The 11th edition of the Japanese Classification of Esophageal Cancer (EC) was published in 2017. Some correction was made in the depth of tumor invasion to be consistent with the TNM classification by the Union for International Cancer Control (UICC). With regard to surgery, short‐term safety and long‐term effectiveness under thoracotomy/video‐assisted thoracoscopic surgery are expected to be proven by the Japan Clinical Oncology Group (JCOG)1409 study. Results of nutritional management and countermeasures for adverse events not only during the perioperative period but also during EC chemotherapy were reported. From now on, the pursuit of low invasiveness and radicality is desired. Esophageal surgery is also expected to be safe at all institutions. To determine the optimal modality of preoperative treatment and a novel chemo(radio)therapy regimen for patients with distant metastasis, the results of the ongoing JCOG1109 and 0807 studies are being released. The effect of the addition of molecular targeted drugs on chemotherapy and concurrent chemoradiation has not yet improved overall survival. Immune checkpoint inhibitor drugs could offer a potential new treatment approach for patients with treatment‐refractory advanced squamous cell carcinoma (SCC). The Cancer Genome Atlas Research Network reported the results of a comprehensive genome analysis and molecular analysis of SCC and adenocarcinoma of the esophagus. Further differentiation of SCC and adenocarcinoma by molecular characterization analysis may be useful for the development of clinical trials and targeted drug therapies as precision medicine. The era of ultimate minimally invasive surgery and personalized treatment has begun. Large, prospective studies will be required to confirm the value of these advancements.

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Background 5FU can be converted to its active metabolite fluoro-deoxyuridine monophosphate (FdUMP) through two pathways: the orotate phosphoribosyl transferase–ribonucleotide reductase (OPRT–RR) pathway and the thymidine phosphorylase–thymidine kinase (TP–TK) pathway. We investigated the mechanism underlying 5FU-resistance, focusing on the changes in the 5FU metabolisms. Methods MKN45 and 5FU-resistant MKN45/F2R cells were treated with 5FU or fluoro-deoxyuridine (FdU) in combination with hydroxyurea (HU) or tipiracil (TPI). The amount of FdUMP was determined by the density of the upper band of thymidylate synthase on Western blotting. Results The MKN45/F2R cells exhibited 5FU resistance (37.1-fold) and showed decreased OPRT and increased TP levels. In both cells, the FdUMP after treatment with 5FU was decreased when RR was inhibited by HU but not when TP was inhibited by TPI. A metabolome analysis revealed the loss of intracellular deoxyribose 1-phosphate (dR1P) in both cells, indicating that FdUMP was synthesized from 5FU only through the OPRT–RR pathway because of the loss of dR1P. After the knockdown of TK, the FdUMP after treatment with FdU was decreased in MKN45 cells. However, it was not changed in MKN45/F2R cells. Furthermore, TP inhibition caused an increase in FdUMP after treatment with 5FU or FdU and reversed the 5FU resistance in MKN45/F2R cells, indicating that FdUMP was reduced through the TP–TK pathway in MKN45/F2R cells. Conclusions In MKN45/F2R cells, the reduction of FdUMP through the TP–TK pathway caused 5FU resistance, and the inhibition of TP reversed the resistance to 5FU, suggesting that the combination of 5FU and TPI is a promising cancer therapy.

Aim The objective of this retrospective, single‐institution study was to assess the safety and feasibility of reconstruction using subtotal stomach (SS) with esophagectomy for patients with esophageal cancer (EC). Although several different gastric‐tube‐making and anastomotic methods have been reported, the incidence rate of anastomotic leakage with EC surgery is generally reported over 10%. Complications should be avoided, and patient quality of life (QOL) should be maintained postoperatively. We have used SS reconstruction and hand‐sutured cervical esophagus‐subtotal gastric anastomosis at the neck wound in EC surgery. Short‐ and long‐term outcomes in cases using SS are not well known. Methods Between January 2008 and September 2019, 300 patients underwent esophagectomy for EC and reconstruction using SS. The primary endpoint was the rate of anastomotic leakage. Secondary endpoints were postoperative morbidities, QOL, and changes in patients’ body weight and skeletal muscle weight. Results Anastomotic leakage was observed in two patients (0.67%), and pneumonia was observed in nine patients (3.0%). Fifteen patients (5.0%) had an anastomotic stenosis requiring a bougie. Nausea occurred in 11 patients (3.7%), and dumping syndrome occurred in seven patients (2.3%). Dysphagia and early feeling of abdominal fullness scores tended to be high after surgery but gradually decreased after 6 months. Good results were obtained for reflux feeling scores. Body weight changed with an average decrease of −2 ± 3.71 kg ( P = .071) over 5 years. Conclusion Reconstruction using SS resulted in an extremely low rate of anastomotic leakage and good QOL postoperatively in patients with EC.

The combination regimen of TAS-102, a novel oral nucleoside antitumor agent containing trifluridine and tipiracil hydrochloride, with bevacizumab (C-TASK FORCE), a selective monoclonal antibody inhibitor of vascular endothelial growth factor-A, as salvage-line therapy for metastatic colorectal cancer (mCRC) was established based on its high clinical effectiveness. The aim of the present study was to evaluate the prognostic accuracy of the modified Glasgow Prognostic Score (mGPS) in patients receiving TAS-102 plus bevacizumab. The study included 17 patients (12 men and 5 women, mean age 60.4±13.4 years) with unresectable mCRC who were confirmed to have wild-type or mutant RAS genes. The patients received salvage-line treatment with TAS-102 plus bevacizumab at the Surgical Oncology

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Background The development of esophago-bronchial fistula after esophagectomy and reconstruction using a posterior mediastinal gastric tube remains a rare complication associated with a high rate of mortality. Case presentation A 63-year-old man with esophageal cancer underwent a thoracoscopic esophagectomy with two-field lymph node dissection and reconstruction via a gastric tube through the posterior mediastinal route. Postoperatively, the patient developed extensive pyothorax in the right lung due to port site bleeding and hematoma infection. Four months after surgery, he developed an esophago-left bronchial fistula due to ischemia of the cervical esophagus and severe reflux esophagitis at the site of the anastomosis. Because of respiratory failure due to the esophago-bronchial fistula and the history of extensive right pyothorax, right thoracotomy and left one-lung ventilation were thought to be impossible, so we decided to perform the surgery in three-step systematically. First, we inserted a decompression catheter and feeding tube into the gastric tube as a gastrostomy and expected neovascularization to develop from the wall of the gastric tube through the anastomosis after this procedure. Second, 14 months after esophagectomy, we constructed an esophagostomy after confirming blood flow in the distal side of the cervical esophagus via gastric tube using intraoperative indocyanine green-guided blood flow evaluation. In the final step, we closed the esophagostomy and performed a cervical esophago-jejunal anastomosis to restore esophageal continuity using a pedicle jejunum in a Roux-en-Y anastomosis via a subcutaneous route. Conclusion This three-step operation can be an effective procedure for patients with esophago-left bronchial fistula after esophagectomy, especially those with respiratory failure and difficulty in undergoing right thoracotomy with left one-lung ventilation.

Fluorouracil (5FU) is converted to its active metabolite fluoro-deoxyuridine monophosphate (FdUMP) through the orotate phosphoribosyl transferase (OPRT)-ribonucleotide reductase (RR) pathway and thymidine phosphatase (TP)-thymidine kinase (TK) pathway and inhibits thymidylate synthase (TS), leading to inhibition of thymidine monophosphate (dTMP) synthesis through a de novo pathway. We investigated the mechanism of 5FU resistance and strategies to overcome it by focusing on 5FU metabolism. Colon cancer cell lines SW48 and LS174T and 5FU-resistant cell lines SW48/5FUR and LS174T/5FUR were used. FdUMP amount was measured by western blotting. The FdUMP synthetic pathway was investigated by combining TP inhibitor (tipiracil hydrochloride; TPI) or RR inhibitor (hydroxyurea; HU) with 5FU. Drug cytotoxicity was observed by crystal violet staining assay. FdUMP was synthesized through the OPRT-RR pathway in SW48 cells but was scarcely synthesized through either the OPRT-RR or TP-TK pathway in SW48/5FUR cells. FdUMP amount in SW48/5FUR cells was reduced by 87% vs. SW48 cells. Expression levels of OPRT and TP were lower in SW48/5FUR when compared with these levels in the SW48 cells, indicating decreased synthesis of FdUMP-led 5FU resistance. These results indicated that fluoro-deoxyuridine (FdU) rather than 5FU promotes FdUMP synthesis and overcomes 5FU resistance. Contrastingly, FdUMP was synthesized through the OPRT-RR and TP-TK pathways in LS174T cells but mainly through the TP-TK pathway in LS174T/5FUR cells. FdUMP amount was similar in LS174T/5FUR vs. the LS174T cells. OPRT and RR expression was lower and TK expression was higher in LS174T/5FUR vs. the LS174T cells, indicating that dTMP synthesis increased through the salvage pathway, thus leading to 5FU resistance. LS174T/5FUR cells also showed cross-resistance to FdU and TS inhibitor, suggesting that nucleoside analogs such as trifluoro-thymidine should be used to overcome 5FU resistance in these cells. 5FU metabolism and mechanisms of 5FU resistance are different in each cell line. Both synthesized FdUMP amount and FdUMP sensitivity should be considered in 5FU-resistant cells.