Intraarterial chemoembolisation with lipiodol and epirubicin in hepatocellular cancer--improved survival in some patients?

BACKGROUND AND AIMS: Arterial chemoembolisation with lipiodol and a cytotoxic drug is reported to give equivocal results in irresectable primary hepatocellular cancer (HCC). In order to further elucidate the possible response to this treatment, we analysed the results of all patients with irresectable HCC treated with chemoembolisation at our hospital. MATERIAL AND METHODS: 58 consecutive patients with HCC were treated with lipiodolepirubicin chemoembolisation between February 1988 - October 1994 and followed until death or October 1998. RESULTS: The average survival was 11.7 months and median survival was 6 months. 17 patients had only one treatment mostly due to death within 6 weeks after the first treatment. Patients with an open portal system at inclusion (50% of all) were found to have significantly increased survival after 6 and 12 months compared to those with portal obstruction. The subgroup of patients displaying a decrease in tumour size as judged by repeated CT scan 6 months after inclusion had significantly increased survival; all survived more than 12 months (median survival 30 months). CONCLUSIONS: Chemoembolisation with lipiodol-epirubicin may have an impact on survival on selected patients with irresectable hepatocellular cancer. The treatment may justifiably be offered patients with an open portal venous system and without liver failure.     

Intravesical combined chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin is not indicated for superficial bladder cancer.

PURPOSE: The short-term effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) administered repeatedly for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 24 patients aged a median of 70 years between March 1996 and February 1999, and were compared with those of BCG monotherapy in 50 patients from March 1990 to February 1999. PATIENTS AND METHODS: The patients underwent intravesical instillation of the Tokyo strain BCG with or without epirubicin after transurethral resection (TUR) of bladder cancer. For the combined treatment, at 1-2 weeks after TUR, epirubicin (40 mg) and BCG (80 mg) were istilled into the bladder by turns once a week for 12 weeks. For the group receiving only BCG, 80-mg instillations were done with the same schedule. Thereafter, the patients were followed by cystoscopy and urinary cytology every 3 months for up to 3 years after intravesical therapy. RESULTS AND CONCLUSIONS: At 2 years after treatment, the simple recurrence rate was 26.1% (6/23) in patients with chemoimmunotherapy and 32.0% (16/50) in BCG-treated patients. Adverse reactions, including increased frequency of urination, urgency and miction pain, were observed in 18 patients (85.7%) undergoing chemoimmunotherapy and 58.0% undergoing BCG monotherapy. One patient receiving chemoimmunotherapy was withdrawn from treatment because of symptoms of severe bladder irritation due to the instillation. Intravesical chemoimmunotherapy using epirubicin and BCG was finally found to be inferior in comparison with BCG monotherapy for the prophylaxis of recurrence of superficial bladder cancer.     

A multicenter phase I–II study of docetaxel plus epirubicin plus bevacizumab as first-line treatment in women with HER2-negative metastatic breast cancer

PurposeTo assess the efficacy and toxicity of docetaxel (D) plus epirubicin (E) in combination with bevacizumab (B) [DEB regimen] as front-line treatment in patients with metastatic breast cancer (MBC).Patients and methodsWomen with previously untreated HER2-negative MBC received B (15 mg/kg), E (75 mg/m²) and D (75 mg/m²) with prophylactic G-CSF support every 3 weeks (q3w) for up to 9 cycles followed by B (15 mg/kg q3w) until disease progression. Primary endpoint was the overall response rate (ORR). Circulating tumor cells (CTCs) were evaluated using the CellSearch system at different time points during therapy.ResultsEighty-three women were enrolled with median age 62 years, performance status 0–1 in 93%, triple negative disease in 12% and liver metastases in 47%. In an intention to treat analysis, complete response was achieved in 13 (15.7%) and partial response in 42 (50.6%) (overall response rate 66.3%; 95% CI 56.09–76.44%). The median time to progression was 20.1 months and the 1-year overall survival rate 82.3%. Grade 3–4 neutropenia occurred in 37%, febrile neutropenia in 10%, anemia in 4%, thrombocytopenia in 2% and diarrhea in 2% of patients. There were two deaths possibly related to study treatment (sigmoid perforation n = 1; sudden death n = 1). Moreover, one patient developed pulmonary embolism and another one myocardial infarction while on treatment. Although DEB administration significantly reduced the proportion of patients presenting CTCs, the detection of ≥5 or ≥1 CTCs before treatment initiation was significantly associated with worse progression-free survival (p = 0.001 and p = 0.004) and overall survival (p = 0.001 and p = 0.027), respectively.ConclusionsThe DEB regimen is a very active but also potentially toxic combination in MBC. Detection of CTCs before treatment is associated with worse outcome.Clinicaltrials.govNCT00705315     

Thrombolytic Treatment with Brinase® of Dogs with Experimental Pulmonary Embolism

This study evaluates the occurrence of various risk indicators, with particular emphasis on serum lipids one year after a coronary event (development of acute mycoardial infarction (AMI); exposure to either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA), prior to and after presentation of the main results from the 4S study. Patients under 70 years of age either hospitalized for AMI or undergoing CABG or PTCA at Sahlgrenska University Hospital in Göteborg were evaluated one year after the event. Patients who had an event during the period January 1, 1993 until December 31, 1993 were evaluated one year later (Period I) and those who had an event during the period September 1, 1995 until August 31, 1996 were evaluated one year thereafter (Period II). In total, 293 patients were evaluated during Period I and 284 during Period II. Mean total serum cholesterol levels fell from 6.2 mmol/l during Period I to 5.3 mmol/l during Period II (p     

Pregnancy in women with Fowler’s syndrome treated with sacral neuromodulation

Introduction and hypothesis

Our aim was to determine the impact of pregnancy on sacral neuromodulation (SNM) and vice versa in patients with Fowler’s syndrome (FS), which is typified by chronic urinary retention (CUR).

Methods

We performed a retrospective study of pregnancy in patients with FS who underwent a two-stage SNM implantation. Data were obtained using a standard questionnaire and clinical interview.

Results

There were a total of ten patients with 13 pregnancies. The SNM was switched off in ten of the 13 pregnancies, with CUR recurring in nine of the ten pregnancies and recurrent urinary tract infections (UTI) occurring in four of these pregnancies (more than three UTI in the pregnancy). Those in whom the device was left on continued to void normally. One woman had a first trimester miscarriage, eight pregnancies went to term, and four deliveries were premature. Caesarean section was performed in eight pregnancies for obstetric reasons. Four pregnancies resulted in a vaginal delivery. There were no congenital anomalies reported. Following delivery, four of nine women experienced dysfunction of their SNM device when it was switched back on.

Conclusion

Turing off the SNM during pregnancy results in recurrence of CUR, with an increased risk of recurrent UTI associated with preterm delivery. This did not impact foetal well-being. The option of keeping the SNM on during pregnancy should therefore be considered, and as caesarean section affects the SNM device, we advise that caesarean section should only be performed for obstetric reasons.     

Dyslipidemia in children with CKD: should we treat with statins?

Dyslipidemia has been shown to be a risk factor for increased cardiovascular morbidity and mortality in adult patients with chronic kidney disease (CKD) stages 2–4. In patients on dialysis, a paradoxical correlation has been found between low cholesterol values and increased mortality rates. No data exist in children. Treatment with statins has been convincingly shown to both reduce blood lipid levels and mortality rates from cardiovascular disease in adult patients in CKD stages 2–4. There is no strong literature support for treating patients on dialysis or after having had a transplant. Data on benefits of statin therapy do not exist in children with CKD. There are many differences between adult and paediatric kidney patients, and I caution on extrapolating the findings in adult patients to children. Studies are thus needed to evaluate the benefits and potential problems of statin treatment in children with CKD.     

Treatment of children with Henoch-Schönlein purpura nephritis with mycophenolate mofetil

Background

Henoch–Schönlein purpura (HSP) can progress to Henoch–Schönlein purpura nephritis (HSPN), and the most effective management remains unclear. Our aim was to evaluate the efficacy of mycophenolate mofetil (MMF) for treating pediatric patients with HSPN and nephrotic-range proteinuria.

Methods

Twelve children, seven boys and five girls, mean age 8.33 (range 6–12) years at the time of HSPN diagnosis with nephrotic-range proteinuria, were treated with MMF. All patients failed steroid treatment, and mean proteinuria at the time of MMF initiation was 5.6 g/d. MMF dosage ranged from 20 to 25 mg/kg per day. Patients also received an angiotensin-converting enzyme inhibitor (cliazapril) at MMF initiation. Mean follow-up was 3.9 (range 2.3–5.5) years.

Results

All patients responded to MMF at a mean of 2.5 (range 1–4 months). Among the 12 patients, MMF was administered for 10 months in five, 12 months in six, and 15 months in one. At last follow-up, all patients had negative proteinuria and normal renal function, and no relapses were noted. No serious adverse effects of MMF were noted in any patient.

Conclusion

MMF is useful for treating pediatric patients with HSPN and nephrotic-range proteinuria.

     

Perioperative Coagulation Changes with Gastric Bypass: association with venous thrombosis?

Blood coagulation protein analyses were obtained before, during and after Roux-Y gastric bypass in 82 patients to observe the individual perioperative changes indicative of clot formation and fibrinolysis. Pneumatic compression devices were placed on the legs during this time in order to provide deep venous thrombosis (DVT) prophylaxis, and non-invasive venous thrombosis detection studies were performed before and after operation. No occasions of DVT or pulmonary emboli were detected postoperatively. Preoperative balanced ratios of antithrombin III/plasminogen were maintained intraoperatively and were increased postoperatively, reflecting on-going fibrinolysis. Changes in alpha-2 antiplasmin confirmed this interpretation. Patients subdivided into super- vs morbid obese groups showed less plasminogen eduction and a lower protein ratio during and after operation, and less antiplasmin consumption intraoperatively, in the heavier group. A linear regression analysis of excess weight on the protein ratio also showed lower ratios in the heavier patients. However, calf or thigh leg circumferences were not different between super- and morbid obese patients. These results suggest that leg pneumatic compression should be as effective but the immobility of super-obese patients may contribute to perioperative hypofibrinolysis and perhaps make them more susceptible to DVT and pulmonary embolism.     

Who's Listening? Experiences of Women with Breast Cancer in Communicating with Physicians

The purpose of this qualitative study was to describe communication behaviors and attitudes of physicians that were most important to women living with breast cancer. Two focus group sessions were conducted, 1 month apart, involving 15 women who were members of a community-based breast cancer support group in Vancouver, British Columbia, Canada. Group dialogue was audiotaped, and notes were taken at each session by the coinvestigators, also members of the support group. Audiotapes, coinvestigators' written notes from the two focus group sessions, and the written homework assignments were used in the qualitative data analysis. Conceptual themes were identified and grouped to discern patterns within the data. The women were asked the following: (a) What were the most helpful things your doctor said or did at the time of your diagnosis? (b) What does a good intervention feel or look like? They were then asked to describe behaviors and attitudes they would like to influence in medical students who might later be communicating with women facing a diagnosis of breast cancer and to indicate which behaviors and attitudes they felt were most important. Women's positive experiences with physicians were characterized by communication based on active listening, awareness of the women's knowledge of their illness, honesty, and partnership. Physicians who showed interest in their patients as persons and who used touch to communicate caring were perceived as supportive communicators. Not surprisingly, there were similarities between the participants' positive experiences with their own physicians and the behaviors and attitudes desired in future physicians. Once again, “listening” was ranked as most important, followed by willingness to discern the individual patient's knowledge level.     

Breast cancer in a male with ankylosing spondylitis treated with TNFα antagonists

A 72-year-old male with a 4-year history of TNFα antagonist therapy (infliximab and etanercept) for ankylosing spondylitis was diagnosed with breast cancer. He had a family history of breast cancer. The low incidence and considerable severity of breast cancer in males, genetic risk factors, and potential role for TNFα antagonist therapy are discussed.     

Does Charlson-comorbidity index correlate with short-term outcome in patients with gastric cancer?

OBJECTIVES: Because of the high prevalence of coexisting medical conditions in patients with gastrointestinal cancer, clinical investigators often need to adjust for comorbidity when assessing the effect of comorbidity on patient outcome. Comorbidity in cancer has been shown to be a major determinant in treatment selection and survival. However, none of the comorbidity studies in patients with gastric cancer reported in the literature have been performed using the Charlson comorbidity index. The purpose of this study was to examine the applicability of the CCI and usefulness of the CCI as a predictor in patients with gastric cancer and to examine whether it correlates with short- term outcome in these patients. METHOD: Study design was a prospective study. The study population was drawn from our department and included 139 patients who underwent curative treatment of gastric cancer between 1.1.1997 and 31.12.2001. All patients were staged by the CCI for comorbidity and divided into three groups based on the comorbidity severity staging. Group 1 included patients with no comorbidity, group 2 included those with low-level comorbidity and group 3 those with severe comorbidity. Outcomes were compared based on these divisions performing uni- and multivariate analysis. RESULTS: 35 patients (25.2 %) had no, 55 (39.6 %) low and 39 (35.2 %) severe comorbidity. 28.8 % of patients showed no or mild, 14.4 % moderate and 14.4 % of patients severe postoperative complications and 5.8 % died in hospital postoperatively. 30-day-mortality was 3.6 % (n = 5). There was no statistical significant correlation between CCI and occurrence of postoperative complications, severity of postoperative course and postoperative stay in hospital. In multivariate analysis only age was an independent factor for postoperative course. CONCLUSION: The method of classifying comorbidity by CCI provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies and in outcomes research from administrative databases. In gastric cancer, however, the CCI was found not to be a valid prognostic indicator.     

Histologically proven hepatic steatosis associates with lower testosterone levels in men with obesity

Men with obesity often present with low testosterone(T)and sex hormone-binding globulin(SHBG)levels.Several mechanisms for this have been proposed,but as SHBG is secreted by hepatocytes and sex steroids undergo hepatic metabolization,this study investigates whether severity and histological components of nonalcoholic fatty liver disease(NAFLD)are associated with sex steroid levels in obese men.This cross-sectional study included 80 obese men(age:46±11 years;body mass index:42.2±5.5 kg m^-2).Serum levels of total T and estradiol(E.)were measured using liquid chromatography coupled with tandem mass spectroscopy(LC/MS-MS)and SHBG and gonadotropins by immunoassay.Liver biopsies were evaluated using Steatosis.Activity,and Fibrosis scoring.Participants with steatohepatitis had similar median(1st quartile-3rd quartile)total T levels(7.6[5.0-11.0]nmol l^-1 vs 8.2[7.2-10.9]nmol l^-1;P=0.147),lower calculated free T(cFT)levels(148.9[122.9-188.8]pmol 1-1 s 199.5[157.3-237.6] pmol l^-1;P=0.006),and higher free E.T ratios(10.0[6.4-13.9]×10^-3 vs 7.1[5.7-10.7]×10^-3;P=0.026)compared to men with only nonalcoholic fatty liver.Among the histological components of NAFLD.only steatosis was independently associated with total T(r=-0.331.P=0.003)and cFT levels(r=-0.255.P=0.025).Obese men with.steatohepatitis have even lower cFT levels compared to those without,an association mainly driven by grade of steatosis.Whether this reflects a subgroup of men with a more severe obesity-related phenotype or results from direct relations between hepatic steatosis and sex steroid metabolism needs further investigation.