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PubMed2002

Routine vs extensive malignancy search for adult dermatomyositis and polymyositis: a study of 40 patients.

OBJECTIVE: To identify potential risk factors and the yield of routine screens for early detection of malignancy associated with dermatomyositis (DM) and polymyositis (PM). DESIGN: Retrospective study of malignancies in all patients with DM or PM followed up between the years 1981 and 2000 and a review of the relationship of DM and PM to malignancy, the usefulness of various tests or examinations for malignancy search, and the patients' course. SETTING: Departments of internal medicine and dermatology in a teaching hospital. PATIENTS: Forty consecutive adult patients with DM (33 cases) or PM (7 cases). MAIN OUTCOME MEASURES: (1) Rate of false-negative results of routine workup and yield (percentage of positive results) of blind malignancy search and (2) comparison of 16 characteristics in patients with malignancy vs those without. RESULTS: Malignancy occurred in 16 patients: 13 with DM and 3 with PM. In all cases, the diagnosis of malignancy was made concurrently with or shortly after the diagnosis of DM or PM. Factors associated with malignancy were recruitment in the internal medicine department (P =.02), constitutional symptoms (P<.01), a rapid onset of DM or PM (P =.02), the lack of Raynaud phenomenon (P<.01), and a higher mean erythrocyte sedimentation rate (P<.01) and creatine kinase level (P<.01). Initial routine search failed to discover 4 malignancies, 3 of which were discovered at an advanced stage by more extensive investigations. The positive result yield of blind malignancy search was only 13% (11 of 87), but reached 28% (5 of 18) for blind abdominal-pelvic and thoracic computed tomographic scans. CONCLUSION: Extensive search for malignancy, particularly computed tomographic scans, may be warranted in at least a subset of patients with DM or PM and risk factors of malignancy.

Adult↗
PubMed2006

EUS-guided paracentesis for the diagnosis of malignant ascites.

BACKGROUND: EUS and EUS-guided fine-needle aspiration (EUS-FNA) have well-defined roles in the diagnosis and staging of GI and pancreaticobiliary malignancy. Malignant ascites usually represents peritoneal carcinomatosis, increases disease stage, and portends a poor prognosis. There are limited data regarding the yield of EUS-guided paracentesis (EUS-P) for the diagnosis of malignant ascites. OBJECTIVE: To determine the usefulness of EUS-P for the diagnosis of malignant ascites. DESIGN: Prospective case series. SETTING: Tertiary referral academic center. PATIENTS: Those presenting for EUS examination for suspected or proven malignancy over a 16-month period were evaluated prospectively for the presence of ascites. INTERVENTIONS: EUS-P was performed via a transgastric or transduodenal approach if ascites was detected. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive predictive value, and negative predictive value of EUS-P for diagnosing malignant ascites. RESULTS: Six hundred twenty-nine patients were studied. Twenty-five patients with ascites who met inclusion criteria comprised the study cohort. The mean volume of ascites aspirated was 6.8 mL (range, 1-20 mL). Sixty-four percent (16 of 25) of EUS-P samples revealed malignant cytology. Of the group with negative ascitic cytology, 67% (6 of 9) had a proven malignancy. There was one false-negative cytology result. The sensitivity, specificity, positive predictive value, and negative predictive value of EUS-P for diagnosing malignant ascites was 94%, 100%, 100%, and 89%, respectively. The complication rate was 4%; 1 patient developed bacterial peritonitis after EUS-P. LIMITATIONS: The study did not address cost savings in patient care based on the diagnosis of malignant ascites. CONCLUSIONS: EUS-P is highly sensitive and specific for diagnosing malignant ascites. The finding of malignant ascites significantly alters patient management, so an active search for ascites and use of EUS-P should be incorporated into the diagnosis and staging of upper GI and pancreaticobiliary malignancy.

Aged↗
PubMed2003

Positive predictive value of liquid-based and conventional cervical Papanicolaou smears reported as malignant.

OBJECTIVES: The predictive value of cervical Papanicolaou (Pap) smears reported as "positive for malignancy," especially those obtained by the liquid-based method, has not been adequately assessed. The objectives of this study are to determine the positive predictive value of Papanicolaou smears with features of malignancy, to compare the accuracy of Papanicolaou smears obtained by the liquid-based method to those obtained by the conventional technique in this setting, and to study the factors influencing a false-positive cytologic diagnosis of malignancy. MATERIALS AND METHODS: Pap smears significant for malignant cytology were identified at Fletcher Allen Health Care Hospital in Burlington, VT, from May 1, 1995, to April 30, 2001. A retrospective review of the hospital records and pathology reports was performed documenting patient characteristics, the collection technique, and the final histology. An independent review of the cytology and histology was performed. The positive predictive value and false-positive rate of malignant cytology were calculated for the liquid-based and conventional Pap smear techniques. RESULTS: A total of 472,743 Pap smears were performed during the period specified. One hundred four Pap smears were reported as positive for malignancy, yielding a prevalence rate of 0.02%. A total of 68 patients had paired cytology and histology specimens. Malignant cytology was identified in 36 smears obtained by the liquid-based technique and 32 smears obtained by the conventional technique. A true-positive result, meaning malignant cytology confirmed by the presence of invasive carcinoma on histology, was obtained in 61 of 68 (89.7%) patients. A false-positive result, meaning malignant cytology not confirmed by histology, was obtained in 7 of the 68 (10.3%) patients. The false-positive rate of malignant cytology was 8.4% for the liquid-based technique and 12.5% for the conventional technique. All 7 false-positive smears were diagnosed with high-grade dysplasia by histology. Three of the 7 patients with high-grade dysplasia had previous treatment for dysplasia, one of whom was also pregnant at the time of the smear. CONCLUSIONS: Malignant cervical Papanicolaou smear cytology has a high positive predictive value in the setting of gynecologic and nongynecologic malignancies. Previous treatment for cervical dysplasia or pregnancy may influence the false-positive rate of malignant cytology.

Adenocarcinoma↗
PubMed2002

Evidence of differential risk for posttransplantation malignancy based on pretransplantation cause in patients undergoing liver transplantation.

Organ transplant recipients are considered to be at greater risk for developing malignancy because of the prolonged immunosuppression associated with organ grafting. The purpose of this study is to determine risk factors, clinical characteristics, and outcomes of de novo nonlymphoid malignancies after liver transplantation from a large single-center series. All patients undergoing liver transplantation at the King's College Hospital (London, UK) between January 1988 and December 1999 were analyzed retrospectively for the development of de novo malignancy in the posttransplantation period. Records were evaluated for age at diagnosis of malignancy, cause of liver disease, interval from transplantation to diagnosis of malignancy, predisposing factors for the development of cancer, immunosuppression regimen, treatment of malignancy, rejection episodes, and patient survival. Of 1,140 patients undergoing 1,271 liver transplantations, 30 patients (2.6%) developed de novo nonlymphoid malignancy after transplantation. Skin cancers were the most common (n = 13), followed by oropharyngeal carcinoma (n = 2), bladder carcinoma (n = 2), acute leukemia (n = 2), breast carcinoma (n = 2), and various other malignancies (n = 9). The mean time of presentation of the malignancy after transplantation was 45.1 +/- 32 months (range, 6 to 133 months), and mean age at diagnosis of malignancy was 55 years (range, 34 to 71 years). The incidence of de novo malignancy was significantly greater in patients who underwent transplantation for alcoholic liver disease compared with other groups (P <.001). Although the incidence of de novo nonlymphoid malignancy after liver transplantation is low, patients who underwent transplantation for alcoholic cirrhosis appear to have an increased risk for developing posttransplantation malignancy.

Adult↗
PubMed1998

Malignant granular cell tumor of soft tissue: diagnostic criteria and clinicopathologic correlation.

Seventy-three cases of malignant, atypical, and multicentric granular cell tumors of soft tissue were studied to clarify criteria for malignancy and prognostic factors. Six histologic criteria were assessed: necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (> 2 mitoses/10 high-power fields at 200x magnification), high nuclear to cytoplasmic (N:C) ratio, and pleomorphism. Neoplasms that met three or more of these criteria were classified as histologically malignant; those that met one or two criteria were classified as atypical; and those that displayed only focal pleomorphism but fulfilled none of the other criteria were classified as benign. Hence, 46 cases were classified as histologically malignant, 21 as atypical (3 were multicentric), and 6 as benign (all were multicentric). The patients with benign multicentric and atypical granular cell tumors had no metastases and there were no tumor deaths. In contrast, 11 of 28 patients (39%) with malignant granular cell tumor with follow-up information died of disease at a median interval of 3 years; 8 of 28 (29%) were alive with disease, and 9/28 (32%) were disease free (median intervals, 2 and 7 years, respectively). There were local recurrences in 9 of 28 malignant cases (32%) and metastases in 14 of 28 (50%) (median intervals, each 2 years). Forty-eight cases were studied immunohistochemically; 100% expressed vimentin, 98% S-100 protein, 98% neuron-specific enolase, 69% CD57, and 65% CD68. Alpha-smooth muscle actin, desmin, epithelial membrane antigen (EMA), cytokeratins (with CAM 5.2 and KL-1), chromogranin, and HMB45 were not detected. The proliferative index with Ki67 (MIB 1) was 10-50% in 14 of 25 malignant tumors (56%), and immunostaining for p53 was detected in 50% or more of tumor cells in 17 of 25 (68%); both of these factors were statistically significant with regard to the histologic classification as benign, atypical, or malignant. Ultrastructural examination of 13 benign, atypical, and malignant granular cell tumors showed engorgement of the cytoplasm with complex granules and lysosomes, as well as Schwannian features. By flow cytometric DNA analysis, two of six malignant tumors were aneuploid, two were hyperdiploid, and two were diploid. One atypical tumor was aneuploid and all 11 benign tumors were either diploid (9 cases) or hyperdiploid (2 cases). Statistically significant adverse prognostic factors with regard to survival included local recurrence, metastasis, larger tumor size, older patient age, histologic classification as malignant, presence of necrosis, increased mitotic activity, spindling of tumor cells, vesicular nuclei with large nucleoli, and Ki67 values greater [corrected] than 10%. This study defines clinical and morphologic criteria for malignancy in granular cell tumors and shows that malignant granular cell tumor is a high-grade sarcoma with a high rate of metastases and a short survival.

Adolescent↗
PubMed2002

Implications of follicular neoplasms, atypia, and lesions suspicious for malignancy diagnosed by fine-needle aspiration of thyroid nodules.

OBJECTIVE: To break out subcategories of atypical and suspicious cytologic interpretations of thyroid aspirations and correlate those with final histologic diagnosis. SUMMARY BACKGROUND DATA: Fine-needle aspiration (FNA) of thyroid nodules has become the primary diagnostic tool in the initial evaluation of thyroid nodules. Management of thyroid nodules is based on statistical data correlating a specific cytologic reading with the probability of malignancy. Two particular cytologic readings that frustrate both cytopathologists and surgeons are follicular neoplasms and cells that show atypia. In most reported series, follicular neoplasms and cells showing atypia are included in a broad "suspicious" category, with reported overall malignancy rates generally between 20% and 30%. However, there is interest in determining whether these suspicious lesions can be subcategorized, allowing a more accurate assessment of the risk of malignancy. In addition, there is recent evidence that the incidence of follicular cancer may be declining in this country, possibly decreasing the probability that a "follicular neoplasm" will prove to be a follicular cancer. METHODS: From January 1994 through December 2000, 709 thyroid FNAs were performed at a single institution. Those interpreted as suspicious and the subsequent histologic reports were reviewed. From this set, four specific categories were defined, and the clinical records for patients whose cytology matched these categories form the subject of this study. These four categories are follicular neoplasms without atypia, follicular neoplasms with atypia, atypia, and suspicious for malignancy. In addition, lesions with nondiagnostic cytology were reviewed. Only lesions for which there was histologic follow-up were considered. RESULTS: Ninety-eight aspirates were categorized as follicular neoplasms without atypia, follicular neoplasms with atypia, or atypia alone. Of 74 follicular neoplasms without atypia, only 5 (6.8%) were malignant, and none of these were follicular thyroid cancers. Nine of the lesions were follicular neoplasms with atypia, and four (44.4%) of these were malignant, including two that were invasive follicular cancers. Of 15 lesions showing atypia alone, 3 (20%) were malignant, all of which were papillary thyroid cancers. Twenty-five additional patients had lesions highly suspicious for malignancy. Twenty-one (84%) of these lesions were malignant, the majority being papillary thyroid cancers. Only one was a follicular cancer. Fifty patients with nondiagnostic cytology had subsequent action taken. Thirty-one of these lesions were resected, with five (16.1%) proving to be malignant. CONCLUSIONS: Thyroid nodules whose FNA is diagnosed as highly suspicious for malignancy should be resected unless there are significant contraindications to a surgical procedure. The extremely low rate (2%) of invasive follicular cancers among all follicular neoplasms may reflect changing histologic criteria for follicular carcinoma, a true change in the disease frequency, or both. For thyroid nodules whose cytology shows a follicular neoplasm without atypia, malignancy rates of 8% or less may allow nonsurgical options, including reevaluation in selected populations. Continued efforts to correlate malignancy rates to specific cytologic criteria will allow patients to make more informed decisions regarding their medical care.

Adenocarcinoma, Follicular↗
PubMed1999

Drug resistance in multiple myeloma: novel therapeutic targets within the malignant clone.

Myeloma is incurable because the malignant stem cell is not eradicated by treatment. Thus, identification of the malignant hierarchy of B lineage cells in myeloma is required to identify potentially generative components and to evaluate their drug resistance properties. BM plasma cells are usually depleted by chemotherapy, but clonotypic B cells survive melphalan/prednisone as well as combination chemotherapy. In vitro, circulating and bone marrow-localized myeloma plasma cells show defective drug export, despite their phenotypic expression of P-glycoprotein, the mdr1 gene product. In contrast to plasma cells, circulating myeloma clonotypic B cells exhibit very efficient drug export. This suggests that circulating clonotypic MM B cells comprise a reservoir of drug resistant disease in myeloma although their stem cell potential remains to be confirmed. The malignant clone in each myeloma patient is defined by a unique IgH VDJ gene rearrangement. Using methods that exclude the possibility that a frequent but non-malignant clone has inadvertently been identified, and after confirming that the sequence identified is expressed by nearly all bone marrow plasma cells, we show that the drug resistant set of myeloma B cells is clonally related to the malignant plasma cells in myeloma. Clonotypic MM B cells survive chemotherapy, persist during clinically defined "minimal residual disease" and remain after autologous transplantation. Thus their malignant status is an important consideration. If malignant, they must be considered in the design of therapy. If non-malignant, they would be expected to have minimal impact on the disease process. A variety of evidence provides strong support for the view that clonotypic drug resistant B cells are malignant and may include the generative compartment of myeloma. The P-gp+ set of clonotypic B cells is extensively DNA aneuploid, an attribute of malignancy. All clonotypic B cells overexpress RHAMM, a novel oncogene involved in malignant spread. Finally, the population of clonotypic B cells lacks intraclonal heterogeneity. Since intraclonal heterogeneity is driven by the response to antigens, its absence in these cells indicates that they are no longer antigen-responsive. Since antigen-independent clonal expansion is characteristic of lymphoid malignancies, these observations provide further proof that clonotypic B cells in myeloma are malignant. Thus, the drug resistance of these cells is highly relevant to understanding why myeloma remains incurable despite the initial chemosensitivity of most bone marrow plasma cells.

B-Lymphocytes↗
PubMed1999

Increased risk of lymphoid and nonlymphoid malignancies in patients with lymphomatoid papulosis.

BACKGROUND: Lymphomatoid papulosis (LyP) is a rare skin disease with malignant potential. The long term outcomes of patients with this disease have not been adequately assessed. METHODS: Fifty-seven patients with biopsy-proven LyP and 67 controls matched for age, gender, and race were followed prospectively from 1988 to 1996. Reported malignancies were confirmed by surgical pathology and/or autopsy reports. A search through the National Death Index through December 1995 was conducted to identify all deaths, and death certificates were procured. Expected numbers of malignancies based on SEER data were calculated for both the patient and the control groups. RESULTS: Six LyP patients (10.5%) and 1 control (1.5%) reported nonlymphoid malignancies (P = 0.047). Two patients and no controls developed lymphoid malignancies (mycosis fungoides and CD30(+) cutaneous lymphoma). The expected numbers of nonlymphoid and lymphoid malignancies in the LyP patient group, based on the SEER data, were 1.93 and 0.15, respectively, yielding a relative risk (with 95% confidence interval) of 3.11 (1.26-6.47) for nonlymphoid malignancies and 13.33 (2.24-44.05) for malignant lymphomas in the LyP patients. There was no significant difference between the observed and expected numbers of malignancies in the control group. Four LyP patients died during the follow-up, three due to malignancies; and one control died of a gunshot wound to the head (suicide). The difference in overall survival between the LyP patients and the controls was not statistically significant (P = 0. 12). CONCLUSIONS: Patients with LyP appear to have an increased risk of both lymphoid and nonlymphoid malignancies. The increased risk of nonlymphoid as well as lymphoid malignancies may suggest a basic underlying genetic defect leading to the development of malignancy in LyP patients.

Adolescent↗
PubMedDate not supplied

Second malignancies after a gastrectomy for gastric cancers: the effects of adjuvant therapies.

Second malignancy after gastrectomy has become one of the important issues in the management of gastric cancer patients. However, the effect of adjuvant therapies has never been surveyed, although there have been many reports on second malignancy after chemotherapy of other malignancies. Between 1979 and 1995, 574 patients with gastric cancer underwent gastrectomies in our department. 563 patients (98.1%) were completely followed-up, and the incidence of second malignancy after gastrectomy was assessed with special emphasis on the effect of adjuvant therapies, namely benefits versus carcinogenesis. The overall postsurgical survival rate was 62.5%, and the survival rate of patients with stage 2-4 cancer was significantly higher in the adjuvant therapy groups than in the surgery alone group. The overall incidence rate of a second malignancy was 3.20% (18/563), including 4 colorectal, 3 liver, 3 head and neck, and 8 other malignancies, and 3.90% (9/231) for the surgery alone group, 1.94% (3/155) for the chemotherapy group, 3.68% (6/163) for the chemoimmunotherapy group, and 0% (0/14) for the immunotherapy alone group. There were no statistical differences in the incidence rates between these 4 groups. The mean duration until the occurrence of second malignancy was 5.1 years for the surgery alone group, 8.6 years for the adjuvant therapy group (9.3 years for chemotherapy and 8.1 years for chemoimmunotherapy; p < 0.1, surgery alone vs. adjuvant therapy). The overall mean actuarial risk of developing a second malignancy was 6% at 5 years and 18% at 10 years. Multivariate analysis demonstrated that chemotherapy decreased the risk of death due to gastric cancer (risk ratio = 0.67, p = 0.017) and the risk of a second malignancy (risk ratio = 0.52, p = 0.261). Oral fluoropyrimidines were found to be particularly effective at decreasing the risk of death due to gastric cancer (risk ratio = 0.66, p = 0.012) and a second malignancy (risk ratio = 0.38, p = 0.136). However, intravenous chemotherapy was demonstrated to have no influence on survival (risk ratio = 0.93, p = 0.692) or a second malignancy (risk ratio = 0.58, p = 0.500). There was no evidence of an increased risk for a second malignancy following adjuvant chemotherapy. Adjuvant chemotherapy with oral fluoropyrimidines was suggested to contribute to the improved survival of patients with stage 2-4 gastric cancer, and to have a decreased the risk of a second malignancy.

Adult↗
PubMed2002

[Analysis of 8 years follow up information of malignant tumor in industrial system of Guangzhou].

BACKGROUND & OBJECTIVE: Guangzhou is one of the advanced industry cities in China. To investigate the mortality of malignant tumor in workers from different industries can identify the high risk people who suffer from malignant tumor and have important significance to identify the relation between occupational factors and malignant tumor. This study was designed to follow up the dead situation of malignant tumor in workers from different industries in Guangzhou, and provide the data for prevention and treatment of tumors. METHODS: A total of 79,573 workers, who exceed 35 years old, from 399 factories of Guangzhou were included in the prospective study for 8 years. It based on individual health files of 399 factories from 1989 to 1992. The total mortality, mortality of malignant tumor, and the disease classification of malignant tumor were investigated by epidemiology and statistics. RESULTS: A total of 633,869 people year (393,373 men, 30,195 women) have been trailed. The trailed time was more than 8 years. Of 1577 dead employees, 801 died of malignant tumor (50.7%). Of all the occupational types of work, the mortality of malignant tumor in metallurgical industry is apparently higher than that in other industries. In rubber industry, the relative risk of malignant tumor mortality in old age group is higher than that in middle age group. The top three malignant tumors of death were digestive system, respiratory system and rhinopharynx malignant tumors. While the top three mortalities for single organ malignant tumor were lung cancer, liver cancer, and rhinopharynx cancer. CONCLUSIONS: At present, malignant tumor is a disease which severely imperil the life of workers in different industries of Guangzhou. It is important to do health check periodically in old age group.

Adult↗
PubMedDate not supplied

[Pheochromocytoma: role of preoperative diagnosis in the assessment of malignancy risk and in the choice of surgical approach].

Pheochromocytomas are malignant in 5-26% of the cases. Differential diagnosis with benign lesions can be difficult even on a pathological basis. Local invasion and distant metastasis are the only well established indicators of malignancy. It has been reported that the risk of malignancy increases with the lesion size. Despite safe laparoscopic adrenalectomy (LA) has been reported for lesions up to 10 cm, it is considered hazardous for pheochromocytoma larger than 6 cm, because of the risk of malignancy and iatrogenic pheochromocytomatosis. We evaluated the possibility to pre-operatively recognize pheochromocytomas at risk of being malignant that should not be selected for LA. The medical records of all the patients who underwent adrenalectomy for pheochromocytoma were reviewed. All the preoperatively available data (demographic, clinical, biochemical and radiological) were recorded as well as final pathological diagnosis. Comparative analysis of patients with benign and malignant pheochromocytomas was performed. Sixty-three adrenalectomies for pheochromocytoma were performed in 60 patients. Fifty-seven benign and 6 malignant pheochromocytomas were identified. No significant difference was found between patients with malignant and benign lesions concerning age, gender, family history, symptoms, laboratory and radiological findings. In particular, no significant difference was found for lesion size between the benign (63.3 +/- 30.6 mm, range, 20-150) and the malignant group (48.6 +/- 16.5 mm; range, 30-70). The largest diameter recorded for a malignant lesion was 70 mm. No preoperatively available data can reliably differentiate between benign and malignant pheochromocytomas. All malignant lesions in this series were smaller than 7 cm. Thus, pheochromocytoma size does not seem a reliable predictor of malignancy. In absence of the evidence of gross local invasion or metastatic disease, LA can be safely proposed also for large lesions. Conversion is mandatory in presence of local invasion or difficult dissection that could involve inadequate resection.

Adrenal Gland Neoplasms↗
PubMed2006

[Increased risk of malignancies in heterozygotes in families of patients with Nijmegen breakage syndrome].

BACKGROUND: The autosomal recessive chromosomal instability and hyperradiosensitivity Nijmegen breakage syndrome (NBS) in consequence of a mutation in the NBSI gene at 8q21 is associated with high occurrence of lymphoreticular malignancies due to deficient DNA reparation (double strand breaks). In the Slavic population the majority of patients are homozygotes of the so-called "Slavic mutation" 657de15 in exon 6. Increased occurrence of malignant solid tumors (1) in families of NBS patients has been described already prior to the identification of the responsible gene, and the increased risk of malignancies in heterozygotes was thus hypothetical. METHODS AND RESULTS: The possibility of discerning mutation carriers in families from normal homozygotes enables verification of that hypothesis. Through molecular genetics investigations of grandparents and immediate relatives, we have been successful in determining the genotype in 79 of 112 grandparents in 28 families of our 39 patients and 54 their parents and siblings. A single family had affected children in consequence of compound heterozygosity of the 657de15 and R215W mutations in the same exon of the NBSI gene. The proband's families were investigated genealogically and data on relatives were obtained over four generations. Obtained data were repeatedly supplemented and objectively verified in church books and in healthcare documentation. Seven families have been followed up for 20-30 years, six families for 10-20 years, and 15 families for 1-10 years. Out of 28 families we were successful in examining the genotype of both grandparents in 18 families, there having been revealed one non-paternity; in five families only one of the grandparents has been examined; in five families we were not successful in examining any grandparent. Among 40 grandparents - normal homozygotes, there has appeared a malignancy in three (7.4 %), while among 39 heterozygotes of mutation 657de15 in the NBSI gene malignancies were documented in 15 (38,2 %). Mean age of NBS heterozygotes at manifestation of malignancy was 59.3 year (range 47-72 years), in the group of homozygotes it was 52.6 years (range 44-62 years). Nine grandparents died of malignancy prior to the discovery of the NBSI gene and their genotype has been deduced genealogically in seven on the basis of the genotype in the sponse and children, in two from preserved DNA. Out of that number, from three grandparents that had died of malignancies we were successful in obtaining neoplastic tissue for molecular genetics investigation, aimed at LOH or amplification of the NBS1 gene. In another seven grandparents - heterozygotes, malignancies were manifested after determination of their genotype by DNA analysis, and consequently also from tumor tissue that has been obtained from three of them for molecular genetic investigation. CONCLUSIONS: The age distribution and socio-economic status of both groups of grandparents did not differ, the sex ratio was slightly shifted towards females in the group of homozygotic grandparents (22 females and 18 males), and in the group of heterozygotes it was towards males (21 males and 18 females). The sex ratio between heterozygotic grandparents with malignancies was likewise shifted towards the male gender (11 males and 4 females), in the group of homozygotic grandparents malignancy affected one male and two females. As verified in healthcare and church books documentation, the occurrence of malignancies was significantly more frequent among grandparents heterozygotic for NBS1 mutation than in healthy homozygotes. Among sibs of grandparents and great-grandparents was found significant difference in frequency of malignancies in heterozygotes (5/18 = 27,7 %) and healthy homozygotes (2/36 = 5,5 %), too.

Adult↗
PubMed1984

Malignant colon polyps--cure by colonoscopy or colectomy?

Although malignant sessile colon polyps usually require colectomy for proper treatment, the vast majority of malignant pedunculated polyps can be removed colonoscopically for cure. The author's experience with 83 consecutively encountered malignant polypoid lesions is reviewed and is the basis for the discussion herein. All 49 malignant pedunculated polyps were removed colonoscopically. Eight of these patients also underwent colectomy because of questionable or definite presence of cancer cells within the stalk portion of the polyp; no residual cancer was identified at the polypectomy site, and all lymph nodes were negative in these patients. Of 34 patients with malignant sessile polypoid lesions, 13 underwent colectomy because of obvious malignancy at colonoscopy. Twenty-one sessile lesions were removed colonoscopically; with malignancy documented, nine of the 21 patients underwent colectomy. Positive findings (either cancer at the polypectomy site or in lymph nodes) at surgery were identified in two of these nine patients. Colonoscopic polypectomy can be considered curative for malignant pedunculated polyps provided the stalk portion of the lesion is totally uninvolved with the malignant process, provided there is no lymphatic or vascular invasion, the malignancy is well differentiated, and follow-up endoscopic examination of the polypectomy site reveals no residual or recurrence. These four criteria must be satisfied in order to consider a malignant pedunculated polyp curatively removed by colonoscopic polypectomy alone. The risk of colectomy in patients satisfying these four criteria is believed to be greater than the risk of metastatic disease and death from this lesion. Colectomy is recommended for all patients with malignant sessile polypoid lesions, provided their general medical condition provides an acceptable operative risk. Although colonoscopic polypectomy is not recommended for obviously malignant sessile polyps, there are instances where sessile lesions are removed colonoscopically and found microscopically to contain focal or minute areas of invasive cancer. In certain of these patients, the risk of colectomy may exceed the risk of recurrence or metastasis, if the polypoid lesion has been totally removed colonoscopically and completeness of the polypectomy has been documented by follow-up colonoscopy. Each patient's clinical history, general condition, and histopathology must be reviewed individually by a clinician experienced in this field in order to reach a wise and proper decision regarding the potential need for colectomy, and limit colectomy to those patients in whom it is absolutely necessary.

Adenoma↗
PubMed2000

Angiotensin-converting enzyme gene I/D polymorphism in malignant hypertension.

BACKGROUND: The mechanism of the rapid transition of a stable benign hypertensive disease to a severe and devastating malignant hypertension is not fully understood. However, the renin angiotensin system, which is highly activated in malignant hypertension, is established as an important pathogenetic factor in different cardiovascular and renal diseases. Over the last decade, a polymorphism in genes regulating this system has been found. This includes the 287 bp sequence deletion (D)/insertion (I) polymorphism in the angiotensin-converting enzyme (ACE) gene and the methionine (M) to threonine (T) point mutation polymorphism in the angiotensinogen (AGT) gene. These gene polymorphisms have been associated with various cardiovascular and renal diseases and the aim of this study was to investigate whether they were linked to malignant hypertension. METHODS: Forty-two patients with malignant hypertension (mean age 55 years), 42 patients with non-malignant hypertension (mean age 57 years) and 85 normotensive control subjects (mean age 42 years) were investigated with respect to ACE I/D and AGT M/T genotypes. DNA was prepared by standard methods from isolated white blood cells and analysed by the PCR technique. The PCR reaction used in the detection of the ACE I/D polymorphism was optimized for an equal amplification of the I and D alleles. RESULTS: The frequency of the DD genotype was significantly increased in patients with malignant hypertension (43%) compared with patients with non-malignant hypertension (14%) and normotensive control subjects (18%) (p <0.01) for both. The frequency distribution of AGT M/T genotype did not differ between patients with malignant and non-malignant hypertension. CONCLUSION: The DD genotype of the ACE gene occurred more than twice as often in malignant hypertension than in non-malignant hypertension and indicates that ACE gene polymorphism is a significant risk factor for initiation of malignant hypertension.

Adult↗
PubMed1994

A clinical grading scale to predict malignant hyperthermia susceptibility.

BACKGROUND: The diagnosis of an acute malignant hyperthermia reaction by clinical criteria can be difficult because of the nonspecific nature and variable incidence of many of the clinical signs and laboratory findings. Development of a standardized means for estimating the qualitative likelihood of malignant hyperthermia in a given patient without the use of specialized diagnostic testing would be useful for patient management and would promote research into improved means for diagnosing this disease. METHODS: Using the Delphi method and an international panel of 11 experts on malignant hyperthermia, a multifactor malignant hyperthermia clinical grading scale comprising standardized clinical diagnostic criteria was developed for classification of existing records and for application to new patients. RESULTS: This scale ranks the qualitative likelihood that an adverse anesthetic event represents malignant hyperthermia (malignant hyperthermia event rank) and that, with further investigation of family history, an individual patient will be diagnosed as malignant hyperthermia susceptible (malignant hyperthermia susceptibility rank). The assigned rank represents a lower bound on the likelihood of malignant hyperthermia. The clinical grading scale requires the anesthesiologist to judge whether specific clinical signs are appropriate for the patient's medical condition, anesthetic technique, and surgical procedure. CONCLUSIONS: The malignant hyperthermia clinical grading scale is recommended for use as an aid to the objective definition of this disease. It use may improve malignant hyperthermia research by allowing comparisons among well-defined groups of patients. This clinical grading system provides a new and comprehensive clinical case definition for the malignant hyperthermia syndrome.

Adult↗
PubMed1998

Novel antipsychotics and the neuroleptic malignant syndrome: a review and critique.

OBJECTIVE: The authors' goal was to analyze reported cases of neuroleptic malignant syndrome in patients given clozapine and risperidone. METHOD: They assessed 19 cases of clozapine-induced neuroleptic malignant syndrome and 13 cases of risperidone-induced neuroleptic malignant syndrome against three criteria sets and against extent of exclusionary workup and then designated them as high or low probability of being neuroleptic malignant syndrome. RESULTS: Nine of the 19 cases of clozapine-related neuroleptic malignant syndrome and eight of the 13 cases of risperidone-related neuroleptic malignant syndrome were designated as having high probability of being neuroleptic malignant syndrome. The remainder were designated as having low probability because presentations were not linked to treatment or failed to meet criteria for the syndrome. CONCLUSIONS: Neuroleptic malignant syndrome can occur in patients given atypical antipsychotics and resembles "classical" neuroleptic malignant syndrome. However, side effect profiles overlap considerably with neuroleptic malignant syndrome criteria, and atypical antipsychotics may cause neurotoxicities unrelated to (but misattributed as) neuroleptic malignant syndrome. Insufficient evidence exists for "atypical" neuroleptic malignant syndrome with novel antipsychotics.

Adolescent↗
PubMed2002

[Thoracoscopy--the method of choice in the determination of a malignancy as the cause of pleural effusion of unknown etiology].

UNLABELLED: After complete pulmological investigation remains about 20% of all the pleural effusions without etiological diagnosis designated as unexplained pleural effusions. Thoracoscopy enables further investigation with the final aim--establishing of the etiological cause of the unexplained pleural effusions. Recently numerous studies demonstrated that the malignancy is the most frequent cause of this aforementioned pleural effusions. OBJECTIVE: Descriptive-analytic appraisal of validity of thoracoscopy in establishing of malignancy as a cause of idiopathic pleural effusions. TASKS: To establish if the malignancy is the most frequent cause of unexplained pleural effusions, to establish diagnostic-thoracoscopic sensitivity and specificity for malignant disease as cause of pleural effusions and to establish positive and negative predictive value of thoracoscopy for malignancy. PATIENTS AND METHODS: In the period between 06.11.1984 and 01.02.2002, included in this investigation were all patients with pleural effusions of unknown origin who were referred to the Clinic for Thoracic Surgery--UCC Sarajevo, for thoracoscopy after less invasive means of diagnosis had failed. Investigation had clinical-manipulative, descriptive-analytic and retrospective-prospective design. RESULTS: There were 74 patients with the pleural effusions of unknown origin. The malignancy was found in 47.3% (35/74) patients. Diagnostic sensitivity of the method for malignancy was 89.7% and the specificity 100.0%. The positive predictive value of the thoracoscopy for malignancy was 100.0% and negative predictive value 89.7%. CONCLUSIONS: The malignancy was the most frequent cause of idiopathic pleural effusions. Thoracoscopy has high specificity and sensitivity in regard to discovering of malignancy as a cause of idiopathic pleural effusions. Undiagnosed malignancy by thoracoscopy excludes malignancy as a cause of pleural effusion with high security.

Adult↗
PubMed2003

Fine-needle aspiration of superficial and deeply seated lymph nodes on patients with and without a history of malignancy: review of 439 cases.

This study addresses the utility of fine-needle aspiration (FNA) in assessing lymphadenopathy in patients with and without a previous history of malignancy. We reviewed the FNAs of superficial and deeply seated lymph nodes performed at our institution over a period of 18 yr (1983-2001). Where applicable, we also reviewed and report here the results of subsequent surgical excisional biopsies. We analyzed data from 439 patients, who ranged in age from 1 to 90 yr. The neck and retroperitoneum were the most frequently sampled sites (47% and 25%, respectively). Among the 439 FNAs, adequate material was obtained in 421 cases (96%); the remaining 18 were unsatisfactory (4.1%). Malignant diagnoses were rendered in 330 cases (75% of 439), four were suspicious for lymphoma (0.9%), and 87 were read as reactive lymph nodes or granulomas (20%). The most common malignant cytologic diagnoses from these lymph node FNAs were adenocarcinoma, squamous cell carcinoma, and lymphoma. We compared results between two major groups: patients with a history of malignancy and those without. FNA showed malignancy in 87% of patients with a history of cancer and 41% without such a history. Thirty-three or 10% of patients with a history of malignancy were given a benign diagnosis and follow-up surgical excisional biopsies were performed in nine of these cases. Four of the nine showed low-grade lymphoma. Of the 18 non-diagnostic FNAs, nine came from patients with a history of malignancy and in six of these nine who had a follow-up surgical excisional biopsy the lymph nodes were positive for malignancy. Of the other nine, who had no history of malignancy, only two had follow-up biopsies and both of these were negative. Patients with a history of malignancy are more than twice as likely to show malignancy on lymph node FNA compared to those without such a history (87% vs. 41%). Knowing whether a patient has a history of malignancy provides the appropriate level of suspicion for ordering ancillary investigations or even recommending excisional biopsy for further evaluation.

Biopsy, Fine-Needle↗