Intravenous hyperalimentation as an adjunct to cancer chemotherapy with 5-fluorouracil.
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When conventional modalities (external beam irradiation and chemotherapy +/- resection) are used in the treatment of locally advanced gastrointestinal malignancies, although useful palliation can be achieved in many patients, local control and long-term survival are infrequent. In recent trials, investigators have used fractionated external beam doses of 4500-5000 rad in 180 rad fractions in combination with irradiation boost techniques of intraoperative electrons, or intraoperative or transcatheter brachytherapy (+/- chemotherapy and resection). With colorectal and biliary cancer, both local control and long-term survival appear to be improved, compared to results achieved with conventional treatment. With pancreatic cancer, an apparent improvement has been noted with local control and median survival, but long-term survival has not been altered. For partially resected gastric cancer, the use of intraoperative irradiation has yielded five year survival rates of approximately 20%. With unresectable or residual gastric cancer, accelerated fractionation alone or in combination with chemotherapy has yielded excellent local control, but patients have died as a result of abdominal failure or lung metastases. Prevention of abdominal failures will be necessary to improve long-term survival with pancreatic and gastric cancer. Randomized trials by site are needed to determine if the observed differences seen in prospective nonrandomized trials are real or due to differences in case selection.
Trends in age-standardised mortality for all cancers and 21 cancers or groups of cancers over the period 1955-1992 were analysed for 33 countries from four continents in a population aged 65-84 years. Mortality from all neoplasms in the elderly showed heterogeneous patterns in various countries and in the two sexes. Trends were generally more favourable for females than for males, reflecting essentially the earlier and more extensive impact of the lung cancer (and other tobacco-related neoplasms) epidemic in elderly males, in addition to the earlier decline of gastric cancer and a widespread decline of cervical cancer rates in females. In several countries, particularly from western Europe, but also Japan, cancer mortality trends were more favourable over the last two decades than in earlier calendar periods. Some countries of northern and central Europe (including Finland, Germany, Austria and Switzerland) showed stable or even downward trends over time for total cancer mortality in both sexes, particularly in males. This reflects the different patterns of the tobacco-related (lung) cancer epidemic in various countries, and the impact of a few other major neoplasms, including in particular the systematic downward trends in stomach cancer. In contrast, rates were moderately upwards in males in North America, and several countries of southern and eastern Europe, where cancer mortality in the elderly was comparatively low in the 1950s, showed appreciable upward trends, mostly in males. Thus, there was a generalised tendency towards a levelling of the differences in certified cancer mortality in the elderly population in various areas of the world. Although there are substantial limits and uncertainties in the reliability and validity of cancer death certification and their trends in the elderly, there is no widespread and generalised upward trend in cancer mortality, with a major exception of lung and other tobacco-related neoplasms. Furthermore, in several countries, cancer mortality trends over the last four decades have been favourable for elderly women.
Colon cancer is one of the leading tumours in the world and is considered among the big killers, together with lung, prostate and breast cancer. In the recent years very important advances occurred in the field of treatment of this frequent disease: adjuvant chemotherapy was demonstrated to be effective, chiefly in stage III patients, and surgery was optimized in order to achieve the best results with a low morbidity. Several new target-oriented drugs are under evaluation and some of them (cetuximab and bevacizumab) have already exhibited a good activity/efficacy, mainly in combination with chemotherapy. The development of updated recommendations for the best management of these patients is crucial in order to obtain the best results, not only in clinical research but also in everyday practice. This report summarizes the most important achievements in this field and provides the readers useful suggestions for their professional practice.
Colorectal cancer invading adjacent organs is a frequent event occurring in 5.5% to 12% of all colorectal malignancies. Colon cancer directly invading the duodenum and pancreas is rare and may require combined resection of the colon, pancreas, and duodenum, which represents a complex operation with significant morbidity and mortality rates. In this article, a case of a 41-year-old patient with a right colon cancer directly infiltrating the duodenum and head of the pancreas is presented. The patient was treated by radical combined resection of the colon, duodenum, and pancreas. Pathological examination confirmed neoplastic invasion of the adjacent organs and absence of lymph node metastasis (T4N0). The patient recovered uneventfully. Patients with colorectal cancer infiltrating adjacent organs such as the duodenum and the pancreas should be treated by radical en bloc resection of the tumor. This procedure is the preferred treatment strategy because it seems to be associated with improved overall survival rates.
We describe a novel application of percutaneous renal surgery for the management of an unusual and challenging urologic problem. Two patients with symptomatic, metastatic adenocarcinoma in the renal pelvis were treated with percutaneous resection. The lesion was in a solitary kidney in 1 patient, and was bilateral in the second. Percutaneous resection resulted in complete relief of symptoms and obstruction. Although both patients ultimately died of their primary disease, their quality of life was significantly improved in the interim. Percutaneous resection of renal pelvic tumors is accepted management for select patients with upper tract transitional cell carcinoma. These 2 cases demonstrated both an unusual presentation for metastatic adenocarcinoma and an expanded application for percutaneous renal surgery.
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A common theme in most anal neoplasms appears to be a delay in diagnosis due to confusion with more common, benign conditions. Thus, the clinician must maintain a high index of suspicion when evaluating lesions of the anal canal and margin. The use of primary chemoradiation for SCC of the anal canal has resulted in equivalent, if not superior, local control and survival compared with radical surgery, and results in sphincter preservation in over two thirds of cases. Nevertheless, abdominoperineal resection still plays an important role in salvage of treatment failures, and also for patients who are unlikely to tolerate chemoradiation or have pre-existing impaired continence. Recent studies indicate that variations in chemotherapeutic agents and radiation technique might potentially produce even better results. The prognosis for anorectal melanoma, as well as for small cell and undifferentiated tumors, continues to be poor. Fortunately, these are relatively rare tumors.
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Staging laparoscopy avoids unnecessary laparotomies in patients with unresectable intra-abdominal malignancies. However, the postoperative oncologic treatment of these patients has not been documented. This study compares rates and timing of postoperative chemotherapy (ChT) and/or radiation therapy (XRT) in patients with unresectable intra-abdominal malignancies initially evaluated by staging laparoscopy (SL) or exploratory laparotomy (EL). The records of patients surgically evaluated for esophageal, gastric, hepatobiliary, and pancreatic cancers or abdominal lymphoma were retrospectively reviewed. Data gathered included type of exploration (SL or EL), resectability, whether postoperative cancer treatment was given (ChT, XRT, or both), and the time from surgery to the beginning of such treatment. This study includes only patients with unresectable malignancies. Twenty-one patients underwent SL and 58 EL. Sixteen of the SL patients (76%) and 25 of the EL patients (43%) received postoperative cancer treatment (P = 0.009). The median number of days from surgery to postoperative cancer treatment was 13 days (range 5 to 41 days) for the SL group and 35 days (range 16 to 89 days) for the EL group (P = 0.0004). We conclude that patients with unresectable intra-abdominal malignancies discovered by SL are more likely to receive postoperative ChT and/or XRT than patients surgically evaluated by EL. Further studies to determine whether this better utilization of postoperative treatment results in better outcomes in these patients are needed.
Laparoscopy identifies radiologically occult advanced disease in patients with pancreatic adenocarcinoma. The value of laparoscopy in the management of peri-ampullary tumors was determined. One hundred forty-four patients with radiologically resectable nonpancreatic adenocarcinoma, periampullary tumors were identified from a prospective database between August 1993 and December 2000. Criteria for laparoscopic unresectability included histologically proved peritoneal or hepatic metastases, distant nodal involvement, arterial involvement, and local extension outside the resection field. Median age at operation was 70 years (range 31 to 87 years) and 56% of the patients were men. An adequate laparoscopy was performed in 134 cases (93%). Laparoscopy identified 13 patients (10%) with unresectable disease. Of 121 patients with laparoscopic resectable disease, 111 (92%) went on to subsequent resection; CT correctly predicted resectability in 82%. Laparoscopy spared 36% of unresectable patients a nontherapeutic laparotomy. Patients with resectable disease were treated by pancreaticoduodenectomy (n = 91, 76%), ampullectomy (n = 12, 10%), duodenal resection (n = 10, 9%), or bile duct excision (n = 6, 5%). The addition of diagnostic laparoscopy to dynamic CT scanning in this selected patient population identifies an additional 10% of patients with unresectable disease. We believe that laparoscopy should be used in a selective manner for preoperative staging of patients suspected of having nonpancreatic periampullary tumors.
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This study involved 97 male veterans (age range, 45-65) in four approximately equal groups, classified as follows: 1) colon or rectal cancer, 2) upper digestive-tract cancers, 3) other cancers, and 4) additional controls (no cancer). Dietary histories of these cancer and noncancer inpatients were recorded to see whether or not consumption of particular substances could be predictive of cancer. The interactions of substances in combination such as sugar x fat, and alcohol x smoking, proved to be important predictors of cancer of the upper digestive tract. The degree of coffee consumption was a predictor of nondigestive-tract cancer. However, colorectal cancer patients could not be distinguished from non-cancer patients by the dietary variables examined.
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The aim of the present study was to verify whether the CMI response of the host's lymphocytes is directed towards tumor-associated antigens (TAA) specific for each histological type of tumor. The leucocyte migration inhibition (LMI) test was selected for this purpose, utilizing the cancer patients' leucocytes and, as neoplastic antigens, formalin-fixed cells of surgically removed cancer tissue. Two hundred and eighteen patients were studied, 110 of whom were affected by breast cancer, 48 by digestive tract and 60 by laryngeal cancer. The total amount of tests performed was 278. The leucocytes of 93 normal subjects were tested against the different tissues' cancer antigens, as were the leucocytes of 41 patients with cancer of different organs tested against the corresponding normal tissues' antigens. The breast cancer patients (122 tests performed) showed 82.35% positive tests against homologous antigen, 72.72% and 95.24% against heterologous (digestive tract and laryngeal cancer, respectively) antigens. The digestive tract cancer patients (69 tests performed) showed 70.27% positive tests against homologous, 66.66% and 43.48% against heterologous antigens (breast and laryngeal cancer respectively). The laryngeal cancer patients (87 tests performed) showed 74.29% positive tests against homologous, 38.10% and 80.65% against heterologous antigens (breast and digestive tract, respectively). The results led to the conclusion that the LMI test response of cancer patients was not "tissue specific": the test did not discriminate between the homologous and the heterologous cancer antigens, and it seems that the response was not directed towards specific TAA but only towards wide-range or "group" TAA, showed by several types of tumors.
BACKGROUND: Although emerging evidence suggests a role for peroxisomes in tumorigenesis, their functions in digestive cancers remain unclear. This study aims to investigate the association between peroxisomes and digestive tract tumors. METHODS: To systematically investigate peroxisomal functions in digestive cancers, we first constructed and validated tumor-specific prognostic signatures based on peroxisome-related genes (PRGs) through univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. We then characterized the tumor immune microenvironment (TIME) with CIBERSORT, X-CELL, and EPIC algorithms, and identified tumor-specific and common signalings via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Focusing on hepatocellular carcinoma (HCC), we experimentally validated peroxisome-related therapeutic responses by profiling signature genes in radioresistant cells and an orthotopic transarterial chemoembolization (TACE) rat model. PEX13 knockdown further assessed peroxisomal role in radiosensitivity and targeted therapy response. Clinical relevance of PEX13 was evaluated in HCC cohort. Single-cell RNA sequencing dataset and lipidomics further revealed peroxisomal mechanisms in HCC progression. Finally, peroxisomal function in colorectal cancer (CRC) was validated in vitro. RESULTS: Novel peroxisome-related prognostic signatures demonstrated strong predictive power in HCC, colon adenocarcinoma, rectal adenocarcinoma, pancreatic adenocarcinoma, gastric adenocarcinoma, esophageal adenocarcinoma, esophageal squamous cell carcinoma, and cholangiocarcinoma. High-risk patients displayed an immunosuppressive microenvironment, characterized by increased infiltration of regulatory T cells, M2 macrophages, Th2 cells, or cancer-associated fibroblasts, or Th1 cells' reduction. Peroxisomes engaged in several distinct yet convergent pathways, most notably "positive regulation of response to stimuli". HCC prognostic genes were dynamically regulated in response to therapeutic stimuli, including radiotherapy, targeted therapy, and TACE. Clinically, the expression of PEX13 was markedly upregulated in tumor tissues from therapy-resistant HCC patients. Mechanistically, peroxisomal dysfunction induced by silencing PEX13 in HCC or UBE2D2 in CRC may overcome therapeutic resistance (radiotherapy/ lenvatinib resistance in HCC, radioresistance in CRC) through reprogramming lipid metabolism. CONCLUSIONS: Peroxisomes act as pivotal regulators of digestive cancer progression by modulating signaling pathways, the TIME, therapeutic resistance, and lipid metabolism. Targeting peroxisomal function, particularly in high-risk subgroups of HCC and CRC, warrants further exploration as a promising therapeutic strategy.
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