New Assay System Elecsys Anti-p53 to Detect Serum Anti-p53 Antibodies in Esophageal Cancer Patients and Colorectal Cancer Patients: Multi-institutional Study.

BACKGROUND: Several recent studies suggest that serum anti-p53 antibodies (s-p53-Abs) may be combined with other markers to detect esophageal and colorectal cancer. In this study, we assessed the sensitivity and specificity of s-p53-Abs detection of a new electrochemiluminescence immunoassay (ECLIA; Elecsys anti-p53). METHODS: Elecsys anti-p53 assay was used to analyze the level of s-p53-Abs in blood sera from patients with esophageal or colorectal cancer taken before treatment. Control blood sera from healthy volunteers, patients with benign diseases, and patients with autoimmune diseases served as a reference. In addition, squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA21-1) were assessed in patients with esophageal cancer, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were assessed in patients with colorectal cancer. RESULTS: Samples from 281 patients with esophageal cancer, 232 patients with colorectal cancer, and 532 controls were included in the study. The median value of s-p53-Abs in control samples was < 0.02 µg/mL (range < 0.02-29.2 µg/mL). Assuming 98% specificity, the cut-off value was determined as 0.05 µg/mL. s-p53-Abs were detected in 20% (57/281) of patients with esophageal cancer and 18% (42/232) of patients with colorectal cancer. In combination with SCC-Ag and CEA, respectively, s-p53-Abs detected 51% (144/281) of patients with esophageal and 53% (124/232) of patients with colorectal cancer. CONCLUSIONS: The new s-p53-Abs assay Elecsys anti-p53 was useful in detecting esophageal and colorectal cancers with high specificity. Adding s-p53-Abs to conventional markers significantly improved the overall detection rates.

Diagnostic performance of diffusion-weighted magnetic resonance imaging in assessing lymph node metastasis of esophageal cancer compared with PET.

BACKGROUND: Although diffusion-weighted magnetic resonance imaging (DWI) for detecting lymph node (LN) metastasis is reported to be a successful modality for primary malignant tumors, there are few studies relating to esophageal cancer. This study aimed to clarify the diagnostic performance of DWI for assessing LN metastasis compared with positron emission tomography (PET) in patients with esophageal squamous cell cancer (eSCC). METHODS: Seventy-six patients with histologically proven eSCC who underwent curative esophagectomy without neoadjuvant treatment were reviewed retrospectively. Harvested LNs were divided into 1229 node stations with 94 metastases. Diagnostic abilities and prognostic significance were compared. RESULTS: In a station-by-station evaluation, the sensitivity was higher in DWI than PET (67% vs. 32%, P < 0.001). DWI showed more than 80% sensitivity for middle- and large-sized cancer nests and large area of cancer nests. The DWI-N0 group had a better 5-year relapse-free survival rate than the DWI-N+ group (78.5% vs. 34.2%, P < 0.001), as did the PET-N0 group. DWI-N status was an independent prognostic factor (hazard ratio [HR], 2.642; P = 0.048), as was PET-N status (HR 2.481; P = 0.033). CONCLUSIONS: DWI, which depends on cancer cell volume followed by elevated intranodal density, is a non-invasive modality and showed higher sensitivity than PET. It has clinical impact in predicting postoperative survival for patients with eSCC alongside its diagnostic ability and has significant performance in clinical practice.

Heterogeneity of Glucose Metabolism in Esophageal Cancer Measured by Fractal Analysis of Fluorodeoxyglucose Positron Emission Tomography Image: Correlation between Metabolic Heterogeneity and Survival.

BACKGROUND: Intratumoral heterogeneity is a well-recognized characteristic feature of cancer. The purpose of this study is to assess the heterogeneity of the intratumoral glucose metabolism using fractal analysis, and evaluate its prognostic value in patients with esophageal squamous cell carcinoma (ESCC). METHODS: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) studies of 79 patients who received curative surgery were evaluated. FDG-PET images were analyzed using fractal analysis software, where differential box-counting method was employed to calculate the fractal dimension (FD) of the tumor lesion. Maximum standardized uptake value (SUVmax) and FD were compared with overall survival (OS). RESULTS: The median SUVmax and FD of ESCCs in this cohort were 13.8 and 1.95, respectively. In univariate analysis performed using Cox's proportional hazard model, T stage and FD showed significant associations with OS (p = 0.04, p < 0.0001, respectively), while SUVmax did not (p = 0.1). In Kaplan-Meier analysis, the low FD tumor (<1.95) showed a significant association with favorable OS (p < 0.0001). In wthe multivariate analysis among TNM staging, serum tumor markers, FD, and SUVmax, the FD was identified as the only independent prognostic factor for OS (p = 0.0006; hazards ratio 0.251, 95% CI 0.104-0.562). CONCLUSION: Metabolic heterogeneity measured by fractal analysis can be a novel imaging biomarker for survival in patients with ESCC.

[A Case of Advanced Gastric Cancer Responding Effectively to Neoadjuvant Chemotherapy].

A 78-year-old man underwent an upper gastrointestinal endoscopy for evaluation of epigastralgia. Endoscopy revealed a bulky type 3 tumor in the lesser curvature of the upper body. A biopsy showed a poorly differentiated adenocarcinoma with signet ring cell carcinoma. Additionally, abdominal computed tomography(CT)showed bulky lymph node metastases leading to a diagnosis of cT3N2M0, Stage III A carcinoma. Following administration of 2 courses of neoadjuvant chemotherapy (NAC)using S-1/cisplatin(CDDP), CT revealed significant regression of the primary lesion and lymph nodes. Eventually, laparoscopic total gastrectomy was performed. Histopathologically, almost all viable cancer cells had been cleared from the primary lesion, and no cancer cells were found in the lymph nodes, which indicated a pathological partial response(Grade 2). NAC could be a valid option for the treatment of advanced gastric cancer.

Efficacy and tolerability of controlled-release oxycodone for oxaliplatin-induced peripheral neuropathy and the extension of FOLFOX therapy in advanced colorectal cancer patients.

BACKGROUND: The oxaliplatin-based regimen FOLFOX is widely used to treat patients with advanced colorectal cancer (CRC). However, dose-limiting toxicity after continuous oxaliplatin administration can lead to peripheral neuropathy. Several agents, including opioids, that have been employed to treat oxaliplatin-induced peripheral neuropathy (OIPN) have been examined in clinical settings regarding their protective and therapeutic effects. However, the pharmacotherapy of these agents has not yet been established. Therefore, we investigated the efficacy and tolerability of oxycodone for OIPN and subsequently with FOLFOX therapy in CRC patients. METHODS: This was a single-center retrospective study of 64 CRC patients who underwent FOLFOX therapy at the Toho University Sakura Medical Center (Sakura, Japan). Controlled-release (CR) oxycodone was concomitantly administered to 29 patients (OXY group), whereas the additional 35 patients (non-OXY group) were not given oxycodone during the FOLFOX treatment course. The incidence and severity of OIPN and the number of FOLFOX cycles were measured and compared between the two groups. Neurological toxicities were assessed according to the Common Terminology Criteria for Advanced Events, version 3.0. RESULTS: All study patients had OIPN. Most patients experienced grade 1 or 2 sensory neuropathy. Grade 3 sensory neuropathy was observed in two patients in the non-OXY group. All patients in the OXY group completed the scheduled FOLFOX therapy, whereas FOLFOX therapy was discontinued in ten patients in the non-OXY group due to severe peripheral neuropathy. The median numbers of FOLFOX cycles in the OXY and non-OXY groups were 13 (range, 6-46) and 7 (range, 2-18), respectively (P < 0.05). The median cumulative oxaliplatin doses were 1072.3 mg/m(2) (range, 408.7-3385.3 mg/m(2)) in the OXY group and 483.0 mg/m(2) (range 76.2-1414.1 mg/m(2)) in the non-OXY group (P < 0.05). CONCLUSIONS: Our findings indicate that CR oxycodone might attenuate the severity of OIPN and extend the use of FOLFOX therapy.

[Usefulness of FDG-PET for superficial esophageal squamous cell carcinoma].

We investigated the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for superficial esophageal squamous cell carcinoma after resection via endoscopic submucosal dissection (ESD). Our case study included 37 patients and 49 tumors resected via ESD in our hospital between January 2012 and December 2013. Histopathological diagnosis confirmed squamous cell carcinoma in all cases. Tumors located near the esophago cardiac junction were excluded. We investigated retrospectively whether the standardized uptake value (SUV) obtained by using FDG-PET could be the criterion to decide whether to perform ESD. At first, the tumor was examined via endoscopy. If tumor depth (T status)was less than cSM1, we performed ESD. When the tumor depth was less than pSM1, no infiltration of the vessel or lymph duct was observed, and the surgical margin was free; therefore, we did not perform any further therapy. On the other hand, we measured the SUV obtained via FDG-PET. The cut-off value was set as 3.0 based on the correlation between the SUV and tumor depth. We investigated if SUV<.0 could be the criterion for further therapy after ESD. In our results, the sensitivity was 95%, specificity was 67%, and accuracy was 90%. The SUV also helped to identify the malignancy of the superficial esophageal cancer and could help to decide whether ESD should be undertaken.

Novel Advances in Qualitative Diagnostic Imaging for Decision Making in Multidisciplinary Treatment for Advanced Esophageal Cancer.

Background: Recently, neoadjuvant therapy and the succeeding surgery for advanced esophageal cancer have been evaluated. In particular, the response to the therapy has been found to affect surgical outcomes, and thus a precise evaluation of treatment effect is important for this strategy. In this study, articles on qualitative diagnostic modalities to evaluate tumor activities were reviewed, and the diagnostic indices were examined. Methods: For prediction of the effect, perfusion CT and diffusion MRI were estimated. For the histological response evaluation, perfusion CT, diffusion-MRI, and FDG-PET were estimated. For downstaging evaluation of T4, tissue-selective image reconstruction using enhanced CT was estimated and diagnostic indices were reviewed. Results: The prediction of the effect using perfusion CT with 'pre CRT blood flow' and diffusion MRI with 'pre CRT ADC value'; the estimation of the histological response using perfusion CT with 'post CRT blood flow reduction, using diffusion MRI with 'post CRT ADC increasing', and using FDG-PET with 'post CRT SUV reduction'; and the downstaging evaluation of T4 using CT image reconstruction with 'fibrous changed layer' were performed well, respectively. Conclusions: Qualitative imaging modalities for prediction or response evaluation of neoadjuvant therapy for progressive esophageal cancer were useful for the decision making of the treatment strategy of the multidisciplinary treatment.

[Evaluation of tumor heterogeneity for esophageal squamous cell cancer by dynamic FDG-PET].

The aim of this study is to assess the tumor heterogeneity of esophageal squamous cell cancer by dynamic FDG-PET (dPET). Thirty patients were enrolled in this study. Images were obtained after intravenous injection of 370 MBq of 18F-FDG for 1 h. The time-density curve of the standardized uptake value( SUV) was evaluated quantitatively by fractal analysis. Tumor fractal dimension (FD) maps were acquired, and the FD of the tumor was measured. There was a significant correlation between FD and the clinical response to adjuvant therapy. The FD reduction rates of adjuvant therapy were 23.23% in the responder group and 5.83% in the nonresponder group. FD may be a valid imaging biomarker for assessing the response to neoadjuvant therapy.

[Evaluation of false-negative lymph nodes diagnosed by fludeoxy glucose-positron emission tomography in cases of metastatic esophageal squamous cell carcinoma].

We have encountered many cases wherein the metastatic nest of esophageal squamous cell carcinoma occupied only a small space in the lymph nodes because of which computed tomography( CT) and fludeoxy glucose( FDG)-positron emission tomography( PET) could not detect the lymph node metastasis satisfactorily. The false-negative lymph nodes that were not detected by FDG-PET before surgery were smaller in diameter, rate of occupation, and area of occupation than the true-positive lymph nodes. The smallest area of the cancer nest in the true-positive group was 7.5 mm2, and therefore, it was reasonable to consider a 5-mm diameter area as the criteria for correct diagnosis by FDG-PET. Most of the false-negative lymph nodes with a large area of carcinoma were attached to the primary tumor; therefore, they could not be precisely identified. The detection of false-negative lymph nodes by FDG-PET was not precise because of increases in the quantity of stroma-like cells in poorly differentiated carcinomas and in fibrosis caused by neoadjuvant therapy in the lymph nodes.

Verification of Safety and Efficacy of Sleeve Gastrectomy Based on National Registry by Japanese Society for Treatment of Obesity.

In Japan, bariatric surgical treatment was started in 1982. The Japanese Society for Treatment of Obesity (JSTO) was established in 2007, and then, JSTO started the national registry of bariatric surgery cases and multidisciplinary educational program. A total of 44 facilities registered 4055 bariatric surgical cases until 2021. In this study, the purpose is to clarify the indication, the safety and the effectiveness of the sleeve gastrectomy using national registry database compiled by JSTO. Preoperative BMI ranged from 27.6 to 90.7 kg/m2, and the mean value was 42.7. With regard to gender, men/women was 1/1.3. Age was 42.2 as mean. As preoperative comorbidities, DM ratio was 54.4% of the patients, hypertension 64.5%, dyslipidemia 65.1%, and sleep apnea syndrome 69.8%. As an operation method, laparoscopic method was conducted in 99.7% of the cases. The intraoperative incidence rate was 0.9%. Conversion rate to open method was 1.1%. Postoperative morbidity ratio was 5.6%, and mortality was 0%. Reoperations were performed in 1.5% of the cases. Postoperative hospital stay was 5 days in median value. Body weight loss was 27.6 kg in the mean value after follow-up days of 279 ± 245. As the effect on the preoperative metabolic comorbidities, DM has improved in 82.9% of the cases, hypertension 67.9% and dyslipidemia 66.6%. In conclusion, using JSTO database, we evaluated the indication, postoperative complications and weight loss effect of sleeve gastrectomy in Japan. Regarding the evaluation of the effect on preoperative comorbidities, future follow-up based on more detailed criteria was considered to be necessary.

Malignant diagnosis and prognostic analysis of 89 GIST patients using preoperative FDG-PET.

There is no preoperative imaging accurately diagnose malignancy of gastrointestinal stromal tumor (GIST). To evaluate the usefulness of preoperative [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the malignant diagnosis and prognostic analysis of GIST. Eighty-nine consecutive patients with GIST who underwent curative surgery were reviewed retrospectively. PET scan was performed within 2-3 weeks before surgery and maximum standardized uptake values (SUVmax) were assessed for GIST. The relationship between prognostic factors and prognosis of GIST and SUVmax were evaluated. Tumor size, mitotic count, and Ki-67 index showed significant positive correlations with the SUVmax. When the cutoff value was set as SUVmax 5.68, the accuracy was 86.5% for the high-risk group, 76.4% for the recurrence group, and 73.0% for the death group. The group with SUVmax ≥ 5.68 demonstrated a significantly lower 10-year relapse-free survival than the group with SUVmax < 5.68 (55.2% vs. 98.2%, P < 0.001), while the group with SUVmax ≥ 5.68 demonstrated a significantly lower 10-year overall survival than the group with SUVmax < 5.68 (68.0% vs. 97.6%, P < 0.001). In GISTs, FDG-PET is a very useful imaging marker for the diagnosis of malignant GISTs, such as those in high-risk and poor-prognosis groups.

Estrogen receptor beta expression in colitis-associated carcinoma in comparison with sporadic colonic tumor: An immunohistochemical study.

Background and Aim: The rate of ulcerative colitis (UC)-related colorectal cancer (colitis-associated carcinoma) is increasing. Estrogen receptor (ER) beta expression has been studied separately in patients with sporadic colorectal cancer and those with colitis-associated carcinoma. However, no study has compared the expression in both of these cancer types. The present study aimed to evaluate the relationship between colitis-associated carcinoma and ERs and assess whether the expression of ER beta influences cell proliferation. Methods: This study included 45 surgically operated colitis-associated carcinomas, 43 high-grade dysplasias, 34 low-grade dysplasias, 36 sporadic colorectal cancers, 44 high-grade adenomas, and 34 low-grade adenomas. ER beta expression was evaluated with immunohistochemistry. Results: Colitis-associated carcinoma showed significantly lower ER beta immunoexpression than sporadic colorectal lesions and high- and low-grade dysplasia. In seven colitis-associated carcinoma harboring both intensity score 3 (strong immunoexpression) and score 1 (weak immunoexpression) areas, the correlation among ER beta intensity, Ki-67, and p21 labeling index was assessed; an area with an ER beta intensity score of 3 showed a higher Ki-67 labeling index than that with score 1. In four out of the seven lesions, p21 labeling index was higher in the area of ER beta score 1 than in that of ER beta score 3. Conclusions: The data suggest that ER beta expression is an accelerating factor in colorectal tumors. This association may be lower in colitis-associated carcinoma than in sporadic colorectal cancer.

Feasibility of Laparoscopic Sleeve Gastrectomy for Patients with Obesity and Disorders of Intellectual Development: a Single Institutional Experience.

BACKGROUND: Owing to their difficulty following clinical advice for procedural safety and ideal surgical outcomes, bariatric and metabolic surgery (BMS) for patients with disorders of intellectual development (DID) is concerning. Studies reporting the feasibility of BMS for this population remain scarce. This study aims to clarify the feasibility of laparoscopic sleeve gastrectomy (LSG) for patients with clinically severe obesity and DID. METHODS: A retrospective analysis of a single institutional prospective database collected from 2010 to 2022 was performed. The Wechsler Adult Intelligence Scale (WAIS) was used to measure intellectual ability before LSG. A multidisciplinary team approach was implemented to give special support and care to patients with DID. Patients were categorized into groups according to their WAIS scores. LSG outcomes were statistically compared between the DID and average intellectual ability groups. RESULTS: Using the WAIS to measure intellectual ability among patients who underwent LSG, we identified 14 patients with DID (IQ score: < 69, mean IQ: 63.4) and 71 with average intellectual ability (IQ score: 90-109, mean IQ: 98.9). Operative outcomes were comparable between the groups as follows: operation time (DID: 163 ± 41 min, average intelligence: 162 ± 30 min), hospital stay (DID: 4 [4-5] days, average intelligence: 5 [4-6] days), and total comorbidities (DID: 7.1%, average intelligence: 8.4%). No reoperations were performed, and no mortalities were observed. CONCLUSIONS: With medical and social support and care, performing LSG on patients with clinically severe obesity and DID is safe, with good short-term results.

Safety and effectiveness of metabolic surgery in older Japanese patients.

Aim: According to the current guidelines in Japan, the upper age limit for bariatric and metabolic surgery is 65 y. This study aimed to examine the appropriateness of this upper age limit. Methods: Using the database maintained by the Japanese Society for Treatment of Obesity, we conducted an analysis of patients in two age groups: those aged <65 y and those aged ≥65 y. Our analysis focused on postoperative weight loss, improvement in comorbidities, and frequency of perioperative complications. Results: A total of 2885 patients aged <65 y (mean, 43.9 ± 9.5 y) with a preoperative body mass index of 42.4 ± 8.1 kg/m2, while 56 aged ≥65 y (mean, 67.3 ± 3.2 y; maximum, 78 y) with a preoperative body mass index of 40.5 ± 6.6 kg/m2. Patients aged ≥65 y had a higher rate of dyslipidemia and hypertension. The rates of reoperation, surgical complications, and postoperative complications did not differ between the age groups. Both groups achieved significant weight loss postoperatively, and no differences in the improvement of comorbidities were noted. After adjusting the covariate balance via propensity score matching, no age-related differences in perioperative and postoperative complications were observed. Conclusion: Metabolic surgery is safe and effective for older patients with clinically severe obesity. Weight loss was less in patients aged ≥65 y, but the percentage of total weight loss did not differ between the groups.

Treatments for Staple Line Leakage after Laparoscopic Sleeve Gastrectomy.

The number of laparoscopic sleeve gastrectomies (LSGs) performed in patients with obesity who are eligible for bariatric and metabolic surgery is currently much lower in Japan than in other countries. Considering the large number of potential patients with obesity and type 2 diabetes and the unique Japanese national health insurance system that guarantees fair healthcare delivery, there is room to increase the number of LSGs in Japan in the near future. However, strict health insurance regulations may limit access to mandatory devices needed to treat postoperative complications, such as staple line leakage, which can cause severe morbidity and even mortality. Therefore, understanding the pathogenesis and treatment options for this complication is crucial. This article examined the current situation in Japan and its impact on staple line leakage management, including the role of endoscopic treatment in reducing reoperation. The authors suggest increasing education and collaboration between healthcare professionals to optimize management and improve patient outcomes.

Factors Associated with Relapse of Type 2 Diabetes Mellitus after Laparoscopic Sleeve Gastrectomy in Japanese Subjects: A Subgroup Analysis of J-SMART Study.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) for morbidly obese patients often results in remission of type 2 diabetes (T2DM), but diabetes relapses in some of those patients. The frequency of T2DM relapse in Asians and the factors involved have not been adequately investigated. METHODS: The J-SMART study was conducted on 322 Japanese subjects with body mass index (BMI) ≥32 kg/m2 who underwent LSG at 10 accredited centers in Japan between 2011 and 2014. Of these, 82 T2DM subjects with diabetes in complete or partial remission at 1 year after LSG and followed postoperatively for 5 years were included in the subgroup analysis and classified into two groups: diabetes remission-maintained and diabetes relapse. RESULTS: The mean age of all included subjects was 49.2 years, median BMI was 41.5 kg/m2, and median HbA1c was 6.7%. Compared with the diabetes remission-maintained group, the diabetes relapse group at 5 years after LSG had significantly higher preoperative HbA1c, number of antidiabetic medications, and high-density lipoprotein cholesterol level; and lower BMI and homeostasis model assessment-beta cell function (HOMA-ß). As many as 83.0% of the subjects were able to achieve HbA1c <7% at 5 years after LSG, but 26.8% of the subjects had diabetes relapse. Preoperative HbA1c significantly contributed to diabetes relapse (odds ratio 1.54, p = 0.049). In addition, the diabetes relapse group tended to have lower percentage total weight loss (%TWL) at 1 year after LSG and higher percentage weight regain (%WR) from postoperative nadir weight, compared with the diabetes remission-maintained group. The hazard ratio for diabetes relapse was 3.14-fold higher in subjects with %TWL ≥20% and %WR ≥25%, and 5.46-fold higher in those with %TWL <20% and %WR ≥25%, compared with %TWL ≥20% and %WR <25%. CONCLUSION: While LSG provides a high remission rate for T2DM, relapse is not uncommon. Preoperative HbA1c, poor weight loss, and excess weight regain after LSG contribute to diabetes relapse, suggesting the importance of treatment strategies focusing on these factors.

Tissue expression of Toll-like receptors 2 and 4 in sporadic human colorectal cancer.

BACKGROUND: Toll-like receptors (TLRs) play an important role in innate immunity by sensing a variety of pathogens and inducing acquired immunity. To test our hypothesis that dysregulation of innate immune responses acts to trigger carcinogenesis, we studied the expression of TLR2 and 4 in sporadic human colorectal cancer tissue. METHODS: In specimens of cancerous and noncancerous colorectal tissue obtained at surgery, mRNA expression levels of TLR2 and 4 were quantified by TaqMan real-time polymerase chain reaction and compared between the two types of tissue. To confirm TLR2 and TLR4 protein expression levels, immunohistochemical analysis was performed using the same samples. RESULTS: TLR2 mRNA expression was significantly higher in cancerous tissue than in noncancerous tissue, while TLR4 mRNA expression did not differ significantly. Immunohistochemical analysis revealed stronger staining for TLR2 in cancerous mucosal epithelial cells than in noncancerous tissue. Staining for TLR4 in the lamina propria of the mucosa was equally weakly positive in noncancerous tissue and cancerous tissue. This TLR-specific difference in expression suggested that such expression does not only reflect a local inflammatory response to cancer infiltration, i.e., if this was the case, both TLR2 and 4 expression would probably be up-regulated. Our results suggest that TLR2 expression might be involved in sporadic colorectal carcinogenesis, whereas TLR4 is not.

Apparent diffusion coefficient correlation with oesophageal tumour stroma and angiogenesis.

OBJECTIVE: Because diffusion-weighted imaging (DWI) can predict the prognosis of patients with oesophageal squamous cell carcinoma (ESCC), we hypothesised that apparent diffusion coefficient (ADC) values might be correlated with the collagen content and tumour angiogenesis. The purpose of this study was to determine the correlation between ADC values of ESCC before treatment and oesophageal tumour stroma and angiogenesis. METHODS: Seventeen patients with ESCC were enrolled. The ADC values were calculated from the DWI score. Seventeen patients who had undergone oesophagectomy were analysed for tumour stroma, vascular endothelial growth factor (VEGF) and CD34. Tissue collagen was stained with azocarmine and aniline blue to quantitatively analyse the extracellular matrix in cancer stroma. Tissues were stained with VEGF and CD34 to analyse the angiogenesis. RESULTS: The ADC values decreased with stromal collagen growth. We found a negative correlation between the tumour ADC and the amount of stromal collagen (r = -0.729, P = 0.001), i.e. the ADC values decreased with growth of VEGF. We also found a negative correlation between the ADC of the tumours and the amount of VEGF (r = 0.538, P = 0.026). CONCLUSION: Our results indicated that the ADC value may be a novel prognostic factor and contribute to the treatment of oesophageal cancer. KEY POINTS: • Magnetic resonance apparent diffusion coefficient values inversely indicate tumour stromal collagen • There is also negative correlation between ADCs and vascular endothelial growth factor • ADC values may contribute to the treatment of oesophageal cancer.

A phase I/II clinical trial of preoperative short-course carbon-ion radiotherapy for patients with squamous cell carcinoma of the esophagus.

BACKGROUND: Carbon-ion radiotherapy (CIR) has been under development. We report the results of a phase I/II clinical trial of preoperative CIR for esophageal squamous cell carcinoma (ESCC). METHODS: Thirty-one thoracic ESCC patients were enrolled. They were first treated with CIR. The radiation dose was escalated from the initial dose of 28.8 GyE up to 36.8. Four to 8 weeks after CIR followed by clinical evaluation of the therapy, surgery was performed. Thereafter, a pathological evaluation was made. RESULTS: Acute toxicity was not seen except in one case (3.2%), and there were no late toxicities. Throughout the study period, there were no cases of withdrawal due to the effects of preoperative CIR. Twelve out of 31 (38.7%) patients achieved a clinical complete response (CR) and 13 patients (41.9%) achieved a partial response. Twelve out of 31 patients (38.7%) achieved a pathological CR. The overall 1-, 3-, and 5-year survival rates in the stage I cases were 91%, 81%, and 61%, and was 100%, 85%, and 77% for the stage II, and 71%, 43%, and 29% for the stage III cases, respectively. CONCLUSIONS: CIR showed strong local tumor control and is highly effective as a neoadjuvant therapy without severe adverse events.

Cancer stem cell markers CD44v9+/CD133- are associated with low apoptosis in both sporadic and ulcerative colitis-associated colorectal cancers.

OBJECTIVE: To elucidate tumor cell behavior associated with cancer stem cell (CSC) marker expression, the expression of CD133, CD44v9, and ALDH1A1, which are considered markers of CSCs, was examined in sporadic and ulcerative colitis (UC)-associated colorectal tumors. METHODS: A total of 23 cases of sporadic colorectal cancer and 44 cases of adenoma were collected. Additionally, 22 cancer lesions and 38 dysplasia lesions were selected from 28 colectomy cases of UC with neoplastic lesions. Lesions were examined by immunohistochemistry using primary antibodies against CD133, CD44v9, ALDH1A1, Ki-67, cleaved-Caspase 3, and p53. RESULTS: CD133, CD44v9, and ALDH1A1 showed higher expression in both sporadic and UC-associated tumors than in the normal mucosa. ALDH1A1 expression in sporadic cancer was higher in the right colon than in the left colon (p=0.0089). ALDH1A1 expression in UC-associated cancer was higher in those with longer disease duration than in those with shorter disease duration (p=0.019). The CD44v9+/CD133- region had fewer cleaved-Caspase 3 positive cells in both sporadic and UC-associated cancers. In sporadic cancer, CD133+/ALDH1A1+ regions had fewer apoptotic cells than CD133+/ALDH1A1- regions, while CD133+/ALDH1A1- regions were less proliferative than CD133+/ALDH1A1+ regions in UC-associated cancer. CONCLUSION: CD44+/CD133- regions were commonly associated with low apoptosis in sporadic and UC-associated cancers; thus, these were considered target areas for CSCs. Additionally, the combination of markers comprising CSCs may differ between sporadic and UC-associated cancers.