Critical considerations for the management of gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms and pure neuroendocrine carcinomas

Mixed neuroendocrine non-neuroendocrine neoplasms constitute rare tumors that are located mainly in the gastrointestinal(GI)tract and have high degrees of malignancy,and the frequency of these tumors has been increasing.They consist of a neuroendocrine neoplastic component with another component of adenocarcinoma usually and have a dismal prognosis.The rare GI pure neuroendocrine carcinoma is highly aggressive and requires complex and extensive management since a genetic distinction exists between it and GI non-neuroendocrine neoplasms,which are generally slow-growing lesions.The most common GI-mixed neuroendocrine non-neuroendocrine neoplasms are colorectal,followed by gastric,mainly in the gastroesophageal junction.Current imaging modalities of nuclear medicine and radiology play important roles in the accuracy of diagnosis.Liquid biopsy may contribute to early detection and timely diagnosis.Ultrasonography,either endoscopic or abdominal,is a technique that contributes to a diagnosis;additionally,contrast-enhanced ultrasonography is very helpful in followup appointments.Histopathology establishes a definite diagnosis and stage by evaluating the cell differentiation grade and the cell proliferation index Ki67.The genetic profile can be valuable in diagnosis and gene therapy.Surgical resection with wide lymphadenectomy,whenever possible,and adjuvant chemotherapy constitute the main therapeutic management strategies.Targeted therapy and immunotherapy achieve encouraging results.

Trends and hotspots in gastrointestinal neoplasms risk assessment: A bibliometric analysis from 1984 to 2022

BACKGROUND Gastrointestinal neoplasm(GN)significantly impact the global cancer burden and mortality,necessitating early detection and treatment.Understanding the evolution and current state of research in this field is vital.AIM To conducts a comprehensive bibliometric analysis of publications from 1984 to 2022 to elucidate the trends and hotspots in the GN risk assessment research,focusing on key contributors,institutions,and thematic evolution.METHODS This study conducted a bibliometric analysis of data from the Web of Science Core Collection database using the"bibliometrix"R package,VOSviewer,and CiteSpace.The analysis focused on the distribution of publications,contributions by institutions and countries,and trends in keywords.The methods included data synthesis,network analysis,and visualization of international collaboration networks.RESULTS This analysis of 1371 articles on GN risk assessment revealed a notable evolution in terms of research focus and collaboration.It highlights the United States'critical role in advancing this field,with significant contributions from institutions such as Brigham and Women's Hospital and the National Cancer Institute.The last five years,substantial advancements have been made,representing nearly 45%of the examined literature.Publication rates have dramatically increased,from 20 articles in 2002 to 112 in 2022,reflecting intensified research efforts.This study underscores a growing trend toward interdisciplinary and international collaboration,with the Journal of Clinical Oncology standing out as a key publication outlet.This shift toward more comprehensive and collaborative research methods marks a significant step in addressing GN risks.CONCLUSION This study underscores advancements in GN risk assessment through genetic analyses and machine learning and reveals significant geographical disparities in research emphasis.This calls for enhanced global collaboration and integration of artificial intelligence to improve cancer prevention and treatment accuracy,ultimately enhancing worldwide patient care.

Perspective on the practical indications of endoscopic submucosal dissection of gastrointestinal neoplasms

Endoscopic submucosal dissection (ESD) is a new endoluminal therapeutic technique involving the use of cutting devices to permit a larger resection of the tissue over the muscularis propria. The major advantages of the technique in comparison with polypectomy and endoscopic mucosal resection are controllable resection size and shape and en bloc resection of a large lesion or a lesion with ulcerative findings. This technique is applied for the endoscopic treatment of epithelial neoplasms in the gastrointestinal tract from the pharynx to the rectum. Furthermore, some carcinoids and submucosal tumors in the gastrointestinal tract are treated by ESD. To determine the indication, two aspects should be considered. The first is a little likelihood of lymph node metastasis and the second is the technical resectability. In this review, practical guidelines of ESD for the gastrointestinal neoplasms are discussed based on the evidence found in the literature.

Ultraslim endoscopy with flexible spectral imaging color enhancement for upper gastrointestinal neoplasms

AIM:To conduct a preliminary study on the effect of flexible spectral imaging color enhancement (FICE) used in combination with ultraslim endoscopy by focusing on the enhanced contrast between tumor and non-tumor lesions. METHODS: We examined 50 lesions of 40 patients with epithelial tumors of the upper gastrointestinal tract before endoscopic submucosal dissection using ultraslim endoscopy with conventional natural color imag ing and with FICE imaging. We retrospectively invest igated the effect of the use of FICE on endoscopic diagn osis in comparison with normal light. RESULTS: Visibility of the epithelial tumors of the upper gastrointestinal tract with FICE was superior to normal light in 54% of the observations and comparable to normal light in 46% of the observations. There was no lesion for which visibility with FICE was inferior to that with normal light. FICE visualized 69.6% of hyperemic lesions and 58.8% of discolored lesions better than conventional endoscopy with natural color imaging. FICE sign if icantly improved the visibility of lesions with hyp ere mia or discoloration compared with normocolored lesions. CONCLUSION: This study suggests that the use of FICE would improve the ability of ultraslim endoscopy to detect epithelial tumors of the upper gastrointestinal tract.

Mixed neuroendocrine–nonneuroendocrine neoplasms of the gastrointestinal system:An update

Mixed neuroendocrine-nonneuroendocrine neoplasms(Mi NENs)of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment.Over the years,the diagnostic criteria,classification,and clinical behavior of these tumors have been the subjects of ongoing debate,and the various changes in their nomenclature have strengthened the challenges associated with Mi NENs.This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as Mi NEN,highlight the current diagnostic criteria,summarize the latest data on pathogenesis and provide information on available treatments.Moreover,this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system(GIS).Currently,the Mi NEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma,depending on the organ of origin.Diagnosis is based on the presence of both morphological components in more than 30%of the tumor.However,this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of Mi NEN by biopsy.Furthermore,available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of Mi NEN is not supportive and warrants further investigation.The diagnosis of these tumors is not solely based on immunohistochemical findings.They are not hybrid tumors and both components can act independently;thus,careful grading of each component separately is required.In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection,the aggressive potential of both components has paramount importance in the choice of treatment.Regardless of the organ of origin within the GIS,almost Mi NENs are tumors with poor prognosis and are frequently encountered in the elderly and men.They are most frequently reported in the colorectum,where data from molecular studies indicate a monoclonal origin;however,further studies are required to provide additional support for this origin.

Gastrointestinal bleeding as initial presentation of extramedullary plasma cell neoplasms: A case report and review of the literature

BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and treatment.CASE SUMMARY Our aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the literature with the view to consolidate and discuss information about diagnosis and management of this rare entity. In addition to our case, a literature search(Pub Med database) of case reports of extramedullary plasma cell neoplasms manifesting as upper gastrointestinal bleeding was performed. Twenty-seven cases of extramedullary plasmacytoma(EMP) involving the stomach and small bowel presenting with upper gastrointestinal bleeding were retrieved. The majority of patients were males(67%). The average age on diagnosis was 62.7 years. The most common site of presentation was the stomach(41%), followed by the duodenum(15%). The most common presenting complaint was melena(44%). In the majority of cases, the EMPs were a secondary manifestation(63%) at the background of multiple myeloma(26%), plasmablastic myeloma(7%) or high-grade plasma cell myeloma(4%). Oesophagogastroscopy was the main diagnostic modality and chemotherapy the preferred treatment option for secondary EMPs.CONCLUSION Despite their rare presentation, upper gastrointestinal EMPs should be considered in the differential diagnosis of patients with gastrointestinal bleeding especially in the presence of systemic haematological malignancy.

A new breakthrough:ESD using a newly developed grasping type scissor forceps for early gastrointestinal tract neoplasms

Endoscopic submucosal dissection(ESD) has allowed the achievement of histologically curative en bloc resection of gastrointestinal neoplasms regardless of size,permitting the resection of previously non-resectable tumors.The ESD technique for treatment of early gastric cancer has spread rapidly in Japan and a few other Asian countries due to its excellent eradication rate compared to endoscopic mucosal resection.Although numerous electrosurgical knives have been developed for ESD,technical difficulties and high complication rates(bleeding and perforation) have limited their use worldwide.We developed the grasping type scissor forceps(GSF) to resolve such ESD-related problems.Our animal and preliminary clinical studies showed that ESD using GSF is a safe(no intraoperative complication) and technically efficient(curative en bloc resection rate 92%) method for dissection of early gastrointestinal tumors.The use of GSF is a promising option for performing ESD on early stage GI tract tumors both safely and effectively.

Conventional radiological strategy of common gastrointestinal neoplasms

This article summarizes the clinical characteristics and imaging features of common gastrointestinal(GI) neoplasms in terms of conventional radiological imaging methods. Barium studies are readily available for displaying primary malignancies and are minimallyor not at all invasive. A neoplasm may be manifested as various imaging findings, including mucosal disruption, soft mass, ulcer, submucosal invasion and lumen stenosis on barium studies. Benign tumors typically appear as smoothly marginated intramural masses. Malignant neoplasms most often appear as irregular infiltrative lesions on barium examination. Tumor extension to adjacent GI segments may be indistinct on barium images. Cross-sectional images such as computed tomography and magnetic resonance imaging may provide more accurate details of the adjacent organ invasion, omental or peritoneal spread.

Endoscopic submucosal dissection for the treatment of neoplastic lesions in the gastrointestinal tract

AIM: To investigate the indications, resection rate, and safety of endoscopic submucosal dissection (ESD) for neoplastic lesions in the gastrointestinal tract at a European referral center. METHODS: We carried out a retrospective analysis of the ESD procedures performed in our center for mucosal neoplastic and submucosal lesions of the gastrointestinal tract. The duration of the procedure, en bloc and complete (R0) resection rates, and complication rates were evaluated. Variables were reported as mean ± SD or simple proportions. Univariate analysis and comparisons of procedure times and resection rates were performed using Mann-Whitney U tests, or χ2 tests for dichotomous variables.RESULTS: Between 2007 and 2011, ESD was performed in a total of 103 patients (46.7% male, mean age 64.0 ± 12.7 years). The indications for the procedure were epithelial tumor (n = 54), submucosal tumor (n = 42), or other (n = 7). The total en bloc resection rate was 90.3% (93/103) and R0 resection rate 80.6% (83/103). The median speed of the procedure was 15.0 min/cm2 . The complete resection rate was lower for submucosal tumors arising from the muscle layer (68%, 15/22, P < 0.05). Resection speed was quicker for submucosal tumors localized in the submucosal layer than for lesions arising from the muscularis propria layer (8.1 min/cm 2 vs 17.9 min/cm 2 , P < 0.05). The R0 resection rate and speed were better in the last 24 mo (90.1%, 49/54 and 15.3 min/cm 2 ) compared to the first 3 years of treatment (73.5%, 36/49, P < 0.05 and 22.0 min/cm2 , P < 0.05). Complications occurred in 14.6% (n = 15) of patients, including perforation in 5.8% (n = 6), pneumoperitoneum in 3.9% (n = 4), delayed bleeding in 1.9% (n = 2), and other in 2.9% (n = 3). Only one patient with delayed perforation required surgical treatment. During the mean follow-up of 26 ± 15.3 mo, among patients with R0 resection, recurrence occurred in one patient (1.2%).CONCLUSION: ESD is an effective and safe method for resection of neoplastic lesions with low recurrence. Speed and the R0 resection rate increased after 50 procedures.

Surgery for gastrointestinal malignant melanoma:Experience from surgical training center

AIM:To characterize clinical features,surgery,outcome,and survival of malignant melanoma(MM) of the gastrointestinal(GI) tract in a surgical training center in Bangkok,Thailand. METHODS:A retrospective review was performed for all patients with MM of the GI tract treated at our institution between 1997 and 2007. RESULTS:Fourteen patients had GI involvement either in a metastatic form or as a primary melanoma. Thirteen patients with sufficient data were reviewed. The median age of the patients was 66 years(range:32-87 years) .Ten patients were female and three were male.Seven patients had primary melanomas of the anal canal,stomach and the sigmoid colon(5,1 and 1 cases,respectively) .Seven patients underwent curative resections:three abdominoperineal resections,two wide local excisions,one total gastrectomy andone sigmoidectomy.Six patients had distant metastatic lesions at the time of diagnosis,which made curative resection an inappropriate choice.Patients who underwent curative resection exhibited a longer mean survival time(29.7 mo,range:10-96 mo) than did patients in the palliative group(4.8 mo,P=0.0006) . CONCLUSION:GI MM had an unfavorable prognosis,except in patients who underwent curative resection(53.8%of cases) ,who had a mean survival of 29.7 mo.

Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract. METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively. RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n=0, stomach: n=10, colorectal: n=47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients. WBRT was applied with daily fractions of 2 Gray (Gy) or 3Gy to a total dose of 50Gy or 30Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6mo vs 8.0mo for patients with primary tumors of the colon/rectum vs other primary tumors, respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n=916) was 3.4mo and 3.2mo for patients with gastrointestinal neoplasms. Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n=57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70 was 5.5mo vs 2.1mo for patients with KPS <70 (P<0.01, log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival. CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the number of brain metastases have a profound influence on treatment outcome.

Surgical intervention for malignant bowel obstruction caused by gastrointestinal malignancies

BACKGROUND Malignant bowel obstruction(MBO)is a common event for end-stage gastrointestinal cancer patients.Previous studies had demonstrated manifestations and clinical management of MBO with mixed malignancies.There still lack reports of the surgical treatment of MBO.AIM To analyze the short-term outcomes and prognosis of palliative surgery for MBO caused by gastrointestinal cancer.METHODS A retrospective chart review of 61 patients received palliative surgery between January 2016 to October 2018 was performed,of which 31 patients underwent massive debulking surgery(MDS)and 30 underwent ostomy/by-pass surgery(OBS).The 60-d symptom palliation rate,30-d morbidity and mortality,and overall survival rates were compared between the two groups.RESULTS The overall symptom palliation rate was 75.4%(46/61);patients in the MDS group had significantly higher symptom palliation rate than OBS group(90%vs 61.2%,P=0.016).Patients with colorectal cancer who were in the MDS group showed significantly higher symptom improvement rates compared to the OBS group(overall,76.4%;MDS,61.5%;OBS,92%;P=0.019).However,patients with gastric cancer did not show a significant difference in symptom palliation rate between the MDS and OBS groups(OBS,60%;MDS,80%;P=1.0).The median survival time in the MDS group was significantly longer than in the OBS group(10.9 mo vs 5.3 mo,P=0.05).CONCLUSION For patients with MBO caused by peritoneal metastatic colorectal cancer,MDS can improve symptom palliation rates and prolong survival,without increasing mortality and morbidity rates.

Endoscopic ultrasound-guided fine-needle aspiration for suspected malignancies adjacent to the gastrointestinal tract

AIM: To investigate the impact of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in association with a multidisciplinary team evaluation for the detection of gastrointestinal malignancies.

Gastrointestinal autonomic nerve tumors:A surgical point of view

AIM: Gastrointestinal autonomic nerve tumors are uncommon stromal tumors of the intestinal tract. Their histological appearance is similar to that of other gastrointestinal stromal tumors. We report two cases and performed an analysis of the literature by comparing our findings with the available case reports in the medical literature.METHODS: Two patients were admitted with abdominal tumor masses. One occurred in the stomach with large multiple liver metastases and the second originated in Meckel's diverticulum. The latter site has never been reported previously. Both patients underwent surgery. In one patient gastrectomy, right liver resection and colon transversum resection were performed to achieve aggressive tumor debulking. In the other patient the tumor bearing diverticulum was removed.RESULTS: Postoperative recovery of both patients was uneventful. Histological examination, immunohistochemical analysis and electron microscopy revealed the diagnosis of a gastrointestinal autonomic nerve tumor. The patient with the tumor in Meckel's diverticulum died 6 mo after surgery because of pneumonia. The patient with liver metastases have been alive 13 years after initial tumor diagnosis and 7 years after surgery with no evidence of tumor progression. In light of our results, we performed athorough comparison with available literature reports.CONCLUSION: Radical surgical resection of gastrointestinal autonomic nerve tumors seems to be the only available curative approach to date, and long term survival is possibleeven in large metastasized tumors.

Opinion: How to manage subepithelial lesions of the upper gastrointestinal tract?

Subepithelial lesions(SELs) in the upper gastrointestinal(GI) tract are relatively frequent findings in patients undergoing an upper GI endoscopy. These tumors, which are located below the epithelium and out of reach of conventional biopsy forceps, may pose a diagnostic challenge for the gastroenterologist, especially when SELs are indeterminate after endoscopy and endoscopic ultrasound(EUS). The decision to proceed with further investigation should take into consideration the size, location in the GI tract, and EUS features of SELs. Gastrointestinal stromal tumor(GIST) is an example of an SEL that has a well-recognized malignant potential. Unfortunately, EUS is not able to absolutely differentiate GISTs from other benign hypoechoic lesions from the fourth layer, such as leiomyomas. Therefore, EUS-guided fine needle aspiration(EUS-FNA) is an important tool for correct diagnosis of SELs. However, small lesions(size < 2 cm) have a poor diagnostic yield with EUS-FNA. Moreover, studies with EUS-core biopsy needles did not report higher rates of histologic and diagnostic yields when compared with EUS-FNA. The limited diagnostic yield of EUS-FNA and EUS-core biopsies of SELs has led to the development of more invasive endoscopic techniques for tissue acquisition. There are initial studies showing good results for tissue biopsy or resection of SELs with endoscopic submucosal dissection, suck-ligate-unroof-biopsy, and submucosal tunneling endoscopic resection.

Role of minimally invasive techniques in gastrointestinal surgery:Current status and future perspectives

In recent years,the incidence of gastrointestinal cancer has remained high.Currently,surgical resection is still the most effective method for treating gastrointestinal cancer.Traditionally,radical surgery depends on open surgery.However,traditional open surgery inflicts great trauma and is associated with a slow recovery.Minimally invasive surgery,which aims to reduce postoperative complications and accelerate postoperative recovery,has been rapidly developed in the last two decades;it is increasingly used in the field of gastrointestinal surgery and widely used in early-stage gastrointestinal cancer.Nevertheless,many operations for gastrointestinal cancer treatment are still performed by open surgery.One reason for this may be the challenges of minimally invasive technology,especially when operating in narrow spaces,such as within the pelvis or near the upper edge of the pancreas.Moreover,some of the current literature has questioned oncologic outcomes after minimally invasive surgery for gastrointestinal cancer.Overall,the current evidence suggests that minimally invasive techniques are safe and feasible in gastrointestinal cancer surgery,but most of the studies published in this field are retrospective studies and casematched studies.Large-scale randomized prospective studies are needed to further support the application of minimally invasive surgery.In this review,we summarize several common minimally invasive methods used to treat gastrointestinal cancer and discuss the advances in the minimally invasive treatment of gastrointestinal cancer in detail.

Prevalence of malignant neoplasms in celiac disease patients-a nationwide United States population-based study

BACKGROUND Celiac disease(CeD)is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals.Recent research has unveiled a heightened risk of developing specific malignant neoplasms(MN)and various malignancies,including gastrointestinal,lymphomas,skin,and others,in individuals with CeD.AIM To investigate the prevalence of MN in hospitalized CeD patients in the United States.METHODS Using data from the National Inpatient Sample spanning two decades,from January 2000 to December 2019,we identified 529842 CeD patients,of which 78128(14.75%)had MN.Propensity score matching,based on age,sex,race,and calendar year,was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio.RESULTS Positive associations were observed for several malignancies,including small intestine,lymphoma,nonmelanoma skin,liver,melanoma skin,pancreas myelodysplastic syndrome,biliary,stomach,and other neuroendocrine tumors(excluding small and large intestine malignant carcinoid),leukemia,uterus,and testis.Conversely,CeD patients exhibited a reduced risk of respiratory and secondary malignancies.Moreover,certain malignancies showed null associations with CeD,including head and neck,nervous system,esophagus,colorectal,anus,breast,malignant carcinoids,bone and connective tissues,myeloma,cervix,and ovary cancers.CONCLUSION Our study is unique in highlighting the detailed results of positive,negative,or null associations between different hematologic and solid malignancies and CeD.Furthermore,it offers insights into evolving trends in CeD hospital outcomes,shedding light on advancements in its management over the past two decades.These findings contribute valuable information to the understanding of CeD’s impact on health and healthcare utilization.

Epidemiology of upper gastrointestinal cancers in Iran:A Sub site analysis of 761 cases

AIM： To define the sub site distribution of upper gastrointestinal cancers in three provinces of Iran. METHODS： The study was carried out in three provinces in Iran： Ardabil, Golestan, and Tehran. In Arbabil and Golestan, the data was collected from the sole referral center for gastrointestinal cancers and the local cancer registry. For Tehran province, data from two major private hospitals were used. All gastric and esophageal cancer patients diagnosed during the period from September 2000 and April 2002 were included in the study.RESULTS： A total of 761 patients with upper gastrointestinal cancers were identified, 314 from Ardabil, 261 from Golestan, and 186 from Tehran. In Tehran, the relative rate of cancer increased from the upper esophagus to the distal stomach. In Golestan, the reverse pattern was observed. In Ardabil, the mid portion （distal esophagus and proximal stomach） was involved most frequently.CONCLUSION： There were considerable variations in the sub site of upper gastrointestinal cancers in the three provinces studied, We cannot provide any explanation for this variation, Further research aimed at explaining the discrepancies in sub site distribution of upper gastrointestinal cancers may help identify important risk factors.

Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

AIM: To establish a relevant animal model of human gastrointestinal cancer, which can be used for repetitive investigations, so as to improve our understanding and management of carcinogenesis and cancer metastasis. METHODS: Intact tissues of human colorectal and pancreatic cancers were transplanted in nude mice. The biological characteristics of the original and the corresponding transplanted tumors were investigated by HE staining, PAS staining and immunostaining. The metastases in the livers and lungs of nude mice were investigated by immunostaining with biotinylated mab KL-1 and by RT-PCR using CK20 specific primers. RESULTS: There were totally 9 of 16 surgical specimens growing in nude mice subcutaneously and/or orthotopically (4 of 6 colorectal and 5 of 10 pancreatic cancer). Tumor cell content of the specimens and freezing of tissue specimens are important factors influencing the growth of transplanted tumor. In the group of fresh tumor tissues with greater than 50% tumor cell content, the success rate of the transplantation was 100% (3 cases of pancreatic cancer and 3 cases of colorectal cancer). The orthotopically trans-planted tumors resemble the original tumor morphologically and biologically, including TAA expression such as CEA by immunohistochemistry, and CEA level in the serum of mice. Ki-67 labeling index and the expression of TAA especially K-ras, 17-1A and RA-96, are associated with the potential of tumor growth in nude mice. Micrometastases in the lungs and livers of tumor bearing mice can be detected by immunostaining with biotinylated mab KL-1 and CK20-specific RT-PCR. CONCLUSION: An orthotopic transplantation model for human colon and pancreatic cancer in nude mice has been set up. We have also established sensitive detection methods with CK-immunohistochemistry and CK20-RT-PCR to study xenotransplanted human cancer and its metastatic cancer cells in the liver and lung of nude mice. This study may be helpful in understanding the mechanism of cancer metastasis and in developing new diagnostic methods and therapeutic strategies for metastases including micrometastases.

Modulation of postoperative immune and inflammatory response by immune-enhancing enteral diet in gastrointestinal cancer patients

AIM: To evaluate if the administration of an enteral diet supplemented with glutamine, arginine and omega-3-fatty acids modulates inflammatory and immune responses after surgery. METHODS: A prospective randomized double-blind, clinical trial was performed. Forty-eight patients with gastrointestinal cancer were randomized into two groups, one group was given an isocaloric and isonitrogenous standard diet and the other was fed with the supplemented diet with glutamine, arginine and omega-3-fatty acids. Feedings were started within 48 hours after operation, and continued until day 8. All variables were measured before operation and on postoperative day 1 and 8. Immune responses were determined by phagocytosis ability, respiratory burst of polymorphonuclear cells, total lymphocytes lymphocyte subsets, nitric oxide, cytokines concentration, and inflammatory responses by plasma levels of C-reactive protein, prostaglandin E2 level. RESULTS: Tolerance of both formula diets was excellent.There were significant differences in the immunological and inflammatory responses between the two groups. In supplemented group, phagocytosis and respiratory burst after surgery was higher and C-reactive protein level was lower (P【0.01) than in the standard group. The supplemented group had higher levels of nitric oxide, total lymphocytes, T lymphocytes, T-helper cells, and NK cells. Postoperative levels of IL-6 and TNF-alpha were lower in the supplemented group (P 【0.05). CONCLUSION: It was clearly established in this trial that early postoperative enteral feeding is safe in patients who have undergone major operations for gastrointestinal cancer. Supplementation of enteral nutrition with glutamine, arginine, and omega-3-fatty acids positively modulated postsurgical immunosuppressive and inflammatory responses.