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Distinctive syndromes correlating skin manifestations and gastrointestinal malignancies are described. The skin lesions may precede, accompany, or follow the primary disease in the gastrointestinal tract and can be important diagnostic clues. They should alert the physician to the possibility that his patient may have an associated internal cancer.
With the development of the Millipore filter, meningeal metastases are being identified more frequently as a complication of many types of carcinoma, including breast, lung, pancreas, stomach, and prostate. Regardless of the primary source, adenocarcinoma cells appear to have a propensity to metastasize to this site. In recent years, carcinomatous meningitis has been reported very infrequently in gastrointestinal malignancies, as compared with other primary sites. We present two cases of carcinomatous meningitis, one in a 29-year-old man with adenocarcinoma of the colon and another in a 51-year-old man with gastric carcinoma. Survival after this complication is presently poor, but treatment may offer amelioration of disabling symptoms. The aggressive nature of these metastases emphasizes the need for early clinical suspicion and examination of spinal fluid in patients with gastrointestinal malignancies.
The value of 67 Ga-citrate scanning in cases of gastrointestinal malignancies is discussed. Seven cases are presented, including lymphomas of the stomach, small bowel, and rectum, and adenocarcinomas of the stomach and colon. In a review of the literature, there is general pessimism regarding the use of 67Ga scans in GI malignancies. Based on previous reports and our own experience, specific clinical situations are cited in which the scan is of considerable value for diagnosis and followup of GI malignancy.
PURPOSE: Fluoropyrimidines are among the most widely used chemotherapeutic agents for gastrointestinal malignancies, but interindividual variability in dihydropyrimidine dehydrogenase (DPD) activity, encoded by DPYD, can lead to severe or lethal toxicities. Most pharmacogenetic data on DPYD originates from European populations, limiting the applicability of current guidelines in admixed groups. METHODS: We evaluated DPYD pharmacogenetic variation and its association with fluoropyrimidine-related adverse events in Mexican patients with gastrointestinal cancers. Adverse events were prospectively assessed using CTCAE v5.0. Genotyping was performed with the Illumina Global Screening Array and analyzed using PLINK and R. RESULTS: A total of 208 patients were enrolled, and 192 samples passed genotyping quality control; 156 patients received fluoropyrimidines. Only three patients (1.5%) carried actionable DPYD variants (rs3918290, rs67376798 and rs75017182), yielding allele frequencies of 0.26%, approximately ten-fold lower than those reported in European cohorts. Genome-wide analyses did not reveal significant genotype-phenotype associations, though suggestive variants in SDK1, ZPBP, and FGF12 were observed. Pharmacodynamic analyses identified frequent variation in TYMS rs2847153 and MTHFR rs1801133, both previously associated with fluoropyrimidine toxicity. Overall, patients exhibited a predominantly Native Mexican ancestry (56.5%), which may explain the markedly low frequency of actionable DPYD alleles commonly found in European populations. CONCLUSIONS: These findings highlight the limited representation of admixed populations in pharmacogenetic research and underscore the need for population-specific data to inform safe and equitable fluoropyrimidine dosing.
Irradiation offers only a palliative treatment for malignant tumours of the gastrointestinal tract. Cancer of the rectum and rectosigmoid represents an exception; above all, preoperative irradiation improves a five year survival rate up to 15%. There is a better prognosis for non-Hodgkin's and Hodgkin's lymphomas of the entire gastrointestinal tract.
The present results of surgery in gastrointestinal carcinoma, including all stages of the disease, show a 20% 5-year-survival-rate in stomach carcinoma, 45% in colon carcinoma and 41% in rectum carcinoma. It can already be demonstrated that improved early diagnosis may improve the results of surgical treatment of stomach carcinoma. Effective local and general follow-up treatment must be demanded.
The chemotherapy of neoplasias of the gastrointestinal tract is still in an experimental phase. Until now, there are not any effective regimens which could be proposed as a standard therapy. Perhaps gastric carcinoma is an exception. The increasing knowledge concerning tumor evolution and especially concerning prognostic factors, justifies admission of patients to well controlled clinical studies.
BACKGROUND: Targeted therapies directed at specific genomic alterations have transformed the management of gastrointestinal (GI) cancers; however, acquired resistance remains inevitable. Circulating tumor DNA (ctDNA) analysis via liquid biopsy provides a non-invasive approach to characterize genomic mechanisms of resistance. We therefore evaluated patterns of acquired genomic resistance in patients with GI cancers treated with targeted therapies. METHODS: Patients with GI cancers treated with standard of care or investigational therapies targeting EGFR, HER2, FGFR, MET, KRAS, BRAF for at least 60 days who underwent both baseline comprehensive genomic profiling and post-progression ctDNA sequencing were retrospectively evaluated. RESULTS: Of 106 patients meeting inclusion criteria, 45 had biliary tract cancer (BTC), 42 colorectal cancer (CRC), and 19 other GI malignancies. At least one putative resistance-associated alteration was detected in ctDNA in 53% of cases. Resistance patterns were heterogeneous with 47% showing no detectable alterations and 33% harboring ≥2 resistance alterations. Among 164 total alterations, the majority were single nucleotide variants (82%), followed by amplifications (17%). Overall, 48% were classified as 'bypass' alterations-activating alternative oncogenic pathways, most commonly MAPK signaling-while 52% were 'on-target' alterations involving secondary changes within the drug target. RAS alterations represented a key mechanism of bypass resistance, accounting for 28% of all resistance alterations. Interestingly, in CRC, bypass alterations predominated (69%), whereas in BTCs, on-target alterations were more frequent (61%). CONCLUSIONS: Liquid biopsies frequently identify acquired resistance following targeted therapy across GI cancers, often revealing multiple concurrent alterations. Patterns of resistance varied by tumor type, with both on-target and bypass mechanisms observed. These findings highlight common themes of resistance and support the growing clinical role of ctDNA analysis in defining resistance and guiding management in GI malignancies.
In addition to lymphoma, there is an increased incidence of gastrointestinal carcinoma in patients with malabsorption due to celiac disease. This is frequently manifested by a loss of response to gluten withdrawal. Four such cases are described: one patient had lymphoma and the other three had cancer of the esophagus, jejunum, and pancreas, respectively. The literature indicates that carcinoma of the esophagus and small bowel is particularly common in patients with celiac disease. These findings suggest that celiac disease should be considered a premalignant condition and that such patients should undergo a regular radiographic survey to detect early cancer.
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A phase I evaluation of a weekly schedule of anguidine was undertaken as an alternative to the present continuous daily schedules. The dose ranged from 1.5 to 7.5 mg/m2 given as an infusion over 3 hours. No myelosuppression was noted at any dose level. The toxic effects included nausea and vomiting, hypotension, CNS symptoms (confusion, hallucinations, and psychomotor seizures), chills, fever, and diarrhea. A dose of 5 mg/m2 of anguidine produced acceptable toxicity.
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The skin and the upper gastrointestinal tract are frequent sites of malignant tumors. However, cutaneous metastasis from primary gastrointestinal tract lesions remains a relative rarity. Similarly rare is spread of primary skin cancer (nonmelanomatous) to upper gastrointestinal tract. This paper presents an unusual example of primary esophageal carcinoma with synchronous skin and bone metastases and a case of squamous cell carcinoma of the stomach, possibly due to spread from a remote squamous cell carcinoma of the skin.
Twenty-five patients with disseminated gastrointestinal malignancies were treated in a phase I study with a combination of ftorafur and mitomycin C or florafur and methyl-CCNU. Most patients had been heavily treated previously. Gastrointestinal, central nervous system, and marrow toxicity were manageable. Tumor regression was noted in five of 25 patients. A large-scale phase II study in untreated patients with gastrointestinal malignancies appears indicated with a combination of these agents.
Sixty-six patients with locally advanced or diffuse gastrointestinal cancer or suffering from major complications due to surgery or radiation therapy, were treated with continuous parenteral hyperalimentation at the Istituto Nazionale Tumori of Milan for a cumulative period of 2101 study-days. Patients were divided into 4 groups: Group 1, malnourished patients with advanced gastrointestinal malignancy; Group 2, patients with gastrointestinal fistulae due to simple surgical complications or to radiation injury of the bowel; Group 3, patients with major postoperative complications; Group 4, surgical patients with gastric or colo-rectal carcinoma treated preoperatively. Mean infusional regime for the various groups included 42-56 Cal/kg/day and 1.5 to 2.4 g amino acid/kg/day, and the duration of the treatment ranged from 7 to 144 days. The results obtained show that protein calorie depletion of cancer patients may depend on malnutrition and that it can be reversed by parenteral nutrition, in patients, that are candidates for surgical treatment or those who qualify for chemotherapy and/or radiotherapy. Parenteral nutrition has a fundamental role in patients with fistulae, even if much attention must be paid to the external care of the fistula and the wound. In addition, nutritional support by intravenous feeding has proven essential for a successful outcome of patients with major postoperative complications. Preoperative protein repletion and central venous nutrition in patients who require gastrintestinal surgery represent a modern advance in the field of cancer surgery.
For many years, the treatment of malignant gastrointestinal tumors has been disappointing. However, recent results have shown an improvement in the rate of remissions and survival, especially in the treatment of gastric, pancreatic and localized rectal carcinoma. The therapy of cancer of the colon still remains unsatisfactory: the rate of remissions could be increased, but survival remains unaltered. Adjuvant chemotherapy is under investigation in many quarters but cannot yet be recommended as an established method of treatment.