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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.

Indicators of effectiveness and quality of care are urgently needed to improve the surgical outcomes. This is particularly felt in the field of complex surgical fields, such as the HPB one. International and national studies have documented an association between the large number of pancreatic surgical procedures and the outcome quality. The aim of this paper is to suggest reliable structural requirements and surgical volume to support pancreatic surgical accreditation, preserving patient's safety. Moreover, an accreditation program is outlined.

The aim of this study was to assess whether the pancreatic phase may replace the arterial phase in the evaluation of endocrine pancreatic tumours.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.For both radiologists, the mean absolute tumour-to-gland attenuation difference was significantly higher (p0.05) 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.In our experience, the pancreatic phase can replace the arterial phase in the evaluation of pancreatic endocrine tumours.

Between 1989 and 1993, 62 patients underwent Whipple pancreatoduodenectomy and 75 pylorus-preserving pancreatoduodenectomy (PPPD); 35 patients in the first group and 37 in the second had pancreatic adenocarcinoma while 17 and 21 patients respectively had periampullary adenocarcinoma. The aim of this retrospective study was the comparison of operative outcome, nutritional recovery and survival of patients who underwent these two operations. No significant differences were found between the two groups in operative mortality or morbidity, duration of gastric aspiration and time to start of solid meals. Patients who underwent PPPD had a better nutritional recovery: the increase of both body-weight and serum albumin level at 6 months after discharge was significantly higher for those who had preservation of the whole stomach (P < 0.001 and P < 0.05 respectively). No significant difference in survival was found between the two procedures when patients with pancreatic or periampullary adenocarcinoma were analysed separately.

Purpose PEFG regimen (P:cisplatin, E:epirubicin, F:5-fluorouracil, G:gemcitabine) significantly prolonged progression-free (PFS) and overall survival (OS) of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine. The current trial was aimed at assessing whether the replacement of E with docetaxel (D) may improve 6 months PFS (PFS6). Methods Chemo-naive patients with stage III or metastatic PA received P (30 mg/m(2) day 1 and 15), G (800 mg/m(2) day 1 and 15), and capecitabine (1,250 mg/m(2)/day days 1-28, without a break) and were randomized to receive either D at 25-30 mg/m(2) day 1 and 15 (arm A: PDXG regimen) or E at 30 mg/m(2) day 1 and 15 (arm B: PEXG regimen). Cycles were repeated every 28 days for a maximum of 6 months. The Fleming design was used to calculate the sample size on the probability of being PFS6. Assuming P0 = 40% and P1 = 60%, alpha = 0.05 and beta = 0.10; the study was to enroll 52 patients per arm. Results Between July 2005 and September 2008, 105 patients were enrolled, stratified by stage and randomized. Patients' characteristics were (A/B) the following: median age 61/59, PS > 70 92/88%, metastatic disease 66/65%. PFS6 was 58%, and median OS was 11 months in both arms. A partial response was observed in 60/37% of patients. Main per cycle G3-4 toxicity was the following: neutropenia 4/13%, thrombocytopenia 2/4%, anemia 4/4%, and fatigue 6/3%. Conclusions The inclusion of D instead of E yielded more objective response and less G3-4 neutropenia but did not improve PFS and OS. The present trial confirms the relevant impact on outcome of advanced PA of 4-drug regimens. PURPOSE: PEFG regimen (P:cisplatin, E:epirubicin, F:5-fluorouracil, G:gemcitabine) significantly prolonged progression-free (PFS) and overall survival (OS) of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine. The current trial was aimed at assessing whether the replacement of E with docetaxel (D) may improve 6 months PFS (PFS6). METHODS: Chemo-naive patients with stage III or metastatic PA received P (30 mg/m(2) day 1 and 15), G (800 mg/m(2) day 1 and 15), and capecitabine (1,250 mg/m(2)/day days 1-28, without a break) and were randomized to receive either D at 25-30 mg/m(2) day 1 and 15 (arm A: PDXG regimen) or E at 30 mg/m(2) day 1 and 15 (arm B: PEXG regimen). Cycles were repeated every 28 days for a maximum of 6 months. The Fleming design was used to calculate the sample size on the probability of being PFS6. Assuming P0 = 40% and P1 = 60%, α = 0.05 and β = 0.10; the study was to enroll 52 patients per arm. RESULTS: Between July 2005 and September 2008, 105 patients were enrolled, stratified by stage and randomized. Patients' characteristics were (A/B) the following: median age 61/59, PS >70 92/88%, metastatic disease 66/65%. PFS6 was 58%, and median OS was 11 months in both arms. A partial response was observed in 60/37% of patients. Main per cycle G3-4 toxicity was the following: neutropenia 4/13%, thrombocytopenia 2/4%, anemia 4/4%, and fatigue 6/3%. CONCLUSIONS: The inclusion of D instead of E yielded more objective response and less G3-4 neutropenia but did not improve PFS and OS. The present trial confirms the relevant impact on outcome of advanced PA of 4-drug regimens.

Background Data on enhanced recovery programmes after pancreatic surgery are sparse. This retrospective cohort study, using historical controls, aimed to evaluate the impact of a fast-track programme after pancreaticoduodenectomy (PD). Methods Between 2004 and 2007, 252 patients undergoing PD were treated by a fast-track programme that included earlier postoperative feeding and mobilization. The patients were compared with an equally sized control group that received a traditional programme from 2000 to 2004. Outcome measures were morbidity, length of stay and readmission rate. Results The rates of pancreatic fistula and other intra-abdominal complications were similar in the two groups. Delayed gastric emptying (DGE) was significantly reduced in the fast-track group (13·9 versus 24·6 per cent; P = 0·004). The independent effect of the fast-track protocol in reducing DGE was confirmed by the multiple regression analysis (adjusted odds ratio 0·477, P = 0·005). Length of stay was reduced with the fast-track protocol (median 13 versus 15 days; P < 0·001), without increasing the readmission rate (7·1 versus 6·3 per cent; P = 0·865). Conclusion A fast-track programme after PD improves gastric emptying and reduces postoperative stay.

There are a large number of stable pancreatic ductal carcinoma cell lines (PDCL) that are used by researchers worldwide. Detailed data about their differentiation status and genetic alterations are present in the literature, but a systematic correlation with cell biological behavior is often lacking. PDCL ( n=12) were clustered by source of tumor cell (ascites, primary tumor, metastasis), and the data of functional cell biology were correlated with the reported structural and genetic profiles. Major histocompatibility complex expression, chemosensitivity and aneuploidia appeared to be related to the source of PDCL, and proliferative capacity appeared to be related to the grade of differentiation. No correlation between genetic/structural features of PDCL and biological behavior was found. All the cell lines appeared generally insensitive to in vitro treatment with 5-fluorouracil and showed variable degrees of susceptibility to gemcitabine, raltitrexed and oxaliplatin. All the PDCL showed resistance to Fas-mediated apoptosis but were significantly sensitive to the pro-apoptotic effect of inflammatory cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)alpha and interferon gamma]. PDCL were characterized for the secretion of several factors relevant to the tumor-immune cross talk. Vascular endothelial growth factor, CCL2, CCL5 and transforming growth factor beta were the factors most frequently released; less frequent was the secretion of CXCL8, CCL22, IL-6 and sporadically CXCL12, IL-10 and hepatocyte growth factor. The cytokines IL-1beta and TNFalpha were always undetectable. In conclusion, a clear correlation between structural/genetic features and function could not be detected, suggesting the weakness of a "morphological" classification for the in vitro studies of pancreatic cancer.

A chronic in ammatory state of the airways is considered the hallmark of asthma (1). However, the incidence, severity, and prognosis of asthma can be affected by a number of factors, including the patient's sex and age. The sex of the fetus seems to in uence the development of the respiratory apparatus. In fact, between weeks 28 and 40 of gestation, the lungs are in a more advanced state in females than in males (2), a fact which could explain, at least in part, the higher incidence of respiratory distress in male infants (3). Clinical observations and epidemiologic studies agree that childhood asthma is more frequent in boys than in girls (4). Moreover, in some children, usually boys, asthmatic symptoms that started in infancy disappear around puberty (5), while many girls have the disease only during adolescence (6). Age has been implicated in the severity of asthma. Asthma beginning during adulthood is generally more severe than childhood-onset asthma (7). Asthma that starts around the menopause or in old age is generally quite severe (5). According to two recent epidemiologic investigations, the patient's sex and age affect the hospitalization rate for asthma (8, 9), which is a marker of severity. In the ®rst study (a retrospective study of 33 269 patients), the admission rate of boys in the 0±10-year age group was almost twice that of girls. In the next decade, sex differences in the hospitalization rate were irrelevant, although there was a small, but signi®cant prevalence of females. At all ages above 20 years, hospital admission rates were higher in women than men, with a female/ male ratio ranging from 3:1 in subjects aged 20±50 years to 2.5:1 in those over 50 years of age (8). Similar data were reported by Elliasson (9). Both studies found a relationship between the age and sex of the patient and the severity of the asthma attack as indicated by duration of hospitalization. In fact, the duration of hospitalization increased with age in both sexes; moreover, hospital stays were longer in women over 30 years of age than in men of the same age (8, 9). Abbreviations. FSH: follicle-stimulating hormone; LH: luteinizing hormone; NK cell: natural killer cell; IL-1, -4, -5, -6: interleukin-1, -4, -5, -6; TGF-b: tumor growth factor-beta; PEFR: peak expiratory ow rate. Allergy 2001: 56: 13±20 Printed in UK. All rights reserved Copyright # Munksgaard 2001

Local recurrence is the most frequent site of failure after resection for pancreatic cancer. We reported our experience in term of tolerance, local control and survival obtained by the association of resection and intraoperative radiation therapy (IORT). Between January 1985 and July 1996 152 resection for pancreatic cancer were performed at the authors' institution. For 77 patients, IORT was added to resection (group 1), whereas the other 75 patients underwent resection alone (group 2), because of either the unavailability of the linear accelerator or the patient's refusal. In group 1, radiation doses from 12.5 to 20 Gy, with electron beam energies between 6 and 12 MeV, were delivered. Extension of the disease, percentage of radical resection and postoperative chemotherapy were similar in the two groups of patients. Operative mortality and overall early postoperative complications were respectively 1.3% and 31.2% in group 1 and 4% and 32% in group 2. The median survival was 17 months in group 1 and 15 months in group 2 and the median disease free survival was 12 months in group 1 and 8 months in group 2. A local recurrence was detected in 31% of patients in group 1 and in 49.3% of patients in group 2 (p0.1). The results suggest a better local control in patients with pancreatic cancer undergoing adjuvant IORT.

Pancreatico-jejunal anastomosis still represents the main source of postoperative complications after pancreatoduodenectomy. In this study our experience on the occlusion of the residual pancreatic stump instead of pancreatico-jejunal anastomosis is reviewed. Between March 1981 and December 1995 we performed 223 pancreatoduodenectomies using Neoprene injection into the Wirsung duct for pancreatic carcinoma of the head (123 cases), ampullary carcinoma (36 cases), distal bile duct cancer (23 cases), islet cells carcinoma (17 cases), chronic pancreatitis (11 cases), duodenal carcinoma (5 cases), miscellaneous diseases (8 cases). Neoprene is a fluid, synthetic glue which polymerized and hardens when in contact with the pancreatic juice, inducing a fibrosis tissue which spares the endocrine component. We observed a 4.9% operative mortality (11 patients): 5 abdominal sepsis, 1 DIC, 1 aortoiliac thrombosis, 1 pulmonary embolism, 1 stroke, 1 hepatic failure, 1 cardiac failure. Overall morbidity was 44.8% (100 patients): in 25 cases (11.2%) a major complication requiring reintervention occurred. In 38 patients (17%) pancreatic fistula was detected: median duration was 43 days, with a mean output of 5.3 ml/day; in all cases a spontaneous solution of the fistula was observed. In conclusion, intraductal injection of Neoprene after pancreatoduodenectomy is a safe procedure, it represents an useful alternative to pancreatico-jejunal anastomosis.

BACKGROUND AND METHODS: The cranio-facial morphology has been evaluated on the basis of cephalometric studies in nine patients with Turner's syndrome. The aim of this study is to identify the growth model and the typical malocclusions of this syndrome. This study has been completed with an evaluation of mesio-distal dimension of permanent teeth. RESULTS: According to the literature, the results show: a flattening of the basal skull; a cross-bite coming from a transversal dimension reduction of the upper maxilla. A Class II malocclusion was found in two patients. All the patients showed a mandibular retrusion associated to maxillary retrusion in eight cases. The growth direction was normal in all the patients. CONCLUSIONS: A reduction of the mesio-distal diameter in all of the permanent teeth, was also found. This last measure was evaluated using the study casts.

The purpose of the present study is to investigate the factors contributing to skeletal relapse after surgical correction of mandibular prognathism. Postoperative follow-up after mandibular setback is carried out to clarify the timing and causes of the relapse. The subjects are mandibular prognathism patients. The etiology of relapse is discussed.

The authors describe the diagnostic-therapeutic protocol of orthodontical-surgical treatments of Angle-class I, II and III used by the Oral and Maxillo-Facial Surgery Department of Second University of Naples. They also present a personal survey.

The physical properties of aerosols are reviewed. The physiological basis of inhalation therapy is then briefly reviewed together with the aerosol devices currently available and the therapeutic uses of inhaled drugs, focusing on the treatment of parenchymal lung diseases and extra respiratory disorders. Finally, new perspectives for inhalation therapy are examined.

Transvaginal absorption of a progesterone (P) oleic formulation, commercially available for intramuscular administration (Gestone, Amsa, Rome), has been investigated in five fertile women in the follicular phase. The contents of a vial, corresponding to P 100 mg, was administered intravaginally by a syringe connected to an atraumatic cannula inserted in the vagina. While administering and for a further 10 minutes the woman remained in the recumbent position. Blood samples for P assay were drawn at the following times: 0, 15, 30, 45, 60, 120, 240, 360, 480 and 1440 minutes. Mean CMax was 5.08 +/- 1.66 ng/ml, and the difference between baseline and CMax values was statistically significant (p0.01). TMax resulted as 60 minutes (range 45-240 minutes). Mean serum levels lowered subsequently but resulted as still significantly higher than baseline (p0.05) after 1440 minutes. Mean AUC 0-1440 value was 4236.75 ng h/ml. Any local or systemic side-effects were noted. No evidence of vaginal irritation was observed in any women. On the basis of the present data it is possible to suggest that a twice daily administration schedule could ensure suitable P serum levels in fertile women.