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Specific gene-expression profiles of noncancerous liver tissue predict the risk for multicentric occurrence of hepatocellular carcinoma in hepatitis C virus-positive patients.

BACKGROUND: Hepatitis C virus (HCV) infection produces chronic hepatitis, cirrhosis, and, ultimately, hepatocellular carcinoma (HCC). A molecular analysis of the damaged liver tissues infected with HCV may identify specific gene-expression profiles associated with a risk for liver carcinogenesis. METHODS: Forty patients with HCV-positive HCC were classified into two groups: single nodular HCC group (n = 28) and multicentric HCC group (n = 12). Using a complementary DNA microarray, we compared the gene-expression patterns of the noncancerous liver tissue specimens between the two groups. We also identified the differentially expressed genes related to multicentric recurrence in the liver remnant. We then evaluated whether a specific gene-expression profile can accurately estimate the risk for multicentric hepatocarcinogenesis. RESULTS: We selected the 230 differentially expressed genes in the multicentric HCC group. A hierarchical clustering analysis identified a cluster that might be closely associated with the multicentric occurrence of HCC. On the basis of the gene-expression profiling of the 36 genes commonly associated with both multicentric HCC and multicentric recurrence, we created a scoring system to estimate the risk for multicentric hepatocarcinogenesis. The prediction score of patients in the multicentric HCC group with multicentric recurrence (19.9 +/- 9.2) was significantly higher (P < .05) than that in the single nodular HCC group without multicentric recurrence (-1.8 +/- 12.7). CONCLUSIONS: Specific gene-expression signatures in noncancerous liver tissue may help to accurately predict the risk for developing HCC.

Aged↗

[Depressive disorders. Risk factors of recurrence].

The prediction of recurrence in affective disorders is very difficult and in individual cases not possible at all. Socio-demographic variables as body build, positive family history, marital status and social class, do not predict recurrence. This is probably true for sex and age, too. The impact of stressors and social support on the course is relatively weak. In this context the research on expressed emotion is of interest, as it gives some evidence that the presence of a sick spouse may increase the relapse rate. On the other hand an inadequate premorbid personality, especially a high neuroticism score, could predict recurrence. Classification of the illness is an other variable with prognostic value. Relapse rate is probably higher in endogenous than in neurotic depressions. Comorbidity and a history of other psychiatric disorders correlate with a high relapse rate. One of the best established clinical and epidemiological finding is the prognostic value of the past course. Recurrence is higher in bipolar disorders and in patients with a high number of previous episodes. An older age of onset probably increases the likelihood of recurrence. A prospective study on the course of affective disorders was initiated in Zurich in 1959. All patients suffering from affective and schizoaffective psychoses (n = 406) who were admitted to the Psychiatric University Clinic of Zurich between 1959 and 1963 were followed up every 5 years. The last assessment was carried out in 1985. On the basis of a multiple regression analysis, we tried to establish correlations of several independent variables with the length of cycles and the number of episodes per year. Correlations were only found in bipolar disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Causality↗

Recurrent PSA after prostatectomy for prostate cancer: implications of PSA doubling time.

After radical prostatectomy for prostate cancer, men frequently develop detectable levels of prostate specific antigen (PSA). A slow rate of increase, as characterized by the PSA doubling time (PSADT) is the principal marker for a favorable prognosis. Data and results presented in 2 recent clinical articles studying cohorts of men with clinical stage T1/T2 prostate cancer are reviewed and used to develop mortality analyses. Life-table analysis shows a mortality ratio of 257% at 5 years for Gleason score < 8, PSA recurrence > 2 years after surgery for clinical stage T1/T2 disease, and PSA doubling time (PSADT) > 10 months. Markov modeling using transition probabilities derived from the clinical articles to develop a life table analysis yields a mortality ratio of 145% at 10 years for similar patients.

Adult↗

Helicoidal suture: alternative treatment for complete rectal prolapse in high-risk patients.

BACKGROUND AND AIMS: Optimal treatment for rectal prolapse is controversial. We describe a novel alternative treatment for high-risk patients with complete rectal prolapse. PATIENTS AND METHODS: Sixteen high-risk patients over 60 years old with complete rectal prolapse were examined. All patients had significant past medical history and were classified as grade III (ASA) surgical risk. The helicoidal suture technique is described. Postoperative parameters evaluated were morbidity, mortality, postoperative symptoms, recurrence and anal incontinence score. Median follow-up was 60 months. RESULTS: There were no operative complications or mortality in the series; one patient experienced recurrence. Median postoperative anal incontinence score was 6.06 (range 1-30; preoperative 23.6). CONCLUSION: This technique provides adequate functional outcomes and could be an effective therapeutic strategy against rectal prolapse in high-risk patients.

Aged↗

Familial aggregation in skin flush response to niacin patch among schizophrenic patients and their nonpsychotic relatives.

Though a reduced flush response to niacin has been found in schizophrenic patients, whether it is a vulnerability indicator to schizophrenia remains little known. We aimed to examine the familial aggregation in niacin flush response among schizophrenic patients and their nonpsychotic relatives. In a sample of 153 schizophrenia probands, 217 parents, 70 siblings, and 94 normal subjects, 3 concentrations (0.001 M, 0.01 M, and 0.1 M) of niacin were applied to the forearm skin and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. Both the heritability for continuous flush scores and the recurrence risk ratios for binary non-flush response in the nonpsychotic relatives of schizophrenic patients were estimated, and ordinal logistic regression analyses of relatives' niacin response on probands' were further conducted to adjust for potential confounders. The greatest heritabilities ranged from 47% (0.01 M at 10 minutes) to 54% (0.1 M at 5 minutes). The risk ratios of 0.01 M at 10 minutes (ranging from 2.60 for using score 1 or less to 5.06 for using score 0 as non-flush) and 5 minutes (1.66 for using score 0 as non-flush) were significantly greater than one. Multiple ordinal logistic regression analyses further revealed that the association between probands and relatives in niacin flush response remained after adjustment for potential confounders, including age, sex, allergy, tobacco smoking, and coffee drinking. These findings provide support for the potential of niacin flush response as a vulnerability indicator to schizophrenia.

Administration, Cutaneous↗

Reoperation for recurrent metastatic brain tumors.

Results of reoperation in 48 patients who developed recurrent brain metastases between January 1984 and April 1993 are presented. Median time from first craniotomy to diagnosis of recurrence (time to recurrence) was 6.7 months. Median Karnofsky performance scale (KPS) score prior to reoperation was 80. Recurrence was local in 30 patients, distant in 16 patients, and both local and distant in two patients. Median survival time after reoperation was 11.5 months. There were no operative mortalities. Multivariate analysis revealed that presence of systemic disease (p = 0.008), KPS scores less than or equal to 70 (p = 0.008), time to recurrence of less than 4 months (p = 0.008), age greater than or equal to 40 years (p = 0.51), and primary tumor type of breast or melanoma (p = 0.028) negatively affected patient survival time. These five factors were used to develop a grading system (Grades I-IV). Patients categorized in Grade I had a 5-year survival rate of 57%, whereas the median survival time of patients in Grades II, III, and IV was 13.4, 6.8, and 3.4 months, respectively (p < 0.0001). Overall, 26 patients developed a second recurrence after reoperation. Seventeen patients underwent a second reoperation, whereas nine did not. Patients undergoing a second reoperation survived a median of 8.6 additional months versus 2.8 months for those who did not (p < 0.0001). This study concludes that reoperation for recurrent brain metastasis can prolong survival and improve quality of life. A second reoperation can also increase survival. Five factors influence survival: status of systemic disease, KPS score, time to recurrence, age, and type of primary tumor. The grading system using these five factors correlates with survival time. Reoperation should be approached with caution in Grade IV patients because of their poor prognosis.

Adolescent↗

Differences in assessment of patients with satisfactory or complicated continuous ambulatory peritoneal dialysis courses.

The aim of our study was a comparison of comorbid scores, peritonitis rates, dialysis adequacy, and nutritional parameters in continuous ambulatory peritoneal dialysis (CAPD) patients. Patients were separated into two groups: those who, in the course of CAPD, were ingood clinical condition and underwent renal transplantation (group I, n = 11), and those who had to discontinue CAPD treatment (group II, n = 16) owing to death caused by comorbid disease or owing to transfer to hemodialysis for technique failure related mainly to recurrent peritonitis. Clinical scores were lower in group II, showing significantly more insomnia, weakness, and anorexia. The PET D/P creatinine, mean adequacy parameter, and urine output were similar in groups I and II. Daily protein intake (DPI) and daily energy intake (DEI) showed higher values in group I than in group II when expressed in g/kg and kcal/kg total body mass (TBM) respectively (DPI 1.09 +/- 0.15 g/kg TBM vs 0.92 +/- 0.31 g/kg TBM, p = 0.036; DEI 36.3 +/- 4.3 kcal/kg TBM vs 31.0 +/- 9.0 kcal/kg TBM, p = 0.048), but the intakes were not significantly different when calculated per kilogram ideal body mass (IBM). Lean body mass as a percent of total mass was 77.7% +/- 7.8% versus 73.9% +/- 6.8% (p = 0.048) in groups I and II respectively. Group I showed lower serum cholesterol than group II (179 +/- 33 mg/dL vs 231 +/- 41 mg/dL, p = 0.001) despite higher dietary intake of cholesterol (367 +/- 137 mg/day vs 251 +/- 97 mg/day, p = 0.016), correlating with DPI (r = +0.673, p = 0.023). Our results indicate that under conditions of similar CAPD adequacy, patients with a satisfactory course of CAPD therapy have higher dietary intake and are better nourished than those with a poor outcome. The changes in nutrition seem to be related to comorbid diseases and complications of CAPD therapy. Increased cholesterol level, associated with a diminished DPI, is prognostic of a poor outcome for CAPD patients.

Adult↗

Permanent neuropsychological impairment after recurrent episodes of severe hypoglycaemia in man.

Seventeen Type 1 (insulin-dependent) diabetic patients with a history of recurrent and severe hypoglycaemia and Type 1 diabetic patients with no severe hypoglycaemia were compared as regarded performances in tests of neuropsychological functioning. To test the hypothesis that recurrent severe hypoglycaemia gives rise to permanent cognitive impairment, the study group was selected among those patients who had met with repeated attacks over the last three years or more as identified by a questionnaire among almost 600 insulin-treated diabetic patients. The comparison group without known severe reactions were comparable to the study group with respect to type of diabetes, sex, age, age at onset, duration of diabetes, socio-economic parameters, and prevalence of neuropathy and retinopathy. The results indicate that Type 1 diabetic patients with recurrent severe hypoglycaemia scored lower than those without severe hypoglycaemia in tests of motor ability, short-term and associative memory and visuospatial tasks assessing ability in general problem-solving. Type 1 diabetic patients with severe hypoglycaemia also displayed a higher frequency of perspective reversals suggesting frontal-lobe involvement. These data can be interpreted in two ways. One interpretation implies that the cognitive impairment of Type 1 diabetic patients with severe hypoglycaemia reflects a selection factor, the other that recurrent episodes of severe hypoglycaemia result in permanent cognitive impairment.

Cognition↗

Assessment of a clinical scoring system for detection of immunodeficiency in children with recurrent infections.

From January, 1982, to July, 1990, 51 children with recurrent infections were investigated for immunodeficiency in this department by testing neutrophil function, lymphocyte subsets and serum immunoglobulin and complement concentrations. The prevalence of immune dysfunction within the group was 39% (20 of 51). A previously described clinical scoring system, which aims to identify children with a history of recurrent infection who merit investigation for immunodeficiency was also applied to all 51 children. The scoring system identified only 55% (11 of 20) of those with laboratory-proved immunodeficiency and had a false negative rate of 45% (9 of 20). This latter group included 2 children with severe combined immunodeficiency and 1 with hypogammaglobulinemia, diagnoses that one cannot afford to miss. The system was not sufficiently sensitive to be of use in deciding which child to test for immunodeficiency.

Adolescent↗

Determinants of handicap after stroke: the North East Melbourne Stroke Incidence Study (NEMESIS).

BACKGROUND AND PURPOSE: Handicap, although more relevant to the patient than impairment or disability, has received little attention in people with stroke. The aim of this study was to identify, in an unselected population, factors determining handicap at 2 years after stroke. METHODS: All first-ever cases of stroke in a population of 306 631 over a 1-year period were assessed. Stroke severity, comorbidity, and demographic information was recorded. Among survivors, 2-year poststroke handicap was assessed with the London Handicap Scale. Disability, physical impairment, depression, anxiety, living arrangements, and recurrent stroke at 2 years were documented. If necessary, proxy assessments were obtained, except for mood. Linear regression analyses were performed to identify factors independently associated with handicap. First, all assessments (proxy and nonproxy) were examined; then, the nonproxy assessments were used to examine the effects of mood. RESULTS: Of 266 patients with incident stroke who were alive at 2 years, 226 (85%) were assessed. Significant determinants of handicap on univariable analysis were age, female sex, socioeconomic status, alcohol intake, stroke subtype, initial stroke severity; 2-year physical impairment, disability, depression and anxiety scores; institutionalization; and recurrent stroke. On multivariable analysis, the independent determinants of handicap were age and 2-year physical impairment and disability. In analysis restricted to nonproxy data, depression and anxiety were also independently associated with handicap. CONCLUSIONS: Age, concurrent disability, and physical impairment were more important determinants of handicap than other demographic factors or initial stroke severity. Because depression and anxiety were independently associated with handicap, their treatment may potentially reduce handicap in stroke patients.

Adult↗

Evaluation of cisplatin in combination with a biologic response modifier in a murine mammary carcinoma model.

The purpose of this study was to determine the efficacy of intracavitary cisplatin against local regrowth and metastasis after resection of a murine mammary carcinoma and the ability of a biologic response modifier (Virulizin) to enhance chemotherapy. C3H-HeJ mice were injected with Gollin-B tumor cells. Once growth reached 8 mm, tumors underwent marginal resection and the mice were assigned randomly to intraperitoneal (i.p.) cisplatin, Virulizin, a controlled release cisplatin-impregnated sponge (OPLA-Pt), a combination of treatments or no treatment and were evaluated for local regrowth, metastasis, and toxicity at 14 or 60 days after surgery. A possible beneficial interaction was seen between OPLA-Pt and Virulizin at 14 days. All cisplatin groups had significant advantages over controls in all variables measured with OPLA-Pt displaying significant advantages over i.p. cisplatin in local recurrence rate, tumor score, survival time, and delay in regrowth at 60 days. No toxicity related to either cisplatin or Virulizin was observed.

Adenocarcinoma↗

Hypofractionated external beam radiotherapy as retreatment for symptomatic non-small-cell lung carcinoma: an effective treatment?

PURPOSE: To evaluate prospectively the efficacy, toxicity, and duration of the palliative effect of retreatment with external beam radiotherapy in symptomatic patients with recurrent non-small-cell lung cancer. METHODS AND MATERIALS: Twenty-eight symptomatic patients with local recurrence of non-small-cell lung cancer underwent repeated treatment after previous radiotherapy (equivalent dose, 46-60 Gy). Reirradiation consisted of two fractions of 8 Gy on Days 1 and 8 with two opposed beams using 6-18-MV photon beams at the site of pulmonary recurrence. The physician scored symptom resolution. RESULTS: Relief of hemoptysis and superior vena cava syndrome could be obtained in all assessable cases (100%). Treatment was less effective for coughing (67%) and dyspnea (35%). The overall median duration of this palliative effect was 4 months. Palliation in almost all patients lasted more than one-half of their remaining life span. The Karnofsky performance score improved in 45% of assessable cases. One patient had Grade 2 esophagitis. Complications consisted of tumor-related fatal hemoptysis in 5 patients (17%) and 1 death from bronchoesophageal fistula (4%). CONCLUSION: External beam hypofractionated reirradiation can be effective as a palliative treatment for local complaints in non-small-cell lung cancer. The complication rate of reirradiation was acceptably low.

Aged↗

The MACIS score predicts the clinical course of papillary thyroid carcinoma in children and adolescents.

MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) scores are employed to predict mortality for papillary thyroid carcinoma (PTC) in adults. However, this system has not been validated in children and adolescents. We hypothesized that MACIS scores would correlate with recurrent and persistent disease in children. Patients with PTC (n = 48) were divided into those with aggressive (invasive, metastasic, recurrent or persistent disease) or indolent (lacking these features) disease. Those with aggressive PTC (n = 11) had average MACIS score = 5.2 +/- 1.3, compared to 3.7 +/- 0.4 in patients with indolent disease (n = 37, p < 0.0005). A cutoff score of 4.0 provides a PPV of 29% and NPV of 94% in predicting recurrence, and a PPV of 43% and NPV of 91% in predicting persistent disease. MACIS scores may be useful in predicting outcome in the pediatric population.

Adolescent↗

Prediction of recurrence and prognosis in patients with hepatocellular carcinoma after resection by use of CLIP score.

AIM: The survival time of patients with hepatocellular carcinoma (HCC) after resection is hard to predict. Both residual liver function and tumor extension factors should be considered. A new scoring system has recently been proposed by the Cancer of the Liver Italian Program (CLIP). CLIP score was confirmed to be one of the best ways to stage patients with HCC. To our knowledge, however, the literature concerning the correlation between CLIP score and prognosis for patients with HCC after resection was not published. The aim of this study is to evaluate the recurrence and prognostic value of CLIP score for the patients with HCC after resection. METHODS: A retrospective survey was carried out in 174 patients undergoing resection of HCC from January 1986 to June 1998. Six patients who died in the hospital after operation and 11 patients with the recurrence of the disease were excluded at 1 month after hepatectomy. By the end of June 2001, 4 patients were lost and 153 patients with curative resection have been followed up for at least three years. Among 153 patients, 115 developed intrahepatic recurrence and 10 developed extrahepatic recurrence, whereas the other 28 remained free of recurrence. Recurrences were classified into early (< or =3 year) and late (>3 year) recurrence. The CLIP score included the parameters involved in the Child-Pugh stage (0-2), plus macroscopic tumor morphology (0-2), AFP levels (0-1), and the presence or absence of portal thrombosis (0-1). By contrast, portal vein thrombosis was defined as the presence of tumor emboli within vascular channel analyzed by microscopic examination in this study. Risk factors for recurrence and prognostic factors for survival in each group were analyzed by the chi-square test, the Kaplan-Meier estimation and the COX proportional hazards model respectively. RESULTS: The 1-, 3-, 5-, 7-,and 10-year disease-free survival rates after curative resection of HCC were 57.2%, 28.3%, 23.5%, 18.8%, and 17.8%, respectively. Median survival time was 28, 10, 4, and 5 mo for CLIP score 0, 1, 2, 3, and 4 to 5, respectively. Early and late recurrence developed in 109 patients and 16 patients respectively. By the chi-square test, tumor size, microsatellite, venous invasion, tumor type (uninodular, multinodular, massive), tumor extension (< or = or >50% of liver parenchyma replaced by tumor), TNM stage, CLIP score, and resection margin were the risk factors for early recurrence, whereas CLIP score and Child-Pugh stage were significant risk factors for late recurrence. In univariate survival analysis, Child-Pugh stages, resection margin, tumor size, microsatellite, venous invasion, tumor type, tumor extension, TNM stages, and CLIP score were associated with prognosis. The multivariate analysis by COX proportional hazards model showed that the independent predictive factors of survival were resection margins and TNM stages. CONCLUSION: CLIP score has displayed a unique superiority in predicting the tumor early and late recurrence and prognosis in the patients with HCC after resection.

Adolescent↗

The high-risk group in early glottic carcinoma.

Classification of glottic squamous cell carcinoma according to Jakobsson's grading system with the use of eight different microscopic measurement of the tumor seems to be important clinically. In this pilot study comprising 31 cases of small glottic squamous cell carcinoma (T1A Union Internationale Contre le Cancer 1972), however, a distinct correlation between high total malignancy score and local recurrent tumor growth is absent.

Carcinoma, Squamous Cell↗

Repair of vaginal vault prolapse and pelvic floor relaxation using polypropylene mesh.

AIMS: The sacrouterine ligament/cardinal (SULC) complex and prerectal fascia attach at the perineal body, forming a single support unit preventing levator descent. Many patients with vault prolapse have levator descent and widening of the hiatus. Existing transvaginal procedures do not address pelvic floor descent. We describe a technique utilizing polypropylene mesh to repair pelvic floor relaxation and prevent levator descent, along with restoration of the SULC complex in vaginal vault repair. MATERIALS AND METHODS: We prospectively evaluated 50 patients who had a transvaginal mesh vault/posterior wall reconstruction. A T-shaped soft prolene mesh is prepared fixing the two arms of the mesh and recreating the SULC complex in support of the cuff. The vertical segment of the mesh is transferred over the prerectal fascia and secured to the pelvic floor musculature. The rectocele is repaired incorporating the mesh distally preventing pelvic floor descent. Surgical outcome was determined by patient self-assessment including quality of life (QoL) measure as well as pelvic examination using POP-Q staging. RESULTS: Mean age was 67 years. Mean follow-up was 6 months (range 3-12). There were no intraoperative complications. There have been two apical (4%) recurrences. Mean QoL score postoperatively on a 0-6 scale was 0.74 (0 = delighted, 1 = pleased). Pelvic floor descent has been repaired on all patients. Postoperative POP-Q reveals restoration of normal anatomy. CONCLUSIONS: We report a new technique that recreates the SULC complex in support of the vaginal vault with the aid of prolene mesh. It is the first transvaginal procedure described to reconstruct the pelvic floor in attempt to prevent pelvic floor descent.

Adult↗

Results of lateral internal sphincterotomy for chronic anal fissure with particular reference to quality of life.

PURPOSE: The aim of this study was to investigate the effects of lateral internal sphincterotomy on quality of life in patients with chronic anal fissure using the Gastrointestinal Quality of Life Index and the Fecal Incontinence Quality of Life Scale. METHODS: Adult patients with chronic anal fissure underwent lateral internal sphincterotomy with the open technique. Two hundred forty-four patients completed the Gastrointestinal Quality of Life Index questionnaire at admission and at 12 months postoperatively. The Fecal Incontinence Severity Index score was calculated preoperatively and at 2 and 12 months postoperatively. The Fecal Incontinence Quality of Life Scale was administered to any patient who had a Fecal Incontinence Severity Index score greater than 0 at 12 months postoperatively. RESULTS: The mean preoperative Gastrointestinal Quality of Life Index score was 118.34 +/- 6.33, which developed to 140.74 +/- 2.38 postoperatively (P< 0.001). At the two-month follow-up, 18 patients (7.38 percent) had a Fecal Incontinence Severity Index score greater than 0. By 12 months, the number of patients with Fecal Incontinence Severity Index score greater than 0 was reduced to seven (2.87 percent). These seven patients had a Gastrointestinal Quality of Life Index score similar to that of the group with postoperative Fecal Incontinence Severity Index score of 0, and only three patients (1.22 percent) had evident deterioration in the Fecal Incontinence Quality of Life Scale. The 12-month total Gastrointestinal Quality of Life Index score of the three patients who developed anal abscess/fistula after sphincterotomy (139.33 +/- 3.21) was similar to the Gastrointestinal Quality of Life Index score of those without complications. However, the Gastrointestinal Quality of Life Index score of the recurrent cases (111.53 +/- 3.53) was apparently low. CONCLUSION: The gastrointestinal quality of life improved significantly following lateral internal sphincterotomy, regardless of the surgical complications or postoperative disturbances of continence. Only 1.2 percent of the patients experienced deterioration in Fecal Incontinence Quality of Life Scale.

Adolescent↗