CD98 heavy chain protein is overexpressed in non-small cell lung cancer and is a potential target for CAR T-cell therapy.

Chimeric antigen receptor (CAR) T cells are effective against hematological cancers, but are less effective against solid tumors such as non-small cell lung cancer (NSCLC). One of the reasons is that only a few cell surface targets specific for NSCLC cells have been identified. Here, we report that CD98 heavy chain (hc) protein is overexpressed on the surface of NSCLC cells and is a potential target for CAR T cells against NSCLC. Screening of over 10,000 mAb clones raised against NSCLC cell lines showed that mAb H2A011 bound to NSCLC cells but not normal lung epithelial cells. H2A011 recognized CD98hc. Although CAR T cells derived from H2A011 could not be established presumably due to the high level of H2A011 reactivity in activated T cells, those derived from the anti-CD98hc mAb R8H283, which had been shown to lack reactivity with CD98hc glycoforms expressed on normal hematopoietic cells and some normal tissues, were successfully developed. R8H283 specifically reacted with NSCLC cells in six of 15 patients. R8H283-derived CAR T cells exerted significant anti-tumor effects in a xenograft NSCLC model in vivo. These results suggest that R8H283 CAR T cells may become a new therapeutic tool for NSCLC, although careful testing for off-tumor reactivity should be performed in the future.

[A Case of 30s Female with Advanced Anal Canal Adenocarcinoma Managed with Adolescent-And-Young-Adult Team].

A 30s female complaining of anal pain and melena was referred to our hospital. The support by adolescent-and-young- adult(AYA)team was initiated after the first encounter. Colonoscopic examination revealed an ulcerated tumor on the anterior wall of anal canal with its anal margin on anal verge and the tumor was diagnosed as an adenocarcinoma. Contrast- enhanced CT and MRI revealed adjacency of tumor and vagina, enlarged lymph nodes and multiple pulmonary nodules. 18F-fluorodeoxyglucose(FDG)-positron emission tomography(PET)additionally revealed tracer accumulation in left sciatica, which led us to the diagnosis of advanced anal cancer. We planned and safely performed concomitant partial vaginal resection in robot-assisted laparoscopic abdominoperineal resection for the palliative purpose after discussion on physical and psychosocial issues including stoma and fertility with the patient, her family and AYA members. The pathological diagnosis was pT4b(vagina)N1aM1b, pStage ⅣB, and the local margin was pathologically negative. The postoperative course was smooth and she was discharged on postoperative day 16. Fifty one days after operation, she started systemic chemotherapy after decision on not to take ovarian samples and continues systemic chemotherapy as of writing. Support by AYA team was effective to facilitate the patient's decision-making and the communication between the patient and the medical team.

[A Case of Diffuse Large B-Cell Lymphoma Which Was Diagnosed during the Best Supportive Care of Recurrent Ascending Colon Cancer].

A 70s male, who had undergone single-incision laparoscopic ileocecal resection for ascending colon cancer with pathological diagnosis of T3N3M0, Stage Ⅲc(without adjuvant chemotherapy), had enhanced-computed tomography(CT)for 3-month follow-up and a hepatic low-density area, an newly emergent nodule behind inferior vena cava and distal ileal tumor were found. Three months later, enhanced CT showed that the distal ileal tumor got exponentially larger and the diagnosis of"malignant lymphoma"was suspected. The patient became sepsis, so we planned and safely performed partial resection of the tumor. The pathological diagnosis was diffuse large B-cell lymphoma. Postoperative course was smooth except for the Clostridium difficile colitis and he was discharged on postoperative day 19. Although the regrowth of the remnant tumor was observed soon after surgery, partial response was confirmed after introduction of systemic chemotherapy. When we cope with malignant lymphoma of small intestine, we need to keep it in mind that surgery is an option for the prevention of perforation and bacterial translocation.

[A Case of Fibromatosis-Like Tumor Which Was Difficult to Differentiate from Local Recurrence of Ascending Colon Cancer].

A 60s female, who had undergone single-incision laparoscopic ileocecal resection for ascending colon cancer with pathological diagnosis of T3N1bM0, Stage Ⅲb, followed by adjuvant therapy with 8 courses CAPOX 2 years ago, had enhanced- computed tomography(CT)for follow-up and a 15-mm nodule near anastomotic site was found. 18F-fluorodeoxyglucose (FDG)-positron emission tomography(PET)CT revealed abnormal accumulation of 18F-FDG only to the lesion and diagnosis of"anastomotic recurrence"was made. We planned and safely performed resection of the anastomotic site and the nodule. The pathological diagnosis was fibromatosis-like tumor without evidence of recurrence, and margin was negative. Postoperative course was smooth and she was discharged on postoperative day 9. When we diagnose local recurrence, we need to keep it in mind that fibromatosis is one of the differential diagnoses, although its incidence rate is low.

Dual-portal robotic-assisted thoracic surgery (DRATS) as a reduced port RATS: early experiences in three institutions in Japan.

Background: Robotic-assisted thoracic surgery (RATS) has gained increasing interest in recent years, with most procedures performed using the conventional multiportal approach. Uniportal RATS (URATS) approaches have recently been reported in the pursuit of minimally invasive procedures. However, URATS requires specific skills. Herein, we introduce dual-portal RATS (DRATS) performed with two incisions. Methods: Data of DRATS procedures performed from December 2022 to May 2023 were retrospectively reviewed. Twenty patients with lung cancer underwent anatomical lung resections via DRATS performed by our group at three institutes. Results: Among 20 cases of planned DRATS for anatomical pulmonary resections, there were no conversions to thoracotomy and no need for extra ports. The mean surgery time was 121±60 minutes and mean console time was 91±47 minutes. The mean intraoperative blood loss volume was 9.6±12.1 g. The mean duration of chest tube drainage and hospital stay were 2±1 and 5±2 days, respectively. The mean numerical rating scale for pain was 2±1 on the first postoperative day, 1±1 on the third day, and 1±1 at discharge. There were no postoperative complications or mortalities. Conclusions: Our primary experience shows that DRATS is safe and feasible for anatomical lung resection. We consider DRATS to be a very good preliminary step in the future transition to URATS.

Salvage Surgery Compared to Surgery After Induction Chemoradiation Therapy for Advanced Lung Cancer.

BACKGROUND: Salvage surgery is performed for selected patients with relapses of locally advanced lung cancer after definitive chemoradiation therapy (CRT), and it seems to be effective. To assess the feasibility of salvage surgery after definitive CRT, this study compared clinical outcomes of surgery after definitive CRT with those of surgery after induction CRT. METHODS: Medical records of patients who underwent surgery from January 2000 to January 2018 were reviewed. The study compared patients with salvage anatomic pulmonary resection after definitive CRT with patients with surgery after induction CRT in terms of perioperative and long-term outcomes. RESULTS: A total of 23 patients underwent salvage surgery after definitive CRT for locally advanced lung cancer (salvage group), and 36 underwent surgery after induction CRT for cN2 stage III non-small cell lung cancer (induction CRT group). The surgical procedures in the salvage group were 2 segmentectomies, 13 lobectomies, 1 bilobectomy, and 7 pneumonectomies, and those in the induction CRT group were 34 lobectomies and 2 bilobectomies. There was no 30-day or 90-day mortality in either group. The 5-year overall survival was 44.7% for the salvage group and 58.6% for the induction CRT group. The 5-year progression-free interval was 42.2% for the salvage group and 47.7% for the induction CRT group. CONCLUSIONS: Salvage anatomic pulmonary resection after definitive CRT for locally advanced lung cancer is feasible, with acceptable morbidity and prognosis in highly selected patients.

Women in thoracic surgery: Asian perspective.

There is a significant shortage of surgeons in Japan similar to many other countries. There are 40,267 registered surgeons for Japan Surgical Society, among them 23,723 are board certificated, and 7,246 are certified instructors. A total of 3,207 surgeons are members of The Japanese Associations for Chest Surgery, and 245 (7.6%) are female surgeons. Approximately 8,000 medical students graduate annually with medical license. The number of newly registered residents and surgeons has recently been declining overall in the last two decades, however, the percentage of female physicians entering into surgery has been increasing gradually along with increasing number of female medical students entering the medical schools and colleges. With regard to the issue of gender gap, our country is ranked as low as 121 out of 153 countries according to global gender gap report 2020 by World Economic Forum, dropping down from 110 out of 149 countries from previous report in 2018. As the numbers of female colleagues in our workplace increases, we must consider what we can do to build a better working environment for them that is more inclusive and supports their career. In this review, the brief history of surgery and female surgeons is described as well as current situations of female surgeons today in Japan.

Salvage surgery after chemotherapy and/or radiotherapy including SBRT and proton therapy: A consecutive analysis of 38 patients.

BACKGROUND: Local recurrence after definitive chemoradiation therapy, chemotherapy or radiotherapy with curative intent is often seen in patients with advanced non-small cell lung cancer. We evaluated the feasibility of salvage pulmonary resection after definitive non-surgical treatments and the postoperative morbidity and mortality rates. METHODS: We retrospectively analyzed the characteristics and medical courses of patients who had undergone salvage pulmonary resections after local relapse or progression between January 2000 and March 2018 at the National Cancer Centre Hospital, Tokyo, Japan. All the candidates were evaluated, and curability by surgical resection was assessed by a multidisciplinary tumor board. RESULTS: A total of 38 patient received salvage surgery: 26 of the patients were men, and the median age was 64.5 years (range, 20-78 years). Among these 38 patients, salvage lung resection was performed after chemoradiotherapy in 23 patients, after chemotherapy in 9 patients, and after radiotherapy with curative intent in 6 patients. The surgical resection methods were as follows: 26 lobectomies (2 bilobectomy, 15 right upper, 5 right lower, 1 right middle, 2 left lower and 1 left upper), 8 pneumonectomies (5 left and 3 right), and 4 segmentectomies. A complete resection (R0 resection) was achieved in 35 cases (92.1 %). Postoperative complications were observed in 3 patients (prolonged air leakage, bronchopleural fistula and surgical site infection in 1 patient each). No postoperative deaths occurred within 30 days after surgery. CONCLUSION: Along with better outcomes after definitive chemoradiotherapy, chemotherapy, and radiotherapy, the frequency of salvage surgery has been increasing in recent years. Salvage pulmonary resections after definitive non-surgical treatments with curative intent are feasible with an acceptable morbidity rate and oncological outcomes in thoroughly assessed patients.

[Extreme Obese Patients who Underwent Cardiac Surgery after Preoperative Weight Reduction;Report of Two Cases].

Obesity is a risk factor of postoperative complications. We experienced 2 extremely obese patients:a 32-year-old male with coronary artery disease and a 75-year-old female with aortic valve stenosis. Their initial body weights were 133 kg and 88.5 kg, respectively, and their initial body mass indexes (BMIs) were both 41. Their BMIs were reduced to 35.5 and 35, respectively, after preoperative weight reduction. Off-pump coronary artery bypass grafting and aortic valve replacement were performed, respectively. After surgery, the non-invasive positive pressure ventilation( NPPV) support was effective, and their postoperative courses were uneventful. Preoperative weight reduction and NPPV are useful for extremely obese patients who undergo cardiac surgery.

Aberrant mediastinal trunk of pulmonary artery.

Anatomic variations of the pulmonary artery (PA) cause vascular injuries and result in critical mistakes. Here we report the first case of lung cancer with a fissureless left upper lobectomy, an aberrant mediastinal trunk of the lingular and basal segments of the PA. A 65-year-old man was referred to our hospital with a solid mass on the left upper lobe. A fissureless left upper lobectomy was performed due to severe incomplete lobulation. Intraoperative findings showed an extremely rare anatomic variation (left A5+A8+A9b) that arose as a common trunk from the left main PA. To prevent intraoperative injury, it is essential to consider the unexpected mediastinal inferior branch and perform a surgical procedure such as fissureless lobectomy upon encountering incomplete lobulation.

Trimodality therapy for superior sulcus tumour: experience of a single institution over 19 years.

OBJECTIVES: Induction chemoradiotherapy followed by surgery is the standard treatment for superior sulcus tumours (SSTs). However, the protocols, chemotherapy agents and cycles used as well as the mode and intensity of radiotherapy vary between institutions. Thus, the objective of the study was to investigate the effects of trimodality therapy on the outcomes of patients with SSTs. METHODS: Sixty patients with SSTs were enrolled between January 1999 and December 2017. Induction therapy consisted primarily of 2 cycles of mitomycin-vindesine-cisplatin or cisplatin-vinorelbine delivered concurrently to the tumour with 40-45 Gy of radiation. Surgery was performed 2-6 weeks after completion of induction therapy. RESULTS: Fifty-four (90%) patients underwent radical surgical resection. Complete pathological resection was achieved in 44 patients (81%). There was no 30-day mortality. After a median follow-up of 57.0 months, 19 (35%) patients experienced recurrence, and 8 (15%) patients showed brain metastasis. A pathological complete response (PCR) was observed in 12 (22%) patients. The 5-year survival rate for the entire population (n = 54) was 69% (95% confidence interval 55-81%). The survival rate was better for patients who underwent complete resection than for those who underwent incomplete resection (73% vs 51%, P = 0.46). A better survival rate was evident in patients with PCR than in those without PCR (92% vs 62%, P = 0.12). CONCLUSIONS: Trimodality therapy for SSTs was efficacious and associated with favourable outcomes, with acceptable morbidity and mortality. PCR in patients with resected SSTs reveals promising long-term survival prospects with the trimodality therapy.

Phenotypic diversification by enhanced genome restructuring after induction of multiple DNA double-strand breaks.

DNA double-strand break (DSB)-mediated genome rearrangements are assumed to provide diverse raw genetic materials enabling accelerated adaptive evolution; however, it remains unclear about the consequences of massive simultaneous DSB formation in cells and their resulting phenotypic impact. Here, we establish an artificial genome-restructuring technology by conditionally introducing multiple genomic DSBs in vivo using a temperature-dependent endonuclease TaqI. Application in yeast and Arabidopsis thaliana generates strains with phenotypes, including improved ethanol production from xylose at higher temperature and increased plant biomass, that are stably inherited to offspring after multiple passages. High-throughput genome resequencing revealed that these strains harbor diverse rearrangements, including copy number variations, translocations in retrotransposons, and direct end-joinings at TaqI-cleavage sites. Furthermore, large-scale rearrangements occur frequently in diploid yeasts (28.1%) and tetraploid plants (46.3%), whereas haploid yeasts and diploid plants undergo minimal rearrangement. This genome-restructuring system (TAQing system) will enable rapid genome breeding and aid genome-evolution studies.

[Long-term progression-free survival after reduction surgery and postoperative low-dose imatinib administration for multiple liver metastases of duodenal gastrointestinal stromal tumor].

A fifty-six year-old woman visited our institute, suffering from lower abdominal pain. A tumor was palpable in the pelvic cavity, having the diameter of 9.7 cm, as measured by transvaginal ultrasonography (US). Computed tomography and magnetic resonance imaging (MRI) revealed a high contrast-enhancement and the central necrosis of the tumor. Surgical resection was performed, and the tumor was found to have originated in the duodenum. Immunohistochemistry confirmed positive KIT, and the mitotic index was 4 per 50 high power field, so that the final diagnosis was a gastrointestinal stromal tumor of intermediate risk. After two years of observation, multiple liver metastases were found. Hepatectomy was performed as a volume reduction surgery, leaving three small lesions in the remnant liver. Imatinib administration was initiated at 400 mg a day two weeks after the surgery, but was interrupted two weeks later because of severe anorexia and a body weight gain of 7 kg due to the increased ascites and edema. Imatinib was resumed at 200 mg/day after a one-month interval. She has been enjoying relapse-free survival for 8 years since the recurrence was diagnosed. Although neither reduction surgery nor dose reduction of imatinib below 300 mg/day is recommended, there may be a possibility that a smaller tumor might be controlled by a lower dose of imatinib.

Functional TFIIH is required for UV-induced translocation of CSA to the nuclear matrix.

Transcription-coupled repair (TCR) efficiently removes a variety of lesions from the transcribed strand of active genes. Mutations in Cockayne syndrome group A and B genes (CSA and CSB) result in defective TCR, but the molecular mechanism of TCR in mammalian cells is not clear. We have found that CSA protein is translocated to the nuclear matrix after UV irradiation and colocalized with the hyperphosphorylated form of RNA polymerase II and that the translocation is dependent on CSB. We developed a cell-free system for the UV-induced translocation of CSA. A cytoskeleton (CSK) buffer-soluble fraction containing CSA and a CSK buffer-insoluble fraction prepared from UV-irradiated CS-A cells were mixed. After incubation, the insoluble fraction was treated with DNase I. CSA protein was detected in the DNase I-insoluble fraction, indicating that it was translocated to the nuclear matrix. In this cell-free system, the translocation was dependent on UV irradiation, CSB function, and TCR-competent CSA. Moreover, the translocation was dependent on functional TFIIH, as well as chromatin structure and transcription elongation. These results suggest that alterations of chromatin at the RNA polymerase II stall site, which depend on CSB and TFIIH at least, are necessary for the UV-induced translocation of CSA to the nuclear matrix.

Evaluation of suicide by hanging : From the video recording.

Most evaluations of the pathophysiological processes of suicidal hangings are based on animal experiments and only a few have examined the hanging process. The little information available is mostly the result of animal experiments that have focused on tracheal obstructions. In the study presented here, a camcorder was set up by the victim to record the entire hanging process. According to the analysis from the recording, the complete asphyxial process lasted only 2 minutes and 43 seconds. Stage 1 (the prodromal stage) was especially short. Typical convulsions were not observed in this case. Body movements, such as clonic and tonic spasms, were not noticed in stage 2 (the dyspnea stage). Because the body did not touch the ground, the pressure on the neck by the ligature caused cerebral ischemia as a result of the obstruction of the neck vessels. Consequently, it can be hypothesized that sui cide by hanging may not be based on the effect of changed concentration in the blood of carbon dioxide and oxygen, but on the effect of cerebral ischemia.