Predictors of disease recurrence after curative surgery for nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNENs): a systematic review and meta-analysis.

PURPOSE: Patients submitted to curative surgery for non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) exhibit a variable risk of disease relapse. Aims of this meta-analysis were to estimate the rate of disease recurrence and to investigate the risk factors for disease relapse in patients submitted to curative surgery for NF-PanNENs. METHODS: Medline/Pubmed and Web of Science databases were searched for relevant studies. A meta-regression analysis was performed to investigate the source of recurrence rate heterogeneity. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CI) were used to assess the effect of each possible prognostic factor on disease-free survival. RESULTS: Fifteen studies, involving 2754 patients submitted to curative surgery for NF-PanNENs, were included. The pooled rate of disease recurrence was 21% (95% CI 15-26%). Study quality (Odds ratio, OR 0.94, P = 0.016) and G3-PanNENs rate (OR 2.18, P = 0.040) independently predicted the recurrence rate variability. Nodal metastases (HR 1.63, P < 0.001), tumor grade G2-G3 (G1 versus G2: HR 1.72, P < 0.001, G1 versus G3 HR 2.57, P < 0.001), microvascular (HR 1.25, P = 0.046) and perineural (HR 1.29, P = 0.019) invasion were identified as significant prognostic factors. T stage (T1-T2 versus T3-T4, P = 0.253) and status of resection margins (R0 versus R1, P = 0.173) did not show any significant relationship with NF-PanNENs recurrence. CONCLUSION: Disease relapse occurs in approximately one out of five patients submitted to curative surgery for NF-PanNENs. Nodal involvement, tumor grade, microvascular and perineural invasion are relevant prognostic factors, that should be taken into account for follow-up and for possible trials investigating adjuvant or neoadjuvant treatments.

Modelling centralization of pancreatic surgery in a nationwide analysis.

BACKGROUND: The benefits of centralization of pancreatic surgery have been documented, but policy differs between countries. This study aimed to model various centralization criteria for their effect on a nationwide cohort. METHODS: Data on all pancreatic resections performed between 2014 and 2016 were obtained from the Italian Ministry of Health. Mortality was assessed for different hospital volume categories and for each individual facility. Observed mortality and risk-standardized mortality rate (RSMR) were calculated. Various models of centralization were tested by applying volume criteria alone or in combination with mortality thresholds. RESULTS: A total of 395 hospitals performed 12 662 resections; 305 hospitals were in the very low-volume category (mean 2·6 resections per year). The nationwide mortality rate was 6·2 per cent, increasing progressively from 3·1 per cent in very high-volume to 10·6 per cent in very low-volume hospitals. For the purposes of centralization, applying a minimum volume threshold of at least ten resections per year would lead to selection of 92 facilities, with an overall mortality rate of 5·3 per cent. However, the mortality rate would exceed 5 per cent in 48 hospitals and be greater than 10 per cent in 17. If the minimum volume were 25 resections per year, the overall mortality rate would be 4·7 per cent in 38 facilities, but still over 5 per cent in 17 centres and more than 10 per cent in five. The combination of a volume requirement (at least 10 resections per year) with a mortality threshold (maximum RSMR 5 or 10 per cent) would allow exclusion of facilities with unacceptable results, yielding a lower overall mortality rate (2·7 per cent in 45 hospitals or 4·2 per cent in 76 respectively). CONCLUSION: The best performance model for centralization involved a threshold for volume combined with a mortality threshold.

ANTECEDENTES: Los beneficios de la centralización de la cirugía pancreática están bien documentados, pero la política de actuación difiere entre los países. Este estudio tuvo como objetivo desarrollar modelos de centralización basados en varios criterios y analizar su aplicación en una cohorte nacional. MÉTODOS: Los datos de todas las resecciones pancreáticas realizadas entre 2014 y 2016 se obtuvieron del Ministerio de Salud italiano. La mortalidad se evaluó para diferentes categorías del volumen hospitalario y para cada centro individualmente. Se calculó la mortalidad observada y la tasa estandarizada de riesgo de mortalidad (risk standardized mortality rate, RSMR). Se analizaron varios modelos de centralización aplicando criterios de volumen solos o en combinación con umbrales de mortalidad. RESULTADOS: Un total de 395 hospitales realizaron 12.662 resecciones; 305 de ellos pertenecían a la categoría de muy bajo volumen (media de 2,6 resecciones/año). La mortalidad nacional fue del 6,2%, aumentando progresivamente del 3,1% en los hospitales de muy alto volumen al 10,6% en los hospitales de muy bajo volumen. Para fines de centralización, al aplicar un umbral de volumen mínimo ≥ 10 resecciones/año, se seleccionarían 92 centros, con una mortalidad global del 5,3%. Sin embargo, la mortalidad sería > 5% en 48 hospitales y > 10% en 17 hospitales. Si el volumen mínimo fuera de 25 resecciones/año, la mortalidad global sería del 4,7% en 38 hospitales, pero aún > 5% en 17 centros y > 10% en seis centros. La combinación de un volumen necesario (≥ 10 resecciones/año) con un umbral de mortalidad (RSMR ≤ 5% o ≤ 10%) permitiría excluir hospitales con resultados inaceptables, determinando una mortalidad global más baja (2,7% en 45 hospitales o 4,2% en 76 hospitales, respectivamente). CONCLUSIÓN: El mejor modelo para la centralización de resecciones pancreáticas incluyó un umbral para el volumen hospitalario combinado con un umbral de mortalidad.

Autologous micrografts and methotrexate in plantar erosive lichen planus: healing and pain control. A case report.

Erosive lichen planus is an uncommon variant of lichen planus. We report a case of longstanding and refractory plantar ELPs causing disabling and opiate-resistant pain treated with 'classic' meshed skin graft combined with Rigenera®  micrografts. After approximately 9 months follow-up, no clinical recurrence or pain were observed. Erosive lichen planus (ELP) is an uncommon variant of lichen planus, involving oral cavity and genitalia and, less often plantar areas, where it usually presents with chronic erosions of the soles, along with intense, disabling pain and progressive loss of toenails. An abnormal immune cellular response (CD8+ lymphocytes and macrophages) and the consequent altered production of multiple mediators (interleukin-12, interferon-γ, tumor necrosis factor-α, RANTES and MMP-9), seem to play a crucial role in the pathogenesis, although the etiology remains uncertain. From a histological point of view, ELP shows keratinocyte apoptosis, intense inflammatory response and basal epithelial keratinocytes TNF-α overexpression. Several therapies have been proposed, with variable and controversial results. While topical corticosteroids and topical calcineurin inhibitors are the treatments of choice for localized forms, short pulses of systemic glucocorticoids, phototherapy, and systemic immunosuppressants are recommended for generalized cases. Surgery has been reported as a possible therapeutic option in refractory and stable cases with localized lesions, either alone or with cyclosporine. Herein, we report a case of longstanding and refractory plantar ELPS causing disabling and opiate-resistant pain treated with 'classic' meshed skin graft combined with Rigenera® micrografts.

Prognostic value of fluorodeoxyglucose positron emission tomography/computed tomography and inguinal sentinel lymph node biopsy in patients with anal cancer.

AIM: The aim of this study was to assess the value of positron emission tomography (PET)/CT and sentinel lymph node (SLN) biopsy in staging inguinal lymph nodes in anal cancer patients and to determine if the results of the two methods could be of prognostic value. METHOD: Sixty-three patients with anal cancer and clinically negative inguinal lymph nodes underwent lymphoscintigraphy and inguinal SLN biopsy and/or fluorodeoxyglucose (FDG) PET/CT scan. All patients were treated with radiotherapy combined with 5-fluorouracil and mitomycin-C. RESULTS: Overall (OS) and disease-free survival (DFS) were 43 months (range 5-211) and 43 months (range 4-142) respectively. PET/CT examination showed high FDG uptake in the inguinal lymph nodes in 25% of patients. Thirty-five patients with inguinal uptake at lymphoscintigraphy underwent inguinal SLN biopsy and metastatic nodes were found in 31.4%. There was no statistical difference in OS (55 vs 41 months; P = 0.652) and DFS (48 vs 38 months; P = 0.992) between the group which showed inguinal uptake on PET/CT and the group which did not, while a positive inguinal SLN was associated with a worse OS (28 vs 59 months; P = 0.028) and DFS (56 vs 21 months; P = 0.046). When the two examinations were compared PET/CT showed a sensitivity, specificity, positive predictive value and negative predictive value of 22%, 82%, 33% and 73% respectively. CONCLUSION: The technique of SLN biopsy had a better diagnostic accuracy than total body FDG-PET/CT for the staging of inguinal lymph nodes in anal cancer patients; moreover it was a stronger predictor of OS and DFS than PET/CT.

Bariatric Surgery to Target Obesity in the Renal Transplant Population: Preliminary Experience in a Single Center.

During the last century, obesity has become a global epidemic. The effect of obesity on renal transplantation may occur in perioperative complications and impairment of organ function. Obese patients have metabolic derangements that can be exacerbated after transplantation and obesity directly impacts most transplantation outcomes. These recipients are more likely to develop adverse graft events, such as delayed graft function and early graft loss. Furthermore, obesity is synergic to some immunosuppressive agents in triggering diabetes and hypertension. As behavioral weight loss programs show disappointing results in these patients, bariatric surgery has been considered as a means to achieve rapid and long-term weight loss. Up-to-date literature shows laparoscopic bariatric surgery is feasible and safe in transplantation candidates and increases the rate of transplantation eligibility in obese patients with end-stage organ disease. There is no evidence that restrictive procedures modify the absorption of immunosuppressive medications. From 2013 to 2016 we performed six bariatric procedures (sleeve gastrectomy) on obese patients with renal transplantation; mean preoperative body mass index (BMI) was 39.8 kg/m2. No postoperative complication was observed and no change in the immunosuppressive medications regimen was needed. Mean observed estimated weight loss was 27.6%, 44.1%, 74.2%, and 75.9% at 1, 3, 6, and 12 months follow-up, respectively. Our recommendation is to consider patients with BMI >30 kg/m2 as temporarily ineligible for transplantation and as candidates to bariatric surgery if BMI >35 kg/m2. We consider laparoscopic sleeve gastrectomy as a feasible, first-choice procedure in this specific population.

Pancreas Transplantation From Very Small Pediatric Donor Using the "Cephalic Placement" Technique: A Case Report.

INTRODUCTION: The gap between the number of diabetic patients on the waiting list for transplantation and the number of pancreas donors is growing and it is mandatory to extend criteria for donor eligibility. Several reports showed the feasibility of pancreas transplantation from pediatric donors with comparable outcomes to adult donors in terms of long-term ß-cell function. However, there is no consensus about donor age and weight limits. CASE REPORT: We present two cases of pancreas transplantation alone (PTA) from very small pediatric donors: a 2-year-old female (weight 13 kg, height 88 cm) and a 6-year-old male (weight 29 kg, height 122 cm). We used a novel "cephalic placement" technique. The pancreas was placed upon the aortic carrefour with cephalic pole upward with 3 anchorage points: the left common iliac vein (or the inferior cava vein), the right common iliac artery, and an ileal loop. RESULTS: No postoperative thrombosis occurred and the patients gained insulin independence instantaneously. CT scan performed on postoperative day 3 showed regular organ perfusion in both cases. Graft volume and surface calculated by CT reconstruction were, respectively, 25 cc and 89 cm(2) in the first case, and 46.5 cc and 123 cm(2) in the second case. Postoperative mixed meal tolerance tests showed normal glycemic profile. Patients are actually insulin independent at 4 years and 8 months. CONCLUSIONS: Pancreases from very young pediatric donors are adequate to restore insulin independence after PTA in adult patients. The "cephalic placement" technique is feasible and effective using very small pancreases.

Hypovitaminosis D is associated with lower urinary tract symptoms and benign prostate hyperplasia in type 2 diabetes.

Lower urinary tract symptoms (LUTS) may develop more commonly in men with type 2 diabetes mellitus (T2DM). LUTS are often associated with benign prostate hyperplasia (BPH), in general population. An association between LUTS and hypovitaminosis D, and between hypovitaminosis D and type 2 diabetes (T2DM), has also been suggested. Thus, we aim to evaluate possible relationships between hypovitaminosis D, LUTS, and BPH in T2DM men. In this prospective observational study, 67 T2DM males (57.9 ± 9.28 years) underwent medical history collection, International Prostate Symptom Score (IPSS) questionnaire, that allows the identification and grading of LUTS, physical examination, biochemical/hormonal blood tests (fasting plasma glucose, glycated haemoglobin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, creatinine, LH, total testosterone, estradiol (E2 ), 25-OH-vitamin D, PTH, calcium, phosphate, and PSA) and ultrasound transrectal prostate examination. Subdividing patients into three groups, on the base of 25-OH-vitamin D concentration (sufficiency ≥50; insufficiency >25 < 50; and deficiency ≤25 nm), a significant progressive increase of prostate volume (p = 0.037), IPSS score (p = 0.019), diastolic blood pressure (p = 0.018), and a significant decrease in HDL cholesterol (p = 0.038) were observed. 25-OH-Vitamin D levels were inversely correlated with both IPSS (R = -0.333; p = 0.006) and prostate volume (R = -0.311; p = 0.011). At multivariate analysis, hypovitaminosis D remained an independent predictor of both IPSS and prostate volume. In conclusion, we showed, for the first time, an association between 25-OH-vitamin D deficiency, LUTS, and BPH in T2DM men.

Conservative surgical treatment of a thin acral lentiginous melanoma of the thumb with no recurrences: a case report.

Surgical treatment for acral lentiginous melanoma (ALM) is usually radical and severely invalidating, given its distinctly aggressive nature and poor prognosis. We report on a 76-year-old male patient with ALM of the left thumb who refused total amputation that would limit his gripping function. A "surgical degloving" was consequently performed, followed by plastic reconstruction with a radial antebrachial (the so-called Chinese) flap. A year after surgery, the patient was able to perform most finalized thumb movements without difficulty, and no metastases were recorded over a 5-year follow-up. The authors discuss the indications for such a treatment for thinner ALM in relation to the biological behavior of ALM.

Microangiopathy is independently associated with presence, severity and composition of carotid atherosclerosis in type 2 diabetes.

BACKGROUND AND AIMS: Common mechanisms for the development of micro- and macroangiopathic diabetic complications have been suggested. We aimed to cross-sectionally investigate strength and characteristics of the association between carotid atherosclerosis and microangiopathy in type 2 diabetic patients. METHODS AND RESULTS: Common carotid artery intima-media thickness (cIMT), carotid plaque (CP) type and degree of stenosis were evaluated by ultrasound, along with the determination of anthropometric parameters, HbA1c, lipid profile, assessment of diabetic retinopathy and nephropathy, in 662 consecutive patients with type 2 diabetes mellitus (T2DM). Patients were divided according to high/low cIMT, presence/absence of CP and of retinopathy and nephropathy. Patients with CP were older, more prevalently males, past smokers, had longer diabetes duration, significantly lower HDL cholesterol and more prevalent ischemic heart disease (all p<0.05) as compared to those with cIMT < 1 mm. Microangiopathies were more prevalent in patients with CP than in those without. At multivariate logistic regression, factors independently associated with the presence of CP were age, past smoke, HDL cholesterol, retinopathy and retinopathy plus nephropathy. A significant independent correlation of CP stenosis with stage of retinopathy and nephropathy was found. Finally, echolucent CPs were associated with a lower prevalence of proliferative retinopathy than CP containing calcium deposits. CONCLUSION: In T2DM, retinopathy, alone or in combination with nephropathy, is independently associated to CP, and severity of microangiopathy correlates with severity of carotid atherosclerosis. These observations, together with the different prevalence of proliferative retinopathy according to CP types, point to possible common pathogenic mechanisms in micro- and macrovascular complications.

Nonalcoholic fatty liver disease (NAFLD) in nonobese patients with diabetes: Prevalence and relationships with hemodynamic alterations detected with Doppler sonography().

AIM: To evaluate the prevalence, severity, and hemodynamic features of nonalcoholic fatty liver disease (NAFLD) in nonobese diabetics. METHODS: We studied 100 consecutive nonobese (body mass index [BMI] < 30) patients with type 1 (n = 17) or type 2 (n = 83) diabetes and no known causes of liver disease. Steatosis was diagnosed and graded with ultrasonography. Digital sonographic images of the liver and right kidney were analyzed with dedicated software (HDI-Lab), and the liver/kidney ratio of grey-scale intensity was calculated as an index of the severity of the steatosis. Severity scores ranging from 0 (none) to 5 (severe) were compared with sonographic and Doppler findings (right liver size, portal vein diameter and flow velocity, hepatic and splenic arterial pulsatility indices, hepatic-vein flow profile and A- and S-wave velocities). RESULTS: The prevalence of steatosis was 24% in type I and 80% in type II diabetes (grade 1 in 17%, grade 2 in 34%, grade 3 in 33%, grade 4 in 9%, grade 5 in 7%). In patients with steatosis (especially those with grades 4-5 disease), hepatic volume was increased (p < 0.005). Portal vein diameter was increased in grade 5 steatosis. The hepatic artery pulsatility index was significantly increased, particularly in grades 4 and 5 (p < 0.0001); portal and A-wave velocities were significantly reduced in grades 3-5 (p < 0.001); and the hepatic vein flow profile was altered in 27% (biphasic: 20%, flat: 7%) patients with steatosis, although there was no correlation with severity. CONCLUSIONS: NAFLD is very frequent in nonobese diabetics with type 2 but not type 1 disease, and it is associated with hepatomegaly and liver hemodynamic alterations only when it is severe.

A phase II study of pegylated liposomal doxorubicin oxaliplatin and cyclophosphamide as second-line treatment in relapsed ovarian carcinoma.

We carried out a phase II nonrandomized study to examine the level of activity of oxaliplatin, pegylated liposomal doxorubicin, and cyclophosphamide in a patient population with relapsed ovarian cancer pretreated with platinum derivatives and paclitaxel. Patients received oxaliplatin (85 mg/m2), pegylated liposomal doxorubicin (30 mg/m2), and cyclophosphamide (750 mg/m2). A total of 49 patients (39 assessable for toxicity and response) were enrolled in this trial. Neutropenia grade 3 was observed in six patients (15%) and anemia grade 3 in one patient (0.2%). Fatigue grade 1-2 occurred in 26 patients (66%), nausea/vomiting grade 1 in 23 patients (58%), and alopecia grade 1-2 in 19 patients (48%). Twenty-one (53%) patients experienced grade 1-2 peripheral neuropathy. The overall response rate was 46% (95% CI 23.6-68.7). Median progression-free survival was 28 weeks (range 12-52 weeks) and median survival was 45 weeks (range 26-136+ weeks). The mean duration of response was 34 weeks (range 16-52 weeks). In platinum-resistant and -refractory ovarian cancer patients, the overall response rate was 37% (CI 95% 14.4-60.8) with a progression-free survival of 28 weeks (range 12-52 weeks) and a median survival of 42 weeks (range 28-84 weeks). This combination chemotherapy is generally well tolerated and is an active second-line regimen against ovarian cancer.

Continuous subcutaneous insulin infusion (CSII) in the Veneto region: efficacy, acceptability and quality of life.

AIM: To study the effect of continuous subcutaneous insulin infusion (CSII) on metabolic control and well-being in patients with Type 1 diabetes. METHODS: Efficacy, safety and interference with everyday life associated with CSII were studied retrospectively in 138 diabetic patients from the Veneto region treated for 7.4 +/- 0.4 years. RESULTS: Glycosylated haemoglobin decreased during the first year of CSII from 9.3 +/- 0.2% to 7.9 +/- 0.1% (P < 0.0001), and then remained unchanged. Serious hypoglycaemia decreased from 0.31 +/- 0.07/year to 0.09 +/- 0.02/year (P < 0.003), as did ketoacidosis (from 0.41 +/- 0.12/year to 0.11 +/- 0.03/year, P < 0.013). During the first year of therapy daily insulin requirement decreased from 49 +/- 1 to 42 +/- 2 U/day (P < 0.0001) and did not change thereafter. The number of out-patient consultations and hospital admissions per year also decreased significantly. CSII was associated with a progressive increase of body weight (P < 0.05) and with 0.2 +/- 0.04 infections/patient per year at the infusion site. Infection was rated as mild in 72%, moderate in 18%, severe in 10%. Patients reported that CSII improved metabolic control (71%), sense of well-being (41%), and allowed more freedom (40%). Quality of life, assessed using the DQOL, after 7 years of CSII was rated as good by patients (score of 73.0 +/- 1.8 on a scale from 0 to 100). CONCLUSIONS: This retrospective analysis suggests that CSII improves metabolic control in Type 1 diabetic patients, reduces hypoglycaemic and ketoacidotic events, is well accepted, allows a good quality of life and decreases out-patient consultations and hospital admissions.

Xanthogranulomatous salpingitis. Case report and review of the literature.

A xanthogranulomatous salpingitis, occurring in a fifty-two year old patient and appearing itself as a hydrosalpinx, is reported. The histological picture was characterized by the presence of several foamy histiocytes admixed with other inflammatory cells. Considerations about epidemiology, etiopathogenetic mechanisms and problems of differential diagnosis with other diseases are discussed.

Effect of GnRH administration on blood polyamines and LH levels in normal and obese children.

Blood polyamines (spermidine and spermine) and LH levels have been studied after acute GnRH injection both in obese and normal weight children. In both groups LH values significantly increased after stimulation but reached higher peaks in normal children than in obese ones (P less than 0.05). On the contrary, polyamine levels increased significantly only in the normal weight children. LH peaked at 30 min and polyamines at 60 min after GnRH injection. On the basis of the proposed role of polyamines in hormone action and of our results, we suggest that polyamines may play a pivotal role in hormone responsiveness of hypothalamic-hypophyseal axis.