Combined tubular adenocarcinoma, neuroendocrine carcinoma and adenocarcinoma with enteroblastic differentiation arising in Barrett esophagus.

Adenocarcinoma (AC) with neuroendocrine carcinoma (NEC) or enteroblastic (ENT) differentiation rarely develops in Barrett's esophagus (BE). A 76-year-old man was diagnosed with Barrett's AC (cT1bN0M0) and underwent thoracoscopic esophagectomy. A type 0-IIc + 0-Is lesion measuring 26 × 21 mm was macroscopically observed on a background of long segment BE (pT1bN0M0). The tumor comprised three different histological types of carcinoma (NEC, AC with ENT differentiation and moderately differentiated AC). NEC showed positivity for synaptophysin, chromogranin A and insulinoma-associated protein 1 with a Ki-67 index of 60.6%. ENT tumors were immunopositive for AFP and sal-like protein 4, and focally immunopositive for human chorionic gonadotrophin. The amounts of NEC, ENT and AC were 40%, 40% and 20%, respectively. p53 expression was positive throughout the tumor. Rb expression was negative at the NEC, but positive at the ENT and AC. CD4 and CD8 densities were lower in the NEC segment than in the AC and ENT segments, and PD-L1 expression was negative throughout the tumor. Early cancer arising in BE with a combination of tubular AC, ENT tumors and NEC is very rare. Our observations might contribute to understanding the carcinogenetic pathways and tumor microenvironment of NEC and ENT tumors.

McKeown esophagectomy for a thoracic esophageal carcinoma patient who has a history of definitive chemoradiotherapy for esophageal carcinoma and total pharyngolaryngectomy for hypopharyngeal cancer.

A 64-year-old man, who had previously undergone definitive chemoradiotherapy (dCRT) and endoscopic resections for metachronous multiple esophageal squamous cell carcinoma (ESCC) and had also received total pharyngolaryngectomy (TPL) for hypopharyngeal cancer, was diagnosed with ESCC in the middle thoracic esophagus (cT3N0M0). Thoracoscopic McKeown esophagectomy was performed for the patient. Although the tumor was tightly adherent to the thoracic duct and both main bronchi, they were successfully mobilized. In order to maintain the blood supply to the trachea, we preserved the bilateral bronchial arteries and avoided prophylactic upper mediastinal lymph node dissection. Cervical end-to-side anastomosis between the jejunum and a gastric conduit was performed. Minor pneumothorax was managed conservatively, and the patient was discharged 44 days after the surgery. Overall, thoracoscopic McKeown esophagectomy was safely performed in a patient with a history of TPL and dCRT. Surgeons should be very careful to prevent tracheobronchial ischemia by optimizing the extent of lymph node dissection.

The Impact of Pretreatment Esophageal Stenosis on Survival of Esophageal Cancer Patients.

BACKGROUND: Little is known about the survival impacts of pretreatment cancerous stenosis on patients with esophageal carcinoma (EC). METHODS: The clinicopathologic characteristics of patients who underwent surgery for EC between January 2010 and December 2018 were retrospectively reviewed. Esophageal stenosis was defined as present when a thin endoscope could not be passed through the tumor site. The impacts of stenosis on overall survival (OS) and cancer-specific survival (CSS) were evaluated using Cox hazards analysis. RESULTS: Of the 496 EC patients in this study, 51 (10.3 %) had pretreatment esophageal stenosis. Stenosis was associated with lower body mass index (P < 0.001) and higher pStage (P < 0.001). The 3-year OS rate for the patients with stenosis was significantly poorer than for the patients without stenosis (40.2 % vs 69.6 %; hazard ratio [HR], 2.19; P < 0.001). The survival outcomes, especially CSS, for the patients with stenosis were significantly poorer than for the patients without stenosis for both pStage II-III (P = 0.009) and pStage IV (P = 0.006) disease. The OS and CSS curves were well stratified by the presence of stenosis even in early-stage (pStage II) patients (P = 0.04 and P < 0.01, respectively). Multivariable analysis showed esophageal stenosis, pStage III-IV disease, and non-curative resection to be independently associated with poor OS (HR, 1.61; P = 0.02) and poor CSS (HR,1.67; P = 0.02). Higher pStage was an independent predictor of poor CSS for patients without stenosis, but not for those with stenosis. CONCLUSIONS: Esophageal carcinoma patients with pretreatment stenosis had significantly poorer survival outcomes, especially poorer CSS, than those without stenosis in both early- and advanced-stage diseases.

Influences of intratumoral heterogeneity on assessment of tumor microenvironment in esophageal squamous cell carcinoma.

The intratumoral heterogeneity (ITH) of the tumor microenvironment (TME) has yet to be addressed in esophageal squamous cell carcinoma (ESCC). Here, we studied the ITH of CD8 and PD-L1 status in ESCC, and examined the potential of the tumor surface for representing the TME. In total, 67 surgically resected clinical Stage II ESCC specimens were analyzed. The CD8-cell density, PD-L1 tumor proportion score (TPS), and combined positive score (CPS) were calculated in three (superficial, middle, and deep) areas of each specimen. ITH was quantified by distance-standardized coefficient variations of the three values. The CD8 and PD-L1 status of each area was dichotomized and tumor-surface capabilities for predicting the entire tumor status were estimated. Variables were compared according to the presence of neoadjuvant chemotherapy (NAC). The ITH, especially PD-L1 heterogeneity, differed markedly among specimens. The concordance rates of CD8 and PD-L1 (CPS and TPS) status among the three different areas were 71.6%, 74.6%, and 73.1%, respectively. The sensitivity and the specificity of the tumor surface for predicting the CD8 status of the whole tumor were high, especially in the NAC- group (both 1.0). The tumor surface also showed high capabilities for representing the whole PD-L1 status, while yielding moderate positive predictive values (0.70). The ITH degrees and predictive capabilities did not differ according to NAC. Taken together, the ITH of CD8 and PD-L1 differed among ESCC specimens, while not being markedly affected by NAC. The use of a biopsy specimen from the tumor surface might be feasible for TME evaluation.

[Para-Aortic Lymphadenectomy and Subsequent Chemotherapy after Resection of the Primary Lesion for Poorly Differentiated Adenocarcinoma of the Sigmoid Colon - A Case Report].

The patient was a 68-year-old male who had bloody stools. A colonoscopy revealed a sigmoid colon stricture, and a histological examination confirmed the presence of a poorly differentiated adenocarcinoma.Computed tomography revealed the involvement of a para-aortic lymph nodes, without other metastatic lesions. The patient underwent a sigmoidectomy (with regional lymph node dissection) and a para-aortic lymph node biopsy to prove the histological conformation. Subsequently, he was provided with 6 courses of modified FOLFOX6(mFOLFOX6) chemotherapy, resulting in a marked decrease in para-aortic lymph node involvement. He subsequently underwent a para-aortic lymphadenectomy. The resected specimen was mostly composed of fibrous degenerative tissue; viable cancer cells were observed only in a 2-mm² area. The patient was provided with 6 more courses of mFOLFOX6 chemotherapy, and has since been free of recurrence (for 6 years and 1 month after the second surgery).