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Cephalic arch stenosis (CAS) is a common cause of vascular access dysfunction in patients undergoing hemodialysis. This report describes a case of recurrent stent fractures and restenosis following endovascular treatment for CAS. A 34-year-old man with diabetic nephropathy and chronic hemodialysis underwent multiple stent placements for CAS. Complications, including stent entanglement during balloon angioplasty and stent fracture due to the cephalic arch's anatomical characteristics, necessitated surgical intervention. This case highlights two critical considerations: the unsuitability of balloon-expandable stents for CAS, as they lack resilience to deformation caused by shoulder movements, and the importance of selecting appropriate balloons to minimize stent damage. The unique anatomical characteristics of the cephalic arch increase the risk of stent bending and fracture, emphasizing the need for careful device selection. This case increases the awareness of stent placement for CAS., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Doita et al.)

Aims: To determine suitable food textures for videofluoroscopic study of swallowing (VFSS), in order to predict and prevent subsequent aspiration pneumonia in esophageal cancer patients with dysphagia after surgery., Materials and Methods: We evaluated 45 hospitalized esophageal cancer patients who underwent surgery between January 2012 and December 2013. The control group consisted of 43 patients treatmed from January 2010 until December 2011 and were not examined by VFSS. Test foods, which were presented in order of increasing thickness, included thin barium sulfate (Ba) liquid (3 or 10 ml), slightly thickened Ba liquid (3 or 10 ml), a spoonful of Ba jelly, and a spoonful of Ba puree., Results: Patients could most safely swallow puree, followed by jelly. The 3mL samples of both the thin and thick liquids put patients at risk for aspiration pneumonia, with incidence rates of 13% and 11%, respectively. While 64.4% of patients could swallow all test foods and liquids safely, 35.6% were at risk for aspiration pneumonia when swallowing liquids. Even though >30% of patients were at risk, only 1 (2.2%) in the VFSS group developed aspiration pneumonia, which occurred at the time of admission. Following VFSS, no incidence of aspiration pneumonia was observed. However, aspiration pneumonia occurred in 4 (9.3%) control patients during hospitalization., Conclusions: Postoperative esophageal cancer patients were more likely to aspirate any kind of liquid than solid foods, such as jellies. VFSS is very useful in determining suitable food textures for postoperative esophageal cancer patients.

Since reported in the JCOG9907 trial, neoadjuvant chemotherapy prior to surgery has become the standard treatment for advanced (Stage II/III) esophageal cancers. However, more powerful neoadjuvant chemotherapy is required for the treatment of locally advanced cases or cases involving multiple lymph node metastases. At our institute, DCF therapy (docetaxel, cisplatin, and 5-fluorouracil) is administered selectively for the treatment of patients with far-advanced esophageal cancer. We treated 53 thoracic esophageal cancer patients who underwent surgery following neoadjuvant chemotherapy between January 2010 and December 2012. FP therapy (cisplatin and 5-fluorouracil) was administered to 43 patients, and DCF therapy to 7 patients who had far-advanced esophageal cancer. All patients treated with DCF therapy experienced grade 3 and 4 adverse events. With the exception of 1 patient, all patients who received DCF therapy could undergo curative surgery. DCF therapy could become an effective preoperative chemotherapy.

An 80-year-old woman, who had been administered α-glucosidase inhibitor for diabetes, was brought to the hospital with the sensation of abdominal fullness and pain. Abdominal computed tomography indicated pneumatosis cystoides intestinalis (PCI) in the small intestinal wall, with free air within the abdomen. A blood examination showed no increases in white blood cells or C-reactive protein level. The patient's condition improved with conservative therapy. PCI with pneumoperitoneum induced by α-glucosidase inhibitor is rare, with only 27 cases (excluding the present case) reported in Japan to date. In PCI with pneumoperitoneum, differentiation from gastrointestinal perforation is important and following the clinical symptoms over time is vital.

Heat shock protein 90 (HSP90), a molecular chaperone, has provoked great interest as a promising molecular target for cancer treatment, due to its involvement in regulating the conformation, stability and functions of key oncogenic proteins. At present, a variety of chemical compounds targeting HSP90 have been developed and have shown convincing anti-neoplastic activity in various preclinical tumor models. The aim of our study was to evaluate the antitumor effects of a novel HSP90 inhibitor, NVP-AUY922, in esophageal squamous cancer cells (ESCC). Four ESCC cell lines (TE-1, TE-4, TE-8, TE-10) were examined. NVP-AUY922 potently inhibited the proliferation of ESCC, particularly in PTEN-null TE-4 cells with a 2-3 times lower IC50 than the other three cell lines. Western blot analysis showed that PTEN-null TE-4 cells exhibited higher AKT and ERK activity, which contribute to cell proliferation and survival. NVP-AUY922 significantly suppressed the activity of AKT and ERK in TE-4 but not in PTEN-proficient TE-10 cells. Genetic modification experiments demonstrated that the sensitivity to NVP-AUY922 was decreased by exogenous transduction of PTEN in TE-4 and increased by silencing PTEN expression in intact PTEN-expressing TE-10, suggesting that the expression of PTEN may be associated with cell sensitivity in HSP90 inhibition. Furthermore, the enhanced activity of AKT in PTEN-silenced TE-10 was more easily suppressed by NVP-AUY922. Collectively, NVP-AUY922 exhibits a strong antiproliferative effect, revealing its potential as a novel therapeutic alternative to current ESCC treatment. The effect may be improved further by impeding PTEN expression.

Aim: To assess the effects of a novel type 1 insulin-like growth factor receptor (IGF-1R) inhibitor, NVP-AEW541, on cell proliferation and signal transduction of esophageal cancer., Materials and Methods: Cell proliferation assay and western blot were conducted to assess the antitumor effects of NVP-AEW541. Genetic modification of RAS by expression vector was applied for overexpression of mutant RAS., Results: More than 2 μmol/l of NVP-AEW541 was required to effectively inhibit the proliferation of esophageal cancer. NVP-AEW541 potently blocked the activation of IGF-1R and protein kinase B (PKB, also known as AKT), but not of mitogen-activated protein kinase kinase (MEK) and extracellular-signal-regulated kinases (ERK). Active RAS was not reduced by NVP-AEW541 in esophageal cancer cells TE-1, suggesting that insensitivity of esophageal cancer to NVP-AEW541 is due to the maintained RAS-MAPK activity, which did not arise from RAS mutation. Moreover, the transduction of mutant RAS reduced the sensitivity of TE-1 cells to NVP-AEW541., Conclusion: Stimulation of RAS-MAPK pathway is associated with resistance to NVP-AEW541 in esophageal cancer. Combining NVP-AEW541 with inhibitors/antibodies against RAS-MAPK signaling molecules might be more effective for use against esophageal cancer.

The functioning of an arteriovenous fistula (AVF) used for vascular access during hemodialysis has been assessed mainly by dilution methods. Although these techniques indicate the immediate recirculation rate, the results obtained may not correlate with Kt/V. In contrast, the clearance gap (CL-Gap) method provides the total recirculation rate per dialysis session and correlates well with Kt/V. We assessed the correlation between Kt/V and CL-Gap as well as the change in radial artery (RA) blood flow speed in the fistula before percutaneous transluminal angioplasty (PTA) in 45 patients undergoing continuous hemodialysis. The dialysis dose during the determination of CL-Gap was 1.2 to 1.4 Kt/V. Patients with a 10% elevation or more than a 10% relative increase in CL-Gap underwent PTA (n = 45), and the values obtained for Kt/V and CL-Gap before PTA were compared with those obtained immediately afterward. The mean RA blood flow speed improved significantly (from 52.9 to 97.5cm/sec) after PTA, as did Kt/V (1.07 to 1.30) and CL-Gap (14.1% to -0.2%). A significant correlation between these differences was apparent (r = -0.436 and p = 0.003). These findings suggest that calculating CL-Gap may be useful for determining when PTA is required and for assessing the effectiveness of PTA, toward obtaining better dialysis.

The HSP90 molecular chaperone family is highly conserved and expressed in various organisms ranging from prokaryotes to eukaryotes. HSP90 proteins play essential housekeeping functions, such as controlling the activity, turnover and trafficking of various proteins, promoting cell survival through maintaining the structural and functional integrity of some client proteins which control cell survival, proliferation and apoptosis, and play an important role in the progression of malignant disease. HSP90 proteins are ATP-dependent chaperones and the binding and hydrolysis of ATP are coupled to conformation changes of HSP90, which facilitate client protein folding and maturation. Many natural and synthetic molecular compounds have been proposed as promising cancer therapy via disrupting the formation of complex ATP-HSP90-client proteins.

Autophagy is a cellular lysosomal degradation pathway involved in proteins and organelles recycling for promoting cell survival, development and homeostasis. It is a multistep process and genetic studies have identified many proteins that participate in autophagosome formation and fusion with lysosomes, and various signaling factors that associate with the regulation of autophagy. In general, autophagy acts as a cell protector and its dysfunction is correlated with diverse pathologies, such as neurodegeneration, liver, heart and muscle diseases, cancer, inflammation and ageing. However, its role in cell death increases the complexity of the autophagic degradation system. A broad understanding of autophagy, ranging from detailed processes, including induction, formation and degradation, to function in physiology and pathology, revealed by accumulating studies, may be helpful for formulating therapeutic strategies for autophagy-associated human diseases.

Esophageal cancer is one of the most frequently occurring cancers in the world. Targeting therapy strategy of cancer with specific inhibitors is developing and has showed promising antitumor efficacy. It is known that mTOR is an important controller of cell growth. RAD001 (everolimus) is a specific inhibitor of mTOR that can block the mTOR signaling pathway. The purposes of this study was to explore the inhibitory effects of RAD001 on mTOR signaling and the mechanism of cell growth suppression by RAD001. We examined both the expression of mTOR, p70S6K and S6 in SEG-1 esophageal cancer cells and KOB-13 normal esophageal epithelial cells and the efficacy of RAD001 against SEG-1 esophageal cancer cells. mTOR, p70S6K and S6 were overexpressed in SEG-1 esophageal cancer cells compared with KOB-13 normal esophageal epithelial cells. SEG-1 esophageal cancer cells were sensitive to RAD001. The survival rate of the cells treated with RAD001 over 0.33 microM was significantly different compared with that of control (P<0.01). RAD001 inhibited the phosphorylation of mTOR (Ser2448) and S6 (Ser240/244) in different grades and the expressions of mTOR, p70S6K and S6. As a result, RAD001 induced a dose-dependent decrease in cell proliferation, G1/S arrest and damage of cell shape. Taken together, these data showed that RAD001 can inhibit mTOR signaling and proliferation in SEG-1 esophageal cancer cells in vitro. It offers a therapeutic intervention through inhibition of mTOR as a potential strategy for esophageal cancer.

Focal adhesion kinase (FAK) is a 125-kDa non-receptor protein tyrosine. Growth factors or the clustering of integrins facilitate the rapid phosphorylation of FAK at Tyr-397 and this in turn recruits Src-family protein tyrosine kinases, resulting in the phosphorylation of Tyr-576 and Tyr-577 in the FAK activation loop and full catalytic FAK activation. FAK plays a critical role in the biological processes of normal and cancer cells including the gastrointestinal tract. FAK also plays an important role in the restitution, cell survival and apoptosis and carcinogenesis of the gastrointestinal tract. FAK is over-expressed in cancer cells and its over-expression and elevated activities are associated with motility and invasion of cancer cells. FAK has been proposed as a potential target in cancer therapy. Small molecule inhibitors effectively inhibit the kinase activity of FAK and show a potent inhibitory effect for the proliferation and migration of tumor cells, indicating a high potential for application in cancer therapy.

In our institute, we introduced PET-CT examination as the preoperative and postoperative screening for esophageal cancer patients in April 2006. During two years before the introduction of PET-CT examination, we performed an intensive local control therapy (operation, RFA, definitive chemoradiotherapy) to 13 cases with single region recurrence (including 5 cases of cervical lymph nodes recurrence, 5 of local recurrence, 3 of distant metastatic recurrence). On the other hand, we performed an intensive local control therapy to 21 cases (including 4 cases of cervical lymph nodes recurrence, 10 of local recurrence, and 7 of distant metastatic recurrence) during two years after the introduction of PET-CT examination. In any pattern, there was a tendency of improvement in the prognosis of recurrent esophageal cancer patients. These results raised the possibility that PET-CT examination was useful for an early detection of the recurrent lesions in postoperative follow-up for esophageal cancer patients. And there might be a chance of curability in patients with single region recurrence by the early detection.

Focal adhesion kinase (FAK) is a 125-kDa non-receptor and non-membrane protein tyrosine. FAK can function with integrins and growth factor receptors to promote cell survival dependent kinase activity and nuclear FAK promotes cell proliferation and survival through FERM (FAK, ezrin, radixin, moesin) domain-enhanced p53 degradation independent kinase activity. Many previous studies have indicated that FAK plays a critical role in the biological processes of normal and cancer cells and FAK has been proposed as a potential target in cancer therapy. Small molecule inhibitors (PF-573,228; PF-562,271 and NVP-226) for use as potential cancer therapies have been developed. However, the detailed mechanism of the role for FAK in tumor cell generation and progression remain unclear, so future work is needed to explore these issues. New inhibitors that can be effectively inhibit the function of FAK still need to be explored due to the low specificity, and resistance.

We report a case of a woman in her sixties having primary duodenal carcinoma with multiple liver metastases who was treated with oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin(FOLFOX regimen). After completing 2 courses of the chemotherapy, computed tomography showed a partial response without any severe adverse events. Now at 8 months, the PR stage has been maintained. So far, no standard therapeutic strategy for metastatic duodenal carcinoma has been developed. However, we suggest a FOLFOX regimen can be highly effective as a safe approach for continuously maintaining the quality of life of patients with this rare type of cancer.

There is currently no suitable animal model of metastasis using cultured human gastrointestinal stromal tumor cells even though the molecular mechanisms of c-KIT-mediated progression and metastasis should be clarified. Ba/F3 murine lymphocyte cells transduced with mutant c-KIT have been utilized to analyze some molecular mechanisms related to a constitutively activated c-KIT signaling and to assess the efficacy of molecular-targeted inhibitors. Using this cellular system, we coincidentally discovered the development of axillary and inguinal lymph node swelling three weeks after subcutaneous injection of Ba/F3 cells with c-KIT mutation into nude mice. Mutation-specific PCR detected c-KIT mutation in the swollen lymph nodes but not in unmetastasized normal lymph nodes, indicating that the lymph nodes contain tumor cells which should come from a primary subcutaneous tumor. Microscopic observation revealed tumor cells infiltrating through lymphatic follicles with Ki-67-positive staining to distinguish them from lymphocytes. The significance of this model is helpful to understand the molecular mechanisms of c-KIT-mediated metastasis and is useful for assessments of molecular therapeutics and in vivo imaging.

Esophageal cancer is one of the most aggressive cancers in the world. Novel preventive and therapeutic strategies tend to target the key molecules involved in the signaling transduction pathways for cell growth. It is known that FAK and mTOR are important controllers of cell growth. TAE226, a novel small molecule compound, is a potent ATP competitive inhibitor of FAK and IGF-IR. TAE226 can block FAK and IGF-IR signaling pathways. The purpose of this study was to explore the inhibitory effects on mTOR signaling and the mechanism of cell growth suppression by TAE226. We examined the expression of mTOR and S6 in esophageal cancer cells (SEG-1) and normal esophageal epithelial cells (KOB-13) and the efficacy of TAE226 against SEG-1 cells. mTOR and S6 were overexpressed in SEG-1 cells compared with KOB-13 cells. TAE226 inhibited the expression of mTOR, Akt, p70S6K and S6 as well as the phosphorylation of mTOR (Ser2448), Akt (Ser473), p70S6K (Thr389) and S6 (Ser240/244). As a result, TAE226 induced a dose-dependent decrease in cell growth (number) and damage in the cell shape. Together, these data show that TAE226 has potent inhibitory effects on mTOR signaling and esophageal cancer cell growth indicating that TAE226 has potential application in esophageal cancer treatment.

We report two resected cases of advanced gastric cancer with peritoneal dissemination after successful treatment with TS-1 plus low-dose CDDP. Patient 1 presented with right hypochondralgia and underwent laparotomy with diagnosis of type 4 gastric cancer by gastrointestinal fiberscopy. However, the tumor was judged to be unresectable due to peritoneal dissemination, and chemotherapy was performed. At the completion of course 1, he underwent laparotomy again. Although the tumor involved the body of the pancreas and transverse colon, there was no peritoneal dissemination. Therefore, a total gastrectomy was performed with distal pancreatectomy, partial colectomy, cholecystectomy, and D2 lymph node dissection. Patient 2 presented with anorexia and was diagnosed with type 3 gastric cancer by gastrointestinal fiberscopy. CT revealed the tumor was unresectable due to peritoneal dissemination, and so chemotherapy was performed. He underwent laparotomy at the completion of course 3. There was no peritoneal dissemination, so a total gastrectomy was performed with cholecystectomy and D2 lymph node dissection. Both patients remain alive and in good condition without any signs of recurrence after surgery.