Experimental Study on Inspiratory Phonation Using Physical Model of the Vocal Folds.

In inspiratory phonation, the air is inhaled from the mouth. The inhaled air passes through the glottis towards the lungs, thereby inducing the vocal fold vibrations. Such phonation takes place in various situations such as sighs, laughter, and crying. To characterize the inspiratory phonation, an experimental study was carried out using a physical model of the vocal folds. By reversing the direction of the airflow that passed through the vocal fold model, the inspiratory phonation was experimentally realized and compared with the normal expiratory phonation. Our experiments revealed that the phonation threshold pressures as well as the volume flow rates decreased under the inspiratory condition. Accordingly, the vocal efficiency was increased. The fundamental frequency was also increased under the inspiratory condition. The kymograms showed that phase of the upper edge of the vocal fold advanced that of the lower edge under the inspiratory phonation. A mathematical model of the vocal folds was further constructed to elucidate these experiments. Except for few aspects, our experimental findings are in good agreement with the preceding studies on inspiratory phonation (e.g., reversed propagation of the mucosal waves observed in a singer, increased pitches in human subjects, and use of inspiratory phonation in speech therapy).

Intraoperative maneuvers may affect the development of early postoperative small bowel obstruction after laparoscopic colorectal cancer surgery: Multicenter prospective cohort study.

BACKGROUND: Early postoperative small bowel obstruction (EPSBO) is one of the most common complications after colorectal cancer (CRC) surgery, and clarification of its causes is desired. Several reports have demonstrated the risks of EPSBO, but few have focused on laparoscopic surgery for CRC and intraoperative maneuvers. We therefore prospectively examined the risk factors for EPSBO after laparoscopic CRC resection. METHODS: We prospectively enrolled 706 patients with CRC that underwent laparoscopic CRC resection in our hospital and affiliated hospitals. We analyzed several factors concerning EPSBO including intraoperative procedures. RESULTS: EPSBO developed in 43 of the 706 cases (6.1%). Univariate analysis showed that risk factors for EPSBO were male sex, increased operative time, repositioning of the small intestine before wound closure and anastomotic leakage. Risk factors for EPSBO according to multivariate analysis were increased operative time (odds ratio (OR) 2.41; P = 0.032), repositioning of the small intestine before wound closure (OR 3.58; P = 0.005) and anastomotic leakage (OR 3.91; P = 0.006). CONCLUSION: To reduce EPSBO after laparoscopic CRC surgery, the operation should be finished as soon as possible without performing optional maneuvers. To avoid development to EPSBO, particular care is required in cases where the risk of anastomotic leakage is predicted to be high.

Laparoscopic anterior resection with or without transanal tube for rectal cancer patients - A multicenter randomized controlled trial.

BACKGROUND: In rectal cancer surgery, insertion of transanal tube has been shown to have efficacy to prevent anastomotic leakage. This randomized controlled study aims to clarify the incidence of anastomotic leakage with or without transanal tube in patients with rectal cancer. METHODS: Patients who underwent elective low anterior resection were randomly allocated to either have transanal tube insertion or not for five days after surgery. We examined the incidence of anastomotic leakage, postoperative 30-day morbidity and mortality. RESULTS: 157 patients were randomized to the transanal tube group or the no-transanal tube group. Symptomatic anastomotic leakage occurred in six patients (7.6%) of the former group and eight patients (10.3%) in the latter group, without significant difference (p = 0.559). There was also no significant difference in morbidity between groups (p = 0.633) and no mortality was detected. CONCLUSIONS: Transanal tube insertion had no significant benefit towards prevention of anastomotic leakage in rectal cancer surgery.

Optimal Assessment of Frailty Predicts Postoperative Complications in Older Patients with Colorectal Cancer Surgery.

OBJECTIVES: The increasingly elderly worldwide population has affected the incidence of colorectal cancer. Establishment of reliable assessment of frailty and proposals for multi-disciplinary interventions are urgently required in oncology practices. Kihon Checklist (KCL) was published by the Japanese Ministry of Health, Labor and Welfare originally to identify individuals ≥ 65 years old at probable risk for requiring care or social support. We investigate the validity of KCL for frailty assessment to predict postoperative complication in older patients with colorectal cancer. METHODS: Consecutive colorectal cancer patients aged ≥ 65 (n = 500) were prospectively examined between May 2017 and December 2018. Preoperative frailty assessment was conducted by the G8 questionnaire and KCL. The main outcome measures were correlation between frailty, other clinical variables, and postoperative complications within 30 days after elective surgery. RESULTS: Of the 500 patients, 278 (55.6%) and 164 (32.8%) patients were classified as 'frail' by G8 and KCL, respectively. Overall complications counted among 97 patients (19.4%), and they were significantly associated with KCL ≥ 8-frail (46/164, p = 0.001), as opposed to G8 ≤ 14-frail (56/278, p = 0.531). Multivariate analysis showed that KCL ≥ 8 (hazard ratio 1.88, 95% confidence interval 1.16-3.04, p = 0.011) was an independent risk factor for these complications. CONCLUSIONS: KCL assessment can identify frail older patients likely to suffer from postoperative complications after colorectal cancer surgery. Preoperative screening of frailty, particularly by KCL, would help older patients prevent their worse outcomes in colorectal cancer. TRIAL REGISTRATION: UMIN000026689.

Ultrasound findings for spontaneous regression of omphalomesenteric remnant after birth.

We report a rare case of spontaneous regression of omphalomesenteric remnant after birth. Unlike previously reported cases, no surgery was required. The omphalomesenteric duct sometimes persists at birth. Its regression after birth, however, is extremely rare. A neonate passed a bloody stool 3 minutes after birth. Meckel's scan detected slight technetium-99 m uptake around the umbilicus. Sonographic examination detected a luminal structure connected to the small bowel, which gradually regressed, however, and was no longer visible by the 52nd day after birth. Careful follow-up is required after occurrence of bloody stool and intestinal obstruction from Meckel's diverticulum.

First-in-human study of CH5132799, an oral class I PI3K inhibitor, studying toxicity, pharmacokinetics, and pharmacodynamics, in patients with metastatic cancer.

PURPOSE: This phase I dose-escalation study investigated the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of CH5132799. EXPERIMENTAL DESIGN: Patients with metastatic solid tumors were eligible for the study. CH5132799 was administered orally once daily or twice daily in 28-day cycles. RESULTS: Thirty-eight patients with solid tumors received CH5132799 at 2 to 96 mg once daily or 48 to 72 mg twice daily. The MTD was 48 mg on the twice-daily schedule but was not reached on the once daily schedule. DLTs were grade 3 elevated liver function tests (LFT), grade 3 fatigue, grade 3 encephalopathy, grade 3 diarrhea, and grade 3 diarrhea with grade 3 stomatitis; all DLTs were reversible. Most drug-related adverse events were grade 1/2. Diarrhea (34%) and nausea (32%) were the most common events. Mean Cmax and AUC0-24 in steady state at MTD were 175 ng/mL and 1,550 ng·h/mL, respectively, consistent with efficacious exposure based on preclinical modeling. Reduction in SUVmax with [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET) was observed in 5 of 7 patients at MTD. A patient with PIK3CA-mutated clear cell carcinoma of the ovary achieved a partial response by GCIG CA125 criteria and further, a heavily pretreated patient with triple-negative breast cancer had marked improvement in her cutaneous skin lesions lasting six cycles. CONCLUSION: CH5132799 is well tolerated at the MTD dose of 48 mg twice daily. At this dose, the drug had a favorable PK and PD profile and preliminary evidence of clinical activity.

Individualized adjuvant chemotherapy guided by chemosensitivity test sequential to extended surgery for advanced gastric cancer.

BACKGROUND AND OBJECTIVES: Various adjuvant chemotherapy regimens have been proposed for patients with advanced gastric cancer; however, the majority of these trials failed to show a clear survival benefit over surgery alone. In this study, the feasibility and efficacy of a strategy of extended surgery combined with individualized adjuvant chemotherapy for advanced gastric cancer with serosal invasion and nodal involvement was examined. PATIENTS AND METHODS: Sixty-four patients with advanced gastric cancer underwent gastrectomy with extended lymph node dissection. After surgery, a chemosensitivity test by MTT assay, using highly purified tumor cells, was performed, and the patients received individualized adjuvant chemotherapy on the basis of the results of this chemosensitivity test. RESULTS: Overall survival in the chemosensitivity-guided chemotherapy (CSC) group was significantly better than the standard chemotherapy (SC) and the no-chemotherapy (NC) group (p<0.05). In patients with stage IV disease, the 5-year survival rate was 38.1% in the CSC group and 0% in the SC + NC group, respectively, with a significant difference being observed in the two survival curves (p<0.01). In patients with paraaortic node involvement, survival in the CSC group was significantly better than that in the SC + NC group (p<0.01). On the other hand, in patients without paraaortic node involvement, no survival difference was observed between the two groups. CONCLUSION: The strategy of extended surgery combined with individualized adjuvant chemotherapy offers a favorable survival outcome for advanced gastric cancer patients with serosal invasion and nodal involvement.

Evaluation of chemosensitivity testing with highly purified tumor cells in 435 patients with gastric carcinoma using an MTT assay.

BACKGROUND: We evaluated the results of chemosensitivity testing for gastric cancer using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in terms of the correlation of chemosensitivity and clinicopathological findings. PATIENTS AND METHODS: We analyzed 435 consecutive patients with gastric cancer treated between January 1991 and January 2002. Highly purified fresh human gastric cancer cells were obtained from 485 lesions including 415 primary tumors and 70 metastatic tumors. RESULTS: CDDP and 5-FU were more potent drugs than MMC, ADR and VP-16. The chemosensitivity of metastatic tumors was lower than that in primary tumors. The chemosensitivity in differentiated cancer was equivalent to that in undifferentiated cancer. The manner of tumor invasion and clinical stage affected chemosensitivity for some drugs. CONCLUSION: Our results suggest that individual chemosensitivity testing is essential to individualize chemotherapy for gastric cancer.

Study of the absorption of cefcapene pivoxil in patients with infectious disease and soft stool or diarrhea.

Cefcapene pivoxil hydrochloride (CFPN-PI), an ester cephem antibiotic, was orally given at a dose of 100 mg three times daily in patients with infection and soft stool or diarrhea, and its absorption was determined using the recovery ratio of 12-h urine pooled after the initial administration as an index. The primary endpoint, the recovery ratio of 12-h urine pooled after oral administration, could be evaluated in six of the eight patients finally gathered, and the mean value was 30.1 +/- 5.8%, which was not considered to differ from the mean value of 34.4 +/- 5.5% obtained in six healthy adult volunteers in the previous phase I study. Clinical efficacy in the eight patients was rated as very effective, effective, and ineffective in two, five, and one patients, respectively, with an effective ratio of 87.5% (7/8). Neither adverse drug reactions nor abnormal laboratory data were observed in any patient. These results indicate that CFPN-PI, at the routine oral dose, does not cause any problems in terms of absorption, efficacy, and safety when it is used in patients with infection and soft stool or diarrhea.

Dendritic cells genetically engineered to simultaneously express endogenous tumor antigen and granulocyte macrophage colony-stimulating factor elicit potent therapeutic antitumor immunity.

Recently, several studies have shown that vaccine therapy using dendritic cells (DCs) genetically engineered to express a surrogate tumor antigen can effectively induce antitumor immunity. In this study, murine bone marrow DCs were adenovirally transduced with murine endogenous tumor antigen gp70 expressed in CT26 cells and granulocyte macrophage colony-stimulating factor (GM-CSF), and we examined whether antigen-specific CTL responses and therapeutic immunity could be induced in mice immunized with those genetically modified DCs. The cytotoxic activity against CT26 in mice immunized with gp70-transduced DCs was significantly higher than that in control (P < 0.01) and was enhanced by GM-CSF-cotransduction (P < 0.001). GM-CSF gene transfer into DCs expressing tumor-associated antigen enhances CC chemokine receptor 7 expression on DCs, leading to improved migratory capacity of DCs to draining lymph nodes. Consequently, an effective antitumor immune response would be induced. Vaccination using gp70-transduced DCs provided remarkable therapeutic efficacy in s.c. models. Moreover, it could be sufficiently augmented by GM-CSF-cotransduction of DCs. These results support that vaccination therapy using DCs simultaneously transduced with tumor-associated antigen can elicit potent CTL response, and GM-CSF-cotransduction of DCs could optimize therapeutic response. Further investigation is needed to optimize this vaccine therapy to achieve the obvious benefit in clinical application.