Comparison of the subtotal and narrow gastric conduit for cervical esophagogastrostomy after esophagectomy in esophageal cancer patients: a propensity score-matched analysis.

BACKGROUND: Several reports have compared narrow gastric conduit (NGC) with subtotal gastric conduit (SGC) for cervical esophagogastrostomy after esophagectomy; however, whether which one is more beneficial in terms of postoperative complications remains unclear. To determine the optimal gastric conduit type, we retrospectively investigated and compared the postoperative complications between NGC and SGC used in cervical circular-tapered esophagogastrostomy after esophagectomy through a propensity score-matched analysis. METHODS: Between 2008 and 2022, 577 consecutive esophageal cancer patients who underwent esophagectomy and cervical circular-stapled esophagogastrostomy were enrolled in this study. RESULTS: Of the 577 patients, 77 were included each in the SGC and NGC groups, after propensity score matching. Clinical characteristics did not differ between the two groups. The anastomotic leakage rate was significantly lower in the SGC group than in the NGC group (5% vs. 22%, p < 0.01). The anastomotic stenosis rate was significantly higher in the SGC group (16% vs. 5%, p = 0.03). Multivariate logistic analysis showed that NGC, subcutaneous route, and age were significant independent factors associated with anastomotic leakage (odds ratios, 8.58, 6.49, and 5.21; p < 0.01, < 0.01 and 0.03, respectively) and that SGC was a significant independent factor associated with anastomotic stricture (odds ratios, 4.91; p = 0.04). CONCLUSIONS: In cervical circular-stapled esophagogastrostomy after esophagectomy, SGC was superior to NGC in terms of reducing the risk of anastomotic leakage, although the risk of anastomotic stricture needs to be resolved.

Evaluation of Quality of Life and Prognosis of Gastric Cancer Patients After Laparoscopic Subtotal Gastrectomy.

BACKGROUND/AIM: The clinical significance of laparoscopic subtotal gastrectomy (LsTG) with a small remnant stomach remains unclear in patients with gastric cancer, including at an advanced stage. The present study assessed postoperative quality of life (QOL) and survival after LsTG compared with laparoscopic total gastrectomy (LTG). PATIENTS AND METHODS: We retrospectively analyzed consecutive patients with gastric cancer who underwent LsTG (n=26) or LTG (n=26). Surgical outcome, postoperative nutritional status, QOL, and prognosis were compared between the LsTG and LTG groups. The Postgastrectomy Syndrome Assessment Scale was used to evaluate postoperative QOL. RESULTS: Operating time was significantly shorter (p<0.01) and postoperative morbidity was significantly lower (p=0.04) in the LsTG than in the LTG group. The reduction in body weight after surgery was significantly greater in the LTG than in the LsTG group (p<0.01). The Postgastrectomy Syndrome Assessment Scale revealed that, compared with LTG, LsTG significantly improved postoperative QOL (p<0.05). There was no significant difference in relapse-free survival and cancer-specific survival between the two groups. Three patients in the LTG group died of pneumonia and overall survival was significantly longer in the LsTG group (p=0.01). CONCLUSION: This study demonstrated the efficacy of LsTG with a small remnant stomach to prevent a decline in postoperative QOL and non-cancer-related death.

Clinical Outcome After Esophagectomy or Definitive Chemoradiotherapy in Elderly Patients (≥80 Years) With Esophageal Cancer.

BACKGROUND/AIM: Given the increased incidence of esophageal cancer (EC) in individuals over 80 years old, the optimum therapeutic strategy for elderly patients is needed to be established with scientific evidence. Here, we studied the short-term and long-term outcomes after treatment of patients aged 80 years old or older with EC. PATIENTS AND METHODS: Eighty patients with EC aged 80 years old or older, who underwent esophagectomy (n=23), definitive chemoradiotherapy (dCRT) (n=46) or best supportive care (n=11) between January 2010 and March 2019 were included in this study, and clinical data were compared among these groups. RESULTS: Surgery had a great benefit on the 3-year overall survival (OS) compared to dCRT (68.4% vs. 29.3%, p<0.01). The cure rates of treatment were 86.9% in surgery and 34.8% in dCRT. dCRT led to a better 3-year OS compared to BSC (29.3% vs. 0%, p<0.01); however, dCRT did not improved OS in patients with T4. Patients with T4 had high frequency of adverse events and treatment-related death in dCRT; CTCAE Grade 3-5 was observed in 100% of all T4 patients and Grade 5 in 57.1%. Multivariate analysis revealed that T4 was an independent risk factor of treatment-related death after dCRT (p<0.01). CONCLUSION: Surgery is the first treatment option for resectable EC even in elderly patients, and dCRT can be considered as an alternative. However, dCRT may induce severe toxicity especially in T4 EC patients.

Additional Effects of Docetaxel on Neoadjuvant Radiotherapy With Cisplatin/5-Fluorouracil for Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: To further improve the prognosis of locally advanced esophageal cancer patients, investigating new perioperative treatment strategies is necessary. The current study aimed to retrospectively investigate neoadjuvant radiotherapy with cisplatin and 5-fluorouracil (CF-RT) and radiotherapy with docetaxel and CF (DCF-RT) and compare their treatment outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: We retrospectively reviewed 95 patients with ESCC who received CF-RT or DCF-RT followed by esophagectomy. The CF-RT group received chemotherapy consisting of two courses of CF repeated every 4 weeks. The DCF-RT group received chemotherapy consisting of two courses of DCF repeated every 2 weeks. A radiotherapy dose of 1.8-2 Gy was administered per session, up to a total of 40-41.4 Gy. Adverse events of neoadjuvant chemoradiotherapy, surgical outcomes, pathological responses, prognosis, and recurrence patterns were evaluated. RESULTS: Both the CF-RT and DCF-RT groups had equivalent pathological complete response rates of the primary tumor at 31.6% and 38.6%, respectively. However, the DCF-RT group had significantly better 5-year disease-free survival and 5-year overall survival than (HR=0.50, 95%CI=0.26-0.97, p=0.0392) than the CF-RT group. CONCLUSION: DCF-RT may be a candidate neoadjuvant therapy for locally advanced ESCC.

A comparison of the surgical invasiveness and short-term outcomes between thoracoscopic and pneumatic mediastinoscopic esophagectomy for esophageal cancer.

PURPOSE: Minimally invasive esophagectomy (MIE) has been widely accepted as a treatment for esophageal cancer. This retrospective study compared the short-term outcomes and surgical invasiveness between thoracoscopic esophagectomy (TE) and mediastinoscopic esophagectomy with pneumomediastinum (pneumatic mediastinoscopic esophagectomy [PME]). METHODS: A total of 72 patients who underwent TE or PME were included and assessed for their surgical findings, postoperative complications, and inflammatory responses on postoperative day (POD) 1, 3, 5, and 7. RESULTS: The PME group exhibited a significantly shorter operative time and fewer lymph nodes retrieved than the TE group. Furthermore, the PME group tended to have greater incidences of recurrent laryngeal nerve palsy and lower incidences of atelectasis than the TE group. The PME group had significantly lower white blood cell counts on POD 5, serum C-reactive protein (CRP) levels on POD 3 than the TE group. CONCLUSION: PME seems to be less invasive than TE and can be considered the preferred option for patients with lower-stage esophageal cancer expected to have severe pleural adhesion or who cannot tolerate TE.

Successful thoracoscopic resection of an esophageal bronchogenic cyst.

Esophageal bronchogenic cysts are rare, and since a limited number of cases has been reported, the treatment plan for asymptomatic patients is difficult. A 55-year-old man without any symptoms visited our hospital for further examination of an esophageal mass detected on simple computed tomography. Upper endoscopy showed the protruding, submucosal mass covered by normal mucosa, and endoscopic sonography confirmed hypoechoic lesions originating from the muscularis propria. The patient was diagnosed as having an esophageal duplication cyst and underwent thoracoscopic resection. Pathological findings were consistent with an esophageal bronchogenic cyst. The patient was discharged without any problems on the 6th postoperative day. Upper endoscopy was performed 6 months after surgery, and no evidence of esophageal diverticula or narrowing was present. In conclusion, early thoracoscopic resection of esophageal bronchogenic cysts, before appearance of the symptom, can be a considerable treatment option because it is less invasive and may be advantageous for obtaining a definitive diagnosis in patients who are candidates for safe surgical resection.

Successful treatment of post chemotherapy esophageal cicatricial atresia in a pediatric patient with anaplastic large cell lymphoma through minimally invasive esophagectomy: a case report.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell lymphoma, which is a rare type of non-Hodgkin lymphoma. ALCL rarely presents in the gastrointestinal tract, and the esophageal involvement in of ALCL is extremely rare. CASE PRESENTATION: An 11-year-old boy who complained of abdominal pain and cough was diagnosed with ALK-positive ALCL on the basis of systemic lymphadenopathy findings and immunohistochemistry results of pleural effusion. Although remission was observed after chemotherapy at 5 months after diagnosis, dysphagia persisted, and esophagoscopy revealed a severe stricture in the middle thoracic esophagus. At 9 months after diagnosis, allogeneic bone marrow transplantation was performed to ensure that complete remission was maintained; however, dysphagia and saliva retention did not improve. Approximately 10 months after diagnosis, esophagoscopy revealed a blind end in the middle thoracic esophagus, similar to that in congenital esophageal atresia. Subsequently, we performed minimally invasive subtotal esophagectomy under thoracoscopy and laparoscopy and gastric conduit reconstruction via the retrosternal route more than 2 years after allogeneic bone marrow transplantation. The final pathological diagnosis was esophageal atresia with esophagitis, with no malignancy. During postoperative evaluation, the patient required swallowing training for a few months, although no major complications were noted. Oral intake was possible, and complete remission was maintained at 14 month post-surgery. CONCLUSIONS: Oncologists must consider the possibility of acquired esophageal cicatricial atresia as a complication during chemotherapy for ALCL. If esophageal obstruction or esophageal atresia occur and if remission is maintained, esophagectomy and esophageal reconstruction are useful treatment options for maintaining oral intake.

Clinical Outcomes of Fully Covered Self-expanding Metallic Stent Placement for Palliation of Incurable Esophageal Cancer With or Without Radiotherapy.

BACKGROUND/AIM: A combination therapy of esophageal stent and chemoradiotherapy (CRT) is currently considered risky for severe complications. The aim of this study was to assess the safety and efficacy of a fully covered self-expandable metallic stent (FCSEMS) placement in palliating incurable esophageal cancer before and/or after CRT. PATIENTS AND METHODS: We retrospectively reviewed clinical outcomes of 64 incurable advanced esophageal cancer patients with FCSEMS placement. Forty-two of 64 patients had FCSEMS placement with RT. RESULTS: The rate of all of stent-related complications tended to be higher in patients who had RT, although no significant difference was observed. The stent-related deaths occurred in one patient due to hemorrhage after FCSEMS placement in the RT-negative group. CONCLUSION: Palliation of dysphagia or fistulas with FCSEMS in patients with incurable esophageal cancer before and/or after RT is not associated with an increased risk of life-threatening complications.

Comparison of greater curvature and lesser curvature circular-stapled esophagogastrostomy after esophagectomy in patients with esophageal cancer: a prospective randomized controlled trial.

PURPOSE: Using a circular stapler to create an anastomosis for esophagogastrostomy after esophagectomy is well accepted; however, it remains uncertain if the greater curvature (GC) or lesser curvature (LC) of the gastric conduit is better for the anastomosis. We conducted this prospective study to compare the integrity of esophagogastrostomy between the esophagus and the GC or LC side of the gastric conduit. METHODS: The subjects of this study were 70 patients who underwent esophagectomy and were randomized to a "GC" group and an "LC" group (n = 35 each). The primary and secondary end points were anastomotic leakage (AL) and anastomotic stricture (AS), respectively. RESULTS: The overall AL rate was 22.1%, without a significant difference between the groups. Stump leakage developed in eight of nine patients in the GC group, whereas leakage developed at the esophagogastric anastomosis in five of six patients in the LC group. The rate of stump leakage was significantly higher than that of esophagogastric AL in the GC group. The overall AS rate was 4.4%, with a significant difference between the groups (0% in the GC group vs. 9.1% in the LC group). CONCLUSIONS: AL rates were comparable in the two groups, but the sites of leakage were significantly different.

Primary monophasic synovial sarcoma of the cervical esophagus confirmed by detection of the SS18-SSX2 fusion transcripts: case report and literature review.

BACKGROUND: Synovial sarcoma (SS) of the esophagus is extremely rare. Because of the microscopic features of SS, the monophasic type can easily be misdiagnosed as other spindle cell tumors. Here, we present the first case of a primary SS of the esophagus in the presence of SS18-SSX2 fusion transcripts. CASE PRESENTATION: A 47-year-old Japanese woman was initially diagnosed with thyroid papillary carcinoma in the left lobe and leiomyoma of the cervical esophagus and subsequently underwent left thyroid lobectomy and enucleation of the esophageal tumor. Four years after the first surgery, the esophageal tumor recurred. Endoscopic biopsy of the tumor revealed atypical cell proliferation with spindle cell features and mitoses. Immunohistochemistry showed focal positivity for bcl-2 and HHF35. Furthermore, the presence of SS18-SSX2 fusion transcripts was confirmed by reverse transcription-polymerase chain reaction analysis, using a paraffin-embedded tumor specimen. Therefore, the tumor was diagnosed as monophasic SS of the cervical esophagus. We re-evaluated the surgical specimen enucleated 3 years previously, which was initially diagnosed as leiomyoma, and the diagnosis of SS was confirmed. The patient underwent cervical esophagectomy with isolated jejunal interposition reconstruction. Three years after the second surgery, SS recurred in the distal anastomotic site between the jejunum and the esophagus, and the patient underwent thoracoscopic esophagectomy with gastric conduit reconstruction. The pathological grade of the lesion worsened with every recurrence. CONCLUSIONS: Monophasic SS can be difficult to discriminate from other spindle cell tumors based on microscopy alone, and molecular analysis could be useful for confirming the precise diagnosis of monophasic SS.

A long-term survivor of recurrent esophagogastric junction adenocarcinoma treated with multidisciplinary therapy: a case report.

BACKGROUND: Patients with esophagogastric junction cancer are increasing in Western and Eastern countries. Conversely, the clinical significance of surgical resection remains controversial in these patients. We report a long-term survivor of recurrent esophagogastric junction adenocarcinoma who underwent constructive multimodal therapy, including surgical resection. CASE PRESENTATION: A 51-year-old man underwent total gastrectomy for esophagogastric junction adenocarcinoma in 2009. In June 2010, computed tomography (CT) indicated a lung nodule and we partially resected the right lower lung. It was pathologically diagnosed as distant metastasis from esophagogastric junction cancer. After lung resection, he received adjuvant chemotherapy with S-1 for 1 year. In September 2014, CT demonstrated a swelling of the upper mediastinal lymph node with abnormal uptake on fluorine-18 fluorodeoxyglucose positron emission tomography. We performed an ultrasonography-guided needle biopsy, and he was diagnosed with lymph nodal recurrence of esophagogastric junction adenocarcinoma by pathological examination and was subsequently treated with capecitabine plus cisplatin plus trastuzumab. Since CT showed a reduction in the metastatic upper mediastinal lymph node after chemotherapy, he underwent upper mediastinal lymphadenectomy in April 2015. Following surgery, we provided radiation therapy to the upper mediastinum and chemotherapy with S-1. At the last report, the patient was alive for 8 years and 3 months since the first surgery. CONCLUSIONS: This case report shows the clinical benefit of constructive multimodal therapy for recurrent esophagogastric junction adenocarcinoma.

Successful conservative treatment of spontaneous intrathoracic esophageal perforation using a temporary covered esophageal stent with a check valve: a case report.

BACKGROUND: Spontaneous esophageal perforation is a potentially life-threatening condition with high morbidity and mortality rates. While surgical treatment has been employed for esophageal perforation, we have adopted conservative treatment with an esophageal stent for patients in a poor physical condition because we consider controlling sepsis and improving the physical status are the highest priorities; additionally, the surgical trauma could be fatal for these patients. CASE PRESENTATION: A 60-year-old male complaining of left chest and back pain after vomiting was transferred to a local hospital. Computed tomography and chest X-ray examinations showed left tension pneumothorax, pneumomediastinum, and bilateral pleural effusion suspicious of spontaneous intrathoracic esophageal perforation. He was transferred to our hospital for further treatment. After arrival, he developed septic shock with acute respiratory failure. We considered that surgical treatment was too invasive and chose conservative treatment with an esophageal stent. Under general anesthesia, we first inserted a 20-Fr. trocar in the left posterior pleural space, and a large volume of the dark pleural effusion was discharged. We then performed endoscopy and found a pinhole perforation in the left posterolateral wall of the lower esophagus. We inserted both a silicon-covered esophageal stent with a check valve and a double elemental diet (W-ED) tube. We then inserted an 18-Fr. trocar into the left anterior wall. These procedures were performed less than 24 h after onset. As intensive medical care, the patient was administered broad-spectrum antibiotics and catecholamine. The two trocars and the W-ED tube were under continuous suction at - 5 cmH2O and at - 20 cmH2O every 30 s. On the 6th day, we inserted an additional thoracic drainage tube into the left pleura under CT guidance. The patient was discharged from the ICU to the general ward on the 7th day. We removed the stent almost triweekly, and the esophageal perforation was completely healed on the 45th day. He was discharged home on the 70th day. CONCLUSION: Conservative treatment with a temporary self-expanding covered stent with a check valve, sufficient drainage, and W-ED tube nutrition was useful and effective in this unstable case of spontaneous intrathoracic esophageal perforation.

Combined neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicts chemotherapy response and prognosis in patients with advanced gastric cancer.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are representative blood markers of systemic inflammatory responses. However, the clinical significance of the combination of these markers is unclear. This study aimed to investigate the NLR and PLR in patients with advanced gastric cancer treated with chemotherapy and assess the clinical utility of a new blood score combining the NLR and PLR (NLR-PLR score) as a predictor of tumor response and prognosis. METHODS: We retrospectively analyzed 175 patients with gastric cancer receiving chemotherapy or chemoradiotherapy. These patients were categorized into progressive disease (PD) and non-PD groups according to tumor response. The NLR and PLR before treatment were examined, and the cut-off values were determined. The NLR-PLR score ranged from 0 to 2 as follows: score of 2, high NLR (> 2.461) and high PLR (> 248.4); score of 1, either high NLR or high PLR; score of 0, neither high NLR nor high PLR. RESULTS: With regard to tumor response, 64 and 111 patients had PD and non-PD, respectively. The NLR-PLR score was significantly higher in patients with PD than in those with non-PD (p = 0.0009). The prognosis was significantly poorer in patients with a higher NLR-PLR score than in those with a lower NLR-PLR score (p <  0.0001). Multivariate analysis demonstrated that the NLR-PLR score was an independent prognostic factor for prediction of overall survival (p = 0.0392). CONCLUSION: Low-cost stratification according to the NLR-PLR score might be a promising approach for predicting tumor response and prognosis in patients with advanced gastric cancer.

Combined endoscopic submucosal dissection and transanal minimally invasive surgery for the management of lower rectal adenoma extending above the dentate line: A case report.

RATIONALE: Minimally invasive surgery is used to treat early colorectal tumors. Endoscopic submucosal dissection (ESD) for resection of tumors extending above the dentate line (particularly those with concomitant hemorrhoids) is technically difficult. We present a case of a patient with a lower rectal adenoma extending above the dentate line, which underwent combined ESD and transanal minimally invasive surgery (TAMIS) to achieve accurate excision and prevent complications. PATIENT CONCERNS: A 68-year-old man with a history of blood in stool over 2 to 3 years underwent colonoscopy, which revealed an adenoma measuring 3 cm in size in the lower rectum extending above the dentate line. The part extending above the dentate line was a type Is lesion and that of oral side was a type IIa lesion. Histopathologically, the lesion was diagnosed as a low-grade intramucosal tubulovillous adenoma. DIAGNOSIS: Intramucosal low-grade adenoma with sessile polyp (type Is). INTERVENTIONS: The cranial portion of the lesion was dissected via ESD and the anal portion via TAMIS with minimal bleeding. En bloc resection of the tumor was performed. OUTCOMES: His postoperative period was uneventful, and he was discharged and regularly followed-up. LESSONS: Combined ESD and TAMIS is effective in patients with benign and early neoplastic lesions of the anorectum extending above the dentate line with concomitant hemorrhoids and can prevent complications.

Radial incision and cutting method using a transanal approach for treatment of anastomotic strictures following rectal cancer surgery: a case report.

BACKGROUND: Development of an anastomotic stricture following rectal cancer surgery is not uncommon. Such strictures are usually managed by manual or instrumental dilatation techniques that are often insufficiently effective, as evidenced by the high recurrence rate. Various surgical procedures using minimally invasive approaches have also been reported. One of these procedures, endoscopic radial incision and cutting (RIC), has been extensively reported. However, RIC by transanal minimally invasive surgery (TAMIS) is yet to be reported. We here report a novel application of TAMIS for performing RIC for anastomotic rectal stenosis. CASE PRESENTATION: A 67-year-old man had suffered from constipation for 6 years after undergoing low anterior resection for stage II rectal cancer 7 years ago. Colonoscopy showed a 1-cm diameter stricture in the lower rectum. Balloon dilatation was performed many times because of repeated recurrences. Thus, surgical management was considered and the stricture was successfully excised via a RIC method using a TAMIS approach. Postoperatively, the patient had minimal leakage that resolved with conservative treatment. CONCLUSIONS: A RIC method using a TAMIS approach is an effective minimally invasive means of managing anastomotic strictures following rectal cancer surgery.

Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for locally advanced esophageal squamous cell carcinoma.

PURPOSE: To further improve the prognosis of esophageal cancer patients, it is necessary to investigate new treatment strategies. The purposes of this study were to retrospectively assess the safety and efficacy of neoadjuvant chemoradiotherapy (CRT) with docetaxel/cisplatin/5-fluorouracil (DCF) (DCF-RT) in patients with thoracic esophageal squamous cell carcinoma (ESCC). METHODS: We reviewed 30 thoracic ESCC patients who underwent neoadjuvant DCF-RT followed by esophagectomy, and evaluated the safety and efficacy of DCF-RT. DCF-RT consisted of 40 Gy radiation with two courses of intravenous DCF (docetaxel, 30 mg/m2/day, day 1; cisplatin, 7 mg/m2/day, day 1; 5-FU, 350 mg/m2/day, days 1-5 and days 8-12) repeated every 2 weeks. Esophagectomy was scheduled 8-10 weeks after completion of DCF-RT. RESULTS: Twenty-nine of thirty patients completed radiotherapy; however, 27 of 30 patients required dose reduction of the second cycle of DCF. Complete response (CR), partial response, and stable disease were observed in 7, 11, and 10 patients, respectively. The number of lymph node metastases after DCF-RT was significantly lower than that before DCF-RT (P < 0.0001). Among the 30 patients, pathological CR (pCR) in the primary tumor was observed in 17 patients, and pCRs in both the primary tumor and lymph nodes were observed in 14 patients. The 3-year overall survival rate was 62.2%, and that of patients who experienced pCR was 84%. CONCLUSIONS: Neoadjuvant DCF-RT was tolerable and yielded a high pCR rate in ESCC. Therefore, neoadjuvant DCF-RT may confer a survival benefit and may be a candidate neoadjuvant therapy regimen for patients with locally advanced thoracic ESCC.

Molecular pathogenesis of esophageal squamous cell carcinoma: Identification of the antitumor effects of miR­145­3p on gene regulation.

Although miR­145­5p (the guide strand of the miR­145 duplex) is established as a tumor suppressive microRNA (miRNA or miR), the functional significance of miR­145­3p (the passenger strand of the miR­145 duplex) in cancer cells and its targets remains obscure. In our continuing analysis of esophageal squamous cell carcinoma (ESCC) pathogenesis, the aim of the present study was to identify important oncogenes and proteins that are controlled by miR­145­3p. Overexpression of miR­145­3p significantly reduced cancer cell proliferation, migration and invasive abilities, and further increased apoptotic abilities. In ESCC cells, 30 possible oncogenic targets were identified that might be regulated by miR­145­3p. Among these targets, dehydrogenase/reductase member 2 (DHRS2) and myosin IB (MYO1B) were focused on to investigate their functional roles in ESCC cells. DHRS2 and MYO1B were directly regulated by miR­145­3p in ESCC cells by dual luciferase reporter assays. Aberrantly expressed DHRS2 and MYOIB were detected in ESCC clinical specimens, and their overexpression enhanced cancer cell aggressiveness. Genes regulated by antitumor miR­145­3p were closely associated with the molecular pathogenesis of ESCC. The approach based on antitumor miRNAs may contribute to the understanding of ESCC molecular pathogenesis.

Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells.

Background & Aims: Oropharyngeal and esophageal squamous cell carcinomas, especially the latter, are a lethal disease, featuring intratumoral cancer cell heterogeneity and therapy resistance. To facilitate cancer therapy in personalized medicine, three-dimensional (3D) organoids may be useful for functional characterization of cancer cells ex vivo. We investigated the feasibility and the utility of patient-derived 3D organoids of esophageal and oropharyngeal squamous cell carcinomas. Methods: We generated 3D organoids from paired biopsies representing tumors and adjacent normal mucosa from therapy-naïve patients and cell lines. We evaluated growth and structures of 3D organoids treated with 5-fluorouracil ex vivo. Results: Tumor-derived 3D organoids were grown successfully from 15 out of 21 patients (71.4%) and passaged with recapitulation of the histopathology of the original tumors. Successful formation of tumor-derived 3D organoids was associated significantly with poor response to presurgical neoadjuvant chemotherapy or chemoradiation therapy in informative patients (P = 0.0357, progressive and stable diseases, n = 10 vs. partial response, n = 6). The 3D organoid formation capability and 5-fluorouracil resistance were accounted for by cancer cells with high CD44 expression and autophagy, respectively. Such cancer cells were found to be enriched in patient-derived 3D organoids surviving 5-fluorouracil treatment. Conclusions: The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine.

Primary Tumor Score Based on Tumor Depth and Length Predicts Prognosis in Esophageal Squamous Cell Carcinoma.

AIM: To examine the depth of tumor invasion and tumor length and assess the clinical impact of the primary tumor score (PTS), based on a combination of tumor invasion and tumor length, in patients with esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: A total of 237 patients with ESCC were classified into three PTS groups based on cut-off values for deeper tumor invasion (pT2-T4) and greater tumor length (≥44 mm). A PTS of 2 indicated the presence of both of these abnormalities, 1 indicated one of these abnormalities, and 0 indicated neither abnormality. RESULTS: PTS was significantly positively correlated with depth of tumor invasion, lymph node metastasis, lymphovascular invasion, and stage (all p<0.001). The prognosis differed significantly among the three groups based on PTS (p<0.0001). Multivariate analysis demonstrated that PTS was an independent prognostic factor (p=0.0004). CONCLUSION: PTS has a clinical utility as a prognostic predictor in patients with ESCC.

Management of a case of high-risk gastrointestinal stromal tumor in rectum by transanal minimal invasive surgery.

BACKGROUND: Rectal gastrointestinal stromal tumor (GIST) is a very rare tumor of gastrointestinal tract. Surgical management of rectal GIST requires special attention for preserving of anal and urinary functions. Transanal minimal invasive surgery (TAMIS) is a well-developed minimally invasive technique for local excision of benign and early malignant rectal tumors; however, the application of TAMIS for rectal GIST is rarely and inadequately reported. We report the novel application of TAMIS for rectal GIST with considerations for anal and urinary functions. CASE PRESENTATION: A 67 years old female, who presented with history of per rectal bleeding, was diagnosed with submucosal GIST of 4.5 cm in diameter at right posterior wall of 7 cm from anal verge. Histology of biopsy showed abundant spindle-shaped cells arranged in bundles that were positive for CD34 and negative for C-Kit, desmin, smooth muscle actin (SMA), and S-100. The tumor was excised by TAMIS successfully. Final histopathology showed pT2 tumor with C-Kit positive and mitosis count 10 per 50 HPF. Postoperative period was uneventful, and she was discharged on adjuvant imatinib mesylate for 3 years. CONCLUSION: TAMIS can be used safely in the management of rectal GIST after appropriate evaluation of tumor size, extent, location, and experience of operating surgeon.