Proposal for a New Pathologic Prognostic Index After Neoadjuvant Chemotherapy in Pancreatic Ductal Adenocarcinoma (PINC).

BACKGROUND: Limited information is available on the relevant prognostic variables after surgery for patients with pancreatic ductal adenocarcinoma (PDAC) subjected to neoadjuvant chemotherapy (NACT). NACT is known to induce a spectrum of histological changes in PDAC. Different grading regression systems are currently available; unfortunately, they lack precision and accuracy. We aimed to identify a new quantitative prognostic index based on tumor morphology. PATIENTS AND METHODS: The study population was composed of 69 patients with resectable or borderline resectable PDAC treated with preoperative NACT (neoadjuvant group) and 36 patients submitted to upfront surgery (upfront-surgery group). A comprehensive histological assessment on hematoxylin and eosin (H&E) stained sections evaluated 20 morphological parameters. The association between patient survival and morphological variables was evaluated to generate a prognostic index. RESULTS: The distribution of morphological parameters evaluated was significantly different between upfront-surgery and neoadjuvant groups, demonstrating the effect of NACT on tumor morphology. On multivariate analysis for patients that received NACT, the predictors of shorter overall survival (OS) and disease-free survival (DFS) were perineural invasion and lymph node ratio. Conversely, high stroma to neoplasia ratio predicted longer OS and DFS. These variables were combined to generate a semiquantitative prognostic index based on both OS and DFS, which significantly distinguished patients with poor outcomes from those with a good outcome. Bootstrap analysis confirmed the reproducibility of the model. CONCLUSIONS: The pathologic prognostic index proposed is mostly quantitative in nature, easy to use, and may represent a reliable tumor regression grading system to predict patient outcomes after NACT followed by surgery for PDAC.

Urgent manifestations of immunoglobulin G4-related disease.

Objective: Immunoglobulin G4-related disease (IgG4-RD) is considered a chronic condition with insidious presentation, but clinical experience suggests that disease onset prompts admission to the emergency department (ED) in a sizeable proportion of patients. We assessed the prevalence of acute manifestations associated with IgG4-RD onset requiring referral to the ED. Method: We revised our database and identified patients admitted to the ED because of symptoms latterly attributed to IgG4-RD onset (Group 1) and those who were referred to our outpatient clinic without previous urgent manifestations (Group 2). Acute manifestations were clustered based on the anatomical region affected by IgG4-RD. Epidemiological, clinical, and serological features of Groups 1 and 2 were compared. Results: The study included 141 patients with IgG4-RD. Of these, 76 (54%) presented to the ED at disease onset. The most common clinical manifestations requiring admission to the ED were jaundice (53%), abdominal pain (41%), and fever (10%). Gastrointestinal involvement was the most frequent cause of referral to the ED (71% of cases), followed by involvement of the retroperitoneum (14.5%) and the nervous system (6.6%). Pancreatobiliary involvement was significantly more frequent in Group 1 than in Group 2. Head and neck, and salivary and lacrimal gland involvement was more frequent in Group 2 than in Group 1. The diagnostic delay was significantly shorter in Group 1 than in Group 2. Conclusion: Clinical manifestations associated with IgG4-RD onset require referral to the ED in most cases. This finding contrasts with the general view of IgG4-RD as a condition with non-acute presentation.

Meta-analysis of mortality in patients with high-risk intraductal papillary mucinous neoplasms under observation.

BACKGROUND: Although consensus guidelines suggest that patients with high-risk intraductal papillary mucinous neoplasms (IPMNs) should have surgery, a non-operative strategy is often selected in patients who are poor surgical candidates. The aim was to determine the risk of disease-related death from IPMN in patients with worrisome features or high-risk stigmata who were kept under observation. METHODS: A PubMed literature search was undertaken of articles published from August 1992 to June 2016 (updated October 2017). The methodology was developed from PRISMA and MOOSE checklists. Incidence proportions and rates of overall and IPMN-related deaths were calculated, with subgroup analyses for main-duct/mixed-type and branch-duct IPMNs. Quality of the studies, publication bias and heterogeneity were explored. RESULTS: Six studies reported data on overall mortality and eight described disease-specific mortality for 556 patients during follow-up ranging from 24·9 to 60·0 months. Pooled rates of overall and IPMN-related mortality were 30·9 (95 per cent c.i. 19·6 to 45·1) and 11·6 (6·0 to 21·2) per cent respectively. The pooled incidence rate for overall mortality was substantially higher than that for IPMN-related mortality: 78 (95 per cent c.i. 44 to 111) and 23 (9 to 37) per 1000 patient-years respectively. The pooled incidence rate for disease-specific mortality was considerably lower for branch-duct than for main-duct or mixed-type IPMNs: 5 (0 to 10) and 32 (12 to 52) per 1000 patient-years respectively. CONCLUSION: In patients unfit for surgery, IPMN-related mortality among patients with worrisome features and high-risk stigmata is low, and the risk of death from other causes much higher.

Selecting patients for resection after primary chemotherapy for non-metastatic pancreatic adenocarcinoma.

BACKGROUND: Patients with borderline (BL) or locally advanced (LA) pancreatic adenocarcinoma are usually treated with primary chemotherapy (CT), followed by resection when feasible. Scanty data are available about the criteria to candidate patients to resection after CT. PATIENTS AND METHODS: Between 2002 and 2016 overall 223 patients diagnosed with BL or LA pancreatic adenocarcinoma were primarily treated with Gemcitabine combination (4-drugs or nab-paclitaxel-gemcitabine) for 3-6 months followed by surgery and/or chemoradiation. Resection was carried out when radical resection could be predicted by imaging studies and intraoperative findings. The prognostic value of both pre-treatment factors and treatment response was retrospectively evaluated, searching for criteria that could improve the selection of patients for surgery. RESULTS: Median survival (MS) for the whole population was 18.3 months. Surgical resection was carried out in 61 patients; MS in resected patients was significantly longer (30.0 months) as compared with 162 non-resected patients (16.5 months) (P < 0.00001). According to response criteria, 48% had a radiological partial response, 47% a stable disease and 5% a disease progression); CA19.9 response (reduction >50%) was obtained in 77.8% of patients. Among resected patients, neither pre-treatment factors, including BL/LA distinction, nor radiological response, were able to prognosticate survival differences. Survival of resected patients having no CA19.9 response was significantly lower as compared with responders (MS 15.0 versus 31.5 months, P = 0.04), and was similar to non-responders patients that did not undergo resection (MS 10.9 months, P= 0.25). Multivariate analysis carried out on the overall population, showed that Karnofsky performance status, T3-T4 status, resection and CA19.9 response were independent prognostic factors, while radiological response, BL/LA distinction and baseline CA19.9 had not significant influence on survival. CONCLUSIONS: CA19.9 response may allow a better selection of patients who will benefit from resection after primary CT for BL or LA pancreatic adenocarcinoma.

Systematic review and meta-analysis of metal versus plastic stents for preoperative biliary drainage in resectable periampullary or pancreatic head tumors.

BACKGROUND: Preoperative biliary drainage (PBD) with stenting increases complications compared with surgery without PBD. Metallic stents are considered superior to plastic stents when considering stent-related complications. Aim of the present systematic review and meta-analysis is to compare the rate of endoscopic re-intervention before surgery and postoperative outcomes of metal versus plastic stents in patients with resectable periampullary or pancreatic head neoplasms. METHODS: We conducted a bibliographic research using the National Library of Medicine's PubMed database, including both randomized controlled trials (RCTs) and non-RCTs. Quantitative synthesis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Statistical heterogeneity was assessed using the I(2) tests. RESULTS: One RCT and four non-RCTs were selected, including 704 patients. Of these, 202 patients (29.5%) were treated with metal stents and 502 (70.5%) with plastic stents. The majority of patients (86.4%) had pancreatic cancer. The rate of endoscopic re-intervention after preoperative biliary drainage was significantly lower in the metal stent (3.4%) than in the plastic stent (14.8%) group (p < 0.0001). The rate of postoperative pancreatic fistula was significantly lower in the meta stent group as well (5.1% versus 11.8%, p = 0.04). The rate of post-operative surgical complications and of - post-operative mortality did not differ between the two groups. CONCLUSIONS: Although the present systematic review and meta-analysis demonstrates that metal stent are more effective than plastic stents for PBD in patients with resectable periampullary tumors, randomized controlled trials are needed in order to confirm these data with a higher level of evidence.

Comparison of capillary versus aspiration technique in endoscopic ultrasound-guided fine-needle aspiration: A preliminary report.

INTRODUCTION: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used to diagnose pancreatic malignancies. Different EUS-FNA techniques have been described to improve sample quality. Recently, a new technique, using capillarity, has been proposed. AIM: To assess the quality of cytological samples, comparing two different FNA techniques, in order to optimize tissue acquisition. METHODS: All consecutive patients with solid pancreatic lesions, requiring an EUS-FNA, were included in the study between July and September 2013. All procedures were done under deep sedation. FNA was performed using a 25 gauge needle, using both capillary and aspiration technique. Patients were randomized to undergo firstly one or the other technique. Samples were evaluated "on site" by expert cytotechnologist. An expert cytopathologist, blinded for the technique used, reviewed the slides, for final diagnosis and assessed sampling quality. Quality of samples was evaluated through the assessment of the amount of blood, cellularity, tumoral versus normal cells ratio and adequacy for final diagnosis. Data were analyzed with Student's t-test and Chi-square test, assuming a significant P value of 0.05. RESULTS: A total of 30 consecutive patients (19 M, mean age 67.8 years) with an EUS finding of pancreatic solid lesion were included in the study. Cytological final diagnosis was adenocarcinoma in 25/30 (83.3%) cases, neuroendocrine tumor 1/30 (3.3%), intraductal papillary mucosal neoplasms with high-grade dysplasia 2/30 (6.7%), gastrointestinal stromal tumor in 1/30 (3.3%) and negative for malignant cells 1/30 (3.3%). The difference between the overall blood amount score per technique was not statistically significant (P = 0.61) as well as the cellularity score (P = 0.08). In 13/30 patients (43%) the two techniques reported concordant T/N ratio. In 6/30 patients (20%) final diagnosis was achieved only by capillary obtained smears. In 1/30 patients (3.3%) the diagnosis was done with aspiration. In the remnant, the ratio between the two techniques was similar. Adequacy was reached in 24/30 (80%) with aspiration and 29/30 (97%) with capillary technique (P = 0.04). CONCLUSIONS: Aspiration and capillary sampling techniques provided similar results in cellularity and blood amount. However, adequacy rate was significantly superior in capillary technique. Furthermore, in 20% of cases, final diagnosis was achieved only with capillary samples.

Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

BACKGROUND: The objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence. PATIENTS AND METHODS: We conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits. RESULTS: Ninety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17-3.96), renal cell carcinoma (6.00; CI 95% 2.74-11.39) and thyroid carcinoma (5.56; CI 95% 1.80-12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline. CONCLUSION: We report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.

Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound (EUS) elastography represents a new imaging procedure that might characterize the differences of hardness and strain between diseased tissue and normal tissue. The aim of this study was to assess the efficiency of EUS elastography for the differentiation of focal masses in chronic pancreatitis and pancreatic cancer. PATIENTS AND METHODS: The study group comprised 258 patients with focal pancreatic masses included prospectively at 13 participating centers. Qualitative analysis of the diagnoses made by two expert doctors using all recorded video clips was performed in order to test the interobserver variability. A post-processing software analysis was used to examine the EUS elastography videos by calculating average-hue histograms of individual elastography images. The quantitative information was used to calculate intra-observer variability and the accuracy of the method. RESULTS: Qualitative analysis of the recorded videos revealed a kappa value of 0.72. Intra-observer variability analysis revealed that the single measure intraclass correlation ranged between 0.86 and 0.94. The average-hue histogram analysis of the data indicated a sensitivity of 93.4 %, a specificity of 66.0 %, a positive predictive value of 92.5 %, a negative predictive value of 68.9 %, and an overall accuracy of 85.4 %, based on a cut-off value of 175. Area under the receiver operating characteristic curve (AUROC) was 0.854 ( P < 0.0001) with a confidence interval of 0.804 - 0.894. CONCLUSION: The value of quantitative analysis of EUS elastography recordings was proven by good reproducibility of the videos, as well as good parameters of the AUROC analysis. (Clinical Trials.gov identifier: CT00909103).

Endoscopic ultrasound in the evaluation of pancreaticobiliary disorders.

The close proximity of the endoscopic ultrasound probe to the pancreas coupled with the ability to perform fine needle aspiration has made endoscopic ultrasound an extremely important technique for the evaluation of both benign and malignant pancreaticobiliary disorders. In parallel to the widespread importance of diagnostic endoscopic ultrasound, the therapeutic and interventional applications of this procedure are expanding and may become a major breakthrough in the management of pancreaticobiliary diseases. This article focuses on the utility and recent advances of endoscopic ultrasound in the diagnostic evaluation pancreaticobiliary disorders and analyses the data of well established interventional procedures such as celiac plexus neurolysis and pseudocyst drainage. Moreover, the more innovative procedures, such endoscopic ultrasound-guided biliary and pancreatic ducts access and drainage and the experimental use of direct endoscopic ultrasound-guided therapy of both solid and cystic pancreatic lesions will also be reviewed.

Investigation of Oddi sphincter structure by optical coherence tomography in patients with biliary-type 1 dysfunction: a pilot in vivo study.

BACKGROUND: Type 1 sphincter of Oddi dysfunction is a clinical entity characterised by biliary-type pain, elevated liver biochemical tests, and common bile duct dilation. Sphincter fibrosis is a common finding in this type of dysfunction and may require in some cases a differential diagnosis with a malignant intra-papillary disease. Optical coherence tomography permits high-resolution, real-time imaging of the sphincter of Oddi microstructure by a probe inserted into the common bile duct through an ERCP catheter. No data exist on the evaluation of sphincter of Oddi fibrosis by optical coherence tomography during ERCP in vivo. OBJECTIVE: To assess the feasibility of optical coherence tomography investigation of the sphincter of Oddi structure and assess its potential for diagnosing type 1 sphincter of Oddi dysfunction. PATIENTS: Ten consecutive patients, five with biliary-type 1 sphincter of Oddi dysfunction and five with pancreatic head/mid-body adenocarcinoma not involving the papillary region, who underwent both endoscopic ultrasound and therapeutic ERCP, were investigated by optical coherence tomography immediately before biliary sphincterotomy or stenting. RESULTS: In all sphincter of Oddi dysfunction patients optical coherence tomography recognised a hyper-reflective intermediate, fibro-muscular layer, significantly thicker than in patients with non-pathological sphincter of Oddi (p<0.0001). CONCLUSIONS: Optical coherence tomography imaging recognised an increased thickness and reflectance of the fibro-muscular layer of the sphincter of Oddi, very likely determined by fibrosis, and was not time-consuming; it can be safely used during ERCP to confirm the diagnosis in difficult cases. Its use in clinical practice has one important limitation since it requires magnification in the post-procedure computer analysis to obtain images useful for diagnosis.

Outcome of upfront combination chemotherapy followed by chemoradiation for locally advanced pancreatic adenocarcinoma.

PURPOSE: The role and timing of chemotherapy and radiation for treating stage III pancreatic adenocarcinoma remains controversial. METHODS: Treatment-naive patients with stage III non-resectable pancreatic adenocarcinoma were treated with PEFG/PEXG (cisplatin, epirubicin, 5-fluorouracil (F)/capecitabine (X), gemcitabine) or PDXG (docetaxel substituting epirubicin) regimen for 6 months followed by radiotherapy (50-60 Gy) with concurrent F or X or G. RESULTS: Ninety-one patients were registered between April 1997 and December 2007. Forty-three patients (47%) had a partial remission and 38 (42%) had a stable disease. Thirteen patients (14%) were radically resected yielding one pathologic complete remission. Median survival (OS) was 16.2 months. Median progression-free survival was 9.9 months. Pattern of failure consisted of isolated local failure (N = 26, 35%); both local and systemic failure (N = 14, 19%); isolated systemic failure (N = 35, 47%). CONCLUSION: Combination chemotherapy with four-drug regimens followed by chemoradiation was a feasible strategy showing relevant results in stage III pancreatic adenocarcinoma.

Diagnostic yield of ERCP and secretin-enhanced MRCP and EUS in patients with acute recurrent pancreatitis of unknown aetiology.

BACKGROUND: Magnetic resonance cholangio-pancreatography (MRCP), endoscopic ultrasonography (EUS), and endoscopic cholangio-pancreatography (ERCP) are the most frequently employed second-step procedures to detect biliary and pancreatic abnormalities in patients with acute recurrent pancreatitis (ARP) of unknown aetiology. MRCP and EUS both give a better view of the bilio-pancreatic ductal system after secretin stimulation (MRCP-S, EUS-S). EUS also serves to identify changes in the pancreatic parenchyma consistent with chronic pancreatitis, at an early stage. However, no studies have compared MRCP-S, EUS-S, and ERCP in the diagnosis of recurrent pancreatitis. AIM: To prospectively compare the diagnostic yield of MRCP-S, EUS-S, and ERCP in the evaluation of patients with acute recurrent pancreatitis with non-dilated ducts, of unknown aetiology. METHODS: Forty-four consecutive patients with ARP were prospectively scheduled to undergo MRCP-S, EUS-S and ERCP, in accordance with a standard protocol approved by the institutional review board. Diagnoses such as biliary microlithiasis, congenital variants of the pancreatic ducts, chronic pancreatitis and sphincter of Oddi dysfunction were compared between the three procedures. The diagnosis of chronic pancreatitis was established according to ductal morphology by MRCP-S and ERCP, ductal and parenchymal morphology by EUS-S. RESULTS: The three procedures combined achieved a diagnosis that could have explained the recurrence of pancreatitis in 28/44 patients (63.6%). EUS-S recognized ductal and/or parenchymal abnormalities with the highest frequency (35/44 patients, 79.5%). Both MRCP-S and EUS-S were superior to ERCP for detecting pancreatic ductal abnormalities. EUS-S showed up pancreatic parenchymal changes in more than half the cases. Both EUS and MRCP secretin kinetics were concordant in identifying two cases with sphincter of Oddi dysfunction. CONCLUSIONS: The diagnostic yield of EUS-S in recurrent pancreatitis with non-dilated ducts and unknown aetiology was 13.6% and 16.7% higher than MRCP-S and ERCP respectively (although not significant), which both gave substantially similar diagnostic yields. In no case did ERCP alone find a diagnosis missed by the other two procedures. MRCP-S and EUS-S should both be used in the diagnostic work-up of idiopathic recurrent pancreatitis as complementary, first-line, techniques, instead of ERCP.

Endoscopic ultrasound-guided application of a new internally gas-cooled radiofrequency ablation probe in the liver and spleen of an animal model: a preliminary study.

BACKGROUND AND STUDY AIMS: In a previous study, a new flexible bipolar hybrid cryotherm probe was applied with success to the pancreas of a living pig. Here we evaluated feasibility, efficacy, and safety of its application to the porcine liver and spleen. MATERIAL AND METHODS: Ten applications to the liver and nine to the spleen were performed in 19 pigs. Power input (16-18 W) and simultaneous cooling with CO(2) (standardized pressure: 675 psi) as the cryogenic agent were investigated. Application time varied from 120 seconds to 900 seconds. The ablation area was measured by endoscopic ultrasound (EUS) after ablation (T0), and before euthanasia (T1). Gross pathology (T2) and histology after necropsy represented the gold standard. The interval from treatment to euthanasia was 1 or 2 weeks. RESULTS: For both organs the correlation between EUS and gross pathology was good (correlation coefficient R(liver) = 0.71; R(spleen) = 0.73). EUS tended to overestimate the area of the ablated zone. EUS observed a time-dependent ablation area: we demonstrated a positive trend of lesion size (T1) over time in liver tissue (R = 0.51 (P = 0.1)). In the spleen we found a clear correlation of lesion area T2 and application time (R = 0.75, P = 0.01). There were no complications. CONCLUSIONS: Selective EUS-guided transgastric cryotherm ablation of the liver and spleen in a pig model is feasible and safe. The new bipolar probe creates a time-dependent ablation area without any complications, and opens a field of new potential indications of RF-ablative therapies.

Role of endosocopic ultrasound in the diagnosis of cystic tumours of the pancreas.

With the increased use of sophisticated imaging, cystic lesions in the pancreas are being recognized with greater frequency. Although imaging alone may not provide a specific diagnosis in many cases, a combination of imaging characteristics, clinical presentation, and additional procedures such as endoscopic ultrasound guided fine needle aspiration of cystic lesion, allows appropriate management. Cystic lesions in the pancreas can be divided pathologically into congenital cysts, pseudocysts and cystic neoplasm. At least four different types of cystic neoplasm have been described: mucinous neoplasms, intraductal papillary mucinous neoplasms, serous neoplasms and papillary cystic neoplasms The most important diagnosis is differentiating between mucinous and non-mucinous cystic lesion because of their different potential of malignancy. Endoscopic ultrasound provides the highest resolution of the pancreas and endoscopic ultrasound-fine needle aspiration can supply further diagnostic information on the basis of cytology, fluid viscosity, concentration of tumour glycoproteins, amylase level, molecular analysis that may contribute to the better clinical outcome of these neoplasms.

Endoscopic ultrasound-guided application of a new hybrid cryotherm probe in porcine pancreas: a preliminary study.

BACKGROUND AND STUDY AIMS: Open, laparoscopic, or percutaneous radiofrequency (RF) ablation of the pancreas is still dangerous, whereas endoscopic ultrasound (EUS)-guided ablation might reduce risk because it is less invasive and provides real-time monitoring. We aimed to demonstrate the feasibility of transluminal RF ablation and to evaluate the efficacy and safety of a new flexible bipolar ablation probe combining RF and cryotechnology. METHODS: 14 ablations were performed in 14 pigs. Energy input (16 W) and simultaneous cryogenic cooling with carbon dioxide (650 psi) were standardized. Application time range was 120 - 900 seconds. Ablation area was measured by EUS immediately after ablation (area T0), and before euthanasia (area T1). Macroscopic findings (area T2) and histological findings after necropsy served as gold standard. The interval from application to euthanasia was either 1 or 2 weeks. RESULTS: The correlation between EUS findings (area T1) and macroscopic appearance (area T2) was good ( R = 0.89). The correlation between the T2 ablation area and the application time showed a fitted ratio of 2.3 ( P < 0.0001) with a 1-week interval and 0.2 ( P = 0.01) with a 2-week interval. No pig died because of the procedure. Two pigs showed histochemical pancreatitis, which was clinically overt in one. Necropsy additionally revealed one burn to the gastric wall and four gut adhesions. CONCLUSIONS: Selective transluminal RF ablation of the pancreas under EUS control in a living pig model is feasible. The new flexible bipolar probe creates an ablation area with extent related to the duration of application, and with fewer complications than conventional RF ablation techniques.

PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) regimen as second-line therapy in patients with progressive or recurrent pancreatic cancer after gemcitabine-containing chemotherapy.

OBJECTIVE: The therapeutic arsenal for salvage therapy in pancreatic cancer is limited. PEFG (cisplatin, epirubicin, 5-fluorouracil [FU], gemcitabine) regimen is an effective upfront treatment in advanced pancreatic cancer. The activity and safety of this combination regimen were assessed by means of an observational study in a population of patients with progressive or recurrent pancreatic adenocarcinoma after gemcitabine-containing chemotherapy. METHODS: Patients with age <76 years, Karnofsky performance status >50 were treated with either classic PEFG (until April 2004: cisplatin and epirubicin 40 mg/m day 1, gemcitabine 600 mg/m day 1 and 8, FU 200 mg/m/d continuous infusion day 1-28) or dose-intense PEFG (since May 2004: cisplatin and epirubicin 30 mg/m, gemcitabine 800 mg/m every 14 days; FU 200 mg/m/d continuous infusion day 1-28) until progressive disease or a maximum of 6 cycles of 28 days. RESULTS: Forty-six patients (37 metastatic) received 69 cycles of classic PEFG (18 patients) or 104 cycles of dose-intense PEFG (28 patients) as second-line therapy. Prior treatment consisted of single agent gemcitabine (N = 17), gemcitabine-based chemotherapy (N = 4), or PEFG regimen (N = 25). Median previous progression-free survival was 7.6 months. Dose intensity (mg/m/wk) with classic PEFG was cisplatin and epirubicin 8.5; gemcitabine 230; FU 1035 and with dose-intense PEFG was cisplatin and epirubicin 11.5 (+36%); gemcitabine 259 (+13%); FU 1046 (+1%). Main grade >2 toxicity consisted of neutropenia in 26 patients (56%), thrombocytopenia in 10 (22%), anemia in 11 (24%), fatigue and stomatitis in 4 (9%), vomiting, diarrhea and hand-foot syndrome in 2 (4%). Partial response was observed in 11 patients (24%) (5 classic PEFG 28% + 6 dose-intense PEFG 21%). Median and 1-year survival was 8.3 months (8.0 vs. 9.0 months) and 26% (17% vs. 32%). Median and 6-months progression-free survival was 5.0 months (4.5 vs. 5.0 months) and 34% (33% vs. 38%). CONCLUSIONS: PEFG regimen in gemcitabine refractory pancreatic cancer had an acceptable toxicity profile and interesting activity, and may constitute a treatment option in this setting.

Arterial vs pancreatic phase: which is the best choice in the evaluation of pancreatic endocrine tumours with multidetector computed tomography (MDCT)?

PURPOSE: The aim of this study was to assess whether the pancreatic phase may replace the arterial phase in the evaluation of endocrine pancreatic tumours. MATERIALS AND METHODS: Twenty-nine endocrine pancreatic lesions with definitive morphological and immunohistochemical characterisation after surgical treatment (n=24) or fine-needle-aspiration cytology under endoscopic ultrasonography guidance (n=5) were retrospectively evaluated. All lesions were studied with triple-phase 16-row multidetector computed tomography (MDCT). Images obtained during each phase were separately interpreted by two senior radiologists experienced in pancreatic pathology and who were blinded to surgical results. Endocrine tumour and normal pancreas attenuation and the mean absolute tumour-to-gland attenuation difference were measured in each phase, and data were analysed with Student's t test. Visualisation of arterial vascular abnormalities and hypervascular liver metastases in the arterial and pancreatic phases and the diagnostic contribution of the two phases were compared. RESULTS: For both radiologists, the mean absolute tumour-to-gland attenuation difference was significantly higher (p<0.05) in the pancreatic phase (40+/-53 HU and 34+/-56 HU) than in the arterial phase (31+/-38 HU and 26+/-43 HU). There were no differences in the detection of arterial vascular abnormalities or hypervascular liver metastases in the two phases. The diagnostic contribution was higher in the pancreatic phase. CONCLUSIONS: In our experience, the pancreatic phase can replace the arterial phase in the evaluation of pancreatic endocrine tumours.

Midazolam and pethidine versus propofol and fentanyl patient controlled sedation/analgesia for upper gastrointestinal tract ultrasound endoscopy: a prospective randomized controlled trial.

BACKGROUND AND OBJECTIVES: The aim of this prospective, randomized study was to compare the standard regimen of midazolam and pethidine administered by the gastroenterologist versus patient controlled sedation with a propofol-fentanyl mixture during upper gastrointestinal tract endoscopic ultrasonography. Our primary end-points were patient satisfaction and patient cooperation assessed by endoscopist. METHODS: Fifty-four consecutive patients, undergoing endoscopic ultrasonography, received sedation with midazolam and pethidine (Group M: n=27) or propofol and fentanyl (Group P: n=27). Group M: pethidine 0.7mg/kg midazolam 0.04mg/kg before examination; boluses of same drugs if the sedation was insufficient plus a sham patient controlled sedation analgesia; Group P: propofol 17mg plus fentanyl 15microg before examination and a patient controlled sedation analgesia pump containing 170mg propofol plus 150microg fentanyl injecting 0.5ml every time the patient pressed the button (no "lock out"). Boluses of 1ml of the same mixture if the sedation was insufficient. RESULTS: Group M: mean dosage of pethidine and midazolam 88.6 and 5mg, respectively. Group P: mean dosage of propofol and fentanyl 119.7mg and 106microg, respectively. Both groups were similar for duration and difficulty of the procedure, the grade of sedation (Observer's Assessment of Alertness/Sedation Score) and judgement by endoscopist and patient about cooperation and satisfaction. The only difference between groups was about the extra boluses administered during the procedure. CONCLUSION: This study demonstrated that a patient controlled sedation analgesia with propofol and fentanyl is an effective and safe technique for upper gastrointestinal tract endoscopic ultrasonography procedures and results in a high level of satisfaction both for patients and operator.