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Salvage surgery for esophageal cancer after definitive chemoradiotherapy (dCRT) is effective, but it is associated with a high rate of perioperative complications. The indications for robot‐assisted minimally invasive esophagectomy (RAMIE) are expanding. However, there are few reports of salvage RAMIE. A 73‐year‐old man was referred to our hospital for residual esophageal cancer with a mediastinal fistula after dCRT. The perioperative diagnosis was T3N1M0‐Stage III, and the salvage RAMIE was performed. Although the dissection was difficult due to fibrosis caused by dCRT and the esophageal mediastinal fistula, RAMIE was performed safely with no complications. Multiple features of RAMIE contributed to stable surgery. The monopolar dissection is effective for hard scar tissue caused by CRT and inflammation. [ABSTRACT FROM AUTHOR]

Conventional imaging techniques are available for clinical identification of tumor sites. However, detecting metastatic tumor cells that are spreading from primary tumor sites using conventional imaging techniques remains difficult. In contrast, fluorescence‐based labeling systems are useful tools for detecting tumor cells at the single‐cell level in cancer research. The ability to detect fluorescent‐labeled tumor cells enables investigations of the biodistribution of tumor cells for the diagnosis and treatment of cancer. For example, the presence of fluorescent tumor cells in the peripheral blood of cancer patients is a predictive biomarker for early diagnosis of distant metastasis. The elimination of fluorescent tumor cells without damaging normal tissues is ideal for minimally invasive treatment of cancer. To capture fluorescent tumor cells within normal tissues, however, tumor‐specific activated target molecules are needed. This review focuses on recent advances in tumor‐targeted fluorescence labeling systems, in which indirect reporter labeling using tumor‐specific promoters is applied to fluorescence labeling of tumor cells for the diagnosis and treatment of cancer. Telomerase promoter‐dependent fluorescence labeling using replication‐competent viral vectors produces fluorescent proteins that can be used to detect and eliminate telomerase‐positive tumor cells. Tissue‐specific promoter‐dependent fluorescence labeling enables identification of specific tumor cells. Vimentin promoter‐dependent fluorescence labeling is a useful tool for identifying tumor cells that undergo epithelial–mesenchymal transition (EMT). The evaluation of tumor cells undergoing EMT is important for accurately assessing metastatic potential. Thus, tumor‐targeted fluorescence labeling systems represent novel platforms that enable the capture of tumor cells for the diagnosis and treatment of cancer. [ABSTRACT FROM AUTHOR]

Esophageal cancer is a disease showing poor prognosis. Although combination chemotherapy using cisplatin (CDDP) and 5‐fluorouracil is standard for unresectable esophageal cancer, the response rate is 35%. Cancer stem cells (CSCs) and inflammation are reportedly responsible for the poor prognosis of esophageal cancer. However, comprehensive analyses have not been conducted and proposals for progress remain lacking. Iron is known to be a key factor in the stemness of CSCs. Our study focused on the therapeutic potential of iron control using iron chelators for CSCs in esophageal cancer. Among 134 immunohistochemically analyzed cases, Nanog expression was high in 98 cases and low in 36 cases. High Nanog expression correlated with low overall and disease‐free survivals. The iron chelators deferasirox (DFX) and SP10 suppressed the proliferation and expression of stemness markers in TE8 and OE33 cells. DFX and SP10 did not induce compensatory interleukin (IL)‐6 secretion, although CDDP did result in high induction. Moreover, BBI608 and SSZ, as other CSC‐targeting drugs, could not suppress the expression of stemness markers. Overall, Nanog expression appears related to poor prognosis in esophageal cancer patients, and inhibition of stemness and compensatory IL‐6 secretion by iron chelators may offer a novel therapeutic strategy for esophageal cancer. What's new? IL‐6 correlates with poor prognosis in esophageal cancer. However, biomarkers specifically related to esophageal cancer stem cells remain to be established. In this study of radical esophagectomy patients, high expression of the stemness marker Nanog correlated with low overall survival in the neoadjuvant therapy group only. Iron chelators, but not other cancer stem cell‐targeting drugs, suppressed Nanog expression without compensatory IL‐6 secretion. Altogether, Nanog could potentially be used as a marker of resistance to conventional 5‐FU and/or cisplatin chemotherapy in esophageal cancer patients, and inhibition of stemness and compensatory IL‐6 secretion by iron chelators could represent a novel therapeutic strategy. [ABSTRACT FROM AUTHOR]

Introduction: Intracorporeal Billroth I (B‐I) reconstruction using an endoscopic linear stapler (ELS) is widely performed in total laparoscopic distal gastrectomy. However, conventional procedures require many ELSs for anastomosis. Here, we introduce the novel intracorporeal semi‐hand‐sewn (SHS) B‐I reconstruction. Materials and surgical technique: After the transection of stomach and duodenum using ELS following adequate lymph node dissection, small entry holes were made on the anterior wall in the greater curvature of the stomach and the duodenal stump. The posterior walls of both the remnant stomach and the duodenum were attached with the ELS and fired to create the posterior wall of the B‐I anastomosis. All the transection line of the duodenum and one‐third of the transection line of the stomach were dissected; finally the anterior wall suturing at the anastomotic site was performed by the laparoscopic hand‐sewn technique. Discussion SHS procedure was performed for 17 gastric cancer patients. There were no intraoperative complications or conversions to open surgery. One intra‐abdominal abscess was observed although there was no anastomotic leakage. The median reconstruction time was 48 minutes (32‐63). The SHS procedure was safe, feasible, and economical, although it requires sufficient laparoscopic suturing and ligation skill. [ABSTRACT FROM AUTHOR]

An aberrant right subclavian artery (ARSA) is one of the famous anatomical abnormalities with a prevalence of 0.16–4.4%. In esophagectomy, anatomical abnormalities of the ARSA could cause complications with some surgical procedures. An 85‐year old man was referred to our department for esophageal adenocarcinoma that was at a slightly high position for esophagectomy with the abdominal approach. However, he had a significant past medical history. This risk factor made it difficult to perform thoracoscopic esophagectomy. He underwent mediastinoscopic esophagectomy (ME) with the left cervical and laparoscopic approach. The ARSA presented no difficulties with the ME surgical technique including the dissection of the left recurrent laryngeal nerve lymph node. Although this patient had a respiratory dysfunction and some difficulties in a prone position, ME enabled a safe esophagectomy with lymph node dissection. [ABSTRACT FROM AUTHOR]

Lymph node metastasis is a pathognomonic feature of spreading tumors, and overcoming metastasis is a challenge in attaining more favorable clinical outcomes. Esophageal cancer is an aggressive tumor for which lymph node metastasis is a strong poor prognostic factor, and the tumor microenvironment (TME), and cancer‐associated fibroblasts (CAFs) in particular, has been implicated in esophageal cancer progression. CAFs play a central role in the TME and have been reported to provide suitable conditions for the progression of esophageal cancer, similar to their role in other malignancies. However, little is known concerning the relevance of CAFs to the lymph node metastasis of esophageal cancer. Here, we used clinical samples of esophageal cancer to reveal that CAFs promote lymph node metastasis and subsequently verified the intercellular relationships in vitro and in vivo using an orthotopic metastatic mouse model. In the analysis of clinical samples, FAP+ CAFs were strongly associated with lymph node metastasis rather than with other prognostic factors. Furthermore, CAFs affected the ability of esophageal cancer cells to acquire metastatic phenotypes in vitro; this finding was confirmed by data from an in vivo orthotopic metastatic mouse model showing that the number of lymph node metastases increased upon injection of cocultured cancer cells and CAFs. In summary, we verified in vitro and in vivo that the accumulation of CAFs enhances the lymph node metastasis of ESCC. Our data suggest that CAF targeted therapy can reduce lymph node metastasis and improve the prognosis of patients with esophageal cancer in the future. What's new? When fighting a tumor, targeting the tumor microenvironment can be more effective than hitting the tumor itself. To study lymph node metastasis in esophageal cancer, these authors tested clinical samples to evaluate expression of fibroblast‐activation protein (FAP) by cancer‐associated fibroblasts in the tumor stroma. The more FAP‐positive CAFs, the greater the likelihood of lymph node metastasis, they found. Next, they tested the effect in vivo. Mice injected with FAP‐positive CAFs developed far more metastases than their control counterparts. Targeting CAFs may improve prognosis and reduce lymph node metastasis in esophageal cancer. [ABSTRACT FROM AUTHOR]

Aim: As a result of the difficulty in effective prevention of gastroesophageal reflux, no standard reconstruction procedure after proximal gastrectomy (PG) has yet been established. The double‐flap technique (DFT), or Kamikawa procedure, is an antireflux reconstruction procedure in esophagogastrostomy. The efficacy of DFT has recently been reported in several studies. However, these were all single‐center studies with a limited number of cases. Methods: We conducted a multicenter retrospective study in which patients who underwent DFT, irrespective of disease type and reconstruction approach, at each participating institution between 1996 and 2015 were registered. Primary endpoint was incidence of reflux esophagitis at 1‐year after surgery, and secondary endpoint was incidence of anastomosis‐related complications. Results: Of 546 patients who were eligible for this study, 464 patients who had endoscopic examination at 1‐year follow up were evaluated for reflux esophagitis. Incidence of reflux esophagitis of all grades was 10.6% and that of grade B or higher was 6.0%. Male gender and anastomosis located in the mediastinum/intra‐thorax were independent risk factors for grade B or higher reflux esophagitis (odds ratio [OR]: 4.21, 95% confidence interval [CI]: 1.44‐10.9, P = 0.0109). Total incidence of anastomosis‐related complications was 7.2%, including leakage in 1.5%, strictures in 5.5% and bleeding in 0.6% of cases. Laparoscopic reconstruction was the only independent risk factor for anastomosis‐related complications (OR: 3.93, 95% CI: 1.93‐7.80, P = 0.0003). Conclusion: Double‐flap technique might be a feasible option after PG for effective prevention of reflux, although anastomotic stricture is a complication that must be well‐prepared for. A multicenter retrospective study in which 546 patients who underwent the double‐flap technique (DFT), irrespective of disease type and reconstruction approach, at each participating institution between 1996 and 2015 were registered, showed that the incidence of reflux esophagitis of all grades was 10.6% and that of grade B or higher was 6.0%, and the total incidence of anastomosis‐related complications was 7.2%, including leakage in 1.5%, strictures in 5.5% and bleeding in 0.6% of cases. DFT might be a feasible option after proximal gastrectomy for effective prevention of reflux, although anastomotic stricture is a complication that must be well‐prepared for. [ABSTRACT FROM AUTHOR]

Iron is an essential element for both normal and cancer cells in humans. Treatment to reduce iron levels has been shown to suppress tumor growth in vivo. However, iron depletion monotherapy by iron decreased treatment has not been thought to be superior to ordinary chemotherapy and is not part of the standard therapeutic strategy for the treatment of cancer. Iron depletion is also known to reduce serum hemoglobin and oxygen supply to the tissue, which indicates that iron depletion may induce angiogenesis. Therefore, we hypothesized that iron depletion with antiangiogenic therapy can have a novel therapeutic effect in the treatment of cancer. Human nonsmall cell carcinoma cell lines A549 and H1299 were used in our study. An iron-deficient diet and an iron chelator were used to simulate an iron-depleted condition. The antitumor effects of iron depletion and antiangiogenic therapy were determined on A549 xenograft mice. The iron-depleted condition produced by an iron-deficient diet suppressed tumor growth. Tumor tissue from the iron-deficient diet group showed that cancer cell proliferation was suppressed and hypoxia was induced. Microvessel density of this group was increased which suggested that the iron-depleted condition induced angiogenesis. Bevacizumab administration had a synergetic effect on inhibiting the tumor growth on Day 39. An iron-depleted condition inhibited cancer cell proliferation and reciprocally induced angiogenesis. Bevacizumab synergistically enhanced the iron-depleted antitumor effect. Treatment to deplete iron levels combined with anti-angiogenic therapy could induce a novel therapeutic effect in the treatment of cancer. [ABSTRACT FROM AUTHOR]

Sonoda R, Naomoto Y, Shirakawa Y, Fujiwara Y, Yamatsuji T, Noma K, Tanabe S, Takaoka M, Gunduz M, Tsujigiwa H, Nagatsuka H, Ohara N, Yoshino T, Takubo K, Vieth M & Tanaka N (2010) Histopathology 57, 90–100 Preferential up-regulation of heparanase and cyclooxygenase-2 in carcinogenesis of Barrett’s oesophagus and intestinal-type gastric carcinoma Aims: Metaplastic changes secondary to chronic inflammation at the gastro–oesophageal junction and at the pyloric antrum are recognized as the premalignant conditions of Barrett’s oesophageal adenocarcinoma and intestinal-type gastric carcinoma (GC), respectively. Heparanase (HPSE) and cyclooxygenase (COX)-2 have been proved to play critical roles in inflammation as well as in cancer. The aim was to examine the meaning of their expression in inflammation-related carcinogenesis. Methods and results: First, expression of HPSE and COX-2 in 78 clinical tissues of Barrett’s oesophagus was examined by immunohistochemistry and in situ hybridization. Their expression was increased during the metaplasia–dysplasia sequence with increased neovascularization. Successively, their expression in Barrett’s dysplasia was compared with that of GC (22 cases of diffuse-type and 10 of intestinal-type). Interestingly, the expression pattern in Barrett’s dysplasia was similar to that in intestinal-type GC, which mainly arises from chronic inflammation. Furthermore, cultured cell lines isolated from differentiated GC tissues, which are often found to be of intestinal-type, revealed up-regulated mRNA expression of HPSE and COX-2. Conclusions: HPSE and COX-2 are preferentially up-regulated in Barrett’s oesophagus and intestinal-type GC. These molecules may play an important role during the development of inflammation-related adenocarcinoma of the upper gastrointestinal tract. [ABSTRACT FROM AUTHOR]