Background/Aims: Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods: In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results: In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperaturetreated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.

Purpose: Pelvic exenteration (PE) is a highly invasive procedure with high morbidity and mortality rates. Promising options to reduce this invasiveness have included laparoscopic and transperineal approaches. The aim of this study was to identify the safety of combined transabdominal and transperineal endoscopic PE for colorectal malignancies. Methods: Fourteen patients who underwent combined transabdominal and transperineal PE (T group: 2-team approach, n = 7; O group: 1-team approach, n = 7) for colorectal malignancies between April 2016 and March 2020 in our institutions were included in this study. Clinicopathological features and perioperative outcomes were compared between groups. Results: All patients successfully underwent R0 resection. Operation time tended to be shorter in the T group (463 minutes) than in the O group (636 minutes, P = 0.080). Time to specimen removal was significantly shorter (258 minutes vs. 423 minutes, P = 0.006), blood loss was lower (343 mL vs. 867 mL, P = 0.042), and volume of blood transfusion was less (0 mL vs. 560 mL, P = 0.063) in the T group, respectively. Postoperative complications were similar between groups. Conclusion Combined transabdominal and transperineal PE under a synchronous 2-team approach was feasible and safe, with the potential to reduce operation time, blood loss, and surgeon stress.

Purpose: Pelvic exenteration (PE) is a highly invasive procedure with high morbidity and mortality rates. Promising options to reduce this invasiveness have included laparoscopic and transperineal approaches. The aim of this study was to identify the safety of combined transabdominal and transperineal endoscopic PE for colorectal malignancies. Methods: Fourteen patients who underwent combined transabdominal and transperineal PE (T group: 2-team approach, n = 7; O group: 1-team approach, n = 7) for colorectal malignancies between April 2016 and March 2020 in our institutions were included in this study. Clinicopathological features and perioperative outcomes were compared between groups. Results: All patients successfully underwent R0 resection. Operation time tended to be shorter in the T group (463 minutes) than in the O group (636 minutes, P = 0.080). Time to specimen removal was significantly shorter (258 minutes vs. 423 minutes, P = 0.006), blood loss was lower (343 mL vs. 867 mL, P = 0.042), and volume of blood transfusion was less (0 mL vs. 560 mL, P = 0.063) in the T group, respectively. Postoperative complications were similar between groups. Conclusion Combined transabdominal and transperineal PE under a synchronous 2-team approach was feasible and safe, with the potential to reduce operation time, blood loss, and surgeon stress.

OBJECTIVE: With the emerging significance of genetic profiles in the management of endometrial cancer, the identification of tumor-driving genes with prognostic value is a pressing need. The LAMC1 gene, encoding the laminin subunit gamma 1 (LAMC1) protein, has been reported to be involved in the progression of various malignant tumors. In this study, we aimed to investigate the role of LAMC1 in endometrial cancer and elucidate the underlying mechanism.METHODS: We evaluated the immunohistochemical expression of LAMC1 in atypical endometrial hyperplasia and endometrial cancer. Within the endometrial cancer cases, we analyzed the association of LAMC1 overexpression with clinicopathological factors and prognosis. Furthermore, to indentify genes influenced by LAMC1 overexpression, we transfected HEC50B and SPAC-S cells with siRNA targeting LAMC1 and conducted microarray gene expression assays.RESULTS: While none of the atypical endometrial hyperplasia specimens exhibited LAMC1 overexpression, endometrial cancer possessed a significantly higher LAMC1 overexpression rate. LAMC1 overexpression was strongly associated with histological type, lymphovascular space invasion, lymph node metastasis, advanced International Federation of Gynecology and Obstetrics stage, and poor overall survival in endometrial cancer. Gene expression microarray analysis identified 8 genes correlated with tumor progression (LZTFL1, TAPT1, SEL1L, PAQR6, NME7, TMEM109, CCDC58, and ANKRD40) that were commonly influenced in HEC50B and SPAC-S by LAMC1 silencing.CONCLUSION: LAMC1 overexpression is a potent biomarker for identifying endometrial cancer patients needing aggressive adjuvant therapy. We elucidated 8 candidate genes that may mediate progression of LAMC1 overexpressing cancer. Further investigation of the underlying mechanism should lead to the discovery of new therapeutic targets.
Endometrial Hyperplasia ; Endometrial Neoplasms ; Female ; Gene Expression ; Gene Expression Profiling ; Gynecology ; Humans ; Laminin ; Lymph Nodes ; Microarray Analysis ; Neoplasm Metastasis ; Obstetrics ; Prognosis ; RNA, Small Interfering

OBJECTIVE: With the emerging significance of genetic profiles in the management of endometrial cancer, the identification of tumor-driving genes with prognostic value is a pressing need. The LAMC1 gene, encoding the laminin subunit gamma 1 (LAMC1) protein, has been reported to be involved in the progression of various malignant tumors. In this study, we aimed to investigate the role of LAMC1 in endometrial cancer and elucidate the underlying mechanism. METHODS: We evaluated the immunohistochemical expression of LAMC1 in atypical endometrial hyperplasia and endometrial cancer. Within the endometrial cancer cases, we analyzed the association of LAMC1 overexpression with clinicopathological factors and prognosis. Furthermore, to indentify genes influenced by LAMC1 overexpression, we transfected HEC50B and SPAC-S cells with siRNA targeting LAMC1 and conducted microarray gene expression assays. RESULTS: While none of the atypical endometrial hyperplasia specimens exhibited LAMC1 overexpression, endometrial cancer possessed a significantly higher LAMC1 overexpression rate. LAMC1 overexpression was strongly associated with histological type, lymphovascular space invasion, lymph node metastasis, advanced International Federation of Gynecology and Obstetrics stage, and poor overall survival in endometrial cancer. Gene expression microarray analysis identified 8 genes correlated with tumor progression (LZTFL1, TAPT1, SEL1L, PAQR6, NME7, TMEM109, CCDC58, and ANKRD40) that were commonly influenced in HEC50B and SPAC-S by LAMC1 silencing. CONCLUSION LAMC1 overexpression is a potent biomarker for identifying endometrial cancer patients needing aggressive adjuvant therapy. We elucidated 8 candidate genes that may mediate progression of LAMC1 overexpressing cancer. Further investigation of the underlying mechanism should lead to the discovery of new therapeutic targets.

OBJECTIVE: Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. METHODS: The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM5 were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. RESULTS: Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM5, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. CONCLUSION: This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients.
Asian Continental Ancestry Group ; Colorectal Neoplasms, Hereditary Nonpolyposis* ; Diagnosis ; DNA Mismatch Repair ; Genetic Testing ; Germ-Line Mutation ; Humans ; Immunohistochemistry ; Mass Screening* ; Medical History Taking ; Methylation ; Microsatellite Instability ; Ovarian Neoplasms* ; Risk Assessment*

It was previously reported the safety and efficacy of oral tapentadol ER switched from other opioids for 8 weeks in subjects with moderate to severe cancer pain, who received opioid analgesics prior to study participation. All treatment emergent adverse events were evaluated in previous safety analysis. In this report, the incidence and timing of opioid specific adverse events related to tapentadol administration were analyzed and compared with those of morphine SR as a reference. Fifty subjects each was randomized to the tapentadol ER group and the morphine SR group. The incidences of major adverse events that are considered related to treatment in the tapentadol ER group and the morphine SR group were nausea (8.0%, 14.0%), vomiting (2.0%, 24.0%), constipation (8.0%, 20.0%), and somnolence (8.0%, 18.0%), the incidences of these events were lower in the tapentadol ER group. These results suggest that tapentadol ER is a orally opioid which has well safety profiles, and is a new option of cancer pain therapy.

The present multicenter, open-label study evaluated the efficacy and safety of tapentadol ER administered at 50 mg/day to 500 mg/day in opioid-naive and opioid-switching subjects with moderate to severe cancer pain. For opioid-naive subjects, the initial dose was tapentadol ER 50 mg/day. For opioid-switching subjects, the initial dose was determined depending on previously used opioid and was dose-adjusted for each subject. The study design consists of two parts of titration period and maintenance period to which a patient who achieves dose adjustment can proceed. The percentage of subjects achieving dose adjustment in the titration period was 93.3% for opioid-naive subjects and 80.6% for opioid-switching subjects. The percentage of subjects who maintained adequate analgesia throughout the maintenance period (primary endpoint) was 89.7% for opioid-naive subjects and 92.9% for opioid-switching subjects. The most frequent adverse events were were nausea, vomiting, somnolence, and constipation, all of which were commonly reported with the use of opioids. These findings showed that tapentadol ER was well tolerated in the dose range of 50 mg/day to 500 mg/day.

A 24-year-old woman underwent successful repair of a traumatic pseudoaneurysm of the aortic isthmus concomitant with right diaphragmatic hernia which developed after a traffic accident, and the steering wheel of the crashed car was considered responsible for both lesions. Due to the right diaphragmatic hernia, she could breathe mainly with the left lung only. The aortic isthmus aneurysm was considered to be a pseudoaneurysm, and because of the potential risk of rupture, we performed urgent aortic surgery. Prior to a left thoracotomy, we anastomosed an 8-mm prosthetic graft to the right axillary artery. When the left lung was collapsed in order to perform a femoro-femoral bypass, the SpO₂ level of her right index finger and her cerebral rSO₂ markedly decreased. Therefore, we administered additional perfusion via the right axillary artery, which provided sufficient oxygen to the upper body and brain. The patient underwent Marlex mesh reinforcement of the right diaphragmatic hernia 30 days after grafting, and is doing well 1 year postoperatively.

A 10-year-old girl was given a diagnosis of mitral stenosis due to a small prosthetic valve. She had undergone intra-cardiac repair operations for a complete atrioventricular septal defect by a two-patch method at 6 months after birth, and for left atrioventricular valve insufficiency by replacement with a mechanical prosthesis (SJM-HP-17mm) at 2 years of age. The cause of mitral stenosis was considered to be that the existing prosthesis was too small for her body growth. Reoperation was done with a trans-septal approach, but despite the resection of the old prosthesis and peripheral fibrous tissue her left atrioventricular annulus was not big enough to insert a larger prosthesis. We thus cut the previous VSD patch about 1cm toward the apex, and sutured a patch for annular enlargement. After this annular enlargement, we could insert a larger prosthesis (SJM-HP-21mm). Her postoperative course was uneventful. There was no left ventricular outflow obstruction and no worsening of her mild right atrioventricular regurgitation. There are few established procedures for enlargement of a left atrioventricular annulus. Our method presented here is safe and effective for left atrioventricular annular enlargement, but can only be applied to patients with atrioventricular septal defect.