Malignant Gastrointestinal Tumor Research Articles

Localized intra-abdominal fibromatosis of the small bowel mimicking a gastrointestinal stromal tumor: a case report.

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 STI571 (imatinib mesylate) has greatly changed the clinical approach to intra-abdominal stromal spindle cell tumors.

TASK-3 immunoreactivity shows differential distribution in the human gastrointestinal tract

The presence and distribution of TASK-3 immunopositivity (a channel with potential oncogenic significance) was investigated in the human gastrointestinal system. The immunohistochemical reactions were performed with two commercially available polyclonal antibodies, targeting different epitopes of the channel protein. Experiments conducted on frozen and formalin-fixed samples indicated that the application of a suitable antigen retrieval (AR) technique was essential to produce consistent, strong and reproducible TASK-3-specific immunolabelling of the formalin-fixed tissue. The lack of or inappropriate selection of the AR resulted in false-negative reactions. As for the distribution of the TASK-3 channels, strong immunolabelling was observed in the gastric and large intestinal mucosa, with particularly prominent immunoreactivity of the epithelial cells. In contrast, the smooth-muscle layers demonstrated weak TASK-3 positivity. Intense TASK-3 expression was noted in both the exocrine and endocrine pancreas, but the islets of Langerhans exhibited more powerful reactions. The ductal apparatus of the submandibular gland and lymphocytes situated in pericolonic lymph nodes were also TASK-3 positive. Strong TASK-3 positivity could also be observed in malignant gastrointestinal tumours, with intense nuclear-perinuclear labelling of some of the tumour cells. The present findings suggest that TASK-3 channels may have roles in the gastrointestinal functions, including insular hormone secretion.

Phase I–II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas

ONYX-015 is a provisionally replication competent adenovirus with oncolytic activity in cells with malfunctioning p53. Sarcomas represent a rational target for this approach given the high frequency of p53 mutations (40-75%) and MDM-2 amplification (10-30%). We, therefore, undertook a phase I/II study of ONYX-015, days 1-5 every month administered intratumorally under radiographic guidance, in combination with MAP (mitomycin-C, doxorubicin, cisplatin) chemotherapy in patients with advanced sarcoma. Six patients were treated. Injected lesions included liver metastases in four patients and chest wall metastases in two patients. Sarcoma histologies were gastrointestinal stromal tumors (GIST, two patients), leiomyosarcoma (two patients), liposarcoma (one patient), and malignant peripheral nerve sheath tumor (1 patient). Dose escalation was performed from 10(9) plaque forming units (PFU)/dose (total dose of 5 x 10(9) PFU/cycle) to 10(10) PFU/dose (total dose of 5 x 10(10) PFU/cycle) without dose-limiting toxicity being encountered. Immunohistochemistry of the metastatic lesions prior to treatment showed that five out of six patients were positive for p53, while two patients also had mdm-2 overexpression. Adenoviral replication was detected in two out of six patient biopsies on day 5 of the first cycle, by in situ hybridization (ISH). Both patients were treated at the highest dose level. ONYX-015 viral DNA was detected by quantitative PCR in the plasma of 5/6 patients on day 5 of the first cycle, and up to day 12 (7 days after the last viral dose) in one patient who had extended sampling for viral kinetics performed, suggesting viral replication in sarcoma tissue. One patient with p53 mutation and MDM-2 amplification achieved a partial response to treatment that lasted 11 months. In conclusion, intratumoral administration of ONYX-015 in combination with MAP chemotherapy is well tolerated with no significant toxicity due to ONYX-015 being encountered. Detection of viral DNA in post treatment tumor specimens by ISH and detection of the ONYX-015 genome in the peripheral blood by quantitative PCR, up to 7 days after the last viral dose provide evidence for adenoviral replication. There was evidence of antitumor activity in one out of six patients. Further investigation of this approach in patients with recurrent sarcomas is warranted.

Effect of Fuzheng Yiliu decoction combined with chemotherapy on patients with intermediate and late stage gastrointestinal cancer

To investigate the therapeutic effects of Fuzheng Yiliu (strengthening the body resistance to inhibit tumor) decoction combined with chemotherapy on the patients with intermediate and late stage gastrointestinal cancer. Sixty patients were randomly divided into treatment group (chemotherapy combined with Fuzheng Yiliu decoction) and control group (chemotherapy alone). Four indexes, including the tumor recent remission rate (RR), the change of main symptoms, the toxic and side effects caused by chemotherapy and the change of performance status, were observed in the patients. Peripheral blood contents of CD3+, CD4+, CD8+ cells, CD4+/CD8+ and soluble interleukin-2 receptor (sIL-2R) were tested before and after treatment and the values were compared with those of healthy peoples. The improving rate of main symptoms (69.6%) and performance status (56.7%) were significantly higher in the treatment group than in the control group (34.8%, 26.7%, P<0.05). The occurrence rates of grade II toxic and side-effects on both bone marrow (13.3%) and digestive tract (30%) were lower in the treatment group compared to the control group (36.7%, 63.3%, P<0.05). Before treatment, the proportion of CD3+, CD4+ and CD4+/CD8+ decreased and the proportion of CD8+ and sIL-2R raised markedly both in the control group and treatment group as compared to the healthy people. After treatment, that increased of CD3+, CD4+, CD4+/CD8+ increased (62.25+/-10.01% vs 68.31+/-9.72%, 36.83+/-10.44% vs 42.6+/-9.62%, 1.24+/-0.65 vs 1.66+/-0.85, P<0.05) and the values of CD8+ and sIL-2R decreased obviously (33.06+/-7.69% vs 29.24+/-6.25%, 588.23+/-216.86 U/mL vs 475.87+/-211.36 U/mL, P<0.05) in the treatment group, whereas these values were opposite in the control group (64.22+/-6.91% vs 60.63+/-5.75%, 35.62+/-7.49% vs 31.53+/-5.53%, 32.95+/-8.28% vs 37.14+/-7.48%, 1.17+/-0.43 vs 0.94+/-0.43, 573.63+/-214.32 U/mL vs 692.17+/-221.33 U/mL, P<0.05). Fuzheng Yiliu decoction can enhance therapeutic effects of chemotherapy on malignant gastrointestinal tumor, and also reduce the toxic and side effects on bone marrow and digestive tract, thereby improving the quality of life and cellular immunity in patients with malignant gastrointestinal tumor.

Collagen type IV, laminin, α-smooth muscle actin (αSMA), α1 and α6 integrins expression in the liver with metastases from malignant gastrointestinal tumours

Basement membrane proteins and integrins can profoundly affect the biological behaviour of metastasic tumour cells. Using light and ultrastructural immunohistochemistry, we showed the presence of alterations in the occurrence of collagen type IV and laminin, and the expression of alpha1 and alpha6 integrin chains in the livers of patients with metastases from gastric, colorectal and pancreatic cancers. The myofibroblast-like cells in the metastatic stroma were studied. Parallel expressions of alpha-SMA, collagen type IV and alpha1 integrin chain, and appearance of laminin and alpha6 integrin chain immunoreactivity in the extratumoral liver tissue were markedly increased in sinusoids associated with metastases. Furthermore, ultrastructural immunohistochemistry detected tumour cells adhered to amorphous laminin deposits in the metastases. Laminin occurrence in liver sinusoids was visible as fine amorphous deposits in the space of Disse. The similarity between alpha-SMA-positive stromal cells in metastatic stroma and hepatic stellate cells (HSCs) was established by the presence of lipid droplets in their cytoplasm. The immune deposits of alpha1 and alpha6 integrin chains were observed on the hepatocyte microvilli and on the membrane of sinusoidal endothelial cells. These findings suggest that metastatic cells produce stimuli that induce HSCs activation and sinusoidal changes. In addition, the enhanced parallel expression of alphaSMA, collagen type IV, laminin and of alpha1 and alpha6 integrin chains in sinusoids associated with metastases, might potentiate the further dissemination of tumour cells in new liver areas.

Adult retrograde triple Jejuno-Jejunal Intussusception mimicking gastric outlet obstruction: Case Report

Jejuno – jejunal intussusception is rare, both in children and in adults. Equally rare is triple intussusceptions. Work done by Gross showed that ileo – ileal intussusception accounted for five percent of 702 cases, ileo –colic for 77%, ileo –colic for 12% multiple intussusception for one percent of cases, retrograde intussusception for 0.2%, and Other types of intussusception for 2.8% of the cases studied. Malignant tumour of the small bowel is relatively infrequent, comprising about two percent of gastrointestinal malignant neoplasms. Adenocarcinoma is however the most frequent. Method and Results: A case is here presented of triple retrograde Jejuno – jejunal intussusception associated with adenocarcinoma of the jejunum, and mimicking gastric outlet obstruction. Key Words: Jejuno – jejunal, intussusception, triple, adenocarcinoma. Tropical Journal of Medical Research Vol.8(1) 2004: 5-9

X-chromosome loss of heterozygosity frequently occurs in gastrinomas and is correlated with aggressive tumor growth.

Recent studies have shown that tumor growth, rather than hormone overproduction, is the leading cause of death among patients with gastrinomas and other malignant gastrointestinal endocrine tumors. No patient/laboratory characteristics accurately predict which tumors will exhibit aggressive growth. Furthermore, little is known regarding the molecular pathogenesis of these tumors. X-chromosome loss of heterozygosity (LOH) occurs in some nonendocrine tumors, and its presence can be associated with aggressive growth/decreased survival. Data on X-chromosome LOH in gastrointestinal endocrine tumors are conflicting. Therefore, the purpose of the current study was to determine whether X-chromosome LOH occurred in gastrinomas and, if so, whether it was correlated with tumor growth, tumor behavior, and/or prognosis. X chromosome allelotyping was performed using 12 microsatellite markers spaced throughout the chromosome using DNA from leukocytes and microdissected gastrinoma specimens from 16 female patients. The presence of X-chromosome LOH was analyzed for correlations with clinical and laboratory tumor characteristics as well as tumor growth characteristics. Nine gastrinoma specimens (56%) had X-chromosome LOH, ranging from 6% to 23% at the 12 different loci studied. X-chromosome LOH was significantly associated with aggressive postoperative tumor growth, increased primary tumor size, and pancreatic primaries. In 6 tumor specimens, LOH occurred on Xp22.1-22.3 over a 28.4-centimorgan region. X-chromosome LOH was common in gastrinoma specimens from female patients, and its presence was found to be a potentially useful molecular/genetic prognostic factor for aggressive growth.

Minimal invasive, endogastrale, endoskopisch assistierte Resektion eines gastrointestinalen Stromatumors des ösophagogastralen Übergangs: Erster Erfahrungsbericht

Minimal Invasive, Endogastric, Endoscopically Assisted Resection of a Esophagogastric Gastrointestinal Stroma Tumor: Initial Experience Combined laparoscopic and endoscopic resection techniques have been applied for benign and early malignant gastrointestinal tumors. Endogastric surgery is a variant of these techniques which combines endocavitary laparoscopic resection with flexible endoscopic guidance. By placing trocars directly into the stomach, a number of procedures seem to be possible such as endogastric resections in anatomic regions not suitable for so-called combined endoscopic laparoscopic transgastric resections. In order to illustrate this technique, the excision of a gastrointestinal stroma tumor located near the esophagogastric junction by percutaneous endogastric resection is reported and discussed. Although the indications for such procedures are limited, the endogastric access is a promising technique that reflects the continuous evolution of open cavitary to totally noninvasive intracavitary surgery.

Genomic imbalances in Korean hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most prevalent gastrointestinal malignant tumors in Southeast Asia. Thirty-one cirrhotic HCC, 14 noncirrhotic HCC, and 13 metastastic HCC in the Korean population were investigated on microdissected tissues for chromosomal aberrations by degenerate oligonucleotide–primed polymerase chain reaction (PCR) comparative genomic hybridization. A number of prominent sites of genomic imbalances were observed. The gains of 1q, 6p, 7, 8q, 12q, 13q31∼q32, 16p, 17q, and 20q and the losses of 1p, 4q, 6q, 8p, 9p, and 13q regions were observed with a similar high frequency in all types. Various chromosomal aberrations were observed preferentially to specific types. Gains of 4p15∼pter, 10q24∼qter, 18p11∼pter, and 19p10∼pter and a loss of 11q14∼q22 were observed in the cirrhotic HCC, whereas losses of 14q21∼q23 and 10q22∼q23 were observed in noncirrhotic HCC. In metastatic HCC, gains of 3q25∼qter and Xp21∼pter and losses of 21q11∼qter and Y were observed. The recurrent gains and losses of chromosomal regions identified in this study are consistent with several previous observations and provide possible candidate regions for the involvement of tumorigenesis and progressions of HCC.

Relationship between expression of CD105 and growth factors in malignant tumors of gastrointestinal tract and its significance.

Angiogenesis is an important step in the growth of solid malignant tumors. A number of angiogenic factors have been found such as transforming growth factor beta1 (TGF-beta1) and vascular endothelial growth factor (VEGF). However, the roles of TGF-beta1 and VEGF in gastrointestinal carcinogenesis are still unclear. This study was to investigate the expressions of TGF-beta1 and VEGF in gastrointestinal tract malignant tumors, as well as their association with microvessel density (MVD). At the same time, we also observed the localization of TGF-beta1 and its receptor CD105 in gastric malignant tumors. The expressions of TGF-beta1 and CD105 were detected in 55 fresh specimens of gastric carcinoma and VEGF and CD105 in 44 fresh specimens of colorectal carcinoma by immunohistochemical staining (S-ABC). TGF-beta1 and CD105 in 55 gastric carcinoma tissues on the same slide were detected by using double-stain Immunohistochemistry (DS-ABC). Among the 55 cases of gastric carcinoma tissues, 30 were positive for TGF-beta1 (54.55%). The MVD of TGF-beta1 strong positive group (++ approximately +++ 23.22 +/- 5.8) was significantly higher than that of weak positive group (+17.56 +/- 7.2) and negative group (- 17.46 +/- 3.9) (q=4.5, q=5.3207, respectively, P<0.01). In the areas of high expression of TGF-beta1, MVD and the expression of CD105 were also high. Among the 44 cases of colonic carcinoma tissues, 26 were positive for VEGF (59.1%). The expressions of both VEGF and CD105 (MVD) were related with the depth of invasion (F=5.438, P<0.05; F=4.168, P=0.05), lymph node metastasis (F=10.311, P<0.01; F=20.282, P<0.01) and Dukes stage (F=6.196, P<0.01; F=10.274, P<0.01), but not with histological grade (F=0.487, P>0.05). There was a significant correlation between the expression of VEGF and CD105 (MVD) (r=0.720, P<0.01). Over-expression of TGF-beta1 and VEGF acts as stimulating factors of angiogenesis in gastrointestinal tumors. CD105, as a receptor of TGF-beta1, can regulate the biological effect of TGF-beta1 in tumor angiogenesis. MVD marked by CD105 is more suitable for detecting newborn blood vessels.

P53 null mutations detected by a p53 yeast functional assay predict a poor outcome in young esophageal carcinoma patients

Esophageal carcinoma is one of the most common gastrointestinal malignant neoplasms in the world. Recent advances in treatment modalities as well as surgical resection techniques have improved the changes of survival of patients with esophageal carcinoma, although the prognosis is worse than for the other gastrointestinal carcinomas. A more precise stratification beyond clinicopathological classification may help determine optimal treatment. The importance of p53 gene mutations in the pathogenesis of human esophageal carcinoma is well established, but it is still controversial whether the presence of p53 mutations adversely affects individual patient prognosis. In this study, we investigated the p53 mutations of esophageal carcinomas and their correlation with clinicopathologic factors. We employed a p53 yeast functional assay because it is highly sensitive and can detect mutations based on the actual function of the p53 gene, clarifying more precisely the role of this gene in esophageal carcinomas. We also studied young patients (< or =65 years old), because our previous study raised the possibility of differences in the importances in esophageal carcinogenesis in young and old patients. Of 43 young esophageal carcinoma patients (42 squamous cell and 1 undifferentiated carcinoma), 38 (88.4%) harbored p53 mutations. Twenty-seven missense and 11 null mutations were detected, but the presence of p53 mutations did not correlate with any clinicopathologic factor. However, the null mutation was a significant indicator of a poor outcome (P=0.0278). All except one patient who harbored null mutation died within 3 years after a macroscopically curative resection. These data suggest that the type of p53 gene mutation may be predictive of outcome in young esophageal carcinoma patients. Furthermore, null mutations causing loss of function of the gene product may play a more important role than missense mutations in tumor progression.

Actualités sur les tumeurs stromales gastro-intestinales : à partir de sept observations de tumeurs malignes

Purpose. – Gastrointestinal stromal tumors (GIST) are rare neoplasms, 1–3% of malignant gastrointestinal tumors. They are immature proliferations of spindled and/or epithelioid cells, developed in the muscular layer of the digestive tract, showing uncompleted or partial muscular, nervous or mixed differentiation. Immunohistologic knowledge about these tumors has recently progressed because of the discovery of specific markers (coexpression vimentin-CD117, oncogenes): GIST can now be distinguished from the other mesenchymal tumors. Methods. – Retrospective study of seven patients with GIST who received the same treatment. Results. – For our seven patients the mean age was 49 years with a male predominance (sex-ratio 4/3). The tumoral localisations are principally the small bowel (four cases), the rectum (two cases) and the stomach (one case). The treatment consisted of a first surgery, adapted to the tumoral localisation and extension, associated to chemotherapy in case of metastasis or local recurrence. The study of the histological grading for the seven patients showed tumors with poor prognoses. Six patients developed recurrence in a 2-year period; for the survey we are too close for a proper view. Conclusions. – A review of the literature on stromal tumors finds older patients (59 years) with an equal sex ratio. Against the results of our series, the most frequent location is the stomach (50%). But the main problem is the better understanding of the particular evolution of these tumors. The bad short-date prognosis imposes carrying out larger studies, in order to confirm the principal hypothesis of histogenesis and to improve the survey by an optimal treatment.

Specific staining of human chorionic gonadotropin beta in benign and malignant gastrointestinal tissues with monoclonal antibodies.

Human chorionic gonadotropin (hCG) beta in serum is a promising tumour marker for gastrointestinal malignancies. Our aim was to investigate the expression of hCGbeta by immunohistochemistry in various gastrointestinal cancers and benign tissues. A monoclonal antibody (MAb) specific for free hCGbeta was used to stain 107 tissue samples from various gastrointestinal malignancies and 36 benign or normal tissue samples. The specificity of the staining was verified and the results compared with those obtained with a widely used commercial polyclonal antibody (PAb) which reacts with both free hCGbeta and intact hCG, as well as with luteinizing hormone beta. With the MAb, we observed positive immunohistochemical staining in 24% of the malignant gastrointestinal tumours. Gastric (60%) and pancreatic (56%) carcinomas, as well as extrahepatic cholangiocarcinomas (36%), were positive most frequently. We also discovered immunoreactivity in half of the non-malignant samples from pancreatic and biliary tissues. With the PAb, hCG immunoreactivity was evident more frequently in some cancers, but the staining was diffuse and occasionally polymorphonuclear leucocytes were strongly stained. This study shows that our MAbs specific for hCGbeta are well suited for immunohistochemistry. Our results confirm previous findings on gastrointestinal cancers and, furthermore, we demonstrate hCGbeta tissue expression in pancreatic adenocarcinoma. The results support reports on hCGbeta as a serum tumour marker for digestive tract diseases.

Increased energy turnover of esophageal squamous cell carcinoma

Background: Tumor tissue differs from healthy tissue in that its cell kinetics have changed and because of dislocations in the relationship of individual metabolic pathways to each other. The objective of the analyses presented was the microcalorimetric measurement of the resulting differences in energy turnover, exemplified by esophageal tumors. Methods: For this purpose, the thermal output of eight biopsy samples from squamous cell carcinomas and four biopsies from Barrett carcinomas was compared with that of 11 samples from normal esophageal mucous membranes at a temperature of 37°C. Results: While the thermal output found for the squamous cell carcinoma was significantly enhanced by a factor of 2–3 in contrast to the healthy esophageal mucous membranes, the values found for the adenocarcinoma remained unchanged. Conclusions: Taking the literature into consideration, the different behavioral patterns of the two carcinoma types can best be explained in terms of a higher degree of glycolysis in the esophageal adenocarcinoma than in the squamous cell carcinomas. Clinical conclusions may be drawn with respect to an appropriate, stage-oriented therapy for the treatment of malignant gastrointestinal tumors.

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) of liver lesions

Background: Endoscopic ultrasonography (EUS) is not traditionally thought to be clinically applicable in liver imaging. EUS-guided fine-needle aspiration of the liver has not been well described. Methods: A prospective study was conducted in which 574 consecutive patients with a history or suspicion of gastrointestinal or pulmonary malignant tumor undergoing upper EUS examinations underwent EUS evaluation of the liver. Fourteen (2.4%) patients were found to have focal liver lesions and underwent EUS-guided fine-needle aspiration. Results: The median largest diameter of the liver lesions was 1.1 cm (range 0.8 to 5.2 cm). The mean number of passes was 2.0 (range 1 to 5 passes). All fine-needle passes yielded an adequate specimen. One of the 14 patients underwent EUS-guided fine-needle aspiration of 2 liver lesions. Fourteen of the 15 liver lesions sampled by means of EUS-guided fine-needle aspiration were malignant and one was benign. Before EUS, computed tomography (CT) depicted liver lesions in only 3 of 14 (21%) patients. Seven of 14 patients had a known cancer diagnosis. For the other 7, the initial diagnosis of cancer was made by means of EUS-guided fine-needle aspiration of the liver. There were no immediate or late complications. Conclusions: EUS can detect small focal liver lesions that are not detected at CT. Findings of EUS-guided fine-needle aspiration can confirm a cytologic diagnosis of liver metastasis and establish a definitive M stage that may change clinical management. (Gastrointest Endosc 1999;50:357-61.)

Spiral CT for the Measurement of Hepatic Metastatic Mass from Gastrointestinal Malignant Tumor: Relative Value of Arterial, Portal and Delayed Phase Scanning

Purpose : To evaluate the relative value of arterial, portal and delayed phase images in the measurement of he-patic metastatic mass arising from gastrointestinal malignant tumor using spiral CT. Materials and Methods : Thirty-three with 45 metastatic tumors of the liver underwent tri-phasic spiral CT. For this purpose one or two lesions were chosen in each patient whose primary tumor was shown to be stomach cancer(n=15), colon cancer(n=16), or ileal cancer(n=1). Tumor size ranged from 1 to 12.2 (mean, 4.3)cm. Arterial, portal and delayed phase images were obtained at 30 -35 seconds, 70 -75 seconds, and 3 minutes, respectively, after the injection of contrast materials. Using a work station, two radiologists independently measured the longest diameter of the selected lesions, and a second measurement was taken three days later. Contrast, as well as intra-and interbserver differences among the three phases, was statistically analysed. Results : Intra- and interobserver difference were, espectively, 2.3 and 3.8 mm during the portal phase; 3.3 and 4.6 mm during the arterial phase; and 2.9 and 4.5 mm during the delayed phase. ANOVA with Tukey’s multiple comparison showed that none of these differences were statistically significant. Contrast between mass and liver parenchyma was especially clear during the portal phase (p=0.0001, using the Kruskal-Wallis test). Conclusion : Intra- and interobserver differences in the measurement of hepatic metastatic tumors were statis-tically insignificant during all three phases. The least difference and best contrast were seen during the portal phase.

Gastrointestinal malignancies in patients with celiac sprue

BACKGROUND: Celiac sprue is a malabsorption disease, which carries an increased risk of gastrointestinal malignancy, often underestimated. The purpose of this study was to examine the management of patients with gastrointestinal neoplasms complicating celiac disease. PATIENTS AND METHODS: The pathology database at our institution was searched from 1986 to present; and the literature from 1966 to 1997 was reviewed to identify reports of celiac sprue complicated by malignancy. A total of 82 cases were available for analysis. RESULTS: Two thirds of patients had carried the diagnosis of celiac sprue for a mean of approximately 10 years. The remaining one third were diagnosed with celiac disease and gastrointestinal malignancy simultaneously. Jejunal T-cell lymphoma was the most common malignancy. There was also an increased frequency of small intestinal adenocarcinoma and squamous cell carcinoma of the esophagus. Prognosis was generally poor, related to the histologic type and stage of the disease. CONCLUSIONS: Gastrointestinal malignant neoplasms, especially small bowel lymphomas, can occur in patients with celiac sprue. Patients with known celiac disease who present with exacerbation of symptoms should be promptly investigated for occult gastrointestinal malignancies, and considered for early surgical exploration.

Peptidergic nerve fibres in the human liver

The autonomic nervous system plays a significant role in liver physiology and pathology. The aim of the present study was to investigate peptidergic nerve fibres in the liver of patients with malignant gastrointestinal tumors that are not metastasizing in this organ. Using light and electron microscopic immunohistochemistry, somatostatin (SOM)-, neuropeptide Y (NPY)-, substance P (SP)- and calcitonin gene-related peptide (CGRP)-immunoreactive (IR) nerve fibres (NF) were detected in the portal tract and perisinusoidally. Histologically, the liver showed dilated sinusoids, filled with lymphoid cells, and scarcely marked perisinusoidal fibrosis. Neuropeptide-IR NF were found in close contact with hepatic sinusoids. Numerous IR varicosities were detected in the sinusoidal wall. We discuss the origin and role of these NF in the liver. Probable quantitative changes in peptidergic NF ensue the inflammatory reaction in sinusoids in malignant gastrointestinal tumors. This could also reflect the increased exposure of the liver to toxic substances in the portal blood flow.

SYNCHRONOUSLY OCCURRED ESOPHAGEAL CANCER AND MULTIPLE GASTRIC CANCERS -A CASE REPORT-

A 63-year-old man was seen at the department of internal medicine in our hospital because of dysphagia. Endoscopic examination of the upper gastrointestinal tract revealed an esophageal cancer of the lower intrathoracic esophagus, but further exploration with endoscopy was impossible because a stricture at the site of cancer was too narrow to pass through the endoscopy. Upper gastrointestinal series performed on another day revealed two elevated lesions in the stomach. The patient was referred to the department for operation. Intra-thoracic esophagectomy, total gastrectomy, and reconstruction with the small intestine were performed. Pathologically the resected specimens were diagnosed as squamous cell carcinoma of the esophagus, and moderately differentiated tubular adenocarcinoma and poorly differentiated adenocarcinoma of the stomach. Esophageal cancers with gastric cancer have been reported to represent 0.3-2.5% of all esophageal cancers, but synchronous double cancer of esophagus and stomach is rare. For the exploration of gastrointestinal malignant tumor, careful attitude entertaining probable double cancer is of importance. And appropriate selection of operative procedure that can provide a cure with minimal surgical stress may be critical to treat such synchronous double cancer of the esophagus and stomach.

Carcinoma-associated collagen type III and type IV immune localization and Ito cell transformation indicate tumor-related changes in sinusoids of the human liver

The deterioration of extracellular matrix turnover is a key event in tumor progression. It has been assumed that Ito cell transformation is stimulated by tumor-derived factors. In the present study changes in the occurrence of collagen type III and IV and Ito cell transformation are described in the sinusoids of patients with malignant gastrointestinal tumors without liver metastases, and around metastatic liver tumors using routine histology, electron microscopy as well as light microscopical and ultrastructural immunohistochemistry. Dilated sinusoids filled with lymphoid cells and variable perisinusoidal fibrosis were detected light microscopically. Collagen type III and IV immune deposits were increased perisinusoidally. Ultrastructural immunohistochemistry showed increased staining in the space of Disse and around Ito and transitional cells for both types of collagen. Ito cells were transformed into transitional cells. Pit cells appeared in the inflammatory infiltrate in sinusoids. Ito cells were significantly increased in number pericentrally and periportally. It is suggested that stimuli, which can influence Ito cellular behaviour are produced by inflammatory cells in sinusoids, resident sinusoidal cells, tumor cells or by tumor stroma. It is concluded that transformed Ito cells and increased amounts of collagen type III and IV in sinusoids of patients with malignant tumors without liver metastases or around metastatic tumors may predict tumor-related alterations of liver parenchyma, which may serve as a barrier for further outgrowths of the cancer cells.