Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

Systemic treatments for resectable carcinoma of the esophagus

One of the most prevalent malignancies in the world is esophageal cancer(EC).The 5-year survival rate of EC remains pitiful despite treatment advancements.Neoadjuvant chemoradiotherapy in conjunction with esophagectomy is the standard of care for patients with resectable disease.The pathological complete response rate,however,is not acceptable.A distant metastasis or a locoregional recurrence will occur in about half of the patients.To increase the clinical effectiveness of therapy,it is consequently vital to investigate cutting-edge and potent therapeutic modalities.The approach to the management of resectable EC using immunotherapy has been considerably altered by immune checkpoint inhibitors.Systemic immunotherapy has recently been shown to have the potential to increase the survival of patients with resectable EC,according to growing clinical data.A combination of chemotherapy,radiation,and immunotherapy may have a synergistic antitumor impact because,according to mounting evidence,these treatments can stimulate the immune system via a number of different pathways.In light of this,it makes sense to consider the value of neoadjuvant immunotherapy for patients with surgically treatable EC.In this review,we clarify the rationale for neoadjuvant immunotherapy in resectable EC patients,recap the clinical outcomes of these approaches,go through the upcoming and ongoing investigations,and emphasize the difficulties and unmet research requirements.

Endoscopic treatment of Barrett's esophagus:From metaplasia to intramucosal carcinoma

The annual incidence of adenocarcinoma arising from Barrett’s esophagus (BE) is approximately 0.5%. Through a process of gradual transformation from lowgrade dysplasia to high-grade dysplasia (HGD), adenocarcinoma can develop in the setting of BE. The clinical importance of appropriate identifi cation and treatment of BE in its various stages, from intestinal metaplasia to intramucosal carcinoma (IMC) hinges on the dramatically different prognostic status between early neoplasia and more advanced stages. Once a patient has symptoms of adenocarcinoma, there is usually locally advanced disease with an approximate 5-year survival rate of about 20%. Esophagectomy has been the gold standard treatment for BE with HGD, due to the suspected risk of harboring occult invasive carcinoma, which was traditionally estimated to be as high as 40%. In recent years, the paradigm of BE early neoplasia management has recently evolved, and endoscopic therapies (endoscopic mucosal resection, radiofrequency ablation, and cryotherapy) have entered the clinical forefront as acceptable non-surgical alternatives for HGD and IMC. The goal of endoscopic therapy for HGD or IMC is to ablateall BE epithelium (both dysplastic and non-dysplastic) due to risk of synchronous/metachronous lesion development in the remaining BE segment.

Human papillomavirus in squamous cell carcinoma of esophagus in a high-risk population

AIM: To investigate the relation of human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) in Iranian patients as compared to normal controls. METHODS: Using MY09/MY11 consensus primers, we compared the prevalence of a HPV L1 gene in tumor tissues from 38 ESCC cases and biopsied tissues from 38 endoscopically normal Iranian individuals. We also compared the presence of HPV16 and HPVA18 in the same samples using type-specific E6/E7 primers. RESULTS: Fourteen (36.8%) of the 38 ESCC samples but only 5 (13.2%) of the 38 control samples were positive for the HPV L1 gene (P= 0.02). Five (13.2%) of the ESCC samples but none of the control samples were positive for the HPV16 E6/E7 gene (P= 0.05). Three (7.9%) of the ESCC samples and 5 (13.2%) of the control samples were positive for the HPV18 E6/E7 gene (P= 0.71). CONCLUSION: Our data are consistent with HPV DNA studies conducted in other high-risk areas for ESCC. HPV should be considered as a potential factor contributing to the high incidence of ESCC in Iran and other high-incidence areas of the world.

Metastatic basaloid-squamous cell carcinoma of the esophagus treated by 5-fluorouracil and cisplatin

Basaloid squamous cell carcinoma （BSC） of the esophagus is a rare malignant disease. We report here a patient with recurrent esophageal BSC, who was successfully treated by systemic chemotherapy containing 5-fluorouracil （5-FU） and cisplatin （CDDP）. A 57-year-old woman was diagnosed as having SCluamous cell carcinoma of the esophagus upon endoscopic examination. Curative esophagectomy with lymph node dissection was performed under the thoracoscope. The pathological diagnosis of the surgical specimen was BSC. Five months after operation, the patient was diagnosed as having a recurrence of the BSC with metastases to the liver and spleen, and a right paraclavicular lymph node. She was given systemic chemotherapy consisting of continuous infusion of 800 mg/d of 5-FU and 3 h infusion of 20 mg/d of CDDP for 5 consecutive days every 4 wk. The metastatic lesions in the spleen and right paraclavicular lymph node disappeared, and the liver metastasis was apparently reduced in size after 2 courses of chemotherapy. The tumor regression was seen over 6 courses, with progression afterwards. Although subsequent treatment with CPT-11 and CDDP was not effective, docetaxel and vinorelbine temporarily controlled the tumor growth for 2 mo. 5-FU and CDDP combination may be useful for the patients with advanced BSC.

Genitourinary small-cell carcinoma： 11-year treatment experience

The predictive factors of prognosis and treatment strategies for small-cell carcinoma （SCC） of the urinary tract are controversial. This study was aimed to investigate the clinical experience and management of patients with SCC of the urinary tract. We collected data of patients who were diagnosed with genitourinary SCC （GSCC） between 2002 and 2013 and were treated in the Fudan University Shanghai Cancer Center. A total of 18 patients were diagnosed with GSCC of which 10 originated from the prostate, seven from the bladder and one from the adrenal gland. The mean follow-up time was 15.5 months and progression-free survival （PFS） was 9.3 months. Primary tumor resection was attempted in 13 of 18 patients （72.2%） in whom radical surgery was performed in six of 14 （42.9%） limited disease patients. Most of the patients （13, 72.2%） received cisplatin-based chemotherapy. Patients who had normal lactic dehydrogenase （LDH） levels showed a significantly higher median PFS and overall survival （OS） compared with patients with high LDH levels （P = 0,030, P = 0.010）. Patients with limited disease treated with a radical operation experienced a non-significant （P = 0,211） longer PFS compared with patients who were not treated, but this reached statistical significance after analyzing OS （P = 0.211, P = 0.039）. Our patients showed a poor prognosis as reported previously. Serum LDH levels beyond the normal range indicate a poor prognosis. For GSCC patients who are diagnosed with limited disease, radical surgery is strongly recommended along with cisplatin-based chemotherapy,

Primary adenosquamous carcinoma of the esophagus

AIM:To investigate the clinical characteristics,diagnosis,treatment,and prognosis of primary adenosquamous carcinoma(ASC)of the esophagus.METHODS:A total of 4015 patients with esophageal carcinoma underwent surgical resection between January 1995 and June 2012 at the Cancer Hospital of Shantou University Medical College.In 37 cases,the histological diagnosis was primary ASC.Clinical data were retrospectively analyzed from these 37 patients,who underwent transthoracic esophagectomy with lymphadenectomy.Theχ2or Fisher’s exact test was used to compare the clinicopathological features between patients with ASC and those with squamous cell carcinoma(SCC).The Kaplan-Meier and Log-Rank methods were used to estimate and compare survival rates.A Cox proportional hazard regression model was used to identify independent prognostic factors.RESULTS:Primary esophageal ASC accounted for0.92%of all primary esophageal carcinoma cases(37/4015).The clinical manifestations were identical to those of other types of esophageal cancer.All of the 24patients who underwent preoperative endoscopic biopsy were misdiagnosed with SCC.The median survival time(MST)was 21.0 mo(95%CI:12.6-29.4),and the1-,3-,and 5-year overall survival rates were 67.5%,29.4%,and 22.9%,respectively.In multivariate analysis,only adjuvant radiotherapy(HR=0.317,95%CI:0.114-0.885,P=0.028)was found to be an independent prognostic factor.The MST for ASC patients was significantly lower than that for SCC patients[21.0 mo(95%CI:12.6-29.4)vs 46.0 mo(95%CI:40.8-51.2),P=0.001].In subgroup analyses,the MST for ASC patients was similar to that for poorly differentiated SCC patients.CONCLUSION:Primary esophageal ASC is a rare disease that is prone to be misdiagnosed by endoscopic biopsy.The prognosis is poorer than esophageal SCC but similar to that for poorly differentiated SCC patients.

Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus–Di?erences in Etiology, Epidemiology and Prevention

In Germany, esophageal carcinoma is one of the ten most frequent causes of death. Normally the disease is found in men over the age of 50. Although squamous cell carcinoma (SCC) of the esophagus has been more commonly diagnosed over the past 30 years, there is increasing incidence of esophageal adenocarcinoma (AC) in Western industrialized countries. For SCC the known etiological risk factors are nicotine and alcohol abuse. For AC, they are moderate nicotine and alcohol consumption as well as gastro-esophageal re?ux and obesity.

Small-cell neuroendocrine carcinoma of the prostate： are heterotransplants a better experimental model？

Small-cell neuroendocrine carcinoma of the prostate （SCNCP） is an uncommon type of prostate cancer. However, it is of clinical importance because it is one of the most aggressive tumors of the prostate with a very poor prognosis. There exist few artificially cultured tumor cell lines to study SCNCE Then, another approach to that study consists in the use of fresh tumor tissue obtained from patients and its heterotransplantation into host mice. The purpose of this review is to integrate data from more than 20 years of heterotransplantation research in the study of small-cell neuroendocrine carcinoma of the prostate （SCNCP）. Heterotransplantation has provided data regarding the histopathology, karyotype, DNA content, cell cycle frequency, tumor markers, androgen receptor expression, metastasis and take rate of this prostate disease. When possible, comparisons between original in situ specimens removed from patients and heterotransplanted tissue from host mice have been made. There are advantages, as well as limitations, that have been identified for SCNCP heterotransplants versus xenotransplantation of cultured cells. Overall, heterotransplanted tumors are better than conventional tumor xenografts at retaining tumor morphology, pathology, secretory activity and expression of tumor markers of the patient＇s original specimen. Furthermore, heterotransplanted tissue preserves the three-dimensional tumor architecture of the prostate to maintain critical stromal-epithelial cell interactions.

Small-cell neuroendocrine carcinoma of the rectum—a rare tumor type with poor prognosis:A case report and review of literature

BACKGROUND Small-cell neuroendocrine carcinoma(SNEC)of the rectum is a rare tumor associated with poor prognosis.CASE SUMMARY We report a case of a 77-year-old male who came into our hospital because of blood with his stool.An endoscopy revealed a cauliflower-like neoplasm in his rectum.Imaging examination showed that the lesion in the upper rectum was likely rectal cancer,and there was no evidence of metastasis.The patient was treated with surgery.Pathological examination confirmed SNEC of the rectum and an R0 resection was achieved.However,1 mo after the operation,the patient developed intestinal and ureteral obstructions due to peritoneal metastases.Finally,the patient died from renal failure.CONCLUSION SNEC of the rectum is a high-grade carcinoma with an aggressive phenotype,and surgery should be cautiously considered.

Multiple carcinosarcomas of the esophagus with adenocarcinomatous components: A case report

BACKGROUND Carcinosarcoma(spindle cell carcinoma) of the esophagus is an extremely rare event;the etiology and origins of this neoplasm have not yet been determined.Epithelial-mesenchymal transition(EMT) has been associated with invasion and metastasis, and may be related to the generation of a stem cell population within this tumor.CASE SUMMARY We present the case of a 61-year-old male with nausea and fever. Upper gastrointestinal endoscopy revealed the presence of type 1 and 0-Ⅱc lesions located 35 cm from the incisors toward the esophago-gastric junction.Thoracoscopic esophagectomy was performed. Macroscopic analysis revealed three polypoid lesions in the abdominal esophagus that accompanied the main lesion in the lower thoracic esophagus and 0-Ⅱc lesions that spread continuously with them. Histologically, the lesions included proliferating spindle cells. Adenocarcinomatous components were detected in a section near the foot, and squamous cell carcinoma was identified in the mucosa at the base of the tumor.The patient was diagnosed with multiple carcinosarcomas, staged at pT1b(SM3),pN1(#110, #7), cM0, Stage Ⅱ(sarcomatous metastasis to the lymph nodes).Spindle cells did not express E-cadherin but were positive for EMT markers,including zinc finger E-box-binding homeobox 1, TWIST, and snail family transcriptional repressor 2. The patient has experienced no recurrence at 5 years and 2 mo after surgery.CONCLUSION This report suggests that multiple sarcomatous tumors may be generated from primary squamous cell carcinoma via mechanisms related to EMT.

A case of EMRC for basaloid squamous carcinoma of the cervical esophagus

Basaloid squamous carcinoma (BSC) of the esophagus is a rare esophageal tumor. A 79-year-old man with a history of proximal gastrectomy for gastric adenocarcinoma in 2000 was followed-up by esophagogastroduodenoscopy (EGD) annually. In June 2010, EGD revealed a new protruding lesion in the cervical esophagus. The small lesion was approximately 5 mm in size. A biopsy specimen showed poorly differentiated squamous cell carcinoma. We performed endoscopic mucosal resection using a cap-fi tted endoscope (EMRC). The histological diagnosis of the endoscopically resected specimen was BSC and the invasion depth was limited to the muscularis mucosae. Horizontal and vertical margins were negative. We report the case of superfi cial BSC in the cervical esophagus successfully resected by EMRC.

Endoscopic submucosal dissection combined with adjuvant chemotherapy for early-stage neuroendocrine carcinoma of the esophagus:A case report

BACKGROUND Neuroendocrine carcinoma(NEC)of the esophagus is rare and highly aggressive,and lacks biological features.Currently,there are no established standard treatments for this cancer.In this report,we describe a patient with large-cell NEC of the esophagus who was successfully treated using endoscopic submucosal dissection(ESD)combined with adjuvant chemotherapy.CASE SUMMARY A 55-year-old woman presented with intermittent mild dysphagia for 2 mo.Gastroscopy revealed a disc-shaped protruding lesion about 18 mm×18 mm in size on the upper esophagus.Endoscopic ultrasonography demonstrated that the bulged lesion originated from the muscularis mucosa.We assessed en bloc resections using ESD for therapeutic diagnosis to devise a safe and appropriate treatment.Histopathological examination revealed a poorly differentiated neoplasm comprising of large cells with marked nuclear atypia and multifocal necrosis.In addition,the specimens had a negative horizontal margin and vertical margins.Depth of invasion was classified as submucosa 2(SM2)without lymphovascular invasion.These histopathological results were consistent with a diagnosis of esophageal NEC,large cell type.Adjuvant therapy has been considered for ESD patients with SM2/SM3 lesions and patients with poorly differentiated lesions.After comprehensive consideration,we initiated combination treatment,i.e.,ESD plus adjuvant chemotherapy.The patient remained disease-free at the 2-year follow-up.CONCLUSION En bloc resection approach using ESD may play a vital role as a diagnostic and therapeutic modality for esophageal NEC.

Development and validation of a prognostic nomogram model for Chinese patients with primary small cell carcinoma of the esophagus

BACKGROUND Primary small cell carcinoma of the esophagus(PSCE)is a highly invasive malignant tumor with a poor prognosis compared with esophageal squamous cell carcinoma.Due to the limited samples size and the short follow-up time,there are few reports on elucidating the prognosis of PSCE,especially on the establishment and validation of a survival prediction nomogram model covering general information,pathological factors and specific biological proteins of PSCE patients.AIM To establish an effective nomogram to predict the overall survival(OS)probability for PSCE patients in China.METHODS The nomogram was based on a retrospective study of 256 PSCE patients.Univariate analysis and multivariate Cox proportional hazards regression analysis were used to examine the prognostic factors associated with PSCE,and establish the model for predicting 1-,3-,and 5-year OS based on the Akaike information criterion.Discrimination and validation were assessed by the concordance index(C-index)and calibration curve and decision curve analysis(DCA).Histology type,age,tumor invasion depth,lymph node invasion,detectable metastasis,chromogranin A,and neuronal cell adhesion molecule 56 were integrated into the model.RESULTS The C-index was prognostically superior to the 7th tumor node metastasis(TNM)staging in the primary cohort[0.659(95%CI:0.607-0.712)vs 0.591(95%CI:0.517-0.666),P=0.033]and in the validation cohort[0.700(95%CI:0.622-0.778)vs 0.605(95%CI:0.490-0.721),P=0.041].Good calibration curves were observed for the prediction probabilities of 1-,3-,and 5-year OS in both cohorts.DCA analysis showed that our nomogram model had a higher overall net benefit compared to the 7th TNM staging.CONCLUSION Our nomogram can be used to predict the survival probability of PSCE patients,which can help clinicians to make individualized survival predictions.

A case of rapidly progressing leiomyosarcoma combined with squamous cell carcinoma in the esophagus

Esophageal leiomyosarcoma is a rare tumor that accounts for less than 1%of all malignant esophageal tumors.Esophageal leiomyosarcoma combined with squamous cell carcinoma is even rarer than solitary leiomyosarcoma.We experienced a case of leiomyosarcoma combined with squamous cell carcinoma that progressed very rapidly.

CARCINOMA ARISING IN BARRETT'S ESOPHAGUS (A REPORT OF 51 CASES)

Fifty-one patients with carcinoma arising in Barrett's esophagus were treated surgically from 1971 to 1990. This represented 10.2% of all treated cases with esophageal carcinoma during the same period. The mean age was 63 years. The most common symptom was dysphagia. According to PTNM staging, 18 were stage II,3 stage III and 3 stage IV. All patients were treated bysurgery. The 30-day hospital mortality was 3.98%. Theone, two and five-year survival rates were 45.9%, 25.0%and 13.6%, respectively. The 5-year survival rate wassignificantly greater for patrents with stage II (25.0%)than for parients with stage III + IV (4.s%) (P<0.05) andfor tumor length less than 6 cm (21%) than for tumorlength greater than 6 cm (0). The results indicate that thesurvival rate following resection is closely related to theclinical stage and tumor size.

Neuroendocrine carcinoma of the esophagus: Report of a case and review of the literature

Esophageal neuroendocrine carcinomas are rare, aggressive and have a poor prognosis. Combined therapy using chemotherapy, radiotherapy and/or surgery appear effective for them. Upper gastrointestinal endoscope of a 65-year-old male revealed a localized ulcerative lesion in the middle esophagus. Histology of biopsy specimens indicated a neuroendocrine carcinoma. A computed tomography showed an esophageal tumor with enlarged mediastinal lymph nodes. The patient was administered neoadjuvant chemo-therapy consisting of 5-fluorouracil and cisplatin, which led to partial response. Subtotal esophagectomy with three-field lymphadenectomy was performed. Pathologically, the tumor was 25 mm and infiltrated the proper muscle layer. The tumor cells were arranged in microtubular structures, with small and round cells containing scanty cytoplasm, and exhibited intense mitosis 51/10 HPF. They were positive for synaptophysin and chromogranin A, and Ki-67 labeling index was 70% - 80%. These findings led to the diagnosis of neuroendocrine carcinoma of small cell type. The patient was administered adjuvant chemotherapy using cisplatin and CPT-11, and he is now alive disease-free at the time of this writing.

Small-Cell Carcinoma of Prostate:A Case Report and Literature Review

One case of small-cell carcinoma（SCC） of prostate was identified at Shangyu people＇s hospital.This 70-year-old male had a prior diagnosis of prostatic adenocarcinoma when he was first admitted to the hospital and received anti-androgen treatment.9 months later,he was readmitted to the hospital and was diagnosed as SCC through biopsy.The article was written to evaluate the clinical and pathological characteristics and treatment of SCC of prostate.

A Novel Peptide from T-Cell Leukemia Translocation-Associated Gene (TCTA) Protein Inhibits Proliferation of a Small-Cell Lung Carcinoma

In 2009, we demonstrated that a peptide, which we named “Peptide A”, derived from the extracellular domain of T-cell leukemia translocation-associated gene (TCTA) protein, inhibited both RANKL-induced human osteoclastogenesis and pit formation of mature human osteoclasts. Here, we examined the effect of Peptide A on the cell proliferation of cell lines of small-cell lung carcinoma, breast cancer, and prostate cancer: RERF-LC-MA, MCF-7, and PC-3, respectively. Peptide A inhibited the proliferation of RERF-LC-MA, but not MCF-7 or PC-3. TCTA protein was immunohistologically detected in RERF-LC-MA and MCF-7. Thus, Peptide A may provide a novel strategy for the therapy of the patients with small-cell lung carcinoma, especially with bone metastasis. In addition, Peptide A may be useful for the treatment of various cancer patients with bone metastasis.

Improvement of dysphagia in patients with esophagus stenosis following carcinoma of esophagus

Objective To investigate the intervention ways of endoscopes in the treatment of esophagus stenosis due to carcinoma of esophagus and improvement of quality. Method 11 cases of advanced carcinoma of esophagus were included in this study. Operation and chemical therapy were unavailable for these patients. Memory trestle with membrane and made of alloy of Nickel-titanium was inserted under intervention of endoscope. Trestle was posed in stenosis part of esophagus under direction of X-ray. Trestle could be dilated 3-7 days after operation due to its reaction characteristics to temperature. So, redilated therapy was unnecessary. Trestle could reconstruct swallowing tract and made feeding through mouth become available during limited survival time.Results All trestles were successfully inserted.Half-fluid feeding was available after operation. Obstruction was removed in all patients(100%).Conclusion Method described in this study was safe and effective .Effective swallowing tracts were reconstructed in all patients after trestle was planted and quality of life and survival time were both improved.