Feasibility and safety of uniport robotic-assisted thoracoscopic surgery in initial series of anatomical pulmonary resections under learning curve.

OBJECTIVES: Uniport robotic assisted thoracoscopic surgery (U-RATS) is a recently adopted approach in thoracic surgery and is assumed to require a learning curve for surgeons because of technical difficulties. We aimed to verify the feasibility and safety of solo surgery in U-RATS in an initial series of patients, comparing with initial series of uniport video-assisted thoracoscopic surgery (U-VATS). METHODS: The surgical and post-operative outcomes of 25 U-RATS cases were compared with 25 U-VATS cases. The da Vinci Xi Surgical System was used for U-RATS procedure. In both groups, the skin incisions were 4 cm in length, and a 30-degree camera was placed at the posterior and upper edges of the incision. RESULTS: Between June and December 2023, 25 patients with lung malignancies underwent anatomical pulmonary resection via U-RATS, including 13 lobectomies and 12 segmentectomies. Patient characteristics did not differ between the groups. The short-term outcomes were similar between the U-RATS and U-VATS groups, except for operation time (median: 214 vs. 157 min, p = 0.0035). The pain scores on postoperative days 1 and 3 were significantly lower in patients who underwent U-RATS than in those who underwent U-VATS (median: 0 vs. 2, p = 0.010; median: 0 vs. 0, p = 0.027, respectively). CONCLUSIONS: The short-term outcomes are similar between the U-RATS and U-VATS groups, except for operation time. U-RATS is considered to be feasible and safe in the initial series of anatomical pulmonary resections performed by a surgeon who was under the learning curve.

Emergency right lower lobectomy for severe pulmonary abscess in a pregnant woman at the 25th week of gestation: a case report.

BACKGROUND: Pulmonary abscess is a severe infection commonly seen in patients with chronic obstructive pulmonary disease, interstitial pneumonia, immune deficiency disease, drug-induced immunocompromised state, and congenital pulmonary disease. The treatment strategy in pregnant women with a pulmonary abscess is considered challenging since adverse effects on the fetus must be avoided to ensure safe delivery. CASE PRESENTATION: A 34-year-old female patient at 24 weeks of gestation (G2P1) was admitted to the Department of Obstetrics and Gynecology due to sudden right chest pain. The patient had no significant medical history, including congenital anomalies, and no history of drug addiction or smoking. Laboratory data indicated high levels of inflammation (white blood cell 12,000/µL, C-reactive protein 16.0 mg/dL), and computed tomography demonstrated a large intrapulmonary cyst located in the middle of the right lower lobe, with some fluid collection. As the patient had no medical history of congenital pulmonary anomalies, she was initially diagnosed with a pulmonary cyst infection and treated with intravenous antibiotics. However, the infection did not resolve for over a week, and a spike in fever developed after admission. There was no definitive evidence concerning the risk of preterm delivery and fetal abortion during non-obstetric surgery. However, to control the severely infected pulmonary abscess that was refractory to antibiotics and obtain a pathological diagnosis while saving the life of both the mother and fetus, we elected to perform an emergent right lower lobectomy by open thoracotomy with a fissureless maneuver after receiving informed consent. Postoperatively, the infection gradually improved, and the patient was discharged on the 16th postoperative day without any major complications in the mother or fetus. Although she later experienced coronavirus disease-19 at 29 weeks of gestation, a boy was born at 40th weeks of gestation without any complications. Pathologically, no infectious agents, malignancies, or congenital anomalies other than lung abscesses associated with the pulmonary infarction were observed. The mother and child were healthy 1 year postoperatively. CONCLUSIONS: We experienced a rare case of a pulmonary abscess in a pregnant woman who needed an emergent right lower lobectomy to control the severe infection and obtain a correct pathological diagnosis. Under cooperation from an obstetrician and anesthesiologist, emergency pulmonary resection can be performed safely for serious abscess formation even for pregnant women who have several months left until delivery.

Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?

BACKGROUND: Colorectal cancer (CRC) is a global health concern, with advanced-stage diagnoses contributing to poor prognoses. The efficacy of CRC screening has been well-established; nevertheless, a significant proportion of patients remain unscreened, with > 70% of cases diagnosed outside screening. Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources, the association between the diagnostic routes and identification of these subgroups has been less appreciated. In the Japanese cancer registry, the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms. AIM: To clarify the stage at CRC diagnosis based on diagnostic routes. METHODS: We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals. The diagnostic routes were primarily classified into three groups: Cancer screening, follow-up, and symptomatic. The early-stage was defined as Stages 0 or I. Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups, referencing the follow-up group. The adjusted covariates were age, sex, and tumor location. RESULTS: Of the 2083 patients, 715 (34.4%), 1064 (51.1%), and 304 (14.6%) belonged to the follow-up, symptomatic, and cancer screening groups, respectively. Among the 2083 patients, CRCs diagnosed at an early stage were 57.3% (410 of 715), 23.9% (254 of 1064), and 59.5% (181 of 304) in the follow-up, symptomatic, and cancer screening groups, respectively. The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group [P < 0.001, adjusted odds ratio (aOR), 0.23; 95% confidence interval (95%CI): 0.19-0.29]. The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups (P = 0.493, aOR for early-stage diagnosis in the cancer screening group vs follow-up group = 1.11; 95%CI = 0.82-1.49). CONCLUSION: CRCs detected during hospital visits for comorbidities were diagnosed earlier, similar to cancer screening. CRC screening should be recommended, particularly for patients without periodical hospital visits for comorbidities.

Alveolar adenoma with a single cyst: A case report.

Alveolar adenoma is a rare and benign pulmonary tumor, which originates from type II pneumocytes and is often incidentally identified on radiographic images. Alveolar adenoma presents as a peripleural, solitary and cystic nodule in the lung and may mimic other types of lung tumors, thus rendering its differential diagnosis difficult. Alveolar adenoma is diagnosed based on histopathological and immunohistochemical analyses. The present study describes the case of a 50-year-old male patient with alveolar adenoma. He visited a local doctor ~3 years prior due to left chest pain. A chest computed tomography scan revealed a cystic lesion in segment 8 of the left lung. A nodular shadow appeared in the cyst and gradually increased in size; the patient was thus referred to the authors' hospital. The nodule was well-defined, solitary and solid; thus, lung cancer or aspergilloma were suspected. Thoracoscopic wedge resection was performed as diagnostic therapy. The frozen sections were non-diagnostic, and a pathological examination revealed an alveolar adenoma with no evidence of malignancy and a negative culture. The patient had a good post-operative course, with no sign of recurrence at the follow-up evaluation 46 months later. On the whole, alveolar adenoma is a rare, benign pulmonary tumor that is difficult to diagnose pre-operatively.

Endoscopist-related factors affecting adenoma detection during colonoscopy: Data from the J-SCOUT study.

OBJECTIVES: Colonoscopy withdrawal times are associated with the adenoma detection rate (ADR). However, the relationship between ADR and cecal insertion time has been inadequately characterized. We aimed to evaluate endoscopist-related factors involved in the ADR, including the average individual colonoscopy insertion and withdrawal times. METHODS: This observational study used a colonoscopy database with pathology data from routine clinical practice in Japanese institutions. The odds ratios (OR) of endoscopist-related factors related to ADRs were examined using a generalized linear mixed model. RESULTS: Of the 186,293 colonoscopies performed during the study period, 47,705 colonoscopies by 189 endoscopists in four hospitals were analyzed for ADR. The overall ADR was 38.3% (95% confidence interval [CI] 37.8, 38.7). Compared to endoscopists with mean cecal insertion times of <5 min, the OR of ADR for those with mean cecal insertion times of 5-9, 10-14, and ≥15 min were 0.84 (95% CI 0.71, 0.99), 0.68 (95% CI 0.52, 0.90), and 0.45 (95% CI 0.25, 0.78), respectively. Compared to endoscopists with mean withdrawal times of <6 min, the OR of ADR for those with mean withdrawal times of 6-9, 10-14, and ≥15 min were 1.38 (95% CI 1.03, 1.85), 1.48 (95% CI 1.09, 2.02), and 1.68 (95% CI 1.04, 2.61), respectively. There were no significant differences in ADRs by endoscopist specialty, gender, or the total number of examinations performed. CONCLUSION: Individual mean colonoscopy insertion time was associated with ADR and might be considered as a colonoscopy quality indicator as well as withdrawal time.

Medical care costs according to the stage and subtype of breast cancer in a municipal setting: a case study of Hachioji City, Japan.

BACKGROUND: It is important to assess whether the early detection of breast cancer affects medical care costs. However, research remains scant on the actual medical care costs associated with breast cancer treatment in Japan. This study aimed to determine the medical care costs of breast cancer treatment based on its stage using national health insurance claims data. METHODS: This was an observational study including patients with breast cancer who had undergone breast cancer treatment, as defined by the disease name and related treatment codes. Between August 2013 and June 2016, patients who underwent surgical treatment without axillary lymph node dissection and other radical treatment were classified as the curable group, while those who underwent palliative treatment were classified as the non-curable group. Patients were further stratified by subtype. The total and treatment-specific medical care costs for the five years were calculated using the national health insurance claims data of Hachioji City between August 2013 and May 2021. RESULTS: The mean total medical care costs for the curable and non-curable groups for the 5 years were JPY 3958 thousand (standard deviation 2664) and JPY 8289 thousand (8482), respectively. The mean medical care costs for specific breast cancer treatment for the curable and non-curable groups were JPY 1142 (728) thousand and JPY 3651 thousand (5337), respectively. Further, human epidermal growth factor receptor 2 + , Hormone + patients had the highest mean cost over the 5 years. CONCLUSIONS: The results suggest that the early detection of breast cancer may reduce medical care costs at the patient level.

MIG6 loss confers resistance to ALK/ROS1 inhibitors in NSCLC through EGFR activation by low-dose EGF.

Although tyrosine kinase inhibitor (TKI) therapy shows marked clinical efficacy in patients with anaplastic lymphoma kinase-positive (ALK+) and ROS proto-oncogene 1-positive (ROS1+) non-small cell lung cancer (NSCLC), most of these patients eventually relapse with acquired resistance. Therefore, genome-wide CRISPR/Cas9 knockout screening was performed using an ALK+ NSCLC cell line established from pleural effusion without ALK-TKI treatment. After 9 days of ALK-TKI therapy, sequencing analysis was performed, which identified several tumor suppressor genes, such as NF2 or MED12, and multiple candidate genes. Among them, this study focused on ERRFI1, which is known as MIG6 and negatively regulates EGFR signaling. Interestingly, MIG6 loss induced resistance to ALK-TKIs by treatment with quite a low dose of EGF, which is equivalent to plasma concentration, through the upregulation of MAPK and PI3K/AKT/mTOR pathways. Combination therapy with ALK-TKIs and anti-EGFR antibodies could overcome the acquired resistance in both in vivo and in vitro models. In addition, this verified that MIG6 loss induces resistance to ROS1-TKIs in ROS1+ cell lines. This study found a potentially novel factor that plays a role in ALK and ROS1-TKI resistance by activating the EGFR pathway with low-dose ligands.

[Multiple Metastatic Lung Tumors in the Left Upper Lobe Complicated with Hypoplasia and Chronic Atelectasis of the Left Lower Lobe:Report of a Case].

An 80-year-old man with surgical history of colon cancer was referred to our department for surgical treatment for multiple metastatic lung tumors in the left upper lobe. The patient had been showing complete atelectasis of the left lower lung lobe one year prior to the consultation. Six months after wedge resections for the pulmonary metastases, the left lower lobe was re-expanded, showing bronchiectasis with rudimentary pulmonary artery branches. Further, the ventilation-perfusion scintigraphy showed decreased uptake in the left lower lobe. These findings indicated that the patient had the hypoplasia of the left lower lobe.

THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer.

Mesenchymal activation, characterized by dense stromal infiltration of immune and mesenchymal cells, fuels the aggressiveness of colorectal cancers (CRC), driving progression and metastasis. Targetable molecules in the tumor microenvironment (TME) need to be identified to improve the outcome in CRC patients with this aggressive phenotype. This study reports a positive link between high thrombospondin-1 (THBS1) expression and mesenchymal characteristics, immunosuppression, and unfavorable CRC prognosis. Bone marrow-derived monocyte-like cells recruited by CXCL12 are the primary source of THBS1, which contributes to the development of metastasis by inducing cytotoxic T-cell exhaustion and impairing vascularization. Furthermore, in orthotopically generated CRC models in male mice, THBS1 loss in the TME renders tumors partially sensitive to immune checkpoint inhibitors and anti-cancer drugs. Our study establishes THBS1 as a potential biomarker for identifying mesenchymal CRC and as a critical suppressor of antitumor immunity that contributes to the progression of this malignancy with a poor prognosis.

[Radiofrequency Ablation for Pulmonary Metastasis of Ovarian Cancer Caused Iatrogenic Pneumothorax, Leading to Empyema].

A female patient in her 40s who underwent surgery for recurrent right lung metastasis from resected ovarian cancer was referred to our department because of the right pneumothorax due to radiofrequency ablation for multiple lung metastases. Methicillin-resistant Staphylococcus epidermidis( MRSE) was detected from the tip of the drainage catheter indicated persistent pulmonary fistula with right empyema, and surgical treatment was performed. A white coat of the whole lung surface and air leakage were observed at radiofrequency ablation (RFA) treated lesion and partial resection of the right lung, debridement, and irrigation were performed. A pathological examination revealed residual viable ovarian cancer cells and pleural fistula.

Sessile serrated lesions with dysplasia: is it possible to nip them in the bud?

The serrated neoplasia pathway constitutes an "alternative route" to colorectal cancer (CRC), and sessile serrated lesions with dysplasia (SSLDs) are an intermediate step between sessile serrated lesions (SSLs) and invasive CRC in this pathway. While SSLs show indolent growth before becoming dysplastic (> 10-15 years), SSLDs are considered to rapidly progress to either immunogenic microsatellite instable-high (MSI-H) CRC (presumably 75% of cases) or mesenchymal microsatellite stable (MSS) CRC. Their flat shapes and the relatively short window of this intermediate state make it difficult to detect and diagnose SSLDs; thus, these lesions are potent precursors of post-colonoscopy/interval cancers. Confusing terminology and the lack of longitudinal observation data of serrated polyps have hampered the accumulation of knowledge about SSLDs; however, a growing body of evidence has started to clarify their characteristics and biology. Together with recent efforts to incorporate terminology, histological studies of SSLDs have identified distinct dysplastic patterns and revealed alterations in the tumor microenvironment (TME). Molecular studies at the single-cell level have identified distinct gene alterations in both the epithelium and the TME. Mouse serrated tumor models have demonstrated the importance of TME in disease progression. Advances in colonoscopy provide clues to distinguish pre-malignant from non-malignant-SSLs. Recent progress in all aspects of the field has enhanced our understanding of the biology of SSLDs. The aim of this review article was to assess the current knowledge of SSLDs and highlight their clinical implications.

Risk factors for postoperative cerebral infarction in Lung Cancer patients: a retrospective study.

BACKGROUND: Postoperative cerebral infarction is a rare but serious complication after lung cancer surgery. We aimed to investigate the risk factors and evaluate the efficiency of our devised surgical procedure to prevent cerebral infarction. METHODS: We retrospectively examined 1,189 patients who underwent a single lobectomy for lung cancer at our institution. We identified the risk factors for cerebral infarction and investigated the preventive effects of performing resection of the pulmonary vein as the last step of the surgical procedure during left upper lobectomy. RESULTS: Among the 1,189 patients, we identified 5 male patients (0.4%) with postoperative cerebral infarction. All five underwent left-sided lobectomy including three upper and two lower lobectomies. Left-sided lobectomy, a lower forced expiratory volume in 1 s, and lower body mass index were associated with postoperative cerebral infarction (Ps < 0.05). The 274 patients who underwent left upper lobectomy were stratified by two procedures: lobectomy with resection of the pulmonary vein as the last step of the surgical procedure (n = 120) and the standard procedure (n = 154). The former procedure significantly shortened the length of the pulmonary vein stump when compared with the standard procedure (mean stump length: 15.1 vs. 18.6 mm, P < 0.01), and the shorter pulmonary vein might possibly prevent postoperative cerebral infarction (frequency: 0.8% vs. 1.3%, Odds ratio: 0.19, P = 0.31). CONCLUSIONS: Resecting the pulmonary vein as the last step during the left upper lobectomy enabled the length of the pulmonary stump to be significantly shorter, which may contribute to preventing cerebral infarction.

[Giant Bullae Misdiagnosed as Pneumothorax:Report of a Case].

A 46-year-old man was taken to a hospital by ambulance because of sudden onset of dyspnea, and was inserted chest drainage tube with a diagnosis of right-sided tension pneumothorax on chest X-ray. Since the chest drainage was not effective, he was transferred to our institute. Based on chest computed tomography (CT) findings, a diagnosis of giant bullae of the right lung was made, and surgical treatment was performed. Postoperatively, the improvement of respiratory function was confirmed.

The surgical Apgar score predicts postoperative complications and the survival in lung cancer patients.

PURPOSE: The surgical Apgar score (SAS)-calculated using the intraoperative variables estimated blood loss, lowest heart rate, and lowest mean systolic pressure-is associated with mortality in cancer surgery. We investigated the utility of the SAS in patients with lung cancer undergoing surgery. METHODS: We retrospectively analyzed the data of 691 patients who underwent surgery for primary lung cancer between 2015 and 2019 in a single institute and analyzed the impact of the SAS. RESULTS: Of the 691 patients, 138 (20%), 57 (8.2%), and 7 (1.0%) had postoperative complications of all grades, grades ≥ III, and grade V, respectively, according to the Clavien-Dindo classification. The C-index for postoperative complications of grades ≥ III was 0.605. A lower score (0-5 points) (odds ratio 3.09 against 8-10 points, P = 0.04) and a lower percentage of vital capacity (odds ratio 0.97, P = 0.04) were independent negative risk factors for major postoperative complications. Patients with a lower score (0-5 points) had poor 5-year overall and cancer-specific survival rates (60.1% and 72.3%, respectively; P < 0.05 for both). CONCLUSIONS: The surgical Apgar score predicted postoperative complications and the long-term survival. Surgeons may improve surgical results using the SAS.

The pulmonary surgical Apgar score for lung cancer surgery predicts postoperative complications and long-term survival.

OBJECTIVES: The surgical Apgar score, calculated using 3 intraoperative variables (blood loss, lowest mean arterial pressure and lowest heart rate), is associated with mortality in cancer surgery. The original score has less applicability in lung cancer surgery; therefore, we innovated the modified pulmonary surgical Apgar score with additional intraoperative oxygen saturation representing pulmonary parenchymal damage and cardiopulmonary dynamics. METHODS: We retrospectively analysed the data of 691 patients who underwent surgery for primary lung cancer between 2015 and 2019 at a single institute. We analysed the utility of the pulmonary surgical Apgar score compared with the original surgical Apgar score. RESULTS: Postoperative complications were observed in 57 (8.2%) and 7 (1.0%) of the 691 patients who were stratified as grade ≥III and V, respectively, according to the Clavien-Dindo classification. We compared the fitness of the score in predicting postoperative complications; the calculated c-index (0.622) was slightly higher than the original c-index (0.604; P = 0.398). Patients were categorized into 3 groups based on their scores as follows: 0-6 points (n = 59), 7-9 points (n = 420) and 10-12 points (n = 212). Univariable and multivariable analyses demonstrated that a lower score was an independent negative risk factor for postoperative complications (odds ratio 3.53; P = 0.02). Patients with lower scores had a considerably poor 5-year overall survival (64.6%) (P = 0.07). CONCLUSIONS: The pulmonary surgical Apgar score predicts postoperative complications and long-term survival in patients with lung cancer undergoing surgery and may be utilized for postoperative management.

Symptom severity trajectories and distresses in patients undergoing video-assisted thoracoscopic lung resection from surgery to the first post-discharge clinic visit.

This study aimed to characterize patients' symptom severity trajectories and distresses from video-assisted thoracoscopic lung resection to the first post-discharge clinic visit. Seventy-five patients undergoing thoracoscopic lung resection for diagnosed or suspected pulmonary malignancy prospectively recorded daily symptom severity on a 0-10 numeric scale using the MD Anderson Symptom Inventory until the first post-discharge clinic visit. The causes of postoperative distresses were surveyed, and symptom severity trajectories were analyzed using joinpoint regression. A rebound was defined as a statistically significant positive slope after a statistically significant negative slope. Symptom recovery was defined as symptom severity of ≤3 in two contiguous measurements. The accuracy of pain severity on days 1-5 for predicting pain recovery was determined using area under the receiver operating characteristic curves. We applied Cox proportional hazards models for multivariate analyses of the potential predictors of early pain recovery. The median age was 70 years, and females accounted for 48%. The median interval from surgery to the first post-discharge clinic visit was 20 days. Trajectories of several core symptoms including pain showed a rebound from day 3 or 4. Specifically, pain severity in patients with unrecovered pain had been higher than those with recovered pain since day 4. Pain severity on day 4 showed the highest area under the curve of 0.723 for predicting pain recovery (P = 0.001). Multivariate analysis identified pain severity of ≤1 on day 4 as an independent predictor of early pain recovery (hazard ratio, 2.86; P = 0.0027). Duration of symptom was the leading cause of postoperative distress. Several core symptoms after thoracoscopic lung resection showed a rebound in the trajectory. Specifically, a rebound in pain trajectory may be associated with unrecovered pain; pain severity on day 4 may predict early pain recovery. Further clarification of symptom severity trajectories is essential for patient-centered care.

On the origin of gastric tumours: analysis of a case with intramucosal gastric carcinoma and oxyntic gland adenoma.

Most gastric cancers develop in inflamed gastric mucosa due to Helicobacter pylori infection, typically with metaplastic changes. However, the origins of gastric cancer remain unknown. Here, we present a case of intramucosal gastric carcinoma (IGC) and oxyntic gland adenoma (OGA) derived from spasmolytic polypeptide-expressing metaplasia (SPEM). Early gastric cancer adjacent to a polyp was found in the upper corpus of a 71-year-old woman without H. pylori infection and was endoscopically resected. Histological examination showed IGC and OGA, both of which had predominant MUC6 expression. Interestingly, gastric glands with enriched MUC6-positive mucous cells, referred to as SPEM, expanded between them. Whole-exome sequencing analysis revealed a truncating KRAS(G12D) mutation in IGC, OGA, and SPEM. In addition, TP53 and CDKN2A mutations and a loss of chromosome 17p were found in the IGC, whereas a GNAS mutation was observed in the OGA. These results indicated that IGC and OGA originated from the KRAS-mutated SPEM. © 2023 The Pathological Society of Great Britain and Ireland.

Adaptive resistance to lorlatinib via EGFR signaling in ALK-rearranged lung cancer.

Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors rarely elicit complete responses in patients with advanced ALK-rearranged non-small cell lung cancer (NSCLC), as a small population of tumor cells survives due to adaptive resistance. Therefore, we focused on the mechanisms underlying adaptive resistance to lorlatinib and therapeutic strategies required to overcome them. We found that epidermal growth factor receptor (EGFR) signaling was involved in the adaptive resistance to lorlatinib in ALK-rearranged NSCLC, activation of which was induced by heparin-binding EGF-like growth factor production via c-Jun activation. EGFR inhibition halted ALK-rearranged lung cancer cell proliferation by enhancing ALK inhibition-induced apoptosis via suppression of Bcl-xL. Xenograft models showed that the combination of EGFR inhibitor and lorlatinib considerably suppressed tumor regrowth following cessation of these treatments. This study provides new insights regarding tumor evolution due to EGFR signaling after lorlatinib treatment and the development of combined therapeutic strategies for ALK-rearranged lung cancer.