Primary duodenal carcinoma suspected to arise from ectopic gastric mucosa: a case report.

BACKGROUND: Ectopic gastric mucosa mainly occurs in the duodenal bulb, and its etiology is thought to be congenital straying of gastric tissues. Primary duodenal carcinoma is a rare disease; however, reports of carcinoma arising from ectopic gastric mucosa are extremely rare. We report a case of primary duodenal carcinoma suspected to arise from ectopic gastric mucosa, which discovered as a result of duodenal stenosis. CASE PRESENTATION: The patient was a 71-year-old man with persistent weight loss and white stools. Enhanced computed tomography showed stenosis of the third portion of the duodenum and main pancreatic duct dilatation. Upper gastrointestinal endoscopy revealed irregularity of the duodenal mucosa from the anorectal side of the papilla of Vater to the stenosis of the third portion. No malignant cells were found by biopsies from the duodenal mucosa. Endoscopic ultrasonography did not detect the tumor in the pancreatic head. The possibility of a pancreatic tumor could not be ruled out based on findings of main pancreatic duct dilatation in the pancreatic head, and the patient had long-term poor oral intake because of duodenal stenosis; thus, surgical treatment was planned. Intraoperative findings showed palpable induration of the third portion of the duodenum and white nodules on the serosal surface. This was diagnosed as primary duodenal carcinoma, and pylorus-preserving pancreatoduodenectomy was performed. Histopathological diagnosis revealed ectopic gastric mucosa in the papilla of Vater and well-differentiated tubular adenocarcinoma invaded the normal duodenal submucosa and extended to the duodenal serosa. No mass lesion was detected in the pancreas, and an intraductal papillary mucinous neoplasm was observed in the branch pancreatic duct. The main pancreatic duct stricture was caused by the duodenal carcinoma invasion. CONCLUSIONS: This case of primary duodenal carcinoma was suspected to arise from ectopic gastric mucosa and review the relevant literature.

Successful Treatment of Pancreatic Fistula Following Surgery for Congenital Biliary Dilatation with Endoscopic Ultrasound-Guided Transduodenal Drainage.

Despite improvements in surgical techniques and perioperative management, postoperative pancreatic fistula (PF) is often difficult to treat and can be fatal due to various complications without effective drainage. Here, we report a case of PF following surgery for congenital biliary dilatation (CBD) successfully managed by endoscopic ultrasound (EUS)-guided transduodenal drainage. A 55-year-old woman underwent extrahepatic bile duct resection, including the gallbladder, and biliary tract reconstruction for CBD. On the 10th postoperative day (POD), computed tomography (CT) showed fluid retention observed from the upper edge of the pancreatic head to the surface of the right lobe of the liver. First, percutaneous fine-needle aspiration was performed on the fluid retention in the lateral part of the liver on the 11th POD. The amylase level in the drainage was high (30,156 U/L), and we diagnosed it as PF. Percutaneous drainage was difficult for fluid retention on the cut surface of the pancreas; thus, drainage under EUS guidance was decided. On the 13th POD, EUS was performed, a scan of the duodenal bulb revealed fluid retention with debris inside, and approximately 20-mL fluid was aspirated (amylase: 139,200 U/L). Although the inflammatory response temporarily improved, it recurred, so we decided to perform continuous drainage. On the 21st POD, EUS was performed again; a 19-G needle was used; a 0.025-in angle-type Jagwire was advanced into the fluid retention and expanded using a 7-Fr dilator; and then, a 6-Fr endoscopic nasoabscess drain (ENAD) tube was placed. On the 29th POD, CT showed that the fluid retention on the upper edge of the head of the pancreas had shrunk to a thickness of approximately 20 mm. On the 30th POD, the patient started eating. The ENAD tube was removed on the 38th POD. The patient was discharged from the hospital on the 45th POD without any symptoms. EUS-guided transduodenal drainage is an effective treatment option for postoperative PF following surgery for CBD.

Successful treatment of enterocutaneous fistula after esophagectomy with scopolamine ointment and negative pressure wound therapy: a case report.

BACKGROUND: Despite improved surgical techniques and perioperative management, anastomotic leakage (AL) after esophageal cancer surgery remains a potential complication. In most cases, spontaneous healing upon proper drainage is observed, but sometimes, AL results in intractable enterocutaneous fistulas. We here report a case of intractable enterocutaneous fistula caused by post-esophagectomy AL and successfully treated by scopolamine ointment and negative pressure wound therapy (NPWT). CASE PRESENTATION: A 77-year-old man underwent thoracoscopic subtotal esophagectomy with 3-field lymph node dissection, followed by gastric tube reconstruction through the posterior mediastinal route. On the 6th postoperative day, AL was identified, forming an enterocutaneous fistula. Initially, conservative treatment was performed, but the fistula failed to close. We hypothesized that the substantial amount of exudate might be hampering fistula closure. Scopolamine ointment was used to reduce the amount of fluid. NPWT was also initiated to promote wound healing. Approximately 3 weeks after the beginning of the treatment, the fistula closed; oral intake became possible, and the patient was discharged from the hospital without any symptoms. CONCLUSIONS: The combination of scopolamine ointment and NPWT may be regarded as one effective treatment option for intractable enterocutaneous fistula due to AL after esophagectomy.

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma.

The relationship between the local immune status and cancer metabolism regarding 18 F-FDG and 18 F-FAMT uptake in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examined the correlations between tumor immune status, clinicopathological factors, and positron emission tomography (PET) tracer uptake in ESCC. Forty-one ESCC patients who underwent 18 F-FDG PET and 18 F-FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD-1), CD8, Ki-67, CD34, GLUT1 (18 F-FDG transporter) and LAT1 (18 F-FAMT transporter). ESCC specimens with high tumoral PD-L1 and high CD8-positive lymphocytes were considered to have "hot tumor immune status." High PD-L1 expression (53.7%) was significantly associated with tumor/lymphatic/venous invasion (P = 0.028, 0.032 and 0.018), stage (P = 0.041), CD8-positive lymphocytes (P < 0.001), GLUT1 (P < 0.001), LAT1 expression (P = 0.006), Ki-67 labelling index (P = 0.009) and CD34-positive vessel counts (P < 0.001). SUVmax of 18 F-FDG was significantly higher in high PD-L1 cases than in low PD-L1 cases (P = 0.009). SUVmax of 18 F-FAMT was significantly higher in high PD-L1 (P < 0.001), high CD8 (P = 0.012) and hot tumor groups (P = 0.028) than in other groups. High SUVmax of 18 F-FAMT (≥4.15) was identified as the only predictor of hot tumor immune status. High PET tracer uptake was significantly associated with cancer aggressiveness and hot tumor immune status in ESCC. PET imaging may be an effective tool to predict tumor immune status in ESCC with respect to immune checkpoint inhibitor sensitivity.

Post-esophagectomy Adjuvant Chemotherapy Benefits Esophageal Cancer Patients.

BACKGROUND/AIM: Postoperative chemotherapy is an absolutely imperative treatment for advanced esophageal cancer patients, while preoperative chemotherapy is the standard therapy for clinical stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. The aim of this study was to report the effect of postoperative chemotherapy on survival after esophagectomy due to thoracic esophageal squamous cell carcinoma. PATIENTS AND METHODS: One hundred thirteen consecutive patients with esophageal carcinoma who underwent esophagectomy were included. Several regiments were performed at various times. RESULTS: Adjuvant chemotherapy brought a significantly superior overall survival (p=0.002), although there was no significant difference in cancer-specific survival (p=0.054) for clinical stage II or stage III esophageal cancer patients. Depth of invasion (p=0.003), number of lymph node metastases (p=0.048), and venous invasion (p<0.001) were risk factors for recurrence in the adjuvant-chemotherapy group with positive lymph nodes. Additionally, a not well-differentiated type, lymphatic and venous invasions were risk factors for recurrence in the surgery-alone group without positive lymph nodes. CONCLUSION: Postoperative adjuvant chemotherapy contributes to the prognosis of clinical stage II or III esophageal cancer patients.

Correlation between high FBXW7 expression in pretreatment biopsy specimens and good response to chemoradiation therapy in patients with locally advanced esophageal cancer: A retrospective study.

BACKGROUND AND OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) exhibits good reactivity to chemoradiation therapy (CRT). The dysregulation of F-Box and WD Repeat Domain Containing 7 (FBXW7) is associated with therapeutic resistance in cancer cells. However, the correlation between FBXW7 expression and CRT sensitivity in patients with clinical ESCC has been investigated only in few studies. Therefore, this study aimed to elucidate the significance of FBXW7 expression in pretreatment biopsy specimens from patients with ESCC receiving CRT. METHODS: We investigated the relationship between FBXW7 expression and CRT sensitivity in 30 pretreatment biopsy specimens with histological grades of post-CRT surgically resected tumors. Furthermore, we evaluated the effects of high FBXW7 expression on the sensitivity to cytotoxic agents, including docetaxel and nedaplatin, and radiation in ESCC cells in vitro. RESULTS: High FBXW7 expression before CRT correlated with a good pathological CRT response in patients with advanced ESCC (P < .05). Further, our in vitro data showed that both chemo and radiation sensitivity increased in TE-8 and KYSE140 cells overexpressing FBXW7 compared with mock cells because of the degradation of the anti-apoptotic protein MCL1. CONCLUSIONS: The evaluation of FBXW7 expression before CRT treatment is a potential predictor of good responders among patients with ESCC receiving CRT.

Association of Preoperative Nutritional Status with Prognosis in Patients with Esophageal Cancer Undergoing Salvage Esophagectomy.

BACKGROUND: To investigate whether malnutrition is associated with poor prognosis of patients who undergo salvage esophagectomy. We examined the association between the preoperative prognostic nutritional index (PNI) and prognosis of patients who undergo salvage esophagectomy. PATIENTS AND METHODS: We conducted a single-center retrospective study and reviewed hospital patient records for tumor characteristics and patient outcomes. Univariate and multivariate survival analyses were carried out using the Cox proportional hazards regression model. RESULTS: Thirty-two patients with esophageal squamous cell carcinoma (ESCC) who underwent salvage esophagectomy between 1998 and 2015 at our Institute were included in this study. Univariate analysis revealed that clinical response (p=0.045), preoperative PNI (p<0.001), pT (p=0.024), pN (p=0.004), and residual tumors (p<0.001) were significant prognostic factor for overall survival. Multivariate analysis using age and these five variables found no independent prognostic factors. Multivariate analysis using three preoperative variables (age, clinical response, and preoperative PNI) revealed that PNI was an independent prognostic preoperative factor for overall survival (p=0.005). CONCLUSION: Preoperative nutritional status is associated with the prognosis of patients undergoing salvage esophagectomy.

Clinical Significance of Salvage Esophagectomy for Patients with Esophageal Cancer and Factors of Influencing Long-term Survival.

BACKGROUND/AIM: Definitive chemoradiotherapy (CRT) without planned surgery has been recently widely used as a therapeutic option for locally advanced esophageal cancer. Salvage esophagectomy can offer the chance of prolonged survival for patients who have locoregional failure after definitive CRT, but many clinicians oppose the use of surgery due to the associated excessive morbidity and mortality. The aim of this study was to identify patients who are good candidates for salvage surgery by investigating factors influencing long-term survival. PATIENTS AND METHODS: A total of 40 patients underwent concurrent CRT or RT followed by esophagectomy for residual tumor or locoregional recurrence of esophageal squamous cell carcinoma without distant organ metastasis at the Department of General Surgical Science, Gunma University, Gunma, Japan, and were included in this study. As short-term outcomes after salvage esophagectomy, pulmonary and cardiovascular complications, anastomotic leakage, and chylothorax, and the length of postoperative stay were evaluated. Survival rates were calculated using the Kaplan-Meier method, and the Cox proportional hazards model was used for univariate and multivariate analyses of disease-specific survival. RESULTS: Postoperative complications were noted in 20 patients (50%), and pulmonary complications were the most common (25%), followed by anastomotic leakage (20%). There was also one case of in-hospital death, caused by multiple organ failure due to chylothorax. Univariate analysis revealed that sex, clinical residual tumor, CRT response, pathological tumor depth, and pathological residual tumor were significant factors affecting disease-specific survival (p=0.034, p=0.009, p=0.014, p=0.020, and p=0.026, respectively). Moreover, multivariate analysis demonstrated that clinical residual tumor was the only independent factor influencing disease-specific survival (p=0.036). Thirteen patients (32.5%) died from other illnesses after salvage surgery, 53.8% patients from pneumonia. CONCLUSION: Based on long-term survival, recurrence rather than residual tumor after definitive CRT was a favorable indicator for salvage esophagectomy. Not only management of postoperative morbidity and curative operation but, also long-term rigorous outpatient management, including respiratory rehabilitation to reduce pneumonia, is necessary.

Clinical Significance and Phenotype of MTA1 Expression in Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: Metastasis-associated gene 1 (MTA1) is considered a potential prognostic factor in esophageal cancer. We investigated the clinical relationship between MTA1, LAT1, and tumor metabolism, as evaluated by positron emission tomography (PET) in esophageal squamous cell carcinoma. MATERIALS AND METHODS: We analyzed 142 esophageal squamous cell carcinoma patients who underwent curative resection without preoperative treatment. MTA1 expression was assessed by immuno-zahistochemistry, and tested against standardized uptake values from preoperative PET-CT. The association among MTA1, LAT1, and 18FAMT PET results were analyzed. RESULTS: MTA1 staining was observed in 82 of 142 cancer tissues. Five-year overall survival was 69.9 % in the absence of MTA1, but 50.7% otherwise (p=0.021), while disease-free survival was 66.5% and 49.0% (p=0.071), respectively. Abnormal 18FAMT accumulation was noted in 13 patients without MTA1 and in 18 patients with MTA1 (p=0.079), with maximum standardized uptake value 1.6±1.6 and 2.7±1.6, respectively (p=0.036). MTA1 expression was positively correlated with LAT1 (p=0.013) and CD34 (p=0.034) expression, but not with Ki-67 (p=0.078). CONCLUSION: MTA1 shows promise as a diagnostic and prognostic marker in esophageal cancer, and we anticipate that the gene will also prove to be a good therapeutic target.

High stathmin 1 expression is associated with poor prognosis and chemoradiation resistance in esophageal squamous cell carcinoma.

Stathmin 1 (STMN1) is a major cytosolic phosphoprotein regulating microtubule dynamics, thereby playing an important role in cancer progression and resistance to microtubule-binding anticancer agents. We assessed the prognostic significance of STMN1 expression and STMN1-associated resistance to docetaxel and radiation in esophageal squamous cell carcinoma (ESCC) patients. STMN1 expression was evaluated by immunohistochemistry in 172 surgical specimens. The association of STMN1 expression with chemoradiation resistance using docetaxel was examined by comparing expression in 15 biopsy specimens obtained before neoadjuvant therapy to histological grades of post-therapy surgically resected tumors. We also evaluated the effects of STMN1 on sensitivity to docetaxel and radiation in ESCC cell lines. High STMN1 immunoexpression was significantly associated with tumor depth, lymph node metastasis, lymphatic invasion and venous invasion. Survival rates were significantly lower in ESCC patients with high STMN1 expression than in those with low STMN1 expression. Multivariable analysis showed that high STMN1 expression was an independent factor for poor survival. High STMN1 expression was also associated with poor response to neoadjuvant chemoradiotherapy using docetaxel. Knockdown of STMN1 expression enhanced ESCC cell line sensitivity to docetaxel and radiation. STMN1 appears critical for ESCC invasiveness and predicts an unfavorable prognosis in ESCC.

Utility of double endoscopic intraluminal operation for esophageal cancer.

OBJECTIVES: Endoscopic submucosal dissection (ESD) is a more difficult technique for esophageal cancer than for gastric cancer because the working space for esophageal ESD is small. Further, the difficulty level gradually increases depending on the size of the carcinoma. To overcome these difficulties, double endoscopic intraluminal operation (DEILO), which enables the resection of mucosal lesions using two fine endoscopes and monopolar shears, was reported previously. Here, we report the utility of DEILO for esophageal cancer. METHODS: A total of 26 esophageal cancer patients (19 men and seven women) with 26 lesions treated using DEILO between 2011 and 2014 at Gunma University Hospital were included. We evaluated the utility and safety of DEILO for early esophageal cancer. RESULTS: For all patients (100%), the DEILO procedure was performed successfully, and en bloc resection was achieved. The median operation time, postoperative hospital stay, and the longitudinal dimension of resected specimens were 123 min (range 45-236 min), 5 days, and 32 mm, respectively. Perioperative perforation, pneumothorax, and mediastinal emphysema were not recognized. Only one patient was diagnosed with a postoperative hemorrhage, but the bleeding was successfully treated by bleeding vessel coagulation. CONCLUSION: DEILO has good utility as a technique of ESD for early esophageal cancers. Additional improvement and advancement of the procedure will increase the indication of DEILO.

Molecular characterization of antitumor effects of the rhizome extract from Curcuma zedoaria on human esophageal carcinoma cells.

Curcuma zedoaria has been used as a traditional agent against malignant diseases. To elucidate detailed mechanisms producing such an activity, characterization and determination of molecular mechanisms of its antitumor effects was conducted. Inhibiting activities against cell proliferation, invasion and colony formation, and expression levels of corresponding molecules were investigated using human esophageal cancer TE-8 cells treated with the rhizome extract from C. zedoaria. Antitumor effect of the extract administered orally was also examined in tumor-bearing mice. The extract possessed strong anti-proliferation and invasion activities against TE-8 cells. Further, upregulated PTEN and downregulated phosphorylated Akt, mTOR and STAT3 expressions in the cells were induced shortly after treatment with the extract, followed by attenuation of FGFR1 and MMP-2, activation of caspase-9, caspase-3 and PARP, and suppression of Bcl-2 expressions, which led the cells to apoptotic cell death. Furthermore, tumor formation in mice was significantly suppressed through the oral administration of the extract. Taken together, these results suggest that the C. zedoaria extract could be a promising agent against esophageal cancer.

Phase II Study of Docetaxel, Nedaplatin, and 5-Fluorouracil Combined Chemotherapy for Advanced Esophageal Cancer.

BACKGROUND: We performed a prospective, multi-institutional, phase-II, clinical trial of a docetaxel, nedaplatin, and 5-fluorouracil (DNF) regimen in patients with unresectable esophageal cancer. Our goal was to determine the efficacy and feasibility of this DNF protocol. METHODS: Thirty-four patients with unresectable esophageal cancer were enrolled and received DNF therapy. The DNF regimen was repeated every 4 weeks for up to 8 weeks, based on the following recommended doses: docetaxel, 60 mg/m(2) (day 1); nedaplatin, 70 mg/m(2) (day 1); and 5-fluorouracil, 700 mg/m(2) (days 1-5). The primary endpoint was the response rate. The secondary endpoints were overall survival and chemotherapy toxicities. RESULTS: The complete response rate and response rate were 5.9 and 47.1 %, respectively. The 2-year overall survival rate and progression-free survival rate were 44.3 and 27.3 %, respectively. The median survival time was 594 days. The median progression-free time was 277 days. No treatment-related deaths occurred. Thirty patients (30/34) with grade 3, 4 neutropenia improved relatively quickly with administration of granulocyte colony-stimulating factor. CONCLUSIONS: DNF combination chemotherapy is a useful regimen with relatively minor adverse events and may serve as an effective protocol in patients with unresectable esophageal cancer.

Planned Esophagectomy after Neoadjuvant Hyperthermo-Chemoradiotherapy using Weekly Low-Dose Docetaxel and Hyperthermia for Advanced Esophageal Carcinomas.

BACKGROUND/AIMS: The optimal treatment for locally advanced esophageal carcinoma has not yet been determined. We report results of neoadjuvant hyperthermo-chemoradiotherapy (HCRT) using weekly low-dose docetaxel followed by surgery in patients with advanced esophageal squamous cell carcinoma. METHODOLOGY: Twenty-four patients were enrolled. 7 patients were considered to have inoperable tumors or rejected surgery after HCRT, and the remaining 17 patients had an esophagectomy. Clinical responses, HCRT toxicity and survival after surgery were evaluated. RESULTS: In the 24 patients, the response rate was 41.7%. The pathological complete response (pCR) rate was 17.6% in the 17 patients. HCRT toxicity grade 2 occurred in six patients (25.0%: esophagitis, 4; leukopenia, 6; neutropenia, 4) and grade 3 (pneumonia) in 3 patients (12.5%). The 3- and 5-year survival rates were 56.3% and 50.0%, respectively. When the patients were divided into a pCR group and a pathological partial response (pPR) group, the 3-year survival rates were 66.7% and 42.9% and the 5-year survival rates were 66.7% and 42.9%, respectively (log-rank P = .5842). CONCLUSIONS: Esophagectomy after docetaxel HCRT may have potential for prolonging survival in patients with locally advanced esophageal cancer. A larger randomized, controlled study will be required to confirm the benefit of esophagectomy after HCRT.

Usefulness of 18f-Fluorodeoxyglucose Positron Emission Tomography for Predicting the Pathological Response of Neoadjuvant Chemoradiotherapy for T4 Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIMS: The purpose of this study is to assess the efficacy of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in predicting the pathological response of neoadjuvant chemoradiation (CRT) for clinically diagnosed T4 esophageal squamous cell carcinoma (SCC). METHODOLOGY: We examined 32 patients with T4 thoracic esophageal SCC who received neoadjuvant CRT followed by surgery. RESULTS: Pathological complete response (pCR) was achieved in 7 patients (21.9%). pCR was significant correlated with standardized uptake value (SUV) after neoadjuvant CRT (P = 0.034) and SUV decrease (%) (P = 0.030). The optimal cut-off values to predict pCR were 2.25 for SUV after neoadjuvant CRT and 79.3 for SUV decrease (%). Of note, no patients who did not reach both cut-off values achieved pCR. Conclusions: SUV after CRT and SUV decrease (%) in FDG-PET of the primary tumor are useful tools to predict pathological response of neoadjuvant CRT for T4 esophageal SCC.

Phase I/II study of docetaxel, cisplatin, and 5-fluorouracil combination chemoradiotherapy in patients with advanced esophageal cancer.

PURPOSE: This phase I/II study was aimed to determine the recommended dose (RD) of docetaxel, cisplatin, and 5-fluorouracil as combination chemoradiotherapy (DCF-RT) for patients with esophageal cancer and to evaluate the efficacy and safety of this protocol. METHODS: Fourteen patients with esophageal cancer enrolled in this dose escalation study to determine the RD for a phase III trial. Efficacy and toxicity in DCF-RT of RD were evaluated in 37 patients with esophageal cancer. RESULTS: The RD for DCF-RT for esophageal cancer in the present study was 50 mg/m(2) docetaxel plus 60 mg/m(2) cisplatin on day 1 and day 29 plus 600 mg/m(2) 5-FU on days 1-4 and days 29-32 and concurrent radiation of 60 Gy/30 fractions/6 weeks. The main toxicities were myelotoxicity and radiation esophagitis. In this phase I/II study, we could have safety and feasibility by RD, because there was low mortality and most toxicities were manageable level. The complete response (CR) rate and response rate were 54.1 and 83.8 %, respectively, in the phase II study. In patients with a classification of clinical T4, the CR rate and response rate were 47.6 and 85.7 %, respectively. The 2-year overall survival rate, 2-year progression-free survival rate, and median survival time (MST) were 52.9, 50.0 %, and 24.7 months, respectively. In patients with clinical T4 classification, the 2-year overall survival rate, 2-year progression-free survival rate, and MST were 43.5, 44.9 %, and 21.6 months respectively. CONCLUSIONS: DCF-RT keeps safety and feasibility by management of myelotoxicity adequately in RD. This protocol might produce a high CR rate and favorable prognosis compared with standard chemoradiotherapy for advanced esophageal cancer.

L-[3-¹8F]-α-methyltyrosine uptake by lymph node metastasis is a predictor of complete response to CRT in esophageal cancer.

BACKGROUND/AIM: The amino acid positron emission tomography (PET) tracer [(18)F]-3-fluoro-alpha-methyltyrosine ((18)F-FAMT) is known to be highly specific for malignancies. We evaluated the accumulation of (18)F-FDG or (18)F-FAMT in lymph nodes (LN) prior to definitive chemoradiotherapy (CRT) for esophageal cancer. PATIENTS AND METHODS: We retrospectively reviewed 30 patients with esophageal squamous cell carcinoma. All patients received definitive CRT. The relationship between the accumulation of (18)F-FDG PET or (18)F-FAMT PET in LNs prior to CRT and clinical outcomes was assessed. RESULTS: A correlation was observed between LNs in which most of (18)F-FAMT was accumulated and complete response (CR) rate, but was not for (18)F-FDG. Additionally, for (18)F-FAMT, the CR rate was significantly higher in the LN accumulated lesion ≤ 1 group than in the LN accumulated lesion >2 group. DISCUSSION: To predict the outcome of definitive CRT in patients with esophageal cancer, it is important to evaluate the LN status.

Use of pre-treatment 18F-FAMT PET to predict patient survival in squamous cell carcinoma of the esophagus treated by curative surgery.

BACKGROUND: [18F]-3-fluoro-alpha-methyl tyrosine (18F-FAMT) as an amino acid tracer in positron emission tomography (PET) has been widely investigated in several tumor types. Herein we investigated the clinical significance of 18F-FAMT PET uptake as a prognostic marker together in our updated data of patients with esophageal cancer. PATIENTS AND METHODS: We retrospectively assessed the treatment outcomes of 42 patients with histologically-confirmed esophageal cancer. The survival rate was analyzed using the median peak standardized uptake value (SUV) with 2.2 as the cut-off value. RESULTS: FAMT uptakes were significantly correlated with factors reflecting tumor progression. Moreover, a significant correlation was observed between FAMT uptake and disease-free survival (p=0.023). Moreover, on evaluation of individual lymph node groups, the specificity and positive predictive value were significantly higher for 18F-FAMT-PET than for 18F-FDG-PET and computed tomography (CT). CONCLUSION: 18F-FAMT is an important pre-treatment diagnostic modality and its accumulation is a good predictor of disease-free survival (DFS) in patients with operable esophageal cancer.

Stathmin1 regulates p27 expression, proliferation and drug resistance, resulting in poor clinical prognosis in cholangiocarcinoma.

Patients with extrahepatic cholangiocarcinoma (EHCC) have a poor prognosis; postoperative survival depends on cancer progression and therapeutic resistance. The mechanism of EHCC progression needs to be clarified to identify ways to improve disease prognosis. Stathmin1 (STMN1) is a major cytosolic phosphoprotein that regulates microtubule dynamics and is associated with malignant phenotypes and chemoresistance in various cancers. Recently, STMN1 was reported to interact with p27, an inhibitor of cyclin-dependent kinase complexes. Eighty EHCC cases were studied using immunohistochemistry and clinical pathology to determine the correlation between STMN1 and p27 expression; RNA interference to analyze the function of STMN1 in an EHCC cell line was also used. Cytoplasmic STMN1 expression correlated with venous invasion (P = 0.0021) and nuclear p27 underexpression (P = 0.0011). Patients in the high-STMN1-expression group were associated with shorter recurrence-free survival and overall survival than those in the low-expression group. An in vitro protein-binding assay revealed that cytoplasmic STMN1 bound to p27 in the cytoplasm, but not in the nucleus of EHCC cells. Moreover, p27 accumulated in EHCC cells after STMN1 suppression. STMN1 knockdown inhibited proliferation and increased the sensitivity of EHCC cells to paclitaxel. STMN1 contributes to a poor prognosis and cancer progression in EHCC patients. Understanding the regulation of p27 by STMN1 could provide new insights for overcoming therapeutic resistance in EHCC.

L-[3-18F]-α-methyltyrosine accumulation as a definitive chemoradiotherapy response predictor in patients with esophageal cancer.

AIMS: L-[3-(18)F]-α-Methyltyrosine ((18)F-FAMT) has high specificity for malignant tumors on positron emission tomography (PET), and its role and potential usefulness has been previously investigated in operable esophageal carcinoma. We aimed to assess the ability of (18)F-FAMT PET to predict the response of esophageal cancer to definitive chemoradiotherapy. PATIENTS AND METHODS: We retrospectively reviewed 40 patients with esophageal cancer imaged with (18)F-FAMT PET. The relationship between (18)F-FAMT PET uptake before chemoradiotherapy and clinical outcomes was assessed. RESULTS: The primary tumor was visualized in 95% patients. (18)F-FAMT uptake was significantly positively correlated with lymph node metastasis. The low-(18)F-FAMT accumulation group had significantly higher complete response (CR) rates than did the high-accumulation group. The addition of a lymph node metastasis category with low (18)F-FAMT uptake provides a more precise predictor of CR. CONCLUSION: (18)F-FAMT uptake prior to treatment is a good predictor of CR rate after CRT for esophageal cancer.