Epidemiology, clinical features and treatment of chronic pancreatitis. current knowledge and future perspectives [Epidemiologia, clinica e terapia medica della pancreatite cronica: evidenze attuali e sviluppi per il futuro]

La pancreatite cronica è una patologia dal complesso inquadramento sia dal punto di vista epidemiologico, con dati incerti sull’esatta prevalenza, sia dell’eziologia, a volte non individuabile e per la quale si sta delineando sempre più la rilevanza delle forme post-pancreatite acuta, con il fumo come fattore di rischio spesso sottovalutato rispetto all’alcol. La pancreatite cronica si associa ad aumento della mortalità e morbilità, legate soprattutto a patologie extrapancreatiche. L’eventuale presenza di insufficienza esocrina o endocrina pancreatica può essere, inoltre, alla base di complicanze anche gravi e spesso non prevenute per tempo. I deficit vitaminici e di micro- e macronutrienti vanno attentamente ricercati e corretti; questo sarà inoltre fondamentale per evitare complicanze quali l’osteoporosi. Il dolore è il sintomo più rilevante, ha una patogenesi complessa, legata non solo a fattori ostruttivi e meccanici o alla flogosi, ma anche un’alterazione cronica del processo di adattamento al dolore a livello del sistema nervoso centrale. Anche per questo la terapia del dolore è spesso inefficace. La chirurgia derivativa è indicata nelle forme con ostruzione duttale con risultati che sembrano superiori a quelli dell’endoscopia, e quella resettiva in quelle associate a massa infiammatoria. Una nuova frontiera è rappresentata poi dalla pancreasectomia totale con trapianto di insule, che offre ottimi risultati in termini di controllo del dolore con possibilità di evitare il diabete in una buona percentuale di pazienti. Questa rassegna discute tali “hot topics” racchiudendo sia le evidenze più recenti sull’argomento sia una riflessione su come evolveranno le nostre conoscenze su tale patologia.Chronic pancreatitis is a complex disease both for the epidemiology, with uncertain data on the exact prevalence, but also for the etiology, often not identified and for whom, compared to the past, post acute pancreatitis forms are showing a high impact; also smoking is an etiological factor often underestimated compared to alcohol. Chronic pancreatitis is associated with high mortality and morbidity, mostly due to extrapancreatic diseases. The eventual occurrence of exocrine or endocrine pancreatic insufficiency can lead to complications, often serious and not prevented in time. It is, in fact, well known how this can cause micro or macronutrient and vitamin deficit which, if not screened and corrected, can cause complications such as osteoporosis. Abdominal pain is the most relevant symptom, with a complex pathogenesis, due not only to obstructive or mechanical factors or inflammation, but also to a chronic alteration of the adaptation process of pain in the central nervous system. Also for this reason, therapies are often not effective. Derivative surgery is indicated in obstructive forms, with results superior to those of endoscopy, while resective surgery is indicated when an inflammatory mass is present. A new opportunity is total pancreatectomy with islet autotransplantation, which offers excellent results in terms of pain relief and possibility to avoid diabetes in a high percentage of patients. This review will discuss these hot topics comprehending both most recent evidence and a view on how our knowledge on this disease will change in the upcoming years

Role of Fibre in Nutritional Management of Pancreatic Diseases

The role of fibre intake in the management of patients with pancreatic disease is still controversial. In acute pancreatitis, a prebiotic enriched diet is associated with low rates of pancreatic necrosis infection, hospital stay, systemic inflammatory response syndrome and multiorgan failure. This protective effect seems to be connected with the ability of fibre to stabilise the disturbed intestinal barrier homeostasis and to reduce the infection rate. On the other hand, in patients with exocrine pancreatic insufficiency, a high content fibre diet is associated with an increased wet fecal weight and fecal fat excretion because of the fibre inhibition of pancreatic enzymes. The mechanism by which dietary fibre reduces the pancreatic enzyme activity is still not clear. It seems likely that pancreatic enzymes are absorbed on the fibre surface or entrapped in pectin, a gel-like substance, and are likely inactivated by anti-nutrient compounds present in some foods. The aim of the present review is to highlight the current knowledge on the role of fibre in the nutritional management of patients with pancreatic disorders

Effect of mitotane on mouse ovarian follicle development and fertility.

Mitotane (MTT) is an adrenolytic drug used in advanced and adjuvant treatment of adrenocortical carcinoma, in Cushing's disease and in ectopic syndrome. However, knowledge about its effects on the ovary is still scarce. The purpose of this study is to investigate the effect of MTT on the ovary using in vivo and in vitro models. The study was performed in CD1 mice and in the COV-434 human ovarian granulosa cell line. We examined ovarian morphology, follicle development, steroidogenesis and procreative function in mice and the effect of MTT on cell growth in vitro. Our results revealed that treatment of CD1 mice with MTT induces a decrease in early antral follicles with a subsequent increase in the secondary follicles, measured by the increased levels of anti-Mullerian Hormone (P < 0.05) and decreased levels of FSH receptor (P < 0.05). Moreover, we observed a significant decrease in Cyp11a1 (P < 0.01) and Cyp17a1 (P < 0.001) mRNA level in MTT-treated animals. Ovulation, induced by PMSG/hCG stimulation, was also significantly impaired, with a reduction in the number of ovulated oocytes (P < 0.01) and fewer corpora lutea in treated animals. Likewise, the mating experiment demonstrated a delay in the time of conception as well as fewer pups per litter in MTT-treated mice (P < 0.05). Experiments performed on the COV-434 cell line showed a significant inhibition of growth followed by apoptosis (P < 0.01). In conclusion, our study highlights the key points of ovarian folliculogenesis affected by MTT and demonstrates impairment of the ovulation process with a negative impact on conception, which is nevertheless preserved

Integrative analysis of hereditary nonpolyposis colorectal cancer: The contribution of allele-specific expression and other assays to diagnostic algorithms

The identification of germline variants predisposing to hereditary nonpolyposis colorectal cancer (HNPCC) is crucial for clinical management of carriers, but several probands remain negative for such variants or bear variants of uncertain significance (VUS). Here we describe the results of integrative molecular analyses in 132 HNPCC patients providing evidences for improved genetic testing of HNPCC with traditional or next generation methods. Patients were screened for: germline allele-specific expression (ASE), nucleotide variants, rearrangements and promoter methylation of mismatch repair (MMR) genes; germline EPCAM rearrangements; tumor microsatellite instability (MSI) and immunohistochemical (IHC) MMR protein expression. Probands negative for pathogenic variants of MMR genes were screened for germline APC and MUTYH sequence variants. Most germline defects identified were sequence variants and rearrangements of MMR genes. Remarkably, altered germline ASE of MMR genes was detected in 8/22 (36.5%) probands analyzed, including 3 cases negative at other screenings. Moreover, ASE provided evidence for the pathogenic role and guided the characterization of a VUS shared by 2 additional probands. No germline MMR gene promoter methylation was observed and only one EPCAM rearrangement was detected. In several cases, tumor IHC and MSI diverged from germline screening results. Notably, APC or biallelic MUTYH germline defects were identified in 2/19 probands negative for pathogenic variants of MMR genes. Our results show that ASE complements gDNA-based analyses in the identification of MMR defects and in the characterization of VUS affecting gene expression, increasing the number of germline alterations detected. An appreciable fraction of probands negative for MMR gene variants harbors APC or MUTYH variants. These results indicate that germline ASE analysis and screening for APC and MUTYH defects should be included in HNPCC diagnostic algorithms

Persistent Megalocystic Ovary Following in Vitro Fertilization in a Postpartum Patient with Polycystic Ovarian Syndrome

SummaryObjectiveOvarian hyperstimulation syndrome (OHSS) is more severe when pregnancy occurs, as the developing pregnancy produces human chorionic gonadotropin, which stimulates the ovary's persistent growth. If no pregnancy occurs, the syndrome will typically resolve within 1 week. In a maintained pregnancy, slow resolution of symptoms usually occurs over 1-2 months.Case ReportA 31-year-old woman, gravida 2, para 1, aborta 1, with polycystic ovary syndrome underwent in vitro fertilization (IVF) with clomiphene citrate and follicle-stimulating hormone/gonadotropin releasing hormone-antagonist stimulation. During transvaginal oocyte retrieval, enlarged bilateral ovaries were noted. She had an episode of OHSS after IVF/embryo transfer, for which paracentesis was performed three times. Pregnancy was achieved. Throughout antenatal examinations, bilateral ovaries were enlarged. She delivered a healthy baby by cesarean section at term. However, 1 month after delivery, the bilateral ovary had not shrunk, and levels of tumor markers CA125 and CA199 were 50.84 and 41.34 U/mL, respectively. At laparotomy for suspected malignancy, both adnexae formed “kissing ovaries”, which were multinodulated with yellow serous fluid. Specimens from wedge resection submitted for frozen section showed a benign ovarian cyst. The final pathology report showed bilateral follicle cysts.ConclusionWith the increasing use of gonadotropins in the management of infertility, ovarian enlargement secondary to hyperstimulation is common. Generally, symptoms appear between the 6th and 13th weeks of pregnancy and disappear thereafter. The hyperstimulated ovary often subsides after the first trimester. This case is unusual as the megalocystic ovary persisted after delivery. To the best of our knowledge, we report the first case of enlarged bilateral ovaries persisting 2 months after delivery

A new micro-forceps for endoscopic ultrasound-guided through-the-needle biopsy in the diagnosis of pancreatic cystic lesions: single center experience

Background and aim: Endoscopic ultrasound (EUS)-guided through-the-needle biopsy (TTNB) has improved the diagnostic algorithm of pancreatic cystic neoplasms (PCNs). Recently, a new through-the-needle micro-forceps device (Micro Bite, MTW Endoskopie Manufakture) has been introduced. The primary aim was to assess the safety and technical success of this new type of micro-forceps. The secondary aim was to evaluate the diagnostic role of EUS-TTNB. Methods: Retrospective study of consecutive patients receiving EUS-TTNB for the diagnosis of PCNs. Two micro-forceps were used: Moray Micro-forceps and Micro-Bite. Cystic fluid was collected for cytological analysis. Categorical variables were analyzed by Fisher's exact test, and continuous variables were analyzed by Student's t-test. P &lt; 0.05 was considered significant. Results: Forty-nine patients enrolled in the study (24% male; mean age 63 ± 14 years). TTNB was successfully performed in all patients. A diagnostic sample was obtained in 67.3% PCNs with TTNB compared with 36.7% with cyst fluid cytology (P 0.01). Adverse events rate was 10.2% and occurred in older patients (76.6 ± 5.4 vs 61.3 ± 13.7 P = 0.02). The 51% underwent EUS-TTNB with Micro Bite. A diagnostic sample was obtained in 52% PCNs with Micro Bite compared with 24% obtained with cyst fluid cytology (P = 0.07). Comparing the two devices, the rate of diagnostic sample obtained with the micro-forceps Moray was higher than that obtained with the Micro Bite (20/24 [83.3%] vs 13/25 [52%] P 0.03). Conclusions: EUS-TTNB increases the diagnostic yield of PCNs. The new Micro-Bite could represent a valid alternative to the currently used Moray Micro-forceps, but its diagnostic rate is still suboptimal and further studies are needed. Keywords: endoscopic ultrasound; increased diagnosis; micro‐forceps; new device; pancreatic cystic neoplasm

The application of pancreatitis activity score system in clinical practice: an italian experience

The improvement of the management strategies in acute pancreatitis (AP) is mainly limited by the lack of early and quickly accepted methods to measure disease activity. The identification of patients that will develop severe AP at the time of hospitalization allows for the selection of patients that could benefit from specific invasive interventions

Early management of acute pancreatitis : A review of the best evidence

In the 20th century early management of acute pancreatitis often included surgical intervention, despite overwhelming mortality. The emergence of high-quality evidence (randomized controlled trials and meta-analyses) over the past two decades has notably shifted the treatment paradigm towards predominantly non-surgical management early in the course of acute pancreatitis. The present evidence-based review focuses on contemporary aspects of early management (which include analgesia, fluid resuscitation, antibiotics, nutrition, and endoscopic retrograde cholangiopancreatography) with a view to providing clear and succinct guidelines on early management of patients with acute pancreatitis in 2017 and beyond

Small Intestine Bacterial Overgrowth Is not Related with Disease Severity and Symptoms in Patients with Chronic Pancreatitis

Context Small intestine bacterial overgrowth (SIBO) is considered as a factor possibly worsening symptoms and nutritional status in patients with chronic pancreatitis (CP) and pancreatic exocrine insufficiency (PEI) not responding to treatment. However, few studies evaluated the rate of SIBO in CP patients (range of positivity ranging 0-92%), employed different substrates and non-standardized procedures, and often investigated CP patients with previous resective surgery (cause of SIBO per se). Objective To assess the prevalence of SIBO in CP patients without history of resective surgery as compared with a control group. Secondary aim is to analyze factors related with SIBO in CP patients. Methods CP patients and controls (outpatients with upper-GI unspecific symptoms; exclusion criteria CP, IBD, celiac disease or previous surgery), had SIBO evaluated by H2 glucose breath test (GBT) with a standard protocol according to Rome consensus conference. Positivity rate, basal, peak over basal (HOB) and H2 values at 120 minutes were evaluated. For CP patients, relation between GBT results, abdominal symptoms, nutritional and clinical variables was analyzed. Results Twenty-six CP patients and 22 controls were enrolled. Of the 26 patients (alcoholic aetiology in 11), 13 had PEI, 5 advanced CP (defined by M-ANNHEIM severity index) and none had previous resective surgery. GBT positivity rate was 5/26 (19.2%) in cases and 3/21 (13.6%) in controls (P=0.71). Mean H2 basal excretion (9.78 ppm in CP vs. 5.47 ppm in controls; P=0.13), HOB (4.6 ppm in CP vs. 4.52 ppm in controls; P=0.95) and H2 at 120 minutes (4.86 in CP vs. 2.20 in controls; P=0.08) were not different between the two groups. Diagnosis of SIBO in the CP group was not correlated with presence of PEI, severity of disease, abdominal symptoms, pancreatic enzymes and proton pump inhibitors therapy. Conclusion The rate of SIBO seems similar in CP patients without previous resective surgery and controls. CP patients with SIBO did not have more severe disease, more symptoms or worse nutritional status. These findings do not suggest a relevant impact of SIBO on the clinical course and management of uncomplicated CP but our findings deserve confirmation in a larger cohort