Effect of revised organ transplant law in Japan on lung transplantation.

PURPOSE: To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country. METHODS: Lung transplant candidates registered between January, 2000 and December, 2009 were designated as the pre-revision group (n = 396) and those registered between January, 2011 and December, 2020, as the post-revision group (n = 1326). Both groups were analyzed retrospectively using data collected by the Japanese Society of Lung and Heart-Lung Transplantation. RESULTS: The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8%, p < 0.01). The median waiting time for BDLT was significantly reduced (708 days vs. 1163 days, p < 0.01) and the mortality rate while waiting for BDLT improved significantly after the law amendment (33.1 vs. 42.6%, p < 0.01). In the post-revision group, 18 pediatric patients underwent BDLT. The 5-year survival rates after BDLT were comparable between the groups (73.5% in the pre-revision group vs. 73.2% in the post-revision group, p = 0.32). CONCLUSIONS: The organ transplant law revision shortened the waiting time for BDLT significantly and decreased the mortality rate while waiting for BDLT. The posttransplant outcomes in Japan remained favorable throughout the study period.

Analysis of 25 surgical cases of thymic neuroendocrine tumors and thymic carcinoma.

BACKGROUND: The purpose of this study was to evaluate the clinicopathological characteristics of patients who underwent surgical resection for thymic neuroendocrine tumors (TNET) or thymic carcinoma. METHODS: In this study, we retrospectively evaluated the clinicopathological characteristics of our surgical patients at Fukuoka University Hospital from January 1995 to December 2018. RESULTS: There were nine cases of TNET and 16 cases of thymic carcinoma. Regarding the pathological type, the TNET group included three atypical carcinoid cases, two large cell neuroendocrine tumor cases, two small cell carcinoma cases, and two other cases. The thymic carcinoma group included 15 squamous carcinoma cases and one case of adenosquamous carcinoma. Based on the Masaoka-Koga staging system, six TNET cases and 11 thymic carcinoma cases were stage III or IV. The complete resection rate was 77% in the TNET group and 81% in the thymic carcinoma group. Additional chemotherapy and/or radiotherapy was performed in five cases of TNET and 11 cases of thymic carcinoma. The five-year survival rate and five-year disease-free survival rate were 87.5% and 75.0% in the TNET group and 58.9% and 57.1% in the thymic carcinoma group, respectively, with no significant difference between the two groups (P = 0.248 and P = 0.894, respectively). In the univariate analysis, complete resection was a statistically significant prognostic factor (P = 0.017). CONCLUSION: In this study, no difference in prognosis was observed between TNET and thymic carcinomas. To understand the characteristics of these tumors, further case accumulation and multicenter clinical studies are needed. (243words).

Factors related to post-thoracotomy pain following robotic-assisted thoracic surgery.

BACKGROUND: Robotic-assisted thoracic surgery (RATS) is a minimally invasive procedure; however, some patients experience persistent postoperative pain. This study aimed to investigate factors related to postoperative pain following RATS. METHODS: The data of 145 patients with lung cancer, who underwent RATS with a four-port (one in the sixth intercostal space [ICS] and three in the eighth ICS) lobectomy or segmentectomy between May 2019 and December 2022, were retrospectively analyzed. Factors associated with analgesic use for at least 2 months following postoperative pain (PTP group) were analyzed. RESULTS: Patients who underwent preoperative pain control for any condition or chest wall resection were excluded. Among the 138 patients, 45 (32.6%) received analgesics for at least 2 months after surgery. Patient height and transverse length of the thorax correlated with PTP in the univariate analysis (non-PTP vs. PTP; height, 166 vs. 160 cm; p < .001; transverse length of the thorax, 270 vs. 260 mm, p = .016). In the multivariate analysis, height was correlated with PTP (p = .009; odds ratio, 0.907; 95% confidence interval, 0.843-0.976). Height correlated with the transverse length of the thorax (r = .407), anteroposterior length of the thorax (r = .294), and width of the eighth ICS in the middle axillary line (r = .210) using Pearson's correlation coefficients. When utilizing a 165-cm cutoff value for height to predict PTP using receiver operating characteristic curve analysis, the area under the curve was 0.69 (95% confidence interval, 0.601-0.779). CONCLUSION: Short stature is associated with a high risk of postoperative pain following RATS.

Effects of case volume on short- and long-term outcomes following cadaveric lung transplantation in Japan.

Background: Despite the low number of lung transplantations (LTs) in Japan, 10 LT facilities are accredited and good outcomes have been reported. A database review was conducted to clarify the impact of case volume at LT facilities in Japan on short- and long-term outcomes. Methods: All cadaveric LT cases treated between 2000 and 2021 in Japan were analyzed using the database of the Japanese Society of Lung and Heart-Lung Transplantation (JSLHT). The nine institutions represented were categorized into the low-volume (LV; <80 cumulative LT cases, <8 LTs/year, n=5) and high-volume (HV; ≥80 cumulative LT cases, ≥8 LTs/year, n=4) centers. Ninety-day and 1-year mortality, as well as 5- and 10-year survival data were evaluated. Results: A total of 658 cadaveric LTs were performed at the nine institutions. The 90-day rates of mortality at the HV and LV centers were 3.5% and 3.9%, respectively (P=0.801), while the 1-year mortality rates were 9.2% and 11.5%, respectively (P=0.199). Additionally, log-rank analysis of Kaplan-Meier curves showing case volume did not reveal a significant difference in long-term survival between the HV and LV centers (P=0.272), though the LV centers had wide differences for long-term outcomes (P=0.030). Conclusions: Case volume did not have effects on short- or long-term outcomes following LT in Japan, while there were large variations in long-term outcomes among the LV centers compared to those of the HV centers.

Impact of a pneumatic surgical robot with haptic feedback function on surgical manipulation.

Although robotic-assisted surgery has the advantages of low patient burden and high precision without unsteady hand movements, the lack of tactile sensations may result in unexpected iatrogenic organ damage. The Saroa (Riverfield Inc., Tokyo, Japan) is a pneumatically driven robot that provides real-time haptic feedback to the surgeon. Using the Saroa robot, six examinees performed puffed rice transfer and four of them performed pig lung resection tasks with the feedback function turned on and off. The puffed rice transfer task consisted of transferring 20 grains of puffed rice from the left to the right compartment in the training box. The mean grasping forces during the puffed rice transfer task with the haptic feedback function turned off and on were 2.14 N and 0.63 N, respectively (P = 0.003). The mean grasping forces during the pig lung resection task were lower with the feedback turned on than turned off. The force that the forceps exerted on the grasping object was weaker in both tasks when the haptic feedback function was turned on, suggesting that the feedback function allows gentler handling of tissues, improving patient safety during robotic surgery.

The history of Japanese lung transplantation: the unique pathway to establishing the program and its initial success.

Japan is a unique country in terms of organ transplantation. Despite the impressive progress in transplant medicine achieved during the late 20th century in many Western countries, Japan was unable to implement a program for organ transplants from brain-dead donors due to persistent public distrust regarding the ethical understanding of "brain death as human death". In 1997, the Japanese Organ Transplant Law was enacted, and organ transplantation from brain-dead donors was finally legalized. However, this law was strongly opposed by religious leaders, philosophers, politicians, and even medical personnel who did not accept the idea that brain death is human death, so transplant physicians had to start performing transplants in the face of strong social resistance. The Japanese National Lung Transplant System was established based on the following three philosophies: (I) an institutional certification system based on strict standards; (II) a rigorous central monitoring system for transplant results; and (III) a third-party review system to determine eligibility for patient registration. The purpose of these policies was to avoid ethical issues at lung transplant institutes, and to achieve high-quality transplant results. The actual progress of Japanese lung transplantation has been quite unusual compared to other countries. The number of brain-dead organ donations was extremely limited at first, so more than 60% of lung transplants were performed as living-donor transplants during the first 9 years [1998-2006]. The number of brain-dead donations subsequently increased, particularly after the revision of the Organ Transplant Law in 2010 such that the majority of lung transplants are now performed as brain-dead transplantations. Regarding the results of lung transplants, the most recent national registry report indicated that a total of 668 lung transplants including 447 from brain-dead donors and 221 from living donors, had been performed as of 2018. The 5- and 10-year survival rates for brain-dead donor lung transplantation were 71.9% and 57.8%, respectively, with no significant difference between the living-donor and brain-dead-donor groups. These results are comparable with the outcome of preceding programs in the US and European countries.

Multicenter phase II study of capecitabine plus oxaliplatin in older patients with advanced gastric cancer: the Tokyo Cooperative Oncology Group (TCOG) GI-1601 study.

BACKGROUND: Capecitabine plus oxaliplatin (CapeOX) is a standard treatment option for advanced gastric cancer (AGC). We conducted a prospective multicenter phase II study to evaluate the efficacy and safety of CapeOX as a first-line therapy for AGC in older patients. METHODS: Chemotherapy-naive patients aged ≥ 70 years with AGC were eligible. Initial treatment comprised capecitabine (2000 mg/m2 on days 1-14) and oxaliplatin (130 mg/m2 on day 1) every 3 weeks. After the initial feasibility assessment, the dose was reduced considering toxicity (capecitabine, 1500 mg/m2 on days 1-14; and oxaliplatin, 100 mg/m2 on day 1 every 3 weeks). The primary endpoint was overall survival (OS). RESULTS: In total, 108 patients were enrolled, of whom 104 were evaluated. Thirty-nine patients received the original-dose treatment, whereas 65 received the reduced-dose treatment. The median OS, progression-free survival (PFS), and time to treatment failure (TTF) were 12.9 (95% CI 11.6-14.8), 5.7 (95% CI 5.0-7.0), and 4.3 (95% CI 3.9-5.7) months, respectively, for all patients; 13.4 (95% CI 9.5-16.0), 5.8 (95% CI 4.1-7.8), and 5.3 (95% CI 3.5-7.2) months in the original-dose group; and 12.8 (95% CI 11.3-15.3), 5.7 (95% CI 4.4-7.0), and 4.1 (95% CI 3.7-5.7) months in the reduced-dose group. The most common grade 3/4 toxicities were neutropenia (17.9%), anemia (12.8%), and thrombocytopenia (12.8%) in the original-dose group and neutropenia (13.8%) and anorexia (12.3%) in the reduced-dose group. CONCLUSIONS: These findings demonstrate CapeOX's efficacy and safety in older AGC patients.

Anterior mediastinal tracheostomy for severe tracheal stenosis in a child with severe motor and intellectual disabilities: a case report.

BACKGROUND: Owing to recurrent aspiration pneumonia and airway stenosis secondary to thoracic deformities, tracheostomy or laryngotracheal separation are often necessary in children with severe motor and intellectual disabilities. However, these procedures are associated with the risks of tracheal stenosis due to tracheal granulation and tracheoinnominate artery fistula formation. We report a case of a child with severe motor and intellectual disabilities treated with an anterior mediastinal tracheostomy. CASE PRESENTATION: The patient was a 15-year-old boy with severe motor and intellectual disabilities due to intractable epilepsy. Due to thoracic deformity and tracheomalacia, the patient had a flattened and narrowed trachea. Accordingly, laryngotracheal separation was performed 4 months before admission to avoid aspiration pneumonia. Due to a common cold, the patient required frequent sputum suctioning, which exacerbated the tracheal stenosis. Bronchoscopy revealed tracheal stenosis 4-5 cm caudal to the tracheostomy site, tracheal mucosal ulcers, and pulsation of the innominate artery on the anterior wall of the trachea. We performed an anterior mediastinum tracheostomy to release the tracheal stenosis and prevent tracheoinnominate artery fistula formation. CONCLUSIONS: Anterior mediastinal tracheostomy has several advantages. Including sufficient release of bony compression, release of tracheal hyperextension, and relief of tracheal and innominate artery contact ensures a cannula-free tracheostomy, and there is no need to dissect the brachiocephalic artery. It is the procedure of choice in cases of head and neck malignancies requiring extensive tracheal resection and could be a good surgical option for severe tracheal stenosis and tracheoinnominate artery fistula in children with severe motor and intellectual disabilities.

Prognostic factors for lung transplant recipients focusing on age and gender: the Japanese lung transplantation report 2022.

PURPOSE: To clarify the impact of donor and recipient characteristics on the survival of recipients before and after lung transplantation in the Japanese population. METHODS: Patients' data were collected for retrospective analysis from all authorized lung transplant centers in Japan. We included 1963 patients listed for lung transplantation by the end of December 2021, comprised of 658 deceased-donor and 270 living-donor lung transplants. RESULTS: Primary disease had a significant impact on the mortality of patients waiting for transplantation. The indications for transplant significantly affected the post-transplant survival rate of deceased-donor lung transplant recipients. The recipient's age also significantly affected the post-transplant survival rate of the deceased-donor and living-donor lung transplant recipients. The recipients of grafts transplanted from donors aged 61 years or older showed a worse post-transplant survival rate (≧60 years old). The survival rate for the combination of a female donor to a male recipient among the deceased-donor lung transplant recipients was the worst among the four combinations. CONCLUSION: The donor and recipient characteristics significantly impacted the survival of recipients after lung transplantation. The underlying mechanism of the negative impact of the gender mismatch of female donor to male recipient on post-transplant survival needs to be investigated further.

Liposarcoma of the pleural cavity.

Liposarcoma rarely occurs in the pleura or thoracic cavity, and few reports appear in the literature. We hypothesized that combining clinicopathologic, immunohistochemical, and fluorescence in situ hybridization methods would allow definite diagnoses. Using formalin-fixed, paraffin-embedded blocks, we examined 6 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLPS), 5 dedifferentiated liposarcomas (DDLPSs), 2 pleomorphic liposarcomas, and 1 myxoid liposarcoma (MLPS). We used the Kaplan-Meier method and the Wilcoxon test for survival analysis for prognostic factor evaluation. Histologically, ALT/WDLPS was composed of a relatively mature adipocytic proliferation, accompanied by some lipoblasts. DDLPS exhibited round-to-oval tumor cells with a high nucleus-to-cytoplasm ratio that had proliferated in nests, accompanied in case 10 by some giant cells but no fatty cells. The pleomorphic type contained a varying proportion of pleomorphic lipoblasts. MLPS displayed uniform round- to oval-shaped cells and small signet-ring lipoblasts in a myxoid stroma. Immunohistochemically, 11 (79%), 11 (79%), and 10 (71%) of 14 cases were positive for S-100, p16, and CDK4, respectively. Six of the 14 cases (43%) were positive for MDM2 and adipophilin. One case of ALT/WDLPS and 3 cases of DDLPS exhibited MDM2 amplification by fluorescence in situ hybridization (Vysis LSI MDM2 SpectrumGreen Probe plus Vysis CEP 12 SpectrumOrange probe). ALT/WDLPS was the most favorable type for survival, while adipophilin tended to be a negative prognostic factor for pleural liposarcoma. For a firm diagnosis of liposarcoma in the pleura, immunohistochemistry for CDK4, MDM2, and adipophilin together with MDM2 gene amplification by fluorescence in situ hybridization may be an important diagnostic tool.

Use of a radiofrequency identification system for precise sublobar resection of small lung cancers.

BACKGROUND: The incidence of sublobar resection is increasing because of the rise in the detection of small lung cancers. However, local recurrence needs to be addressed, and several methods are needed for the resection with secure margins of non-visible and non-palpable tumors. METHODS: We retrospectively reviewed the use of a radiofrequency identification (RFID) system in sublobar resection of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) at our institute. RESULTS: From June 2020 to June 2022, 39 patients underwent sublobar resection for AIS or MIA. The median age was 69 years (interquartile range, 64-76). Among the 39 patients, 24 were diagnosed with AIS and 15 with MIA. Segmentectomy, subsegmentectomy, and wedge resection were performed in nine, six, and 24 patients, respectively. The median size of the target tumor was 9.0 mm (8.1-12.9) and the median distance between the tag and the tumor was 2.9 mm (0-7.5). The median pathological surgical margin was 15.0 mm (10-17.5). Complete resection of all lesions was performed with a secure surgical margin. The median follow-up duration was 6 months, during which no local recurrence was detected in any of the patients. CONCLUSIONS: The RFID marking system accurately informed the surgeons of the tumor location and helped them to perform precise sublobar resection.

Development of a Novel Material to Promote Wound Healing at Bronchial Defects.

BACKGROUND: Bronchopleural fistula (BPF) is a critical complication that may progress to pneumonia and empyema, but optimal treatment remains uncertain. Our purpose was to develop a novel material for bronchial occlusion that can be used to treat BPF by blocking airflow and promoting wound healing. METHODS: Sponges were prepared in concentrations of 25, 40, and 50 mg/dL of silk-elastin by hydrophobic processing. Five adult Beagle dogs underwent right anterior lobectomy, and 5 underwent left posterior lobectomy. Silk-elastin sponges were placed at bronchial stumps of 8 dogs, and silicone plugs were placed at the stumps of 2 dogs as a control. RESULTS: Postoperative complications were not observed, except in 1 dog in which the silicone plug had been placed and which had massive subcutaneous emphysema at 4 weeks after operation. Histologic examination revealed that stumps were covered with connective tissue and that there was more regeneration of airway epithelium in the silk-elastin sponge group than in the silicone plug group. There were increased numbers of myofibroblasts around the bronchial stump occluded by silk-elastin sponges at 2 weeks after placement, which completely disappeared after 2 months, during which abundant neovascularization occurred. CONCLUSIONS: We showed that silk-elastin sponges can manage and promote regeneration of bronchial epithelium. Our results demonstrate that bronchial occlusion with a silk-elastin sponge is a promising option for treatment of BPF.

Initial Safety Analysis of CapeOx for Elderly Patients With Advanced Gastric Cancer Patients: A Phase II Trial.

BACKGROUND: Safety of combination chemotherapy using platinum and fluorouracil has not been evaluated adequately for advanced gastric cancer (AGC) in elderly patients. PATIENTS AND METHODS: We initiated a phase II study to evaluate the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) as first-line therapy for patients with AGC aged ≥70 years. Planned assessment of toxicity was made upon recruitment of the first 20 patients. RESULTS: In five out of 20 patients, unacceptable toxicity was observed, including three patients who were unable to complete the initial two courses due to adverse events. Among the other 15 patients, dose reduction due to toxicity were needed in 10 and treatment delay for adverse events also occurred in 12 patients during the first two courses. CONCLUSION: Early analyses of safety suggest that the CapeOX regimen was not tolerated without dose reduction for elderly patients with AGC in this study.

[Gastrointestinal Complication after Lung Transplantation].

A total number of 1,787 patients have been registered in the Japan Organ Transplantation Network (JOTN), of whom 838 (46.9%) have received cadaveric lung transplantation or living-donor lobar lung transplantation since The Japanese Organ Transplant Law took effect in 1997. Subsequent to four other university hospitals( Tohoku, Kyoto, Osaka and Okayama), Fukuoka University Hospital was authorized to start lung transplantation in 2005. The survival rates after lung transplantation are lower than other solid organ transplantations not only in Japan but also around the world due to complications including infections and rejections. Between December 2005 and June 2021, 129 patients from the Fukuoka University Hospital were registered in the JOTN, and 50 underwent lung transplantation( five living-donor lobar lung transplantations and 45 cadaveric lung transplantations). Herein, we report our single-center experience of lung transplant program and an overview of the observed gastrointestinal complications associated with lung transplantation at our center.

Current status of inhaled nitric oxide therapy for lung transplantation in Japan: a nationwide survey.

OBJECTIVES: Currently, inhaled nitric oxide (NO) therapy for lung transplantation is not covered by public health insurance in Japan. In this study, we evaluated the perioperative use and safety of inhaled NO therapy for lung transplantation. METHODS: Data regarding the duration of treatment and adverse events of inhaled NO therapy were collected for all lung transplantations performed from January 1, 2015, to December 31, 2019, at nine lung transplant facilities in Japan. RESULTS: During the study period, lung transplants were performed in 357 patients, among whom inhaled NO therapy was administered to 349 patients (98%). The median initial and median maximum inhaled NO doses were 10 and 20 ppm, respectively. Inhaled NO therapy was introduced during surgery and continued postoperatively in 313 patients (90%) for a median of 4 days. Significant improvements in oxygenation and decreases in pulmonary arterial pressure were observed in patients receiving inhaled NO therapy. Side effects of inhaled NO therapy, such as methemoglobinemia, were observed in 15 patients (4%), with a significant incidence in patients aged < 18 years. CONCLUSIONS: Inhaled NO therapy was performed in almost all patients who underwent lung transplantation in Japan and showed reasonable efficacy. Therefore, public health insurance coverage for inhaled NO therapy during lung transplantation is recommended.

Elucidation of prognostic factors and the effect of anti-fibrotic therapy on waitlist mortality in lung transplant candidates with idiopathic interstitial pneumonias.

BACKGROUND: Lung transplantation (LTx) is the last resort for patients who fail to respond to drug therapy and progress to advanced idiopathic interstitial pneumonias (IIPs). However, more than one-third of patients registered for LTx face despair because of rapid disease progression and donor shortage. This study aimed to identify the risk factors of waitlist mortality in LTx candidates with IIPs and investigate the association of anti-fibrotic therapy with waitlist mortality. METHODS: We retrospectively investigated 56 patients with IIPs, including 29 patients with idiopathic pulmonary fibrosis (51.7%) and 11 patients with idiopathic pleuroparenchymal fibroelastosis (19.6%), registered for LTx at Fukuoka University Hospital between January 2006 and June 2020. The risk factors affecting transplantation-censored survival were evaluated. RESULTS: The waitlist mortality rate of patients with nonspecific interstitial pneumonia was significantly lower than that of others. Multivariate survival analysis using Cox's model identified a history of pneumothorax (P = 0.029) and short 6-min walk distance (6MWD) (P = 0.012) to be significant variables affecting waitlist mortality. Patients receiving anti-fibrotic therapy (n = 27, 48.2%) had a lower risk of pneumothorax (P = 0.017) and their 6MWD was longer than that of non-therapy patients (P < 0.001). The waitlist mortality rate of patients on anti-fibrotic therapy was significantly lower (P = 0.012). CONCLUSIONS: History of pneumothorax and short 6MWD were independent predictors of waitlist mortality in LTx candidates with IIPs. The anti-fibrotic therapy may potentially reduce mortality in patients with IIPs on the waiting list for LTx.

Outcomes of lung transplantation for idiopathic pleuroparenchymal fibroelastosis.

PURPOSE: This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF). METHODS: We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018. RESULTS: There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/m2, respectively; P < 0.01). However, Kaplan-Meier survival curves showed no significant difference in overall survival between the groups. The BMI did not increase in patients with IPPFE, even 1 year after LT (pretransplant, 16.5 ± 3.2 kg/m2 vs. 1 year post-transplant, 15.6 ± 2.5 kg/m2; P = 0.08). The percent predicted forced vital capacity (%FVC) 1 year after LT was significantly lower in the IPPFE group than in the IPF group (48.4% ± 19.5% vs. 68.6% ± 15.5%, respectively; P < 0.01). CONCLUSIONS: Despite extrapulmonary problems such as a flat chest, low BMI, and associated restrictive impairment persisting in patients with IPPFE, patient survival after LT for IPPFE or IPF was equivalent.

Severe scoliosis with an impaired pulmonary allograft function after pediatric unilateral lung transplantation.

Left-unilateral single-lobe lung transplantation from a living donor was performed in a 4-year-old boy who suffered from severe respiratory failure caused by bronchiolitis obliterans (BO) as a result of graft versus host disease (GVHD) after peripheral blood stem cell transplantation (PBSCT). The patient grew well during his early childhood years, with an excellent lung allograft function. However, severe thoracic scoliosis occurred 7 years after lung transplantation, which ultimately resulted in compression of the lung allograft followed by severe respiratory dysfunction, and the patient became dependent on mechanical ventilation support. Posterior spinal fusion of Th2-L3 with instrumentation and bone grafting was performed to correct scoliosis in the hope of recovering his thoracic capacity. The left thoracic volume was dramatically improved immediately after spinal fusion surgery, and the patient was ultimately weaned off of mechanical ventilation after a year of pulmonary rehabilitation.

A phase II study of FOLFOXIRI plus bevacizumab as initial chemotherapy for patients with untreated metastatic colorectal cancer: TRICC1414 (BeTRI).

PURPOSE: FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. METHODS: Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). RESULTS: Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8-77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. CONCLUSIONS: FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.

A successful surgical tracheobronchoplasty in a case of expiratory collapse of central airways associated with tracheobronchomalacia in a severely deformed single lung patient.

A 67-year-old male with a severe body deformity and a total collapse of the left lung due to infantile paralysis was admitted to a regional hospital for a spinal fracture. He suffered from cardiopulmonary arrest during the hospitalization. Although extubation was tried several times after resuscitation, he went into cardiopulmonary arrest repeatedly. The expiratory collapse of the central airways due to tracheobronchomalacia was suspected, requiring tracheostomy with persistent positive pressure ventilation. He was transferred to our hospital after several unsuccessful endobronchial interventions. Severe tracheobronchomalacia was diagnosed with dynamic bronchoscopy, and surgical tracheobronchoplasty using a polypropylene mesh was performed. A modified surgical approach was utilized to stabilize the intraoperative respiratory status in this particular patient with a severely deformed body and a single lung. Consequently, the tracheobronchoplasty was completed without intraoperative complications. The postoperative course was also uneventful, and the patient was ventilator-free on postoperative day 7.