Real-world efficacy and safety data of nivolumab and ipilimumab combination therapy in Japanese patients with advanced melanoma

The efficacy and safety of nivolumab + ipilimumab combination therapy were retrospectively examined in Japanese patients with unresectable advanced melanoma in clinical practice. Fifty-seven patients with advanced melanoma received the nivolumab + ipilimumab combination therapy. The primary site was cutaneous, mucosal, uveal and unknown in 35, 16, two and four patients, respectively. The overall response rate was 26.3%, with complete response observed in two (3.5%) patients, partial response in 13 (22.8%), stable disease in 12 (21.1%) and progressive disease in 30 (52.6%). The response rate in the treatment-naive and prior systemic therapy group was 40.7% and 13.3%, respectively. For those treated with a single immune checkpoint inhibitor followed by the nivolumab + ipilimumab combination therapy as second-line therapy after disease progression, the response rate was 18.8%. Median progression-free survival (PFS) and overall survival (OS) in all patients was 3.3 and 14 months, respectively. Median PFS in the treatment-naive and prior systemic therapy groups was 13 and 2 months, respectively. Median OS was unreached in the treatment-naive group and was 6.3 months in prior systemic therapy groups. There was no significant difference in PFS and OS for non-acral, acral and mucosal melanoma. Adverse events occurred in 86% of patients; 56.1% were grade 3 or worse. The response rate in an actual clinical setting, including the prior systemic therapy group, was lower than that in the global study and the Japanese phase II study. However, in the treatment-naive group, the rate was equivalent to that in the Japanese phase II study. PFS and OS in the treatment-naive group were comparable with those in the global study and Japanese phase II study, suggesting that the treatment was effective. The proportion of grade 3 and 4 immune-related adverse events was as high as that in the global study and Japanese phase II study.     

The effects of professional oral health care on patients in the subacute stage of emergent neurosurgical disorders

This study evaluated the effectiveness of professional oral health care (POHC) on patients who were in the subacute stage of neurosurgical disorders. Forty subjects (26 male, 14 female) with acute cerebrovascular disorders or neurotrauma were randomly divided into two groups. The intervention group (n = 21) received POHC treatment by dental hygienists, and the control group (n = 19) did not. To evaluate the change in oral health status of the subjects, an oral examination was carried out at baseline and four weeks later. For the subjects in the intervention group, periodontal condition, oral hygiene status, and oral function improved statistically significantly. The detection rate for methicillin‐resistant Staphylococcus aureus (MRSA) was statistically significantly lower in the intervention group than in the control group. These results suggest that POHC performed by dental hygienists in collaboration with nurses plays an important role in the promotion not only of oral health but also of general health.     

Serum zinc deficiency in patients after gastrectomy for gastric cancer

International Journal of Clinical Oncology - Zinc is an essential dietary component for humans and the second most prevalent trace element; however, serum zinc levels after gastrectomy have not...     

Hydroxymatairesinol and sesaminol act differently on tocopherol concentrations in rats

We have previously reported that sesame seed with the tetrahydrofurofuran type lignans sesamin and sesaminol (SeOH) produced higher tocopherol concentrations, while flaxseed with the dibenzylbutyrolactone type lignans did not cause higher tocopherol concentrations in rats. Sesame seeds also contain the dibenzylbutyrolactone type lignan 7-hydroxymatairesinol (HMR). To clarify whether or not the tocopherol elevating effect is affected by the chemical structure of lignans, the effect of HMR isolated from Norway spruce, was compared with SeOH, isolated from sesame seed. The lignans were added to a low alpha-tocopherol (10 mg/kg) diet, and rats were maintained on these diets for 8 wk. The experimental diet containing 0.2% SeOH elevated alpha-tocopherol content in the plasma liver, kidney, and brain, but HMR (0.2% or 0.5%) had no effects. Dietary HMR and SeOH (both in concentrations of 0.2%) were further compared in rats fed on a gamma-tocopherol (50 mg/kg) containing diet. SeOH produced significantly higher g-tocopherol content in the plasma and tissues, and significantly lower 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC, a gamma-tocopherol metabolite) content in the urine. However, HMR did not show such effects. These results suggest that the sesame lignan SeOH increases tocopherol concentrations in animals by suppressing the conversion of gamma-tocopherol to gamma-CEHC. HMR, a structurally different plant lignan, does not have such properties. Further studies are needed to show the potential health effects associated with an increased tocopherol concentration in the body.     

Laparoscopy‐assisted distal gastrectomy for multiple adenocarcinomas in intrathoracic upside‐down stomach

Herein we report on a case of two adenocarcinomas arising from an upside‐down stomach in an elderly patient. An 83‐year‐old man was referred to our hospital with gastric cancer. Esophagogastroduodenoscopy showed two superficial depressed lesions in the stomach that were confirmed on biopsy as constituting a moderately differentiated tubular adenocarcinoma. CT and an upper gastrointestinal barium study revealed that the entire stomach and parts of the duodenum were located in the mediastinum. The patient underwent laparoscopy‐assisted distal gastrectomy and regional lymph node dissection with Billroth I reconstruction, followed by reduction of the migrated stomach. The hiatal defect was closed by primary suturing of the right and left crura at the anterior space of the esophagus. The patient's postoperative course was good, and follow‐up after discharge was uneventful. To the best of our knowledge, this is the first case report of multiple adenocarcinomas in an upside‐down stomach treated by laparoscopy‐assisted distal gastrectomy.     

Human hematopoietic cells and thymic epithelial cells induce tolerance via different mechanisms in the SCID-hu mouse thymus

To study the role of thymic education on the development of the human T cell repertoire, SCID-hu mice were constructed with fetal liver and fetal thymus obtained from the same or two different donors. These animals were studied between 7 and 12 mo after transplantation, at which times all thymocytes and peripheral T cells were derived from stem cells of the fetal liver graft. Immunohistology of the thymus grafts demonstrated that thymic epithelial cells were of fetal thymus donor (FTD) origin. Dendritic cells and macrophages of fetal liver donor (FLD) origin were abundantly present in the medullary and cortico-medullary areas. Thymocytes of SCID-hu mice transplanted with liver and thymus of two different donors (FLDA/FTDB animals) were nonresponsive to Epstein-Barr virus-transformed B cell lines (B-LCL) established from both the FLDA and FTDB, but proliferated vigorously when stimulated with third-party allogeneic B-LCL. Mixing experiments showed that the nonresponsiveness to FTDB was not due to suppression. Limiting dilution analysis revealed that T cells reacting with the human histocompatibility leukocyte antigens (HLA) of the FLD were undetectable in the CD8+ T cell population and barely measurable in the CD4+ subset. On the other hand, CD4+ and CD8+ T cells reactive to the HLA antigens of the FTD were readily detectable. These results indicate that FLD-reactive cells were clonally deleted, whereas FTD-reactive cells were not. However, the frequencies of FTD-reactive T cells were consistently twofold lower than those of T cells specific for any third-party B-LCL. In addition, the cytotoxic activity and interleukin 2 production by FTD-specific T cells were lower compared with that of third-party-reactive T cell clones, suggesting that FTD-specific cells are anergic. These data demonstrate that T cells become tolerant to autologous and allogeneic HLA antigens expressed in the thymus via two different mechanisms: hematopoietic cells present in the thymus induce tolerance to "self"-antigens by clonal deletion, whereas thymic epithelial cells induce tolerance by clonal energy and possibly deletion of high affinity clones.     

Efficacy of endoscopic filling with polyglycolic acid sheets and fibrin glue for anastomotic leak after esophageal cancer surgery: identification of an optimal technique

Background

Anastomotic leak is a potentially life-threatening complication following esophageal cancer surgery. In this study, we aimed to clarify the efficacy of endoscopic filling with polyglycolic acid (PGA) sheets and fibrin glue for anastomotic leak after esophageal cancer surgery.

Methods

Consecutive patients who underwent endoscopic filling with PGA sheets and fibrin glue for anastomotic leak after esophageal cancer surgery between August 2014 and January 2020 were included in the study, with its efficacy retrospectively reviewed. We performed endoscopic filling using two methods: (1) filling the fistula with PGA sheets, followed by the application of a fibrinogen and thrombin solution (conventional method) and (2) filling the fistula with PGA sheets pre-soaked in a fibrinogen solution, followed by the application of a thrombin solution (pre-soak method).

Results

A total of 14 patients underwent endoscopic filling procedures within the study period. The endoscopic filling procedures were successfully performed in all cases and no adverse events associated with the procedures were observed. Fistula closure was obtained in 10 (71%) cases. In the 10 successful cases, the median number of procedures was 1 (range 1–3) and the median time from the first procedure to oral intake was 7.5 days (range 4–36 days). The success rate of the pre-soak method was significantly higher than that of the conventional method (90% vs. 25%, P?=?0.041).

Conclusions

Endoscopic filling with PGA sheets and fibrin glue is a safe and effective treatment for the closure of an anastomotic leak. The pre-soak method can achieve successful endoscopic filling.

     

Husband's smoking status and breast cancer risk in Japan: From the Takayama study

The effects of smoking on breast cancer remain unclear. We assessed the associations of subjects' or husbands' smoking status with breast cancer incidence in a population‐based prospective study in Japan. The subjects were 15 719 women aged 35 years or older. The follow up was conducted from September 1992 to March 2008. Cancer incidence was mainly confirmed through regional population‐based cancer registries. Breast cancer was defined as code C50 according to the International Classification of Diseases and Health Related Problems, 10th Revision. Lifestyle, including smoking status, was assessed with a self‐administered questionnaire. Alcohol consumption was assessed with a validated food‐frequency questionnaire. After multivariate adjustments for age, body mass index, alcohol consumption, physical activity, education, age at menarche, age at first delivery, menopausal status, number of children and history of hormone replacement therapy, active smoking was not associated with the risk of breast cancer. Compared with never smokers whose husband had never smoked, the risks of breast cancer were 1.98 (95% CI: 1.03–3.84) among never smokers whose husband was a current smoker of 21 cigarettes per day or more. The increased risk of breast cancer among women having a smoking husband was pronounced among those who did not habitually consume alcohol. These results suggest that exposure to smoke from husbands is a potential risk factor for breast cancer. The impact of alcohol consumption on the increased breast cancer risk from passive smoking needs to be addressed in further studies.     

Risk of lung cancer and consumption of vegetables and fruit in Japanese: A pooled analysis of cohort studies in Japan

International reviews have concluded that consumption of fruit and vegetables might decrease the risk of lung cancer. However, the relevant epidemiological evidence still remains insufficient in Japan. Therefore, we performed a pooled analysis of data from four population‐based cohort studies in Japan with >200 000 participants and >1700 lung cancer cases. We computed study‐specific hazard ratios by quintiles of vegetable and fruit consumption as assessed by food frequency questionnaires. Summary hazard ratios were estimated by pooling the study‐specific hazard ratios with a fixed‐effect model. In men, we found inverse associations between fruit consumption and the age‐adjusted and area‐adjusted risk of mortality or incidence of lung cancer. However, the associations were largely attenuated after adjustment for smoking and energy intake. The significant decrease in risk among men remained only for a moderate level of fruit consumption; the lowest summary hazard ratios were found in the third quintile of intake (mortality: 0.71, 95% confidence interval 0.60–0.84; incidence: 0.83, 95% confidence interval 0.70–0.98). This decrease in risk was mainly detected in ever smokers. Conversely, vegetable intake was positively correlated with the risk of incidence of lung cancer after adjustment for smoking and energy intake in men (trend P, 0.024); the summary hazard ratio for the highest quintile was 1.26 (95% confidence interval 1.05–1.50). However, a similar association was not detected for mortality from lung cancer. In conclusion, a moderate level of fruit consumption is associated with a decreased risk of lung cancer in men among the Japanese population.