Expression patterns of novel immunotherapy targets in intermediate- and high-grade lung neuroendocrine neoplasms.

BACKGROUND: Advancements in immunotherapeutic approaches only had a modest impact on the therapy of lung neuroendocrine neoplasms (LNENs). Our multicenter study aimed to investigate the expression patterns of novel immunotherapy targets in intermediate- and high-grade LNENs. METHODS: The expressions of V-domain Ig suppressor of T cell activation (VISTA), OX40L, Glucocorticoid-induced TNF receptor (GITR), and T cell immunoglobulin and mucin domain 3 (TIM3) proteins were measured by immunohistochemistry in surgically resected tumor samples of 26 atypical carcinoid (AC), 49 large cell neuroendocrine lung cancer (LCNEC), and 66 small cell lung cancer (SCLC) patients. Tumor and immune cells were separately scored. RESULTS: Tumor cell TIM3 expression was the highest in ACs (p < 0.001), whereas elevated tumor cell GITR levels were characteristic for both ACs and SCLCs (p < 0.001 and p = 0.011, respectively). OX40L expression of tumor cells was considerably lower in ACs (vs. SCLCs; p < 0.001). Tumor cell VISTA expression was consistently low in LNENs, with no significant differences across histological subtypes. ACs were the least immunogenic tumors concerning immune cell abundance (p < 0.001). Immune cell VISTA and GITR expressions were also significantly lower in these intermediate-grade malignancies than in SCLCs or in LCNECs. Immune cell TIM3 and GITR expressions were associated with borderline prognostic significance in our multivariate model (p = 0.057 and p = 0.071, respectively). CONCLUSIONS: LNEN subtypes have characteristic and widely divergent VISTA, OX40L, GITR, and TIM3 protein expressions. By shedding light on the different expression patterns of these immunotherapy targets, the current multicenter study provides support for the future implementation of novel immunotherapeutic approaches.

The Effects of Antibiotics on the Development and Treatment of Non-Small Cell Lung Cancer.

There have been studies on antibiotic use concerning lung cancer and its potential impact on carcinogenesis and microbiome. However, subsequent research has failed to support these associations consistently. In terms of the potential carcinogenic of antibiotics on lung cancer, the available evidence has not been sufficient to draw any definitive conclusions. Maintaining immune homeostasis and preventing pathogen invasion is critically dependent on the microbiome. The subtle balance of the body microbiota, including the lungs, is susceptible to disruption by antibiotic use. There is an association between disruptions of the lung microbiome and respiratory diseases, including lung cancer, and decreased efficacy of treatments. Patients with lung cancer are often indicated for antibiotic treatment due to respiratory infections or other comorbidities. Pulmonary infections in the area of undetected lung tumors are not uncommon. They can be an early sign of malignancy, which may explain the association between antibiotic use and lung cancer diagnosis. Antibiotic use can also affect the effectiveness of immune checkpoint inhibitor therapy. Studies suggest that antibiotic use can impair the efficacy of immune checkpoint inhibitor therapy in lung cancer patients, particularly around the time when treatment is initiated. These findings require further study, understanding underlying mechanisms, and identifying microbiota signatures associated with treatment response.

Microbiota Diversity in Non-Small Cell Lung Cancer Gut and Mouth Cavity Microbiota Diversity in Non-Small Cell Lung Cancer Patients.

Lung malignancies have a substantial impact on cancer incidence and mortality worldwide. Even though many factors involved in the development of the disease are known, many questions remain unanswered. Previous studies suggest that the intestinal microbiota may have a role in developing malignant diseases. According to some findings, the microbiota has proven to be a key modulator of carcinogenic processes and the immune response against cancer cells, potentially influencing the effectiveness of immunotherapy. In our study, we characterized culturable microorganisms associated with non-small cell lung cancer (NSCLC) that can be recovered from rectal swabs and mouthwash. In addition, we also explored differences in the culturable microbiota with two main types of NSCLC - adenocarcinoma (ADC) and squamous cell carcinoma (SCC). With 141 patients included in the study (86 ADC and 55 SCC cases), a significant difference was observed between the two types in seven bacterial species (Collinsella, Corynebacterium, Klebsiella, Lactobacillus, Neisseria, Rothia, and Streptococcus), including the site of origin. The relationship between microbial dysbiosis and lung cancer is poorly understood; future research could shed light on the links between gut microbiota and lung cancer development.

Radicality and safety of mediastinal lymphadenectomy in lung resection: a comparative analysis of uniportal thoracoscopic, multiportal thoracoscopic, and thoracotomy approaches.

BACKGROUND: Lung cancer poses a significant challenge with high mortality rates. Minimally invasive surgical approaches, including the uniportal thoracoscopic technique, offer potential benefits in terms of recovery and patient compliance. This study focuses on evaluating the radicality of mediastinal lymphadenectomy during uniportal thoracoscopic lung resection, specifically assessing the reachability of established lymphatic stations. METHODS: A comparative study was conducted at the University Hospital Ostrava from January 2015 to July 2022, focusing on the evaluation of radicality in mediastinal lymphadenectomy across three patient subgroups: uniportal thoracoscopic approach, multiportal thoracoscopic approach, and thoracotomy approach. The study implemented the routine identification and excision of 8 lymph node stations from the respective hemithorax to assess the radicality of lymph node harvesting. RESULTS: A total of 428 patients were enrolled and evaluated. No significant differences were observed in the number of lymph nodes removed between the subgroups. The mean number of lymph nodes removed was 6.50 in the left hemithorax and 6.49 in the right hemithorax. The 30-day postoperative morbidity rate for the entire patient population was 27.3%, with 17.5% experiencing minor complications and 6.5% experiencing major complications. Statistically significant differences were observed in major complications between the uniportal approach and the thoracotomy approach (3.5% vs 12.0%, p = 0.002). The overall mortality rate in the study population was 3%, with a statistically significant difference in mortality between the uniportal and multiportal approaches (1.0% vs 6.4%, p = 0.020). CONCLUSIONS: The uniportal approach demonstrated comparable accessibility and lymph node yield to multiportal and thoracotomy techniques. It is equivalent to established methods in terms of postoperative complications, with fewer major complications compared to thoracotomy. While our study indicates a potential for lower mortality following uniportal lung resection in comparison to multiportal lung resection, and demonstrates comparable outcomes to thoracotomy, it is important to approach these findings cautiously and refrain from drawing definitive conclusions.

Is abdominal pain after an injury just an injury? Case report of rare aspiration pneumonia with lung gangrene and peritoneal response in a 5-year-old child.

Although pneumonia presents a relatively common diagnosis, it does not always present with classic clinical symptoms, nor does it follow a regular course without complications. The presented case describes a rare case of aspiration necrotizing pneumonia, which despite intensive therapy, progressed to lung gangrene and required a lung lobectomy. Another peculiarity is that the correct diagnosis was established only after the onset of abdominal pain, surprisingly by a trauma surgeon. This case emphasizes the necessity of a thorough general examination and draws attention to a rare, but conservatively intractable necrotizing pneumonia complicated by lung gangrene.

Impact of the coronavirus disease 2019 pandemic on the management of acute peptic ulcer perforation: to be reconsidered(?).

OBJECTIVE: Peptic ulcer perforation presents the most serious complication of ulcer disease with mortality that varies significantly depending on the age and conditions. The coronavirus disease 2019 pandemic was effective worldwide in 2020 and continues to date. The aim of this study was to investigate the initial clinical parameters and short-term outcomes of patients with acute peptic ulcer perforation before and during the coronavirus disease 2019 pandemic. METHODS: A retrospective cohort study was conducted in the Department of Surgery, University Hospital Ostrava, Czech Republic. The patients undergoing surgical modality of a simple suture of peptic ulcer perforation with/without omentoplasty in the post-coronavirus disease 2019 (January 1, 2020 to December 31, 2021) and the pre-coronavirus disease 2019 (January 1, 2018 to December 31, 2019) had been incorporated in this study. RESULTS: This study included a total of 46 cases (26 in the pre-coronavirus disease 2019, 20 in the post-coronavirus disease 2019). The age, body mass index, Boey score, duration of symptoms, surgery time, and length of hospital stay were comparable in both study subgroups. During the coronavirus disease 2019 pandemic, patients were admitted with a statistically significantly lower degree of perioperative risk according to the American Society of Anesthesiologists classification (p=0.013). Notably, 30-day postoperative morbidity was significantly higher in pre-coronavirus disease 2019 (73.1 vs. 55.0%, p=0.038). The mortality rate in the laparoscopic group was 13.6%, in the laparotomy group 41.4%, and the mortality rate was higher in pre-coronavirus disease 2019 than in post-coronavirus disease 2019 (34.6 vs. 20.0%, p=0.166). CONCLUSION: In fact, the coronavirus disease 2019 pandemic had not significantly influenced therapeutic management and short-term outcomes of patients undergoing acute surgical repair of peptic ulcer perforation.

Impact of the coronavirus disease 2019 pandemic on the management of acute peptic ulcer perforation: to be reconsidered(?)

SUMMARY OBJECTIVE: Peptic ulcer perforation presents the most serious complication of ulcer disease with mortality that varies significantly depending on the age and conditions. The coronavirus disease 2019 pandemic was effective worldwide in 2020 and continues to date. The aim of this study was to investigate the initial clinical parameters and short-term outcomes of patients with acute peptic ulcer perforation before and during the coronavirus disease 2019 pandemic. METHODS: A retrospective cohort study was conducted in the Department of Surgery, University Hospital Ostrava, Czech Republic. The patients undergoing surgical modality of a simple suture of peptic ulcer perforation with/without omentoplasty in the post-coronavirus disease 2019 (January 1, 2020 to December 31, 2021) and the pre-coronavirus disease 2019 (January 1, 2018 to December 31, 2019) had been incorporated in this study. RESULTS: This study included a total of 46 cases (26 in the pre-coronavirus disease 2019, 20 in the post-coronavirus disease 2019). The age, body mass index, Boey score, duration of symptoms, surgery time, and length of hospital stay were comparable in both study subgroups. During the coronavirus disease 2019 pandemic, patients were admitted with a statistically significantly lower degree of perioperative risk according to the American Society of Anesthesiologists classification (p=0.013). Notably, 30-day postoperative morbidity was significantly higher in pre-coronavirus disease 2019 (73.1 vs. 55.0%, p=0.038). The mortality rate in the laparoscopic group was 13.6%, in the laparotomy group 41.4%, and the mortality rate was higher in pre-coronavirus disease 2019 than in post-coronavirus disease 2019 (34.6 vs. 20.0%, p=0.166). CONCLUSION: In fact, the coronavirus disease 2019 pandemic had not significantly influenced therapeutic management and short-term outcomes of patients undergoing acute surgical repair of peptic ulcer perforation.

Thoracoscopic approach in the treatment of thoracic duct injuries - case reports and review of the literature.

Thoracic duct injuries are very rare due to its protected location. Duct is most often injured in polytraumas and during operations in his vicinity. Treatment is primarily conservative, based on a low-fat diet or parenteral nutrition and adequate chest drainage. If the conservative management fails, a surgical duct ligation via thoracotomy, or more conveniently thoracoscopic approach, is necessary. The presented case reports describe the surgical treatment of isolated injury of the thoracic duct via thoracoscopic approach.

Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small-cell lung cancer: an international multicenter study.

The tissue distribution and prognostic relevance of subtype-specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small-cell lung cancer (SCLC). The expression of subtype-specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype-specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines. Besides SCLC-A (ASCL1-dominant), SCLC-AN (combined ASCL1/NEUROD1), SCLC-N (NEUROD1-dominant), and SCLC-P (POU2F3-dominant), IHC and cluster analyses identified a quadruple-negative SCLC subtype (SCLC-QN). No unique YAP1-subtype was found. The highest overall survival rates were associated with non-neuroendocrine subtypes (SCLC-P and SCLC-QN) and the lowest with neuroendocrine subtypes (SCLC-A, SCLC-N, SCLC-AN). In univariate analyses, high ASCL1 expression was associated with poor prognosis and high POU2F3 expression with good prognosis. Notably, high ASCL1 expression influenced survival outcomes independently of other variables in a multivariate model. High POU2F3 and YAP1 protein abundances correlated with sensitivity and resistance to standard-of-care chemotherapeutics, respectively. Specific correlation patterns were also found between the efficacy of targeted agents and subtype-specific protein abundances. In conclusion, we investigated the clinicopathological relevance of SCLC molecular subtypes in a large cohort of surgically resected specimens. Differential IHC expression of ASCL1, NEUROD1, and POU2F3 defines SCLC subtypes. No YAP1-subtype can be distinguished by IHC. High POU2F3 expression is associated with improved survival in a univariate analysis, whereas elevated ASCL1 expression is an independent negative prognosticator. Proteomic and cell viability assays of human SCLC cell lines revealed distinct vulnerability profiles defined by transcription regulators. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Obesity paradox in patients undergoing lung lobectomy - myth or reality?

BACKGROUND: The aim of the present study was to evaluate the impact of BMI on the short-term outcomes of patients undergoing lung lobectomy. METHODS: This was a retrospective clinical cohort study conducted in a single institution to assess the short-term outcomes of obese patients undergoing lung resection. Intraoperative and postoperative parameters were compared between the two study subgroups: obese (BMI ≥30 kg/m2) and non-obese patients (BMI < 30 kg/m2). RESULTS: In total, 203 patients were enrolled in the study (70 obese and 133 non-obese patients). Both study subgroups were comparable with regards to demographics, clinical data and surgical approach (thoracoscopy vs. thoracotomy). The surgery time was significantly longer in obese patients (p = 0.048). There was no difference in the frequency of intraoperative complications between the study subgroups (p = 0.635). The postoperative hospital stay was similar in both study subgroups (p = 0.366). A 30-day postoperative morbidity was higher in a subgroup of non-obese patients (33.8% vs. 21.7%), but the difference was not significant (p = 0.249). In the subgroup of non-obese patients, a higher frequency of mild and severe postoperative complications was observed. However, the differences between the study subgroups were not statistically significant due to the borderline p-value (p = 0.053). The 30-day postoperative mortality was comparable between obese and non-obese patients (p = 0.167). CONCLUSIONS: Obesity does not increase the incidence and severity of intraoperative and postoperative complications after lung lobectomy. Slightly better outcomes in obese patients indicate that obesity paradox might be a reality in patients undergoing lung resection.

Intrathoracic splenosis - lesson learned: a case report.

BACKGROUND: Intrathoracic splenosis presents an extremely rare thoracic lesion occurring after a simultaneous rupture of the spleen and diaphragm as a consequence of heterotopic autotransplantation and implantation of splenic tissue. Intrathoracic splenosis is usually an asymptomatic, incidental finding, which should be ideally managed without surgical intervention. CASE PRESENTATION: We present a case of 68-year old woman with intrathoracic splenosis. Patient presented with a 2-month history of a dry cough unresponsive to administered antibiotics and antimycotics. Computed tomography (CT) of the chest revealed two homogeneous pleural nodules (diameters of 2 and 4 cm) in the left upper lung field. Two consequent CT-assisted transthoracic core-cut biopsies were performed. Histopathology examination of both biopsy specimens was inconclusive (haemorrhagic and non-specific tissue). After that, patient was referred to the department of thoracic surgery with a suspicion of malignant mesothelioma or metastatic lesions. Thoracoscopic revision of the left pleural cavity was performed and the presence of pleural nodules was confirmed. Bloody looking nodules were resected (standard thoracoscopic resection). Postoperative recovery was uneventful. The histopathology examination of the specimen showed normal splenic tissue. Only with the histopathology report in hand, a detailed medical history was taken. It revealed a gunshot injury requiring splenectomy (without known diaphragm or lung injury) 44 years ago (one of the longest time periods in the literature). CONCLUSIONS: We would like to point out that following the recommendations regarding splenosis may be very difficult in daily routine practice. The simple question regarding abdominal trauma in a patient's history can lead the clinician to the diagnosis of splenosis, which can be unequivocally established via scintigraphy. The importance of thorough medical history taking, therefore, cannot be underestimated.

Quality of life after laparoscopic and open resection of colorectal cancer.

BACKGROUND: The aim of the study was to evaluate quality of life (QOL) outcomes after colorectal surgery for cancer from a 6-month perspective at a single institution. METHODS: Cohort study to prospectively assess postoperative QOL in patients who underwent elective colorectal resection at the University Hospital Ostrava. QOL was assessed using the validated Short Form 36 (SF-36v2™) questionnaire at fixed time points. RESULTS: A total of 148 patients were enrolled in the study (83 and 65 patients underwent laparoscopic and open colorectal resection, respectively). Operative time was significantly longer (161 vs. 133 min; p = 0.0073) and length of hospital stay was significantly shorter (10.7 vs. 13.1 days; p = 0.0451) in the laparoscopic group. Overall 30-day morbidity rates were lower in the laparoscopic group, but the difference was not significant (27.7 vs. 33.8%; p = 0.2116). QOL scores were comparable in both study groups before surgery (p ≥ 0.05). QOL was statistically significantly lower 2 days and 1 week after open colorectal surgery compared with laparoscopic surgery. One month and 6 months after surgery, there were no statistically significant differences between groups. CONCLUSION: The present study suggests a higher postoperative QOL during the first month after laparoscopic colorectal resection could be one of the benefits of laparoscopy.

[Bronchobiliary fistulae as a complication of hepatic cystic echinococcosis]. / Bronchobiliární pístel jako komplikace echinokokové cysty jater.

Cystic hydatid disease or cystic echinococcosis (CE) rarely occurs in the Czech Republic. In 2005 - 2009, eleven cases were recorded, mostly among immigrants from the Balkans. Presented here is a case report of a 38-year-old patient with hepatic CE complicated by bronchobiliary fistulae. Ten days before surgical removal of the hydatid cysts, treatment with mebendazole was started. During surgery the affected part of the lungs was resected and the liver cysts were drained using transthoratic access. The follow-up was complicated by leakage of bile into the pleural cavity. The leakage was associated with continued communication between the liver cyst and the pleural cavity which did not close spontaneously after removal of the drain. Endoscopic nasobiliary drainage decreased pressure in the bile duct and within 14 days, it led to the spontaneous closure of the communication between the liver cyst and the pleural cavity. Seven months after the operation, the patient was in a very good clinical condition.