Poor Predictive Factors Research Articles

Carcinomatosis matters: clinical outcomes and prognostic factors for clinical success of stent placement in malignant gastric outlet obstruction

Although carcinomatosis is not a contraindication to stenting in selected patients with malignant gastric outlet obstruction (GOO), associate factors for clinical success rate of self-expandable metallic stent (SEMS) placement in GOO patients with carcinomatosis have not been fully characterized. We analyzed a total 228 patients who were scheduled for SEMS placement for malignant GOO in tertiary-care academic medical center. All patients were treated with an uncovered or covered SEMS by using the over-the-wire placement procedure. We retrospectively evaluated clinical outcomes of SEMS placement. Technical success was achieved in all patients. Patients were categorized into two groups according to the presence of carcinomatosis. Clinical success rates of patients without carcinomatosis group and with carcinomatosis group were 93.9 % (92 of 98) and 80.8 % (105 of 130), respectively (P = 0.004). In subgroup analysis of patients with carcinomatosis, the clinical success rate was lower in patients with ascites (64.8 %) than in those without ascites (92.1 %, P < 0.001). Multivariate logistic regression model revealed that carcinomatosis without ascites did not decrease clinical success rate compared with absence of carcinomatosis; meanwhile, carcinomatosis with ascites showed lower clinical success rates compared with absence of carcinomatosis (adjusted odds ratio 0.163, 95 % confidence interval 0.058-0.461). In addition, poor performance status [Eastern Cooperative Oncology Group (ECOG) status ≥ 3, adjusted odds ratio 0.178, 95 % confidence interval 0.078-0.409] was also an independent poor predictive factor for clinical success of SEMS placement. In palliation for malignant GOO, the status of carcinomatosis with ascites and poor performance status (ECOG status ≥ 3) are significant predictive factors for poor clinical success of SEMS placement.

Predictive factors of solid food intake in patients with malignant gastric outlet obstruction receiving self‐expandable metallic stents for palliation

As for self-expandable metallic stents (SEMS) for malignant gastric outlet obstruction (GOO), some predictive factors of stent patency have been reported, although re-canalization of GOO by SEMS does not necessarily lead to favorable food intake. Therefore, we analyzed the predictive factors of oral food intake following SEMS placement. A total of 97 consecutive patients in whom SEMS were placed for malignant GOO in five hospitals were included in this retrospective study. Clinical outcomes and predictive factors influencing solid food intake were analyzed. The technical and clinical success rates were 97.9% and 87.6%, respectively. The mean gastric outlet obstruction scoring system (GOOSS) improved from 0.39 to 2.24 after SEMS placement (P<0.01). The median eating period was 2.1 months (95% CI, 1.1-3.0 months), and the median survival time was 3.1 months (95% CI, 2.0-4.2 months). A Karnofsky performance status of ≤ 50 (odds ratio, 3.65; 95% CI, 1.17-13.1; P=0.03) and ascites (odds ratio, 3.28; 95% CI, 1.23-9.05; P=0.02) were identified as statistically significant independent poor predictive factors of solid food intake. SEMS is an effective treatment for patients with malignant GOO. Ascites and a poor performance status were poor predictive factors of solid food intake.

The Use of Anti-Human T Lymphocyte Porcine Immunoglobulin and Cyclosporine A to Treat Patients with Acquired Severe Aplastic Anemia

Objective: To evaluate the treatment efficacy and tolerance of anti-human T lymphocyte porcine immunoglobulin (p-ALG) plus cyclosporine A (CsA) in acquired severe aplastic anemia (SAA). Method: Forty-eight SAA patients [31 males and 17 females; 17 with very SAA (VSAA)] were treated with p-ALG plus CsA and were analyzed retrospectively according to early mortality, response rate and quality, survival rate, toxicity, and complications. They were stratified further by gender, age, disease severity, interval from diagnosis to treatment, and preexisting infections. Result: The median age was 28 years (range 13–64). The interval from diagnosis to treatment was 45 days. The median neutrophil count was 0.178 × 10⁹/l. The overall response was 83.3% (54.2% complete and 29.2% partial) with a 90-day median time (range 23–380), and 10.4% died of infection within 30 days. The 1.5-year survival was 87.5%. vSAA patients had less response, a higher early mortality, and less survival (64.7, 29.4, 51.8%) compared to SAA patients (93.5, 0, and 100%, respectively; p < 0.05). Groups with different age, gender, intervals between diagnosis and treatment, and preexisting infections had the same response. Mild toxicities were observed. Conclusion: p-ALG plus CsA is a reliable and well-tolerated treatment for SAA, and it has the great advantage of a much lower cost compared to horse/rabbit ATG. VSAA was a poor predictive factor for the response rate.

The Achievement of a 3-Month Complete Cytogenetic Response (3-mo CCyR) to Second Generation (2nd) Tyrosine Kinase Inhibitors (TKI) Post Imatinib Failure Is the Only Predictive Factor for Event-Free (EFS) and Overall Survival (OS)

AbstractAbstract 22892nd TKIs such as dasatinib and nilotinib have shown significant activity post imatinib failure, with high rates of hematologic and cytogenetic responses. Achieving early cytogenetic response is a known major determinant of outcome in patients (pts) treated with imatinib. In a previous report from our institution, we reported that the achievement of a previous cytogenetic response to imatinib therapy is a major predictive factor in pts receiving a 2nd TKI. The aim of our study was to assess the impact of a 3-mo CCyR on EFS and OS of pts treated with 2nd TKI post imatinib failure. 123 pts with chronic phase (CP) CML after imatinib failure were treated with dasatinib (n=78) or nilotinib (n=45). Median age was 56 years (range, 21–83). Median duration of CP (CML diagnosis to start of second generation TKI) was 67 months (range, 2–268). Their best response to imatinib was complete hematologic response (CHR) only in 24%, and cytogenetic response in 63% (28% complete, 17% partial, 18% minor). The CHR rates were 87% and 84% in pts treated with dasatinib and nilotinib, respectively (p=0.75). The major cytogenetic response rates were 64% and 62% (p=0.85), and the complete cytogenetic response rates were 60% and 56% (p=0.70). The rates of cytogenetic response at 3-, 6- and 12-mo were 59%, 63% and 69% (p=0.39) and 60%, 55% and 51% (p= 0.7) in pts treated with dasatinib and nilotinib, respectively, and the rates of CCyR at these same time-points were 32%, 41% and 48% (p= 0.13) and 36%, 36% and 35% (p= 0.99), respectively. The 3-year EFS and OS rates were 53% and 84%, respectively. Factors associated with poor EFS in the univariate were older age (> 55 years), lack of any cytogenetic response to previous imatinib therapy, more than ≥90% Philadelphia-positive metaphases (Ph) at the start of 2nd TKI therapy, and lack of a 3-mo CCyR to 2nd TKI therapy. In a multivariate analysis, the lack of a 3-mo CCyR to 2nd TKI therapy (HR= 4.5; p<0.001) was selected as the only independent factor associated with poor EFS, with a 3-year EFS rates of 74% and 43% for pts with and without 3-mo CCyR, respectively. Factors associated with poor OS in the univariate analysis were older age (>55 years), increasing marrow blasts, lack of any cytogenetic response to previous imatinib therapy, and lack of a 3-mo CCyR to 2nd TKI therapy. In a multivariate analysis, only a lack of a 3-mo CCyR to 2nd TKI therapy (HR=5.4; p = 0.03) was independently associated with a lower probability of survival; the 3-year OS rates were 98% and 79% for pts with and without 3-mo CCyR, respectively.Therefore we analyzed factors that were associated with the 3-mo achievement of a CCyR. In the univariate analysis, high hemoglobin level, previous cytogenetic response to imatinib therapy, and ≤90% Ph, and increasing marrow blast% were associated with the achievement of a CCyR at 3 months of therapy with 2nd TKI. In the subsequent multivariate analysis for response, Ph% >90 and Hgb <12.0 were independent poor predictive factor for 3-mo CCyR. In conclusion, the achievement of a 3-mo CCyR is the only predictor of outcome in pts treated with 2nd TKI post imatinib failure. Pts with high tumor burden (defined Ph >90%) and anemia (Hgb< 12.0) have a low likelihood of achieving a 3-mo CCyR to 2nd TKI therapy and therefore should be offered additional options. Disclosures:Jabbour: BMS: Honoraria; Novartis: Honoraria. Cortes: Novartis: Research Funding; BMS: Consultancy; Pfizer: Consultancy, Research Funding.

Predictive Factors for Response and Outcome in Patients (pts) Treated with Second Generation Tyrosine Kinase Inhibitors (2-TKI) for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Post Imatinib Failure.

Abstract 509The availability of 2-TKIs has provided new therapeutic options for pts with CML post imatinib failure. We assessed the predictive factors of outcome of pts in CML-CP treated with 2-TKI. A total of 128 pts with CML-CP after imatinib failure treated with dasatinib (n=76) or nilotinib (n=52) were analyzed. Median age was 56 years (range, 21-83). The median duration of CP (CML diagnosis to start of 2-TKI) was 66 months (range, 2-241). Their best response to imatinib was complete hematologic response only in 33%, and cytogenetic response in 55% (23% complete, 16% partial, 15% minor). 4 pts were refractory to imatinib, 3 had unknown response, and 8 were intolerant. At the start of 2-TKI, 94 (73%) pts had active disease. 23% had clonal evolution (CE), and 73% had more than 90% Philadelphia positivity. The median follow-up time was 39 months (range, 15-61) from the start of the 2-TKI. At the time of last follow-up, 108 of the 128 pts (85%) were alive, 86 (67%) in CP on 2-TKI therapy; 17 pts had died. Responses to 2-TKI are shown in Table 1. In the univariate analysis (UA) for event-free survival (EFS), factors associated with poor EFS were splenomegaly, anemia (hemoglobin ≤12g/dL), lack of any cytogenetic response to previous imatinib therapy, ≥ 90% Philadelphia-positive (Ph+) metaphases at the start of 2-TKI therapy, nilotinib therapy, and high sokal risk score disease. In the subsequent multivariate analysis (MVA), splenomegaly, anemia (hemoglobin ≤12g/dL), lack of any cytogenetic response to previous imatinib therapy, and ≥ 90% Ph+ metaphases were selected as independent factors associated with poor EFS. Factors associated with poor overall survival (OS) in the UA were CE, performance status (PS) ≥1, and high sokal risk score at the start of 2-TKI therapy. In the MVA, only CE and a PS ≥1 were selected as independent poor prognostic factors for OS. High hemoglobin level (≥12g/dL), 0% bone marrow blasts, previous cytogenetic response to imatinib therapy, ≤90% Ph+ metaphases, and low sokal risk score were associated with the achievement of a major cytogenetic response (MCyR) by 12 months of therapy with 2-TKI in the UA. In the subsequent MVA for response, the lack of any cytogenetic response to imatinib therapy, anemia (hemoglobin ≤12g/dL) and ≥90% Ph+ metaphases at the start of 2-TKI therapy were selected as poor predictive factors for 12-month MCyR. Pts with 0, 1, 2, or 3 adverse factors had a 12-month probability of achieving a MCyR with 2-TKI therapy of 85%, 79%, 35%, and 14%, respectively. Based on these findings, we developed a score model that included the factors identified as independent predictive for a MCyR by 12 months of therapy with 2-TKI. Three prognostic risk groups are proposed for the new score model: 1) low score (no adverse factors; 16% of pts), in which pts have a 12-month probability of achieving a MCyR of 85%, after therapy with 2-TKI; 2) intermediate score (1-2 adverse factors; 67% of pts), in which pts have a 12-month probability of achieving a MCyR of 56%; and 3) high score (3 adverse factors; 17% of pts), in which pts have a 12-month probability of achieving a MCyR of 14% (Table 2). This score model predicts significantly for EFS (p=0.003) with a trend for OS (p=0.18). In conclusion, the outcome of pts post imatinib failure treated with 2-TKIs is dependent on previous cytogenetic response to imatinib, absence of anemia, and disease burden at the start of therapy. Pts with no previous cytogenetic response to imatinib therapy with anemia and high disease burden have a low likelihood of responding to 2-TKI with poor EFS, and therefore should be offered alternative treatment options.Table 1Response to second generation TKIsParameter%ResponseOverallDasatinibNilotinibp-valuen=128n=76n=52CHR8386780.34Cytogenetic response7070710.86Major5958600.85Complete5253520.9436-month EFS5864480.0336-month OS8285780.27CHR = complete hematologic response; EFS = event-free survival; OS = overall survival.Table 2Predicted outcome by number of risk factors (No cytogenetic response on imatinib, Hgb<12, %Ph>90 at the 2-TKI)Risk (# risk factors)Number patients (%)MCyR 12m (%)OS 36m (%)EFS 36m (%)Low (0)20 (16)859585Intermediate (1-2)85 (67)568257High (3)21 (17)147238CG=cytogenetic; CCGR=complete cytogenetic response; m=month; OS=overall survival; EFS=event-free survival; NA=not applicable. Disclosures:Jabbour:Novartis: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Kantarjian:Novartis: Research Funding; Bristol Myers Squibb : Research Funding; Wyeth: Research Funding. Wierda:Bayer: Research Funding; Sanofi Aventis: Research Funding; Abbott: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Trubion: Consultancy; Ligand: Consultancy; Genetech: Consultancy, Honoraria; Medimmune: Consultancy; Celegene: Speakers Bureau. Borthakur:Novartis: Speakers Bureau; Bristol Myers Squibb : Speakers Bureau. Rios:Novartis: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb : Consultancy, Honoraria, Speakers Bureau. Cortes:Bristol Myers Squibb: Research Funding; Novartis: Research Funding.

Outcome After Liver Transplantation for NASH Cirrhosis

Nonalcoholic steatohepatitis (NASH) associated cirrhosis is an increasing indication for liver transplant (LT). The aim of this study was to determine outcome and poor predictive factors after LT for NASH cirrhosis. We analyzed patients undergoing LT from 1997 to 2008 at a single center. NASH was diagnosed on histopathology. LT recipients with hepatitis C, alcoholic or cholestatic liver disease and cryptogenic cirrhosis acted as matched controls. Ninety-eight LT recipients were identified with NASH cirrhosis. Compared to controls, NASH patients had a higher BMI (mean 32.3 kg/m2), and were more likely to be diabetic and hypertensive. Mortality after transplant was similar between NASH patients and controls but there was a tendency for higher earlier mortality in NASH patients (30-day mortality 6.1%, 1-year mortality 21.4%). Sepsis accounted for half of all deaths in NASH patients, significantly higher than controls. NASH patients > or =60 years, BMI > or =30 kg/m2 with diabetes and hypertension (HTN) had a 50% 1-year mortality. In conclusion, patients undergoing LT for NASH cirrhosis have a similar outcome to patients undergoing LT for other indications. The combination of older age, higher BMI, diabetes and HTN are associated with poor outcome after LT. Careful consideration is warranted before offering LT to these high-risk patients.

耳下腺ｓａｌｉｖａｒｙ ｄｕｃｔ ｃａｒｃｉｎｏｍａの３例と本邦における臨床的検討

Salivary duct carcinoma (SDC) is a high-grade aggressive malignancy originating from the salivary gland, which was first described by Kleinsasser et al. in 1968. We reported here three cases of salivary duct carcinoma in the parotid gland. The first patient was a 66-year-old male, who presented with a mass in the left parotid region. The patient underwent superficial parotidectomy followed by radiotherapy. The second patient was an 85-year-old female, who presented with parapharyngeal extension. She underwent total parotidectomy with mandibulotomy and upper neck dissection. The third patient was a 76-year-old male. He underwent total parotidectomy with resection of the facial nerve and neck dissection. After surgery, he was treated with radiotherapy. These three patients were not diagnosed as having SDC before surgery and are currently alive without recurrence or metastasis despite differences in treatment. When we analyzed 61 patients in the Japanese literature, patients with SDC showed an extremely poor prognosis. Moreover, the English literature also showed a poor prognosis and predictive factors included sex, tumor size and neck lymph node metastasis. Therefore, radical surgery with neck dissection and radiotherapy followed by complete follow-up is important to treat patients with SDC.

P26.09: Is cardiomegaly diagnosed at 11–14 weeks of gestation a poor predictive diagnostic factor

P26.09: Is cardiomegaly diagnosed at 11–14 weeks of gestation a poor predictive diagnostic factor

Carcinome canalaire in situ (CCIS) chez les femmes de moins de 40 ans : une prise en charge particulière ?

Ductal carcinoma in situ of the breast (DCIS) is rare in younger women, accounting for about 4% of all cases of DCIS in France, and tends to be diagnosed by clinical findings or casually, after plastic surgery. After breast conserving treatment, young age ( less than 40) is a predictive factor of relapses in patients with DCIS. Age may serve as one more parameter that should be considered in the complex decision-making process necessary to create a treatment plan for a woman with DCIS. Breast conservative treatment (BCT) could be used if: margins are free and more than 10 mm; if DCIS size is less than 11 mm and DCIS is free of necrosis and comedocarcinoma. Mastectomy ought to be proposed in case of: multifocal DCIS, or DCIS size more than 30 mm; invaded margins after re-excision; radiotherapy contraindicated; small breasts and patient choice. Immediate breast reconstruction should be proposed for patients with all the poor predictive factors. In other cases, treatment procedure will be explained to the patient and the treatment will be chosen by the patient in consultation with the medical team (radiologist, surgeon, pathologist and oncologist). Radiotherapy with boost or hormonotherapy with tamoxifen should not be used routinely but may be proposed individually.

Postoperative prognosis in acromegaly: a role of immunohistochemical markers

The aim of the investigation was to examine the markers of tumor progression in pituitary adenomas in acromegalic patients and to study their relationship to the poor postoperative predictive factors. Case histories were analyzed in 39 arcomegalic patients undergone transphenoidal adenomectomy as the method of choice at the Endocrinology Research Center, Russian Academy of Medical Sciences. The immunohistochemical technique was used to explore Ki-67, CD31, and galectin-3 in the cells of removed adenomas. Young age, high postoperative growth hormone (GH) levels, a large adenoma, and signs of its paracellular dissemination were poor postoperative predictors. Ki-67 was present In 9 (23%) of the 39 patients, CD31 in 16 (31%), galectin-3 in 11 (28%), and prolactin in 9 (23%). The preoperative GH levels were significantly higher in patients with positive immunostaining for the potential malignancy marker galectin3 and the angiogenetic marker CD31. The cell proliferation marker Ki-67 was present only in adenomas positive for prolactin. Positive immunostaining for Ki-67 and prolactin correlated with large adenoma sizes and intracavernous extension.

Pilot study of interferon‐α–ribavirin–interleukin‐2 for treatment of nonresponder patients with severe liver disease infected by hepatitis C virus genotype 1

The aim of this randomized prospective study was to assess the efficacy and safety of a triple therapy with interferon-alpha (IFN-alpha)-ribavirin-interleukin-2 (IL-2) for the treatment of patients with genotype 1 infection and high viral load nonresponsive to primary IFN-ribavirin therapy. Twenty hepatitis C virus (HCV) genotype 1 patients with high viral load and Metavir fibrosis score >or=2 without HIV co-infection who were previously nonviral responders to standard treatment with IFN plus ribavirin were intensively re-treated with IFN-alpha2a (3 millions (M) IU every 2 days) combined with ribavirin (1000-1200 mg/day) for a 24-week period. Patients were randomized to receive four cycles of subcutaneous injection of IL-2 (3 MIU/day, 5 days a week every 3 weeks) during either the first 12 weeks (group 1, n = 10) or the last 12 weeks (group 2, n = 10) of combination therapy. At the end of triple therapy, six patients (30%) achieved a biochemical response and 4 (20%) a viral response followed by a relapse after triple therapy withdrawal. After 12 weeks of therapy, no difference in viral load was observed between the groups. The decrease in viral load in group 2 was not raised after the addition of IL-2 to IFN plus ribavirin combination therapy. No serious adverse effects were observed. In conclusion, in patients with poor predictive factors of response, the addition of IL-2 to IFN ribavirin combination therapy does not exert a favourable impact on HCV treatment.

Influence of global sperm DNA methylation on IVF results

In cases of male infertility, routine analysis for sperm characteristics is a poor predictive factor for the segmentation rate and embryo development in assisted reproductive technologies. It is assumed that epigenetic factors could have an influence on the embryo's quality. The aim of this work was to determine the relationship between sperm DNA methylation level and fertilization and pregnancy rates according to the assisted reproduction technique performed. A prospective study was undertaken. Ejaculates were obtained from men (n = 63) undergoing an assisted reproduction procedure. 5-Methylcytosine was immunostained with a polyclonal antibody and revealed by fluorescein isothiocyanate. The DNA methylation level was then quantified by flow cytometry. Sixty-three conventional IVF cycles were performed, 760 oocytes were retrieved, an average of 8.1 +/- 4.8 embryos was obtained, and 2.4 embryos were transferred. Neither the fertilization rate nor the rate of good quality embryos was correlated with the DNA methylation level (r = -0.1 and r = -0.08 respectively; not significant). When sperm DNA methylation was >555 arbitrary units, the pregnancy rate was 33.3% compared with 8.3% in the lower (<555) group (P<0.05). DNA methylation level in human sperm could represent a new approach to study the ability of sperm to lead to pregnancy in an assisted reproduction procedure, especially when sperm samples with normal characteristics are used.

Vascularites, collagénoses et tube digestif

Vasculitis, defined as a non-infectious inflammatory disorder of blood vessels, can affect vessels of any type in any organ. The gastrointestinal tract may thus also be involved. In few cases, it may first present with gastrointestinal symptoms. In some diseases, the digestive disorder can dominate the clinical presentation, and be therefore a poor predictive factor. Digestive symptoms are not specific of a disease, but they result from tissue ischemia. In systemic disorders as mixed connective tissue disease and systemic lupus erythematosus, patients may present with symptoms of gastrointestinal dysfunction such as motility disorders, caused by alterations in the connective tissue. This article reviews the various manifestations of vasculitis and connective tissue disease on the digestive system.

Predicting success after gastric bypass: the role of psychosocial and behavioral factors

Background Success after bariatric surgery requires behavioral modification. This study analyzes outcomes after Roux-en-Y gastric bypass surgery performed by a single surgeon between 1994 and 2002, and correlates preoperative factors with long-term outcome. Methods A bariatric database has been maintained since 1994. Beginning in April 1997, patients completed preoperative and annual postoperative questionnaires that collected an array of psychosocial information. We hypothesized that certain attributes are predictive of success after surgery. Results Of the 243 patients in our database, 181 enrolled after 1997. A total of 149 were seen for follow-up at 1 year. Life Experiences Survey (LES) scores and sexual satisfaction improved significantly. Perceived obesity-related health problems, motivation unrelated to social distress about obesity, a Sense of Coherence (SOC) score >110, and an LES score <−1 each independently predicted better weight loss ( P<.05). A history of sexual abuse correlated with poorer weight loss ( P<.05). Patients with more confidants, multiple previous dieting attempts, and greater anticipated postoperative diet-related stress tended toward better weight loss, but these data did not reach significance. Conclusions Intrinsic motivational factors appear to predict greater weight loss after surgery. Ongoing follow-up will help determine the utility of preoperative evaluations and the role of preoperative intervention in those with poor predictive factors.

Recours à l’hospitalisation en unité de soins intensifs après chirurgie colorectale

Objective: Intensive care units (ICU) support critically ill patients during the perioperative period. Few studies exist focusing on ICU hospitalisation after colorectal surgery. The objective of the study was to 1) detect predictive factors of mortality and length of stay in ICU after colorectal procedures, and 2) compare the autonomy status of the patients before and 30 days after their ICU stay. Patients and methods: This study followed a prospective non randomized cohort in our colorectal surgery unit. During a period of one year (January 1 st to December 31 th, 2000) 351 colorectal procedures were performed and 54 patients were admitted to ICU after surgery. For each patient, 37 parameters were collected on a standardized register. Predictive factors of mortality (30 days after the procedure) and ICU stay (up to 3 days) were studied by univariate and multivariate statistical analysis. Self autonomy before surgery and 30 days after was also investigated. Results: “Multiple-intervention” was the only independent factor influencing mortality. Both “low autonomy status before surgery” and “pulmonary comorbidity” increased the length of stay. Regarding the 48 survivors, 45 (94%) recovered the same autonomy index as in the preoperative period 30 days after the procedure. Conclusion: This study highlights the poor predictive factors influencing mortality during or after ICU stay following colorectal surgery, and emphazises two preoperative parameters increasing the length of stay up to 3 days.This should guide the informations given to the patients families. Finally, this study confirms the good quality of self-sufficiency after ICU stay even for a long time (over 3 days).

Combination of interferon and ribavirin in chronic hepatitis C: Re-treatment of nonresponders to interferon

Chronic infection with hepatitis C virus (HCV) may result in cirrhosis, liver failure, and hepatocellular carcinoma. A minority of patients have a sustained response to antiviral therapy, and nonresponders remain at risk of developing progressive liver disease. We conducted a randomized, controlled trial of therapy with the combination of interferon (IFN) and ribavirin in patients with chronic hepatitis C who had not responded to an initial course of therapy with IFN alone. A total of 124 patients were randomized to receive the combination of IFN and ribavirin for either 24 or 48 weeks and followed for an additional 24 weeks after stopping therapy. Thirty-eight treated patients (30.6%) achieved a sustained virologic response (undetectable HCV RNA at the 24-week follow-up point). This was associated with significant improvement in necroinflammatory activity noted on liver biopsy. Interestingly, there was not a statistically significant difference in response rates based on the duration of treatment; HCV genotype was the strongest predictor of a sustained response. Sustained responses were noted even in patients with poor predictive factors, including those with advanced hepatic fibrosis or cirrhosis, high levels of HCV RNA in serum, and those infected with HCV genotype 1. The study included 24 patients with normal serum alanine transaminase (ALT) values before therapy who had similar responses to those with initially elevated transaminase values. This study suggests that the combination of IFN and ribavirin is a useful modality of therapy in patients with chronic hepatitis C who did not respond to IFN alone.

Cell biological factors associated with the response of breast cancer to systemic treatment

A large number of cell biological parameters are currently available to predict the prognosis of patients with breast cancer, but it is still difficult accurately to predict the response to treatment. A valuable prognostic factor can be a poor predictive factor for response, and vice versa. High tumor levels of ER, PgR, AR and pS2 predict a relatively good response to endocrine therapy, while EGF-R positivity, HER2/neu positivity, aneuploidy, high proliferation indices and possibly high uPA levels indicate a high chance of poor response to endocrine therapy in metastatic breast cancer. With respect to chemotherapy, a high proliferation rate and H ER2/neu amplification predict a good response to therapy in metastatic disease, while MDR gene expression and possibly c-myc amplification are related to a worse response. In conclusion, the newer cell biological parameters can be used to select high and low-risk patients, type of systemic treatment, and as targets for new treatment modalities.

Relationship between preoperative status of the fibrinolytic system and occurrence of deep vein thrombosis after major abdominal surgery

This study comprised 50 patients subjected to major abdominal surgery, of which 13 developed deep vein thrombosis (DVT) according to the 125I-fibrinogen test. Plasma was sampled preoperatively, for the specific analysis of tissue plasminogen activator (t-PA) before and during venous occlusion. The recently described fast t-PA inhibitor and plasmin alpha2-antiplasmin complex (PAP) were also measured. The result of the laboratory analyses were correlated to the development of DVT. From the data obtained it is concluded that the evaluation of t-PA release during venous occlusion is a poor predictive factor for the occurrence of DVT after major abdominal surgery. The level of the t-PA inhibitor appears to be raised in these patients, but the values obtained in this material were not related to the development of postoperative DVT. Patients with elevated PAP levels, as shown previously, have a lesser tendency to develop postoperative DVT.