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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]

Introduction: Although some studies have reported on the relationship between appendiceal stump closure methods and postoperative complications, there is no fixed method for this procedure. This study aimed to compare treatment outcomes of the existing procedures. Methods: We retrospectively analyzed the records of 200 patients who underwent urgent laparoscopic surgeries and investigated whether the difference in the appendiceal stump closure method was a risk factor for surgical site infection. The patients were divided into the Endoloop and endostapler groups, and 45 propensity score‐matched patients were included. The treatment outcomes of the two groups were compared. Results: The patients with high body temperature showed significantly developed surgical site infection in multivariate analysis (P =.036). There was no significant difference in the appendix stump methods (Endoloop vs endostapler). Regarding postoperative complications, superficial and deep incisional surgical site infection, organ/space surgical site infection, ileus, and complications of Clavien–Dindo grade IIIa or higher; there was no significant difference between the endoloop and endostapler groups after propensity score matching (P =.725, 1.000,.645 and.557, respectively). Conclusion: By properly using the Endoloop and endostapler according to the severity of inflammation, the Endoloop can be safely performed in many cases. Inexpensive Endoloop as an option for stump closure methods should positively impact medical costs. [ABSTRACT FROM AUTHOR]

We present a case of early gastric cancer in the pylorus with a type 3 hiatal hernia, which was treated by endoscopic submucosal dissection (ESD). A 70‐year‐old man was referred to our hospital with a hiatal hernia. Endoscopy revealed early gastric cancer, and we performed an ESD adaptation at the pylorus. The ESD was successful, but post‐ESD pyloric stenosis occurred. Symptoms of hiatal hernia worsened because of the pyloric stenosis. Laparoscopic hiatal hernia repair with Toupet fundoplication and Heineke‐Mikulicz pyloroplasty was simultaneously performed. The postoperative course was good, and follow‐up after discharge was uneventful. To our knowledge, there have been no reports in which laparoscopic hiatal hernia repair, fundoplication, and pyloroplasty were simultaneously performed for a substantial hiatal hernia with post‐ESD pyloric stenosis. [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]

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]

We examined whether dynamically changing light across a scheduled 16‐h waking day influences sleepiness, cognitive performance, visual comfort, melatonin secretion, and sleep under controlled laboratory conditions in healthy men. Fourteen participants underwent a 49‐h laboratory protocol in a repeated‐measures study design. They spent the first 5 hours in the evening under standard lighting, followed by an 8‐h nocturnal sleep episode at habitual bedtimes. Thereafter, volunteers either woke up to static light or to a dynamic light that changed spectrum and intensity across the scheduled 16‐h waking day. Following an 8‐h nocturnal sleep episode, the volunteers spent another 11 hours either under static or dynamic light. Static light attenuated the evening rise in melatonin levels more compared to dynamic light as indexed by a significant reduction in the melatonin AUC prior to bedtime during static light only. Participants felt less vigilant in the evening during dynamic light. After dynamic light, sleep latency was significantly shorter in both the baseline and treatment night while sleep structure, sleep quality, cognitive performance, and visual comfort did not significantly differ. The study shows that dynamic changes in spectrum and intensity of light promote melatonin secretion and sleep initiation in healthy men. [ABSTRACT FROM AUTHOR]

Over the past decade there has been tremendous development in the clinical application of minimally invasive esophagectomy (MIE) for the treatment of squamous esophageal carcinoma. The major challenges in the performance of MIE include limitations in visualization and manipulation within the confined, rigid thoracic cavity; the need for adequate patient positioning and anesthetic techniques to accommodate the surgical exposure; and changes in the surgical steps for achieving radical nodal dissection, especially for the superior mediastinum. The surgical procedure for MIE is more and more standardized, and there is an increasing practice of MIE worldwide. Randomized trials and meta‐analyses have confirmed the advantages of MIE over open esophagectomy, including a significantly lower rate of complications and shorter hospital stays. The recent application of robotics technologies for MIE has further enhanced the quality and safety of the surgical dissection, while intraoperative nerve monitoring has contributed to a lower rate of recurrent laryngeal nerve palsy. With the application of new technologies, we expect further improvement in surgical outcomes for MIE in the treatment of squamous esophageal cancer. [ABSTRACT FROM AUTHOR]

Several virulence factors of Aeromonas such as hemolysin, proteases and lipases have been characterized. The relationship between these virulence factors and disease remains unclear. A 71‐year‐old man underwent thoracoscopic esophagectomy, lymph node dissection and Roux‐en‐Y reconstruction for esophageal cancer. On postoperative day 1, redness around the wound on the thoracic abdominal wall gradually enlarged and necrosis became apparent with septic shock. Necrotizing soft tissue infection was suspected and emergency surgical debridement was performed. Blood and wound cultures were positive for Aeromonas hydrophila. The strain was found to have hemolytic activity, proteolytic activity and extremely high elastolytic activity. In addition, the strain actively produced elastolytic metalloprotease, which may contribute to extensive tissue necrosis. [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]

We recently reported that heparanase, one of the extracellular matrix-degrading enzymes, which plays a critical role in cancer progression, is located not only in the cytoplasm but also in the nucleus. Here we identified nuclear translocation of heparanase as a key step in cell differentiation. We applied an in vitro differentiation model of HL-60 cells with 12–0-tetradecanoylphorbol-13-acetate (TPA), in which nuclear translocation of heparanase was observed using immunohistochemical analysis. In this system, nuclear translocation of heparanase was abolished by inhibitors of heat shock protein 90 (HSP90), suggesting the involvement of HSP90 in translocation of heparanase. We further confirmed that overexpression of active form of heparanase induced differentiation of HL-60 cells, although the catalytic negative form of heparanase did not. Therefore we speculate that nuclear translocation of enzymatically active heparanase may be involved in cellular differentiation. Our results suggest that a novel function of heparanase upon cell differentiation would raise a potential new strategy for cancer therapy of promyeloid leukemia and other types of cancer. ( Cancer Sci 2007; 98: 535–540) [ABSTRACT FROM AUTHOR]

With steady aging of society, the number of patients with dysphagia due to esophageal cancer and to muscular and neural diseases is increasing. This tendency is a problem from the viewpoint of social welfare. We intended to develop a simple quantitative evaluation method for the swallowing function, and we propose impedance pharyngography (IPG), which can measure noninvasively the electrical impedance of the neck during swallowing. Although the swallowing function is reflected in the IPG, the effect of swallowing function degradation on the waveform varies depending on the cause of the problem, making it difficult to compare simply the IPGs of subjects with various states of the swallowing function. In this study, four parameters are defined, based on the normal IPGs of normal young subjects, in order to evaluate the waveform features representing the swallowing function, namely, the pharynx transit time, the rate of impedance change, the similarity, and the timing of the swallowing sound. Then, a method is proposed to evaluate the IPG quantitatively. IPGs of two groups, young and elderly, are analyzed in terms of these parameters, and it is shown that the degradation of the lifting speed and the lifting distance of the larynx, and also degradation of smooth activity of the organs related to swallowing, can be detected as differences in the parameters. © 2006 Wiley Periodicals, Inc. Syst Comp Jpn, 37(13): 20–27, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.20588 [ABSTRACT FROM AUTHOR]

Temsirolimus (CCI-779), a recently synthesized analogue of rapamycin, specifically inhibits mTOR and has been approved for clinical use in renal cell carcinoma. Recent reports have indicated the growth inhibitory effect of temsirolimus in some cancers including non-small-cell lung carcinoma (NSCLC). In this study, we aimed to explore the potential therapeutic use of temsirolimus as a treatment for NSCLC. Using cultured NSCLC cells (A549, H1299, and H358), we determined the effect of temsirolimus on cell proliferation and its antitumor effects on subcutaneous tumors, as well as its contribution to the survival of mice having pleural dissemination of cancer cells, mimicking advanced NSCLC. Temsirolimus suppressed proliferation of NSCLC cells in a dose-dependent manner, with an IC of <1 nM. Western blot analysis revealed that temsirolimus treatment specifically inhibited the phosphorylation of mTOR and its downstream effectors in 1 h, accompanied by an increased cell population in the G/G phase, but according to flow cytometry, the cell population did not increase in the sub-G phase. When NSCLC subcutaneous tumor-bearing mice were treated with temsirolimus, tumor volume was significantly reduced (tumor volume on day 35: vehicle vs temsirolimus = 1239 vs 698 cm; P < 0.05). Furthermore, prolonged survival was observed in pleural disseminated tumor-bearing mice with temsirolimus treatment (median survival: vehicle vs temsirolimus = 53.5 vs 72.5 days; P < 0.05). These results suggest that temsirolimus could be useful for NSCLC treatment, due to its antiproliferative effect, and could be a potential treatment for advanced NSCLC, giving prolonged survival. ( Cancer Sci 2011; 102: 1344-1349) [ABSTRACT FROM AUTHOR]