[Significance and Points to Note of Perioperative Oral Care].

With the development of minimally invasive surgery for lung cancer, surgical indications for elderly patients have been increasing. However, elderly patients are at risk for aspiration pneumonia, which is accompanied by a decline in swallowing function and results in aspiration pneumonia. More than 700- 1,000 species are present in the oral microbiome, and the progression of the oral microbiome to the lung has been reported to be associated with poor prognosis. Perioperative complications include dental injuries associated with intubation for general anesthesia and postoperative pneumonia. Preoperative tooth extractions and mouth protectors are effective in preventing dental injuries. Perioperative oral care is often reported to be effective in preventing postoperative pneumonia by removing dental calculus and plaque and cleaning the tongue and stimulating saliva production. Oral care should be continued after as well as before surgery to avoid delaying adjuvant therapy. If the hospital performing the surgery has the department of dentistry and oral surgery, oral care can be completed in the hospital. However, if the hospital does not have that department, it is necessary to collaborate with a local dental clinic in various ways.

Single-cell sequencing on CD8+ TILs revealed the nature of exhausted T cells recognizing neoantigen and cancer/testis antigen in non-small cell lung cancer.

BACKGROUND: CD8+tumor infiltrating lymphocytes (TILs) are often observed in non-small cell lung cancers (NSCLC). However, the characteristics of CD8+ TILs, especially T-cell populations specific for tumor antigens, remain poorly understood. METHODS: High throughput single-cell RNA sequencing and single-cell T-cell receptor (TCR) sequencing were performed on CD8+ TILs from three surgically-resected lung cancer specimens. Dimensional reduction for clustering was performed using Uniform Manifold Approximation and Projection. CD8+ TIL TCR specific for the cancer/testis antigen KK-LC-1 and for predicted neoantigens were investigated. Differentially-expressed gene analysis, Gene Set Enrichment Analysis (GSEA) and single sample GSEA was performed to characterize antigen-specific T cells. RESULTS: A total of 6998 CD8+ T cells was analyzed, divided into 10 clusters according to their gene expression profile. An exhausted T-cell (exhausted T (Tex)) cluster characterized by the expression of ENTPD1 (CD39), TOX, PDCD1 (PD1), HAVCR2 (TIM3) and other genes, and by T-cell oligoclonality, was identified. The Tex TCR repertoire (Tex-TCRs) contained nine different TCR clonotypes recognizing five tumor antigens including a KK-LC-1 antigen and four neoantigens. By re-clustering the tumor antigen-specific T cells (n=140), it could be seen that the individual T-cell clonotypes were present on cells at different stages of differentiation and functional states even within the same Tex cluster. Stimulating these T cells with predicted cognate peptide indicated that TCR signal strength and subsequent T-cell proliferation and cytokine production was variable but always higher for neoantigens than KK-LC-1. CONCLUSIONS: Our approach focusing on T cells with an exhausted phenotype among CD8+ TILs may facilitate the identification of tumor antigens and clarify the nature of the antigen-specific T cells to specify the promising immunotherapeutic targets in patients with NSCLC.

New evaluation of the tumor immune microenvironment of non-small cell lung cancer and its association with prognosis.

BACKGROUND: A better understanding of the tumor immune microenvironment (TIME) will facilitate the development of prognostic biomarkers and more effective therapeutic strategies in patients with lung cancer. However, little has been reported on the comprehensive evaluation of complex interactions among cancer cells, immune cells, and local immunosuppressive elements in the TIME. METHODS: Whole-exome sequencing and RNA sequencing were carried out on 113 lung cancers. We performed single sample gene set enrichment analysis on TIME-related gene sets to develop a new scoring system (TIME score), consisting of T-score (tumor proliferation), I-score (antitumor immunity) and S-score (immunosuppression). Lung cancers were classified according to a combination of high or low T-score, I-score, and S-scores (eight groups; G1-8). Clinical and genomic features, and immune landscape were investigated among eight groups. The external data sets of 990 lung cancers from The Cancer Genome Atlas and 76 melanomas treated with immune checkpoint inhibitors (ICI) were utilized to evaluate TIME scoring and explore prognostic and predictive accuracy. RESULTS: The representative histological type including adenocarcinoma and squamous cell carcinoma, and driver mutations such as epidermal growth factor receptor and TP53 mutations were different according to the T-score. The numbers of somatic mutations and predicted neoantigens were higher in Thi (G5-8) than Tlo (G1-4) tumors. Immune selection pressure against neoantigen expression occurred only in Thi and was dampened in Thi/Ilo (G5-6), possibly due to a reduced number of T cells with a high proportion of tumor specific but exhausted cells. Thi/Ilo/Shi (G5) displayed the lowest immune responses by additional immune suppressive mechanisms. The T-score, I-score and S-scores were independent prognostic factors, with survival curves well separated into eight groups with G5 displaying the worst overall survival, while the opposite group Tlo/Ihi/Slo (G4) had the best prognosis. Several oncogenic signaling pathways influenced on T-score and I-scores but not S-score, and PI3K pathway alteration correlated with poor prognosis in accordance with higher T-score and lower I-score. Moreover, the TIME score predicted the efficacy of ICI in patients with melanoma. CONCLUSION: The TIME score capturing complex interactions among tumor proliferation, antitumor immunity and immunosuppression could be useful for prognostic predictions or selection of treatment strategies in patients with lung cancer.

Efficacy of preoperative inhaled LAMA/LABA combinations in patients with lung cancer and untreated COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a high incidence of postoperative pulmonary complications (PPCs). When untreated COPD is found before lung cancer surgery, we have been actively intervening therapeutically with inhaled long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) combinations. We investigated the efficacy of preoperative LAMA/LABA treatment. METHODS: We reviewed data from 261 patients who underwent pulmonary resection for primary lung cancer. Of these, 59 patients showed unrecognized obstructive ventilatory impairment on respiratory function testing. We administered inhaled drugs for 38 patients, of whom 22 patients treated with LAMA/LABA combinations and diagnosed with COPD were retrospectively analyzed regarding improvement of respiratory function and postoperative course. RESULTS: Median duration of LAMA/LABA treatment was 19.5 days (interquartile range (IQR), 10.5-28.3 days). Percentage predicted vital capacity (%VC) (pretreatment: 95.6%, IQR 91.9-111.7 vs. posttreatment 102.8%, IQR 92.3-113.0), forced expiratory volume in 1 s (FEV1) (1.76 L, 1.43-2.12 vs. 2.00 L, 1.78-2.40), forced VC (FVC) (2.96 L, 2.64-3.47 vs. 3.22 L, 2.95-3.74) and percentage predicted FEV1 (80.1%, 68.4-97.0 vs. 91.6%, 80.3-101.9) were all significantly improved (P<0.05 each). FEV1/FVC tended to be improved, but not significantly. No significant difference in improvement of respiratory function was seen between short-term (≤2 weeks) and normal-term (>2 weeks) treatment. PPCs occurred in 4 of 22 patients (18.2%), showing no significant difference compared to patients with COPD previously treated with inhaled drugs (2/20; 10.0%). CONCLUSIONS: Respiratory function is improved by preoperative LAMA/LABA treatment even in the short term. Starting treatment allows even COPD patients diagnosed on preoperative screening to experience the same frequency of PPCs as previously treated patients.

Utility of Coaxial Angioplasty-thrombectomy for Acute Tandem Occlusion of Intracranial and Extracranial Arteries.

Objective: We report a novel technique for acute occlusion of both intracranial and extracranial arteries (tandem lesions [TL]). Case Presentation: A 67-year-old male was transferred to our hospital because of right hemiparesis and aphasia. MRA revealed occlusion of the left cervical internal carotid artery (ICA) and middle cerebral artery (MCA). A balloon guide catheter (BGC) was advanced into the left common carotid artery (CCA). A microcatheter was advanced over a microwire through the intracranial thrombus. A stent retriever (SR) was deployed from the MCA to the ICA through the microcatheter. Next, with the SR anchored to the thrombus, the microcatheter was withdrawn. The extracranial percutaneous transluminal angioplasty (PTA) balloon was coaxially advanced over the SR's delivery wire and angioplasty was performed. Then, an aspiration catheter was coaxially advanced to the proximal aspect of the intracranial thrombus over the delivery wire by pump aspiration. We removed the SR and the aspiration catheter as a single unit into the BGC, resulting in sufficient recanalization. The puncture to recanalization time was 29 minutes. Conclusion: This technique can lead to faster recanalization in cases of TL.

Preoperative screening for nasal carriage of methicillin-resistant Staphylococcus aureus in patients undergoing general thoracic surgery.

Objectives: Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for surgical site infections (SSIs). However, few studies have evaluated the rate of nasal carriage of MRSA and its effect on SSIs in patients undergoing general thoracic surgery. We investigated the importance of preoperative screening for nasal carriage of MRSA in patients undergoing general thoracic surgery. Patients and Methods: We retrospectively analyzed 238 patients with thoracic diseases who underwent thoracic surgery. We reviewed the rates of nasal carriage of MRSA and SSIs. Results: Results of MRSA screening were positive in 11 of 238 patients (4.6%), and 9 of these 11 patients received nasal mupirocin. SSIs occurred in 4 patients (1.8%). All 4 patients developed pneumonia; however, MRSA pneumonia occurred in only 1 of these 4 patients. No patient developed wound infection, empyema, and/or mediastinitis. SSIs did not occur in any of the 11 patients with positive results on MRSA screening. Conclusions: The rates of nasal carriage of MRSA and SSIs were low in this case series. Surveillance is important to determine the prevalence of MRSA carriage and infection in hospitals, particularly in the intensive care unit. However, routine preoperative screening for nasal carriage of MRSA is not recommended in patients undergoing general thoracic surgery.

Division of the intersegmental plane using electrocautery for segmentectomy in clinical stage I non-small cell lung cancer.

BACKGROUND: Division of intersegmental planes is one of the important practical issues for segmentectomy to obtain feasible outcomes without relapse for clinical stage I non-small cell lung cancer. Almost all surgeons perform this procedure using a stapler. However, division of intersegmental planes for segmentectomy can also be performed by electrocautery. In this article, we demonstrate the merits and drawbacks of division of the intersegmental plane by electrocautery for segmentectomy. METHODS: Of those 125 patients who underwent segmentectomy with clinical stage I primary lung cancer, we compared cautery cases (n=50) with stapler cases (n=75). The cautery group included 29 cases (58.0%) with partial use of a staple at the end of division. RESULTS: Operative time was significantly longer in cautery cases (281±72 min) than stapler in cases (235±86 min; P=0.003). No difference in the duration of chest tube placement was evident between cautery (3.0±3.0 days) and stapler groups (2.8±1.7 days; P=0.613). However, delayed air leakage occurred significantly more frequently in cautery cases (14.0%) than in stapler cases (4.0%; P=0.048). Five-year overall survival (OS) in clinical stage I was 94.7% in cautery cases and 80.5% in stapler cases (log-rank P=0.047). Five-year disease-free survival (DFS) was 80.0% and 71.3%, respectively (log-rank P=0.075). CONCLUSIONS: The merits of cautery division include the ability to achieve meticulous division of the intersegmental plane and good preservation of the shape of residual segments. Conversely, the drawbacks include prolonged air leakage. Pleural suture or closure of residual segments may be useful to prevent delayed air leakage.

Thoracoscopic segmentectomy: hybrid approach for clinical stage I non-small cell lung cancer.

BACKGROUND: Recently, minimally invasive surgical approaches have been developed, typified by video-assisted thoracic surgery (VATS). A meticulous surgical procedure to prevent local recurrence is required during segmentectomy for clinical stage I non-small-cell primary lung cancer. In this article, we demonstrated the validity of hybrid VATS segmentectomy. METHODS: Of these 125 patients, 62 (49.6%) underwent intensively radical segmentectomy (RS). The remaining 63 (50.4%) patients underwent palliative segmentectomy (PS). We used two 2-cm ports and performed a muscle-sparing mini-thoracotomy in which a partially open metal retractor allowed direct, thoracoscopic visualization as hybrid VATS segmentectomy in 63.2% of our cases. RESULTS: The consolidation/tumor ratio obtained with thin-sliced computed tomography was significantly lower in RS cases than in PS cases (P=0.001). The proportion of pathological stage IA cases was significantly higher in RS cases (95.2%) than in PS cases (66.7%; P<0.01). Five-year overall survival (OS) for clinical stage I was 100.0% in RS cases and 73.5% in PS cases (log-rank P<0.001). Five-year disease-free survival (DFS) was 95.5% and 55.7%, respectively (log-rank P<0.001). CONCLUSIONS: During segmentectomy, the most critical consideration is establishment of sufficient surgical margins around the cancer. Our hybrid approach that includes meticulous surgical manipulations may produce sufficient surgical margins.

Necrotizing soft tissue infection of the thigh associated with retroperitoneal abscess in a patient with locally advanced ascending colon cancer: A case report.

Necrotizing soft tissue infection (NSTI) is a rare but rapidly progressing soft-tissue infection. Few reports of NSTI caused by colon cancer have been published. We present a rare case of NSTI of the thigh associated the retroperitoneal spread of ascending colon cancer. A 64-year-old man had noticed right hip pain since 3 months before admission, he felt pain in the right thigh which was reddening, and he had difficulty in walking. He was referred to Yokosuka general hospital Uwamachi. Anterolateral aspect of his right thigh was reddening and swelling. The patient was diagnosed with a psoas abscess and a NSTI of the right thigh caused by penetration of ascending colon tumor. The patient underwent debridement of severely necrotized tissue in the right thigh, diverting ileostomy and subsequently a right hemicolectomy with reversal of the ileostomy were performed. He was discharged 70 days after the first surgery. Colon cancer can be a cause of retroperitoneal abscess accompanied by NSTI of the thigh. Two-stage surgery was an efficient option in this patient with NSTI of the thigh associated with locally advanced ascending colon cancer.

Successful treatment with hyperbaric oxygen therapy for pneumatosis cystoides intestinalis as a complication of granulomatosis with polyangiitis: a case report.

BACKGROUND: Although gastrointestinal involvement in patients with granulomatosis with polyangiitis is uncommon, it is associated with mild to severe life-threatening complications. We present a case of pneumatosis cystoides intestinalis in a patient with granulomatosis with polyangiitis that was treated successfully with hyperbaric oxygen. CASE PRESENTATION: A 70-year-old Japanese man with a 3-year history of granulomatosis with polyangiitis consulted our hospital with a complaint of severe back pain. Computed tomography showed a large amount of gas located in his bowel wall and mesentery. He underwent urgent exploratory laparotomy, which led to a diagnosis of pneumatosis cystoides intestinalis without intestinal perforation or necrosis. He consequently underwent 13 sessions of hyperbaric oxygen therapy and was discharged from our hospital without complications. CONCLUSIONS: Several previous reports have supported the efficacy of hyperbaric oxygen for treating pneumatosis cystoides intestinalis. The present case, however, is the first in which pneumatosis cystoides intestinalis in a patient with granulomatosis with polyangiitis was successfully treated with hyperbaric oxygen. We therefore suggest that hyperbaric oxygen therapy could be a candidate treatment for pneumatosis cystoides intestinalis in patients with granulomatosis with polyangiitis.

Toxic shock syndrome caused by suture abscess with methicillin-resistant Staphylococcus aureus (MRSA) with late onset after Caesarean section.

Toxic shock syndrome (TSS) is a rare but life-threatening multisystem disease known to develop in the early postoperative period after various surgery. We report a rare case in which a patient who underwent Caesarean section developed TSS caused by methicillin-resistant Staphylococcus aureus (MRSA) on the 39th postoperative day. She was treated with debridement because of the possible diagnosis of necrotizing soft tissue infections. Culture test from the resected specimen was positive for MRSA. She was diagnosed with TSS caused by suture abscess and was treated with intensive care including antimicrobials. After a good postoperative course, she was discharged on the 30th postoperative day. TSS occurring 4 weeks after operation is extremely rare, but late-onset of suture abscess is known to occur. We should becognizant of development with TSS beyond early postoperative period.

Ascending colon cancer associated with deposited ova of Schistosoma japonicum in non-endemic area.

Some reports suggest the positive correlation between Schistosoma japonicum infection and colorectal cancer, however the sufficient evidence that supports a causal relationship between them has not been established. Japan used be an endemic area of S. japonicum infection for 40 years ago. But now all of Japan is a non-endemic area of S. japonicum infection. We report a case of ascending colon cancer associated with deposited ova of S. japonicum in non-endemic area.

Flare-Up Diverticulitis in the Terminal Ileum in Short Interval after Conservative Therapy: Report of a Case.

Diverticulitis in the terminal ileum is uncommon. Past reports suggested that conservative therapy may be feasible to treat terminal ileum diverticulitis without perforation; however, there is no consensus on the therapeutic strategy for small bowel diverticulitis. We present a 37-year-old man who was referred to our hospital for sudden onset of abdominal pain and nausea. He was diagnosed with diverticulitis in the terminal ileum by computed tomography (CT). Tazobactam/piperacillin hydrate (18 g/day) was administered. The antibiotic treatment was maintained for 7 days, and the symptoms disappeared after the treatment. Thirty-eight days after antibiotic therapy, he noticed severe abdominal pain again. He was diagnosed with diverticulitis in terminal ileum which was flare-up of inflammation. He was given antibiotic therapy again. Nine days after antibiotic therapy, laparoscopy assisted right hemicolectomy and resection of 20 cm of terminal ileum were performed. Histopathology report confirmed multiple ileal diverticulitis. He was discharged from our hospital 12 days after the surgery. Colonoscopy was performed two months after the surgery and it revealed no finding suggesting inflammatory bowel disease. Surgical treatment should be taken into account as a potential treatment option to manage the diverticulitis in the terminal ileum even though it is not perforated.

Propensity score-matching analysis of hybrid video-assisted thoracoscopic surgery and thoracoscopic lobectomy for clinical stage I lung cancer†.

OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) lobectomy is classified into hybrid VATS (direct and video vision) and thoracoscopic VATS (video vision only). In this study, the outcomes of hybrid VATS and thoracoscopic VATS for clinical stage I lung cancer were compared using a propensity score-matching analysis. METHODS: Hybrid and thoracoscopic VATS were performed in 178 and 76 patients, respectively. Propensity scores were calculated using logistic regression analysis and matched within a score of ±0.03 for age, sex, size of tumour, Charlson comorbidity index, preoperative therapy, percent vital capacity, forced expiratory volume in 1 s, clinical stage, pathological stage and histology. RESULTS: In the non-matched analysis, the results for hybrid and thoracoscopic VATS, respectively, were as follows: mean age, 69 ± 9 and 66 ± 10 years (P = 0.04); tumour size, 24 ± 10 and 20 ± 7 mm (P < 0.01); 2-deoxy-2 [F-18]fluorodeoxyglucose positron emission tomography SUV, 5.6 ± 4.4 and 3.6 ± 3.2 (P < 0.01); clinical stage (IA/IB), 130/48 and 69/7 (P < 0.01); pathological stage (IA/IB/IIA and IIB/IIIA and IIIB), 89/56/15/18 and 57/14/2/3 (P < 0.01); postoperative complications, 66 (37.1%) and 16 (21.1%; P = 0.01); respiratory complications, 32 (18.0%) and 6 (7.9%; P = 0.04); 5-year overall survival (OS), 77.0 and 88.8% (log-rank P = 0.045); and 5-year disease-free survival (DFS), 67.2 and 81.1% (log-rank P = 0.02). In 66 matched cases, the results for hybrid and thoracoscopic VATS, respectively, were as follows: mean operative time, 245 ± 96 and 285 ± 85 min (P = 0.01); blood loss, 95 ± 100 and 86 ± 123 ml (P = 0.67); mean duration of drainage, 3.6 ± 2.7 and 3.2 ± 2.2 days (P = 0.37); postoperative complications, 21 (31.8%) and 14 (21.2%; P = 0.17); respiratory complications, 11 (16.7%) and 5 (7.6%; P = 0.11); 5-year OS, 72.5 and 86.0% (log-rank P = 0.25); and 5-year DFS, 68.4 and 77.2% (log-rank P = 0.17). CONCLUSIONS: In this single-institution, propensity score-matched study, hybrid VATS showed a shorter operative time and similar outcomes compared with thoracoscopic lobectomy for clinical stage IA lung cancer.