Reporting of paediatric osteoporotic vertebral fractures in Duchenne muscular dystrophy and potential impact on clinical management: the need for standardised and structured reporting.

BACKGROUND: In boys with Duchenne muscular dystrophy (DMD), initiation of bisphosphonate is recommended upon identification of moderate or severe vertebral fractures, even if asymptomatic. Clear radiological reporting is important for consistency of clinical interpretation and management. OBJECTIVES: To audit radiology reports of spine imaging for vertebral fracture assessment in DMD, and assess potential impact on diagnosis and management. MATERIALS AND METHODS: Lateral thoracolumbar spine imaging (71 lateral spine radiographs and 13 lateral dual energy absorptiometry spine image) in 84 boys with DMD performed across two centres. Anonymised radiology reports by paediatric radiologists were circulated to two neuromuscular clinicians and two endocrinologists. Clinicians determined if there was vertebral fracture, no vertebral fracture, or unclear interpretation. Endocrinologists also determined if bisphosphonate was indicated. A single observer (a clinician with expertise in vertebral fracture assessment) performed vertebral fracture assessment in 37 images and re-reported using a structured format. Structured reports were re-circulated to the four clinicians to re-evaluate the degree of concordance in clinical diagnosis of vertebral fracture and treatment decisions with bisphosphonate. RESULTS: The term "fracture" was used in 25/84 (30%) radiology reports and only in 8/43 (19%) with description of vertebral body abnormalities. Fracture grading was included in 7/43 (16%) radiology reports. Diagnostic concordance by the clinicians was noted in 36/84 (43%). Unclear interpretation was noted in 22% to 51% based on radiology reports. No unclear interpretation was noted with structured reports. Complete diagnostic (37/37, 100%) and treatment (37/37, 100%) concordance was noted with the structured reports, whereas complete diagnostic and treatment concordance was noted in only 16/37 (43%) and 17/37 (46%) of the radiology reports, respectively. CONCLUSION: Only a third of radiology reports of spine imaging in DMD explicitly used the terminology "fracture". Grading was only noted in a small percentage. Variability in diagnostic interpretation by clinicians may lead to differing management plans. As identification of vertebral fracture is a trigger for treatment, developing reporting guidelines for paediatric vertebral fracture assessment will improve care. A structured template should be introduced for radiological reporting of paediatric vertebral fracture assessment.

Effects of treatment for psoriasis on circulating levels of leptin, adiponectin and resistin: a systematic review and meta-analysis.

BACKGROUND: Metabolic syndrome, a risk factor of cardiovascular disease, is more common in patients with psoriasis than in the general population. Circulating adipokine concentrations are altered in patients with psoriasis and are suggested to represent the pathophysiological link between psoriatic lesions and metabolic alterations. OBJECTIVES: To perform a systematic review of the literature for studies that investigated possible differences in circulating levels of leptin, adiponectin or resistin in patients with psoriasis before and after any treatment intervention, and to meta-analyse the best evidence available. METHODS: A search was conducted in three databases (PubMed, Central and Embase). Eligible for the review were studies that assessed leptin, adiponectin or resistin concentrations in patients with psoriasis before and after any topical or systemic treatment. RESULTS: After treatment, blood concentrations of leptin were similar to those before treatment [standardized mean difference (SMD) 0·06, 95% confidence interval (CI) -0·09 to 0·20], with no heterogeneity among studies (I2 = 0%, P = 0·88). After treatment, blood concentrations of adiponectin were similar to those before treatment (SMD -0·14, 95% CI -0·34 to 0·05), with significant heterogeneity among studies (I2 = 36·8%, P = 0·032). After treatment, blood concentrations of resistin were significantly lower than those before treatment (SMD 0·50, 95% CI 0·20-0·79), with significant heterogeneity among studies (I2 = 61·4%, P < 0·001). CONCLUSIONS: There is no evidence that treatment for psoriasis modifies leptin and adiponectin concentrations. However, treatment intervention reduces resistin concentrations, a finding that is expected to be of clinical importance.

Improving biogas production from anaerobic co-digestion of sewage sludge with a thermal dried mixture of food waste, cheese whey and olive mill wastewater.

Anaerobic co-digestion of sewage sludge and other organic wastes at a wastewater treatment plant (WWTP) is a promising method for both energy and material recovery. However, transportation and storage of wastes to WWTP may be the bottleneck for the successful implementation of this technology. In case of wet wastes and wastewater it is possible to reduce their volume and as a result the transportation and storage cost by using a drying process. During this study, the optimization of biogas production from sewage sludge (SS) was attempted by co-digesting with a dried mixture of food waste, cheese whey and olive mill wastewater (FCO). A series of laboratory experiments were performed in continuously-operating reactors at 37°C, fed with thermal dried mixtures of FCO at concentrations of 3%, 5% and 7%. The overall process was designed with a hydraulic retention time (HRT) of 24days. FCO addition can boost biogas yields if the mixture exceeds 3% (v/v) concentration in the feed. Any further increase of 5% FCO causes a small increase in biogas production. The reactor treating the sewage sludge produced 287ml CH4/Lreactor/d before the addition of FCO and 815ml CH4/Lreactor/d (5% v/v in the feed). The extra FCO-COD added (7% FCO v/v) to the feed did not have a negative effect on reactor performance, but seemed to have the same results. In all cases, the estimated biodegradability of mixtures was over 80%, while the VS removal was 22% for the maximum biomethane production (5% v/v). Moreover, co-digestion improved biogas production by 1.2-2.7 times.

Boosting biogas production from sewage sludge by adding small amount of agro-industrial by-products and food waste residues.

In Greece, in many cities, wastewater treatment plants (WWTPs) operate their own anaerobic digestion (AD) facility in order to treat sewage sludge rather than achieve optimum biogas production. Nowadays, there is a growing interest regarding the addition of other co-substrates in these existing facilities in order to increase gas yield from the biomass. This practice may be possible by adding small amount of co-substrates which will not affect significantly in the designed hydraulic retention time. Nonetheless, the lack of experimental data regarding this option is a serious obstacle. In this study, the effect of co-digestion sewage sludge, with small amount of agro-industrial by-products and food wastes is examined in lab-scale experiments. Specifically, co-digestion of SS and food waste (FW), grape residues (GR), crude glycerol (CG), cheese whey (CW) and sheep manure (SM), in a small ratio of 5-10% (v/v) was investigated. The effect of agro-industrial by-products and food waste residues on biogas production was investigated using one 1L and three 3L lab-scale reactors under mesophilic conditions at a 24-day hydraulic retention time. The biogas production rate reached 223, 259, 406, 572, 682 and 1751 mlbiogas/lreactor/d for 100% SS, 5% SM & 95% SS, 10% CW & 90% SS, 5% FW & 95% SS, 5% FW & 5% CG & 90% SS and 5% CG & 95% SS respectively. Depending on the co-digestion material, the average removal of total chemical oxygen demand (TCOD) ranged between 20% (5% SM & 95% SS) and 76% (5% FW & 5% CG & 90% SS). Reduction in the volatile solids ranged between 26% (5% SM & 95% SS) and 62% (5% FW & 5% CG & 90% SS) for organic loading rates between 0.8kgVSm-3d-1 and 2.0kgVSm-3d-1. Moreover, co-digestion improved biogas production from 14% (5% SM & 95% SS) to 674% (5% CG & 95% SS). This work suggests that WWTPs in Greece can increase biogas production by adding other wastes to the sewage sludge without affecting the operation of existing digesters and without requiring additional facilities.

Prevalence of endocrine and genetic abnormalities in boys evaluated systematically for a disorder of sex development.

STUDY QUESTION: What is the likelihood of identifying genetic or endocrine abnormalities in a group of boys with 46, XY who present to a specialist clinic with a suspected disorder of sex development (DSD)? SUMMARY ANSWER: An endocrine abnormality of the gonadal axis may be present in a quarter of cases and copy number variants (CNVs) or single gene variants may be present in about half of the cases. WHAT IS KNOWN ALREADY: Evaluation of 46, XY DSD requires a combination of endocrine and genetic tests but the prevalence of these abnormalities in a sufficiently large group of boys presenting to one specialist multidisciplinary service is unclear. STUDY, DESIGN, SIZE, DURATION: This study was a retrospective review of investigations performed on 122 boys. PARTICIPANTS/MATERIALS, SETTING, METHODS: All boys who attended the Glasgow DSD clinic, between 2010 and 2015 were included in the study. The median external masculinization score (EMS) of this group was 9 (range 1-11). Details of phenotype, endocrine and genetic investigations were obtained from case records. MAIN RESULTS AND THE ROLE OF CHANCE: An endocrine abnormality of gonadal function was present in 28 (23%) with a median EMS of 8.3 (1-10.5) whilst the median EMS of boys with normal endocrine investigations was 9 (1.5-11) (P = 0.03). Endocrine abnormalities included a disorder of gonadal development in 19 (16%), LH deficiency in 5 (4%) and a disorder of androgen synthesis in 4 (3%) boys. Of 43 cases who had array-comparative genomic hybridization (array-CGH), CNVs were reported in 13 (30%) with a median EMS of 8.5 (1.5-11). Candidate gene analysis using a limited seven-gene panel in 64 boys identified variants in 9 (14%) with a median EMS of 8 (1-9). Of the 21 boys with a genetic abnormality, 11 (52%) had normal endocrine investigations. LIMITATIONS, REASONS FOR CAUTION: A selection bias for performing array-CGH in cases with multiple congenital malformations may have led to a high yield of CNVs. It is also possible that the yield of single gene variants may have been higher than reported if the investigators had used a more extended gene panel. WIDER IMPLICATIONS OF THE FINDINGS: The lack of a clear association between the extent of under-masculinization and presence of endocrine and genetic abnormalities suggests a role for parallel endocrine and genetic investigations in cases of suspected XY DSD. STUDY FUNDING/COMPETING INTEREST(S): RN was supported by the James Paterson Bursary and the Glasgow Children's Hospital Charity Summer Scholarship. SFA, RM and EST are supported by a Scottish Executive Health Department grant 74250/1 for the Scottish Genomes Partnership. EST is also supported by MRC/EPSRC Molecular Pathology Node and Wellcome Trust ISSF funding. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: None.

FCGR3A-V158F polymorphism is a disease-specific pharmacogenetic marker for the treatment of psoriasis with Fc-containing TNFα inhibitors.

Psoriasis is a multifactorial skin disease affecting ~2% of world's population, causing a dramatic decrease in patients' quality of life and a significant increase in health-care expenses. Biological agents such as the anti-TNFα ones had an enormous impact in patients' therapy; however, a significant proportion of them do not respond well, an outcome attributed mainly to genetic factors. Recently, in a large European cohort of rheumatoid arthritis patients we have shown association with variation in the receptors that correspond to the Fc portion of the biological agents. As both diseases share common immunological fingerprints, we examined the hypothesis that they share common pharmacogenetic markers. Analysis of FCGR2A-H131R and FCGR3A-V158F polymorphisms in 100 psoriasis patients showed association only with respect to FCGR3A-V158F and response to etanercept (P=0.018). Interestingly, no association was found between FCGR2A-H131R and response to anti-TNFα therapy (P=0.882). This study suggests a role for FCGR3A-V158F polymorphism unique for psoriasis.

Shorter anogenital and anoscrotal distances correlate with the severity of hypospadias: A prospective study.

INTRODUCTION: Anogenital distance (AGD) is a recognised marker of in utero androgen action. OBJECTIVE: This study aimed to evaluate the relationship between severity of hypospadias and AGD. STUDY DESIGN: Boys undergoing hypospadias repair in a single tertiary centre between May 2012 and February 16 were included in the study. Anogenital distance was measured from the centre of the anus to the base of the penis, and anoscrotal distance (ASD) from the centre of the anus to the junction between the smooth perineal skin and scrotal skin. Trained paediatric urologists made all measurements using digital callipers. RESULTS: Fifty-nine boys with hypospadias and 31 age-matched controls undergoing circumcision (median age 1.37 years, range 1.01-1.96) had AGD and ASD measured under anaesthetic. The patients were divided into two groups, according to hypospadias severity: group 1 - distal penile/subcoronal/glandular (n = 40); and group 2 - perineal/penoscrotal/midshaft (n = 19). The median AGD for controls was 74.0 mm (range 53.2-87.8) and for hypospadias it was 72.3 mm (range 50.7-90.0) (P = 0.816). The median ASD for controls was 42.3 mm (range 31.0-56.1) and for hypospadias it was 39.4 mm (range 20.7-77.0) (P = 0.224). Considering severity of hypospadias, the median AGD for group 1 and group 2 was 73.7 mm (range 50.7-90.0) and 63.3 mm (range 53.6-77.0), respectively (P < 0.001). The median ASD was also higher in group 1, at 41.3 mm (range 20.7-65.0), compared to 35.2 mm (range 23.5-77.0) in group 2 (P = 0.119) (Summary Fig.). DISCUSSION: This study showed that more severe forms of hypospadias are associated with shorter AGD and ASD. These findings agree with two previous studies that identified reduced AGD in boys with hypospadias. However, these studies did not investigate an association with severity of hypospadias. As hypospadias is multifactorial, only a small proportion of cases are thought to be associated with impaired in utero androgen exposure. The shorter AGD in boys with severe hypospadias compared with mild hypospadias would indicate that AGD is a marker of the severity of androgen production. This may also suggest that less severe forms of hypospadias have a different aetiology involving a later stage of development, and that they are not the result of reduced androgen exposure in the male programming window between the 8-14 weeks gestation. CONCLUSION: This study identified that boys with more severe hypospadias are more likely to have a shorter AGD and ASD than boys with mild hypospadias. This may indicate that there is a more profound impairment of in utero androgen action in severe hypospadias.

Pilot-scale anaerobic co-digestion of sewage sludge with agro-industrial by-products for increased biogas production of existing digesters at wastewater treatment plants.

Due to low degradability of dry solids, most of the digesters at wastewater treatment plants (WWTP) operate at low loading rates resulting in poor biogas yields. In this study, co-digestion of sewage sludge (SS) with olive mill wastewater (OMW), cheese whey (CW) and crude glycerol (CG) was studied in an attempt to improve biogas production of existing digesters at WWTPs. The effect of agro-industrial by-products in biogas production was investigated using a 220L pilot-scale (180L working volume) digester under mesophilic conditions (35°C) with a total feeding volume of 7.5L daily and a 24-day hydraulic retention time. The initial feed was sewage sludge and the bioreactor was operated using this feed for 40days. Each agro-industrial by-product was then added to the feed so that the reactor was fed continuously with 95% sewage sludge and 5% (v/v) of each examined agro-industrial by-product. The experiments showed that a 5% (v/v) addition of OMW, CG or CW to sewage sludge significantly increased biogas production by nearly 220%, 350% and 86% as values of 34.8±3.2L/d, 185.7±15.3L/d and 45.9±3.6L/d respectively, compared to that with sewage sludge alone (375ml daily, 5% v/v in the feed). The average removal of dissolved chemical oxygen demand (d-COD) ranged between 72 and 99% for organic loading rates between 0.9 and 1.5kgVSm-3d-1. Reduction in the volatile solids ranged between 25 and 40%. This work suggests that methane can be produced very efficiently by adding a small concentration (5%) of agro-industrial by-products and especially CG in the inlet of digesters treating sewage sludge.

Genetic defects of the CYP21A2 gene in girls with premature adrenarche.

OBJECTIVES: To seek evidence on the prevalence of CYP21A2 genetic defects and consequences in girls with premature adrenarche (PA). METHODS: The study included 59 girls diagnosed with PA. Direct DNA sequencing and MLPA analysis were performed to identify mutations in CYP21A2 gene. RESULTS: Twelve girls were diagnosed with non-classic congenital adrenal hyperplasia (NC-CAH) based on stimulated 17-hydroxyprogesterone (17-OHP) levels and the presence of two mutations in CYP21A2, 19 were heterozygotes. The most frequent mutations detected were the mild p.Val281Leu and p.Pro453Ser. Higher levels of mean stimulated 17-OHP were found in the carriers of the p.Val281Leu mutation. The detection rate for two CYP21A2 mutations was higher in girls with PA than in adult females with hyperandrogenemia in our studied population. A notable increased allelic frequency for the known p.Asn493Ser polymorphism was observed in the pool of the 28 girls with PA in whom no mutation was identified. CONCLUSIONS: In girls with PA, the frequency of the underlying CYP21A2 genetic defects is similar to that observed in other populations. The carrier status is likely a contributing factor in the genotype-phenotype correlation in NC-CAH. However, polymorphisms and other genes may be implicated in the clinical manifestation of the disease.

Therapeutic efficacy of topical calcineurin inhibitors in plasma cell balanitis: case series and review of the literature.

Plasma cell balanitis of Zoon (PCBZ) and plasma cell vulvitis (PCV) are characterized as idiopathic, benign, chronic irritant mucositis. The clinical symptoms and signs usually persist or reappear after treatment withdrawal. Therefore, many therapies have been tried and are available. Recently, several reports of PCBZ and PCV treated with calcineurin inhibitors, tacrolimus and pimecrolimus, have been reported in the literature. We present 9 cases of PCBZ treated with tacrolimus 0.1% ointment (Protopic, Toyama, Japan) that showed good therapeutic results within 4 weeks of treatment, and we review the literature of PCBZ and PCV and their response to these topical immunomodulators. Based on the current literature and on the anecdotal experience, we believe that topical calcineurin inhibitors may serve as a therapeutic option in recalcitrant plasma cell balanitis and vulvitis.

Primary cutaneous diffuse large B-cell lymphoma, leg type, with multiple local relapses: case presentation and brief review of literature.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBL-LT) is a primary cutaneous B-cell lymphoma of intermediate behavior. The disease predominantly affects elderly patients. A 76-year old man presented with red to violaceous nodules in the anterior aspect of both tibias. Histology confirmed the diagnosis of PCDLBL-LT. A thorough clinical and laboratory investigation was negative for any systemic involvement. However, computed tomography of the thorax showed mediastinal lymphadenopathy. Both bone marrow aspiration and trephine did not show any evidence of bone marrow infiltration. Initially R-CHOP regimen (rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone) achieved a total clearance of the lesions. Nevertheless, five months later patient presented with a relapse and was managed with palliative radiotherapy. The same treatment modality was applied for the second recurrence, as well. PCDLBL-LT affects mostly elderly patients. The consequent age related comorbidities and the frequent relapses require a strict follow up of the patients.

Genetic defects in the cyp21a2 gene in heterozygous girls with premature adrenarche and adolescent females with hyperandrogenemia.

UNLABELLED: Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder primarily caused by mutants in the CYP21A2 gene. Heterozygosity for CYP21A2 mutations in females increases their risk of clinically manifesting hyperandrogenism and the present study was designed to seek evidence on the prevalence and consequences of heterozygous CYP21A2 mutations in children with premature adrenarche and adolescents with hyperandrogenemia. The hormonal response to ACTH was evaluated in 17 girls with clinical signs of premature adrenarche and 17 adolescent females with hyperandrogenemia, along with direct DNA sequencing and MLPA analysis for mutations in the CYP21A2 gene. The suspicion of heterozygote state was based on the median plasma 17-OHP before and 60 minutes after ACTH stimulation. All 34 patients were identified as carriers of CYP21A2 mutations. The most frequent mutations among this cohort of carriers were the mild p.V281L (52.9%), followed by p.Q318stop (20.6%), p.V304M (8.9%), p.P482S (5.9%), p.P453S (5.9%), large deletion/conversion exons 1-4 (2.9%) and large deletion/conversion exons 6-8 (2.9%). Higher values of stimulated 17-OHP levels were found in the carriers of the p.V281L mutation compared with carriers of other mutations (mean=21.9 nmol/L vs 17.0 nmol/L). This finding supports the already identified notion that carriers of the mild p.V281L are at higher risk for hyperandrogenism than carriers of severe mutations. IN CONCLUSION: a. Females with premature adrenarche and hyperandrogenemia are likely to bear heterozygous CYP21A2 mutations, therefore systematic evaluation of 17-OHP values in combination with the molecular testing of CYP21A2 gene is beneficial, b. carriers of the mild p.V281L, are at higher risk of androgen excess compared to carriers of other types of mutations.

Necrobiosis lipoidica: early diagnosis and treatment with tacrolimus.

We present a case of necrobiosis lipoidica (NL) with atypical early lesions and good response to topical tacrolimus. NL is a disease with clinical features that are seldom misinterpreted. Often histology just confirms the clinician's diagnosis. Only in rare cases, the clinical presentation and the involved body sites may be misleading. A 67-year-old diabetic woman was admitted to our department with a well-defined, persistent plaque on her left arm and on her right shin. Histologic examination of both lesions revealed features of NL despite the dissimilar clinical presentation. The patient was treated with 0.1% topical tacrolimus ointment twice daily for 8 weeks and once daily for 8 weeks. A significant improvement and no further lesions were observed after 1 year of follow-up. A high index of suspicion regarding NL lesions with atypical clinical presentation on different body sites is advised in order to avoid misdiagnosis, wrong treatment decisions and ulceration. Additionally, it appears that topical tacrolimus treatment is an effective therapeutic option in patients with recent, non-ulcerated NL lesions.

The IVS1-2A>G mutation in the SRD5A2 gene predominates in Cypriot patients with 5α reductase deficiency.

BACKGROUND: 5α steroid reductase deficiency (5αSRD) is an autosomal recessive enzymatic deficiency and mutations in the 5α steroid reductase type 2 gene (SRD5A2) result in male pseudohermaphrodism caused by decreased dihydrotestosterone (DHT) synthesis. AIM: To identify the specific mutations of the SRD5A2 gene in Cypriot patients with 5αSRD. SUBJECTS AND METHODS: Five unrelated patients with 46,XY karyotype were examined. Four of them were born with ambiguous genitalia and 1 patient, who was raised as girl, presented with primary amenorrhea. The hCG test was informative (elevated testosterone/DHT) of 5αSRD in 3 out of 4 subjects. Sequencing of the SRD5A2 gene was completed for all patients. Genomic DNA was also isolated from a total of 204 healthy unrelated Cypriot subjects. Screening for the IVS1-2A>G mutation was performed by using direct sequencing and restriction enzyme analysis. RESULTS: The IVS1-2A>G was identified in homozygosity in 3 patients and in a compound heterozygote state in the other 2 patients, in combination with p.P181L and p.R171S in exon 3, respectively. The carrier frequency in the Cypriot population for the IVS1-2A>G mutation was estimated to be 0.98% or 2 in 204. CONCLUSIONS: The same IVS1-2A>G mutation in the SRD5A2 gene seems to characterize all Cypriot patients with 5αSRD diagnosed so far. Furthermore this relatively rare genetic defect, which has only been reported previously in a single case in the Eastern Mediterranean region, is very likely to be the result of a founder effect.

Intrasplenic immunostimulation in malignancies fact or fiction? Present and future.

BACKGROUND/AIMS: The clinical application of intrasplenic immunostimulation with IL-2 in a group of patients suffering from metastatic renal carcinoma, melanoma, recurrent rectal carcinoma, lung carcinoma and gastric carcinoma are discussed in terms of clinical applicability, effectiveness and survival. METHODOLOGY: From May 1996 to February 1998, 45 patients with advanced malignancies were admitted to Athens Medical Center for intrasplenic immunostimulation. Transplenic immunostimulation was carried out via a subcutaneously implanted port. The injected therapy included IL-2 (Proleukin) 1 ml 18 x 10(6) suspended in 1.5 ml of lipiodol and 0.5 ml of urografin. In conjunction gamma-INF (Immukin) 0.5 ml 100 mcg, was administered. RESULTS: Patients included in this study have completed their treatment, or are still undergoing maintenance treatment. The duration of the CR was between 11 and 16 months, and for PR was between 10-14 months. For melanoma patients (n = 9), 3 patients with PD died 9, 10 and 12 months after initial treatment began. The remaining patients (n = 6) are alive with a mean survival rate of 16 months. Of those patients, 4 have been classified as complete responders, being completely free of disease at this time. The number of CR for patients with lung, renal and recurrent rectal cancer was achieved as a result of the continuing maintenance treatment. Twenty-two patients remain alive and 23 patients have died. From those alive (n = 22), 10 patients are complete responders and free of disease, 10 are partial responders with controlled disease and 2 remain with standard disease. For those surviving patients with lung cancer, the mean survival time is 14 months. Patients with recurrent rectal cancer and renal cancer were shown to have a mean survival time of 15 and 13 months, respectively. CONCLUSION: The safety, effectiveness and feasibility of long-lasting administration of high dosages of IL-2 are documented from the data of this study. Intrasplenic immunostimulation utilizing lipiodol-urografin emulsion as a carrier, offers new possibilities for the safe administration of long lasting high dosages of IL-2 and gamma-INF. Further studies are warranted, to further elucidate the results of this phenomenon.

Pancreatic resection for pancreatic carcinoma combined with neo- and adjuvant locoregional targeting immuno-chemotherapy--a prospective randomized study.

BACKGROUND/AIMS: The effects on early and late results of combined pancreatic resection with neo- and adjuvant immuno-chemotherapy for patients undergoing pancreatic resection are prospectively evaluated. METHODOLOGY: A group of 26 patients was divided into two groups, which were matched in terms of age-sex ratio, stage of disease, histological diagnosis and mode of pancreatic resection. Group A patients received a multimodality therapy, combining pancreatic resection with neo- and adjuvant locoregional targeting immunochemotherapy. Group B received pancreatic surgery only. RESULTS: For Group A patients (n = 14pts), a complete response was seen in 11 patients with a time interval ranging from 9 to 29 months. In the remaining 3 patients liver secondaries developed 12 months after pancreatic resection in 2 patients and the other patient developed pulmonary metastases 22 months after pancreatic resection. All patients (n = 3pts) are alive, but continue to have the disease. For Group B patients (n = 12pts), a complete response was seen in 3 patients with a survival of 9, 10 and 20 months following pancreatic resection. Six patients died due to locoregional recurrence of the disease, with the survival rate ranging from 7 to 18 months (mean 10 months). Locoregional recurrence was complicated with liver secondaries (n = 3) and with peritoneal dissemination of the disease in a further 3 patients. The remaining 3 patients are alive, but continue to have the disease due to locoregional recurrence. CONCLUSIONS: Patients in whom neo- and adjuvant locoregional immunochemotherapy was carried out in conjunction with pancreatic resection, demonstrated a significantly higher response rate to treatment. Therefore the data collected offers clear evidence, regarding the usefulness, applicability and safety of combined neo- and adjuvant therapy with pancreatic resection. A Multi-modality approach is therefore highly recommended.