Influence of ABO blood group on susceptibility to different pathological types of lung cancer: a retrospective study.

PURPOSE: Current research has shown a link between ABO blood group and many diseases. The purpose of this study aimed to investigate the influence of the ABO blood group on the risk of developing different pathological types of lung cancer. MATERIALS AND METHODS: This retrospective study was composed of 7681 patients with lung cancer and 12, 671 non-lung cancer patients who were admitted to the First Affiliated Hospital of Nanchang University from January 2016 to January 2021. The subjects with lung cancer were grouped into small cell lung cancer group (n = 725), lung adenocarcinoma group (n = 4520), and lung squamous cell carcinoma group (n = 2286) according to pathological types. The ABO blood group distribution of each lung cancer type group was compared with that of the control group. Statistical analysis was determined with chi-square and logistic regression. RESULTS: Univariate analysis showed that the ABO blood group distribution of lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer was different from that of the control group (P < 0.01). After adjusting for age, sex, smoking history, and drinking history, logistic regression analysis showed that the risk of lung adenocarcinoma in blood type O was higher than that in blood type A (P < 0.01). There was no significant difference in ABO blood group composition between small cell lung cancer group, lung squamous cell carcinoma group, and control group (P > 0.05). In addition, gender and age have an influence on all three types of lung cancer (P < 0.01). Smoking was a risk factor in lung squamous cell carcinoma and small cell carcinoma (P < 0.01). Alcohol consumption was a risk factor in lung adenocarcinoma (P < 0.01). CONCLUSION: ABO blood group may be correlated with the occurrence of lung adenocarcinoma in Jiangxi province, but not with lung squamous cell carcinoma and small cell carcinoma.

Increased activity of procoagulant factors in patients with small cell lung cancer.

Small cell lung cancer (SCLC) patients have augmented risk of developing venous thromboembolism, but the mechanisms triggering this burden on the coagulation system remain to be understood. Recently, cell-derived microparticles carrying procoagulant phospholipids (PPL) and tissue factor (TF) in their membrane have attracted attention as possible contributors to the thrombogenic processes in cancers. The aims of this study were to assess the coagulation activity of platelet-poor plasma from 38 SCLC patients and to provide a detailed procoagulant profiling of small and large extracellular vesicles (EVs) isolated from these patients at the time of diagnosis, during and after treatment compared to 20 healthy controls. Hypercoagulability testing was performed by thrombin generation (TG), procoagulant phospholipid (PPL), TF activity, Protein C, FVIII activity and cell-free deoxyribonucleic acid (cfDNA), a surrogate measure for neutrophil extracellular traps (NETs). Our results revealed a coagulation activity that is significantly increased in the plasma of SCLC patients when compared to age-related healthy controls, but no substantial changes in coagulation activity during treatment and at follow-up. Although EVs in the patients revealed an increased PPL and TF activity compared with the controls, the TG profiles of EVs added to a standard plasma were similar for patients and controls. Finally, we found no differences in the coagulation profile of patients who developed VTE to those who did not, i.e. the tests could not predict VTE. In conclusion, we found that SCLC patients display an overall increased coagulation activity at time of diagnosis and during the disease, which may contribute to their higher risk of VTE.

Pan-cancer Convergence to a Small-Cell Neuroendocrine Phenotype that Shares Susceptibilities with Hematological Malignancies.

Small-cell neuroendocrine cancers (SCNCs) are an aggressive cancer subtype. Transdifferentiation toward an SCN phenotype has been reported as a resistance route in response to targeted therapies. Here, we identified a convergence to an SCN state that is widespread across epithelial cancers and is associated with poor prognosis. More broadly, non-SCN metastases have higher expression of SCN-associated transcription factors than non-SCN primary tumors. Drug sensitivity and gene dependency screens demonstrate that these convergent SCNCs have shared vulnerabilities. These common vulnerabilities are found across unannotated SCN-like epithelial cases, small-round-blue cell tumors, and unexpectedly in hematological malignancies. The SCN convergent phenotype and common sensitivity profiles with hematological cancers can guide treatment options beyond tissue-specific targeted therapies.

Spread Through Air Spaces (STAS) Is Prognostic in Atypical Carcinoid, Large Cell Neuroendocrine Carcinoma, and Small Cell Carcinoma of the Lung.

INTRODUCTION: Tumor spread through air spaces (STAS) has prognostic significance in lung adenocarcinoma and squamous cell carcinoma. We sought to investigate the prognostic importance of STAS in lung neuroendocrine tumors (NETs). METHODS: All tumor slides from patients with resected pathologic stage I to III lung NETs (N = 487) (299 with typical carcinoid [TC], 38 with atypical carcinoid [AC], 93 with large cell neuroendocrine carcinoma [LCNEC], and 57 with SCLC) treated between 1992 and 2012 were evaluated for presence of STAS. Cumulative incidence of recurrence (CIR) and lung cancer-specific cumulative incidence of death (LC-CID) were analyzed by using a competing-risks approach. RESULTS: STAS was identified in 26% of NETs (16% of TCs, 37% of ACs, 43% of LCNECs, and 46% of SCLCs). STAS was associated with distant metastasis, as well as with higher CIR and LC-CID in the overall cohort and in the AC, LCNEC, and SCLC cohorts (owing to a small number of recurrences and deaths [<5], prognostic analysis was not performed in the TC cohort). In multivariable analysis stratified by stage, STAS was significantly associated with higher CIR (subhazard ratio = 2.85, 95% confidence interval: 1.73-4.68, p < 0.001) and LC-CID (subhazard ratio = 2.72, 95% confidence interval: 1.57-4.70, p < 0.001), independent of histologic subtype. STAS was independently associated with CIR and LC-CID in the LCNEC cohort and LC-CID in the SCLC cohort. CONCLUSIONS: In patients with lung NETs, STAS is associated with early distant metastasis and worse LC-CID. In patients with LCNEC or SCLC, STAS is an independent poor prognostic factor.

Small cell carcinoma of the kidney: a case report and analysis of data from the Surveillance, Epidemiology, and End Results registry.

BACKGROUND: Primary small cell carcinoma of the kidney is an extremely rare neoplasm. The clinical features of small cell carcinoma of the kidney are not well established due to its rarity and scarcity of case reports. We present an unusual case of small cell carcinoma of the kidney complicated by syndrome of inappropriate antidiuretic hormone secretion. We identify cases using a population-based dataset from the Surveillance, Epidemiology, and End Results registry and compare small cell carcinoma of the kidney with small cell carcinoma of the lung. CASE PRESENTATION: A 69-year-old Filipino man presented with hematuria for 1 month. A computed tomography scan demonstrated a large left kidney mass with biopsy demonstrating small cell carcinoma. Within 2 months he developed dizziness and was found to have a metastatic lesion to his brain. He was hyponatremic due to syndrome of inappropriate antidiuretic hormone secretion. He did not receive chemotherapy due to his poor functional status. He died within 8 months of presentation. RESULTS: From 1973 to 2013, 60 cases with small cell carcinoma of the kidney were identified in the Surveillance, Epidemiology, and End Results registry. Most (62%) presented with extensive stage, which occurred predominantly in white men in their seventh decade. The median overall survival with extensive stage small cell carcinoma of the kidney was 3 months versus 11 months with limited stage of small cell carcinoma of the kidney; this was worse than small cell carcinoma of the lung with a median survival of 5 and 13 months, respectively. CONCLUSION: We present a rare case of small cell carcinoma of the kidney complicated by syndrome of inappropriate antidiuretic hormone secretion. This adds to our understanding of the clinical features of small cell carcinoma of the kidney. Furthermore, this is the first population-based study of small cell carcinoma of the kidney using the Surveillance, Epidemiology, and End Results database. Analysis shows that overall survival is worse in small cell carcinoma of the kidney relative to that of small cell carcinoma of the lung. Small cell carcinoma of the kidney presents very aggressively, and further studies are needed to develop a standard of care.

Primary small cell carcinoma after renal transplant: A case report.

INTRODUCTION: Primary small cell carcinoma (SCC) after renal transplantation is very rare. Here, we reported 1 case of primary SCC after renal transplantation and analyzed its clinical and pathological characteristics. CASE PRESENTATION: A 55-year-old female underwent renal transplantation in our hospital 2 years ago and had been using tacrolimus for immunosuppressive therapy. Because of abdominal distention, the patient was admitted to our hospital. Computed tomography (CT) showed a malignant tumor of left kidney. Patient underwent surgical treatment and radical nephrectomy and lymph node dissection were selected. Postoperative pathological diagnosis was primary renal parenchyma and ureteral SCC. The patient has been treated with combination chemotherapy of lowpol (100 mg per day) and etoposide (10 mg per day). His vital signs are stable now, and he is receiving further treatment in our hospital. CONCLUSION: Because of immunosuppressive drugs use, the incidence of malignancies has increased significantly after renal transplantation. This case highlights the difficulty of diagnosis of primary SCC and the necessity of checking for neuroendocrine tumor after organ transplantation.

A robust response to combination immune checkpoint inhibitor therapy in HPV-related small cell cancer: a case report.

BACKGROUND: Human papillomavirus-related small cell carcinoma of the head and neck is an extremely rare, aggressive subtype with poor outcomes. Therapeutic options are limited and are largely adopted from small cell lung cancer treatment paradigms. CASE PRESENTATION: This report describes a 69-year old male who was diagnosed of HPV-related oropharyngeal cancer with mixed small cell and squamous cell pathology which was clinically aggressive and progressed through multimodal platinum-based therapies. Upon manifestation of worsening metastatic disease, the patient was initiated on a combination of ipilimumab and nivolumab. Within 2 months of starting immunotherapy, a robust partial response was observed. During the treatment course, the patient developed immune-related adverse effects including new diabetes mellitus, colitis, and hypothyroidism. The disease-specific survival was 26 months. CONCLUSION: Combination immunotherapy may be an attractive option for HPV-related small cell head and neck cancers resistant to other treatment modalities and thus warrants further evaluation.

Lambert-Eaton myasthenic syndrome: mouse passive-transfer model illuminates disease pathology and facilitates testing therapeutic leads.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder caused by antibodies directed against the voltage-gated calcium channels that provide the calcium ion flux that triggers acetylcholine release at the neuromuscular junction. To study the pathophysiology of LEMS and test candidate therapeutic strategies, a passive-transfer animal model has been developed in mice, which can be created by daily intraperitoneal injections of LEMS patient serum or IgG into mice for 2-4 weeks. Results from studies of the mouse neuromuscular junction have revealed that each synapse has hundreds of transmitter release sites but that the probability for release at each one is likely to be low. LEMS further reduces this low probability such that transmission is no longer effective at triggering a muscle contraction. The LEMS-mediated attack reduces the number of presynaptic calcium channels, disorganizes transmitter release sites, and results in the homeostatic upregulation of other calcium channel types. Symptomatic treatment is focused on increasing the probability of release from dysfunctional release sites. Current treatment uses the potassium channel blocker 3,4-diaminopyridine (DAP) to broaden the presynaptic action potential, providing more time for calcium channels to open. Current research is focused on testing new calcium channel gating modifiers that work synergistically with DAP.

Small-Cell Carcinomas of the Bladder and Lung Are Characterized by a Convergent but Distinct Pathogenesis.

Purpose: Small-cell carcinoma of the bladder (SCCB) is a rare and aggressive neuroendocrine tumor with a dismal prognosis and limited treatment options. As SCCB is histologically indistinguishable from small-cell lung cancer, a shared pathogenesis and cell of origin has been proposed. The aim of this study is to determine whether SCCBs arise from a preexisting urothelial carcinoma or share a molecular pathogenesis in common with small-cell lung cancer.Experimental Design: We performed an integrative analysis of 61 SCCB tumors to identify histology- and organ-specific similarities and differences.Results: SCCB has a high somatic mutational burden driven predominantly by an APOBEC-mediated mutational process. TP53, RB1, and TERT promoter mutations were present in nearly all samples. Although these events appeared to arise early in all affected tumors and likely reflect an evolutionary branch point that may have driven small-cell lineage differentiation, they were unlikely the founding transforming event, as they were often preceded by diverse and less common driver mutations, many of which are common in bladder urothelial cancers, but not small-cell lung tumors. Most patient tumors (72%) also underwent genome doubling (GD). Although arising at different chronologic points in the evolution of the disease, GD was often preceded by biallelic mutations in TP53 with retention of two intact copies.Conclusions: Our findings indicate that small-cell cancers of the bladder and lung have a convergent but distinct pathogenesis, with SCCBs arising from a cell of origin shared with urothelial bladder cancer. Clin Cancer Res; 24(8); 1965-73. ©2017 AACRSee related commentary by Oser and Jänne, p. 1775.

[Disseminated combined small cell carcinoma with graft involvement after kidney transplantation from a deceased donor to two patients]. / Disseminirovannyi kombinirovannyi melkokletochnyi rak s porazheniem transplantatov posle peresadki pochek ot umershego donora dvum bol'nym.

The paper describes cases of disseminated small-cell carcinoma after kidney transplantation from a deceased donor to two patients. Microscopic examination showed that the kidney graft tumor consisted of tightly packed small rounded cells with hyperchromatic nuclei and a narrow cytoplasmic rim with invisible nucleoli. The mitotic index was 25-40/2 mm2. Azzopardi's phenomenon and crush artifact were detected in the tumor. Giant cell and large cell components were 30-40% of the area of sections. Immunohistochemical examination revealed the expression of synaptophysin, chromogranin A, CD56, TTF-1, HMWK, СК7, СК18, and Ki-67 (80% of tumor cells). Histological findings and immunophenotype in both cases led to the conclusion about combined small cell carcinoma with renal graft involvement. Both patients died from tumor dissemination 9 and 11 months after transplantations. In reviewing the literature, the authors found only one such observation.

Pure small cell recurrent prostate cancer developing syndrome of inappropriate antidiuretic hormone secretion.

PURPOSE: Pure small cell neuroendocrine carcinoma of the prostate is a rare entity characterized by a poor prognosis due to early metastatic spread as well as resistance to treatment. Considering its increasing occurrence, clinicians should be aware of its aggressive behavior, the relevance of an early diagnosis, and proper management. METHODS: A 71-year-old man treated with brachytherapy for localized low-risk prostate cancer developed widespread disease 7 years later with a prostate-specific antigen-negative neuroendocrine small cell phenotype. He was also diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH) soon after starting chemotherapy. RESULTS: A substantial radiologic and clinical response to chemotherapy was observed and the paraneoplastic SIADH was successfully treated with oral vaptan therapy. CONCLUSIONS: Secondary small cell prostate carcinoma is an underestimated entity with high sensitivity to chemotherapy, although a standard treatment has not yet been defined. Moreover, oral vaptans demonstrated prompt efficacy and simple management in correcting SIADH-related hyponatremia.

Small Cell Lung Cancer. Methodology and Preliminary Results of the SMALL CELL Study. / Cáncer de pulmón microcítico. Metodología y resultados preliminares del estudio SMALL CELL.

INTRODUCTION: Small cell lung cancer (SCLC) is the most aggressive histologic type of lung cancer, and accounts for approximately 10%-15% of all cases. Few studies have analyzed the effect of residential radon. Our aim is to determine the risk factors of SCLC. METHODS: We designed a multicenter, hospital-based case-control study with the participation of 11 hospitals in 4 autonomous communities. RESULTS: Results of the first 113 cases have been analyzed, 63 of which included residential radon measurements. Median age at diagnosis was 63 years; 11% of cases were younger than 50 years of age; 22% were women; 57% had extended disease; and 95% were smokers or former smokers. Median residential radon concentration was 128Bq/m3. Concentrations higher than 400Bq/m3 were found in 8% of cases. The only remarkable difference by gender was the percentage of never smokers, which was higher in women compared to men (P<.001). Radon concentration was higher in patients with stageIV disease (non-significant difference) and in individuals diagnosed at 63 years of age or older (P=.032). CONCLUSIONS: A high percentage of SCLC cases are diagnosed early and there is a predominance of disseminated disease at diagnosis. Residential radon seems to play an important role on the onset of this disease, with some cases having very high indoor radon concentrations.

Smoking, inflammation and small cell lung cancer: recent developments.

Small cell lung cancer (SCLC) accounts for 15 % of all lung tumors and represents an invasive neuroendocrine malignancy with poor survival rates. This cancer is highly prevalent in smokers and characterized by inactivation of p53 and retinoblastoma. First in vitro expansion of circulating tumor cells (CTCs) of SCLC patients allowed for investigation of the cell biology of tumor dissemination. In the suggested CTC SCLC model, the primary tumor attracts and educates tumor-promoting and immunosuppressive macrophages which in turn arm CTCs to spread and generate distal lesions. Preexisting inflammatory processes associated with chronic obstructive pulmonary disease (COPD) seem to potentiate the subsequent activity of tumor-associated macrophages (TAM). Activation of signal transducer and activator of transcription 3 (STAT3) and expression of chitinase-3-like 1/YKL-40 in SCLC CTCs seems to be associated with drug resistance. In conclusion, inflammation-associated generation of invasive and chemoresistant CTCs most likely explains the characteristic features of SCLC, namely early dissemination and rapid failure of chemotherapy.

Genitourinary small cell malignancies: prostate and bladder.

Small cell carcinoma is an aggressive malignancy often associated with dismal prognosis due to the presence of advanced disease. Small cell malignancies, initially described in the lung (small cell carcinoma of the lung), can occur in extrapulmonary sites, such as prostate (small cell carcinoma of the prostate) and bladder (small cell carcinoma of the bladder), with similar clinicopathologic outcomes. There has been a paradigm shift in the management of small cell carcinoma of the lung from initial surgical treatment to use of chemotherapy followed by local therapies. Such treatment modalities have been applied to small cell carcinoma of the prostate and the bladder, with promise in improving patient survival. Use of platinum-based combination chemotherapy followed by surgical resection and/or radiation offers the most benefit. Further investigation at the molecular level may offer targeted therapies earlier in the course of the disease.

Lung cancer risk among bricklayers in a pooled analysis of case-control studies.

Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case-control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28-1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32-1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93-1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42-1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44-2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95-1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos.

Heavy smoking and lung cancer: are women at higher risk? Result of the ICARE study.

BACKGROUND: Whether women are more or equally susceptible to the carcinogenic effects of cigarette smoke on the lungs compared with men is a matter of controversy. Using a large French population-based case-control study, we compared the lung cancer risk associated with cigarette smoking by gender. METHODS: The study included 2276 male and 650 female cases and 2780 male and 775 female controls. Lifetime smoking exposure was represented by the comprehensive smoking index (CSI), which combines the duration, intensity and time since cessation of smoking habits. The analysis was conducted among the ever smokers. All of the models were adjusted for age, department (a regional administrative unit), education and occupational exposures. RESULTS: Overall, we found that the lung cancer risk was similar among men and women. However, we found that women had a two-fold greater risk associated with a one-unit increase in CSI than men of developing either small cell carcinoma (OR=15.9, 95% confidence interval (95% CI) 7.6, 33.3 and 6.6, 95% CI 5.1, 8.5, respectively; P<0.05) or squamous cell carcinoma (OR=13.1, 95% CI 6.3, 27.3 and 6.1, 95% CI 5.0, 7.3, respectively; P<0.05). The association was similar between men and women for adenocarcinoma. CONCLUSION: Our findings suggest that heavy smoking might confer to women a higher risk of lung cancer as compared with men.

Radiation-associated small cell neuroendocrine carcinoma of the thyroid: a case report with molecular analyses.

BACKGROUND: Neuroendocrine tumor (NET) of the thyroid other than medullary carcinoma is extremely rare. We describe here a case of calcitonin-negative small cell neuroendocrine carcinoma (SCNEC), which occurred in a thyroid gland that had previously been irradiated at high dose (60 Gy) for pharyngeal cancer, with molecular analyses for follicular cell origin. PATIENT FINDINGS: The tumor cells were small with fine chromatin, inconspicuous nucleoli, and inapparent cytoplasm, and showed neuroendocrine architectures such as palisading, rosettes, and trabeculae. Mitotic figures were numerous exceeding 10 mitoses per 10 high-power fields. The tumor cells invaded into several vessels and metastasized to regional lymph nodes. Immunohistochemically, the tumor cells were strongly positive for neuroendocrine markers and thyroglobulin (Tg), a marker of thyroid follicular cells but negative for calcitonin and carcinoembryonic antigen (CEA). Expression of Tg and thyrotropin receptor (TSHR) were confirmed by quantitative real-time polymerase chain reaction (RT-PCR). Ki-67 labeling index was more than 70% in the tumor cells. Taken together, the tumor was diagnosed as SCNEC of the thyroid. Genetic analyses also revealed microsatellite abnormalities of the phosphatase and tensin homolog (PTEN) gene, suggesting that functional loss of PTEN contributes to carcinogenesis. CONCLUSIONS: This is the first report describing a SCNEC of the thyroid with molecular analyses that provide evidence for a follicular epithelial origin.

Etoposide and temozolomide in combination for the treatment of progressive small-cell lung cancer central nervous system metastases: two cases.

INTRODUCTION: Progression of central nervous system (CNS) metastases from small cell lung cancer (SCLC) after radiation therapy is associated with a poor prognosis. CASE REPORTS: We present two cases of patients with progressive CNS metastases from SCLC treated with oral temozolomide and etoposide. Sustained clinical responses and radiographic stability were demonstrated. The palliative chemotherapy regimen was well tolerated. DISCUSSION: A regimen of oral temozolomide and etoposide for progressive CNS metastases from SCLC is well tolerated and may be associated with sustained stability of disease.

Small cell carcinoma of the colon arising in a carcinoid tumor.

Small cell carcinomas of the gastrointestinal tract are rare and clinically aggressive tumors. A case is presented of a 70 year-old woman who presented with small bowel obstruction and was found to have a cecal mass. She underwent right hemicolectomy, and histopathology showed a small cell carcinoma arising in the background of a carcinoid tumor. Although small cell carcinomas of the colon have frequently been found in association with colonic adenomas, this appears to be the first report of a low-grade carcinoid tumor in combination with a small cell carcinoma.