Development Of Carcinoma In Patients Research Articles

Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced colitis model.

As an important mechanism underlying the increased risk of colorectal carcinoma development in patients with long-standing ulcerative colitis, promotion as a result of the regenerative process has been proposed. In the present study, a dysplasia-carcinoma sequence in a novel repeated colitis model in mice is documented. Repeated colitis was induced by nine administration cycles of 3% dextran sulfate sodium (DSS; molecular weight, 54 000): each administration cycle comprised 3% DSS for 7 days followed by distilled water for the subsequent 14 days, to give conditions similar to the clinically observed active and remission phases in humans. Multiple colorectal tumors (nine low- and four high-grade dysplasias and two carcinomas) developed in 25 mice. These neoplastic lesions consisted of tubular structures, presenting as various types of elevated, flat and depressed tumor, similar to those in ulcerative colitis patients. A time-course study with assessment of the severity of colitis and in vivo bromodeoxyuridine uptake during a single 3% DSS administration cycle revealed a high level of regenerative activity in the colitis-affected mucosal epithelia. Thus, with the present repeated colitis model, regeneration and neoplastic lesions were apparent, the biological features of which provide evidence of a colorectal dysplasia-invasive carcinoma sequence in ulcerative colitis.

Angiogenesis correlates with development of hepatocellular carcinoma in patients with HCV-associated liver cirrhosis

Angiogenesis correlates with development of hepatocellular carcinoma in patients with HCV-associated liver cirrhosis

Histological changes associated with long-term urethral stents.

To assess the histological changes found in patients with long-term external sphincter, prostatic and urethral stents. Eighteen patients with long-term stents (mean time since insertion 3.5 years) were investigated. Three had external sphincter stents for detrusor-sphincter dyssynergia secondary to spinal injury, eight had prostatic stents for obstruction secondary to benign prostatic hyperplasia and seven had urethral stents for recurrent strictures. Nine stents were occluded at investigation, of which seven were entirely removed. The mucosae overlying the remaining two were biopsied, as were mucosae over the nine patent stents, at urethroscopy. The changes observed included polypoid hyperplasia (11 of 18 patients) between and around the stent mesh wires, nonkeratinizing squamous metaplasia (two) or hyperkeratotic squamous metaplasia (seven), chronic inflammation (15) with prominent plasma cell infiltrates (11), variable foreign-body granuloma (two) and microabscess formation (five), usually associated with clefts formed around the stent wires (three of five). Stents become incorporated into the urethral wall by a process of polypoid hyperplasia through the stent mesh, with at least focal covering of the stent in most cases, and with variable inflammatory infiltrates, most of which are rich in plasma cells. The urothelial and connective tissue proliferation resulted in obstruction of the stent lumen in nine of the patients studied. Further long-term study is necessary to exclude the development of carcinoma in patients with keratinizing squamous metaplasia, although no malignancy was seen in this study.

Could thymostimulin prevent hepatocellular carcinoma occurrence in patients with liver cirrhosis?

On the basis of a possible pathogenetic role of immunodepression in the development of hepatocellular carcinoma in patients with chronic hepatitis B/C viral infection and liver cirrhosis, we treated 34 liver cirrhosis patients (M/F 24/10; age: 14 pts less than or equal to 60 years, 20>60; Performance status: 22 0-1, 12 2-3; Childs' grade: 21 A, 13 B; ascites yes/not: 4/30) employing thymostimulin (TST), at the dosage of 50 mg/m(2) i.m. 3 times a week, until death or severe toxicity occurrence. Etiology of cirrhosis was viral in all cases. The patients were followed up every 3 months by means of clinical examination and biochemical analyses; every 6 months by checking viral serum markers, alpha-fetoprotein and by means of ultrasounds. To date, 34 patients have been treated, with a median follow-up of 6 (1-8) years. No occurrence of hepatocellular carcinoma has been observed, with a statistically significant difference between observed and expected HCC (p<0.05). Thymostimulin treatment was well tolerated. Our data seem to suggest that the immunomodulating treatment could significantly reduce the risk of HCC occurrence in patients with liver cirrhosis.

An Association between Acromegaly and Thyroid Carcinoma

Acromegaly has been associated with goiter as well as with benign and malignant tumors. Three cases of thyroid carcinoma in patients with acromegaly had been reported in the literature. We previously reported two additional cases of thyroid carcinoma and now present a third from 100 patients with acromegaly, exceeding the expected prevalence. All three thyroid carcinomas were multifocal, suggesting a generalized promotion toward malignancy. These patients had elevated levels of growth hormone and somatomedin-C [insulin-like growth factor (IGF-1)] at the time of thyroid carcinoma diagnosis. We discuss the role of IGF-1 in both benign and malignant thyroid growth, including the presence of IGF-1 receptors on thyroid cells, stimulation of thyroid cell replication by IGF-1, and paracrine secretion of IGF-1 and its binding proteins by thyroid cells. We propose possible mechanisms for the development of thyroid carcinoma in patients with acromegaly and discuss implications for the physician treating patients with acromegaly.

Increased risk of hepatocellular carcinoma development in patients with cirrhosis and with high hepatocellular proliferation

The immunohistochemical determination of the accessory protein of DNA-polymerase delta (PCNA), a marker of an early S-phase of the cell cycle, was used to evaluate cell proliferation retrospectively in formalin-fixed, paraffin-embedded liver biopsy sections in a group of patients with cirrhosis of similar age and duration of follow up, and with no evidence of hepatocellular carcinoma (41), including 17 patients with and 24 without hepatocellular carcinoma appearance during follow up. Proliferation was expressed as total (PCNA-TOT) and strongly (PCNA-STRO) positive nuclei per 1000 hepatocytes. The presence of dysplasia was also recorded. Histological findings and biochemical data, at the time of liver biopsy, were compared in the two groups. While total PCNA positivities were not significantly different in the two groups, strong reactivity was significantly higher in patients who eventually developed hepato-cellular carcinoma (median 0.7 vs 2.6). Univariate analysis of histological and biochemical data at the time of biopsy, followed by a stepwise regression study, showed that the significant parameters for a time-dependent disease-free state were, in decreasing order: cholesterol, PCNA-STRO, PCNA-TOT and alpha foeto-protein. Other clinical, biochemical and histological parameters, including dysplasia, provided no further information. From these data, hepatocellular proliferation can be evaluated in patients with cirrhosis with a currently available technique. Patients with high cell proliferation are at increased risk of developing hepatocellular carcinoma and may require differentiated follow up.

Congenital genitourinary anomalies. Is there a predilection for multiple primary malignant neoplasms?

A case of simultaneous uterine and renal cell carcinoma in an elderly woman who had a septate vagina, double cervix, uterus didelphys, and a single kidney secondary to contralateral renal agenesis is reported. She was treated for a period of 8 months, first with pelvic irradiation followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy and subsequently with heminephrectomy. Her renal function was normal postoperatively. The patient died of congestive heart failure in June 1990 after being free of carcinoma for approximately 18 years. The authors believe that this is the only case of its kind currently reported in the literature. Four of her family members died of either gastric (n = 3) or lung (n = 1) cancer, and one sister is alive with colon cancer. Only 19 proven cases of this constellation of congenital anomalies have been reported in the literature, and none have been associated with genitourinary (GU) carcinomas. There is a 50% to 70% incidence rate of genital tract anomalies in female patients with unilateral renal agenesis, secondary to the intimate association of the mesonephric and müllerian ducts. It has been suggested that the GU tract is prone to multiple primary malignant neoplasms, and there are families genetically predisposed to the development of large bowel and GU carcinomas. No conclusions can be drawn concerning the development of carcinoma in patients with congenital GU anomalies because of the small number of patients and the lack of follow-up in the literature.

The value of mucin histochemistry, autoradiography and analysis of cellular DNA content for cancer surveillance in patients with ulcerative colitis.

Although only a small proportion of patients with ulcerative colitis (UC) will develop cancer, colorectal carcinoma is still an important complication of UC. Traditionally, histopathological dysplasia has been used as a marker for colorectal carcinogenesis in patients with UC, however, wide within- and between-observer disagreements regarding the grading of dysplasia have become evident of late. Recently, mucin histochemistry, autoradiography and flow cytometric or static cytophotometric DNA analysis have been used for monitoring the development of colorectal carcinoma in patients with UC. A brief review of the recent literatures, however, has disclosed that the value of these modern techniques in the follow up surveillance of patients with UC of long standing is rather limited and that none of these measures should be used in isolation for the early detection of colorectal carcinoma arising in UC, or for selecting candidates for colectomy. Rather, the possible role of these modern techniques appears to be as a tool for elucidating the mechanism of colorectal carcinogenesis in patients with UC.

Natural Killer Cell Activity Is Reduced in Patients With Severe Forms of Inherited Epidermolysis Bullosa

Natural killer (NK) cell activity was evaluated in 34 patients with inherited forms of epidermolysis bullosa (EB). While the NK activity of EB simplex patients did not differ from that of control subjects, persons with more severe forms of EB demonstrated significant reductions in NK activity. The degree of this reduction was directly related to the severity of the skin involvement by EB with recessive dystrophic EB patients having the lowest NK activity. The absolute number of cells bearing NK surface markers in the peripheral blood of patients with recessive dystrophic EB did not differ from that of normal control subjects. This reduced NK activity may be at least partially responsible for the occurrence of septicemia in some persons with severe forms of EB and for the development of metastatic squamous cell carcinoma in patients with dystrophic EB.

Relationship between Natural Killer Activity and Development of Hepatocellular Carcinoma in Patients with Cirrhosis of the Liver

Natural killer (NK) activities of peripheral blood lymphocytes (PBL) in 50 patients with non-alcoholic liver cirrhosis (LC) were prospectively studied in order to clarify the relation between the development of hepatocellular carcinoma (HCC) and impaired NK activities. Patients were divided into two groups according to their NK activities at the beginning of the study, namely, Group A with normal NK activity (n = 21) and Group B with decreased NK activity (n = 29). NK activities were serially determined in each patient for up to 40 months. During the observation period, the occurrence of HCC was identified in 12 patients (four to 36 months). Of the patients who developed HCCs, two belonged to Group A (9.5%) and 10 belonged to Group B (34.5%). These results suggest decreased NK activity in LC patients to be one of the critical factors increasing their risk of developing HCC, and serial determinations of NK activities to be important in predicting the occurrence of HCCs in following the clinical course of LC patients.

Epidemiologic Studies of Mortality in Patients With Ulcerative Colitis

Ulcerative colitis is a relatively common condition that is amenable to treatment and is often managed by outside specialist referral centers. The risks of acute toxic dilatation and the development of colonic carcinoma in patients with chronic disease have long been recognized. In recent years, the relative risk of developing either of these complications has been shown to be low compared with views previously held. The exact cause of death can be difficult to define in some cases. Patients may die of the disease itself, complications of medical therapy, or following surgical intervention. In this editorial, we have considered mortality from all causes in various centers where population-based studies have been conducted. Such deaths are relatively uncommon and occur with a frequency that ranges from 0.3 deaths per million per year in France to 16.4 deaths per million per year in Venezuela. The average figure seen in Scandinavia is about

Association of depressed mixed lymphocyte reactivity with the development of bladder carcinoma in patients with papillomas.

Patients with bladder papillomas have an excellent overall prognosis, although approximately 10% of such patients develop frank bladder cancer. It is therefore important to devise methods for subclassifying bladder papillomas in an attempt to identify those patients at high risk for progression to carcinoma. The lymphoproliferative responses in 27 patients with bladder papillomas were tested in the mixed lymphocyte reaction (MLR). Patient responses were compared to those of normal individuals tested simultaneously. A relative proliferation index (RPI) was defined as a percent response relative to the mean normal response. A RPI less than 0.5 was defined as a depressed MLR and greater than 0.5 as a normal MLR. All patients were followed at three-month intervals for at least five years for the development of superficial or invasive bladder carcinoma. Of the 27 patients, 12 had a depressed MLR and 10/12 (83%) developed cancer within five years. Of the 15 patients with a normal MLR, only three developed bladder carcinoma. The number of papilloma patients surviving free of bladder carcinoma at five years was 12/15 (80%) with a normal MLR and 2/12 (17%) with a depressed MLR (P less than 0.01). Measurement of the MLR appeared to offer a useful adjunct in the evaluation of staging and biologic potential of bladder papilloma.