Novel ALK immunohistochemistry assay (clone OTI1A4, Dako) is a sensitive, reliable marker for identifying ALK rearrangements in lung adenocarcinomas: A validation study.

OBJECTIVES: We present the first study validating the recent Dako ALK assay (clone OTI1A4, in vitro diagnostic) for detecting ALK rearrangements in lung adenocarcinoma. METHODS: Lung adenocarcinoma cases between 2011 and 2023 were retrospectively collected to create a cohort of 203 samples. Cases were stained with Dako ALK OTI1A4 and Ventana ALK D5F3 and reviewed by 3 pathologists independently. Correlation between assays, including their sensitivity and specificity, was evaluated. RESULTS: The cohort (n = 203) consisted of resections, core needle biopsies, and cell blocks. Agreement between Dako ALK OTI1A4 and Ventana ALK D5F3 assays was "almost perfect," with κ = 0.89. The sensitivity and specificity of the Dako ALK OTI1A4 assay were 93.3% and 96%, respectively, in a subgroup of 55 molecularly confirmed cases (n = 30 with and n = 25 without ALK rearrangement). CONCLUSIONS: Immunohistochemistry-based assays provide a valid and reasonably priced alternative, especially in settings where molecular confirmatory tests are neither offered nor accessible. Given high interassay and molecular concordance, we propose that the novel Dako OTI1A4 assay can be reliably used to identify cases with ALK rearrangement.

Results of surgical treatment of pulmonary artery sarcomas: Does histology affect survival?

Background: In this study, we aimed to describe our experience with primary pulmonary artery sarcoma in patients who underwent pulmonary endarterectomy and to evaluate clinical features, treatment, outcomes, and survival rates according to the histological subtypes of this malignant disease. Methods: Between March 2011 and May 2022, a total of 13 patients (7 males, 6 females; mean age: 52.6±13.0 years; range, 30 to 69 years) who underwent pulmonary endarterectomy and diagnosed with a pulmonary artery sarcoma were retrospectively analyzed. The diagnosis was confirmed histopathologically in all patients. Data including demographics, clinical characteristics, intra- and postoperative complications, length of hospital stay, morbidity, mortality, and short-term and long-term outcomes were recorded. Operative mortality was defined as death in the hospital or within 30 days of surgery. Results: Mortality was observed in one patient due to massive hemoptysis. Morbidity developed in two patients due to acute respiratory distress. Pulmonary vascular resistance improved significantly from 508 dyn/s/cm-5 to 191 dyn/s/cm-5 (p<0.004). All patients received chemotherapy following surgery. Median followup was 14 months. Median survival for the entire series was 18 months. One-year and three-year survival rates were 60.6% and 30.3%, respectively. Median survival for leiomyosarcomas (n=6) was seven months, while it was 44 months for intimal sarcomas (p=0.004). Three-year survival was 66.7% for intimal sarcomas and 0% for leiomyosarcomas. Conclusion: Pulmonary artery sarcoma may mimic chronic thromboembolic pulmonary hypertension. Patients with a suspected diagnosis of pulmonary artery sarcoma should be referred to expert pulmonary endarterectomy centers for surgery where a multidisciplinary team is available. Pulmonary endarterectomy has both diagnostic and therapeutic value and may improve survival and quality of life. Patients with intimal sarcoma have longer survival compared to those with leiomyosarcoma.

Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency.

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA-/-) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4+/-) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown. OBJECTIVE: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up. METHODS: The 98 patients (63 LRBA-/- and 35 CTLA4+/-) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies. RESULTS: The LRBA-/- patients exhibited a more severe disease course than did the CTLA4+/- patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA-/- patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival. CONCLUSIONS: Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation.

Optimal waiting period to surgical treatment after neoadjuvant chemoradiotherapy for locally advanced rectum cancer: a retrospective observational study.

BACKGROUND: The optimal waiting period after neoadjuvant treatment in patients with locally advanced rectal cancers is still controversial. The literature has different results regarding the effect of waiting periods on clinical and oncological outcomes. We aimed to investigate the effects of these different waiting periods on clinical, pathological, and oncological outcomes. METHODS: Between January 2014 and December 2018, a total of 139 consecutive patients with locally advanced rectal adenocarcinoma, who were treated in the Department of General Surgery at the Marmara University Pendik Training and Research Hospital, were enrolled in the study. The patients were split into three groups according to waiting time for surgery after neoadjuvant treatment: group 1 (n = 51) included patients that have 7 weeks and less (≤ 7 weeks) time interval, group 2 (n = 45) 8 to 10 weeks (8-10 weeks), group 3 (n = 43) 11 weeks and above (11 weeks ≤). Their database records, which were entered prospectively, were analyzed retrospectively. RESULTS: There were 83 (59.7%) males and 56 (40.3%) females. The median age was 60 years, and there was no statistical difference between the groups regarding age, gender, BMI, ASA score, ECOG performance score, tumor location, and preoperative CEA values. Also, we found no significant differences regarding operation times, intraoperative bleeding, length of hospital stay, and postoperative complications. According to the Clavien-Dindo (CD) classification, severe early postoperative complications (CD 3 and above) were observed in 9 patients. The complete pathological response (pCR, ypT0N0) was observed in 21 (15.1%) patients. The groups had no significant difference regarding 3-year disease-free and 3-year overall survival (p = 0.3, p = 0.8, respectively). Local recurrence was observed in 12 of 139 (8.6%) patients and distant metastases occurred in 30 of 139 (21.5%) patients during the follow-up period. There was no significant difference between the groups in terms of both local recurrence and distant metastasis (p = 0.98, p = 0.43, respectively). CONCLUSION: The optimal time for postoperative complications and sphincter-preserving surgery in patients with locally advanced rectal cancer is 8-10 weeks. The different waiting periods do not affect disease-free and overall survival. While long-term waiting time does not make a difference in pathological complete response rates, it negatively affects the TME quality rate.

Severe allergic dysregulation due to a gain of function mutation in the transcription factor STAT6.

BACKGROUND: Inborn errors of immunity have been implicated in causing immune dysregulation, including allergic diseases. STAT6 is a key regulator of allergic responses. OBJECTIVES: This study sought to characterize a novel gain-of-function STAT6 mutation identified in a child with severe allergic manifestations. METHODS: Whole-exome and targeted gene sequencing, lymphocyte characterization, and molecular and functional analyses of mutated STAT6 were performed. RESULTS: This study reports a child with a missense mutation in the DNA binding domain of STAT6 (c.1114G>A, p.E372K) who presented with severe atopic dermatitis, eosinophilia, and elevated IgE. Naive lymphocytes from the affected patient displayed increased TH2- and suppressed TH1- and TH17-cell responses. The mutation augmented both basal and cytokine-induced STAT6 phosphorylation without affecting dephosphorylation kinetics. Treatment with the Janus kinase 1/2 inhibitor ruxolitinib reversed STAT6 hyperresponsiveness to IL-4, normalized TH1 and TH17 cells, suppressed the eosinophilia, and improved the patient's atopic dermatitis. CONCLUSIONS: This study identified a novel inborn error of immunity due to a STAT6 gain-of-function mutation that gave rise to severe allergic dysregulation. Janus kinase inhibitor therapy could represent an effective targeted treatment for this disorder.

Outcome of solid and cavitary pulmonary nodules in rheumatoid arthritis patients-case series.

BACKGROUND: Rheumatoid pulmonary nodule can be detected in up to 32% of rheumatoid arthritis (RA) patients and approximately one-third of nodules may cavitate. We aimed to evaluate characteristics of patients with RA developing cavitary pulmonary nodular (CPN) lesions under disease-modifying antirheumatic drugs (DMARDs), follow-up of both cavitary and solid nodules, and their outcome with the treatment. METHODS: RA patients who presented with CPN lesions during follow-up were recruited retrospectively in this case series analysis. Total numbers and mean diameters of cavitary and solid nodules in each thorax computed tomography (CT) have been determined and followed up by two experienced pulmonary physicians. Moreover, changes in treatment after the development of the CPN lesions and characteristics of cavitary nodules were collected. RESULTS: Eleven patients with CPN lesions were reported. At the time of CPN diagnosis, more patients were taking leflunomide than methotrexate (81% vs 19%). Half of the patients were receiving biologic therapy and only 18% were taking anti-TNF drugs. After a median of 24 (3-65) months of follow-up, the regression of CPN lesions was determined in 45% (5/11) of patients. Four of these 5 (80%) patients were switched to a treatment regimen without leflunomide and three of them to nonanti-TNF biologic treatment or targeted synthetic DMARDs (tocilizumab, tofacitinib, and rituximab). DISCUSSION: CPN lesions seen in RA patients are often pulmonary manifestations of the underlying disease; however, one must rule out malignancies or infections. If lesions progress under DMARDs, it is advised to discontinue synthetic DMARDs (LEF/MTX) and switch to another biological DMARD with different modes of action.

Pulmonary artery sarcoma treated with pulmonary endarterectomy and leaflet reconstruction using Ozaki technique.

Pulmonary arterial intimal sarcomas (PAIS) are rare malignancies with a poor prognosis. Sarcomas present with signs and symptoms mimicking pulmonary thromboembolic disease, delaying the diagnosis. We present a 29-year-old male patient diagnosed with PAIS in the right and main pulmonary arteries extending to the left pulmonary leaflet. The patient was treated with pulmonary endarterectomy and pulmonary leaflet reconstruction using the Ozaki technique.

FDG PET/CT Features of Polysaccharide-Based Hemostatic Agent: Chronic Inflammatory Changes Can Mimic Metastatic Lesions.

PURPOSE: To prevent hemorrhagic complications, hemostatic agents (HAs) have been widely used in recent years. The use of HAs can lead to false-positive results on postoperative imaging. There exists only 1 study in the literature evaluating these applications during surgical procedures. Therefore, we aimed to evaluate the postoperative imaging features of polysaccharide-based HAs in thoracic surgery patients who have had 18F-FDG PET/CT scans. PATIENTS AND METHODS: Two hundred nine consecutive patients who underwent thoracic surgery were enrolled in this study. A topical polysaccharide-based HA was applied to the surgical bed for all of the patients. The patients diagnosed with cancer were followed up with subsequent thoracic CT scans, and 42 of these patients were also imaged with 18F-FDG PET/CT, which then comprised the main study group. Due to suspicion of metastasis, 19/42 patients were reoperated or rebiopsied. The latest histopathological findings were accepted as criterion standard, and previous FDG PET/CT images were retrospectively reevaluated. RESULTS: Polysaccharide-based HAs that appear as amorphous basophilic material were identified in histopathological samples of 11/19 patients. Lymphocytes, plasma cells, and histiocytes, which formed foreign body reaction and/or foreign body granuloma, indicating the presence of chronic inflammation, were seen in all of the samples. 18F-FDG PET/CT showed increased FDG uptake in all of these lesions. CONCLUSIONS: Despite the inconsistency of the literature, polysaccharide-based HAs can be demonstrated in human surgical specimens as amorphous basophilic materials even after a long time from the initial surgical procedure. These agents almost always cause chronic inflammatory changes. In addition, these agents may mimic "false-positive" findings on postoperative FDG PET/CT scans.

Diagnosis of Pulmonary Artery Sarcoma with Multi-modality Imaging.

Pulmonary artery sarcoma is an extremely uncommon malignancy with a poor prognosis. It is often difficult to distinguish it from pulmonary thromboembolic disease because of nonspe cific signs and symptoms as well as similar imaging findings. We present a 46-year-old man who had initially been diagnosed with presumed asthma that later proved to be pulmonary artery sarcoma. The patient was evaluated with multi-modality imaging studies which showed a mass in the pulmonary artery, its extension, mobility and invasion, and attachment to the artery wall. Pulmonary artery mass was excised and pulmonary artery endarterectomy was performed. The histopathological diagnosis was undifferentiated sarcoma with pleomorphic morphology.

Multimodal Approach of Isolated Pulmonary Vasculitis: A Single-Institution Experience.

BACKGROUND: Isolated pulmonary vasculitis (IPV) is a single-organ vasculitis of unknown etiology and may mimic chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to review our clinical experience with pulmonary endarterectomy in patients with CTEPH secondary to IPV. METHODS: Data were collected prospectively for consecutive patients who underwent pulmonary endarterectomy and had a diagnosis of IPV at or after surgery. RESULTS: We identified 9 patients (6 women; median age, 48 years [range, 23-55]) with IPV. The diagnosis was confirmed after histopathologic examination of all surgical materials. The mean duration of disease before surgery was 88.0 ± 70.2 months. Exercise-induced dyspnea was the presenting symptom in all patients. Pulmonary endarterectomy was bilateral in 6 patients and unilateral in 3. No deaths occurred; however 1 patient had pulmonary artery stenosis, and stent implantation was performed. All patients received immunosuppressive therapies after surgery. Mean pulmonary artery pressure decreased significantly from 30 mm Hg (range, 19-67) to 21 mm Hg (range, 15-49) after surgery (P < .05). Pulmonary vascular resistance also improved significantly from 270 dyn/s/cm-5 (range, 160-1600) to 153 dyn/s/cm-5 (range, 94-548; P < .05). After a median follow-up of 41 months, all but 1 patient had improved to the New York Heart Association functional class I. CONCLUSIONS: IPV can mimic CTEPH, and these patients can be diagnosed with pulmonary endarterectomy. Furthermore surgery has not only diagnostic but also therapeutic value for IPV when stenotic and/or thrombotic lesions are surgically accessible. A multidisciplinary experienced CTEPH team is critical for management of these unique patients.

Is There Any Role of Pulmonary Endarterectomy in Pulmonary Arterial Hydatidosis?

BACKGROUND: Hydatid cyst is a zoonosis caused by Echinococcus granulosis. Pulmonary artery involvement is a rare condition. The aim of this study was to review the investigators' experience with the surgical treatment of pulmonary arterial hydatidosis. METHODS: Data were collected prospectively for consecutive patients who underwent pulmonary endarterectomy (PEA) and who had a diagnosis of hydatidosis at or after PEA. RESULTS: A total of 8 patients (2 male and 6 female; mean age, 31.25 ± 13.68 years) with hydatidosis were defined. Only 1 patient presented with hemoptysis, whereas the rest of the patients reported exertional dyspnea as their main symptom. Cardiac hydatidosis associated with pulmonary arterial involvement was noted in 1 patient. The mean time interval for duration of disease was 12 ± 24.29 months before PEA. Mortality was observed in 2 patients as a result of massive hemoptysis in 1 patient and right-sided heart failure in the other. No anaphylactic reaction was observed. Significant difference was detected in mean pulmonary vascular resistance as a decline from 442.38 ± 474.20 dyn/s/cm-5 to 357.25 ± 285.34 dyn/s/cm-5 after PEA (P = .011). Two patients had recurrence of the disease after a median follow-up of 9.1 months All survivors improved to New York Heart Association functional classes I and II. CONCLUSION: Pulmonary arterial hydatidosis may mimic chronic thromboembolic pulmonary hypertension, and in these patients the diagnosis can be made with PEA. Pulmonary endarterectomy may be a therapeutic option for patients who do not respond to medical therapy if the cystic lesions are surgically accessible. PEA should be performed only in expert centers because of the high risk of perioperative morbidity, mortality, and postoperative recurrence.

Infiltration pattern predicts metastasis and progression better than the T-stage and grade in pancreatic neuroendocrine tumors: a proposal for a novel infiltration-based morphologic grading.

The advancing edge profile is a powerful determinant of tumor behavior in many organs. In this study, a grading system assessing the tumor-host interface was developed and tested in 181 pancreatic neuroendocrine tumors (PanNETs), 63 of which were <=2 cm. Three tumor slides representative of the spectrum (least, medium, and most) of invasiveness at the advancing edge of the tumor were selected, and then each slide was scored as follows. Well-demarcated/encapsulated, 1 point; Mildly irregular borders and/or minimal infiltration into adjacent tissue, 2 points; Infiltrative edges with several clusters beyond the main tumor but still relatively close, and/or satellite demarcated nodules, 3 points; No demarcation, several cellular clusters away from the tumor, 4 points; Exuberantly infiltrative pattern, scirrhous growth, dissecting the normal parenchymal elements, 5 points. The sum of the rankings on the three slides was obtained. Cases with scores of 3-6 were defined as "non/minimally infiltrative" (NI; n = 77), 7-9 as "moderately infiltrative" (MI; n = 68), and 10-15 as "highly infiltrative" (HI; n = 36). In addition to showing a statistically significant correlation with all the established signs of aggressiveness (grade, size, T-stage), this grading system was found to be the most significant predictor of adverse outcomes (metastasis, progression, and death) on multivariate analysis, more strongly than T-stage, while Ki-67 index did not stand the multivariate test. As importantly, cases <=2 cm were also stratified by this grading system rendering it applicable also to this group that is currently placed in "watchful waiting" protocols. In conclusion, the proposed grading system has a strong, independent prognostic value and therefore should be considered for integration into routine pathology practice after being evaluated in validation studies with larger series.

The role of adjuvant chemotherapy in resected stage I non - small cell lung cancer: A Turkish Oncology Group Study.

PURPOSE: The benefit of adjuvant chemotherapy for tumors smaller than 4 cm is not clear. We aimed to evaluate the prognostic impact of adjuvant platin-based chemotherapy in high-risk stage I patients with non-small cell lung cancer (NSCLC). METHODS: This cooperative group study included 232 NSCLC patients who underwent curative surgery for stage I disease with tumor size 2-4 cm. Re ults: Median age at presentation was 63 years (range 18-90). The mean tumor size was 29.6 ± 7.3 mm. The frequency of patients with specified risk factors were: visceral pleural effusion (VPI): n: 82 (36.6%); lymphovascular invasion (LVI): n: 86 (39.1%); Grade 3: n: 48 (32.7%); Solid micropapillary pattern (SMP): n: 70 (48.3%). Adjuvant platin-based chemotherapy was administered to 51 patients. During a median follow-up period of 50.5 months 68 patients (29.3%) developed recurrence, 54 (23.3%) died from any cause and 38 (16.4%) of them died of lung cancer. Patients who received chemotherapy compared with the non-chemotherapy group had a longer 5-years relapse-free survival (RFS) (84.5 vs 61.1%). Also on multivariate analysis, adjuvant chemotherapy was a significant independent prognostic factor for RFS. CONCLUSION: Adjuvant platin-based chemotherapy should be considered for patients with small tumors with adverse risk factors. Key words: adjuvant chemotherapy, lung cancer, oncology, lymphovascular invasion, solid-micropapillary pattern, platinum-based therapy.

Chronic thromboembolic pulmonary hypertension: evaluation of V/Q SPECT/CT and V/Q Quotient SPECT findings with postoperative results of pulmonary endarterectomy.

OBJECTIVES: We aimed to perform a comparison between V/Q single-photon emission computed tomography/computed tomography (SPECT/CT) and V/Q Quotient single-photon emission computerized tomography (SPECT) in the detection of chronic thromboembolic pulmonary hypertension (CTEPH) and in depicting the extent of the disease on per-segment basis in patients with CTEPH. METHODS: Between January 2015 and November 2019, a total of 412 patients with pulmonary hypertension secondary to CTEPH at the preoperative assessment underwent pulmonary endarterectomy (PEA), of whom 92 consecutive patients with their V/Q SPECT/CT scans have been performed in our institution prior to PEA were included in this study. Histopathological findings and post-PEA fully resected surgical specimens were used as the reference standard. RESULTS: On a per-patient basis analysis, V/Q SPECT/CT and V/Q Quotient SPECT both revealed CTEPH in the same 85 of the 92 patients (κ = 1) with a detection rate of 92.4%. In six of these patients, chronic thromboembolic disease could not be reported on both of these two methods due to extensive 'matched' V/Q defects. On a per-segment basis analysis, V/Q SPECT/CT and V/Q Quotient SPECT showed a sensitivity of 75.8 and 73.1%, respectively. Correlation analysis results showed a significant correlation (κ = 0.933) between these two methods on a per-segment basis analysis. CONCLUSION: In the light of histopathological findings and post-PEA surgical specimen examinations, the results of the present study indicated that both V/Q SPECT/CT and V/Q Quotient SPECT showed relatively high efficacy for the detection of CTEPH on per-patient and per-segment bases with an excellent agreement.

Differences in PET/CT standardized uptake values involvement and survival compared to histologic subtypes of lung adenocarcinoma.

PURPOSE: Lung adenocarcinoma is histologically diverse but has distinct histologic growth patterns. There is no consensus on the clinical benefit of this histologic model. We aimed to evaluate the differences in the distribution of the preoperative primary tumor positron emission tomography (PET)/computed tomography (CT) standardized uptake values (SUVs) and survival in the lung adenocarcinoma subtypes. METHODS: We retrospectively evaluated the data of 107 patients with resected lung adenocarcinoma who had preoperative PET/CT between 2005 and 2017 in a single center. Patients had lepidic, acinar, papillary, micropapillary, and solid histologic subtypes. We compared fluorodeoxyglucose SUVs and survival data of histologic subtypes. RESULTS: The median age of the patients was 62 years (40-75), 76.4% were male, the median SUVmax was 9.4 (1-36.7), and the median follow-up time was 29 months (3-135 months). The median overall survival (OS) was 71 months and the median progression-free survival (PFS) was 33 months. SUVmax was significantly different in histologic subtypes: values for papillary, micropapillary, solid, acinar, and lepidic subtypes were 9.7, 8, 12, 9.1, and 3.9, respectively (p = 0.000). Solid predominant adenocarcinoma had significantly higher SUVmax than the other subtypes (p = 0.001). Lepidic predominant adenocarcinoma had significantly lower SUVmax than the other subtypes (p = 0.000). There was no significant difference in OS between histologic subtypes (p = 0.66), but PFS was significantly different between the groups (p = 0.017), and the solid subtype had a shorter PFS than the other histologic subtypes. CONCLUSION: Lung adenocarcinoma consists of a diverse group of diseases. Different SUVmax values are seen in different histologic subtypes of nonmetastatic lung adenocarcinoma. Solid predominant types have high SUVmax values while lepidic predominant types have lower SUVmax values. The solid subtype had a shorter PFS than the other histologic subtypes.

Endotracheal metastasis of colon cancer on FDG PET/CT.

Although tracheal involvement of lung cancer is frequently seen, endotracheal metastasis of colon cancer is a rare entity. Since endotracheal lesion gives no symptom until tracheal lumen nearly occluded, the diagnosis of endotracheal metastasis could be challenging. F-18 fluorodeoxyglucose positron emission tomography/computed tomography may be crucial to detect this unusal distant metastasis of colon cancer. Herein, we report FDG avid endotracheal lesion that was confirmed as metastasis from colon cancer in 56-year-old female patient.

FDG-Avid Lung Nodule Formation by the Use of Hemostatic Powder: A Potential Cause of False-Positive FDG PET/CT.

ABSTRACT: FDG PET/CT is used in the diagnosis and follow-up of various malignant tumors and changes patient management in routine clinical practice. However, inflammatory, infectious, physiological, and technical causes and benign pathological conditions may lead to false-positive FDG uptake. We report a case of a 59-year-old man who was considered having a false-positive FDG-PET pulmonary nodular lesion in favor of metastasis, which was formed by the use of hemostatic powder.

The impact of tumor invasion to muscularis mucosaevascular plexus on patient outcome in pT1 bladder urothelial carcinoma.

OBJECTIVES: T1 bladder cancer has a wide range of tumor behavior and lamina propria invasion depth has a high potential risk of disease progression. To evaluate the patient outcome according to the tumor invasion to the muscularis mucosae-vascular plexus (MM-VP) in pT1 bladder urothelial carcinoma (BUC). MATERIALS AND METHODS: This study is a retrospective analysis of patients consecutively recorded from 2007 to 2013. A total of 93 patients with a history of primary pT1 BUC and complete follow-up were included. We used a pathological substaging system according to the tumor invasion regarding the MM-VP: pT1a (invasion above MM-VP) and pT1b (MM-VP invasion). We evaluated recurrence-free survival (RFS), progression- free survival (PFS), disease-specific-survival (DSS) based on this sub-staging system. RESULTS: Pathological evaluation regarding the MM-VP invasion revealed 53 patients (57%) as pT1a BUC and 40 patients (43%) as pT1b BUC. The mean follow-up was 78.8 months. During the follow-up period; 60 patients (64.5%) had tumor recurrences, 32 patients (34.4%) had progression to invasive disease, 18 patients (19.4 %) died during follow-up related to the BUC. In 29 (54.7%) of pT1a and in 31(77.5%) of pT1b tumors, the recurrent disease was recorded during the followup period (p = 0.023). DSS rates at 5 years for pT1a and pT1b were 80.2% and 60.8%, respectively. PFS, RFS, and DSS rates were similar for pT1a/pT1b and did not reach statistical significance (p > 0.05). CONCLUSIONS: Sub-staging of pT1 BUC according to the MM-VP invasion showed a limited impact on the outcome in our patient cohort. However, the presence of pT1b disease caused a significantly higher rate of recurrence.

Concordance of PD-L1 expression and CD8+ TIL intensity between NSCLC and synchronous brain metastases.

Programmed death-ligand 1 (PD-L1) is suggested to be a predictive biomarker in non-small-cell lung carcinoma (NSCLC). However, the differential expression of PD-L1 in primary lung tumor vs. synchronous metastases, especially brain metastasis (BM), remains unclear. This study assessed the concordance of PD-L1 expression on tumor cells and tumor-infiltrating lymphocytes (TILs) and CD8+ TIL intensity between primary lung tumors and synchronous BMs from 24 NSCLC patients. PD-L1, CD3, and CD8 positivity was determined by immunohistochemistry (IHC). PD-L1 scoring was based on the proportion of tumor cells with membranous expression of PD-L1 and the cutoff values <1%, 1-49%, and ≥50%. CD3 and CD8 positivity in TILs was evaluated semi-quantitatively and the proportion of CD3+/CD8+ TILs was determined. PD-L1 expression on tumor cells and TILs was evaluated in relation to CD3+/CD8+ TIL proportions and the intensity of CD8+ TILs between the paired primary lung and BM tissues. In the primary lung tumors, PD-L1 positivity was observed in 25%, 37.5%, and 37.5% cases for the cutoff values <1%, 1-49%, and ≥50%, respectively. PD-L1 expression on tumor cells was strongly correlated between the paired primary lung and BM tissues, in all cutoff groups. However, PD-L1 expression on TILs and the proportion of CD3+/CD8+ TILs were not strongly correlated in all three groups between the paired primary lung tumors and BMs. The intensity of CD8+ TILs was concordant in only 54.16% of the paired primary lung tumors and BMs. This study showed a high concordance of PD-L1 expression in neoplastic cells between primary NSCLC and synchronous BMs.

Endobronchial ultrasound transbronchial needle aspiration in elderly patients: safety and performance outcomes EBUS-TBNA in elderly.

AIM: Complication rates are low and endobronchial ultrasound guided needle aspiration (EBUS-TBNA) is generally regarded as a safe procedure, but there is a very limited number of studies evaluating the efficacy and safety of the procedure in advanced ages. The aim of this study is to assess the safety and performance outcomes of EBUS-TBNA in elderly. METHODS: It was a retrospective observational study; patients who received EBUS-TBNA between September 2016 and January 2018 were evaluated. We analyzed patient's characteristics, doses of midazolam, and lidocaine used, regions of lymph node biopsies, and complications. Also, functionality and general physical status of patients over 65 years of age were evaluated. RESULTS: During study period 132 cases of EBUS-TBNA were evaluated. 39 (29.5%) cases were aged 70 years, and over. There were more comorbidities in older group. Performance status of older group was worse. Furthermore, when evaluated according to American College of Cardiology (ACC)/American Heart Association (AHA) and American Society of Anesthesiologists (ASA), the older group was found to be composed of the riskier patients. When patients aged between 65 and 69, and over 70 compared, older patient's Barthel, EQ 5-D, SGA, and G8 scores were found to be worse. Despite that, there was no difference in the frequency, and types of complications between both groups. Diagnostic performance was not different between age groups. CONCLUSIONS: Independent from comorbidities, general health status, and functionality EBUS-TBNA procedure in 70-year-old and over patients is a safe minimally invasive procedure.