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Background: Head and neck small-cell carcinoma (HNSmCC) is a rare and aggressive cancer with a high tendency for distant metastasis. It is treated with multimodal treatment involving chemotherapy. Occasionally, surgery is performed for the management of locoregional HNSmCC. However, the benefits of surgery in this context have not yet been elucidated. Therefore, in this study, we aimed to investigate whether surgery could improve the survival of patients with HNSmCC., Patients and Methods: We obtained data from patients with locoregional HNSmCC treated with chemoradiation therapy (CRT) from the Surveillance, Epidemiology, and End Results database. Patients who did and did not undergo surgery were matched using propensity scores. The overall survival (OS) and disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios (HRs) were calculated using the Cox proportional hazard model., Results: The 5-year OS rates of the patients who did and did not undergo surgery were 57.2% and 50.6%, respectively (P = 0.689); the corresponding 5-year DSS rates were 61.0% and 57.5% (P = 0.769). The adjusted HRs for surgery were 0.85 (95% confidence interval [CI]: 0.54-1.33) for OS and 0.87 (95% CI: 0.51-1.49) for DSS., Conclusion: The addition of surgery to CRT did not improve the survival of patients with locoregional HNSmCC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hosokawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Abstract: Postpneumonectomy syndrome (PPS) is a rare, life-threatening complication characterized by dynamic airway obstruction due to mediastinal rotation at any time point following pneumonectomy. This can produce life-threatening respiratory and cardiovascular complications. We report a case who developed PPS following right pneumonectomy in a 55-year-old female patient with small cell carcinoma (SCC) right lung., (Copyright © 2024 Copyright: © 2024 Annals of Cardiac Anaesthesia.)

Small cell carcinoma of the bladder (SCCB) is a rare cancer that accounts for approximately 1% of primary malignant bladder tumors. It is highly malignant and has a poor prognosis. Similar to small cell lung cancer, platinum-based chemotherapy is recommended as the first-line therapy, and amrubicin (AMR) is recommended as the second-line therapy, but there is no established therapy after the second line. We report a case of SCCB that was refractory to multiple chemotherapies but responded to pembrolizumab. A 77-year-old male, diagnosed with clinical stage T3N0M0 small cell carcinoma and invasive urothelial carcinoma by transurethral resection of bladder tumor (TURBT), underwent robot-assisted radical cystectomy after three cycles of neoadjuvant cisplatin-irinotecan chemotherapy, and pathological examination revealed only small cell carcinoma in his cystectomy specimen. After three courses of adjuvant carboplatin-etoposide chemotherapy, the patient developed liver and bone metastases. Furthermore, after two courses of amrubicin, we started pembrolizumab due to the progression of metastases. Metastases decreased after starting pembrolizumab and continued to decrease after discontinuation because of immunerelated adverse events (irAEs). Therefore, pembrolizumab may be an option for the treatment of refractory SCCB.

Small-cell neuroendocrine carcinoma of the cervix (SCNCC) is a rare and aggressive tumor with a poor prognosis. Surgical resection followed by adjuvant therapy is the standard treatment for early-stage disease but the influence of different neo/adjuvant treatment approaches remains unclear. Retrospectively, we collected patients' characteristics and treatments in two medical centers. Disease status and survival outcomes were renewed through follow-up. Statistics analysis mainly included Kaplan-Meier methods for survival curve estimation, log-rank test for survival curve comparison, and Cox proportional hazards models for independent prognostic factors prediction. Finally, 51 patients treated by radical surgery between January 2010 and April 2020 were enrolled with a median age of 50 years (range: 32-68). 12 (23.5%) patients were at stage IIIC1 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging systems and the rest were at the early stage. The mean tumor size was 3.6±1.3 cm. Pathological examination found 24 cases with pure SCNCC and 27 cases with admixed SCCC. 29 (56.9%) patients had deep stromal infiltration and 19 (37.3%) patients had lymphovascular space invasion. 34 (66.7%) patients received neo/adjuvant chemotherapy and pelvic radiation was conducted in 41 (80.39%) patients with a median dose of 46 Gy (range: 40-50.4 Gy). The median follow-up time was 25.0 months. The median disease-free survival (DFS) time was 23.0 months. 27 (52.9%) patients developed distant metastasis and 14 (27.5%) experienced local failure. The median overall survival (OS) was 32.0 months. Univariate and multivariate analysis showed neoadjuvant chemotherapy as negative (HR=2.081, 95% CI 1.030-4.203, p=0.041) and adjuvant chemotherapy (HR=0.409, 95% CI 0.213-0.784, p=0.020) as positive independent prognostic factor for DFS. For OS, only lymph node metastasis was confirmed as an independent prognostic factor in both univariate analysis (HR=1.528, 95% CI 1.011-2.308, p=0.044) and multivariate analysis (HR=1.697, 95% CI 1.041-2.768, p=0.034). In conclusion, for surgically treated SCNCC, adjuvant chemotherapy showed a positive influence on DFS while neoadjuvant chemotherapy harmed DFS. OS was unaffected by either treatment choice.

Background: This study aimed to investigate the efficacy of surgery in the treatment of small cell carcinoma of the esophagus (SCCE) and explore potential prognostic factors., Methods: We screened patients with SCCE who underwent esophagectomy from 2010 to 2018 at three institutes. Differences in survival were analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were identified using univariate and multivariate analyses., Results: A total of 69 patients were included. Multivariate analysis showed that TNM stage (hazard ratio [HR]: 4.10, 95% confidence interval [CI]: 1.57-10.75, p = 0.004) and adjuvant therapy (HR: 0.28, 95% CI: 0.16-0.51, p < 0.001) were independent prognostic factors. Stage I, stage IIA, and stage IIB disease were merged into the surgery response disease (SRD), whereas stage III disease into the surgery nonresponse disease (SNRD). The SRD group had significantly improved survival compared to the SNRD group (HR: 0.33, 95% CI: 0.19-0.58, p < 0.001). In addition, adjuvant therapy increased survival benefit in the SNRD group (p < 0.001) but not in the SRD group (p = 0.061)., Conclusions: Surgery alone appears to be adequate for disease control in the SRD group, whereas multimodality therapy was associated with improved survival in the SNRD group., (© 2022 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Small cell carcinoma of the ovary (SCCO) is a rare type of ovarian cancer with high aggressiveness. The optimal treatment modality remains elusive. This study aims to comprehensively investigate the survival impact of clinical characteristics and treatments including lymphadenectomy in SCCO. A retrospective cohort study was performed and included patients from the Surveillance, Epidemiology, and End Results (SEER) database. Data collected included demographics, therapeutic details, and pathologic characteristics. Propensity-score matching analysis (PSM) was carried out to balance baseline variables between SCCO and non-SCCO. Cox regression, Kaplan-Meier, and stratified analyses were conducted before and after PSM. After filtering, 80 records on SCCO and 39,662 records on non-SSCO were obtained. Patients with SCCO were more prone to present unilateral tumor (57.6% and 85.0%, p < 0.001), larger tumor size (>15 cm: 9.5% and 32.5%; 10-15 cm: 13.2% vs. 22.5%, p < 0.001), younger age (59.1 ± 14.91 vs. 37.2 ± 19.05; p < 0.001), single status (17.0% vs. 45.0%; p < 0.001), single malignant tumor in a lifetime (76.1% vs. 87.5%; p = 0.0244), and pathologic grade IV diseases (14.5% vs. 40.0%; p < 0.001) compared with non-SCCO. After balancing the baseline clinical characteristics with a 1:4 ratio PSM, a total of matched 72 patients with SCCO and 254 patients with non-SCCO were identified. The survival rate of SCCO was distinctly inferior to non-SCCO, particularly in FIGO I, II, and III stages. Lymphadenectomy was performed in 37 (51.39%) SCCO patients, of whom 12 (32.43%) were found to have pathologically positive lymph nodes. Lymphadenectomy was linked to favorable overall survival in SCCO, particularly in the advanced stage, and was also an independent prognostic factor, whereas lymphadenectomy did not reveal an edge in matched non-SCCO. There was a pronounced survival benefit for SCCO when at least 10 or more nodes were resected. Lymphadenectomy in a non-stage-dependent way should be considered and deserves further clinical validation to promote the overall survival in SCCO.

Background: The optimal treatment approach for limited-stage small cell carcinoma of the esophagus remains uncertain. This study aimed to evaluate the efficacy and safety of preoperative chemotherapy in combination with surgery vs upfront surgery in those patients., Methods: From June 2001 to June 2015, a total of 280 patients with limited-stage small cell carcinoma of the esophagus were screened from 60 131 patients with esophageal cancer. Outcome analysis of those patients who underwent preoperative chemotherapy in combination with surgery or upfront surgery was conducted. The primary end point was overall survival, and secondary end points included progression-free survival and safety., Results: Of the 280 patients, 200 were men (71.4%), the median age was 64 years (range, 42-75 years), 171 patients (61.1%) patients had preoperative chemotherapy in combination with surgery, and 109 patients (38.9%) underwent upfront surgery. A pathologic complete response rate of 8.8% was noted in patients who received preoperative chemotherapy. Compared with the upfront surgery group, the preoperative chemotherapy group had a better median overall survival (26.0 months vs 19.5 months, respectively; hazard ratio, 0.69; 95% CI, 0.51 to 0.92; P = .011) and a prolonged progression-free survival (16.0 months vs 13.0 months, respectively; hazard ratio, 0.75; 95% CI, 0.57 to 0.99; P = .039). Postoperative complications and peritreatment mortality were comparable between both groups., Conclusions: Compared with upfront surgery, preoperative chemotherapy in combination with surgery improves overall survival in patients with limited-stage small cell carcinoma of the esophagus., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Thymic neuroendocrine tumours are rare anterior mediastinal neoplasms often associated with paraneoplastic syndromes. A patient presented with intractable hyponatraemia and a DOTATATE-avid mediastinal mass. Following medical optimization, she underwent thoracoscopic thymectomy with en bloc thymic small-cell carcinoma resection. Her symptoms resolved and her sodium levels normalized. In localized disease, curative-intent, minimally invasive thymic neuroendocrine tumour resection is safe and effective following preoperative staging and paraneoplastic syndrome management., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

A 60-year-old woman was not accompanied by any symptom. She had a gallstone which was identified 20 years prior. Ultrasonography performed by a local doctor revealed that the gallbladder was filled with small stones, and the patient was referred to our department for further examination and treatment for gallbladder stone. Tumor markers are elevated. Contrast- enhanced CT revealed gallbladder stones and thickening in the gallbladder body. PET-CT showed abnormal accumulation of FDG-PET with SUVmax 3.6 in the body of the gallbladder. With a diagnosis of gallbladder cancer, extended cholecystectomy and gallbladder bed resection with regional lymph node dissection were performed. The tumor was diagnosed histologically as small cell type neuroendocrine carcinoma of the gallbladder(pT2a[SS], pN0, pStage ⅡA; Japanese society of hepato-biliary-pancreatic surgery, the 7th edition). The postoperative course was uneventful. This patient has been followed up for 8 years without obvious signs of recurrence. R0 resection and lack of lymph node metastasis can allow long- term survival.

Objective: To compare the prognostic value of International Federation of Gynecology and Obstetrics (FIGO) 2009 and 2018 staging systems in surgical patients with small cell neuroendocrine carcinoma of the cervix (SCNEC)., Methods: We re-staged 64 surgical IB-IIA (FIGO 2009) SCNEC patients according to the FIGO 2018 system and refined stage IIIC of FIGO 2018 based on tumor local invasion. The prognostic factors were analyzed, and the advantages of FIGO 2018 were compared with 2009., Results: The 5-year overall survival rate (OS) was 78.5% for stage I and 22.2% for stage II (FIGO 2009). In FIGO 2018, there was no difference between stage I and II, and the 5-year OS was 74.1%, 60.2%, and 0% for stage I/II, IIIC1, and IIIC2. After combining stage IIIC with the local invasion stage (T1 was limited to the cervix and vagina; T2 involved the parametrium; T3 involved the pelvic or abdominal cavity), the 5-year OS for stage IIICT1, IIICT2, and IIICT3 was 83.3%, 30.0%, and 0%, respectively., Conclusions: For stage II SCNEC patients, FIGO 2009 underestimated the prognosis, while FIGO 2018 was more accurate. For stage IIIC, FIGO 2018 might be more individualized and accurate after combining stage IIIC with tumor local invasion.

Objective: To analysis the prognosis related factors of patients with small cell cancer of the esophagogastric junction treated by surgery. Methods: The clinicopathologic data of 129 patients with small cell cancer of the esophagogastric junction underwent surgery treatment in the Fourth Hospital of Hebei Medical University from January 2004 to December 2010 were retrospectively analyzed. Univariate survival survival was performed by Kaplan-Meier method and Log rank test. Multivariate survival was analyzed by using Cox proportional hazard model. Results: Radical surgery was performed in 123 patients, whereas other 6 cases were conducted palliative operation. The 5-year overall survival (OS) rate of this cohort was 21.0% and median survival time was 25.7 months. The 5-year progression free survival (PFS) rate of this cohort was 11.0% and median PFS time was 19.1 months. The univariate analysis result showed that operation manner, radical or not, tumor length, lymph node metastasis, TNM stage, intravascular cancer embolus surgical margin positive or not, the expression of Syn, comprehensive treatment and radiochemotherapy after progression were associated with the OS of these patients ( P <0.05). Multivariate analysis result showed that lymph node metastasis, radiochemotherapy after progression were independent risk factors of OS ( P <0.05). Univariate analysis result showed that operation manner, radical or not, tumor length, TNM stage, lymph node metastasis, intravascular cancer embolus, surgical margin positive or not, the expression of Syn, comprehensive treatment and radiochemotherapy after progression were associated with PFS ( P <0.05). Multivariate analysis showed that lymph node metastasis and radiochemotherapy after progression were independent risk factors of PFS ( P <0.05). Conclusions: The prognosis of small cell cancer of the esophagogastric junction patients remains poor. Lymph node metastasis and radiochemotherapy after progression are regarded as independent prognostic factors of these patients.

Background: A combined transcranial and transfacial approach has long been the gold standard for surgical management of large tumors with sinonasal and skull base involvement. The extended endoscopic endonasal approach for such pathologies has its advantages, but it has flaws as well, such as anatomic limitations and more ponderous skull base reconstruction and thus higher risk of postoperative complications. Our primary technique for surgical treatment of these pathologies has been a combination of transfacial and minimally invasive transciliary supraorbital keyhole approaches. With the aim to further minimize invasiveness, potential complications, and unsatisfactory aesthetic outcomes during surgical treatment of large tumors invading both the sinonasal area and the skull base, we abandoned the transfacial approach and simultaneously combined the transciliary supraorbital keyhole approach with the endoscopic endonasal approach., Methods: The well-known microscope-assisted minimally invasive approach via a transciliary supraorbital keyhole craniotomy was combined with the endoscopic endonasal approach., Results: Six patients with different histologic types of tumors affecting the sinonasal area and the skull base were operated on. The mean operative time was 3 hours, there were no unexpected intraoperative or postoperative complications, and total tumor removal was achieved in each patient. None of the patients experienced complications associated with the surgery during follow-up., Conclusions: Our combined simultaneous multiportal approach enables total tumor eradication with reduced operative time and is associated with minimal intraoperative and postoperative complications, low mortality rate, and excellent cosmetic results., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

p16 is generally considered to be a surrogate maker of human papillomavirus (HPV) infection and also a predictive marker of favorable clinical outcome of patients with squamous cell carcinoma of the oropharynx. p16 overexpression is also known to be induced by deregulation of RB1 in neuroendocrine carcinomas. In highly malignant esophageal neoplasms, however, the status of p16 has remained largely unknown. We immunolocalized p16 and Rb1 in 82 surgically resected esophageal high-grade squamous cell carcinomas (46 poorly differentiated and 36 basaloid squamous cell carcinomas) and 15 esophageal small-cell carcinomas in order to clarify the clinical and biological significance of p16. p16 immunoreactivity was detected in 7/82 (9%) high-grade squamous cell carcinomas and 15 (100%) small-cell carcinomas. p16 immunoreactivity was significantly associated with Rb1 protein loss in both groups (P < 0.001). HPV was detected in none of the p16-positive cases examined. Clinical outcome of the p16-positive high-grade squamous cell carcinomas was not different from that of the p16-negative counterparts (P = 0.687) but significantly better than those with the small-cell carcinomas (P = 0.023). p16 was therefore considered to be induced through an inactivation of the RB1 signaling pathway and not through HPV infection in highly malignant esophageal neoplasms. Nevertheless, patients' clinical outcome of these neoplasms significantly differs; therefore, small-cell carcinomas have to be carefully differentiated from other neoplasms. In addition, p16 overexpression is not predictive of favorable clinical outcome in high-grade squamous cell carcinomas of the esophagus.

Competing Interests: Competing interests: None declared.

Background: Primary small cell carcinoma of the esophagus (SCCE) is a rare and extremely fatal disease. We aim to evaluate the efficacy of radical surgery for resectable SCCE and to explore potential prognostic factors., Methods: We retrospectively reviewed 52 consecutive SCCE patients who underwent radical surgery from February 1993 to November 2014 at a single institution. The Kaplan-Meier estimator with log-rank test was used to assess overall survival (OS), disease-free survival (DFS) and median survival time. Univariate and multivariable analyses were used to evaluate prognostic factors through Cox proportional hazard regression model., Results: Twenty-five (48.1%) patients were treated with surgery alone, whereas 27 (51.9%) patients underwent adjuvant therapy after surgery. The median OS time was 17.4 months (95% CI: 13.5-21.3). The median DFS time was 13.4 months (95% CI: 7.7-19.0). Patients whose tumors were located in the lower part of thoracic esophagus and the esophagogastric junction showed significantly better OS (27.0 vs. 13.2 months, P = 0.016) and DFS (27.0 vs. 11.3 months, P = 0.017) than those located in the upper and middle parts. Patients with N0 status experienced significantly better OS (21.4 vs. 11.6 months, P = 0.012) and DFS (21.4 vs. 8.6 months, P = 0.012) than those with N+ status. Patients whose tumor lengths were shorter than 5 cm had a better OS (17.4 vs. 5.7 months, P = 0.035) than those longer than 5 cm. Patients who underwent chemotherapy experienced a significantly improved OS (21.0 vs. 14.1 months, P = 0.032) compared to surgery alone. Multivariable analysis showed that lower tumor location, shorter tumor length, pN0 status and chemotherapy independently predicted better OS; lower tumor location and pN0 status independently predicted better DFS., Conclusions: Radical surgery in combination with chemotherapy has better outcomes than surgery alone for resectable SCCE. Higher tumor location, longer tumor length, lymph node metastasis and not undergoing chemotherapy independently predict worse prognoses.

Primary esophageal small cell carcinoma (PESCC) is a weakly prevalent but lethal malignancy with early metastasis and a poor prognosis. Currently, neither effective prognostic indicators nor curative therapies are available for PESCC. Immunotherapy has now evolved into one of the most promising therapies for cancer patients. Tumor-infiltrating immune cells which are integral to the tumor immune microenvironment (TIME) are recognized as highly important for prognosis prediction, while the responsiveness to immune checkpoint blockade may be subject to the features of TIME. In this study, we aim to identify the TIME and provide indication for the applicability of immune checkpoint therapy in PESCC. We found that PD-L1 expression was detected in 33.33% (27/81) of all the patients, mostly exhibiting a stroma-only pattern and that it was positively associated with tumor-infiltrating immune cells (CD4 + , CD8 + , and CD163 + ). In 74.07% of PD-L1-positive specimens, PD-L1 + CD163 + cells were colocalized more with CD4 + than CD8 + T cells. 83.95% (68/81) of all the specimens were infiltrated with more CD4 + than CD8 + T cells. Further analysis showed FoxP3 + Tregs constituted 13-27% of the total CD4 + T cell population. The Kaplan--Meier analysis indicated several factors that contribute to poor survival, including negative PD-L1 expression, rich CD4 expression, rich FoxP3 expression, a low CD8/CD4 ratio, and a high FoxP3/CD8 ratio. A nomogram model was constructed and showed good performance for survival prediction. These results highlight that a suppressive TIME contributes to poor survival of patients with PESCC. TIME analyses might be a promising approach to evaluate the possibility and effect of immune checkpoint-based immunotherapeutics in PESCC patients., Competing Interests: The authors declare that they have no potential conflict of interests., (Copyright © 2020 Xiao Wu et al.)

Diagnosis of malignant uterine tumor with continuous lesions from the uterine body to the cervix, i.e., endometrial or cervical cancer, depends on the main site of the lesions. However, it may be difficult to differentiate advanced cancer that is widespread in the uterus. We experienced a patient who was diagnosed with small cell neuroendocrine carcinoma (SCNEC) based on histopathological characteristics of SCNEC in the endometrium. This tumor frequently coexists with endometrioid carcinoma, but we had difficulty finding the original site of SCNEC in the endometrium. The patient was a 59-year-old, two-parous woman who underwent hysterectomy after diagnosis of malignant uterine tumor. Preoperative cervical and endometrial histology permitted diagnosis of SCNEC. Imaging showed that most of the anterior uterine wall from the uterine body to cervix was replaced by tumors. Histopathologic findings for the resected uterus showed that most of these tumors were SCNEC, but components of endometrioid carcinoma had developed from the endometrium just beneath the fundus to the lower uterine body. The growth pattern of endometrioid carcinoma was endophytic. Based on this finding, the patient was diagnosed with endometrial SCNEC associated with endometrioid carcinoma. The patient initially responded well after postoperative chemotherapy, but early recurrence led to death at three months after the first treatment. This case shows that SCNEC in the uterine body is likely to coexist with endometrioid carcinoma. These findings are useful to determine the original site in postoperative pathological diagnosis of highly advanced tumors. SCNEC is a rapidly progressive and aggressive tumor in clinical practice, but some cases have a relatively good initial response to chemotherapy and it is important to start treatment early.

Background/aim: Primary small cell neuroendocrine carcinoma (SCNEC) of the adrenal gland is extremely rare with limited reports in the literature. There remain no definitive treatment guidelines, largely due to the rarity of the malignancy., Case Report: We present the case of a 62-year-old Caucasian male who presented with low back pain and was found to have a large retroperitoneal mass arising from the left adrenal gland, measuring 18.3 × 12.2 centimeters (cm). Biopsy was consistent with small cell carcinoma/high grade neuroendocrine carcinoma. Staging workup including CT chest and bone scan was negative. The patient was treated with chemotherapy, radiation therapy, and surgery; complete pathological response of the left adrenal tumor was achieved. Surveillance imaging every three months continued to show no evidence of recurrent disease., Conclusion: Primary SCNEC of the adrenal gland is rare and lacks standard treatment guidelines. Our case represents a possible treatment approach that may provide better clinical outcomes, however, further investigations are necessary to help define ideal treatment guidelines., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: The study aimed to analyze the clinicopathological features, treatment, and prognosis factors of primary esophageal small-cell carcinoma (PESC). Methods: The clinical records and follow-up data of 100 patients with PESC were collected, and the clinicopathological features and treatments were examined. Log-rank test and Cox regression model were performed to identify the independent prognostic factors. Results: Progressive dysphagia, weight loss, and abdominal pain were the most common initial symptoms in the 100 patients with PESC. The primary tumor site mainly occurred in the middle of the chest (51%, 51/100), and the ulcer type was the most common under gastroscope (31%, 31/100). One or more positive markers of epithelial origin were present in all of the enrolled patients. At the time of diagnosis, 80 cases had limited disease (LD) and 20 cases had extensive disease (ED). The 1-, 3-, and 5-year survival rates of PESC patients were 57.0%, 18.0%, and 11.0%, respectively, with a median survival time (MST) of 13.8 months. In all PESC patients, multivariate Cox regression analysis indicated that the significant prognostic factors included the lesion length ( OR =2.661, P <0.001), TNM staging ( OR =1.464, P =0.016), and treatment methods ( OR =0.333, P <0.001). Besides, in patients with LD, the lesion length ( OR =2.638, P =0.001) and treatment methods ( OR =0.285, P <0.001) were independent prognostic factors. The MST of patients in surgery + chemotherapy group (21.6 months) was longer than that of the surgery only group (8.3 months, P =0.021), while patients in surgery+ chemotherapy+ radiotherapy group were also associated with a longer MST than the chemotherapy + radiotherapy group (31.0 months, 9.8 months, respectively; P <0.001). Conclusions: PESC is a rare esophageal malignant tumor with poor prognosis. Our findings reveal that the lesion length, TNM staging, and treatment method are independent prognostic factors for PESC patients. Moreover, surgery-based comprehensive treatments may prolong the survival of patients with LD.

Primary small cell carcinoma (SCC) of the pancreas is a rare disease with poor prognosis. Very few cases have been reported in the literature. It is a type of poorly differentiated variety of neuroendocrine tumours of the pancreas with specific immunohistochemical markers. Imaging is not diagnostic for disease, and diagnosis is mainly by biopsy. We report a rare case of SCC of the pancreas who presented with features of obstructive jaundice without any paraneoplastic features. The patient is planned for palliative chemotherapy because of metastasis and is under regular follow-up., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Small cell carcinoma of the esophagus (SCCE) is an uncommon but lethal disease characterized by dismal prognosis. Only 10% of advanced SCCE patients survive longer than 1 year. Resection is a choice for limited-stage cases, whereas the optimal treatment regimen for primary SCCE is yet to be elucidated. To the best of our knowledge, the efficacy of S-1 plus apatinib for irinotecan-refractory SCCE has not been reported before., Patient Concerns: A 61-year old, previously healthy male was admitted for dysphagia and fatigue. Endoscopic biopsy revealed a tumor in the middle third of the esophagus. Further exams including abdomen computed tomography excluded distant metastasis., Diagnoses: Primary SCCE (pT1bN1M0, IIB) was established after salvage operation., Interventions: The tumor was enlarged after 1 cycle of first-line chemotherapy using irinotecan plus cisplatin, which indicated drug resistance. Second-line oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval) for a month showed efficacy, as shown by decreased serum neuron-specific enolase and stable of the esophageal lesion. Thereafter, salvage minimally invasive Ivor-Lewis esophagectomy and 2-field lymph node dissection was performed, followed by oral apatinib plus S-1 at the prior dosage for 6 months. In addition, maintenance therapy using low-dose apatinib (250 mg daily) plus S-1 (40 mg, twice daily for 4 weeks with a 2-week interval) were administered for another 6 months. Then the patient was followed up irregularly at the outpatient clinic., Outcomes: The adverse events including hand-foot syndrome, hypertension, vomiting, leukopenia, impaired hepatic function, and fatigue were mainly tolerable. Forty months after the operation, he was readmitted for back pain and disseminated bone metastases appeared in magnetic resonance images. His progression-free survival could not be obtained precisely, and his overall survival was longer than 40 months up to September 2019., Lessons: S-1 plus apatinib followed by a timely esophagectomy with curative intent might be an alternative option for chemotherapy-refractory SCCE in selected patients. Better evidence is warranted.

Background: The side-to-side anastomosis was considered a promising approach to create an intrathoracic esophagogastrostomy in the minimally invasive esophagectomy, with advantages over the side-to-end anastomosis with aspects of no need for additional mini-thoracotomy and lower occurrence of stenosis. The hand-sewing anterior aspect of the anastomosis is technically challenging in the thoracoscopic Ivor Lewis esophagectomy. Here we introduced our initial experience to facilitate this approach by using the surgical robot and barbed suture., Methods: A retrospective study of all patients underwent robot-assisted Ivor Lewis esophagectomy with side-to-side esophagogastrostomy from February 2016 to September 2018 was performed. The technical details are described in this paper., Results: A total of 37 patients (35 male and 2 female, median age of 62.7 years) were successfully treated with completely robot-assisted Ivor Lewis esophagectomy. The median total surgical time was 340 minutes including 65 minutes to perform the anastomosis. Median estimated blood loss was 120 mL and the length of hospital stay was 10 days. There was no 90-day mortality. Three patients suffered anastomotic leakage (8.1%,3/37), who were successfully treated without reoperation., Conclusion: Our initial results imply that it is technically feasible to perform intrathoracic gastroesophageal anastomosis by taking advantage of a robotic system and knotless suturing., (© 2019 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc.)

Objective: To determine the prognostic effect of adjuvant radiation and clinicopathological variables in surgically treated patients with small cell carcinoma of the cervix (SCCC)., Methods: Clinical data of SCCC patients with International Federation of Gynaecology and Obstetrics (FIGO) stage I-II underwent radical surgery from May 2000 to August 2014 at Sun Yat-sen Memorial Hospital were retrospectively reviewed. Forty-three patients with SCCC were included to this study. Chi-square test or Fisher's exact test, Student's t test or Mann-Whitney U test, Kaplan-Meier method and multivariate analysis of Cox proportional hazards regression were used for statistical analysis. P < 0.05 was considered to be statistically significant., Results: Among 43 patients (median age, 49 years old) recruited, 25(58.1%) had stage I, 18(41.9%) had stage II disease. The 5-year overall survival (OS) rate was 39.54%, and the 5-year disease free survival (DFS) was 27.91%. Distant metastasis was the main cause of treatment failure (71.9%). Patients with adjuvant chemoradiation displayed lower rate of local recurrence than those with adjuvant chemotherapy (10.7% vs 60.0%, P < 0.0001). Multivariable analysis identified lymph node metastasis as a significant prognostic factor for both DFS and OS (P = 0.001, 0.004 respectively). Age was also an independent predictor of OS (P = 0.004). Adjuvant radiation appeared to significantly improve DFS (HR = 0.383, 95% CI, 0.185-0.791), but not OS., Conclusions: Adjuvant radiotherapy could improve the local control and prolong DFS in surgically treated SCCC. However, a large prospective clinical trial is needed to confirm this.

Postoperative vision loss is a rare complication. When visual loss does occur, it is rarely associated with ophthalmoplegia. We report a case of postoperative bilateral visual field deficits with concomitant complete bilateral ophthalmoplegia in a patient with a known pituitary macroadenoma after surgical excision of a small cell carcinoma of the bladder. Emergency postoperative imaging showed that the macroadenoma had increased in size and was associated with new right optic nerve edema. The patient underwent urgent excision of the macroadenoma 5 days after the onset of symptoms. Visual field deficits and associated ophthalmoplegia had completely resolved at 3-month follow-up.

Objective: We conducted a retrospective, multi-institutional, collaborative study to accumulate cases of neuroendocrine carcinoma of the endometrium, to clarify its clinicopathologic features, treatment, prognosis and prognostic factors to collate findings to establish future individualized treatment regimens. To our knowledge, this is the largest case study and the first study to statistically analyze the prognosis of this disease., Methods: At medical institutions participating in the Kansai Clinical Oncology Group/Intergroup, cases diagnosed at a central pathologic review as neuroendocrine carcinoma of the endometrium between 1995 and 2014 were enrolled. We retrospectively analyzed the clinicopathologic features, treatment, prognosis and prognostic factors of this disease., Results: A total of 65 cases were registered from 18 medical institutions in Japan. Of these, 42 (64.6%) cases were diagnosed as neuroendocrine carcinoma of the endometrium based on the central pathological review and thus included in the study. Advanced International Federation of Gynecology and Obstetrics stages (stage III and IV) and pure type small cell neuroendocrine carcinoma cases had a significantly worse prognosis. Upon multivariate analysis, only histologic subtypes and surgery were significant prognostic factors. Pure type cases had a significantly worse prognosis compared to mixed type cases and complete surgery cases had a significantly better prognosis compared to cases with no or incomplete surgery., Conclusion: Our findings suggest that complete surgery improves the prognosis of neuroendocrine carcinoma of the endometrium. Even among cases with advanced disease stages, if complete surgery is expected to be achieved, clinicians should consider curative surgery to improve the prognosis of neuroendocrine carcinoma of the endometrium., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Introduction : Authors present their 7-year experience since the introduction of minimal-invasive (VATS) lobectomies for lung cancer in regard to their surgical technique, results and oncological follow-up. Method: 173 VATS lobectomies were performed between June 2011 and December 2017, 105 men and 68 women. The mean age of patients was 64.1 years. Duration of surgery was 130 minutes on average. Results: Conversion to thoracotomy was required in 8 cases (3 bleedings, 3 pulmonary vessel lymph node infiltrations, 2 bronchial suture insufficiencies). Twenty persistent air leaks developed postoperatively, requiring 10 re-drainages and 10 re-operations: 7 re-VATS and 3 thoracotomies. Two hematomas were evacuated by re-VATS, 1 postoperative atrial fibrillation required cardioversion. There were no perioperative deaths. The 164 malignant cases were: 110 adenocarcinomas, 32 squamous cell carcinomas, 6 small cell neuroendocrine carcinomas, 4 undifferentiated carcinomas, 4 carcinoid tumours, 1 synchronous adenocarcinoma and squamous cell carcinoma, 1 synchronous adenocarcinoma and small cell carcinoma, 1 carcinosarcoma and 5 metastasis from other primary tumours. 118 patients received adjuvant chemotherapy. Tumour staging distribution was: IA 40, IB 53, IIA 29, IIB 16 and IIIA 21 cases. During an average follow-up time of 19.5 months, 9 local tumour recurrence and 27 distant metastasis evaluated, of which 11 were pulmonary (3 multiplex), 10 bone, 6 cerebral, 3 hepatic (1 multiplex), and 3 suprarenal gland. Conclusion: Our results correlate with published literature. During the period of this review, VATS lobectomies became a routine surgical technique in our department. Our experience proved that axillary thoracotomy is an advantage to learn the anterior VATS lobectomy technique.

Background: Bipartite combined oesophageal tumours are an exceedingly rare entity and much less is known about the natural history of these tumours following curative surgery. The authors present a case of a bipartite combined oesophageal tumour comprising of sarcomatoid carcinoma and small cell carcinoma with early postoperative recurrence., Case Presentation: A 63-year-old Chinese male with a smoking history presents with hemoptysis on a background of dysphagia and odynophagia for 1 month. An endoscopic evaluation found an exophytic oesophageal tumour with contact bleeding for which biopsy of this lesion returned as a malignant high-grade tumour where immunohistochemistry staining was unable to establish the lineage of the tumour. Differential diagnoses include sarcomatoid carcinoma and malignant undifferentiated sarcoma. With the provisional diagnosis of a high-grade oesopheageal sarcoma, the patient underwent minimally invasive McKeown's oesophagectomy. Final histological assessment was pT1bN0 with two histological types of malignancy within a single tumour-70% poorly differentiated spindle cell squamous carcinoma and small cell carcinoma. He was planned for adjuvant chemotherapy in view of the small cell carcinoma component after the resolution of the postoperative infective collections. A computed tomographic scan performed 4 months postoperatively demonstrated metastasis to the lung, pleura, thoracic nodes and liver. Biopsy of the largest lung nodule confirmed small cell neuroendocrine carcinoma with features similar to the small cell carcinoma component in the prior oesophagectomy specimen. He was thereafter initiated on palliative chemotherapy aimed at three weekly carboplatin and etoposide aimed at a total of 4 cycles with peglasta support. Etoposide was stopped during the first cycle due to asymptomatic bradycardia. The regime was then converted to carboplatin with irinotecan for 5 cycles. Repeat computed tomographic scan performed 3 weeks after the completion of chemotherapy showed a complete response of lung and liver metastasis and no evidence of local recurrence or distant metastasis., Conclusion: The management of bipartite combined oesophageal tumours should be guided by its more aggressive component. Bipartite combined oesophageal tumours with a small cell carcinoma component are believed to demonstrate aggressive tumour biology likened to that of primary oesophageal small cell carcinoma. Preoperative confirmation of a combined tumour may be challenging, and biopsy results may only yield one of the two components. The more aggressive component is usually a small cell carcinoma, for which the mainstay of therapy is platinum-based chemotherapy rather than surgery.

Objectives: Thrombus formation in the pulmonary vein stump after left upper lobectomy is supposedly a risk factor for systemic thrombosis, resulting in a critical course for the patient. The purpose of this study was to assess the efficacy of the proximal ligation method preventing thrombus formation and thrombosis comparing the two groups of patients (those who did and those who did not undergo pulmonary vein ligation)., Methods: We performed a surgical procedure to shorten the pulmonary vein stump in the left upper lobectomy. In this procedure, we first dissected the pericardium from the left upper pulmonary vein, and then we ligated the pulmonary vein at the pericardial reflection before stapling transection., Results: In the group that was not treated with the proximal ligation method, thrombus formation in the pulmonary vein stump was detected in all four cases. In contrast, thrombus formation in the pulmonary vein stump was detected in one only case of the eight cases treated with the proximal ligation method, which was significantly fewer than among those not treated with the ligation method (p = 0.010). The logistic regression analysis revealed in both the univariate (p = 0.0014) and multivariate analyses (p = 0.0071) that the proximal ligation method was significantly associated with reduced thrombus formation in the pulmonary vein stump., Conclusions: Thrombus formation in the pulmonary vein stump was significantly reduced by ligating the pulmonary vein at the pericardial reflection.

Rationale: Primary extrapulmonary small-cell carcinoma (SCC) of appendix is reported very rarely. We report herein a case of mixed SCC and adenocarcinoma of appendix., Patient's Concern: A 70-year-old female was consulted to our Emergency Department with the right lower abdominal pain and low-grade fever for 2 days., Diagnosis: Abdominal ultrasonography revealed the perforated appendicitis with periappendiceal abscess. Postoperative histology confirmed the diagnosis of mixed SCC and adenocarcinoma., Interventions: After laparoscopic appendectomy, she underwent right hemicolectomy for radical surgery., Outcomes: Laparoscopic appendectomy was performed and histological examination showed mixed SCC and adenocarcinoma. After confirming that there was no other organ metastasis, right hemicolectomy was performed for radical surgery. Five months after surgery, the patient expired due to multiple organ metastases., Lessons: Further studies are required for better understanding of disease entities, and clinical trials are needed to define adequate treatment strategies for extrapulmonary SCC.

Background: Colorectal neuroendocrine tumors are a rare malignancy, yet their incidence appears to be increasing. The optimal treatment for the high-grade subset of these tumors remains unclear. We aimed to examine the relationship between different treatment modalities and outcomes for patients with high-grade neuroendocrine carcinomas (HGNECs) of the colon and rectum., Methods: The National Cancer Database (2004-2015) was used to identify patients diagnosed with colorectal HGNECs. The primary outcome was overall survival. A Cox Proportional hazard model was used to identify risk factors for survival., Results: Overall, 1208 patients had HGNECs; 452 (37.4%) patients had primary tumors of the rectum, and 756 (62.5%) patients had primary tumors of the colon. A total of 564 (46.7%) patients presented with stage IV disease. The median survival was 9.0 months [95% confidence interval (CI) 8.2-9.8]. In multivariable analysis, surgical resection [hazard ratio (HR) 0.54, 95% CI 0.44-0.66; p < 0.001], chemotherapy (HR 0.74, 95% CI 0.69-0.79; p < 0.001), and rectum as the primary site of tumor (HR 0.62, 95% CI 0.51-0.76; p < 0.001) were associated with better overall survival, while older age (HR 1.01, 95% CI 1.00-1.01; p = 0.02) and the presence of metastatic disease (HR 3.34, 95% CI 2.69-4.15; p < 0.001) were associated with worse survival., Conclusions: Patients with colorectal HGNECs selected for chemotherapy and surgical resection of the primary tumor demonstrated better overall survival than those managed without resection. Patients who were able to undergo systemic chemotherapy may benefit from potentially curative resection of the primary tumor.

Esophageal small cell carcinoma (E-SmCC) and basaloid squamous cell carcinomas (BSCCs) are both highly aggressive malignancies, but their detailed differences in clinical behaviors have remained virtually unknown. In addition, treatment strategies of the patients with E-SmCC have not been established. 29 cases of E-SmCC and 39 with BSCC were examined in this study to clarify the clinical features and outcome of the patients with E-SmCC and to compare the findings with those of BSCC. E-SmCCs presented a more advanced status than BSCC (TNM Stage: P = .002). Esophagectomy was performed in 15 small cell carcinoma patients and 14 were treated with non-surgical/systemic therapy. The clinical outcome of the small cell carcinoma cases was significantly worse than those with BSCC (P = .001), but results of a stage-stratified analysis revealed that the Stage I small cell carcinoma patients presented favorable prognosis (3-year survival rate 100%, n = 4). In contrast, among those with Stage II-IV, clinical outcome tended to be better in the systemic therapy group (3-year survival rate 49%, n = 13) than the surgically treated group (3-year survival rate 0%, n = 12). E-SmCC was a more aggressive neoplasm than BSCC. However, early detection could possibly improve the clinical outcome of patients with E-SmCC. Systemic therapy could also benefit the patients with advanced disease (Stage II-IV).

Purpose: To determine a subset of women who could undergo ovary-sparing radical cystectomy (OSRC) for bladder cancer without compromising oncologic safety., Patients and Methods: A retrospective review was performed of 164 consecutive women who underwent cystectomy at a single tertiary-care center from 1997 to 2018. Clinicopathologic and preoperative radiographic data were reviewed. Univariable and multivariable logistic regression models adjusting for pathologic stage, lymphovascular invasion (LVI), and carcinomain-situ were performed to evaluate the risk of ovarian and reproductive organ (RO) involvement., Results: A total of 123 women with a median age of 71 years underwent radical cystectomy (RC) with removal of ROs for primary bladder cancer. Nineteen women (15%) had RO involvement by bladder cancer, and 5 of them (4%) were specifically found to have ovarian involvement. Patients with ovarian involvement of bladder cancer had more locally advanced disease (P = .01), LVI (P = .003) and positive margins (P = .003). On multivariable logistic regression, ≥ pT3 (odds ratio = 10.2; 95% confidence interval, 2.0-51.6; P = .005) and LVI (odds ratio = 3.9; 95% confidence interval, 1.1-14.2; P = .037) were associated with increased risk of RO involvement. Among 15 patients excluded for having a nonbladder primary malignancy, a third had RO involvement, and 2 (13%) had ovarian metastases. No women in our cohort had a primary ovarian malignancy detected at the time of RC., Conclusion: Women with ovarian involvement by malignancy at the time of RC either had locally advanced disease with LVI or a non-bladder primary malignancy. The risk of incompletely resecting the primary malignancy would be rare if OSRC was performed on women with organ-confined (≤T2) urothelial carcinoma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The patient was a 59-year-old man with type 2 advanced gastric cancer in the antrum. Abdominal computed tomography revealed the primary tumor with regional lymph node metastasis. Distal gastrectomy and D2 lymph node dissection were performed. Histopathological findings indicated gastric small cell carcinoma. Lymph node metastasis was observed microscopically in the #6 lymph nodes. Peritoneal lavage cytology was positive. The pathologic stage of the disease was pT2(MP), med, INF b, ly2, v2, pPM0, pDM0, pN2(6/33: #5, #6), M1, P0, CY1, H0, stage Ⅳ, R1(cy+). After surgery, he received chemotherapy with capecitabine plus oxaliplatin. However, after 1 course of therapy the disease had progressed, and the patient was diagnosed with peritoneal metastasis. Chemotherapy of CDDP plus CPT-11 was initiated, and after 5 courses the patient died.

Programmed death ligand 1 (PD-L1) is a transmembrane protein that plays a major role in immune suppression. Its interaction with the receptor PD-1 results in downregulation of antitumoral immunity. Humanized monoclonal antibodies that interrupt the PD-L1/PD-1 interaction have shown therapeutic efficacy in patients with advanced urothelial cancer. However, immunohistochemical staining of PD-L1 in bladder tumors and its relationship to tumor histologic type, grade, and overall survival has been incompletely analyzed. Slides from 165 cystectomy specimens were reviewed for tumor type, grade of urothelial carcinoma, pathologic stage, and overall survival. A tissue microarray (TMA) using four 0.6 mm cores from each case was constructed. Immunohistochemistry was performed on the TMA using a variety of new PD-L1 antibodies and platforms now widely available. For each case, the percent of tumor cells positive for PD-L1 and the percent of positive immune cells were scored. The overall number of bladder cancers positive for PD-L1 depended on the antibody/platform combination used and the threshold for considering a tumor "PD-L1-positive." Squamous cell carcinomas (SCCs) of the bladder demonstrated PD-L1 positivity more frequently than urothelial cell carcinomas (UCCs). High-grade UCCs were positive for PD-L1 on tumor cells more frequently than low-grade UCCs. There was no difference in survival between PD-L1-positive and PD-L1-negative bladder cancers in our study. Further studies should consider examining the predictive significance of PD-L1 IHC in bladder cancers., (Copyright © 2018 Elsevier Inc. All rights reserved.)