A new spray-type adhesion barrier (AdSpray) improves condition for surgical treatment in the reversal of Hartmann procedure: A case report

Rationale:Hartmann procedure (HP) often causes severe postoperative adhesions in the pelvic space; therefore, the reversal of Hartmann procedure (RHP) is a challenging surgery. A new spray-type antiadhesion agent, AdSpray, has been reported to be useful in three-dimensional fields such as the liver. However, there are no reports of its use in HP. We present a case of a male patient with rectal cancer who underwent laparoscopic HP with AdSpray to prevent postoperative adhesions.Patient concerns:A 52-year-old man presented with melena and constipation.Diagnosis:Colonoscopy revealed an almost obstructive type II tumor at the rectosigmoid colon, and histopathological examination revealed moderately differentiated adenocarcinoma. Enhanced abdominal computed tomography revealed slightly enlarged regional lymph nodes but no ascites around the tumor, and there was no metastasis to the liver or lungs. Therefore, we diagnosed clinical stage T4aN1bM0 rectosigmoid colon cancer. Intraoperatively, a metastatic tumor of the liver surface and a high degree of valve retention in the oral colon were identified.Interventions:After performing laparoscopic HP with AdSpray, we scheduled a laparoscopic RHP with staged hepatic surgery for synchronous liver metastasis from colorectal cancer 1 month later.Outcomes:No postoperative inflammatory adhesions were observed in the pelvis or around the rectal stump, allowing us to perform RHP by a single-incision laparoscopic surgery from the stoma site without any problem. The operation time for RHP was 80 minutes; the patient was in good general condition after the operation, and he was discharged on postoperative day 7.Lessons:In laparoscopic HP, Adspray was easy to use for three-dimensional fields such as the pelvis and effectively prevented postoperative inflammatory adhesions. Thus, RHP may become less risky and be performed more as a minimally invasive surgery.     

Non–clinical efficacy,safety and stable clinical cell processing of induced pluripotent stem cell‐derived anti–glypican‐3 chimeric antigen receptor‐expressing natural killer/innate lymphoid cells

The use of allogeneic, pluripotent stem‐cell‐derived immune cells for cancer immunotherapy has been the subject of recent clinical trials. In Japan, investigator‐initiated clinical trials will soon begin for ovarian cancer treatment using human leukocyte antigen (HLA)‐homozygous‐induced pluripotent stem cell (iPSC)‐derived anti–glypican‐3 (GPC3) chimeric antigen receptor (CAR)‐expressing natural killer/innate lymphoid cells (NK/ILC). Using pluripotent stem cells as the source for allogeneic immune cells facilitates stringent quality control of the final product, in terms of efficacy, safety and producibility. In this paper, we describe our methods for the stable, feeder‐free production of CAR‐expressing NK/ILC cells from CAR‐transduced iPSC with clinically relevant scale and materials. The average number of cells that could be differentiated from 1.8‐3.6 × 10⁶ iPSC within 7 weeks was 1.8‐4.0 × 10⁹. These cells showed stable CD45/CD7/CAR expression, effector functions of cytotoxicity and interferon gamma (IFN‐γ) production against GPC3‐expressing tumor cells. When the CAR‐NK/ILC cells were injected into a GPC3‐positive, ovarian‐tumor‐bearing, immunodeficient mouse model, we observed a significant therapeutic effect that prolonged the survival of the animals. When the cells were injected into immunodeficient mice during non–clinical safety tests, no acute systemic toxicity or tumorigenicity of the final product or residual iPSC was observed. In addition, our test results for the CAR‐NK/ILC cells generated with clinical manufacturing standards are encouraging, and these methods should accelerate the development of allogeneic pluripotent stem cell‐based immune cell cancer therapies.     

The impact of visceral obesity on surgical outcomes of laparoscopic surgery for colon cancer

Purpose

Although obesity is considered as a risk factor for postoperative morbidity in abdominal surgery, its effect on the outcomes of laparoscopic-assisted colectomy (LAC) is still unclear. The technical difficulty and risk factor for postoperative complication in LAC are thought to be influenced by visceral obesity. The aim of this prospective study was to evaluate the impact of visceral fat on the surgical outcomes of LAC.

Methods

Between April 2005 and December 2010, consecutive patients with preoperatively diagnosed colon cancer, excluding medium and low rectal cancer, who underwent LAC, were enrolled. Their visceral fat area (VFA) and body mass index (BMI) were prospectively collected. The VFA was assessed by Fat Scan software. The patients were classified into two groups as follows: VFA nonobese with VFA <100 cm² (VNO) and VFA obese with VFA ≧100 cm² (VO). The predictive factors for surgical complications of LAC were evaluated by univariate and logistic regression analyses.

Results

A total of 338 consecutive patients were enrolled in this study. Of the 338 patients, 194 (57.4 %) and 138 (42.6 %) were classified into the VNO and VO groups, respectively. Logistic regression analysis showed that high BMI (≧25 kg/m²) and VO independently predicted the incidence of overall postoperative complications (p?=?0.040 and 0.007, respectively). VO was more highly related to the incidence of overall postoperative complications, anastomotic leakage (p?=?0.021), and surgical site infection (SSI) (p?=?0.013) than high BMI.

Conclusions

VFA is a more useful parameter than BMI in predicting surgical outcomes after LAC.     

Successful perioperative blood purification therapy in patients with maintenance hemodialysis therapy who underwent living donor liver transplantation

Living donor liver transplantation (LDLT) is a treatment for end-stage liver failure, and was developed to overcome the distinct insufficiency of cadaveric donors. Case 1 is a 56-year-old man who had undergone maintenance hemodialysis therapy for 4 years. An LDLT was performed for the treatment of advanced liver cirrhosis and hepatocellular carcinoma. Continuous hemodiafiltration (CHDF) was performed from the 2nd to 5th days after the operation. Case 2 is a 55-year-old man with primary amyloidosis and chronic renal failure. An LDLT was performed for the treatment of severe abdominal distention caused by a large liver volume. Although CHDF was started at the 3rd day after the operation, it was discontinued within 24 hours because of an increased urinary volume. CHDF was required again from the 6th-8th days, after which the blood purification mode was switched to regular intermittent hemodialysis. Meanwhile, no major problems occurred in either case. In conclusion, CHDF was required for about 5 days from the 2nd day after the operation. The application of careful and aggressive blood purification therapy during the perioperative period is a key to successful LDLT in dialysis patients.     

Elevated Von Willebrand factor propeptide for the diagnosis of thrombotic microangiopathy and for predicting a poor outcome

Thrombotic microangiopathy (TMA) is associated with vascular endothelial cell injury and is sometimes linked with poor outcome. Von Willebrand factor (VWF) propeptide (VWFpp) is considered to be a marker of vascular endothelial cell injury. The plasma levels of VWF, VWFpp, and thrombomodulin (TM) were evaluated for their use in the diagnosis of TMA in 75 patients with TMA. There were 30 TMA patients with marked decreases in ADAMTS13 (TMA/ADAMTS13) and 45 without the decrease (TMA/other). The plasma levels of TM, VWF, and VWFpp values were significantly high in patients with TMA, especially TMA/other group. The plasma levels of TM and VWFpp were significantly high in non-survivor with TMA. In the TMA/other group, the plasma levels of VWFpp were negatively correlated with ADAMTS13 activity. The plasma levels of TM correlated with the renal function, but the plasma levels of VWFpp did not. A ROC analysis indicated that VWFpp and TM were useful markers for the prediction of a poor outcome. These findings suggest that VWFpp is an useful marker for the diagnosis of TMA and for the prediction of poor outcome.     

Leg Muscle Strength Correlates with Gait Performance in Advanced Parkinson Disease

Objective Leg muscle strength (LMS) is decreased in early-stage Parkinson disease (PD) patients and is associated with slower walking and falls. However, LMS in advanced PD has not been well investigated. The purpose of this study was to evaluate LMS in advanced PD patients and its effects on gait performance, activities of daily living, and the cognitive function. Methods The medical records of 132 patients with idiopathic advanced PD [Hoehn and Yahr (H&Y) stages 3 and 4] with a mean disease duration of 9.6 years were retrospectively reviewed. Leg extensor muscle strength of the patients was measured using a Strength Ergo 240. The associations between the LMS and gait performance, Barthel index, H&Y stage, and Mini-Mental State Examination (MMSE) score were analyzed. Results A Spearman''s correlation analysis showed that LMS was correlated with the sex, age, age of disease onset, H&Y stage, Barthel index, MMSE score, and gait parameters. A multivariable linear regression analysis for identifying predictors of LMS showed that the gait velocity (β=0.377), Barthel index (β=0.281), sex (β=-0.187), and disease duration (β=-0.155) were significant. A receiver operating characteristic curve analysis for discriminating between H&Y stage 3 and 4 was performed for LMS; the area under the curve was 0.774 (95% confidence interval=0.696-0.851). Conclusions LMS was strongly associated with multiple domains of clinical characteristics, especially gait velocity and the Barthel index. Our study also suggested that LMS can be a predictor of PD progression.     

The Inverse Correlation of Isoflavone Dietary Intake and Headache in Peri- and Post-Menopausal Women

This study investigated the relationship between headache and dietary consumption of a variety of nutrients in middle-aged women. This cross-sectional analysis used first-visit records of 405 women aged 40–59 years. The frequency of headaches was assessed using the Menopausal Health-Related Quality of Life Questionnaire. Of the 43 major nutrient intakes surveyed using the brief-type self-administered diet history questionnaire, those that were not shared between women with and without frequent headaches were selected. Multiple logistic regression analysis was used to identify nutrients independently associated with frequent headaches. After adjusting for background factors related to frequent headache (vasomotor, insomnia, anxiety, and depression symptoms), the estimated dietary intake of isoflavones (daidzein + genistein) (mg/1000 kcal/day) was negatively associated with frequent headaches (adjusted odds, 0.974; 95% confidence interval, 0.950–0.999). Moreover, the estimated isoflavone intake was not significantly associated with headache frequency in the premenopausal group, whereas it significantly correlated with that in the peri- and post-menopausal groups. Headache in peri- and post-menopausal women was inversely correlated with the dietary intake of isoflavones. Diets rich in isoflavones may improve headaches in middle-aged women.