Objective: To study the expression of cyclooxygenase-2 (COX-2) protein in different subtypes of intestinal metaplasia (IM) and gastric carcinoma, evaluate the possibility of COX-2 forecasting the risk of malignant pot...Objective: To study the expression of cyclooxygenase-2 (COX-2) protein in different subtypes of intestinal metaplasia (IM) and gastric carcinoma, evaluate the possibility of COX-2 forecasting the risk of malignant potential of IM, and the relationship between COX-2 expression and gastric carcinogenesis. Methods: Forty cases of chronic atrophic gastritis (CAG) with IM, 40 cases of gastric carcinoma and corresponding paracancerous tissues were selected to construct a tissue microarray. High iron diamine/alcian blue (HID/AB) staining and Hematoxylin and Eosin (HE) staining was used to classify IM and gastric carcinoma, and the expression of COX-2 protein detected in different subtypes of IM and gastric cancer by using immunohistochemistry. Results: The positive expression rate of COX-2 was 45.65%, 59.38% and 77.27% in IM foci in CAG, IM foci in paracancerous tissues, and intestinal-type gastric carcinoma, respectively, significantly higher than in diffuse-type gastric cancer (16.67%)(P<0.05, 0.005 and 0.005, respectively), and the expression intensity of COX-2 protein showed a increased tendency gradually in the sequence of IM foci in CAG→IM foci in paracancerous tissues→intestinal-type gastric carcinoma (P<0.005). The positive expression rate of COX-2 protein in type Ⅲ IM was significantly higher than in type Ⅰ and type Ⅱ IM (P<0.005 and 0.05, respectively), and the expression intensity also showed a increased tendency gradually from type Ⅰ to type Ⅲ IM (P<0.005). Conclusion: The expression level of COX-2 was increased gradually along with the increase of the risk of malignancy of IM, and its expression level may be a useful index to forecast the risk of malignant potential of IM. COX-2 expression was associated with intestinal-type gastric carcinoma, but it might also have some role in the carcinogenesis of diffuse-type gastric carcinoma.展开更多
AIM: To identify the gastrointestinal stromal tumors(GISTs) that are negative for CD117 expression by immunohistochemistry and to characterize their malignant potential.METHODS: A total of 108 primary mesenchymal tumo...AIM: To identify the gastrointestinal stromal tumors(GISTs) that are negative for CD117 expression by immunohistochemistry and to characterize their malignant potential.METHODS: A total of 108 primary mesenchymal tumors of the gastrointestinal tract were screened to select CD117-negative tumors, from which KIT(exons 9, 11, 13, and 17)and PDGFRA (exons 10, 12, 14, and 18) were sequenced to identify GISTs. Tumor recurrence and distant metastasis were used as the criteria of malignancy.RESULTS: The result showed that approximately 25%(29/108) of the gastrointestinal mesenchymal tumors were negative for CD117 and approximately 6% (7/108)of the tumors were CD117-negative GISTs. All these CD117-negative tumors had a mutated KITand a wildtype PDGFRA. All CD117-negative GISTs with mutations at codons 557/558 of KIThad mitotic counts >10/50 high power field, and 75% (3/4) of them showed multiple recurrence or distant metastasis.CONCLUSION: CD1 17-negative KITmutated GISTs account for approximately 6% of the gastrointestinal mesenchymal tumors. Tumor recurrence or distant metastasis correlates to both theKITmutations at codons 557/558 and the mitotic counts, but not to the tumor size.展开更多
AIM: To investigate the effects of 7.5% hypertonic saline on positive fluid balance and negative fluid balance, after radical surgery for gastrointestinal carcinoma. METHODS: Fifty-two patients with gastrointestinal c...AIM: To investigate the effects of 7.5% hypertonic saline on positive fluid balance and negative fluid balance, after radical surgery for gastrointestinal carcinoma. METHODS: Fifty-two patients with gastrointestinal carcinoma undergoing radical surgery were studied. The patients were assigned to receive either Ringer lactate solution following 4 mL/kg of 7.5% hypertonic saline (the experimental group, n = 26) or Ringer lactate solution (the control group, n = 26) during the early postoperative period in SICU. Fluid infusion volumes, urine outputs, fluid balance, body weight change, PaO2/FiO2 ratio, anal exhaust time as well as the incidence of complication and mortality were compared between the two groups. RESULTS: Urine outputs on the operative day and the first postoperative day in experimental group were significantly more than in control group (P<0.000001, P=0.000114). Fluid infusion volumes on the operative day and the first postoperative day were significantly less in experimental group than in control group (P= 0.000042, P= 0.000415). The volumes of the positive fluid balance on the operative day and during the first 48 h after surgery, in experimental group, were significantly less than in control group (P<0.000001). Body weight gain post-surgery was significantly lower in experimental group than in control group (P<0.000001). The body weight fall in experimental group occurred earlier than in control group (P<0.000001). PaO2/FiO2 ratio after surgery was higher in experimental group than in control group (P= 0.000111). The postoperative anal exhaust time in experimental group was earlier than in control group (P= 0.000006). The overall incidence of complications and the incidence of pulmonary infection were lower in experimental group than in control group (P= 0.0175, P= 0.0374). CONCLUSION: 7.5% hypertonic saline has an intense diuretic effect and causes mobilization of the retained fluid, which could reduce fluid infusion volumes and positive fluid balance after radical surgery for gastrointestinal carcinoma, as well as, accelerate the early appearance of negative fluid balance after the surgery, improve the oxygen diffusing capacity of the patients' alveoli, and lower the overall incidence of complications and pulmonary infection after the surgery.展开更多
AIM: This study shares Asian clinical experiences of carcinoid tumors that originated in the upper gastrointestinal tract.METHODS: From May 1987 to June 2002, we had found only 13 cases of histologically confirmed car...AIM: This study shares Asian clinical experiences of carcinoid tumors that originated in the upper gastrointestinal tract.METHODS: From May 1987 to June 2002, we had found only 13 cases of histologically confirmed carcinoid tumors in the upper gastrointestinal tract by endoscopic examinations. There were eight males and five females.The mean age was 53.16±20.51 years that ranged from 26 to 82 years. Each of their clinical presentations,locations, tumor morphology, and size and the treatment outcome were analyzed and discussed.RESULTS: One patient had a polypoid lesion at the lower esophagus, nine were stomach lesions and three located at the duodenum. All patients with polypoid and submucosal tumor types were of small size (<1.7 cm) and all patients survived after simple excision or polypectomy.Four of the five patients in tumor mass forms died and the tumors were more than 2.0 cm in size.CONCLUSION: Carcinoid tumors rarely originated from the upper gastrointestinal tract and are usually found accidentally after endoscopic study. Bigger size (more than 2 cm) tumor masses may indicate a more severe disease and poor prognosis.展开更多
AIM: To examine the prevalence and prognostic significance of C-kit gene mutation and analysis the correlation of C-kit gene mutation and the clinicalpathologic parameters of GISTs. METHODS: Eighty-two GISTs were stud...AIM: To examine the prevalence and prognostic significance of C-kit gene mutation and analysis the correlation of C-kit gene mutation and the clinicalpathologic parameters of GISTs. METHODS: Eighty-two GISTs were studied for the mutation of C-kit gene by PCR-SSCP, DNA sequence. Statistical comparison were used to analysis the correlation of C-kit gene mutation and clinicalpathology, clinical behavior, recurrence. RESULTS: (1) Mutation-positive and mutation-negative GISTs were 34 and 48,respectively; (2) Among the sepatients with C-kit mutation remained a significantly poor prognosis associated with 59% 3-year survival compared to those whose tumors did not; (3) Tumor size, PCNA index, mitotic cell number, presence of necrosis, microscopic invasion to adjacent tissues, recurrence and distant metastasis among mutation-positive and mutation-negative GISTs were significantly different. CONCLUSION: C-kit mutation is a undoubtedly pivotal event in GIST and may be associated with poor prognosis. Evaluation of C-kit gene mutation may have both prognosis and therapeutic significances.展开更多
Gastrointestinal stromal tumour (GIST) is a rare tumour of the gastrointestinal tract which does not generally originate in the rectum. The authors describe a case of a 70-year-old man who underwent an anterior rese...Gastrointestinal stromal tumour (GIST) is a rare tumour of the gastrointestinal tract which does not generally originate in the rectum. The authors describe a case of a 70-year-old man who underwent an anterior resection of the rectum for a low-risk GIST. The patient was not given adjuvant chemotherapy with imatinib and is still disease-free 30 mo after surgery. The authors conclude that although rectal GIST is extremely uncommon, it should be included in differential diagnosis when a tumour in the rectum is detected. Biopsy of the tumour is essential, since this makes it possible to reach a sure preoperative diagnosis based on the immunohistological features of the CDl17 and CD34. Although complete surgical resection with negative tumour margins is the principal curative procedure for primary and nonmetastatic tumours, further studies are still needed for the determination of the most effective treatment strategy for patients with rectal GIST.展开更多
AIM: To explore the difference between cancer cells and normal cells, we investigated the Raman spectra of singlecells from gastrointestinal cancer patients. METHODS: All samples were obtained from 30 diagnosed as gas...AIM: To explore the difference between cancer cells and normal cells, we investigated the Raman spectra of singlecells from gastrointestinal cancer patients. METHODS: All samples were obtained from 30 diagnosed as gastrointestinal cancer patients. The flesh tumor specimen is located in the center of tumor tissue, while the normal ones were 5 cm away from the outside tumor section. The imprint was put under the microscope and a single cell was chosen for Raman measurement. All spectra were collected at confocal Raman micro-spectroscopy (British Renishaw) with NIR 780 nm laser.RESULTS: We measured the Raman spectra of several cells from gastrointestinal cancer patients. The result shows that there exists the strong line at 1 002/cm with less half-width assigned to the phenylalanine in several cells. The Raman lines of white cell were lower and less, while those of red cell were not only higher in intensity and more abundant, but also had a parti cular C-N breathing stretching band of pyrrole ring at 1 620-1 540/cm. The line at 1 084/cm assigned to phosphate backbone of DNA became obviously weaker in cancer cell. The Raman spectra of stomach cancer cells were similar to those of normal cells, but the Raman intensity of cancer cells was much lower than that of normal cells, and even some lines disappear. The lines of enteric cancer cells became weaker than spectra above and many lines disappeared, and the cancer cells in different position had different fluorescence intensity.CONCLUSION: The Raman spectra of several cells from cancer patients show that the structural changes of cancer cells happen and many bonds rupture so that the biological function of cells are lost. The results indicate that Raman spectra can offer the experiment basis for the cancer diagnosis and treatment.展开更多
AIM: To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor (VEGF) in the gastrointestinal stromal tumor (GIST) cells. METHODS: We used GIST cell line, GIST-T1. It has a hetero...AIM: To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor (VEGF) in the gastrointestinal stromal tumor (GIST) cells. METHODS: We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor (SCF). Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by PITT assay. RESULTS: Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by S-13571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by PTT assay. CONCLUSION: Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by ST571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.展开更多
AIM: To examine the impact of imatinib mesylate (Glivec) on patient survival and response and its safety, and the correlation of the response rate with the kit gene mutation status. METHODS: Thirty-three of 74 (4...AIM: To examine the impact of imatinib mesylate (Glivec) on patient survival and response and its safety, and the correlation of the response rate with the kit gene mutation status. METHODS: Thirty-three of 74 (44.6%) small bowel gastrointestinal stromal tumor (GIST) patients who developed recurrence after curative resection and not treated with Glivec were classified as group A patients. Twenty-two advanced small bowel GIST patients treated with Glivec were classified as group B patients. Clinicopathological features, post-recurrence and overall survival rates were compared. Each tumor in group B patients was investigated for mutations of kit or plateletderived growth factor alpha (PDGFRA). The mutation type was correlated with clinical outcomes. The antitumor effect and safety of Glivec in group B patients were also assessed. RESULTS: Advanced small bowel GIST patients treated with Glivec had substatntially longer post-recurrence survival and higher overall survival rates than those not treated with Glivec. A total of 15 patients had a partial response (PR) (67.8%). Activated mutations of c-kit were found in 16 of 19 tested patients and no PDGFRA mutant was identified. In 13 patients with GISTs harboring exon 11 kit mutations, the partial response rate (PR) was 69.3%, whereas two of three patients with tumors containing an exon 9 kit mutation had an overall response rate (ORR) of 66.7% (not significant). CONCLUSION: Glivec significantly prolongs the postrecurrence and overall survival of Asian patients with advanced GISTs. Glivec induces a sustained objective response in more than half of Asian patients withadvanced small bowel GISTs. Activated mutations of kit exon 11 are detectable in the vast majority of GISTs. There is no difference in the PR rate for patients whose GISTs have kit exon 9 and exon 11 mutations.展开更多
AIM: This study is aimed at investigating the expression and possible significances of very low-density lipoprotein receptor (VLDLR) subtypes in gastroenteric adenocarcinoma tissues and cells with various differentiat...AIM: This study is aimed at investigating the expression and possible significances of very low-density lipoprotein receptor (VLDLR) subtypes in gastroenteric adenocarcinoma tissues and cells with various differentiations. METHODS: Thirty-one cases of gastroenteric carcinoma/ adjacent normal tissues were enrolled in the study, which were diagnosed and classified by the clinicopathological diagnosis. The expression of VLDLR subtypes was detected in gastroenteric carcinoma/adjacent normal tissues and three various differentiated human gastric adenocarcinoma cell lines (MKN28, SGC7901 and MKN45) by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis.RE,SULTS: Two VLDLR subtypes, namely, type Ⅱ VLDLR and type Ⅰ VLDLR, were found to express changes in gastroenteric carcinoma tissues, their adjacent normal tissue, and gastric adenocarcinoma cell lines as well. Type Ⅱ VLDLR is predominantly expressed in poorly- or moderately-differentiated gastroenteric carcinoma tissues and gastric adenocarcinoma cell lines, whereas type ⅠVLDLR is mainly detected in well-differentiated intestinal carcinoma tissues and gastric adenocarcinoma cells compared with the adjacent normal tissues. CONCLUSION: The results suggested that the variations of the VLDLR subtype expression might be correlated with the progress and differentiation of gastroenteric carcinoma.展开更多
Intra-abdominal fibromatosis (IAF) is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age....Intra-abdominal fibromatosis (IAF) is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age. We describe a rare case of primary IAF involving the mesentery and small bowel which clinically, macroscopically and histologically mimicked malignant gastrointestinal stromal tumor (GIST). This report highlights the fact that benign IAF can be misdiagnosed as a malignant GIST localized in the mesentery or arising from the intestinal wall. Their diagnostic discrimination is essential because of their very different biological behaviors and the fact that the introduction of effective therapies involving tyrosine kinase inhibitor ST1571 (imatinib mesylate) has greatly changed the clinical approach to intra-abdominal stromal spindle cell tumors.展开更多
Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms, although their prevalence has increased substantially over the past three decades. Moreover, there has been an increased clinical recogni...Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms, although their prevalence has increased substantially over the past three decades. Moreover, there has been an increased clinical recognition and characterization of these neoplasms. They show extremely variable biological behavior and clinical course. Most NETs have endocrine function and secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome; however, many are clinically silent until late presentation with mass effects. Investigation and management should be individualized for each patient, taking into account the likely natural history of the tumor and general health of the patient. Management strategies include surgery for cure or palliation, and a variety of other cytoreductive techniques, and medical treatment including chemotherapy, and biotherapy to control symptoms due to hormone release and tumor growth, with somatostatin analogues (SSAs) and alphainterferon. New biological agents and somatostatintagged radionuclides are under investigation. Advances in the therapy and development of centers of excellence which coordinate multicenter studies, are needed to improve diagnosis, treatment and therefore survival of patients with GEP NETs.展开更多
AIM: To explore the feasibility of local interleukin 2 (IL-2) in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of ...AIM: To explore the feasibility of local interleukin 2 (IL-2) in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of application. METHODS: Sixteen patients with stages Ⅲ and Ⅳ of gastrointestinal malignancies (primary or metastatic) who were admitted to our Department of Gastroenterology were treated with Iocoregionally applied IL-2 in low doses. RESULTS: No major problems applying Iocoregional IL-2 were encountered. In 6 out of 16 patients, a modest but clinically worthwhile improvement was obtained. Adverse effects were minimal. The therapeutic scheme was well tolerated, even in patients in a poor condition. CONCLUSION: This study demonstrates the feasibility of low dose Iocoregional IL-2 application in advanced abdominal cancer. Local IL-2 therapy gives only negligible adverse effects. The results suggest that it is important to apply intratumorally. Local IL-2 may be given adjunct to standard therapeutic regimes and does not imply complex surgical interventions. These initial results are encouraging.展开更多
AIM: Gastrointestinal stromal tumors (GISTs) are rare. GISTs differ from other mesenchymal tumors of the gastrointestinal tract (e.g. leiornyomas and schwannomas). The purpose of this study was to investigate the...AIM: Gastrointestinal stromal tumors (GISTs) are rare. GISTs differ from other mesenchymal tumors of the gastrointestinal tract (e.g. leiornyomas and schwannomas). The purpose of this study was to investigate the role of Ets-1 in the growth and differentiation of GISTs. METHODS: Twenty-eight GISTs, nine leiomyomas and six schwannomas were examined by immunohistochemical staining method for Ets-1 in this study. Specimens were selected from surgical pathology archival tissues at Nagasaki University Hospital. RESULTS: Ets-1 protein was expressed in the cytoplasm of cells in all of these tumors. Immunohistochemical staining revealed that 27 GISTs (96.4%), six leiomyomas (66.7%), and five schwannomas (83.3%) were positive for Ets-1. Ets-1 expression was statistically different between GISTs and leiomyomas (P〈0.005). However, there was no correlation between Ets-1 expression and clinical risk categories. CONCLUSION: Ets-1 plays an important role in the growth and differentiation of GISTs, leiomyomas and schwannomas.展开更多
Plexiform fibromyxoma is a very rare mesenchymal tumor of the stomach, found almost exclusively in the antrum/pylorus region. The most common presenting symptoms are anemia, hematemesis, nausea and unintentional weigh...Plexiform fibromyxoma is a very rare mesenchymal tumor of the stomach, found almost exclusively in the antrum/pylorus region. The most common presenting symptoms are anemia, hematemesis, nausea and unintentional weight loss, without sex or age predilection. We describe here two cases of plexiform fibromyxoma, involving a 16-year-old female and a 34-year-old male. Both patients underwent complete resection(R0) by distal gastrectomy and retrocolic gastrojejunostomy(according to Billroth 2); for both, the postoperative course was uneventful. Histology showed multiple intramural and subserosal nodules with characteristic plexiform growth, featuring bland spindle cells situated in an abundant myxoid stroma with low mitotic activity. Immunohistochemistry showed α-smooth muscle actin-positive spindle cells, focal positivity for CD10, and negative staining for KIT, DOG1, CD34, S100, β-catenin, STAT-6 and anaplastic lymphoma kinase. One of the cases showed focal positivity for h-caldesmon and desmin. Upon followup, no sign of disease was found. In the differential diagnosis of plexiform fibromyxoma, it is important to exclude the more common gastrointestinal stromal tumors as they have greater potential for aggressivebehavior. Other lesions, like neuronal and vascular tumors, inflammatory fibroid polyps, abdominal desmoid-type fibromatosis, solitary fibrous tumors and smooth muscle tumors, must also be excluded.展开更多
Gastric submucosal tumors(SMTs) less than 2 cm are generally considered benign neoplasms, and endoscopic observation is recommended, but SMTs over 2 cm, 40% of which are gastrointestinal stromal tumors(GISTs), have ma...Gastric submucosal tumors(SMTs) less than 2 cm are generally considered benign neoplasms, and endoscopic observation is recommended, but SMTs over 2 cm, 40% of which are gastrointestinal stromal tumors(GISTs), have malignant potential. Although the Japanese Guidelines for GIST recommend partial surgical resection for GIST over 2 cm with malignant potential as well as en bloc large tissue sample to obtain appropriate and large specimens of SMTs, several reports have been published on tissue sampling of SMTs, such as with endoscopic ultrasound sound fine needle aspiration, submucosal tunneling bloc biopsy, and the combination of bite biopsy and endoscopic mucosal resection. Because a simpler, more accurate method is needed for appropriate treatment, we developed oval mucosal opening bloc biopsy after incision and widening by ring thread traction for submucosal tumor(OMOB) approach. OMOB was simple and enabled us to obtain large samples under direct procedure view as well as allowed us to restore to original mucosa.展开更多
AIM: To investigate the expression of cyclin-dependent kinase inhibitors p21 and p27 in gastric well differentiated endocrine tumors (GWDET) (ECLocell carcinoids).METHODS: The expressions of p21 and p27 were exa...AIM: To investigate the expression of cyclin-dependent kinase inhibitors p21 and p27 in gastric well differentiated endocrine tumors (GWDET) (ECLocell carcinoids).METHODS: The expressions of p21 and p27 were examined immunhistochemically in endoscopic biopsy specimens from 16 patients matching the diagnostic criteria of GWDET. Percentage of positive nuclear staining either weak or strong was noted. The association of immunoexpressions with age, gender, tumor localization, multifocality and accompanying chronic atrophic gastritis, neuroendocrine cell hyperplasia (NEH), neuroendocrine dysplasia (NED), intestinal metaplasia (IM), Ki-67 proliferation index and clinical outcome were also evaluated.RESULTS: All cases expressed p27 with a mean expression score of 43.6%, while 31.3% of the cases showed any p21 expression, p21 and p27 immunoexpressions were significantly correlated with each other (P 〈 0.01), and the p21-expressing group had higher p27 expression scores (68% vs 22%). p21 and p27 expressions were lower in women, in non-atrophic mucosa and cases whose tumors were located somewhere other than fundus without submucosal extension. On contrary, p21 and p27 expressions were higher in males and the patients with submucosal extension and atrophic gastritis. Cases presenting lower p27 scores had solitary tumors showing neither NEH-NED nor IM. Despite, cases with lower p21 expression presented multifocal tumors accompanied by NEH-NED. However, no correlation of p21 and p27 expressions was found with age and Ki-67 expression.CONCLUSION: p27 is widely expressed in GWDETs, while p21 expression is sparse and observed in two thirds of the cases. Loss of p21 and p27 expressions may be correlated with different carcinoid tumor subtypes; however,more studies are needed to assess the role of these prospective markers in gastrointestinal endocrine tumors.展开更多
Until the late 1980s, gastroenterology (GE) was considered a subspecialty of Internal Medicine. Today, GE also incorporates Hepatology. However, Digestive Oncology training is poorly defined in the Hepatogastroenterol...Until the late 1980s, gastroenterology (GE) was considered a subspecialty of Internal Medicine. Today, GE also incorporates Hepatology. However, Digestive Oncology training is poorly defined in the Hepatogastroenterology (HGE)-curriculum. Therefore, a Digestive Oncology curriculum should be developed and this document might be a starting point for such a curriculum. HGE-specialists are increasingly resisting the paradigm in which they play only a diagnostic and technical role in the management of digestive tumors. We suggest minimum endpoints in the standard HGE-curriculum for oncology, and recommend a focus year in the Netherlands for Digestive Oncology in the HGE-curriculum. To produce welltrained digestive oncologists, an advanced Digestive Oncology training program with specific qualifications in Digestive Oncology (2 years) has been developed. The schedule in Belgium includes a period of at least 6 mo to be spent in a medical oncology department. The goal ofthese programs remains the production of well-trained digestive oncologists. HGE specialists are part of the multidisciplinary oncological teams, and some have been administering chemotherapy in their countries for years. In this article, we provide a road map for the organization of a proper training in Digestive Oncology. We hope that the World Gastroenterology Organisation and other (inter)national societies will support the necessary certifications for this specific training in the HGE-curriculum.展开更多
基金This study was supported by the Key Clinical Project of the Chinese Ministry of Health (No. 20012130)
文摘Objective: To study the expression of cyclooxygenase-2 (COX-2) protein in different subtypes of intestinal metaplasia (IM) and gastric carcinoma, evaluate the possibility of COX-2 forecasting the risk of malignant potential of IM, and the relationship between COX-2 expression and gastric carcinogenesis. Methods: Forty cases of chronic atrophic gastritis (CAG) with IM, 40 cases of gastric carcinoma and corresponding paracancerous tissues were selected to construct a tissue microarray. High iron diamine/alcian blue (HID/AB) staining and Hematoxylin and Eosin (HE) staining was used to classify IM and gastric carcinoma, and the expression of COX-2 protein detected in different subtypes of IM and gastric cancer by using immunohistochemistry. Results: The positive expression rate of COX-2 was 45.65%, 59.38% and 77.27% in IM foci in CAG, IM foci in paracancerous tissues, and intestinal-type gastric carcinoma, respectively, significantly higher than in diffuse-type gastric cancer (16.67%)(P<0.05, 0.005 and 0.005, respectively), and the expression intensity of COX-2 protein showed a increased tendency gradually in the sequence of IM foci in CAG→IM foci in paracancerous tissues→intestinal-type gastric carcinoma (P<0.005). The positive expression rate of COX-2 protein in type Ⅲ IM was significantly higher than in type Ⅰ and type Ⅱ IM (P<0.005 and 0.05, respectively), and the expression intensity also showed a increased tendency gradually from type Ⅰ to type Ⅲ IM (P<0.005). Conclusion: The expression level of COX-2 was increased gradually along with the increase of the risk of malignancy of IM, and its expression level may be a useful index to forecast the risk of malignant potential of IM. COX-2 expression was associated with intestinal-type gastric carcinoma, but it might also have some role in the carcinogenesis of diffuse-type gastric carcinoma.
文摘AIM: To identify the gastrointestinal stromal tumors(GISTs) that are negative for CD117 expression by immunohistochemistry and to characterize their malignant potential.METHODS: A total of 108 primary mesenchymal tumors of the gastrointestinal tract were screened to select CD117-negative tumors, from which KIT(exons 9, 11, 13, and 17)and PDGFRA (exons 10, 12, 14, and 18) were sequenced to identify GISTs. Tumor recurrence and distant metastasis were used as the criteria of malignancy.RESULTS: The result showed that approximately 25%(29/108) of the gastrointestinal mesenchymal tumors were negative for CD117 and approximately 6% (7/108)of the tumors were CD117-negative GISTs. All these CD117-negative tumors had a mutated KITand a wildtype PDGFRA. All CD117-negative GISTs with mutations at codons 557/558 of KIThad mitotic counts >10/50 high power field, and 75% (3/4) of them showed multiple recurrence or distant metastasis.CONCLUSION: CD1 17-negative KITmutated GISTs account for approximately 6% of the gastrointestinal mesenchymal tumors. Tumor recurrence or distant metastasis correlates to both theKITmutations at codons 557/558 and the mitotic counts, but not to the tumor size.
文摘AIM: To investigate the effects of 7.5% hypertonic saline on positive fluid balance and negative fluid balance, after radical surgery for gastrointestinal carcinoma. METHODS: Fifty-two patients with gastrointestinal carcinoma undergoing radical surgery were studied. The patients were assigned to receive either Ringer lactate solution following 4 mL/kg of 7.5% hypertonic saline (the experimental group, n = 26) or Ringer lactate solution (the control group, n = 26) during the early postoperative period in SICU. Fluid infusion volumes, urine outputs, fluid balance, body weight change, PaO2/FiO2 ratio, anal exhaust time as well as the incidence of complication and mortality were compared between the two groups. RESULTS: Urine outputs on the operative day and the first postoperative day in experimental group were significantly more than in control group (P<0.000001, P=0.000114). Fluid infusion volumes on the operative day and the first postoperative day were significantly less in experimental group than in control group (P= 0.000042, P= 0.000415). The volumes of the positive fluid balance on the operative day and during the first 48 h after surgery, in experimental group, were significantly less than in control group (P<0.000001). Body weight gain post-surgery was significantly lower in experimental group than in control group (P<0.000001). The body weight fall in experimental group occurred earlier than in control group (P<0.000001). PaO2/FiO2 ratio after surgery was higher in experimental group than in control group (P= 0.000111). The postoperative anal exhaust time in experimental group was earlier than in control group (P= 0.000006). The overall incidence of complications and the incidence of pulmonary infection were lower in experimental group than in control group (P= 0.0175, P= 0.0374). CONCLUSION: 7.5% hypertonic saline has an intense diuretic effect and causes mobilization of the retained fluid, which could reduce fluid infusion volumes and positive fluid balance after radical surgery for gastrointestinal carcinoma, as well as, accelerate the early appearance of negative fluid balance after the surgery, improve the oxygen diffusing capacity of the patients' alveoli, and lower the overall incidence of complications and pulmonary infection after the surgery.
文摘AIM: This study shares Asian clinical experiences of carcinoid tumors that originated in the upper gastrointestinal tract.METHODS: From May 1987 to June 2002, we had found only 13 cases of histologically confirmed carcinoid tumors in the upper gastrointestinal tract by endoscopic examinations. There were eight males and five females.The mean age was 53.16±20.51 years that ranged from 26 to 82 years. Each of their clinical presentations,locations, tumor morphology, and size and the treatment outcome were analyzed and discussed.RESULTS: One patient had a polypoid lesion at the lower esophagus, nine were stomach lesions and three located at the duodenum. All patients with polypoid and submucosal tumor types were of small size (<1.7 cm) and all patients survived after simple excision or polypectomy.Four of the five patients in tumor mass forms died and the tumors were more than 2.0 cm in size.CONCLUSION: Carcinoid tumors rarely originated from the upper gastrointestinal tract and are usually found accidentally after endoscopic study. Bigger size (more than 2 cm) tumor masses may indicate a more severe disease and poor prognosis.
文摘AIM: To examine the prevalence and prognostic significance of C-kit gene mutation and analysis the correlation of C-kit gene mutation and the clinicalpathologic parameters of GISTs. METHODS: Eighty-two GISTs were studied for the mutation of C-kit gene by PCR-SSCP, DNA sequence. Statistical comparison were used to analysis the correlation of C-kit gene mutation and clinicalpathology, clinical behavior, recurrence. RESULTS: (1) Mutation-positive and mutation-negative GISTs were 34 and 48,respectively; (2) Among the sepatients with C-kit mutation remained a significantly poor prognosis associated with 59% 3-year survival compared to those whose tumors did not; (3) Tumor size, PCNA index, mitotic cell number, presence of necrosis, microscopic invasion to adjacent tissues, recurrence and distant metastasis among mutation-positive and mutation-negative GISTs were significantly different. CONCLUSION: C-kit mutation is a undoubtedly pivotal event in GIST and may be associated with poor prognosis. Evaluation of C-kit gene mutation may have both prognosis and therapeutic significances.
文摘Gastrointestinal stromal tumour (GIST) is a rare tumour of the gastrointestinal tract which does not generally originate in the rectum. The authors describe a case of a 70-year-old man who underwent an anterior resection of the rectum for a low-risk GIST. The patient was not given adjuvant chemotherapy with imatinib and is still disease-free 30 mo after surgery. The authors conclude that although rectal GIST is extremely uncommon, it should be included in differential diagnosis when a tumour in the rectum is detected. Biopsy of the tumour is essential, since this makes it possible to reach a sure preoperative diagnosis based on the immunohistological features of the CDl17 and CD34. Although complete surgical resection with negative tumour margins is the principal curative procedure for primary and nonmetastatic tumours, further studies are still needed for the determination of the most effective treatment strategy for patients with rectal GIST.
基金Supported by the National Natural Science Foundation of China,No. 60471049the Natural Science Foundation of Shandong Province of China, No. Y2004G09
文摘AIM: To explore the difference between cancer cells and normal cells, we investigated the Raman spectra of singlecells from gastrointestinal cancer patients. METHODS: All samples were obtained from 30 diagnosed as gastrointestinal cancer patients. The flesh tumor specimen is located in the center of tumor tissue, while the normal ones were 5 cm away from the outside tumor section. The imprint was put under the microscope and a single cell was chosen for Raman measurement. All spectra were collected at confocal Raman micro-spectroscopy (British Renishaw) with NIR 780 nm laser.RESULTS: We measured the Raman spectra of several cells from gastrointestinal cancer patients. The result shows that there exists the strong line at 1 002/cm with less half-width assigned to the phenylalanine in several cells. The Raman lines of white cell were lower and less, while those of red cell were not only higher in intensity and more abundant, but also had a parti cular C-N breathing stretching band of pyrrole ring at 1 620-1 540/cm. The line at 1 084/cm assigned to phosphate backbone of DNA became obviously weaker in cancer cell. The Raman spectra of stomach cancer cells were similar to those of normal cells, but the Raman intensity of cancer cells was much lower than that of normal cells, and even some lines disappear. The lines of enteric cancer cells became weaker than spectra above and many lines disappeared, and the cancer cells in different position had different fluorescence intensity.CONCLUSION: The Raman spectra of several cells from cancer patients show that the structural changes of cancer cells happen and many bonds rupture so that the biological function of cells are lost. The results indicate that Raman spectra can offer the experiment basis for the cancer diagnosis and treatment.
文摘AIM: To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor (VEGF) in the gastrointestinal stromal tumor (GIST) cells. METHODS: We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor (SCF). Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by PITT assay. RESULTS: Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by S-13571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by PTT assay. CONCLUSION: Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by ST571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.
文摘AIM: To examine the impact of imatinib mesylate (Glivec) on patient survival and response and its safety, and the correlation of the response rate with the kit gene mutation status. METHODS: Thirty-three of 74 (44.6%) small bowel gastrointestinal stromal tumor (GIST) patients who developed recurrence after curative resection and not treated with Glivec were classified as group A patients. Twenty-two advanced small bowel GIST patients treated with Glivec were classified as group B patients. Clinicopathological features, post-recurrence and overall survival rates were compared. Each tumor in group B patients was investigated for mutations of kit or plateletderived growth factor alpha (PDGFRA). The mutation type was correlated with clinical outcomes. The antitumor effect and safety of Glivec in group B patients were also assessed. RESULTS: Advanced small bowel GIST patients treated with Glivec had substatntially longer post-recurrence survival and higher overall survival rates than those not treated with Glivec. A total of 15 patients had a partial response (PR) (67.8%). Activated mutations of c-kit were found in 16 of 19 tested patients and no PDGFRA mutant was identified. In 13 patients with GISTs harboring exon 11 kit mutations, the partial response rate (PR) was 69.3%, whereas two of three patients with tumors containing an exon 9 kit mutation had an overall response rate (ORR) of 66.7% (not significant). CONCLUSION: Glivec significantly prolongs the postrecurrence and overall survival of Asian patients with advanced GISTs. Glivec induces a sustained objective response in more than half of Asian patients withadvanced small bowel GISTs. Activated mutations of kit exon 11 are detectable in the vast majority of GISTs. There is no difference in the PR rate for patients whose GISTs have kit exon 9 and exon 11 mutations.
基金Supported by the National Natural Science Foundation of China, No. 30470872
文摘AIM: This study is aimed at investigating the expression and possible significances of very low-density lipoprotein receptor (VLDLR) subtypes in gastroenteric adenocarcinoma tissues and cells with various differentiations. METHODS: Thirty-one cases of gastroenteric carcinoma/ adjacent normal tissues were enrolled in the study, which were diagnosed and classified by the clinicopathological diagnosis. The expression of VLDLR subtypes was detected in gastroenteric carcinoma/adjacent normal tissues and three various differentiated human gastric adenocarcinoma cell lines (MKN28, SGC7901 and MKN45) by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis.RE,SULTS: Two VLDLR subtypes, namely, type Ⅱ VLDLR and type Ⅰ VLDLR, were found to express changes in gastroenteric carcinoma tissues, their adjacent normal tissue, and gastric adenocarcinoma cell lines as well. Type Ⅱ VLDLR is predominantly expressed in poorly- or moderately-differentiated gastroenteric carcinoma tissues and gastric adenocarcinoma cell lines, whereas type ⅠVLDLR is mainly detected in well-differentiated intestinal carcinoma tissues and gastric adenocarcinoma cells compared with the adjacent normal tissues. CONCLUSION: The results suggested that the variations of the VLDLR subtype expression might be correlated with the progress and differentiation of gastroenteric carcinoma.
文摘Intra-abdominal fibromatosis (IAF) is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age. We describe a rare case of primary IAF involving the mesentery and small bowel which clinically, macroscopically and histologically mimicked malignant gastrointestinal stromal tumor (GIST). This report highlights the fact that benign IAF can be misdiagnosed as a malignant GIST localized in the mesentery or arising from the intestinal wall. Their diagnostic discrimination is essential because of their very different biological behaviors and the fact that the introduction of effective therapies involving tyrosine kinase inhibitor ST1571 (imatinib mesylate) has greatly changed the clinical approach to intra-abdominal stromal spindle cell tumors.
文摘Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms, although their prevalence has increased substantially over the past three decades. Moreover, there has been an increased clinical recognition and characterization of these neoplasms. They show extremely variable biological behavior and clinical course. Most NETs have endocrine function and secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome; however, many are clinically silent until late presentation with mass effects. Investigation and management should be individualized for each patient, taking into account the likely natural history of the tumor and general health of the patient. Management strategies include surgery for cure or palliation, and a variety of other cytoreductive techniques, and medical treatment including chemotherapy, and biotherapy to control symptoms due to hormone release and tumor growth, with somatostatin analogues (SSAs) and alphainterferon. New biological agents and somatostatintagged radionuclides are under investigation. Advances in the therapy and development of centers of excellence which coordinate multicenter studies, are needed to improve diagnosis, treatment and therefore survival of patients with GEP NETs.
文摘AIM: To explore the feasibility of local interleukin 2 (IL-2) in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of application. METHODS: Sixteen patients with stages Ⅲ and Ⅳ of gastrointestinal malignancies (primary or metastatic) who were admitted to our Department of Gastroenterology were treated with Iocoregionally applied IL-2 in low doses. RESULTS: No major problems applying Iocoregional IL-2 were encountered. In 6 out of 16 patients, a modest but clinically worthwhile improvement was obtained. Adverse effects were minimal. The therapeutic scheme was well tolerated, even in patients in a poor condition. CONCLUSION: This study demonstrates the feasibility of low dose Iocoregional IL-2 application in advanced abdominal cancer. Local IL-2 therapy gives only negligible adverse effects. The results suggest that it is important to apply intratumorally. Local IL-2 may be given adjunct to standard therapeutic regimes and does not imply complex surgical interventions. These initial results are encouraging.
文摘AIM: Gastrointestinal stromal tumors (GISTs) are rare. GISTs differ from other mesenchymal tumors of the gastrointestinal tract (e.g. leiornyomas and schwannomas). The purpose of this study was to investigate the role of Ets-1 in the growth and differentiation of GISTs. METHODS: Twenty-eight GISTs, nine leiomyomas and six schwannomas were examined by immunohistochemical staining method for Ets-1 in this study. Specimens were selected from surgical pathology archival tissues at Nagasaki University Hospital. RESULTS: Ets-1 protein was expressed in the cytoplasm of cells in all of these tumors. Immunohistochemical staining revealed that 27 GISTs (96.4%), six leiomyomas (66.7%), and five schwannomas (83.3%) were positive for Ets-1. Ets-1 expression was statistically different between GISTs and leiomyomas (P〈0.005). However, there was no correlation between Ets-1 expression and clinical risk categories. CONCLUSION: Ets-1 plays an important role in the growth and differentiation of GISTs, leiomyomas and schwannomas.
文摘Plexiform fibromyxoma is a very rare mesenchymal tumor of the stomach, found almost exclusively in the antrum/pylorus region. The most common presenting symptoms are anemia, hematemesis, nausea and unintentional weight loss, without sex or age predilection. We describe here two cases of plexiform fibromyxoma, involving a 16-year-old female and a 34-year-old male. Both patients underwent complete resection(R0) by distal gastrectomy and retrocolic gastrojejunostomy(according to Billroth 2); for both, the postoperative course was uneventful. Histology showed multiple intramural and subserosal nodules with characteristic plexiform growth, featuring bland spindle cells situated in an abundant myxoid stroma with low mitotic activity. Immunohistochemistry showed α-smooth muscle actin-positive spindle cells, focal positivity for CD10, and negative staining for KIT, DOG1, CD34, S100, β-catenin, STAT-6 and anaplastic lymphoma kinase. One of the cases showed focal positivity for h-caldesmon and desmin. Upon followup, no sign of disease was found. In the differential diagnosis of plexiform fibromyxoma, it is important to exclude the more common gastrointestinal stromal tumors as they have greater potential for aggressivebehavior. Other lesions, like neuronal and vascular tumors, inflammatory fibroid polyps, abdominal desmoid-type fibromatosis, solitary fibrous tumors and smooth muscle tumors, must also be excluded.
文摘Gastric submucosal tumors(SMTs) less than 2 cm are generally considered benign neoplasms, and endoscopic observation is recommended, but SMTs over 2 cm, 40% of which are gastrointestinal stromal tumors(GISTs), have malignant potential. Although the Japanese Guidelines for GIST recommend partial surgical resection for GIST over 2 cm with malignant potential as well as en bloc large tissue sample to obtain appropriate and large specimens of SMTs, several reports have been published on tissue sampling of SMTs, such as with endoscopic ultrasound sound fine needle aspiration, submucosal tunneling bloc biopsy, and the combination of bite biopsy and endoscopic mucosal resection. Because a simpler, more accurate method is needed for appropriate treatment, we developed oval mucosal opening bloc biopsy after incision and widening by ring thread traction for submucosal tumor(OMOB) approach. OMOB was simple and enabled us to obtain large samples under direct procedure view as well as allowed us to restore to original mucosa.
文摘AIM: To investigate the expression of cyclin-dependent kinase inhibitors p21 and p27 in gastric well differentiated endocrine tumors (GWDET) (ECLocell carcinoids).METHODS: The expressions of p21 and p27 were examined immunhistochemically in endoscopic biopsy specimens from 16 patients matching the diagnostic criteria of GWDET. Percentage of positive nuclear staining either weak or strong was noted. The association of immunoexpressions with age, gender, tumor localization, multifocality and accompanying chronic atrophic gastritis, neuroendocrine cell hyperplasia (NEH), neuroendocrine dysplasia (NED), intestinal metaplasia (IM), Ki-67 proliferation index and clinical outcome were also evaluated.RESULTS: All cases expressed p27 with a mean expression score of 43.6%, while 31.3% of the cases showed any p21 expression, p21 and p27 immunoexpressions were significantly correlated with each other (P 〈 0.01), and the p21-expressing group had higher p27 expression scores (68% vs 22%). p21 and p27 expressions were lower in women, in non-atrophic mucosa and cases whose tumors were located somewhere other than fundus without submucosal extension. On contrary, p21 and p27 expressions were higher in males and the patients with submucosal extension and atrophic gastritis. Cases presenting lower p27 scores had solitary tumors showing neither NEH-NED nor IM. Despite, cases with lower p21 expression presented multifocal tumors accompanied by NEH-NED. However, no correlation of p21 and p27 expressions was found with age and Ki-67 expression.CONCLUSION: p27 is widely expressed in GWDETs, while p21 expression is sparse and observed in two thirds of the cases. Loss of p21 and p27 expressions may be correlated with different carcinoid tumor subtypes; however,more studies are needed to assess the role of these prospective markers in gastrointestinal endocrine tumors.
文摘Until the late 1980s, gastroenterology (GE) was considered a subspecialty of Internal Medicine. Today, GE also incorporates Hepatology. However, Digestive Oncology training is poorly defined in the Hepatogastroenterology (HGE)-curriculum. Therefore, a Digestive Oncology curriculum should be developed and this document might be a starting point for such a curriculum. HGE-specialists are increasingly resisting the paradigm in which they play only a diagnostic and technical role in the management of digestive tumors. We suggest minimum endpoints in the standard HGE-curriculum for oncology, and recommend a focus year in the Netherlands for Digestive Oncology in the HGE-curriculum. To produce welltrained digestive oncologists, an advanced Digestive Oncology training program with specific qualifications in Digestive Oncology (2 years) has been developed. The schedule in Belgium includes a period of at least 6 mo to be spent in a medical oncology department. The goal ofthese programs remains the production of well-trained digestive oncologists. HGE specialists are part of the multidisciplinary oncological teams, and some have been administering chemotherapy in their countries for years. In this article, we provide a road map for the organization of a proper training in Digestive Oncology. We hope that the World Gastroenterology Organisation and other (inter)national societies will support the necessary certifications for this specific training in the HGE-curriculum.