Effect of elevated serum prolactin concentrations on cytokine production and natural killer cell activity.

In vitro and in vivo studies in rodents and human suggested an immunostimulatory effect of prolactin. The aim of the present study was to determine the impact of chronically elevated serum prolactin concentrations on the immune system in patients with prolactinomas. For this purpose parameters of the humoral and cellular immune system were studied in seven patients with prolactinomas on two occasions (1) when their serum prolactin concentration had been normalized through treatment with dopamine agonists and (2) when their serum prolactin concentration was high. Serum concentrations of immunoglobulines, interleukin 1, 3 and 6, TNF-alpha, interferon-gamma and the soluble interleukin 2 receptor, leukocyte subsets and the natural killer cell activity were found to be within the normal range on both occasions, i.e. at normal and at high serum prolactin concentrations. The assumption could be made that long-lasting elevation of serum prolactin concentration induces adaptive changes when the acute stimulatory effects of prolactin on several parameters of the immune system have subsided.     

Cetuximab-based or bevacizumab-based first-line treatment in patients with KRAS p.G13D-mutated metastatic colorectal cancer: a pooled analysis

KRAS p.G13D mutant metastatic colorectal cancer (mCRC) has been identified as representing a cetuximab-sensitive subtype of KRAS mutant mCRC. This analysis aims to answer the question of whether first-line treatment of p.G13D mCRCs should include cetuximab or bevacizumab. Fifty-four patients with p.G13D mutant mCRC were pooled in this analysis. All patients underwent systemic first-line treatment with a fluoropyrimidine and oxaliplatin/irinotecan that was combined with either cetuximab or bevacizumab. The analysis of cetuximab-based and bevacizumab-based regimens in mCRC patients with p.G13D-mutated tumours indicated comparable data for the overall response rate (58 vs. 57%) and progression-free survival (8.0 vs. 8.7 months; hazard ratio: 0.96, P=0.9). Overall survival (OS) was 20.1 months in patients treated with cetuximab-based first-line therapy compared with 14.9 months in patients receiving bevacizumab-containing regimens (hazard ratio: 0.70, P=0.29). Logistic regressions modelling OS revealed oxaliplatin-based first-line treatment to correlate with a poor outcome (P=0.03). Moreover, a strong trend in favour of capecitabine compared with infusional 5-FU (P=0.06) was observed. Response to treatment correlated with OS in patients receiving cetuximab-based, but not bevacizumab-based regimens. This retrospective pooled analysis suggests comparable efficacy of cetuximab-based and bevacizumab-based first-line therapy in patients with p.G13D mutant mCRC. The combination with capecitabine and irinotecan was associated with a more favourable outcome compared with infusional 5-FU and oxaliplatin.     

Transcutaneous electrical stimulation of urinary bladder in patients with spinal cord injuries

Introduction  The treatment of neurogenic dysfunctions of micturition, both surgical and conservative, aims primarily to protect upper urinary tract function. This goal can be achieved by lowering intravesical pressure and increasing urinary bladder capacity in the urine collection phase or by facilitating bladder emptying. Objective  The objective of this paper was to assess the outcome of transcutaneous stimulation of the urinary bladder in the treatment of neurogenic disorders of micturition. Materials and methods  The effect of urinary bladder stimulation was assessed in 22 patients (4 females, 18 males) with spinal injuries (19 with injuries to the lumbo-sacral spine and 3 with cervical spine injuries) treated at the Department of Rehabilitation of the Military Hospital in Bydgoszcz, Poland, in 2006 and 2007. The treatment consisted of 30 procedures of transcutaneous electrical stimulation of the urinary bladder. A pulsed sinusoid current was used with a pulse duration of 200 ms, break duration of 1,000 ms, intensity of 15–20 mA, frequency of 50 Hz, and duration of stimulation of 15 min. A urodynamic study was carried out in each patient at baseline and on completion of the electrical stimulation therapy (immediately and after 2 months). Results  Electrical stimulation of the neurogenic urinary bladder produced increases in the cystometric bladder capacity and reduction in the amount of residual urine (72% of patients), with reduction of intravesical pressure at peak urine flow (59% of the patients). The dynamic aspects of micturition also improved with increased peak voiding velocity in 77.3% of the patients. More than half of the patients (57%) still had elevated intravesical pressures during micturition that posed a risk to the function of the upper urinary tract despite significant decreases following the stimulation therapy. Micturition, which was absent at baseline, was restored in three patients. No local complications were observed. Conclusions  Transcutaneous electrical stimulation of the urinary bladder in patients with neurogenic bladder dysfunction improves lower urinary tract function. Urodynamic studies executed 2 months after finishing TES show persistent results.     

Poor-risk high-grade gliomas in three survivors of childhood acute lymphoblastic leukaemia—an overview of causative factors and possible therapeutic options

Purpose  Malignant high-grade gliomas are the most common secondary neoplasms in children cured of acute lymphoblastic leukaemia (ALL). Although many predisposing factors exist (including systemic or intrathecal chemotherapy, young age, brain infiltration and genetic predispositions), cranial irradiation appears to be the strongest one. Methods  Three cases of secondary high-grade gliomas (two multiform glioblastomas, grade IV; one anaplastic astrocytoma, grade III) developed in ALL survivors (F–M, 1:2) 3 to 6.3 years after stopping ALL therapy according to BFM-90 trial. Results  All tumours were supratentorial, contrast-enhancing, space-occupying, highly advanced and aggressive. Possible risk factors and current therapeutic options for paediatric ALL and malignant gliomas are reviewed and discussed. Conclusions  Prognosis in secondary malignant gliomas in children is poor (overall survival of 5, 10 and 19 months) despite intense therapy. Thus, protocols for paediatric ALL reduce prophylactic cranial irradiation in favour of intrathecal and intravenous high-dose MTX. Nevertheless, ALL survivors must undergo systematic, long-term surveillance for early detection of intracranial neoplasms.     

Comparison of Surgically Resected Polypoid Lesions of the Gallbladder to their Pre-operative Ultrasound Characteristics

Background  Polypoid lesions of the gallbladder (PLG) have been a common finding on ultrasound examinations of the abdomen and are more prevalent since our use of equipment incorporating pulse shaping increased bandwidth, and enhanced phase use for image reconstruction began in 1996. Our study correlates the pre-operative ultrasonographic findings of these lesions to the surgically resected specimen with specific regard to identifying neoplastic polyps. Methods  A retrospective review was performed of 130 patients who had a pre-operative ultrasound of the gallbladder and subsequently underwent cholecystectomy between August 1996 and July 2007 at the Mayo Clinic Rochester. Results  Seventy-nine pseudopolyps (cholesterol polyps, inflammatory polyps, and adenomyomas) and 15 neoplastic polyps were identified on histopathologic analysis. However, 36 patients (27%) did not have a PLG upon histopathologic analysis. Thirty-one polyps had suspicious ultrasonographic characteristics for neoplastic changes. Twenty-nine were ≥10 mm, 12 had vascularity, and one demonstrated invasion. Of these, there were 23 pseudopolyps and six true polyps with neoplastic changes on final pathology (four dysplastic adenomas and two adenocarcinomas). Three asymptomatic polyps ≤10 mm (4%) in maximum diameter based on pre-operative ultrasound imaging (US) had neoplastic changes at pathology (two dysplastic adenomas and one adenocarcinoma). Several statistically significant risk factors were identified that increased the likelihood for malignancy in a PLG: history of primary sclerosing cholangitis (PSC), local invasion, vascularity, and ≥6 mm maximum diameter based on pre-operative US. Of PLGs ≤10 mm, 7.4% were neoplastic. Twenty-five patients were followed up with at least two serial ultrasound examinations. Of these, seven demonstrated polyp growth. None of these specimens demonstrated neoplastic changes. The positive predictive value (PPV) and negative predictive value (NPV) for ultrasound diagnosing neoplastic changes based on current criteria was 28.5% and 93.1%, respectively, with a false negative rate of 5.0%. Expanding the criteria to include cholecystectomy for PLGs ≥ 6 mm changes the positive predictive value and negative predictive value to 18.5% and 100%, respectively, with a false negative rate of 0%. Conclusion  Histopathologic analysis of polypoid lesions of the gallbladder continues to be the gold standard to identify malignancy. Ultrasound has been used extensively in the pre-operative management of these lesions, but modern ultrasound techniques are unable to differentiate between benign and malignant PLGs with any certainty. We recommend that strong consideration be given to surgical resection of PLGs ≥ 6 mm based on pre-operative US due to the significant risk of neoplasm. Additionally, PLGs in all patients with PSC, any patient in whom diligent long-term follow-up cannot be completed, and lesions that demonstrate growth, vascularity, invasion, or are symptomatic require cholecystectomy. Presented at SSAT at the DDW     

Impact of Body Mass Index on Left Ventricular Function

Background

Obesity is associated with increased cardiovascular morbidity and mortality. A direct effect of isolated obesity on cardiac function is not well established. The study was designed to determine the direct effect of various grades of isolated obesity on echocardiographic indices of systolic and diastolic left ventricular function.

Methods

Fifty one obese and 25 normal weight, serving personnel without any other pathological condition were studied. Group I (n=25) consisted of subjects with normal weight and body mass index (BMI <25kg/m²), Group II (n=34) of overweight subjects (BMI 25-29.9 kg/m²) and Group III (n=17) of obese subjects (BMI >30 kg/m²). Echocardiographic indices of systolic and diastolic function were obtained and dysfunction was assumed when at least two values differed by ≥ 2 SD from the normal weight group.

Result

Ejection fraction, fractional shortening were increased (p<0.05) in Group II and III. Left ventricular dimensions were increased (p< 0.001) but relative wall thickness was unchanged. Systolic dysfunction was not observed in any of the obese patients. The mitral valve pressure half time (p< 0.01), left atrial diameter (p < 0.01) and the deceleration time were increased (p< 0.01) in obese subjects, while other diastolic variables were unchanged. No difference were found between obesity subgroups. Subclinical diastolic dysfunction was more prevalent among obese subjects. BMI correlated significantly with indices of left ventricular systolic and diastolic function.

Conclusion

Subclinical left ventricular diastolic dysfunction was noted in all grades of obesity which correlates with BMI.Key Words: Obesity, Systolic function, Diastolic function, Echocardiography     

Chromosomal abnormalities of young multiple myeloma patients (<45 yr) are not different from those of other age groups and are independent of stage according to the International Staging System

Little is known about tumor-related prognostic factors, in particular specific chromosomal abnormalities, in young patients with multiple myeloma (MM). We therefore investigated the chromosomal pattern by interphase fluorescence in situ hybridization (chromosomes 13q14, 14q32-translocations, chromosomes associated with hyperdiploidy) in 38 young patients with MM (age <45 yr) and compared the results with those observed in 69 patients with intermediate age (45-70 yr) and 64 elderly patients (age >70 yr). All chromosomal patterns were not significantly different between the three age cohorts. Similarly, standard MM parameters were equally distributed between these MM patient populations. However, survival by the International Staging System (ISS) for MM revealed marked differences between stage I/II (median survival not yet reached) and stage III (23.4 months; P < 0.0003) among young MM patients. A significant survival difference between ISS-stage I/II and ISS-stage III patients was also noted in the intermediate age group (median 65.4 months vs. 24.6 months; P = 0.0009). However, this difference disappeared among elderly MM patients (39.6 months in ISS-stage I/II vs. 32 months in ISS-stage III patients; P = 0.94), but it was unrelated to the cytogenetic pattern. Our results indicate that MM in young patients does not represent a distinct biologic entity, and that short survival of younger MM patients at ISS-stage III is independent of the molecular cytogenetic pattern.     

Prognostic relevance of demographics and surgical practice for patients with gastric cancer in two centers: in Poland versus Germany

Background  

Although studies comparing the surgical treatment of gastric carcinoma in Japan and Western industrialized countries have revealed differing survival rates, no studies to date have been performed comparing Western and Eastern Europe. This study aimed to compare demographics and surgical practice as well as the related prognostic impact on gastric cancer patients treated in Poland and Germany.