[Study of Eight Cases of Retroperitoneal Liposarcoma].

Retroperitoneal liposarcoma is a relatively rare disease, with a high recurrence rate and poor prognosis. We encountered 8 patients with retroperitoneal liposarcoma who underwent surgery in Shiga University of Medical Science Hospital. We often encounter elderly male patients without symptoms. Of the 8 patients, 6 received extensive resection that included the surrounding organs or tissues; however, 3 patients demonstrated positive surgical margins, which resulted in liposarcoma recurrence. Despite the additional resection in the 3 recurrent cases, all the patients had a tumor relapse. One patient with an unresectable tumor received chemotherapy. The other patients received surgical treatment 3 times. One patient developed an unresectable relapse after receiving chemotherapy. Another patient attained long-term survival by adjuvant chemoradiotherapy combined with 3 surgeries. Aggressive surgical resection to achieve a negative surgical margin and careful postoperative follow-up seem important for the treatment of retroperitoneal liposarcoma. This study suggests that postoperative adjuvant therapy may contribute to the improvement of prognosis. Further findings must be accumulated to clarify the significance of postoperative adjuvant therapies in the future.

In vivo antitumor function of tumor antigen-specific CTLs generated in the presence of OX40 co-stimulation in vitro.

Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor-specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine. The cells were then incubated for 7 days in vitro with a major histocompatibility complex (MHC) class I peptide derived from neu, in the presence or absence of an agonistic anti-OX40 monoclonal antibody, before CD8+ T cells were isolated for use in ACT therapy. The proliferative ability of OX40-driven tumor Ag-specific effector CD8+ T-cells in vitro was less than that of non-OX40-driven tumor Ag-specific effector CD8+ T-cells, but they expressed significantly more early T-cell differentiation markers, such as CD27, CD62L and CCR7, and significantly higher levels of Bcl-2, an anti-apoptotic protein. These OX40-driven tumor Ag-specific effector CD8+ T-cells, when transferred into tumor-bearing recipients, demonstrated potent proliferation capability and successfully eradicated the established tumor. In addition, these cells exhibited long-term antitumor function, and appeared to be established as memory T-cells. Our findings suggest a possible in vitro approach for improving the efficacy of ACT, which is simple, requires only a small amount of modulator, and can potentially avoid several toxicities associated with co-stimulation in vivo.

[Prognosis of Patients after Palliative Stoma Creation].

INTRODUCTION: We evaluated the effectiveness of palliative stomas created to resolve symptoms of bowel obstruction. METHODS: We retrospectively evaluated patient characteristics and outcomes in 16 cases of palliative enterostomy performed to resolve malignant bowel obstruction. RESULTS: The median age of the patients was 64 years, and the most common original cancer was colorectal cancer(11 cases, 69%). Oral intake was recovered in 15 patients after the surgery(94%), and the colorectal obstruction scoring system(CROSS)score improved from 2 to 4. Postoperative complications(Clavien-Dindo grade Ⅱ or higher)were observed in 8 cases(50%), in which serum albumin levels were less than 3.5 g/dL(p=0.077), resulting in longer hospital stays(p=0.041). The median overall survival time was 107 days, and longer survival time was achieved in patients aged younger than 70 years, with CA19-9 levels C37.7 U/mL and postoperative CROSS score of 4, who were administered postoperative chemotherapy. The chemotherapy was feasible after surgery when CROSS scores improved to 4(p=0.019). CONCLUSION: Palliative stomas contributed to the improvement in oral intake of patients with terminal cancer. This improvement may allow patients to receive postoperative chemotherapy, which leads to longer survival times.

[A Surgically Resected Case of Retroperitoneal Liposarcoma with Metastasis].

An 80s man presenting with general malaise and anorexia was referred for treatment of abdominal tumor. Abdominal contrast-enhanced CT revealed a tumor in the left renal cavity. The inside of the tumor coexisted with a fat component and a solid component having a contrast effect. In addition, 2 solid tumors were found to be in contact with the stomach, away from the primary lesion. Based on these findings, retroperitoneal liposarcoma with intraperitoneal metastases was diagnosed. The patient underwent excision of the retroperitoneal tumor and local gastrectomy. The size of the main tumor was 21×18 cm, and the weight was 2.0 kg. Histopathology of the resected specimen showed dedifferentiated liposarcoma and its metastases. The resected margin of the excised tumor was negative. Liposarcoma has a high local recurrence rate, and the status of a resected margin of the tumor is an important factor for prognosis. Here, we report a case of dedifferentiated liposarcoma with metastatic lesions that could be completely resected.

[A Case of Gastric Cancer Underwent Two-Stage Gastrectomy after Chemotherapy-Induced Perforation].

A 70's man presenting with a chief complaint of stomachache was found to have advanced gastric cancer with a deep ulcer and some lymph-node metastases. We decided performing a curative operation after 2 courses of S-1 plus cisplatin. On the first course day 13 of chemotherapy, he complained of severe epigastralgia, and we diagnosed as generalized peritonitis due to perforation of gastric cancer. We performed an urgent laparoscopic operation, which made perforation simple closure and omentopexy. Curative distal gastrectomy with D2 lymph node dissection was successfully performed on postoperative day 16.

Endotoxin adsorption: Direct hemoperfusion with the polymyxin B-immobilized fiber column (PMX).

Toraymyxin® is a medical device developed to adsorb circulating endotoxins in the blood using direct hemoperfusion therapy for patients with septic shock. In 1994, the Japanese National Health Insurance system approved the use of Toraymyxin for the treatment of endotoxemia and septic shock. Since then, Toraymyxin has been safely used in more than 100,000 cases in emergency and intensive care units in Japan. Toraymyxin is currently available for use in the clinical setting in 14 countries worldwide. In this study, we reviewed and introduced the development, clinical use, and efficacy of Toraymyxin and commented on its anticoagulant use and cartridge clotting issue in the treatment of severe sepsis and septic shock. We also highlighted potential new applications of Toraymyxin for longer duration therapy and pulmonary diseases.

[A Case of Small Intestinal GIST with Long-Term Survival after Tumor Resection for Repeated Peritoneal Recurrence].

A 70-year-old woman presenting with abdominal pain was admitted to our hospital. Abdominal contrast CT revealed a small intestine tumor of 10 cm with active bleeding and performed partial resection of the small intestine including tumor. Pathological findings were high risk GIST of the small intestine because of spindle cells and c-kit positive. Imatinib 400mg/day as adjuvant chemotherapy was administered. However administration was stopped for 15 days because of the Grade 4 erythema multiforme. Recurrence of peritoneal dissemination was observed in 2 years after surgery and tumor resection was performed, but complete resection was difficult. Within 5 years after surgery, tumor resection was performed on a total of 5 times peritoneal disseminative recurrences, and it was possible to avoid the appearance of symptoms due to tumor augmentation.

[A Case of Breast Metastasis of Eccrine Porocarcinoma].

An 80's woman was diagnosed with eccrine porocarcinoma of the head in 2010.T he tumor was removed surgically but relapsed in the cervical and axillary lymph nodes 2 years later.The patient underwent surgery, and received systemic chemotherapy and radiation.Chest CT after treatment revealed an irregular mass and thickened skin in the left breast.Core needle biopsy specimens were used to diagnose metastasis of eccrine porocarcinoma.A wide excision with a 1 cm margin was performed under local anesthesia.After surgery, supraclavicular lymph node recurrence was detected.The patient received palliative care because there was no effective treatment available.Eccrine porocarcinoma is a rare malignant tumor of the intraepidermal sweat duct.Breast metastasis from malignant disease is also rare.To our knowledge, breast metastasis of eccrine porocarcinoma has not been reported.

CD44-positive Cancer Stem-like Cells as a Potential Source of Peritoneal Metastasis After Surgery.

BACKGROUND/AIM: The role of CD44 in gastric cancer-derived peritoneal metastasis is currently unknown. It was previously shown that viable, tumorigenic cancer cells are spilled into the peritoneal cavity during surgery, providing a potential cause of peritoneal recurrence after surgery. The purpose of this study was to elucidate the mechanism of peritoneal metastasis of gastric cancer through the expression of CD44 and to propose a method for preventing peritoneal recurrence. MATERIALS AND METHODS: Gastric cancer cell line MKN-45 was sorted into CD44+ and CD44- cells and then injected intraperitoneally into NOD/ShiJic-scidJcl mice. Differences in tumor-initiating capacity between the two groups were assessed using in vivo limiting dilution assays. Tumors harvested from both groups were examined for CD44 and ALDH1A1 expression using immunohistochemistry. The effects of CD44 blockade with anti-CD44 antibody on cell invasion and peritoneal metastasis formation in vivo were assessed. RESULTS: CD44+ cells showed significantly higher efficiency in initiating peritoneal tumor than CD44- cells. Blockade of CD44 significantly reduced peritoneal dissemination of CD44+ cells in vivo, indicating that the CD44 function of intraperitoneally disseminated cancer cells helped promote the formation of peritoneal metastasis. The margin of established tumors showed clusters of cells co-expressing CD44 and ALDH1A1. Peritoneally administered CD44- cells resulted in peritoneal metastases consisting of CD44+ and CD44- cancer cells. CONCLUSION: CD44 expressing cells are a potential source of peritoneal metastasis after surgery and could be a promising target for preventing peritoneal recurrence.

Nrk, an X-linked protein kinase in the germinal center kinase family, is required for placental development and fetoplacental induction of labor.

The complete mechanism of labor induction in eutherian mammals remains unclear. Although important roles for the fetus and placenta in triggering labor have been proposed, no gene has been shown to be required in the fetus/placenta for labor induction. Here we show that Nrk, an X-linked gene encoding a Ser/Thr kinase of the germinal center kinase family, is essential in the fetus/placenta for labor in mice. Nrk was specifically expressed in the spongiotrophoblast layer, a fetus-derived region of the placenta, and Nrk disruption caused dysregulated overgrowth of the layer. Due to preferential inactivation of the paternally derived X chromosome in placenta, Nrk heterozygous mutant placentas exhibited a similar defect to that in Nrk-null tissues when the wild-type allele was paternally derived. However, the phenotype was weaker than in Nrk-null placentas due to leaky Nrk expression from the inactivated X chromosome. Crossing of Nrk-null females to wild-type and Nrk-null males, as well as uterine transfer of Nrk-null fetuses to wild-type females, revealed that pregnant mice exhibit a severe defect in delivery when all fetuses/placentas are Nrk-null. In addition, Nrk was not expressed in female reproductive tissues such as the uterus and ovary, as well as the fetal amnion and yolk sac, in pregnant mice. Progesterone and estrogen levels in the maternal circulation and placenta, which control the timing of labor, were unaffected upon Nrk disruption. We thus provide evidence for a novel labor-inducing fetoplacental signal that depends on the X chromosome and possibly arises from the placenta.

Postoperative analgesic effect of ultrasound-guided rectus sheath block and local anesthetic infiltration after laparoscopic cholecystectomy: Results of a prospective randomized controlled trial.

INTRODUCTION: Even if laparoscopic cholecystectomy (LC) has lower invasiveness through small incisions compared with laparotomy, postoperative pain control is important. METHODS: This prospective, randomized, single-blinded, interventional, single-center study was conducted from December 2016 to March 2018 at the Shiga University of Medical Science Hospital in Japan. Enrolled patients were assigned to either a rectus sheath block (RSB) group or an infiltrative local anesthesia (LA) group. After LC, the RSB group received bilateral RSB with 10 mL of 0.375% ropivacaine and the LA group received subcutaneous and fascial injection with 10 mL of 0.75% ropivacaine at the umbilical wound. The primary endpoint was a visual analog scale (VAS) score on postoperative day (POD) 1. RESULTS: This study enrolled 62 patients (RSB group = 31, LA group = 31). On POD1, the mean VAS scores were 36.4 ± 18.9 and 29.4 ± 15.4 in the RSB group and LA groups, respectively, showing that the LA group tended to describe lesser postoperative pain than the RSB group (P = 0.062). CONCLUSIONS: VAS scores on POD1 were not different between the groups. LC patients might obtain postoperative pain control via long-acting local analgesia.

Successful treatment of rectal cancer with pelvic abscess using transrectal drainage followed by laparoscopic radical resection: a case report.

The incidence of rectal cancer with a pelvic abscess is rare; hence, treatment strategies are difficult because both malignant and infectious inflammation need to be addressed. Here, we report the case of a 53-year-old man diagnosed with rectal cancer accompanied by a pelvic abscess. We performed transrectal drainage of the abscess, and a transanal rectal drainage tube was inserted into the abscess cavity. His symptoms rapidly improved, and computed tomography showed that the pelvic abscess had disappeared. Six weeks after drainage, radical laparoscopic Hartmann's procedure with resection of the rectal cancer and incision drainage scar was performed. After adjuvant chemotherapy, laparoscopic stoma closure was performed a year after the operation. The patient showed no evidence of cancer recurrence 1.5 years after radical surgery. Transrectal drainage followed by laparoscopic radical resection can be a less invasive and effective treatment for rectal cancer accompanied by a pelvic abscess.

Regulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma.

Hepatocyte growth factor (HGF) is a multifunctional molecule that acts as mitogen, motogen, and/or morphogen in a variety of cells. MET, a specific receptor tyrosine kinase for HGF, is upregulated in various tumors including squamous cell carcinoma of the human head and neck (HNSCC), but how HGF affects the expression of downstream functional genes has not yet been elucidated in detail. In the present study, we examined the expression of microRNA (miRNA), non-coding small RNA that regulate cell proliferation and functions by interfering with the translation of target mRNA, with or without HGF stimulation in HNSCC cell line HSC3. Among several miRNAs, in which the expression was altered after HGF stimulation, we focused on miR-200c and miR-27b, both of which were drastically downregulated after HGF stimulation. Expression of ZEB1, a target mRNA for miR-200c, was upregulated 3 and 6 h after HGF stimulation, and that of E-cadherin, a downstream molecule of ZEB1, was downregulated 12 h after HGF stimulation. Expression of ST14/matriptase, an enzyme for extracellular matrix (ECM) degradation and HGF activation and a target mRNA for miR-27b, was drastically upregulated in the protein level after HGF stimulation, although it was not statistically altered in the mRNA level. These results suggest that miR-200c and miR-27b downregulated by HGF might play an important role in epithelial-mesenchymal transition mediated by ZEB1/E-cadherin and ECM degradation and HGF autoactivation mediated by ST14/matriptase, respectively. Altered expression of miRNA directly regulated by HGF might contribute enhanced progressive and invasive characteristics of HNSCC by regulating the translation of HGF-induced functional molecules.

[A case of small intestinal GIST maintained as a long stable disease by imatinib mesylate 400 mg/day, alternate-day administration for 2 weeks followed by a 2 week interval].

UNLABELLED: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. The recent molecular-targeted therapies (imatinib and sunitinib) have improved the treatment of GIST remarkably. However, it would be ideal if the amount of these drugs could be adjusted according to each patient because they have various side effects and are very expensive. We experienced a case of non-curative resectable GIST maintained as a long, stable disease after operation, despite tapering down the dose of imatinib mesylate for personal reasons. CASE: A woman aged 50. She had received surgery for a lower abdominal tumor, and had been diagnosed with GIST of the small intestine and disseminations. When she suspended taking imatinib (400 mg/day) after her operation, these tumors regrew. After restarting imatinib at 400 mg/day in an alternate-day administration lasting 2 weeks followed by a 2 week interval, the disseminated tumors were in significant for 60 months after the operation.

Successful laparoscopy-assisted repair of a rectovaginal fistula after low anterior resection for rectal cancer: a report of two cases.

BACKGROUND: Rectovaginal fistula (RVF) after low anterior resection for rectal cancer is troublesome and refractory. Although various surgical procedures have been previously described, no definitive procedure has shown a satisfactory outcome. We present two consecutive Japanese patients who underwent successful surgery for an RVF after low anterior resection. CASE PRESENTATION: The patients were two women (61-year-old and a 64-year-old). They were admitted to our hospital with a chief complaint of fecal discharge from the vagina after low anterior resection using the double-stapling technique for rectal cancer. They were diagnosed with RVF. Local surgical procedures, including diverting ileostomy, were unsuccessful in previous hospitals. Therefore, we performed laparoscopy-assisted repair of the RVF. In both patients, laparoscopically robust pelvic adhesions were dissected, and the sigmoid colon was transected at just oral side to the RVF. Thereafter, in combination with a perineal approach, the rectum, along with a previous anastomosis and fistula, were completely removed. Surgeries were completed after vaginal repair, redo coloanal anastomosis, and interposition of the dissected connective tissue. In both patients, the postoperative courses were uneventful. They complained of neither recurrence of any RVF nor fecal incontinence 1 year and 10 months after diverting stoma closure. CONCLUSIONS: A laparoscopy-assisted procedure with reanastomosis and interposition of the perineal connective tissue can be an effective treatment for RVF after low anterior resection for rectal cancer.

Gastric volvulus and giant Bochdalek hernia in an adult patient that were safely repaired by endoscopic reduction and elective laparoscopic surgery.

A Bochdalek hernia (BH) is a congenital abnormality with incomplete closure of the diaphragm. It is usually manifested in infants but rarely in adults. Here, we report an adult patient with gastric volvulus and giant BH that were safely repaired by endoscopic reduction and elective laparoscopic surgery, respectively. A 79-year-old woman presented with left upper abdominal pain but no history of trauma. CT revealed a giant BH with gastric volvulus. After emergency endoscopic reduction of the volvulus, elective laparoscopic repair of the BH was performed. The 8 × 8-cm defect was repaired with interrupted nonabsorbable sutures and a mesh. The patient's postoperative course was uneventful, and no complications or recurrence were observed in the 6 months that followed.

The impact of blood type on the mortality of patients with severe abdominal trauma: a multicenter observational study.

Few studies have investigated the relationship between blood type and trauma outcomes according to the type of injury. We conducted a retrospective multicenter observational study in twelve emergency hospitals in Japan. Patients with isolated severe abdominal injury (abbreviated injury scale for the abdomen ≥ 3 and that for other organs < 3) that occurred between 2008 and 2018 were divided into four groups according to blood type. The association between blood type and mortality, ventilator-free days (VFD), and total transfusion volume were evaluated using univariate and multivariate regression models. A total of 920 patients were included, and were divided based on their blood type: O, 288 (31%); A, 345 (38%); B, 186 (20%); and AB, 101 (11%). Patients with type O had a higher in-hospital mortality rate than those of other blood types (22% vs. 13%, p < 0.001). This association was observed in multivariate analysis (adjusted odds ratio [95% confidence interval] = 1.48 [1.25-2.26], p = 0.012). Furthermore, type O was associated with significantly higher cause-specific mortalities, fewer VFD, and larger transfusion volumes. Blood type O was associated with significantly higher mortality and larger transfusion volumes in patients with isolated severe abdominal trauma.

Nucleophosmin/B23 regulates ubiquitin dynamics in nucleoli by recruiting deubiquitylating enzyme USP36.

The nucleolus is a subnuclear compartment with multiple cellular functions, including ribosome biogenesis. USP36 is a deubiquitylating enzyme that localizes to nucleoli and plays an essential role in regulating the structure and function of the organelle. However, how the localization of USP36 is regulated remains unknown. Here, we identified a short stretch of basic amino acids (RGKEKKIKKFKREKRR) that resides in the C-terminal region of USP36 and serves as a nucleolar localization signal for the protein. We found that this motif interacts with a central acidic region of nucleophosmin/B23, a major nucleolar protein involved in various nucleolar functions. Knockdown of nucleophosmin/B23 resulted in a significant reduction in the amount of USP36 in nucleoli, without affecting the cellular USP36 level. This was associated with elevated ubiquitylation levels of fibrillarin, a USP36 substrate protein in nucleoli. We conclude that nucleophosmin/B23 recruits USP36 to nucleoli, thereby serving as a platform for the regulation of nucleolar protein functions through ubiquitylation/deubiquitylation.

Induction of UGT1A1 and CYP2B6 by an antimitogenic factor in HepG2 cells is mediated through suppression of cyclin-dependent kinase 2 activity: cell cycle-dependent expression.

Hepatocyte growth factor (HGF), an antimitogenic factor for HepG2 cells, increased mRNA and protein levels of UGT1A1 and CYP2B6, as well as the endogenous cyclin-dependent kinase (CDK) inhibitors p16, p21, and p27 in HepG2 cells but not in HuH6, Caco2, or MCF7 cells. Treatment with 1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene (U0126) (an extracellular signal-regulated kinase inhibitor) suppressed the HGF-induced expression of UGT1A1 and CYP2B6, as well as p16, p21, and p27 in HepG2 cells. The CDK inhibitor roscovitine also enhanced the expression of UGT1A1, CYP2B6, and CYP3A4. Transfection of anti-CDK2 siRNA led to elevated levels of UGT1A1, CYP2B6, and CYP3A4 in HepG2 and SW480 cells, whereas anti-CDK4 small interfering RNA (siRNA) did not significantly enhance the expression of these enzymes. In fact, CDK2 activity was decreased in HGF-treated HepG2 cells. In cells arrested in S phase by a thymidine block and then released into a synchronous cell cycle, there was a clear dissociation among the activation of CDK2 and the expression of UGT1A1, CYP2B6, and CYP3A4. Furthermore, the induction of CYP3A4 but not UGT1A1 or CYP2B6 mRNA expression by roscovitine was repressed in pregnane X receptor (PXR) siRNA-transfected HepG2 cells. Transfection with constitutive androstane receptor siRNA or PXR siRNA in HepG2 cells did not repress the HGF-stimulated expression of UGT1A1 mRNA. Taken together, our results show that the expression of UGT1A1 and CYP2B6 is negatively regulated through a CDK2 signaling pathway linked to cell cycle progression in HepG2 and SW480 cells, the mechanism of which may differ from that of CYP3A4 expression through PXR phosphorylated by CDK2.