Carbon-ion radiotherapy for hepatocellular carcinoma with major vascular invasion: a retrospective cohort study.

BACKGROUND: Macroscopic vascular invasion (MVI) significantly impacts survival in patients with hepatocellular carcinoma (HCC), warranting systemic therapy over locoregional therapy. Despite novel approaches, HCC with MVI has a poor prognosis compared to early-to intermediate-stage HCC. This study aimed to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for HCC characterized by MVI. METHODS: This retrospective cohort study evaluated HCC patients with MVI treated using C-ion RT with a dose of 45.0-48.0 Gy/2 fractions or 52.8-60.0 Gy/4 fractions between 1995 and 2020 at our institution in Japan. We analyzed the prognostic factors and rates of local recurrence, survival, and adverse events. The local recurrence rate was determined using the cumulative incidence function, with death as a competing event. Survival rates were determined using the Kaplan-Meier method. The log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis were used to compare subgroups. RESULTS: In total, 76 patients with a median age of 71 years (range, 45-86 years) were evaluated. Among them, 68 had Child-Pugh grade A while eight had grade B disease. In 17 patients, the vascular tumor thrombus reached the inferior vena cava or main trunk of the portal vein. Over a median follow-up period of 27.9 months (range, 1.5-180.4 months), the 2-year overall survival, progression-free survival, and local recurrence rates were 70.0% (95% confidence interval [CI]: 57.7-79.4%), 32.7% (95% CI: 22.0-43.8%), and 8.9% (95% CI: 1.7-23.5%), respectively. A naïve tumor and a single lesion were significant prognostic factors for overall survival in the univariate analysis. Albumin-bilirubin grade 1 and a single lesion were independent prognostic factors in the multivariate analysis. Overall, four patients (5%) experienced grade 3 late adverse events, with no observed grade 4 or 5 acute or late adverse events. CONCLUSIONS: C-ion RT for HCC with MVI showed favorable local control and survival benefits with minimal toxicity.

[Treatment Experience of Chemotherapy and Carbon-Ion Radiotherapy followed by Curative Conversion Surgery for Initially Locally Advanced Unresectable Pancreatic Cancer after Distal Gastrectomy].

BACKGROUND: Carbon-ion radiotherapy(CIRT)has an advantage over conventional radiotherapy by its dose distribution and biological effect for locally advanced unresectable pancreatic cancer(UR-PC). Conversion surgery(CS)might be attempted for UR-PC with favorable response by chemotherapy and radiotherapy. CASE PRESENTATION: A 67-year-old female who have a history of distal gastrectomy. CT scan revealed locally advanced UR-PC with invasion to celiac artery, 60 mm in size. Systemic chemotherapy with gemcitabine and nab-paclitaxel was continued for 15 months, showing decrease of tumor markers and radiological shrinkage of the tumor. The patient was referred to our hospital for surgical consultation. Since there was no metastasis in staging laparoscopy, CIRT with gemcitabine was administered for 3 weeks. After completion of CIRT, distal pancreatectomy with celiac axis resection and total remnant gastrectomy for direct invasion of the tumor was performed as CS, resulting R0 resection. Her postoperative course was uneventful with 17 days of hospital stay. DISCUSSION: CS after CIRT was safely performed. Clinical trial of total neoadjuvant therapy with systemic chemotherapy, CIRT, followed by CS for locally advanced CIRT is ongoing in our hospital. CIRT could be an effective treatment in locally advanced UR-PC in the context of multi-modal treatment including CS.

Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review.

This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0-13%) than after photon-based RT (7.1-30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence.

Implementation rate and effects of multidisciplinary team meetings on decision making about radiotherapy: an observational study at a single Japanese institution.

BACKGROUND: Cancer treatment requires a multidisciplinary approach. Therefore, multidisciplinary team meetings (MDTMs) have been widely used to determine the direction of treatment. However, no standard provisions exist for conducting MDTMs, and recommendations discussed in MDTMs are sometimes not implemented. ​This study analyzed the indications for radiotherapy discussed and recommended at MDTMs, identified the rate of radiotherapy recommendations for patients that were not implemented, and clarified the reasons at a single academic center in Japan. METHODS: This was a cross-sectional study that analyzed the minutes and electronic medical records of cases discussed at MDTMs held between April 2012-March 2017 at Yamagata University Hospital. We categorized how radiotherapy was initially presented at MDTMs, determined the rate of radiotherapy recommendations made through MDTMs, analyzed whether treatment recommendations were subsequently implemented, and examined the causes of non-implementation. We performed a statistical analysis to assess some clinical factors (sex, age, number of multidisciplinary team meetings, and classification of planned treatment) associated with the non-implementation of radiotherapy recommendations from MDTMs. RESULTS: A total of 1813 cases were discussed at MDTMs, of which 71% (1293 cases) were presented with treatment plans, including radiotherapy. Further, 66% (1205 cases) were recommended for radiotherapy through the MDTMs. Recommendations from MDTMs were not implemented in 7% (142 cases). The most typical reason for non-implementation was the clinician's opinion (30%), followed by patient preferences (27%) and disease progression (20%). Change in cancer stage and improvement in symptoms were 12% and 4%, respectively. These ratios were similar each year. We could not find the factors associated with the non-implementation of radiotherapy recommendations from MDTMs. CONCLUSIONS: MDTMs had a significant effect on the recommendation of radiotherapy for each patient with a tumor. The primary reason for the non-implementation of decisions made at MDTMs was the opinion of clinicians and the patient's preference. These results were similar to previous studies. We need to establish a monitoring system where patients themselves can decide the treatments based on their choices while using the recommendations from MDTMs.

Increased salt intake is associated with diabetes and characteristic dietary habits: a community-based cross-sectional study in Japan.

We investigated the association of salt intake with lifestyle-related diseases and also the association of habitually consumed foods with salt intake. A cross-sectional study was conducted using data from a baseline survey of 2,129 residents of Yonezawa city (980 males and 1,149 females), Yamagata prefecture. The residents were divided into three groups based on their estimated daily salt intake: low, medium, and high. In both genders, the prevalence of hypertension and diabetes increased in the order of high > medium > low salt intake (trend p<0.001). Similar trends were observed in the prevalence of hyperlipidemia in females and metabolic syndrome in males. The prevalence of diabetes in the high salt intake group was significantly higher than that in the control group (matched from the low and medium salt intake groups), even when confounding factors were excluded by propensity score matching (p<0.01). Network analysis showed that the low salt intake group had a greater tendency to habitually consume various vegetables than the high salt intake group. Our findings reveal that the prevalence of lifestyle-related diseases increased with higher salt intake. We speculate that a dietary shift to multiple vegetable consumption could have salt-lowering effects.

Detection of Variants With Reduced Baloxavir Marboxil and Oseltamivir Susceptibility in Children With Influenza A During the 2019-2020 Influenza Season.

BACKGROUND: We aimed to detect influenza variants with reduced susceptibility to baloxavir marboxil (baloxavir) and oseltamivir and identify differences in the clinical course between children with and without these variants after antiviral treatment. METHODS: During the 2019-2020 influenza season, we enrolled children with confirmed influenza A (20 treated with baloxavir and 16 with oseltamivir). We analyzed patients' sequential viral RNA loads and infectious virus titers, the drug susceptibilities of clinical isolates, and amino acid substitutions in the viral polymerase acidic protein subunits or neuraminidase. We assessed patients' clinical information using questionnaires. RESULTS: All viral RNA loads and virus titers were significantly decreased after treatment, but we detected baloxavir-resistant and oseltamivir-resistant variants in 5 of 20 and 3 of 16 patients, respectively. The duration of fever was similar between patients with and without the variants, but infectious viral shedding lasted 3 days longer in patients with baloxavir-resistant variants. In addition, the duration to improvement of clinical symptoms was longer in these patients (75.0 vs 29.5 hours; P = .106). CONCLUSIONS: After antiviral treatment, the emergence of baloxavir-resistant variants may affect the patients' clinical course, but oseltamivir-resistant variants had no clinical impact.

Endoscopic imaging modalities for diagnosing the invasion depth of superficial esophageal squamous cell carcinoma: a systematic review.

Endoscopic diagnosis of the invasion depth of superficial esophageal squamous cell carcinoma (ESCC) is an important determinant of the treatment strategy. The three endoscopic imaging modalities commonly used to predict the invasion depth of superficial ESCC in Japan are non-magnifying endoscopy (non-ME), magnifying endoscopy (ME), and endoscopic ultrasonography (EUS). However, which of these three modalities is most effective remains unclear. We performed a systematic review of the literature to compare the diagnostic accuracy of the three modalities for prediction of the invasion depth of superficial ESCC. We used Medical Subject Heading terms and free keywords to search the PubMed, Cochrane Central, and Ichushi databases to identify direct comparison studies published from January 2000 to August 2020. The results of direct comparison studies were used to compare the diagnostic accuracy of each modality. The primary outcome was defined as the proportion of overdiagnosis of pT1b-SM2/3 cancers, and the main secondary outcome was the proportion of underdiagnosis of pT1b-SM2/3 cancers. Other secondary outcomes were the sensitivity and specificity values of the modalities. Four articles were finally selected for qualitative evaluation. Although ME showed no significant advantages over non-ME in terms of sensitivity and specificity, it had a slightly lower proportion of overdiagnosis. EUS had sensitivity and specificity similar to those of non-ME and ME, but EUS had a higher proportion of overdiagnosis. Non-ME and ME are useful for the diagnosis of cancer invasion depth. EUS may increase overdiagnosis, and caution is required in determining its indications.

The potential for reducing alcohol consumption to prevent esophageal cancer morbidity in Asian heavy drinkers: a systematic review and meta-analysis.

Alcohol consumption is a major risk factor for esophageal cancer. In Asia, heavy drinkers are considered to have a higher risk of esophageal cancer than nondrinkers and light drinkers. However, no study has shown an association between alcohol reduction and the morbidity of esophageal cancer in Asian heavy drinkers. Therefore, this study investigated the significance of reducing alcohol consumption to prevent esophageal cancer in Asian heavy drinkers by conducting a systematic review and meta-analysis. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 1995 to December 2020. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a random-effects model. I2 statistics were used to detect heterogeneity. This study included 21 articles in the qualitative synthesis. Light drinkers and heavy drinkers were categorized based on alcohol consumption amount as ≤ 25 ethanol g/day and ≥ 66 ethanol g/day, respectively, as described in many previous studies, and five cohort studies were eligible for this meta-analysis. The HR of esophageal cancer among heavy drinkers versus nondrinkers was 4.18 (95% CI 2.34-7.47, I2 = 74%). On the other hand, the HR of esophageal cancer among light drinkers was 1.82 compared with nondrinkers (95% CI 1.57-2.10, I2 = 0%). Heavy drinkers have a higher esophageal cancer incidence than light drinkers and nondrinker. It is possible that alcohol reduction may decrease the risk of esophageal cancer in Asian heavy drinkers.

Fruit and vegetable consumption and risk of esophageal cancer in the Asian region: a systematic review and meta-analysis.

The consumption of fruit and vegetables was reported to be associated with a reduced risk of esophageal cancer (EC) in many studies of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) from different regions worldwide. Therefore, to provide precise information to reduce the risk of EC in Asia, we performed a systematic review and meta-analysis of studies conducted in the Asian region about fruit and vegetable consumption and the risk of EC. We searched the MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases from January 2010 to December 2020. The summary relative risk (SRR) and 95% CI were calculated using a random-effects model. In addition, I2 statistics were used to detect heterogeneity. Twenty-two studies were eligible for meta-analysis (16 case-control studies and 6 cohort studies). The SRR for the lowest versus highest fruit consumption was 0.64 (95% CI 0.53-0.77, I2 = 82%). That for the lowest versus highest vegetable consumption was 0.61 (95% CI 0.50-0.74, I2 = 81%). Based on subgroup analysis, a validated Food Frequency Questionnaire (FFQ) was significantly associated (SRR for fruit: 0.54; 95% CI 0.40-0.74, SRR for vegetable: 0.60; 95% CI 0.48-0.76) with low heterogeneity (I2 = 48% for fruit, I2 = 0% for vegetables). Egger's funnel plot asymmetry test demonstrated publication bias (P < 0.001 for fruit, P = 0.009 for vegetables). Fruit and vegetable consumption might be associated with a lower risk of EC in the Asian region. However, further substantial prospective studies with a validated FFQ and well-controlled important confounding factors are required to confirm the association.

Long-term clinical outcomes after 12-fractionated carbon-ion radiotherapy for localized prostate cancer.

There are no clinical reports of long-term follow-up after carbon-ion radiotherapy (CIRT) using a dose of 51.6 Gy (relative biological effectiveness [RBE]) in 12 fractions for localized prostate cancer, or of a comparison of clinical outcomes between passive and scanning beam irradiation. A total of 256 patients with localized prostate cancer who received CIRT at a dose of 51.6 Gy (RBE) in 12 fractions using two different beam delivery techniques (passive [n = 45] and scanning [n = 211]), and who were followed for more than 1 year, were analyzed. The biochemical relapse-free (bRF) rate was defined by the Phoenix definition, and the actuarial toxicity rates were evaluated using the Kaplan-Meier method. Of the 256 patients, 41 (16.0%), 111 (43.4%), and 104 (40.6%) were classified as low, intermediate, and high risk, respectively, after a median follow-up of 7.0 (range 1.1-10.4) years. Androgen deprivation therapy was performed in 212 patients (82.8%). The 5-year bRF rates of the low-, intermediate-, and high-risk patients were 95.1%, 90.9%, and 91.1%, respectively. The 5-year rates of grade 2 late gastrointestinal and genitourinary toxicities in all patients were 0.4% and 6.3%, respectively. No grade ≥3 toxicities were observed. There were no significant differences in the rates of bRF or grade 2 toxicities in patients who received passive irradiation versus scanning irradiation. Our long-term follow-up results showed that a CIRT regimen of 51.6 Gy (RBE) in 12 fractions for localized prostate cancer yielded a good therapeutic outcome and low toxicity rates irrespective of the beam delivery technique.

Detection of Variants With Reduced Baloxavir Marboxil Susceptibility After Treatment of Children With Influenza A During the 2018-2019 Influenza Season.

During the 2018-2019 influenza seasons, we detected reduced baloxavir marboxil (baloxavir) susceptible variants with I38S or I38T amino acid substitutions on the PA subunit of influenza virus ribonucleic acid polymerase in 7 of 18 baloxavi-treated children and found that virus titer rebounded in some of these children with variants. We also found fever durations to be similar between patients with or without the variants, but the patients with variants shed the virus 3 days longer and took longer to improve clinical symptoms than those without variants. The emergence of these variants should be monitored during future influenza seasons.

A High Plasma Lamotrigine Concentration at Week 2 as a Risk Factor for Lamotrigine-Related Rash.

BACKGROUND: Reportedly, a high plasma concentration of lamotrigine plays a role in the development of lamotrigine-related rash. The relationship between plasma concentrations of lamotrigine at week 2 and the lamotrigine-related rash was prospectively studied in 84 patients (22 males and 62 females) with treatment-resistant depressive disorder during an 8-week treatment of lamotrigine augmentation. METHODS: Eighty-four depressed patients with an insufficient response to at least 3 psychotropics, including antidepressants, mood stabilizers, and atypical antipsychotics, were included. The diagnoses were major depressive disorder (n = 39), bipolar I disorder (n = 10), and bipolar II disorder (n = 35). The final doses of lamotrigine were 100 mg/d for 57 subjects who were not taking valproate and 75 mg/d for 27 subjects taking valproate. Blood sampling was performed at week 2. Lamotrigine plasma concentrations were measured using high-performance liquid chromatography. The development of lamotrigine-related rash was assessed during the 8-week treatment. RESULTS: Six females developed lamotrigine-related rash. The mean plasma lamotrigine concentrations at week 2 were significantly (P = 0.009) higher in the rash group (4.81 ± 1.23 µmol/L) than in the nonrash group (3.35 ± 1.39 µmol/L). Receiver-operating characteristic analysis indicated that a plasma lamotrigine concentration of 4.38 µmol/L or greater at week 2 was significantly (P < 0.0001) predictive of lamotrigine-related rash. The proportion of patients with a lamotrigine concentration of 4.38 µmol/L or greater was significantly divided by the cutoff point into the rash group and the nonrash group (5/1 versus 13/65, P = 0.001). CONCLUSIONS: This study suggests that a high plasma lamotrigine concentration during week 2 is a risk factor for lamotrigine-related rash and a plasma lamotrigine concentration of 4.38 µmol/L may be a considered a threshold for rash in treatment-resistant depressive disorder.

Clinical and microbiological effect of pulsed xenon ultraviolet disinfection to reduce multidrug-resistant organisms in the intensive care unit in a Japanese hospital: a before-after study.

BACKGROUND: No-touch environmental disinfection using ultraviolet devices has been highlighted in the past several years to control the transmission of multidrug-resistant organisms (MDROs). However, its effectiveness in non-US healthcare settings is yet to be examined. This study aimed to evaluate the effectiveness of disinfection by portable pulsed xenon ultraviolet (PX-UV) devices in controlling transmission of MDROs in a non-US healthcare setting. METHODS: All patients admitted in the intensive care unit in a 629-bed tertiary referral hospital in Japan from August 2016 to February 2019 were enrolled. During the study period, PX-UV disinfection was added to manual terminal cleaning after every patient transfer/discharge. For microbiological evaluation, surfaces were selected for sampling by contact plates before/after manual cleaning and after PX-UV. After overnight incubation, colonies on the plates were counted. RESULTS: The incidence of newly acquired methicillin-resistant Staphylococcus aureus (MRSA) declined significantly (13.8 to 9.9 per 10,000 patient days, incidence rate ratio 0.71, p = 0.002), as well as that of newly acquired drug-resistant Acinetobacter (48.5 to 18.1, 0.37, p < 0.001). The percent reduction of the microbiological burden by manual cleaning was 81%, but a further 59% reduction was achieved by PX-UV. CONCLUSIONS: PX-UV is effective in further reducing the microbial burden and controlling MDROs in a non-US healthcare setting.

A case of Marfan syndrome with massive haemoptysis from collaterals of the lateral thoracic artery.

BACKGROUND: Marfan Syndrome (MFS) is a heritable connective tissue disorder with a high degree of clinical variability including respiratory diseases; a rare case of MFS with massive intrathoracic bleeding has been reported recently. CASE PRESENTATION: A 32-year-old man who had been diagnosed with MFS underwent a Bentall operation with artificial valve replacement for aortic dissection and regurgitation of an aortic valve in 2012. Warfarin was started postoperatively, and the dosage was gradually increased until 2017, when the patient was transported to our hospital due to sudden massive haemoptysis. Computed tomography (CT) with a maximum intensity projection (MIP) revealed several giant pulmonary cysts with fluid levels in the apex of the right lung with an abnormal vessel from the right subclavian artery. Transcatheter arterial embolization was performed with angiography and haemostasis was achieved, which suggested that the bleeding vessel was the lateral thoracic artery (LTA) branch. CT taken before the incident indicated thickening of the cystic wall adjacent to the thorax; therefore, it was postulated that the bleeding originated from fragile anastomoses between the LTA and pulmonary or bronchial arteries. It appears that the vessels exhibited inflammation that began postoperatively, which extended to the cysts. CONCLUSION: We experienced a case of MFS with massive haemoptysis from the right LTA. We have to be aware of the possibility that massive haemoptysis could be induced in MFS with inflamed pulmonary cysts.

Chemoradiotherapy and radiotherapy alone in patients with esophageal cancer aged 80 years or older based on the Comprehensive Registry of Esophageal Cancer in Japan.

BACKGROUND: There has been no definitive evidence of chemoradiotherapy being superior to radiotherapy alone in patients aged 80 years or older. The purpose of the present study was to evaluate the results of radiotherapy and chemoradiotherapy in patients aged 80 years or older with esophageal cancer in the Japanese Nationwide Cancer Database. METHODS: A total of 358 patients aged 80 years or older who were treated with radiotherapy alone or with chemoradiotherapy for esophageal cancer between 2009 and 2011 were enrolled. RESULTS: The 5-year overall survival (OS) rates in patients with cStages 0-I, II, III and IV were 40.9%, 24.7%, 12.2% and 4.9%, respectively. The 5-year cause-specific survival (CSS) rates in patients aged 80 years or older with cStages 0-I, cStage II, cStage III and cStage IV were 73.5%, 41.4%, 25.3% and 7.4%, respectively. In patients treated with radiotherapy alone, the 5-year OS rates for patients with cStages 0-I, II, III and IV were 36.5%, 12.0%, 5.4% and 0%, respectively. In patients treated with chemoradiotherapy, the 5-year OS rates for patients with cStages 0-I, II, III and IV were 45.0%, 36.1%, 16.4% and 7.1%, respectively. In multivariate analysis, chemoradiotherapy, early stage and squamous cell carcinoma were significantly favorable prognostic factors for OS in patients aged 80 years or older (p < 0.001, p < 0.001 and p = 0.0323, respectively). We were unable to evaluate toxicities, because of lack of information in the registry. CONCLUSION: Concurrent chemotherapy with radiotherapy for esophageal cancer in patients aged 80 years or older is a significantly favorable prognostic factor for OS. However, chemoradiotherapy should be carefully selected in elderly patients.

Comparison of the effects of radiotherapy doses of 50.4 Gy and 60 Gy on outcomes of chemoradiotherapy for thoracic esophageal cancer: subgroup analysis based on the Comprehensive Registry of Esophageal Cancer in Japan from 2009 to 2011 by the Japan Esophageal Society.

BACKGROUND: In definitive chemoradiotherapy (CRTx) for esophageal cancer, a radiotherapy (RT) dose of 50.4 Gy in 28 fractions has been the standard in many countries, while 60 Gy in 30 fractions has been frequently used in Japan. To clarify the optimal RT dose in CRTx for esophageal cancer, we compared clinical outcomes with the two doses using data from the Comprehensive Registry of Esophageal Cancer in Japan by the Japan Esophageal Society (JES). METHODS: Of the patients enrolled in the registry for 2015-2017 surveys (patients treated between 2009 and 2011), 996 patients who received definitive CRTx with 50.4 Gy or 60 Gy for thoracic esophageal cancer were eligible for analysis. RESULTS: The complete response (CR) rates in the 50.4 Gy and 60 Gy groups were 49.1% and 46.4%, respectively (p = 0.5851). The 5-year overall survival (OS) rates in the 50.4 Gy group and 60 Gy group for stages I, II/III and IV were 64.2% and 57.2%, 35.0% and 27.0%, and 18.0% and 15.3%, respectively. Since no significant difference was found between the two groups, the 50.4 Gy group was not inferior to the 60 Gy group with regard to OS. CONCLUSIONS: The analysis revealed that the 50.4 Gy group had a non-inferior outcome in comparison with the 60 Gy group for stages I, II/III and IV thoracic esophageal cancer. These results were obtained from a large database for the first time in Japan.

Current status of radiotherapy for patients with thoracic esophageal cancer in Japan, based on the Comprehensive Registry of Esophageal Cancer in Japan from 2009 to 2011 by the Japan Esophageal Society.

BACKGROUND: Although esophagectomy is the standard treatment for resectable esophageal cancer, chemoradiotherapy or radiotherapy alone is also selected for some cases. However, there have been very few detailed studies conducted on a large scale on the efficacy of these treatments in Japan. METHODS: Of the patients enrolled in the Comprehensive Registry of Esophageal Cancer in Japan by the Japan Esophageal Society for the 2015-2017 surveys (patients treated between 2009 and 2011), the data of 388 patients treated by definitive radiotherapy alone (RTx) and 1964 patients treated by definitive chemoradiotherapy (CRTx) were analyzed. RESULTS: The median age of the patients was 78 years in the RTx group and 69 years in the CRTx group; thus, the proportion of elderly patients was significantly higher in the RTx group than in the CRTx group (p < 0.0001). With regard to the rates of treatment by the two modalities according to the depth of invasion, extent of lymph node metastasis, and disease stage, the treatment rate by CRTx increased more significantly than that by RTx as the disease progressed (p < 0.0001). With regard to the distribution of the total irradiation dose, 11.4% and 2.3% of patients in the RTx and CRTx groups, respectively, received a dose of 67 Gy or more; thus, the RTx group received significantly higher total irradiation doses (p < 0.0001). In the RTx group, the 5-year overall survival rate was 23.2%, and the rates in patients with cStage 0-I, II, III, and IV disease were 41.8%,18.5%, 9.3%, and 13.9%, respectively. In the patients of the RTx group showing complete response (CR), the 5-year overall survival rate was 46.6% and the rates in patients with cStage 0-I, II, III, and IV disease were 54.8%, 39.6%, 32.4%, and 38.9%, respectively. In the CRTx group, the 5-year overall survival rate was 30.6% and the rates in patients with cStage 0-I, II, III, and IV disease were 57.8%, 47.8%, 23.4%, and 13.0%, respectively. In the patients of the CRTx group showing CR, the 5-year overall survival rate was 59.2% and the rates in patients with cStage 0-I, II, III, and IV disease were 67.9%, 59.5%, 56.5%, and 39.6%, respectively. CONCLUSION: This study revealed the current status of treatment of esophageal cancer in Japan, and we think that we have been able to establish the grounds for explaining to patients with esophageal cancer and their families the treatment decisions made for them in daily clinical practice.

Relationship Between UGT1A4 and UGT2B7 Polymorphisms and the Steady-State Plasma Concentrations of Lamotrigine in Patients With Treatment-Resistant Depressive Disorder Receiving Lamotrigine as Augmentation Therapy.

BACKGROUND: In a previous study, the authors had shown that in treatment-resistant depressive disorder, an early therapeutic response to lamotrigine augmentation therapy is dependent on its plasma concentrations. Lamotrigine is mainly metabolized by UGT1A4 and UGT2B7, and polymorphisms of said UGTs that affect enzyme activities have been reported. This study investigated the effect of these polymorphisms on the steady-state plasma concentrations (Css) of lamotrigine in patients with treatment-resistant depressive disorder receiving lamotrigine as augmentation therapy. METHODS: The subjects were 103 depressed patients who had already shown insufficient response to at least 3 psychotropics including antidepressants, mood stabilizers, and atypical antipsychotics. The diagnoses were major depressive disorder (n = 46), bipolar II disorder (n = 44), and bipolar I disorder (n = 13). They received augmentation therapy with lamotrigine for 8 weeks. The final doses of lamotrigine were 100 mg/d for 67 subjects who were not taking valproate and 75 mg/d for 36 subjects taking valproate, respectively. Blood sampling was performed at the 8th week. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography. The genotypes of UGT1A4 142T>G, UGT2B7 -161C>T, and UGT2B7 372A>G were identified by polymerase chain reaction analyses. RESULTS: There were no significant relationships between these polymorphisms and the Css of lamotrigine in the subjects regardless of valproate comedication. CONCLUSIONS: This study suggests that these genetic polymorphisms do not affect the Css of lamotrigine in patients with treatment-resistant depressive disorder receiving lamotrigine as augmentation therapy.

Borderline pulmonary hypertension is associated with exercise intolerance and increased risk for acute exacerbation in patients with interstitial lung disease.

BACKGROUND: Pulmonary hypertension (PH) is traditionally defined as a resting mean pulmonary artery pressure (mPAP) of ≥25 mmHg, while mPAP in the range of 21 to 24 mmHg is recognized as "borderline PH." Interstitial lung disease (ILD) is complicated by the development of PH, which is known to be linked with exercise intolerance and a poor prognosis. Even though it has recently been recommended that PH is redefined as a mPAP of > 20 mmHg, little is known about the clinical significance of borderline PH in ILD. We evaluated whether borderline PH has an impact on the exercise capacity, risk of acute exacerbation (AE), and mortality in patients with ILD. METHODS: A total of 80 patients with ILD who underwent right heart catheterization (RHC) between November 2013 and October 2016 were included. The patients were divided into 3 groups according to the mPAP values: mPAP ≤20 mmHg (No-PH group; n = 56), 20 < mPAP < 25 mmHg (Bo-PH group; n = 18), and mPAP ≥25 mmHg (PH group; n = 6). The demographic, hemodynamic, spirometric, and 6-min walk test (6MWT) data of the patients were collected. In addition, the 1-year incidence of AEs and 1-year survival of the patients after the initial RHC were also evaluated. RESULTS: There were no significant differences among the 3 groups in the mean age, pulmonary function parameters or the PaO2, however, 6-min walk distance was significantly lower in both the Bo-PH and PH groups (p < 0.001 for both) as compared to the No-PH group. The results of the Kaplan-Meier analysis revealed that while there was no significant difference in the 1-year survival rate among the three groups, the 1-year incidence of AEs was significantly higher in both the Bo-PH and PH groups (p < 0.001, p = 0.023, respectively) as compared to the No-PH group. CONCLUSIONS: The current study suggested that borderline PH may be associated with poorer exercise tolerance and an increased risk of AEs in patients with ILD. Therefore, the physicians should pay close attention to the presence of even mild elevation of the mPAP at the initial evaluation in patients with ILD.

A retrospective multicenter study of carbon-ion radiotherapy for major salivary gland carcinomas: Subanalysis of J-CROS 1402 HN.

A retrospective multicenter study was carried out to assess the clinical outcomes of carbon-ion radiotherapy for head and neck malignancies (Japan Carbon-Ion Radiation Oncology Study Group [J-CROS] study: 1402 HN). We evaluated the safety and efficacy of carbon-ion radiotherapy in patients with major salivary gland carcinoma. Sixty-nine patients treated with carbon-ion radiotherapy at four Japanese institutions were analyzed. Thirty-three patients (48%) had adenoid cystic carcinomas, 10 (14%) had mucoepidermoid carcinomas, and 26 (38%) had other disease types. Three patients (4%) had T1 disease, 8 (12%) had T2, 25 (36%) had T3, and 33 (48%) had T4. The median radiation dose was 64 Gy (relative biological effectiveness) in 16 fractions. The median gross tumor volume was 27 mL. The median follow-up period was 32.7 months. The 3-year local control rate and overall survival rate were 81% and 94%, respectively. Regarding acute toxicities, seven patients had grade 3 mucositis and seven had grade 3 dermatitis. Regarding late toxicities, one patient had grade 3 dysphagia and one had a grade 3 brain abscess. No grade 4 or worse late reactions were observed. In conclusion, definitive carbon-ion radiotherapy was effective with acceptable toxicity for major salivary gland carcinomas.