant transabdominal ultrasonography was conducted in cases with extensive and dense adhesions.There were no complications associated with the hysteroscopic procedure. Normal menstrual cycles resumed in all cases. Of the 16 infertile patients, 9 conceived. Three patients achieved term deliveries and one patient is currently pregnant. None of the patients had obstetric complications. Two patients had spontaneous abortions, one had an ectopic pregnancy, one had an abortion at 16 weeks' gestation due to cervical incompetence, and one had a molar pregnancy and required uterine artery embolization for uncontrolled hemorrhaging during a dilatation and curettage procedure.Hysteroscopic adhesiolysis with transabdominal ultrasonography is a suitable treatment method for Asherman's syndrome. Subfertile patients with Asherman's syndrome undergoing adhesiolysis should be appropriately informed about the risk of associated life-threatening complications and preterm delivery.

BACKGROUND: Cystic lesions of the liver consist of a heterogeneous group of disorders that can present diagnostic and therapeutic challenges. METHODS: A retrospective review of all medical records of adult patients diagnosed with large (>7 cm) cystic lesions of the liver between January 2000 and December 2011, at Kurume University Hospital. Cases with polycystic disease were excluded. RESULTS: Twenty three patients were identified. The mean size was 13.9 cm (range, 7-22cm). The majority of simple cysts were found in women (females: males, 2: 21). In 19 patients, the cyst was removed surgically by wide deroofing (laparoscopically in 16 cases, combined with ethanol sclerotherapy in 13 cases). Infection of the liver cyst occurred in one patient, who later underwent central bi-segmentectomy. CONCLUSION: Simple large cysts of the liver can be successfully treated by laparoscopic deroofing and alcohol sclerotherapy. Large hepatic cyst considered to need drainage should be removed surgically to avoid possible infection.

For the majority of patients, ductal adenocarcinoma of the pancreas remains a lethal disease. Currently, surgical extirpation for localized disease offers the only chance for long-term survival.We report a patient who underwent successful resection of isolated lung metastasis occurring 13 years after pancreatic cancer resection. A 59-year-old woman underwent distal pancreatectomy for pancreatic cancer 13 years previously, followed by adjuvant chemotherapy, and was followed-up at the outpatient clinic of a local hospital. From around June 2010, she noticed bloody sputum, so she visited a local hospital. Since her chest X-ray and CT revealed a 1.5 cm mass shadow in the segment 10 of her right lung and she was referred to the Respiratory Disease Center of our hospital. As a result of through examinations, she was strongly suspected of having lung metastasis of pancreatic cancer, and underwent partial pneumonectomy. Postoperative histopathological examination of the resected specimen was consistent with lung metastasis of pancreatic cancer. She is still alive and currently receives third line of chemotherapy.Patients who have achieved long-term survival after pancreatic cancer resection and can tolerate surgery may benefit from resection of a lung metastasis of pancreatic cancer in terms of survival, if it controls the metastasis.

最近,腹部超音波診断法(ECHO)で,単発あるいは多発の肝内小結節性病変を指摘され,肝生検施行すると凝固壊死を伴う肉芽組織が採取され,質的診断が困難な症例を著者らの施設では,しばしば経験するようになった.このような凝固壊死を呈する肉芽性結節14例について検討した.対象とした14例は臨床的に2例を除きウイルスマーカーは陰性,腫瘍マーカーは全例が陰性であり,ECHOでは14例中10例(71.4%)が結節内に2本の線状エコー(bead sign)を有し,病理学的には凝固壊死と肉芽組織で構成され,凝固壊死部をさらに詳しく検討すると,著明な好酸球浸潤や14例中7例(50%)にCharcot-Leyden結晶が認められることから,寄生虫感染(特にイヌ・ネコ蛔虫症や肝蛭症)との密接な関連が示唆される病変である.

外科切除された慢性肝炎を合併する肝細胞癌(CH群)94例の臨床病理学的特徴について,肝硬変合併群(LC群)156例と比較検討した.HBsAg, HCV抗体陽性率では,CH群,LC群ともにほぼ同率で有意差はなく,CH群では,HBsAg陽性群の方がHCV抗体陽性群より有意に平均年齢が低かった.細小肝癌における高分化型の頻度はCH群50.0%, LC群74.5%とLC群に高く(p

Ovarian mucinous neoplasms of gastro-intestinal type (GI-type) are known to be a heterogeneous tumor composed of benign, borderline and non-invasive and invasive malignant lesions. The presence of infiltrative invasion is also known to be an important prognostic factor of this neoplasm. Laminin γ 2 chain, known to stimulate tumor cell invasion and migration, has not been sufficiently investigated in ovarian mucinous neoplasms. The purpose of this study was thus to clarify the role of laminin γ 2 in ovarian mucinous neoplasms of GI-type. We selected each morphological phase of tumor development from 61 cases of mucinous neoplasms of the GI-type: 55 adenoma lesions, 60 borderline lesions, 20 microinvasive lesions, 17 intra-epithelial carcinoma lesions, 38 expansile invasive carcinoma lesions, 19 infiltrative invasive carcinoma lesions and 5 mural nodules lesions; and evaluated the localization of laminin γ 2 in the lesions using immunohistochemical method. The staining pattern was classified into i) basement membranous (BM), ii) cytoplasmic (CYT) and iii) stromal (S) pattern. The BM pattern was characteristic in adenoma, borderline, and interaepithelial and expansile invasive carcinoma lesions. The CYT and S patterns were characteristic in infiltrative invasive lesions. The staining pattern of mural nodules was similar to that of infiltrative invasion. The infiltrative invasion of GI-type ovarian mucinous neoplasms may be promoted by cytoplasmic and/or stromal expression of laminin γ 2 chain.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers and is associated with an extremely poor prognosis, since it is difficult to diagnose pancreatic cancer at an early stage despite its remarkably aggressive features. However, the molecular mechanism underlying the development of aggressive PDAC remains elusive. Rho guanine nucleotide exchange factors (ARHGEFs) are known to activate the RhoA signaling pathway in several types of tumor, although its association with the outcome of PDAC has not been reported. Here, we report that a higher expression of ARHGEF15 is significantly associated with a poor prognosis among PDAC patients, and an increase in ARHGEF15 expression plays pivotal roles in the enhancement of cellular motility and the proliferation of PDAC cells. Firstly, we found that a higher level of ARHGEF15 was significantly correlated with a poor prognosis among 39 Japanese patients with PDAC using global gene expression profiling with an Affymetrix microarray. We then showed that RNA interference-mediated gene silencing of ARHGEF15 inactivated the RhoA signaling pathway when examined using a RhoA pull-down assay. Next, the assessment of cellular migration using both a transwell chamber assay and a wound healing assay showed that ARHGEF15 silencing down-regulated cellular migration and invasive ability in pancreatic cancer cell lines with high levels of endogenous ARHGEF15 expression. Since the RhoA signaling pathway is involved in cell proliferation, we also examined the effect of ARHGEF15-silencing on cell viability and observed that ARHGEF15-knockdown markedly retarded cellular growth in the pancreatic cell lines. In parallel with the gene-silencing studies, the effect of ARHGEF15-overexpression was also investigated in pancreatic cell lines with low levels of endogenous ARHGEF15 expression. We observed opposite phenotypes to those observed in the gene-silencing studies: increased cellular motility and viability, compared with the controls, was observed as a result of overexpression. This is the first study to suggest that a higher expression of ARHGEF15 was correlated with a poor prognosis among patients with pancreatic cancer. In addition, these data suggested that the overexpression of ARHGEF15 contributed to a poor prognosis among PDAC patients by enhancing tumor motility and proliferation, suggesting that ARHGEF15 could be a prognostic biomarker as well as a novel therapeutic target for PDAC. Citation Format: Hiroto Fukushima, Makiko Yasumoto, Sachiko Ogasawara, Jun Akiba, Yuhei Kitasato, Yoshiki Naito, Masamichi Nakayama, Yoshinobu Okabe, Masafumi Yasunaga, Hiroyuki Horiuchi, Etsuko Sakamoto, Hiraku Itadani, Shinji Mizuarai, Shinji Oie, Hirohisa Yano. ARHGEF15 is associated with a poor prognosis in patients with pancreatic ductal adenocarcinoma through a mechanism involving the enhancement of cellular motility and proliferation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 514. doi:10.1158/1538-7445.AM2015-514

The aim of the study was to determine the treatment for Tis and T1 colorectal cancer and the depth of cancer invasion which was examined preoperatively by intraductal ultrasonography (IDUS) using a 20 MHz high frequency thin sonoprobe. IDUS was performed on 62 patients with Tis and T1 colorectal cancer using 20 MHz radial images. The tumors imaged by IDUS were classified into 3 groups according to the degree of lesions in the 5 layers of the large intestinal wall: Tis showing no changes in the third layer, T1 with slight invasion in which the ruptured region in the third layer occupied less than 50% of the tumor diameter, and T1 with massive invasion in which the ruptured region in the third layer occupied more than 50% of the tumor diameter. The correct preoperative diagnosis of the depth of the lesions was obtained in 21 of the 23 patients with Tis (91.3%), in 18 of the 21 patients with T1 with slight invasion (85.7%), and in 8 of the 11 patients with T1 with massive invasion (72.7%). In conclusion, IDUS can be used for endoscopic examination of the large intestinal cancer to judge whether local treatment or not.

Endoscopic removal of colonic lipoma of 2 cm in size or more is not widely used because of the risk of complications which are a hemorrhage and a perforation associated with endoscopic resection. We report here safety endoscopic removal using a bipolar snare and clipping the mucosa of the defective region in three cases with large colonic lipoma. We consider that this technique enhanced the safety of the endoscopic procedure.

Summary Although an accurate anatomical understanding of the hepatic arteries is the most and essential step in living-related liver transplantation (LRLT), the need to reduce the burden place on the donor should be considered in imaging diagnosis. The present study examined the reliability of intravenously enhanced three-dimensional (3D) angiography from multidetector-row computed tomography (MDCT) in evaluating the anatomical configuration of the hepatic arteries comparing with those from conventional angiography by Seldinger method. A total of 109 patients underwent MDCT and 3D images were reconstructed on arterial phase using the volume rendering (VR) method. In the case of 3D angiography, at an infusion rate of 4 ml/s, the extrahepatic hepatic arteries were visualized successfully in all cases (the right, left and middle hepatic artery). The aberrant hepatic arteries were successfully visualized in 23 of 24 cases. The 3D angiography is a reliable method of visualizing the extrahepatic and aberrant hepatic arteries. This minimally invasive examination procedure is useful in individual operative planning and is help to increase the safety of surgery.

In order to clarify the incidence of the delta agent among hepatocellular carcinomas (HCCs) in Kurume, where the hepatitis B infection and its related HCC are most prevalent in Japan, liver tissues from sero hepatitis B surface antigen-positive autopsy cases, with or without HCC, were immunohistochemically investigated for detection of the delta antigen. Only one patient (1.7%) among 58 patients with HCC was found to have delta-antigen in the nuclei in the hepatocytes, which were diffusely distributed throughout the non-cancerous liver. None of 26 patients with liver cirrhosis showed delta-antigen in the liver tissue. The incidence is so low that the delta agent is unlikely to have a role in the development of HCC in our areas.

The fine structural characteristics of the bile duct in patients with alcoholic disease are described. Dark cell metamorphosis, edematous microvilli, and increased number of pinocytotic vesicles on the basal wall surface of the duct epithelium were observed. These alterations may be interpreted as evidence of disordered water metabolism, probably reflecting secretion and reabsorption hyperfunction in the duct epithelium. In addition, widened intercellular spaces in the basal half of the epithelium suggested retention of fluid following reverse pinocytosis along the lateral cell surface. Although no alterations of the duct epithelium distinct from those in patients with other liver diseases were apparent in patients with alcoholic liver disease, the basement membrane of the bile duct exhibited unusual duplication with multiple layers and occasional loop-formation in lacunae on the basal surface.