Capecitabine as a radiosensitizing agent in neoadjuvant treatment of locally advanced resectable rectal cancer: prospective phase II trial

Aim

To evaluate the efficacy and toxicity of preoperative chemoradiotherapy with capecitabine in locally advanced rectal cancer.

Methods

Between June 2004 and January 2005, 57 patients with operable, clinical stage II-III adenocarcinoma of the rectum entered the prospective phase II study. Radiation dose was 45 Gy (25 × 1.8 Gy). Concurrent chemotherapy with a daily dose of 1650 mg/m² capecitabine was administered orally, divided into two equal doses per day, including weekends. Patients were evaluated weekly for acute toxicity and compliance with the protocol. Surgery was scheduled 6 weeks after the completion of the chemoradiotherapy.

Results

A single female patient died after receiving 27 Gy, because of pulmonary embolism. All other patients completed the preoperative chemoradiotherapy according to the protocol and a definitive operation was performed in all but one of these patients. The complete pathological response was recorded in 5 patients (9.1%). Tumor (T), lymph nodes (N), and overall downstaging rates were 40%, 52.9%, and 49.1%, respectively. Total sphincter preservation rate was 65.5% (36 out of 55 patients) and the rate in 27 patients with tumors located within 5 cm of the anal opening was 37% (10 out of 27 patients). The most frequent side-effect of the combined therapy was dermatitis (grade 3 in 19 patients). After surgery, a single patient died due to sepsis during the early perioperative period. Nonlethal perioperative complications were recorded in 24/55 patients.

Conclusion

Preoperative chemoradiotherapy with oral capecitabine is safe and well tolerated. It has a downstaging potential and can increase the possibility for sphincter preservation surgery.Preoperative chemoradiation has become a standard part of treatment protocols in stage II and III rectal cancer. Compared to postoperative chemoradiotherapy, the advantage of preoperative application of chemotherapeutics and irradiation includes improved compliance, reduced toxicity, and downstaging of the tumor in a substantial number of patients. The latter may enhance the rate of curative surgery, permit sphincter preservation in patients with low-sited tumors, and have a positive impact on the quality of life of these patients (1).Although several innovative agents are being investigated in combination with radiotherapy, 5-fluorouracil (5-FU) in continuous infusion remains the gold standard in preoperative chemoradiotherapy schedules. The prolongation of exposure of cells to 5-FU results in improved antitumor activity, but requires prolonged infusion, usually through a vascular access port (VAP). Complications resulting from long-term venous access, such as bleeding and thrombosis, are not uncommon (2).Orally administered capecitabine (Xeloda^®, Hoffmann-La Roche Ltd, Basel, Switzerland) mimics the pharmacokinetics of continuous 5-FU infusion and makes chemoradiotherapy more patient-friendly. The mechanism of capecitabine activation, preferably in tumor cells, may further enhance its efficacy and tolerability, offering the potential for an enhanced therapeutic ratio (3-5). The use of capecitabine allows chronic dosing and, at the same time, avoids the discomfort and complications associated with prolonged intravenous infusion of 5-FU (2,6). Thus, the majority of patients prefer oral chemotherapy to 5-FU infusions (7).The aim of the present prospective phase II study was to evaluate the efficacy and toxicity of preoperative chemoradiotherapy with capecitabine in patients with locally advanced rectal cancer. The primary endpoint of the study was a pathologically determined complete remission rate of the disease, locally and regionally. Secondary outcomes were the rate of sphincter preservation in low-sited tumors, overall downstaging rate, and toxicity.     

Combination treatment with intrahepatic arterial infusion and intratumoral injection chemotherapy in patients with far-advanced hepatocellular carcinoma and arterioportal or arteriovenous shunts: preliminary results

Background/Aims

Combination treatment consisting of hepatic arterial infusion chemotherapy with epirubicin and cisplatin (HAIC-EC) and systemic infusion of low-dose 5-fluorouracil (5-FU) are sometimes effective against advanced hepatocellular carcinoma (HCC). However, there is no effective treatment for advanced HCCs with arterioportal shunts (APS) or arteriovenous shunts (AVS).

Methods

We investigated a response and adverse events of a new combination protocol of repeated HAIC-EC and percutaneous intratumoral injection chemotherapy with a mixture of recombinant interferon-gamma (IFN-γ) and 5-FU (PIC-IF) in patients with far-advanced HCCs with large APSs or AVSs.

Results

There was a complete response (CR) for the large vascular shunts in all three patients and for all tumor burdens in two patients. Significant side effects were flu-like symptoms (grade 2) and bone marrow suppression (grade 2 or 3) after each cycle, but these were well-tolerated.

Conclusions

These results suggest that the combination of HAIC-EC and PIC-IF is a new and promising approach for advanced HCC accompanied by a large APS or AVS.     

Feasibility of Sorafenib Combined with Local Radiotherapy in Advanced Hepatocellular Carcinoma

Purpose

Sorafenib is an effective systemic agent for advanced hepatocellular carcinoma. To increase its efficacy, we evaluated the feasibility and benefit of sorafenib combined with radiotherapy.

Materials and Methods

From July 2007 to July 2011, 31 patients were treated with a daily dose of 800 mg of sorafenib and radiotherapy. Among them, 13 patients who received radiotherapy on the bone metastasis were excluded. Thirteen patients received 30-54 Gy of radiotherapy on the primary tumor (primary group) and 5 patients received 30-58.4 Gy on the measurable metastatic lesions (measurable metastasis group). Tumor responses at 1 month after the completion of radiotherapy and overall survival were evaluated.

Results

The in-field response rate was 100% in the primary group and 60% in the measurable metastasis group. A decrease of more than 80% in the tumor marker α-fetoprotein was observed in 7 patients in the primary group (54%). Toxicities of grades 3-4 were hand-foot syndrome in 3 (17%) patients, duodenal bleeding in 1 (6%) patient, thrombocytopenia in 3 (17%) patients and elevation of aspartate transaminase in 1 (6%) patient. The median overall survival was 7.8 months (95% confidence interval, 3.0-12.6).

Conclusion

The combined treatment of sorafenib and radiotherapy was feasible and induced substantial tumor responses in the target lesions. The results of this study emphasize the importance of individualized approach in the management of advanced hepatocellular carcinoma and encourage the initiation of a controlled clinical trial.     

Heterogeneity of Adenosine Triphosphate-Based Chemotherapy Response Assay in Colorectal Cancer - Secondary Publication

Purpose

Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) is a well-documented and validated technology that can individualize chemotherapy for patients with lung, stomach, or breast cancer. This study explored the feasibility of ATP-CRA as a chemosensitivity test in patients with colorectal cancer.

Materials and Methods

A total of 118 patients who underwent surgical resection for colorectal adenocarcinoma were analyzed for chemosensitivity to 6 anticancer drugs using ATP-CRA. We calculated the cell death rate (CDR) by measuring intracellular ATP levels of drug-exposed cells and untreated controls.

Results

Interpretable results were available for 85.5% (118/138) of patients. The mean coefficient of variation for triplicate ATP measurements was 9.2%. The highest CDR was observed in irinotecan (34.0%) and the lowest CDR in etoposide (21.0%). Paclitaxel had the broadest range of CDR (0-86.7%) and 5-FU had the narrowest range of CDR (0-56.8%). The overall highest responsiveness was seen most prevalently in irinotecan (24.7%, 23/93 patients). Irinotecan had the greatest responsiveness in patients with well differentiated and moderately differentiated carcinoma.

Conclusion

Our study suggests that ATP-CRA could be used to identify patients with colorectal cancer who might benefit from treatment with a specific chemotherapeutic agent.     

Gemcitabine concurrent with radiation therapy for locally advanced head and neck carcinomas

Background

Management of advanced head and neck carcinoma is a challenging proposition. Presently concomitant chemo-irradiation has become the standard of care in such patients. Many chemotherapeutic drugs have shown radio-sensitising effects when used concomitantly along with radiation. The present study was carried out with the objective of assessing the feasibility and efficacy of low dose gemcitabine as radiosensitizer when used during radical radiotherapeutic management of patients with locally advanced head and neck carcinomas.

Patients and methods

From November 2000 to March 2003, Eighty histopathologically proven cases of squamous cell head and neck carcinoma were included in this trial, 40 patients were randomly assigned to receive radiotherapy alone and 40 patients to receive gemcitabine along with radiotherapy.

Results

All patients were assessable for toxicity and response. Severe mucositis (WHO level 5 reactions were observed in 67% patients in the CT/RT group vs 16% patients in the RT only group. No severe hematological toxicity was seen. The rates of complete and partial responses were 42.5% & 57.5% respectively for RT only and 62.5% &37.5%, respectively for CT/RT group. There was no significantdifference in the response rates at the end of treatment but disease free survival at three years was better in the CT/RT group (63.3% vs 20%). Nine of the 17 patients with complete response in the radiation only group developed relapse while no relapses were seen in CT/RT group.

Conclusion

In the present study the combination of gemcitabine and radiotherapy has not shown any statistical difference in locoregional control but survival advantage was seen as compared to radiotherapy alone. At the same time more mucosal and skin toxicity was encountered when Gemcitabine is given concurrently with radiation.     

Dengue in an area of the Colombian Caribbean

Background:

In Colombia, dengue is an endemic disease and the four serotypes have been reported.

Objective:

To describe the frequency and severity of dengue in an area of the Colombian Caribbean (Department of Cordoba)

Methods:

A retrospective study was conducted. Two data sources were analysed: The database from the Direction of Health in Córdoba, and clinical registers of patients diagnosed with haemorrhagic fevers and fevers of unknown origin in reference hospitals.

Results:

The mean incidence of dengue between 2003-2010 was 36.5 cases/10⁵ inhabitants (CI95%: 34.3-37.5) and adjusted for sub-reporting, could be between 178.5 and 521.6. The mean incidence of severe dengue was 4.7 cases/10⁵ inhabitants (CI95%: 4.3-5.0). Mean mortality rate due to dengue was 0.3 cases/10⁵ inhabitants. The fatality rate was below 1%. The mean total leukocyte count in patients with dengue was 6,181 mm³ (CI95%: 5,973-6,389) and with severe Dengue was 4,729 mm³ (CI95%: 4,220-5,238). The average platelet count in patients with Dengue was 118,793/mm³ (CI95%: 107,255-130,331) and in patients with Severe Dengue 77,655 (CI95%: 59,640-95,670). Both differences were statistically significant (p <0.05). The frequency of laboratories test per patient in patients with Dengue and severe Dengue were different.

Conclusion:

The department of Cordoba is a highly endemic zone of Dengue and severe Dengue in the Colombian Caribbean. Moreover, the results show significant differences between dengue and severe dengue so much in tests as in frequency of use of healthcare services.     

Induction chemotherapy with paclitaxel, ifosfamide, and cisplatin followed by concurrent chemoradiotherapy for unresectable locally advanced head and neck cancer

Objective:

Induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) for locally advanced head and neck cancer has been studied in many clinical trials. This study was conducted to determine the response rate of IC with paclitaxel, ifosfamide, and cisplatin followed by CCRT with cisplatin for this group of patients, and the effect of the entire treatment on survival and time to disease progression.

Methods:

Thirty patients with advanced and unresectable head and neck cancer were treated with 2 cycles of induction paclitaxel/ ifosfamide/ cisplatin. If the primary tumor had a complete or partial response, patients were treated with 2 more cycles of IC followed by radiotherapy 70 Gy plus 3 cycles of cisplatin. For those with less than partial response or disease progression were treated according to the discretion of the physicians.

Results:

Ninety percent of patients had stage IV disease and 40% of them had primary tumor at maxillary sinus and nasal cavity. One patient (3%) achieved complete response (CR) and 18 patients had partial responses (PR) to IC. CCRT enhanced the response rate, resulting in a total of 3 CR (10%) and 16 PR (53%) to treatment. The median time to progression was 11.5 months. The median overall survival was 27 months. The most severe hematologic toxicity occurred during IC was grade3-4 neutropenia (40%). Grade 3-4 mucositis occurred in 68% of patients during CCRT.

Conclusion:

This novel combined-modality treatment program, is toxic but feasible, and can be administered for selected patients with advanced and unresectable head and neck cancer. © 2010 Biomedical Imaging and Intervention Journal. All rights reserved.     

Adjuvant Radiotherapy Outcome of Stage I Testicular Seminoma: A Single Institution Study

Purpose

To analyze treatment outcome and side effects of adjuvant radiotherapy using radiotherapy fields and doses which have evolved over the last two decades in a single institution.

Materials and Methods

Forty-one patients received radiotherapy after orchiectomy from 1996 to 2007. At our institution, the treatment field for stage I seminoma has changed from dog-leg (DL) field prior to 2003 to paraaortic (PA) field after 2003. Fifteen patients were treated with the classic fractionation scheme of 25.5 Gy at 1.5 Gy per fraction. Other patients had been treated with modified schedules of 25.05 Gy at 1.67 Gy per fraction (n=15) and 25.2 Gy at 1.8 Gy per fraction (n=11).

Results

With a median follow-up of 112 months, the 5-year and 10-year survival rates were 100% and 96%, respectively, and 5-year and 10-year relapse-free survival rates were both 97.1%. No in-field recurrence occurred. Contralateral seminoma occurred in one patient 5 years after treatment. No grade III-IV acute toxicity occurred. An increased rate of grade 1-2 acute hematologic toxicity was found in patients with longer overall treatment times due to 1.5 Gy per fraction. The rate of grade 2 acute gastrointestinal toxicity was significantly higher with DL field than with PA field and also higher in the 1.8-Gy group than in the 1.5-Gy and 1.67-Gy groups.

Conclusion

Patients with stage I seminoma were safely treated with PA-only radiotherapy with no pelvic failure. Optimal fractionation schedule needs to be explored further in order to minimize treatment-related toxicity.     

Peginterferon alpha and ribavirin combination therapy in patients with hepatitis C virus-related liver cirrhosis

Background/Aims

Pegylated interferon (peginterferon) and ribavirin combination therapy is less effective and associated with a higher frequency of serious complications in chronic hepatitis C patients with cirrhosis than in noncirrhotic patients. This study evaluated the efficacy and tolerability of peginterferon and ribavirin treatment in patients with hepatitis C virus (HCV)-related cirrhosis.

Methods

Eighty-six patients with clinically diagnosed liver cirrhosis were treated with either peginterferon alpha-2a (n=51) or peginterferon alpha-2b (n=35) plus ribavirin. The sustained virologic response (SVR) and adverse effects were analyzed retrospectively.

Results

Of the 86 patients (55 males), 48 patients (55.8%) had HCV genotype 1 infection and 38 (44.2%) had genotype non-1 infection. The overall SVR rate was 34.9% (30/86), and the rates of SVR in the genotype 1 and non-1 patients were 20.8% (10/48) and 52.6% (20/38), respectively. The multivariate analysis revealed that having HCV genotype 1 (P=0.003) and high baseline viral load (>8.0×10⁵ IU/mL, P=0.012) were the independent predictive factors for SVR failure. In 20.9% (18/86) of the patients, treatment was not completed due to adverse events (27.8%), loss to follow-up (50.0%), and other reasons (22.2%).

Conclusions

Peginterferon and ribavirin combination therapy was relatively effective and feasible for clinically diagnosed HCV patients, especially in those with genotype non-1 infection and low baseline viral load.     

Renal function in children with congenital neurogenic bladder

AIMS:

Preservation of renal function in children with congenital neurogenic bladder is an important goal of treatment for the disease. This study analyzed the evolution of renal function in patients with congenital neurogenic bladder.

METHODS:

We reviewed the records of 58 pediatric patients with respect to the following attributes: gender, age, etiology of neurogenic bladder, reason for referral, medical/surgical management, episodes of treated urinary tract infections, urodynamics, DMSA scintigraphy, weight, height, blood pressure, glomerular filtration rate, microalbuminuria and metabolic acidosis. Statistical analysis was performed, adopting the 5% significance level.

RESULTS:

The mean age at presentation was 4.2 ± 3.5 years. Myelomeningocele was the most frequent etiology (71.4%). Recurrent urinary tract infection was the reason for referral in 82.8% of the patients. Recurrent urinary tract infections were diagnosed in 84.5% of the patients initially; 83.7% of those patients experienced improvement during follow‐up. The initial mean glomerular filtration rate was 146.7 ± 70.1 mL/1.73 m²/min, and the final mean was 193.6 ± 93.6 mL/1.73 m²/min, p  =  0.0004. Microalbuminuria was diagnosed in 54.1% of the patients initially and in 69% in the final evaluation. Metabolic acidosis was present in 19% of the patients initially and in 32.8% in the final assessment.

CONCLUSIONS:

Patient referral to a pediatric nephrologist was late. A reduction in the number of urinary tract infections was observed with adequate treatment, but microalbuminuria and metabolic acidosis occurred frequently despite adequate management.     

Anaesthetic and Obstetric challenges of morbid obesity in caesarean deliveries-a study in South-eastern Nigeria

Background

Morbid obesity of parturient has become very important in perinatal medicine because of a worldwide obesity epidemic. Morbid obesity of parturient is reportedly associated with severely increased anaesthetic and obstetric risk.

Objective

To determine the prevalence rate, anaesthetic and obstetric complications in morbidly obese parturient that had caesarean delivery in a Nigerian tertiary care centre.

Methods

The obstetric theatre records and case files were reviewed for caesarean deliveries in the University of Nigeria Teaching Hospital, Enugu, Nigeria from May 2008 to December 2010. A sample size of 250 patients, calculated based on a prevalence rate of 19%, confidence interval of 95% , a power of 80% and a finite population of zero was used to determine the prevalence rate of morbid obesity (Body Mass Index of greater than or equal to 35kg/m²).

Results

There were thirty-one patients with morbid obesity (12.4%). The average Body Mass Index (BMI) was 38.3kg/m²(SD ± 2.99). Other findings included macrosomia (7 or 25.8%), gestational diabetes (13%) and pregnancy induced hypertension (7 or 22.5%).There were two neonatal deaths but no maternal deaths.

Conclusion

The prevalence rate of morbid obesity is about 10% in Nigerian women of child bearing age. This mirrors a World Health Organisation report published in the World Health Organisation Global Information Base.     

T-cell large granular lymphocytic leukemia: treatment experience with fludarabine

OBJECTIVES:

The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival.

METHODS:

We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m², for three to five days per month and 6 to 8 cycles.

RESULTS:

Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4×10⁹/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment due to liver toxicity, and one (16.6%) due to dyspesia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%.

CONCLUSION:

T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.     

Reduction of G0 phase cells of colon cancer caco-2 cells may enhance 5-fluorouracil efficacy

Objective

A major problem in the chemotherapy of colon caner may be due to those cells that are in residence in the G₀ phase where they are less vulnerable to conventional therapy. To overcome this phenomenon, we attempted to recruit the reentry of these cells into the cell cycle via a signaling pathway that manipulates tumor growth.

Methods

Epidermal growth factor (EGF) was used to stimulate colon cancer caco-2 cells. FACS analysis and proliferating cell nuclear antigen (PCNA) staining were used to estimate the cell cycle transition and cell proliferation activated by EGF, and a MTT assay was used to evaluate the synergistic effect of EGF and chemotherapy.

Results

The percentage of caco-2 cells in the G₀/G₁ phase was significantly reduced by nearly 20% and the percentages in the S and G₂/M phases were increased by EGF. The combined use of EGF and 5-fluorouracil (5-FU) enhanced the caco-2 cell chemosensitivity to 5-FU, reaching a maximum of an approximately threefold greater sensitivity than to 5-FU alone as judged by the 50% inhibiting concentration (IC₅₀).

Conclusion

Our study demonstrated that stimulation by EGF enhanced the chemosensitivity of caco-2 cells to 5-FU, which may be a novel therapeutic protocol in colon cancer.     

Efficacy of peginterferon and ribavirin is associated with the IL28B gene in Korean patients with chronic hepatitis C

Background/Aims

Sustained virologic response (SVR) for the treatment of chronic hepatitis C (CHC) may differ with ethnicity due to differences in genetic traits. This study evaluated the efficacy of peginterferon and ribavirin, and the association between IL28B genotypes and the treatment efficacy in Korean CHC patients.

Methods

This was a retrospective cohort study using data from medical records. Eighty-five CHC patients were eligible for assessment of the efficacy of antiviral therapy, and 47 patients were available for an IL28B genetic study, which was performed using the Multiplex tetra-primer PCR method for rs12979860.

Results

Overall, the early virologic response rate was 87.1%: 84.9% in HCV genotype 1 and 90.6% in genotype 2. The overall end-of-treatment virologic response rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. The overall SVR rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. For rs12979860, the frequencies of polymorphisms were 89% for the CC type, 11% for the CT type, and 0% for the TT type. Their overall SVR rate was 87% (39/47): 90.5% (38/42) for the CC type and 20% (1/5) for the CT type. For genotype 1, SVR rates were 88% (21/24) for the CC type and 0% (0/4) for the CT type. Multivariate analysis revealed that the IL28B-CC type was a good predictor for SVR.

Conclusions

The SVR of the combination therapy in Koreans was higher than that observed in Western countries. This finding might be attributable to the high prevalence of IL28B-CC type among Koreans, which may be a good predictor of SVR.     

A comparative study of high-dose hepatic arterial infusion chemotherapy and transarterial chemoembolization using doxorubicin for intractable,advanced hepatocellular carcinoma

Background/Aims

Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC.

Methods

The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m² on days 1~3) and cisplatin (60 mg/m² on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks.

Results

Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The objective response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%, P=0.030). Overall survival was longer in the high-dose HAIC group than in the TACE group (median survival, 193 vs. 119 days; P=0.026). There were no serious adverse effects in the high-dose HAIC group, while hepatic complications occurred more often in the TACE group.

Conclusions

High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC.     

Effect of shared care on blood pressure in patients with chronic kidney disease: a cluster randomised controlled trial

Background

Chronic kidney disease (CKD) is highly prevalent in patients with diabetes or hypertension in primary care. A shared care model could improve quality of care in these patients

Aim

To assess the effect of a shared care model in managing patients with CKD who also have diabetes or hypertension.

Design and setting

A cluster randomised controlled trial in nine general practices in The Netherlands.

Method

Five practices were allocated to the shared care model and four practices to usual care for 1 year. Primary outcome was the achievement of blood pressure targets (130/80 mmHg) and lowering of blood pressure in patients with diabetes mellitus or hypertension and an estimated glomerular filtration rate (eGFR)<60ml/min/1.73m².

Results

Data of 90 intervention and 74 control patients could be analysed. Blood pressure in the intervention group decreased with 8.1 (95% CI = 4.8 to 11.3)/1.1 (95% CI = −1.0 to 3.2) compared to −0.2 (95% CI = −3.8 to 3.3)/−0.5 (95% CI = −2.9 to 1.8) in the control group. Use of lipid-lowering drugs, angiotensin-system inhibitors and vitamin D was higher in the intervention group than in the control group (73% versus 51%, 81% versus 64%, and 15% versus 1%, respectively, [P = 0.004, P = 0.01, and P = 0.002]).

Conclusion

A shared care model between GP, nurse practitioner and nephrologist is beneficial in reducing systolic blood pressure in patients with CKD in primary care.     

Rescue therapy with adefovir in decompensated liver cirrhosis patients with lamivudine-resistant hepatitis B virus

Background/Aims

Adefovir dipivoxil (ADV) is a nucleotide analogue that is effective against lamivudine-resistant hepatitis B virus (HBV). The aim of this study was to determine the long-term clinical outcomes after ADV rescue therapy in decompensated patients infected with lamivudine-resistant HBV.

Methods

In total, 128 patients with a decompensated state and lamivudine-resistant HBV were treated with ADV at a dosage of 10 mg/day for a median of 33 months in this multicenter cohort study.

Results

Following ADV treatment, 86 (72.3%) of 119 patients experienced a decrease in Child-Pugh score of at least 2 points, and the overall end-stage liver disease score decreased from 16±5 to 14±10 (mean ± SD, P<0.001) during the follow-up period. With ADV treatment, 67 patients (56.3%) had undetectable serum HBV DNA (detection limit, 0.5 pg/mL). Virologic breakthrough occurred in 38 patients (36.1%) and 9 patients had a suboptimal ADV response. The overall survival rate was 89.9% (107/119), and a suboptimal response to ADV treatment was associated with both no improvement in Child-Pugh score (≥2 points; P=0.001) and high mortality following ADV rescue therapy (P=0.012).

Conclusions

Three years of ADV treatment was effective and safe in decompensated patients with lamivudine-resistant HBV.     

Allogeneic Blood Transfusion Given Before Radiotherapy Is Associated with the Poor Clinical Outcome in Patients with Cervical Cancer

Purpose

To analyze the effect of allogeneic blood transfusion on clinical outcome in 119 patients with stage IIB cervical cancer who were treated with radiotherapy ± chemotherapy.

Patients and Methods

Medical records were examined for hemoglobin levels before and during radiotherapy, history of allogeneic blood transfusions and the time point when transfusions were given. These factors were retrospectively analyzed along with other clinical risk factors for influences on the patients'' clinical outcomes.

Results

Thirty-two patients (26.9%) received packed red blood cell transfusion (mean, 3.4 units; range, 1 - 12 units) before or during radiotherapy. Median follow-up period was 39.3 months (range, 7.6 - 58.4 months). Patients with history of transfusion showed poorer metastasis-free survival and a trend toward poorer overall survival than non-transfused patients. When patients who received transfusions were sub-divided by the time of transfusion, those who received transfusions before radiotherapy had significantly poorer clinical outcome than those who received transfusions during radiotherapy. In a multivariable analysis, patients with pretreatment transfusion showed a higher risk of distant metastasis (HR = 3.75, 95% CI: 1.28 - 12.15, p = 0.017) and decreased overall survival rates (HR = 4.62, 95% CI: 1.15-18.54, p = 0.031) compared with those of other patients.

Conclusion

Our results suggest that allogeneic blood transfusions given before radiotherapy may be associated with higher incidence of distant metastases and decreased survival in patients with stage IIB cervical cancer.     

Metabolism of a Lipid Nanoemulsion Resembling Low-Density Lipoprotein in Patients with Grade III Obesity

INTRODUCTION:

Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood.

OBJECTIVE:

To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate.

METHODS:

A low-density emulsion was labeled with [¹⁴C]-cholesterol ester and [³H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m²] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate.

RESULTS:

There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h⁻¹) was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971) in the controls.

CONCLUSION:

Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower.