[Results of a multicentric colorectal cancer screening program in Chile]. / Programa multicéntrico de cribado de cáncer colorrectal en Chile.

BACKGROUND: Colorectal Cancer Screening Programs (CRCSP) are widely accepted in developed countries. Unfortunately, financial restrictions, low adherence rate and variability on colonoscopy standardization hamper the implementation of CRCSP in developing countries. AIM: To analyze a multicentric pilot model of CRCSP in Chile. MATERIAL AND METHODS: A prospective model of CRCSP was carried out in three cities, from 2012 to 2015. The model was based on CRC risk assessment and patient education. Health care personnel were trained about logistics and protocols. The endoscopy team was trained about colonoscopy standards. A registered nurse was the coordinator in each center. We screened asymptomatic population aged between 50 and 75 years. Immunological fecal occult blood test (FIT) was offered to all participants. Subjects with positive FIT underwent colonoscopy. RESULTS: A total of 12,668 individuals were enrolled, with a FIT compliance rate of 93.9% and 2,358 colonoscopies were performed. Two hundred and fifty high-risk adenomas and 110 cancer cases were diagnosed. One patient died before treatment due to cardiovascular disease, 74 patients (67%) underwent endoscopic resection and 35 had surgical treatment. Ninety one percent of patients had an early stage CRC (0-I-II). Among colonoscopy indicators, 80% of cases had an adequate bowel preparation (Boston > 6), cecal intubation rate was 97.7%, adenoma detection rate was 36.5%, and in 94.5% of colonoscopies, withdrawal time was adequate (> 8 min). CONCLUSIONS: This CRCS pilot model was associated to a high rate of FIT return and colonoscopy quality standards. Most CRCs detected with the program were treated by endoscopic resection.

Programa multicéntrico de cribado de cáncer colorrectal en Chile / Results of a multicentric colorectal cancer screening program in Chile

Background: Colorectal Cancer Screening Programs (CRCSP) are widely accepted in developed countries. Unfortunately, financial restrictions, low adherence rate and variability on colonoscopy standardization hamper the implementation of CRCSP in developing countries. Aim: To analyze a multicentric pilot model of CRCSP in Chile. Material and Methods: A prospective model of CRCSP was carried out in three cities, from 2012 to 2015. The model was based on CRC risk assessment and patient education. Health care personnel were trained about logistics and protocols. The endoscopy team was trained about colonoscopy standards. A registered nurse was the coordinator in each center. We screened asymptomatic population aged between 50 and 75 years. Immunological fecal occult blood test (FIT) was offered to all participants. Subjects with positive FIT underwent colonoscopy. Results: A total of 12,668 individuals were enrolled, with a FIT compliance rate of 93.9% and 2,358 colonoscopies were performed. Two hundred and fifty high-risk adenomas and 110 cancer cases were diagnosed. One patient died before treatment due to cardiovascular disease, 74 patients (67%) underwent endoscopic resection and 35 had surgical treatment. Ninety one percent of patients had an early stage CRC (0-I-II). Among colonoscopy indicators, 80% of cases had an adequate bowel preparation (Boston > 6), cecal intubation rate was 97.7%, adenoma detection rate was 36.5%, and in 94.5% of colonoscopies, withdrawal time was adequate (> 8 min). Conclusions: This CRCS pilot model was associated to a high rate of FIT return and colonoscopy quality standards. Most CRCs detected with the program were treated by endoscopic resection.

A prospective study of nutritional supplementation for preventing oral mucositis in cancer patients receiving chemotherapy.

BACKGROUND AND OBJECTIVES: Patients undergoing chemotherapy often develop distressing adverse effects such as oral mucositis and diarrhea. Nutritional support with elemental diet is effective against various gastrointestinal complications and may exert protective effects against adverse effects induced by chemotherapy. To evaluate the influence of elemental diet on chemotherapy-induced oral mucositis and diarrhea, we conducted a randomized control trial in patients with esophageal cancer undergoing chemotherapy. METHODS AND STUDY DESIGN: Twenty esophageal cancer patients receiving chemotherapy with 5-fluorouracil plus cisplatin were assigned randomly to one of the following two groups: (1) receiving elemental diet with Elental (one pack per day) for 14 days and (2) not receiving Elental during chemotherapy. The severity of oral mucositis and diarrhea was graded using clinical examination by doctors and a standard questionnaireon days 1-14. RESULTS: Based on the analysis of the standard questionnaire, the distribution of the maximum severity of oral mucositis showed a statistically significant reduction in the Elental group (p=0.020), while clinical examination showed insignificant reduction but shift toward lower grade. In the Elental group, the incidence of oral mucositis (grade >=2) reduced consistently and the median grade was lower at all-time points. Regarding diarrhea, no difference was observed between the two groups based on the analysis of the standard questionnaire and clinical examination results. CONCLUSIONS: This study illustrates the effectiveness of oral elemental diet in preventing oral mucositis during chemotherapy. This is a preliminary report and further study with larger patients groups should be devoted to optimization of efficacy.

[Laparoscopic Gastrectomy for Gastric Adenocarcinoma of the Fundic Gland Type - Report of a Case].

A 69-year-old man underwent esophagogastroduodenoscopy, which showed a slightly depressed lesion at the greater curvature of the gastric body. We diagnosed gastric adenocarcinoma of the fundic gland type(GA-FG)from examination of the biopsy specimen. Endoscopic submucosal dissection(ESD)was performed for curative resection. The pathological examination revealed a positive vertical margin. Consequently, laparoscopic gastrectomy was additionally performed. GA-FG has recently been proposed as a new entity of gastric adenocarcinoma. GA-FG mostly develops without Helicobacter pylori infection and often invades the submucosa, regardless of size. However, GA-FG rarely demonstrates lymphatic and venous invasion despite deep submucosal invasion. Since most GA-FG cases undergo ESD, few reports of surgical resection exist. Here, we report our experience of laparoscopic gastrectomy for GA-FG.

International collaboration between Japan and Chile to improve detection rates in colorectal cancer screening.

BACKGROUND: In Chile, mortality from colorectal cancer (CRC) has increased rapidly. To help address this issue, the Prevention Project for Neoplasia of the Colon and Rectum (PRENEC) program was initiated in 2012 with intensive support from Tokyo Medical and Dental University (TMDU) in Tokyo, Japan, as part of an international collaboration. METHODS: From June 2012 to July 2014, a total of 10,575 asymptomatic participants were enrolled in PRENEC. Participants with positive immunochemical fecal occult blood test (iFOBT) results or a family history of CRC underwent colonoscopy. The colonoscopy results from a similar, previous project in Chile (PREVICOLON) were compared with those from PRENEC. Furthermore, the initial colonoscopies of 1562 participants in PRENEC were analyzed according to whether the colonoscopists were from TMDU or Chile. RESULTS: The complete colonoscopy, adenoma detection, and cancer detection rates were 88.0%, 26.7%, and 1.1%, respectively, in PREVICOLON, while the corresponding values were 94.4%, 41.8%, and 6.0%, respectively, in PRENEC. In PRENEC, 107 cases of CRC were detected, amounting for 1.0% of all participants. Considering initial colonoscopies in PRENEC, the complete colonoscopy, adenoma detection, and cancer detection rates were 97.4%, 45.3%, and 9.3%, respectively, for physicians at TMDU and 93.3%, 41.5%, and 5.1%, respectively for Chilean physicians. The detection rates of intramucosal cancer were 7.3% and 3.7%, respectively, for TMDU and Chilean physicians. CONCLUSIONS: Quality indicators of colonoscopy substantially improved from PREVICOLON to PRENEC. The assessments made by Chilean physicians alone were improved in PRENEC, but remained better in the TMDU group. Moreover, physicians from TMDU detected more CRCs than Chilean physicians, especially at earlier stages.

Changes in the microvascular structure of mucosal squamous cell carcinoma of the esophagus and their significance in tumor progression.

BACKGROUND: To identify the clinical T stage by endoscopy is a major diagnostic goal for superficial esophageal squamous cell carcinoma (ESCC). The completion of a microvascular morphological study of mucosal lesions is necessary to optimize therapy. MATERIALS AND METHODS: Images of 197 intra-papillary capillary loops (IPCLs) captured by magnified endoscopy from 15 esophagectomy specimens were studied for their morphological features and IPCL dimensions. RESULTS: The microvascular morphology was classified into four basic major patterns: 1. spiral loop, 2. wide loop (WL), 3. globular (G) and 4. reticular pattern. The microvascular features and dimensions differed according to the depth of tumor invasion. Especially the mean bundle outline (IPCL diameter) showed significant changes as 20.02, 22.32, and 27.08 µm, respectively, for M1, M2 and M3, respectively (M1:M2 P < 0.05, M2:M3 P < 0.01). CONCLUSIONS: During tumor stage progression, a high-volume blood demand and cancer cell overgrowth to occupy the laminar propria mucosa (LPM) cause obvious elongation, thickening, branching, irregularity and deformity of the IPCL, which were characteristics of M3 lesions. The results of the present study support and can be applied with the current Japanese classification for improving the diagnostic accuracy, especially to differentiate between M2 and M3 lesions based on the endoscopic findings.

Esophageal squamous cell carcinoma developed 11 years after allogeneic bone marrow transplantation for acute lymphatic leukemia.

Younger patients (aged <30 years) presenting with esophageal cancer are rare. Bone marrow transplantation offers a curative therapy in patients with malignant and nonmalignant lymphohematopoietic diseases and other disorders. However, one important late complication in transplantation survivors is the development of secondary malignancies including solid tumors. Although some solid cancers have been demonstrated to occur after bone marrow transplantation, only a few cases of esophageal squamous cell carcinoma have thus far been reported. We herein describe the case of a 27-year-old male with esophageal squamous cell carcinoma, who was diagnosed with T-cell-type acute lymphatic leukemia at the age of 12 and relapsed 5 years later. He achieved a second complete remission and underwent bone marrow transplantation at the age of 17. A genetic analysis revealed germ-line lineage-derived chimeric cellular populations of the donor and patient on both the esophageal squamous cell carcinoma and non tumorous portions of the patient's esophageal mucosa with a preponderance of the patient's germ-line lineage-derived cells, suggesting that repopulated donor-derived hemopoietic stem cells in the esophageal epithelia only partially contributed to the carcinogenesis of esophageal squamous cell carcinoma several years after bone marrow transplantation. Multiple events occurring during the course of treatment for primary hematological disorder may play an important role in the development of esophageal squamous cell carcinoma.

A pilot trial of S-1 plus irinotecan chemotherapy for esophageal adenocarcinoma.

BACKGROUND/AIMS: This study investigated the clinical efficacy and toxicity of the combination chemotherapy using S-1 plus irinotecan for esophageal adenocarcinoma. METHODOLOGY: This study included 10 patients with histologically confirmed adenocarcinoma of the esophagus or esophagogastric junction between April 2005 and August 2011. S-1 was administered orally at a dose of 80 mg/m²/day from day 1 to 14 and irinotecan was given intravenously on day 1 and 8 at a dose of 80 mg/m². RESULTS: A total of 65 cycles were administered and the response rate was 62.5%. The 50% progression-free survival period and the 50% overall survival period for all of the patients was 8.4 months and 19.1 months, respectively and 5.9 months and 16.3 months for the 8 patients with unresectable or recurrent tumors, respectively. The 2 patients that received adjuvant chemotherapy demonstrated a prophylactic effect for the post-operative recurrence. On the other hand, this therapy showed no severe non-hematological toxicity and only 20% experienced grade 3 neutropenia. As a result, the treatment regimen could generally be performed in an outpatient basis. CONCLUSIONS: The combination chemotherapy using S-1 and irinotecan showed tolerable clinical efficacy in terms of the response rate, survival and toxicity for esophageal adenocarcinoma.

Osteoplastic bone metastasis in esophageal squamous cell cancer: report of a case.

This report presents a case of esophageal squamous cell cancer with osteoplastic bone metastasis. A 58-year-old male patient underwent multimodality treatment for esophageal cancer. Sclerotic changes resembling bone metastasis from prostate cancer were detected in the 4th thoracic and the 5th lumber vertebral body soon after the adjuvant chemoradiotherapy. Systemic examinations revealed no primary cancer as a cause of osteoplastic bone metastasis and no esophageal cancer recurrence. A needle biopsy revealed metastases of esophageal squamous cell cancer with osteoplastic changes. Multiple sclerotic changes were detected in the systemic bones at that time, and new carcinomatous bilateral pleural effusion developed. The drastic systemic progression of the cancer caused the rapid deterioration of the patient's general condition.

Subcutaneous reconstruction using ileocolon with preserved ileocolic vessels following esophagectomy or in esophageal bypass operation.

BACKGROUND: When forming an esophageal substitute with an ileocolon in esophageal reconstruction with cervical anastomosis, the ileocolic vessels should be divided in many cases and this may be followed by the occurrence of poor blood circulation in the pulled-up substitute. METHODS: Twenty-two consecutive esophageal reconstructions using an all-main-vessel-preserving ileocolon had been performed in the past 4 years and we evaluated the usefulness of this surgical modality. RESULTS: In every case, the extension length of the ileocolon was sufficient for esophageal reconstruction. There were no serious surgical complications concerning the esophageal substitutes such as necrosis of the pulled-up ileocolon. CONCLUSIONS: Although it was thought that the surgical techniques shown here were possible only in selected patients, successful esophageal reconstructions were achieved with this new concept in 22 consecutive patients with various backgrounds. The procedures shown here are not new; however, the concept of using the all-main-vessel-preserving ileocolon as an esophageal substitute for every patient requiring esophageal reconstruction is new.

A pilot trial of docetaxel and nedaplatin in cisplatin-pretreated relapsed or refractory esophageal squamous cell cancer.

BACKGROUND/AIMS: This study documents the clinical efficacy and toxicity of docetaxel and nedaplatin in cisplatin-pretreated relapsed or refractory esophageal squamous cell cancer. METHODOLOGY: From February 2002 to February 2007, 20 patients with metastatic or locally recurrent or residual disease previously treated with cisplatin-based chemotherapy or chemoradiotherapy were included. The median age was 66.0 (range 52-74) years, and 17 patients had undergone a previous esophagectomy. A total of 36 cycles with docetaxel 60 mg/m2 plus nedaplatin 80 mg/m2 were administered. RESULTS: The response rate was 25% including one complete response, and the rate of disease stabilization (% of complete response, partial response and stable disease) was 80%. The median progression-free survival was 14 weeks and the median overall survival was 26 weeks. Severe neutropenia occurred in 12 patients (grade 3/4 = 4/8) and 5 out of 20 patients showed severe febrile neutropenia (grade 3/4 = 4/1), whereas no severe non-hematological toxicity was observed. CONCLUSIONS: In conclusion, the combination chemotherapy of docetaxel and nedaplatin did not show drastic clinical efficacy. However, it was considered to be a feasible regimen as tumor dormancy therapy in CDDP-pretreated esophageal cancer, and to have a potent possibility to become a useful second-line chemotherapy for relapsed or refractory esophageal cancer. The control and prevention of severe neutropenia and febrile neutropenia is also very important in use of this regimen.

[Esophageal carcinoma - from the viewpoint of surgery].

Therapeutic performance of the esophageal cancer has improved rapidly. Now in the decision of therapeutic strategy not only life prognosis but also treatments-related morbidity and late term quality of life should be considered. The most important factor of the improvement of esophageal cancer treatment is a progress in early detection of esophageal cancers and active use of treatment methods such as endoscopic mucosal resection. In addition,the role of radiotherapy and chemotherapy has improved as an arm of multidisciplinary therapy,and the establishment of chemoradiotherapy as one of the standard therapy for esophageal cancer is also very important. This shows that surgical and non-surgical approach has been getting more interactive and the relationship to one another should always be considered. Surgical therapy is very effective in patients with localized esophageal tumor and the patient's satisfaction is high. However, many problems are remained, and the improvement of diagnosis for metastasis and lessening surgical invasiveness and early/late complications are expected. Moreover,the chemoradiotherapy as an esophagus preserving method will establish more important standpoint and the salvage surgery will be applied more actively. On the other hand, a new strategy such as chemoradiotherapy immediate after esophagectomy for the patients with possible residual tumor for improving therapeutic results may be considered under the status of reliable surgical procedures.

[Progress of diagnosis for esophageal cancer].

Although the possible existence of micrometastasis in superficial esophageal cancer cases is the most important factor in deciding the therapeutic strategy, it is difficult. There are also limits to the diagnosis of the depth of tumor invasion by endoscopy and EUS. Therefore, the extension of the indication of EMR is planned. Then, the complement of diagnostic ability by EMR is being tried. Sentinel lymph node (s) identification and its biopsy also seem to be useful. In advanced esophageal cancer cases, diagnostic accuracy has been improving by speedup of CT and MRI scans and various image processing technology. More accurate diagnosis of metastasis using PET is much awaited. However, there is still insufficient ability to detect micrometastasis to date. Molecular bio-markers with comprehensiveness are not a valuable selection at this stage. Although advanced equipment has brought more diagnostic accuracy, ways to integrate or use these tools at the clinical level are sought. Some equipment developing and how to integrate them and how to select the appropriate examination in each patient are problems which are required in clinical practitioners.

IFN-gamma production from liver mononuclear cells of mice in burn injury as well as in postburn bacterial infection models and the therapeutic effect of IL-18.

Hosts after severe burn injury are known to have a defect in the Th1 immune response and are susceptible to bacterial infections. We herein show that liver NK cells are potent IFN-gamma producers early after burn injury. However, when mice were injected with LPS 24 h after burn injury, IFN-gamma production from liver mononuclear cells (MNC; which we previously showed to be NK cells) was suppressed, and the serum IFN-gamma concentration did not increase, while serum IL-10 conversely increased compared with control mice. Interestingly, a single injection of IL-18 simultaneously with LPS greatly restored the serum IFN-gamma concentration in mice with burn injury and also increased IFN-gamma production from liver MNC. Nevertheless, a single IL-18 injection into mice simultaneously with LPS was no longer effective in the restoration of serum IFN-gamma and IFN-gamma production from the liver MNC at 7 days after burn injury, when mice were considered to be the most immunocompromised. However, IL-18 injections into mice on alternate days beginning 1 day after burn injury strongly up-regulated LPS-induced serum IFN-gamma levels and IFN-gamma production from liver and spleen MNC of mice 7 days after burn injury and down-regulated serum IL-10. Furthermore, similar IL-18 therapy up-regulated serum IFN-gamma levels in mice with experimental bacterial peritonitis 7 days after burn injury and greatly decreased mouse mortality. Thus, IL-18 therapy restores the Th1 response and may decrease the susceptibility to bacterial infection in mice with burn injury.