Preoperative risk-factors for secondary spontaneous pneumothorax surgery in Japan: a nationwide database study.

PURPOSE: We aimed to identify preoperative risk factors for secondary spontaneous pneumothorax surgery. METHODS: The National Clinical Database of Japan, with six annual datasets from 2014 to 2019, was used. All patients who underwent surgery for secondary spontaneous pneumothorax were included, excluding those < 15 years old and those with incomplete data. The effects of preoperative risk factors were analyzed for operative mortality (mortality during hospitalization or within 30 days, regardless of hospitalization status), 30-day mortality, and postoperative respiratory morbidities. RESULTS: Of the 18,309 patients enrolled in the study, operative mortality, 30-day mortality, and postoperative respiratory morbidities were observed in 654 (3.6%), 343 (1.9%), and 2258 (12.3%) patients, respectively. Increasing age, male sex, body mass index < 18.5 or > 30, performance status > 2, emergent surgery, interstitial pneumonia, and diabetes in preoperative co-morbidity, tumors, and other diseases in underlying lung disease were significant risk factors for operative mortality. Those for 30-day mortality included autoimmune disease instead of male sex and diabetes, while those for postoperative respiratory morbidities included lymphangiomyomatosis instead of a body mass index > 30. CONCLUSION: We identified many preoperative risk factors for operative mortality, 30-day mortality, and postoperative respiratory morbidities in secondary spontaneous pneumothorax surgery. These findings will assist in selecting appropriate surgical candidates.

[11C]Methionine PET vs. [18F]Fluorodeoxyglucose PET Whole-body Imaging to Determine the Extent of Methionine-addiction Compared to Glucose-addiction of Primary and Metastatic Cancer of the Trunk in Patients.

BACKGROUND/AIM: Positron emission tomography (PET) is an important imaging modality, especially in oncology. [18F]fluorodeoxyglucose PET (FDG-PET) is the most used cancer PET imaging. However, since the elevated glucose use by cancers, termed the Warburg effect, is usually only moderate, FDG often does not provide a strong or well-delineated signal. Malignancies have a stronger addiction to methionine, known as the Hoffman effect, and thus [11C]methionine PET (MET-PET) has demonstrated superiority over FDG-PET in gliomas and other brain tumors. Our team is pioneering the use of MET-PET for tumors of the trunk for both better detection of cancer and to determine candidates for methionine-restriction therapy. The present study provides examples of cancers of organs in the trunk in which MET-PET outperforms FDG-PET in detecting and delineating primary and metastatic cancer. PATIENTS AND METHODS: In all cases, MET-PET and FDG-PET were performed simultaneously. An evaluation of the images was conducted by a nuclear medicine physician. RESULTS: Four cases, including prostate, bladder, esophageal, and breast cancer demonstrated the superiority of MET-PET compared to FDG-PET. CONCLUSION: MET-PET can out-perform FDG PET for accurate detection of primary and metastatic cancer in the trunk and can determine the extent of methionine addiction of cancer, thereby indicating whether cancer patients can benefit from methionine-restriction therapy.

Stromal CD73 Expression in Breast Cancer: Subtype-specific Expression and its Prognostic Significance.

BACKGROUND/AIM: Invasive ductal carcinoma (IDC) is classified into distinct subtypes with varying prognoses and treatment sensitivities. For instance, triple-negative breast cancer (TNBC) is associated with poorer outcomes than other subtypes. We have previously reported the role of interstitial CD73 in tumor invasion and its correlation with prognosis in other cancers. This study aimed to investigate the expression of stromal CD73 (sCD73) in IDC and its potential prognostic significance. PATIENTS AND METHODS: We analyzed 61 cases of human epidermal growth factor receptor 2-negative IDC, including TNBC and hormone receptor-positive (luminal-type) cases, treated surgically at our institution from 2005 to 2010. Cases that received preoperative drug therapy were excluded. CD73 expression was evaluated by immunostaining of the tumor stroma. RESULTS: sCD73 expression was observed in 70% of all cases, with a significantly higher rate in TNBC (93%) compared with luminal breast cancer (48%). High sCD73 expression was associated with poor prognosis in terms of overall survival (OS) and disease-free survival (DFS) across all cases. In patients with luminal breast cancer, high sCD73 expression was also indicative of poor prognosis with respect to both OS and DFS. CONCLUSION: High expression of sCD73 is associated with poor prognosis in IDC, particularly in luminal breast cancer. Further research is needed to establish sCD73 as an independent prognostic factor.

Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201).

BACKGROUND: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. METHODS: In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. RESULTS: Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. CONCLUSION: The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).

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).

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.

Chest wall tuberculosis: precision surgery with indigo carmine in limited cases for safe and intuitive lesion excision.

In addition to treatment with antituberculosis drugs, complete surgical excision is important for the cure of chest wall tuberculosis. However, surgery is often challenging to perform due to different factors such as the strong adhesion of tuberculous lesions to the surrounding normal tissue, growth of neovascularization and presence of fragile necrotic tissues. Firm adhesions, bleeding and fragile tissue make it difficult to determine the boundary with normal tissue and completely excide the lesion. Moreover, ingenuity is required. Herein, we report the identification of the boundary between the lesion and normal tissue by injecting indigo carmine into the abscess to completely excide the lesion, which is considered an intuitive and safe method.

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.

Relationship between ankle-foot-complex mobility during static loading and frontal moment impulses of knee and hip joints during the stance phase.

BACKGROUND: Ankle-foot-complex mobility impairments, which can be assessed by the difference between the sitting and standing positions, are related to an increase in the load on the knee and hip joints during the stance phase of the gait. RESEARCH QUESTION: What is the relationship between the ankle-foot-complex mobility during static weight bearing and the mechanical stresses on the knee and hip joints throughout the stance phase? METHODS: Ankle-foot-complex mobility and gait data were collected from 26 healthy adults. The complex mobility was established by comparing the foot indices, measured using a three-dimensional foot scanner, in sitting and standing positions. The gait data were acquired using eight cameras (recording at 100 Hz) and three force plates (recording at 1000 Hz). Stance phase data were collected via ground reaction forces. The stance phase was dissected into shock absorption and propulsion phases, during which the external knee and hip adduction moment impulses (KAMi, HAMi) were recorded. The correlation between the ankle-foot-complex mobility during static weight bearing and KAMi and HAMi during the stance phase was examined using Pearson's product-moment correlation coefficients. RESULTS: This study revealed that KAMi correlated with medial malleolus mobility (r = -0.44) throughout the stance phase. Furthermore, in the propulsive phase, KAMi correlated with calcaneus (r = 0.51) and navicular (r = -0.50) mobilities, whereas HAMi correlated with calcaneus mobility (r = -0.40). SIGNIFICANCE: The study provides insights into the relationship between the static mobility of the ankle-foot complex in healthy individuals and mechanical stress during the stance phase. Calcaneus and navicular mobilities were related to efficient push-off in the propulsive phase. Medial malleolus mobility was related to the control of the lateral tilt of the lower limb and ankle dorsiflexion motion throughout the stance phase.

Efficacy and safety of add-on mirogabalin to conventional therapy for the treatment of peripheral neuropathic pain after thoracic surgery: the multicenter, randomized, open-label ADMIT-NeP study.

BACKGROUND: For chronic pain after thoracic surgery, optimal timing of its diagnosis and effective treatment remains unresolved, although several treatment options are currently available. We examined the efficacy and safety of mirogabalin, in combination with conventional pain therapy (nonsteroidal anti-inflammatory drugs and/or acetaminophen), for treating peripheral neuropathic pain (NeP) after thoracic surgery. METHODS: In this multicenter, randomized, open-label, parallel-group study, patients with peripheral NeP were randomly assigned 1:1 to mirogabalin as add-on to conventional therapy or conventional treatment alone. RESULTS: Of 131 patients of consent obtained, 128 were randomized (mirogabalin add-on group, 63 patients; conventional treatment group, 65 patients). The least squares mean changes (95% confidence interval [CI]) in Visual Analogue Scale (VAS) score for pain intensity at rest from baseline to Week 8 (primary endpoint) were - 51.3 (- 54.9, - 47.7) mm in the mirogabalin add-on group and - 47.7 (- 51.2, - 44.2) mm in the conventional group (between-group difference: - 3.6 [95% CI: - 8.7, 1.5], P = 0.161). However, in patients with Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) score (used for the screening of NeP) ≥ 12 at baseline, the greater the S-LANSS score at baseline, the greater the decrease in VAS score in the mirogabalin add-on group, while no such trend was observed in the conventional treatment group (post hoc analysis). This between-group difference in trends was statistically significant (interaction P value = 0.014). Chronic pain was recorded in 7.9% vs. 16.9% of patients (P = 0.171) at Week 12 in the mirogabalin add-on vs. conventional treatment groups, respectively. Regarding activities of daily living (ADL) and quality of life (QOL), changes in Pain Disability Assessment Scale score and the EQ-5D-5L index value from baseline to Week 8 showed significant improvement in the mirogabalin add-on group vs. conventional treatment group (P < 0.001). The most common adverse events (AEs) in the mirogabalin add-on group were dizziness (12.7%), somnolence (7.9%), and urticaria (3.2%). Most AEs were mild or moderate in severity. CONCLUSIONS: Addition of mirogabalin to conventional therapy did not result in significant improvement in pain intensity based on VAS scores, but did result in significant improvement in ADL and QOL in patients with peripheral NeP after thoracic surgery. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs071200053 (registered 17/11/2020).

[11C] Methionine-PET Imaging as a Cancer Biomarker for Methionine Addiction and Sensitivity to Methionine-restriction-based Combination Chemotherapy.

BACKGROUND/AIM: Methionine addiction is a fundamental and universal hallmark of cancer, termed the Hoffman effect. Methionine addiction of cancer is greater than glucose addiction, termed the Warburg effect, as shown by the comparison of PET imaging with [11C]methionine and [18F]fluorodeoxyglucose. The aim of the present study was to determine whether [11C]methionine PET (MET-PET) images could be a biomarker of methionine addiction of cancer and potential response to methionine-restriction-based combination chemotherapy. PATIENTS AND METHODS: In the present study a patient with invasive lobular carcinoma of the breast metastatic to axillary lymph nodes was imaged by both MET-PET and [18F]fluorodeoxyglucose PET (FDG-PET) before and after combination treatment with methionine restriction, comprising a low-methionine diet and methioninase, along with first-line chemotherapy. RESULTS: MET-PET gave a much stronger and precise image of the patient's metastatic axillary lymph nodes than FDG-PET. The patient had a complete response to methionine restriction-based chemotherapy as shown by MET-PET. CONCLUSION: MET-PET imaging is a biomarker of methionine-addicted cancer and potential response to methionine-restriction-based chemotherapy.

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.

A case of sacrococcygeal teratoma associated with antenatally acquired urethrovaginal fistula and hydrocolpos.

BACKGROUND: Sacrococcygeal teratomas (SCTs) are known to cause urological complications, but urethrovaginal (UV) fistula as a complication of SCT is rare. We herein report a case of SCT with UV fistula and hydrocolpos. CASE PRESENTATION: A 1-day-old female neonate presented to our department with prominent swelling in the sacrococcygeal region. She was born at 37 gestational weeks via spontaneous vaginal delivery from a 39-year-old woman. The weight of the baby was 2965 g, and her Apgar scores were 4/10 (at 1 and 5 min). An MRI examination confirmed an 11 × 11 cm Altman classification typeII SCT associated with hydrocolpos, a dilated urinary bladder, and bilateral hydronephrosis. When she was 5 days, the SCT was excised totally and a coccygectomy was performed. After the operation, as her urinary output appeared unstable, a cystoscopic examination was performed on the third postoperative day. This revealed that the UV fistula was located approximately 1 cm from the urethral opening. In addition, the proximal urethra was unobstructed and connected to the bladder. The cystoscope allowed for the passage of a urinary catheter through the urethra. After 1 month of catheter placement, she was discharged from the hospital at 57 days of age. Follow-up was uneventful, with neither urinary infection nor retention. CONCLUSIONS: SCTs are associated with not only trouble with rectal function and lower extremity movement but also urinary complications. The pathogenesis of this UV fistula is thought to be the rapid growth of the SCT that developed in the fetal period, resulting in obstruction of the urethra by the tumor and the pubic bone, which in turn caused urinary retention and the formation of a fistula as an escape route for the pressure. Because SCTs can cause a variety of complications depending on the course of the disease, careful examination and follow-up are necessary.

Prognostic factors in patients with high-risk stage II colon cancer after curative resection: a post hoc analysis of the JFMC46-1201 trial.

PURPOSE: The goal of the current study was to identify prognostic factors for disease-free survival (DFS) and overall survival (OS) in high-risk stage II colon cancer. METHODS: The subjects were patients with histologically confirmed stage II colon cancer undergoing R0 resection who met at least one of the following criteria: T4, perforation/penetration, poorly differentiated adenocarcinoma, mucinous carcinoma, and < 12 examined lymph nodes. Patients self-selected surgery alone or a 6-month oral uracil and tegafur plus leucovorin (UFT/LV) regimen. Serum CEA mRNA at ≥ 24 h after surgery and < 2 weeks after registration was also examined as a potential prognostic factor for stage II colon cancer. This study is registered with UMIN-CTR (protocol ID: UMIN000007783). RESULTS: 1880 were included in the analysis to identify prognostic factors for DFS and OS in patients with high-risk stage II colon cancer. In multivariate analyses, gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and postoperative adjuvant chemotherapy (POAC) emerged as significant independent prognostic factors for DFS. Similarly, multivariate analysis showed that age, gender, depth of tumor invasion, perforation/penetration, extent of lymph node dissection, number of examined lymph nodes, and POAC were significant independent prognostic factors for OS. Univariate analyses showed no significant difference in DFS or OS for CEA mRNA-positive and mRNA-negative cases. CONCLUSION: This study showed that gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and lack of use of POAC were significant independent prognostic factors in stage II colon cancer.

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.

Phase II study of biweekly cetuximab plus mFOLFOX6 or mFOLFIRI as second-line treatment for metastatic colorectal cancer and exploratory analysis of associations between DNA methylation status and the efficacy of the anti-EGFR antibody: T-CORE1201.

Background: Little is known about the biweekly combined use of cetuximab and chemotherapy as second-line treatment of metastatic colorectal cancer (mCRC). Recently, DNA methylation status has been reported to be a new possible predictor of the efficacy from the anti-epidermal growth factor receptor (EGFR) antibody treatment. The purpose of this study was to examine the efficacy and safety of biweekly cetuximab plus mFOLFOX6 or mFOLFIRI as a second-line treatment for KRAS exon 2 wild-type mCRC. We also investigated the predictability of DNA methylation status on the efficacy of the EGFR antibody-containing treatment. Methods: Patients who were refractory or intolerant to the first-line chemotherapy were enrolled and received biweekly cetuximab plus mFOLFOX6 or mFOLFIRI. The primary endpoint was progression-free survival (PFS). Tumor evaluations were performed every 2 months using Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Adverse events (AEs) were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. DNA methylation status of colorectal cancer cells was defined by a modified MethyLight assay. Results: Sixty-six cases were enrolled. The median PFS (mPFS) was 5.1 [95% confidence interval (CI), 3.8-7.6] months. The median overall survival (mOS) was 12.7 (95% CI, 7.5-15.3) months. Grade 3 or higher neutropenia occurred in 53.0% of patients, whereas skin disorders with a grade 3 or higher occurred in <15% of patients. In multivariate analysis, DNA methylation status could not be an independent predictor of PFS [hazard ratio (HR), 1.43; P=0.39] and OS (HR, 2.13; P=0.086). However, in RAS/BRAF wild-type patients, the mPFS and mOS in the low-methylated colorectal cancer (LMCC) group was numerically better than those in the highly-methylated colorectal cancer (HMCC) group, although the difference was not statistically significant [mPFS: 8.5 (95% CI, 6.1-10.9) vs. 3.3 (95% CI, 1.2-not reached) months, P=0.79; ΔmPFS, 5.2 months; mOS: 15.3 (95% CI, 11.9-23.5) vs. 6.5 (95% CI, 3.1-not reached) months, P=0.53; ΔmOS, 8.8 months]. Conclusions: Biweekly cetuximab plus mFOLFOX6 or mFOLFIRI is a useful second-line therapy for mCRC. DNA methylation status warrants further exploration as a predictive biomarker for anti-EGFR efficacy in mCRC.

Optimal bowel resection margin in colon cancer surgery: prospective multicentre cohort study with lymph node and feeding artery mapping.

Background: There are no standardised criteria for the 'regional' pericolic node in colon cancer, which represents a major cause of the international uncertainty regarding the optimal bowel resection margin. This study aimed to determine 'regional' pericolic nodes based on prospective lymph node (LN) mapping. Methods: According to preplanned in vivo measurements of the bowel, the anatomical distributions of the feeding artery and LNs were determined in 2996 stages I-III colon cancer patients who underwent colectomy with resection margin >10 cm at 25 institutions in Japan. Findings: The mean number of retrieved pericolic nodes was 20.9 (standard deviation, 10.8) per patient. In all patients except seven (0.2%), the primary feeding artery was distributed within 10 cm of the primary tumour. The metastatic pericolic node most distant from the primary tumour was within 3 cm in 837 patients, 3-5 cm in 130 patients, 5-7 cm in 39 patients and 7-10 cm in 34 patients. Only four patients (0.1%) had pericolic lymphatic spread beyond 10 cm; all of whom had T3/4 tumours accompanying extensive mesenteric lymphatic spread. The location of metastatic pericolic node did not differ by the feeding artery's distribution. Postoperatively, none of the 2996 patients developed recurrence in the remaining pericolic nodes. Interpretation: The pericolic nodes designated as 'regional' were those located within 10 cm of the primary tumours, which should be fully considered when determining the bowel resection margin, even in the era of complete mesocolic excision. Funding: Japanese Society for Cancer of the Colon and Rectum.

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.