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Background Among liver cystic lesions, mucinous cystic neoplasm of the liver (MCN-L) constitutes a challenging issue in terms of management: preoperative diagnosis is often unachievable and this may mislead to inappropriate treatment [1-3]. We present the case of an otherwise healthy 29-year-old female who underwent laparotomic cyst unroofing in segment 4 and cholecystectomy in another institution. Post-operative course was complicated by biliary leakage that was endoscopically treated. Short term follow-up showed early recurrence with a volumetric enlargement of the cyst occupying most of the left hepatic lobe and new satellite cyst in Sg5. The doubt of MCN-L arose, and the patient was scheduled for laparoscopic removal at our Centre, despite the previous laparotomic procedure. Methods An optic port was placed into right upper abdominal quadrant and 3 further ports were placed. A long and difficult adhesiolysis was performed and Pringle's manoeuver was settled. Intraoperative US confirmed the anatomic limits of the cysts in Sg5 and in the left hepatic lobe. The cyst on Sg5 was resected first and frozen section was suspicious for MCN-L. In order to prevent recurrence, left laparoscopic hepatectomy was performed. The specimen was extracted through the previous midline laparotomy. Results Post-operative course was uneventful and the patient was discharged on POD 5. Pathology and immunochemistry confirmed the diagnosis of MCN-L. Conclusion Hepatic cystic lesions may be insidious and preoperative biopsy is not always possible due to lack of solid tissue. In unclear settings, an intraoperative frozen section is mandatory to guide intraoperative decisions. In the suspicion of malignancy, resection with oncologic criteria must be chosen as the most appropriate treatment, as well as the retrieving of MCN-L requires hepatic resection to avoid early recurrence [4, 5]. Despite of previous laparotomy, we consider a laparoscopic approach could be attempted in selected cases, in institution with particular expertise in laparoscopic liver surgery.

Cystic fibrosis-related diabetes (CFRD) is associated with worsening of inflammation and infections, and the beginning of insulin treatment is debated.To verify high-mobility group box 1 protein (HMGB1) levels in CF patients according to glucose tolerance state, and analyze relationships with insulin secretion and resistance. To verify, in an in vitro model, whether HMGB1 gene expression and protein content were affected by insulin administration and whether these changes were dependent on CF transmembrane conductance regulator (CFTR) loss of function.Forty-three patients in stable clinical conditions and 35 age- and sex-matched controls were enrolled. Glucose tolerance was established in patients based on a 5 point oral glucose tolerance test (OGTT). Fasting glucose to insulin ratio (FGIR), HOMA-IR index, whole-body insulin sensitivity index (WIBISI), and the areas under the curve for glucose (AUCG) and insulin (AUCI) were calculated. HMGB1 was assayed in serum, in cell lysates and conditioned media using a specific ELISA kit. For the in vitro study we used CFBE41o- cells, homozygous for the F508del mutation, and 16HBE14o- as non-CF control. HMGB1 gene expression was studied by real-time RT-PCR. Cells were stimulated with insulin at 2.5 and 5 ng/mL. The CFTR inhibitor 172 and CFTR gene silencing were used to induce CFTR loss of function in 16HBE14o- cells.HMGB1 levels were increased at onset of CFRD (5.04 ± 1.2 vs 2.7 ± 0.3 ng/mL in controls; P.05) and correlated with FGIR (R = +0.43; P = .038), and AUCI (R = +0.43; P = .013). CFTR loss of function in the 16HBE14o- cells increased HMGB1 and was lowered by insulin.HMGB1 was increased in CF patients with deranging glucose metabolism and showed relationships with indexes of glucose metabolism. The increase in HMGB1 was related to CFTR loss of function, and insulin lowered HMGB1. Further research is required to verify whether HMGB1 could potentially be a candidate marker of onset of CFRD and to establish when to start insulin treatment.

Highly active antiretroviral therapy (HAART) has been able to improve the immune system function and survival of HIV patients with a consequent increase in the number of HIV patients affected by end-stage liver disease (ESLD). Between June 2003 and October 2006, 10 HIV-positive patients underwent liver transplantations in our center.All patients were treated with HAART before transplantation; treatment was interrupted on transplantation day and was restarted once the patients' conditions stabilized. Five patients were hepatitis C virus (HCV)-positive, 3 were hepatitis B virus (HBV)-positive, and 2 were HBV-HCV coinfected. HIV viral load before transplantation was50 copies/mL in all cases. CD4+ cell count before transplantation ranged between 144 and 530 c/microL. Immunosuppression was based on Cyclosporine (CyA) and steroid weaning for 8 patients, and on Tacrolimus and steroid weaning for 2 patients.Five patients were cytomegalovirus (CMV)-positive pp65 antigenemia posttransplantation, and 1 patient was EBV-positive; 2 patients had a coinfection with HHV6. Four patients suffered from a cholestatic HCV recurrent hepatitis treated with antiviral therapy (peginterferon and Ribavirin). Three patients died after transplantation.The outcome of liver transplantation in HIV patients was influenced by infections (HCV, CMV, and EBV) and Kaposi's Sarcoma. HCV recurrence was more aggressive, showing a faster progression in this patient population. Drug interaction between HAART and immunosuppressants occurs; longer follow-up and better experience may improve the management of these drug interactions.

Cystic fibrosis-related diabetes (CFRD) is the most frequent and severe co-morbidity in cystic fibrosis (CF). Presentation and severity are quite variable.To investigate changes in microRNAs (miRNAs) due to CF transmembrane conductance regulator malfunctioning in vitro, to study the circulating levels of selected miRNAs in serum samples from patients, and to assess their relationships in different age groups with genotype, glucose tolerance state, and at onset of CFRD. Design/Setting/Patients/Interventions: Transcriptional profiling of all known miRNAs in CFBE41o- cells, in their normal counterparts (16HBE14o- cells), and in IB3 cells was performed. A set of miRNAs was differentially expressed in the CF cells. By in silico analysis, four miRNAs (miR-146a, miR-155, miR-370, and miR-708) were selected as potential regulators of the FOXO1 gene. Seventy-four CF patients and 50 healthy subjects whose glucose tolerance was characterized by an oral glucose tolerance test were enrolled in the study, and the identified miRNAs were quantified in serum by quantitative RT-PCR. Main Outcome Measurements/Results: A total of 111 miRNAs were differentially expressed in the two CF cell lines. miR-155, miR-370, and miR-708 were up-regulated and miR-146a was down-regulated in vitro, whereas in vivo, miR-146a, miR-155, and miR-370 were up-regulated, and miR-708 was down-regulated. These changes showed relationships with genotype, glucose tolerance state, and onset of CFRD.The data showed significant changes in miRNAs dependent on genotype and glucose tolerance state in CF patients and highlighted some miRNAs of importance in CFRD at onset. miRNAs could explain some of the variability observed in CF.

Objective The CAP cycle is a module of activation (phase A) and inhibition (phase B) which repeats itself in sequences. The study aims at testing the hypothesis that the duration of CAP sequences is determined primarily by the number and not by the length of CAP cycles. Methods The polysomnographic recordings of 24 normal subjects, 12 males and 12 females, ranging in age from 20 to 35 years (mean 27.8 ± 7.2), were examined. Results A total of 1053 CAP sequences were counted with an average of 43.9 sequences per night. The mean duration of CAP sequences was 2 min and 33 s. Each CAP sequence was composed of an average of 5.6 CAP cycles. All subjects presented CAP sequences lasting at least 5 min and 30 s. The mean duration of CAP cycles was 26.9 ± 4.1 s. CAP cycles including subtypes A1 presented the highest correlation with the CAP sequence length (r = 0.92; p Conclusions The progressive increase of CAP sequences length is linked to the progressive accumulation of CAP cycles. Significance CAP sequences can be considered as strings of time-constant modules, i.e., CAP cycles, which are involved in the dynamic tailoring of sleep structure.

Objective To determine whether the prescription of aripiprazole, compared with olanzapine and haloperidol, was associated with a lower frequency of metabolic syndrome (MS) and treatment discontinuation at 1 year. Method Patients were randomly assigned to be treated open-label and according to usual clinical practice with either aripiprazole, olanzapine, or haloperidol and followed up for 1 year. Results Three hundred out-patients with persistent schizophrenia were recruited in 35 mental health services. The intention-to-treat (ITT) analysis found no significant differences in the rate of MS between aripiprazole (37%), olanzapine (47%), and haloperidol (42%). Treatment discontinuation for any cause was higher for aripiprazole (52%) than for olanzapine (33%; OR, 0.41; P = 0.004), or haloperidol (37%; OR, 0.51; P = 0.030). No significant difference was found between olanzapine and haloperidol. Time to discontinuation for any cause was longer for olanzapine than for aripiprazole (HR, 0.55; P

Background and purpose Narcolepsy is a sleep disorder with clinical symptoms attributed to a reduced activation of the arousal system. Cyclic alternating pattern (CAP) is the expression of rhythmic arousability during non-rapid eye movement (NREM) sleep. CAP parameters, arousals and conventional sleep measures were studied in narcoleptic patients with cataplexy. Patients and methods Data were collected from all-night polysomnographic (PSG) recordings and the multiple sleep latency test (MSLT) on the intervening day of 25 drug-naive patients (10 males and 15 females; mean age: 34±16 years) after adaptation and exclusion of other sleep disorders. A group of 25 age- and gender-matched normal sleepers were selected as controls. Each PSG recording was subdivided into sleep cycles. Analysis of CAP included classification of A phases into subtypes A1, A2, and A3. Results There was an increase in sleep period time mainly due to an increased wake time after sleep onset. REM latency was sharply reduced. The percentage of NREM sleep was slightly reduced and the balance between light sleep (S1 + S2) and deep sleep (S3 + S4) showed a curtailment of the former, while deep sleep was slightly increased. Excluding sleep cycles with sleep onset REM periods (SOREMPs), the duration of ordered sleep cycles was not different between narcoleptics and controls. The two groups showed similar values of arousal index, while CAP time, CAP rate, number of CAP cycles and of phase A subtypes (in particular subtypes A1) were significantly reduced in narcoleptic patients. Conclusions The reduced periods of CAP in narcoleptic NREM sleep could be the electroencephalographic (EEG) expression of a generally reduced arousability or an increased strength of sleep-promoting forces in the balance between sleep and arousal systems. This can explain some of the clinical correlates of the disorder, i.e. excessive sleepiness, short sleep latency and impaired attentive performances, even without any sign of arousal-induced sleep fragmentation.

Objective To evaluate the immediate and long-term recovery processes of sleep and daytime vigilance in patients with sleep apnea syndrome (OSAS) after continuous CPAP treatment. Methods Five consecutive polysomnographic (PSG) studies were carried out on 10 male patients with severe OSAS. The first recording (baseline) was accomplished without ventilatory support (N0). The other 4 recordings were carried out during the CPAP titration night (N1), during the second night of treatment (N2), during the third night of treatment (N3), and after 30 days of regular CPAP use (N30). Ten age-balanced healthy male subjects were selected from the Parma Sleep Center database as controls. Respiratory variables, conventional PSG variables, arousals, CAP (cyclic alternating pattern) variables, and daytime function (including MSLT) were quantified. ANOVA followed by post-hoc tests explored the differences between controls and OSAS patients in the different recording conditions (N0, N1, N2, N3, N30). The PSG measures that showed significant ANOVA values were correlated with the MSLT scores. Results Values of control subjects were recovered by REM sleep, REM latency, subtypes A3 and arousal index during N1, by CAP rate and total arousals during N2, by deep sleep (stages 3+4) during N3, by light sleep (stages 1+2) during N30. The only measures which remained below control values even after 1month of sustained treatment were the amount of CAP cycles and A1 subtypes. MSLT scores correlated significantly with CAP rate, deep sleep and arousals. Conclusions The changes induced by CPAP treatment do not restore immediately a normal sleep structure, which is re-established with different time scales Significance The modifications of sleep patterns and the different adjustments of phase A subtypes allow us to monitor the reorganization of sleep in OSAS patients treated with CPAP and the hierarchy of the mechanisms involved in sleep regulation.

A number of phasic events influence sleep quality and sleep macrostructure. The detection of arousals and the analysis of cyclic alternating patterns (CAP) support the evaluation of sleep fragmentation and instability. Sixteen polygraphic overnight recordings were visually inspected for conventional Rechtscaffen and Kales scoring, while arousals were detected following the criteria of the American Sleep Disorders Association (ASDA). Three electroencephalograph (EEG) segments were associated to each event, corresponding to background activity, pre-arousal period and arousal. The study was supplemented by the analysis of time-frequency distribution of EEG within each subtype of phase A in the CAP. The arousals were characterized by the increase of alpha and beta power with regard to background. Within NREM sleep most of the arousals were preceded by a transient increase of delta power. The time-frequency evolution of the phase A of the CAP sequence showed a strong prevalence of delta activity during the whole A1, but high amplitude delta waves were found also in the first 2/3 s of A2 and A3, followed by desynchronization. Our results underline the strict relationship between the ASDA arousals, and the subtype A2 and A3 within the CAP: in both the association between a short sequence of transient slow waves and the successive increase of frequency and decrease of amplitude characterizes the arousal response.

Introduction Highly effective antiretroviral therapy in the last decade has increased the survival rates of HIV-positive patients, yielding a greater number of HIV patients suffering from liver-related disease. Liver transplantation (LT) is the only curative treatment for end-stage liver disease (ESLD) associated or not with hepatocellular carcinoma (HCC). Patients and methods From June 2003 to September 2010, 23 patients underwent cadaveric donor LT for ESLD at our institution. Inclusion criteria followed the Italian Protocol for LT in HIV-positive patients. Immunosuppressive regimens were based on cyclosporine or tacrolimus, eventually switched to Rapamycin. Results The median CD4 T-cell count was 275/mmc (range = 119–924). All patients were affected by ESLD, which was associated with HCC in 14 cases. Ten patients were within the Milan criteria and four patients exceeded them but were within the San Francisco criteria. Conversion from calcineurin inhibitors (CNI) to rapamycin occurred in ten cases. Hepatitis C virus (HCV) recurrence occurred in 13/21 HCV-positive patients. Acute cellular rejection occurred in eight patients with one developing chronic cellular rejection. Overall patient and graft survivals at 80 months were 50% and 45% respectively. Discussion LT in HIV-positive patients is a feasible procedure, even if in our experience was burdened by a greater incidence of complications including HCV recurrence and infection compared with HIV-negative patients.

The average age of patients undergoing liver transplantation (LT) is consistently increasing. The aim of this case-control study is to evaluate survival and outcome of patients ≥65 yr compared to younger patients undergoing LT.From 10/00 to 4/08 we performed 330 primary LT, 31 (9.4%) of these were in patients aged 65-70. Following a case-control approach, we compared these patients with 31 patients aged between 41 and 64 yr and matched according to sex, LT indication, viral status, cadaveric/living donor, LT timing, and Model for End-Stage Liver Disease (MELD) score.There were no statistically significant differences in demographic and surgical donor characteristics. The mean MELD score was under 18 in both groups. Post-LT complications occurred with a similar incidence in the two groups. one-, three-, and five-yr survival was 83.9%, 80.6%, and 80.6%, respectively, for the elderly group, and 80.6%, 73.8%, and 73.8%, respectively, for the young group (p = 0.61).Patients aged between 65 and 70 with low MELD score who undergo LT have the same short- and middle-term survival expectancy, morbidity, and outcome quality as younger patients with the same indication and same pre-LT pathology severity, whatever they might be. Thus, chronological age alone should not deter LT workup in patients65 and70.

There has been a dramatic increase in the number of pancreatic cystic lesions observed in the past two decades but data regarding the prevalence of cysts in the general population are lacking.All the individuals who undergo CT at the San Marino State Hospital are residents of the Republic of San Marino; their demographic distribution is available and precise. CT scans carried out over 1 year at the State Hospital were reviewed for asymptomatic pancreatic cysts.1061 relevant CT scans were carried out on 814 patients; 762 individuals were eligible for the study and 650 patients underwent contrast-enhanced CT. Thirty-five patients had at least one cyst at contrast-enhanced CT (5.4%). The prevalence of cysts increased with increasing age up to 13.4% (95% CI 6.6-20) in individuals 80-89 years of age (p .001). Cyst prevalence was significantly higher in patients who underwent CT for malignancy (p = .038) but this difference was no longer significant in multivariate analysis. The odds of a cyst being present increased by 1.05 (95% CI 1.02-1.09) for each increasing year of age (p = .002). Approximately a quarter of the patients with cysts died within 1 year after CT from non pancreas-related disease. The estimated standardized age-adjusted cyst prevalence is 2194 per 100,000 people.The likelihood of having a pancreatic cyst correlates with increasing age, not with the presence of extra-pancreatic malignancies. The estimated prevalence of CT-detectable asymptomatic pancreatic cysts in the general population is 2.2%.

To assess the safety and efficacy of antibiotics treatment for suspected acute uncomplicated appendicitis and to monitor the long term follow-up of non-operated patients.Right lower quadrant abdominal pain is a common cause of emergency department admission. The natural history of acute appendicitis nonoperatively treated with antibiotics remains unclear.In 2010, a total of 159 patients [mean AIR (Appendicitis Inflammatory Response) score = 4.9 and mean Alvarado score = 5.2] with suspected appendicitis were enrolled and underwent nonoperative management (NOM) with amoxicillin/clavulanate. The follow-up period was 2 years.Short-term (7 days) NOM failure rate was 11.9%. All patients with initial failures were operated within 7 days. At 15 days, no recurrences were recorded. After 2 years, the overall recurrence rate was 13.8% (22/159); 14 of 22 patients were successfully treated with further cycle of amoxicillin/clavulanate. No major side effects occurred. Abdominal pain assessed by the Numeric Rating Scale and the visual analog scale; median Numeric Rating Scale score was 3 at 5 days and 2 after 7 days. Mean length of stay of nonoperatively managed patients was 0.4 days, and mean sick leave period was 5.8 days. Long-term efficacy of NOM treatment was 83% (118 patients recurrence free and 14 patients with recurrence nonoperatively managed). None of the single factors forming the Alvarado or AIR score were independent predictors of failure of NOM or long-term recurrence. Alvarado and AIR scores were the only independent predictive factors of NOM failure after multivariate analysis, but both did not correlate with recurrences. Overall costs of NOM and antibiotics wereOV0556;316.20 per patient.Antibiotics for suspected acute appendicitis are safe and effective and may avoid unnecessary appendectomy, reducing operation rate, surgical risks, and overall costs. After 2 years of follow-up, recurrences of nonoperatively treated right lower quadrant abdominal pain are less than 14% and may be safely and effectively treated with further antibiotics.

Study Objectives: Besides arousals (according to the ASDA definition), sleep contains also K-complexes and delta bursts which, in spite of their sleep-like features, are endowed with activating effects on autonomic functions. The link between phasic delta activities and enhancement of vegetative functions indicates the possibility of physiological activation without sleep disruption (i.e., arousal without awakening). A functional connection seems to include slow (K-complexes and delta bursts) and rapid (arousals) EEG events within the comprehensive term of activating complexes. CAP (cyclic alternating pattern) is the spontaneous EEG rhythm that ties both slow and rapid activating complexes together during NREM sleep. The present study aims at exploring the relationship between arousals and CAP components in a selected sample of healthy sleepers. Design: Polysomnographic analysis according to the scoring rules for sleep stages and arousals. CAP analysis included also tabulation of subtypes A1 (slow EEG activating complexes), A2 and A3 (activating complexes with fast EEG components). Setting: 40 sleep-lab accomplished recordings. Participants: Healthy subjects belonging to a wide age range (38 ± 20 yrs.). Interventions: N/A Measurement and Results: Of all the arousals occurring in NREM sleep, 87% were inserted within CAP. Subtypes A2 and A3 of CAP corresponded strikingly with arousals (r=0.843; p

Non-rapid eye movement (NREM) sleep contains periods of arousal instability (cyclic alternating pattern or CAP) and periods of arousal stability (non-CAP). During CAP, arousal oscillates between higher (phase A) and lower (phase B) levels of activation. We evaluated the relationship between CAP and the occurrence of epileptic events, i.e. clinical seizures and generalized interictal discharges, during sleep in 10 patients with Lennox-Gastaut syndrome (LGS). The macro- and microstructure of sleep of 10 attended overnight polysomnograms were analyzed. Compared with 10 age- and gender-matched controls, patients with LGS had significantly less stage 2 and REM sleep and higher amounts of CAP rate (68% vs. 33%; P

Aims and Background The role of chemotherapy in locally advanced or metastatic gastric cancer has been controversial, but chemotherapy has recently been shown to relieve tumor-related symptoms, improve quality of life and prolong survival when compared with best supportive care. Furthermore, palliative chemotherapy is also cost-effective. “Second-generation” combination chemotherapy regimens were developed in the 1980s with high activity in advanced or metastatic gastric cancer (EAP, FAMTX, PELF, ECF). In randomized studies, EAP demonstrated no difference in activity but a significantly higher overall toxicity and toxic death rate than FAMTX, and the ECF (epirubicin, cisplatin, 5-fluorouracil) regimen gave a survival and response advantage, tolerable toxicity, better quality of life and was more cost-effective than FAMTX. Methods Sixty patients with locally advanced or metastatic gastric cancer were treated with the ECF regimen (21 weeks of 5-fluorouracil given by continuous infusion through a central line at 200 mg/m2 for 24-hr combined with cisplatin at 60 mg/m2 iv and epirubicin at 50 mg/m2 iv beginning on day 1 and repeated every 3 weeks for 8 courses). There were 42 males and 18 females, with a median age of 64 years (range, 40-74). The median performance status was 1. The histologic type was adenocarcinoma in 44 patients and undifferentiated carcinoma in 16 (27%). Three patients had locally advanced disease (5%) and 57 had metastatic disease (95%). Seven patients (12%) had received prior chemotherapy for advanced disease. Results All patients were assessable for toxicity and 55 for response (5 had insufficient treatment). Toxicity was mild or moderate, and there was no toxic death. Incidence of WHO toxicity ≥ 2 was nausea and vomiting in 3%, mucositis in 3%, leukopenia in 7%, anemia in 3%, and thrombocytopenia in 2%. Port-a-Cath toxicity was thrombosis in 4, dislocation in 2 and infection in 3 patients. Seven complete responses and 13 partial responses (overall response rate, 36%) were achieved, with a response rate of 39% in untreated and 17% in pretreated patients. Nine patients (16%) had stable disease and 26 (47%) progressive disease. Most patients felt symptomatically improved on ECF. Conclusions Our study confirms that the ECF regimen has a favorable pattern of toxicity and is feasible on an outpatient basis. However, it did not confirm the high response rate reported in other phase II trials.

Objective To analyze sleep architecture and NREM sleep alterations by means of the Cyclic Alternating Pattern (CAP) in children with Down syndrome (DS) and Fragile-X syndrome (fraX), the two most common causes of inherited mental retardation, in order to find out eventual alterations of their sleep microstructure related to their mental retardation phenotypes. Methods Fourteen patients affected by fraX (mean age 13.1 years) and 9 affected by Down syndrome (mean age 13.8 years) and 26 age-matched normal controls were included. All subjects underwent overnight polysomnography in the sleep laboratory, after one adaptation night and their sleep architecture and CAP were visually scored. Results FraX subjects showed a reduced time in bed compared to DS subjects, whereas DS subjects showed a lower sleep efficiency, a higher percentage of wakefulness after sleep onset, and a reduced percentage of stage 2 NREM compared to the other groups. Furthermore, DS and fraX subjects, compared to normal controls, showed a higher percentage of stage 1 NREM and a lower percentage of REM sleep. FraX subjects showed the most disrupted sleep microstructure with low total CAP rate and CAP rate in S2 NREM. Both patient groups showed a lower percentage of A1 and higher percentage of A2 and A3 compared to normal controls. Conclusions The analysis of CAP might be able to disclose new important findings in the sleep architecture of children with mental retardation and might characterize sleep microstructural patterns of the different phenotypes of intellectual disability. Significance The NREM sleep microstructure alterations found in our subjects, associated with the reduction in REM sleep percentage, seem to be distinctive features of intellectual disability.

Summary Background: A phase II trial of a new intra-arterial chemotherapy regimen for unresectable pancreatic cancer (UPC). Patients and methods: Ninety-six patients with UPC were treated with intra-arterial chemotherapy at three-weekly intervals. The schedule used was FLEC: 5-fluorouracil 1000 mg/m 2 , folinic acid 100 mg/m 2 , carboplatin 300 mg/m 2 ; epirubicin 60 mg/m 2 . Results: The overall response rates by CT-scan evaluation were: 15% partial response (PR), 44% stable disease (SD), 17% progressive disease (PD). The overall median survival was 9.9 months, and 10.6 and 6.8 for UICC stage III and IV, respectively. Pain reduction occurred in 42% of patients. A weight gain > 7% from baseline occurred in 8% of patients. A total of 341 courses of FLEC were administered. Grade 3-4 hematological toxicity was seen in 25% of patients; ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%; and grade 3 alopecia in 16%. One sudden death, a pre-infarction angina, and a transitory ischemic attack were observed. The only complication related to the angiographic procedure was an intimal dissection of the iliac artery. Conclusions: The intra-arterial FLEC regimen was well tolerated and active. It requires only one day of hospitalization. Efficacy could only be assessed in a randomized study against a gemcitabine containing regimen.

Objectives : The present study aimed at offering a standardized database for cyclic alternating pattern (CAP) parameters across representative ages of life. Methods : CAP parameters were quantified in 40 healthy sleepers and polygraphically investigated in a partially sound-proof recording chamber under a standard laboratory setting. Four age groups were investigated (teenagers: 10–19 years; young adults: 20–39 years; middle-aged: 40–59 years; elderly: 60 years). Each group included 10 subjects (5 males and 5 females). Nocturnal recordings were accomplished after adaptation to the sleep laboratory that also served to rule out the presence of sleep-related disorders. The study indicated that CAP is a natural phenomenon of NREM sleep, with specific age-related characteristics across the life cycle. Results : CAP rate in NREM sleep, defined as the percentage ratio of total CAP time to total NREM sleep time, showed a U-shape profile with minimum in young adults (31.9%), maximum in the elderly group (55.3%), and intermediate values in teenagers (43.4%) and in middle-aged subjects (37.5%). The longest duration of CAP cycles was found among the older subjects (31 s). The highest amounts of subtypes A1 were identified in teenagers ( n =261), while the highest amounts of A2 and A3 subtypes occurred in the elderly group ( n =183). Across the ages, the level of arousal mostly fluctuated in stages 1 and 3, whereas stage 4 emerged as the most stable NREM stage. Overall, stage 2 better reflected the CAP values referred to as total NREM sleep. Conclusions : The periodic arousal fluctuations reflected by CAP are a natural phenomenon of NREM sleep with specific age-related variations across the life cycle.

presented by Dr Di Saverio at the Conference o Appendectomy,WorldTraumaCongress,RioDe Janeiro,Braz Received September 4, 2013; Revised November 20, 2 December 3, 2013. From the Emergency and General Surgery Departmen Maggiore Hospital, Bologna Local Health District, Bolog Mandrioli, Sibilio, Smerieri, Lombardi, Tugnoli, Masetti, gency and Trauma Surgery Department, Maggiore Hosp Parma (Catena), General and Emergency and Trauma S Ospedali Riuniti, Bergamo (Ansaloni), Italy, and Upper G Frenchay Hospital, North Bristol NHS Trust, Bristol, UK Correspondence address: Salomone Di Saverio, MD, PhD, General Surgery Department, CA Pizzardi Maggiore Ho Nigrisoli 2, 40133 Bologna, Italy. email: salo75@inwind.it ausl.bologna.it a 2014 by the American College of Surgeons Published by Elsevier Inc. SURGEON AT WORK A Cost-Effective Technique for Laparoscopic Appendectomy: Outcomes and Costs of a Case-Control Prospective Single-Operator Study of 112 Unselected Consecutive Cases of Complicated Acute Appendicitis Salomone Di Saverio, MD, PhD, Matteo Mandrioli, MD, Andrea Sibilio, MD, Nazareno Smerieri, MD, Raffaele Lombardi, MD, Fausto Catena, MD, PhD, FRCS, Luca Ansaloni, MD, PhD, FRCS, Gregorio Tugnoli, MD, PhD, FRCS, Michele Masetti, MD, PhD, FRCS, Elio Jovine, MD, PhD, FRCS Appendicitis is the most common cause of intra-abdominal surgical emergency in the Western world, and its differential diagnosis is often challenging because of several other conditions causing right iliac fossa pain. Ultrasound has a limited sensitivity (ranging from 74% to 83%) and better specificity (89% to 94%) compared with CT scan. However, although CT guarantees higher sensitivity rates (94%), it does carry the potential risks of radiation exposure. Since its introduction, open appendectomy (OA) has been the gold standard of care for more than a century. Laparoscopic appendectomy (LA) was first described in 1983, and some of its benefits were immediately clear, including better visualization of the peritoneal cavity, which made it possible to diagnosis alternative diseases in the case of a normal appendix, and improved cosmesis. However, the laparoscopic procedure has not superseded OA, even in Western countries, especially in hospitals with limited resources, equipment, and budget limitations, and where the surgical staff are dedicated to emergency surgery and potentially have poor laparoscopic skills. Cost effectiveness of LA is the greater matter of debate when choosing either open or laparoscopic approach. The first randomized trials showed that LA paradoxically increased n Laparoscopic il, August 2012.

Since homogeneous samples of insomniacs are difficult to recruit for pharmacotherapy studies, normal sleepers can be used to assess the protective effect of hypnotic drugs, under standardized nonconducive conditions. In particular, a noisy environment is a typical cause of situational insomnia that can be counteracted by a sedative-hypnotic agent. Six healthy middle-aged subjects (three men and three women), with no complaints about sleep, underwent a completely randomized double-blind series of 10 nocturnal polysomnograms with at least 72-h washout intervals. All subjects received a single dose of placebo, zolpidem 10 mg, zopiclone 7.5 mg, lorazepam 1 mg, and triazolam 0.25 mg both under basal and under perturbed conditions. For each individual, five recordings were carried out under basal conditions (sound pressure level not higher than 30 dB) and five recordings under acoustically perturbed conditions (continuous white noise at 55 dB). Sleep quality was assessed by means of a visual analogue scale (VAS). All recordings were scored according to conventional rules (macro-structure) and cyclic alternating pattern (CAP) methodology (microstructure). Statistical analysis was based on a repeated measures analysis-of-variance design integrated by Bonferroni adjusted probabilities. Under placebo, situational insomnia was confirmed by the significant increase in sleep fragmentation (intrasleep wakefulness) and by the significant enhancement of arousal instability (CAP parameters). In contrast to macrostructural information, CAP parameters were highly sensitive in detecting the perturbing effects of noise (mean CAP rate under placebo, 57%) and the protective action of hypnotic drugs during perturbation (mean CAP rate under active medication, 41%). Microstructural analysis enabled us to discriminate hypnotic drugs from placebo, nonbenzodiazepine compounds from benzodiazepine agents, and zopiclone from zolpidem. The latter, in fact, induced the lowest values of CAP rate both under basal (30%) and under noisy (39%) conditions and determined a significant decrease in electroencephalogram arousals. All CAP parameters were significantly correlated with the visual-analogue-scale scores for sleep quality. The use of CAP methodology in a highly standardized model of situational insomnia can be a valid alternative to conventional sleep scoring for the investigation of drug effects on disturbed sleep.

There is a need to identify simple biochemical markers at birth that may predict subjects at risk of growth failure and metabolic complications in later life. Limited research to date has been performed on relationships of specific biochemical determinants at birth with postnatal weight gain and growth. We proposed to establish whether placental cortisol and IL-6 concentrations and cord serum IGF-II and IGFBP-2 concentrations influenced postnatal growth. We followed up from pregnancy 23 IUGR and 37 AGA subjects, and determined placental cortisol and IL-6 concentrations, and cord serum IGF-II, and IGFBP-2 concentrations at birth. We obtained height and weight measurements at 3, 6, 12, 24 months and 5 years of age in 20 IUGR and 15 AGA subjects of comparable gestational age. A multiple linear regression model was designed to establish the effect of the placental and cord serum peptides on postnatal linear growth and weight gain. All IUGR subjects had catch-up growth before 2 years of age. Placental cortisol concentration correlated positively with weight gain during the first 5 years of postnatal growth (P0.05). Subjects with the highest placental cortisol concentrations were those who showed a greater increase in weight. Cord serum IGFBP-2 concentrations correlated positively with weight gain throughout the 5 year observation period (P:0.003). The subjects with the highest concentrations showed a greater weight gain. Placental cortisol and cord serum IGFBP-2 concentrations were related to postnatal weight gain, suggesting that the fetal environment has long-term effects on growth.

Background and Purpose: Treatment of chronic insomnia with nightly hypnotics is efficacious, but discontinuation is recommended after 1 month, less than the average disease duration. This study was undertaken to determine the efficacy of intermittent administration. Patients and Methods: A double-blind study was carried out on 8 patients (age, 32.8 ± 9 years; 3 men) with primary sleep maintenance insomnia longer than 1 month. Polysomnography of conventional sleep parameters, cyclic alternating patterns (CAPs), and arousals was performed. Perception of sleep quality was assessed on a visual analog scale. After an adaptation night, baselines were recorded followed by 6 consecutive nights of alternating treatment with zolpidem (10 mg) or placebo. Results: Significant improvements on baseline values (P < 0.0001) were observed on all 3 active treatment nights for total sleep time, sleep efficiency, CAP time, CAP rate, subtype A2, arousals, and arousal index. Deep non-rapid eye movement sleep increased with the second and third doses of active treatment (P < 0.0001). Rapid eye movement sleep increased during the last 3 polysomnographic recordings (P < 0.014). Sleep quality (visual analog scale) improved on all nights after the initial dose of active treatment (P < 0.0001). There was no evidence of rebound insomnia with placebo. Conclusions: Intermittent treatment with zolpidem in primary insomnia patients improves CAP parameters and arousals, as well as sleep duration and quality, in the absence of rebound insomnia.

There is growing evidence that cyclic alternating pattern (CAP) and arousals are woven into the basic mechanisms of sleep regulation. In the present study, the overnight sleep cycles (SC) of 20 normal subjects were analyzed according to their stage composition, CAP rate, phase A subtypes and arousals. Individual SC were then divided into 10 normalized temporal epochs. CAP parameters and arousals were measured in each epoch and averaged in relation to the SC order. Subtypes A2 and A3 of CAP in non-rapid eye movement (NREM) sleep, and arousals, both in REM and NREM sleep when not coincident with a A2 or A3 phases, were lumped together as fast electroencephalographic (EEG) activities (FA). Subtypes A1 of CAP, characterized by slow EEG activities (SA), were analyzed separately. The time distribution of SA and FA was compared to the mathematical model of normal sleep structure including functions representing the homeostatic process S, the circadian process C, the ultradian process generating NREM/REM cycles and the slow wave activity (SWA) resulting from the interaction between homeostatic and ultradian processes. The relationship between SA and FA and the sleep-model components was evaluated by multiple regression analysis in which SA and FA were considered as dependent variables while the covariates were the process S, process C, SWA, REM-on and REM-off activities and their squared values. Regression was highly significant (P < 0.0001) for both SA and FA. SA were prevalent in the first three SC, and exhibited single or multiple peaks immediately before and in the final part of deep sleep (stages 3 + 4). The peaks of FA were delayed and prevailed during the pre-REM periods of light sleep (stages 1 + 2) and during REM sleep. SA showed an exponential decline across the successive SC, according to the homeostatic process. In contrast, the distribution of FA was not influenced by the order of SC, with periodic peaks of FA occurring before the onset of REM sleep, in accordance with the REM-on switch. The dynamics of CAP and arousals during sleep can be viewed as an intermediate level between cellular activities and macroscale EEG phenomena as they reflect the decay of the homeostatic process and the interaction between REM-off and REM-on mechanisms while are slightly influenced by circadian rhythm.

Objective To assess inter-rater reliability between different scorers, from different qualified sleep research groups, in scoring visually the Cyclic Alternating Pattern (CAP), to evaluate the performances of a new tool for the computer-assisted detection of CAP, and to compare its output with the data from the different scorers. Methods CAP was scored in 11 normal sleep recordings by four different raters, coming from three sleep laboratories. CAP was also scored in the same recordings by means of a new computer-assisted method, implemented in the Hypnolab 1.2 (SWS Soft, Italy) software. Data analysis was performed according to the following steps: (a) the inter-rater reliability of CAP parameters between the four different scorers was carried out by means of the Kendall W coefficient of concordance; (b) the analysis of the agreement between the results of the visual and computer-assisted analysis of CAP parameters was also carried out by means of the Kendall W coefficient; (c) a ‘consensus' scoring was obtained, for each recording, from the four scorings provided by the different raters, based on the score of the majority of scorers; (d) the degree of agreement between each scorer and the consensus score and between the computer-assisted analysis and the consensus score was quantified by means of the Cohen's k coefficient; (e) the differences between the number of false positive and false negative detections obtained in the visual and in the computer-assisted analysis were also evaluated by means of the non-parametric Wilcoxon test. Results The inter-rater reliability of CAP parameters quantified by the Kendall W coefficient of concordance between the four different scorers was high for all the parameters considered and showed values above 0.9 for total CAP time, CAP time in sleep stage 2 and percentage of A phases in sequence; also CAP rate showed a high value (0.829). The most important global parameters of CAP, including total CAP rate and CAP time, scored by the computer-assisted analysis showed a significant concordance with those obtained by the raters. The agreement between the computer-assisted analysis and the consensus scoring for the assignment of the CAP A phase subtype was not distinguishable from that expected from a human scorer. However, the computer-assisted analysis provided a number of false positives and false negatives significantly higher than that of the visual scoring of CAP. Conclusions CAP scoring shows good inter-rater reliability and might be compared in different laboratories the results of which might also be pooled together; however, caution should always be taken because of the variability which can be expected in the classical sleep staging. The computer-assisted detection of CAP can be used with some supervision and correction in large studies when only general parameters such as CAP rate are considered; more editing is necessary for the correct use of the other results. Significance This article describes the first attempt in the literature to evaluate in a detailed way the inter-rater reliability in scoring CAP parameters of normal sleep and the performances of a human-supervised computerized automatic detection system.

Objective : Polysomnographic (PSG) measures consistently reflect poor sleep quality and effective treatment in insomniac patients. Methods : The PSG findings of 47 patients (18 M and 29 F, 42.5±10 years) meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a diagnosis of primary insomnia were compared with those of 25 age- and gender-balanced healthy subjects (controls) without sleep complaints. After one adaptation night to the sleep lab, each patient underwent two randomized double-blind PSG recordings. Twenty-four patients followed a placebo-drug sequence and 23 a drug-placebo succession. Active treatment consisted of widely used hypnotic drugs, i.e. zolpidem, triazolam, zopiclone, brotizolam. Conventional PSG measures, electroencephalogram (EEG) arousals and CAP variables (including phase A subtypes) were quantified and statistically analyzed. Results : Compared to controls, insomniac patients under placebo showed a significant increase of CAP rate, subtypes A1 and A2, EEG arousals, nocturnal wakefulness and stage 1, associated with reduced values of total sleep time and slow wave sleep (stages 3 and 4). In insomniac patients, sleep quality was significantly improved by hypnotic treatment. Compared to placebo, active medication significantly reduced CAP rate, subtypes A1 and A2, but had only marginal effects on subtypes A3 and on EEG arousals. Under hypnotic treatment total sleep time, nocturnal awakenings, stage 1 and slow wave sleep recuperated normal values. The most significant correlation between sleep quality and PSG variables was found for CAP rate ( P Conclusions : PSG investigation extended to CAP variables and EEG arousals can be an important procedure for the diagnosis of primary insomnia and evaluation of treatment efficacy.

The objective of this work was to study the non-linear aspects of sleep EEG, taking into account the different sleep stages and the peculiar organization of its phasic events in ordered sequences (CAP) by applying a series of new non-linear measures (non-linear cross prediction or NLCP), which appear more reliable for the detection and characterization of non-linear structures in experimental data than the commonly used correlation dimension. Eight healthy subjects aged 18-20 years participated in this study. Polysomnography was performed in all subjects; signals were sampled at 128 Hz and stored on hard disk. The C3 or C4 derivation was used for all the subsequent computational steps, which were performed on EEG epochs (4096 data points) selected from sleep stage 2 (S2) and slow-wave sleep (SWS), in both CAP and non-CAP (NCAP) conditions. Also, epochs from sleep stage 1 (S1), REM and wakefulness preceding sleep were recorded. The dynamic properties of the EEG were assessed by means of the non-linear cross-prediction test, which uses three different 'model' time series in order to predict non-linearly the original data set (Pred, Ama, and Tir). Pred is a measure of the predictability of the time series, and Ama and Tir are measures of asymmetry, indicating non-linear structure. The non-linear measures applied in this study indicate that sleep EEG tends to show non-linear structure only during CAP periods, both during S2 and SWS. Moreover, during CAP periods, non-linearity can only be detected during the phase A1 subtypes (and partially A2) of CAP. The A3 phases show characteristics of non-stationarity and bear some resemblance to wakefulness. Based on the results of this study, sleep might be considered as a dynamically evolving sequence of different states of the EEG, which we could track by detecting non-linearity, mostly in association with CAP. Our results clearly show that detectable non-linearity in the EEG is closely related to the occurrence of the phase A of CAP.

Riedel's thyroiditis (RT) is an extremely rare form of chronic thyroiditis, characterised by a fibroinflammatory process which partially destroys the thyroid, often involving surrounding tissues. We describe an unusual case of RT in a 38-year-old woman, and discuss its typical clinical, pathological, ultrasound, radionuclide scanning and magnetic resonance findings. We conclude that the diagnosis of RT is highly suggestive in the presence of a hard gland (or nodule), fixed to adjacent structures; 'cold' on Tc99 scan; hypoechoic with absence of vascular flow, invading the adjacent neck structures on ultrasound; hypointense in T1- and T2-weighted MR images; and showing fibrous tissue fragments with inflammatory cells at cytological examination. Thyroidectomy has to be performed to confirm the diagnosis and to relieve pressure symptoms.

Purpose : to analyze the activating role of cyclic alternating pattern (CAP) and EEG synchrony on generalized interictal paroxysms in the first part of the night, when all sleep patterns are represented. Methods : nocturnal polysomnographic investigation was accomplished on a randomized series of 18 subjects with an active form of primary generalized epilepsy (PGE), but only six patients showed a complete and regular profile of the first two sleep cycles (SCs). Completeness and regularity of the selected SCs consisted in the absence of intervening wakefulness, in the presence of all sleep stages, and in the identification of three main units, (a) a descending branch, dominated by the build-up of EEG synchrony in the transition from light to deep non-rapid eye movement (NREM) sleep; (b) a trough, where the magnitude of EEG synchrony is greatest and gives rise to stages 3 and 4; (c) an ascending branch characterized by a decrease of EEG synchrony preceding the onset of rapid eye movement (REM) sleep. Generalized paroxysms were evaluated in terms of discharge rates (number of interictal bursts per minute of sleep) and distribution within the investigated sleep parameters. Results : the discharge rates decreased from SC1 to SC2, with higher values quantified during NREM sleep (mean, 2.8) compared with REM sleep (mean, 0.8). Both SCs showed a progressive decrease of activation across the three units, from the highest discharge rates reached during the descending branches (mean, 3.6) to the more attenuated discharge rates during the troughs (mean, 2.4) down to the lowest rates during the ascending limbs (mean, 1.1). The magnitude of activation during the descending branches was closely related to the CAP condition (mean, 5.2) and to the powerful effect of phase A (mean, 13.9). The great majority (82%) of EEG discharges occurring in phase A were distributed within the A1 subtypes (identified by sequences of k-complexes or delta bursts). Conclusions : within the first two SCs, the features of NREM sleep endowed with the major activating power on generalized bursts are represented by the rise of EEG synchrony (descending branch) and by the A phases of CAP involved in the regulation of its build-up.

Objective: To measure the readjustments of sleep macro- and microstructure in patients with obstructive sleep apnea syndrome (OSAS) after acute nasal continuous positive airway pressure (NCPAP) treatment. Background: The conventional polysomnographic analysis (macrostructure of sleep) does not necessarily provide the best measures of sleep disruption associated with OSAS. In contrast, microstructural methods of analyzing sleep (i.e., arousals and cyclic alternating pattern) may improve evaluation of patients with OSAS. Method:— Ten patients with OSAS were monitored polygraphically before and during the first night of NCPAP therapy. The results were compared with those of 10 age- and sex-matched controls without sleep-related breathing disorders. Each nocturnal recording was followed by daytime observation using the multiple sleep latency test and Visual Analogue Scale (VAS). Results: The first night of ventilatory therapy was characterized by a remarkable expansion of stages 3 and 4 and of REM sleep. In addition, NCPAP suppressed the presence of cyclic alternating pattern (CAP) in REM sleep and induced an impressive rebound of arousals and of certain CAP variables—i.e., CAP rate, CAP time, number of CAP cycles—which dropped well below the physiologic values expressed by controls. A normal duration of phases A and B was re-established starting the first treatment night. When we matched sleep variables with the indices of daytime function, a significant correlation emerged only between the variations of CAP rate and VAS scores. In particular, improvement of daytime sleepiness was less evident when the ventilatory-induced drop of CAP rate was more pronounced. Conclusions: The application of CAP variables to the microstructural analysis of sleep may expand our knowledge regarding sleep and respiration.

Objective: There is consolidated evidence that stage changes in sleep are closely related to spontaneous EEG fluctuations centered on the 20–40 periodicity of the cyclic alternating pattern (CAP). The present investigation aimed at assessing the involvement of the different components of CAP in the process of build-up, maintenance and demolition of deep non-REM (NREM) sleep. Methods: CAP parameters were quantified in the first 3 sleep cycles (SC1, SC2, SC3), selected from polysomnographic recordings of 25 healthy sound sleepers belonging to an extensive age range (10–49 years). Only ideal SCs were selected, i.e. the ones uninterrupted by intervening wakefulness and in which all stages were represented and linked in a regular succession of a descending branch, a trough and an ascending branch. Results: Among the first 3 SCs, a total amount of 45 (SC1, 16; SC2, 13; SC3, 16) met the inclusion requirements. SC1 contained the highest amount of slow wave sleep (43.7 min) and the lowest values of CAP rate (31.6%). The number of phase A1 subtypes remained unmodified across the 3 SCs (SC1, 48; SC2, 48; SC3, 48), whereas both subtypes A2 (SC1, 9; SC2, 14; SC3, 14) and A3 (SC1, 2; SC2, 8; SC3, 10) increased significantly (P

To find a means of achieving operability very quickly without the additional discomfort of prolonging systemic chemotherapy. To improve the patient's quality of life by obtaining quick tumor reduction and decreasing systemic toxicity.From January 1991 to January 1995, 13 patients with locally advanced breast cancer (LABC) and 8 patients with recurrent breast cancer (RBC), were treated by transfemoral Seldinger technique, with the catheter tip placed into the subclavian artery at the basis of the internal mammary artery. The patients received 5-fluorouracil (5FU) 1000 mg, epirubicin (EPI) 30 mg/m2, mitomycin (MMC) 7 mg/m2 over an infusion for 30 minutes. The cycle was repeated every two weeks for three times.The overall response rate was 62%. Stage IIIb and RBC patients had a response rate of 100% and 25% respectively. In respondent patients a measurable response was seen after the first cycle. Ten patients were radically operated. After a media follow-up of 21 months, the overall survival is 52% at 48 months (68% at 48 months and 65% at 34 months for stage IIIb and RBC patients respectively).PIAC is feasible and effective. In LABC patients it reaches 100% of response rate. Systemic toxicity was absent and the local one was mild. The interval between the starting of PIAC and operation is short. There was an optimal compliance of the patients.

To test the effects of a hypnotic drug administered on a regular basis, six adults (four women and two men; mean age 37 years) who complained of transient or short-term insomnia, took zolpidem 10 mg at bedtime for 4 consecutive weeks. The period of active treatment, preceded by a baseline placebo night, ended with a 4-night gradual tapering phase followed by 3 nights of placebo administration. After adaptation to the sleep laboratory, all subjects underwent five polysomnographic recordings; baseline placebo (night 1); 1st, 7th and 28th nights of hypnotic medication (nights 2, 3, and 4 respectively); 3rd placebo night after complete tapering (night 5) and completed a morning visual analogue scale (VAS) for evaluating sleep quality. The sleep recordings were scored according to the conventional procedures (macrostructure) and to the cyclic alternating pattern (CAP) rules (microstructure). Data analysis was based on a repeated-measures analysis of variance integrated by post-hoc comparisons. At the macrostructural level, significant overall modifications (p < 0.035) emerged only from slow-wave sleep (SWS). The amounts of SWS were enhanced along the entire drug period, but a significant difference was found only between the baseline night (10%) and the first night of drug administration (20%). At the microstructural level, CAP rate (the ratio of CAP time to non-rapid eye movement sleep time) showed overall significant variations throughout the entire protocol period (p < 0.0001). Compared with baseline night 1 (59%), the CAP rate was significantly lower on drug nights 2 (32%), 3 (37%), and 4 (38%). The increase in the CAP rate found on night 5 (43%) was still significantly below the baseline value. The VAS scores showed significant overall changes (p < 0.0001), with improved values during the active treatment period.

Intra-arterial hepatic chemotherapy (LAHC) results in significantly higher response rate than the best systemic treatment of liver metastases from colorectal cancer, but no survival advantage has to date shown because of extra-hepatic progression. From June 1991 to December 1994, twenty patients with hepatic metastases from colorectal cancer were enrolled. All patients underwent laparotomy for the placement of an intra-arterial catheter into the gastroduodenal artery connected with a subcutaneous port. All patients underwent cholecystectomy and biopsy of liver lesion to confirm metastatic disease. Locoregional schedule was: 5-fluorouracil (5FU) 500 mg/sqm, epirubicin (EPI) 13 mg/sqm, mitomycin-C (MMC) 7 mg/sqm, in bolus every 3 weeks. Systemic therapy consisted of leucovorin 500 mg/sqm, over 2 hours and 5FU 600 mg/sqm in bolus every week. Treatment was planned over a six month period. The complete response (CR) plus partial response (PR) rate was 50% of the entire group. The median survival was 18 months and 1- and 2- and 3-year survival rates were 71%, 38% and 20% respectively. Prior to chemotherapy, LDH value and % of liver involvement were the only significant prognostic parameters. Toxicity was absent or mild and no patient stopped treatment because of side effects. Combined systemic and IAHC is an effective treatment for liver metastases from colorectal cancer, with a mild or moderate toxicity. However, more trials are needed, to improve the control of the extrahepatic disease.

Intraarterial chemotherapy is studied as an alternative procedure for the neoadjuvant treatment of locally advanced and recurrent breast cancer. Our study was aimed at investigating the feasibility, the toxicity and the local response rate of an intraarterial chemotherapy regimen including 5-fluorouracil, epirubicin and mitomycin. These drugs were administered angiographically into the subclavian and internal mammary arteries ipsilateral to the lesion. We treated 20 women with a median age of 58 years (range: 42-74 years); 12 patients had locally advanced breast cancer with a median tumor size of 12 cm (range: 6-20 cm) and 8 patients exhibited cutaneous, thoracic or axillary recurrences, with a median lesion size of 6 cm (range: 3-12 cm). In all, we administered 54 cycles of chemotherapy drugs (mean: 2.7 cycles a patient). Most patients were submitted to selective catheterization of the internal mammary artery (44/54 cycles); all the drugs were injected into the subclavian artery only when catheterization of this vessel was unfeasible. No angiography-related toxicity was observed. No systemic, particularly hematological, toxicity was observed. Four patients exhibited skin erythema in the feeding region of the internal mammary artery, 2 hemialopecia, 1 cutaneous steatonecrosis and 1 transient hemiplegia. We obtained 1 complete remission and 11 partial responses, with 60% overall response rate (12/20 patients). All the patients with locally advanced breast cancer had an objective response and the mean interval between the start of therapy and radical mastectomy was only 49 days. In conclusion, intraarterial chemotherapy for locally advanced or recurrent breast cancer is a feasible and well-tolerated tool which needs further studies, particularly to assess its efficacy.

The optimal management of primary gastric lymphomas has yet to be defined. In the past surgery was advocated as the optimal first step for patients with PGL. Recently, an increasing number of studies suggest that chemotherapy is as effective as surgery.Fourteen patients with PGL were treated with chemotherapy alone. For patients with low-grade lymphoma, chemotherapy consisted of mitoxantrone 5 mg/sqm on days 1 to 3. Treatment courses were administered every 3 weeks up to a maximum of 6 cycles. Patients with high-grade lymphoma received chemotherapy according to the CHOP schedule every 4 weeks up to a maximum of 6 cycles. Two patients with high-grade lymphoma were treated as low-grade lymphoma patients (one because of age and poor performance status, the other because she refused chemotherapy that would cause hair loss). Two patients with low-grade lymphomas who did not respond to mitoxantrone were crossed over to CHOP.All patients were evaluable for toxicity, 13 for response to therapy and survival. Toxicity was mild or moderate. Neither perforation nor hemorrhage was observed. Eleven patients achieved a complete remission (85%), 1 a partial remission (7.5%) and 1 underwent disease progression (7.5%). At a median follow-up of 12 months (range 4-44 months) all complete responders are alive and disease free.Although the number of evaluable patients is too small to draw any final conclusions, chemotherapy seems to be as effective as surgery in PGL, and stomach preservation improves the quality of life of the patients.

Thirty-three patients with microscopically verified primary or metastatic malignant pleural effusion were studied: 7 had malignant mesothelioma and 26 metastatic pleural disease. The treatment was based on biochemical and clinical studies which show a synergy between cytosine-arabinoside (Ara-C) and cisplatin. These drugs were instilled in the pleural cavity at the dose of 100 mg for Ara-C and 100 mg/m2 for cisplatin. The cavity was drained after 4 h. If it was possible, the treatment was repeated weekly for 3 times and, after a 6-week rest, it could be started again with the same schedule. The overall response rate (complete plus partial remissions) was 74%. Toxicity was mild or moderate. We conclude that the combination of Ara-C and cisplatin is well tolerated and produces a high response rate in the treatment of malignant pleural effusions.

Acute suppurative thyroiditis is an uncommon thyroid disorder usually caused by bacterial infection. The most common route of infection is a fistula that originates from the fundus of the pyriform sinus. Pre-existing thyroid disease, most commonly nodular goiter, has been reported to be present in acute suppurative thyroiditis. A 44 year old man presented a subacute thyroiditis, resolved by nonsteroidal antiinflammatory treatment. One year later, the patient abruptly complained of fever and painful swelling in the thyroid region. A relapse subacute thyroiditis was diagnosed and prednisone treatment was started. A few days later owing to a worsening of the pain and of the clinical features the patient was referred to our department. He presented dysphagia and he was feverish, the overlying skin of the neck swelling was erythematous and warm. There was a neutrophilia (83.7%). Plasma FT4, FT3 and TSH were normal. Anterior neck region ultrasonography showed an enlargement of the left thyroid lobe with poorly defined shapes and inhomogeneous parenchyma while the right lobe of the gland was normal. The 131-I thyroid scan showed a large cold area in the upper part of the left thyroid lobe and preserved radionuclide uptake in the residual parenchyma. The RAIU was normal. We diagnosed acute suppurative thyroiditis and started antibiotics treatment. The day after the patient was still feverish and he gave out from the mouth a great quantity of sero-purulent material with a swelling reduction and improvement of the neck pain. Barium swallow examination did not show any fistula in the cervical esophagus. The fistula opening was demonstrated by indirect laryngoscopy in the postero-lateral side of hypopharynx.(ABSTRACT TRUNCATED AT 250 WORDS)

38 patients with advanced breast adenocarcinoma were treated in a phase II study with 5-fluorouracil and high-dose folinic acid combined with cyclophosphamide and mitoxantrone. 6 patients had received prior chemotherapy for advanced disease, all with an anthracycline-containing regimen. Treatment was generally well tolerated. The most common side-effect was myelosuppression, with 1 toxic death due to leukopenia-related sepsis. 1 patient developed severe congestive heart failure 12 months from the end of therapy. 36 patients were evaluable for response. The overall response rate was 55%. Median duration of response was 8 months and median survival time was 16 months. This regimen warrants further investigations.

Summary In a multicentre Phase III trial, 182 patients were randomized to either folinic acid (FA) (200 mg/sqm i.v. × 5 days) + 5-fluorouracil (5-FU) (400 mg/sqm i.v. in 15' × 5 days) every 4 weeks (Arm A), or to 5-FU one at the same dosage (Arm B). Response rates were 20.6% (Arm A) and 10% (Arm B) with a significant (p = 0.046) advantage for FA + 5-FU. Median time to progression (6 and 6 months) and overall survival (11.5 and 11 months) were similar in the 2 groups of patients, while neither treatment was effective in reducing pain or improving performance status. Univariate analysis showed that no prognostic factors other than treatment influenced response, although survival was affected by the number and site of metastases, performance status, and the presence and degree of pain. Toxicity was acceptable and lower in comparison with other Phase II-III trials, with no significant difference between the 2 arms. However, in individual patients, grade 3-4 side effects (mainly stomatitis and diafrrhoea) were observed, particularly in patients receiving FA: this led to interruption of the treatment in 7 cases. The superiority, in terms of objective response, of FA + 5-FU over 5-FU alone would seem to justify a large-scale evaluation of this combination in the adjuvant setting. Further improvements in relation to advanced disease (i.e, modifications to the schedule and/or introduction of other modulators) are warranted.

Forty-one patients suffering from primary non-Hodgkin lymphomas of the digestive tract have been observed over a period of 15 years. The primary sites were: the stomach in 27 cases, the small bowel in 8, the ileocecal region in 5, and the mesentery in 1. Patients were staged according to the modified Ann Arbor staging system proposed by Mushoff (20). Four kinds of management were employed: 1) surgery alone; 2) surgery and radiotherapy; 3) surgery, radiotherapy and chemotherapy; 4) surgery and chemotherapy. One patient was treated by chemotherapy alone. Radiotherapy was administered postoperatively and chemotherapy after or during radiotherapy. Generally, 2 opposed fields largely encompassing the tumor area and lomboaortic nodes if necessary, up to 25-30 Gy to the midline, were employed, with a booster dose up to 40-45 Gy to the involved area. Total abdominal irradiation was never employed. No clear difference emerged in survival rate nor in relapse-free survival among the four subgroups, but patients who underwent complete resection fared better than incompletely resected patients. However, these two subgroups were not homogeneous. A clear difference in survival rate did not emerge between patients treated or not with postoperative chemotherapy, whereas patients who relapsed after complete remission or those who never had complete remission had a poor prognosis.

15 patients with primary or metastatic pleural effusion were studied: 2 had diagnosis of malignant mesothelioma and 13 of metastatic pleural disease. The treatment used was based on in vitro and in vivo studies which show a synergy between ARA-C and Cisplatin. These drugs were instilled in pleural cavity at the dose of 100 mg./m2 for Cisplatin and 100 mg. for ARA-C. The cavity was drained after 4 hours. The treatment was repeated weekly. All patients had not been previously treated with loco-regional therapy. The response rate was 93% with 10 loco-regional complete remissions (66%). The two patients with malignant mesothelioma achieved a complete remission. The overall toxicity was acceptable. We conclude that combination of Cisplatin and ARA-C is well-tolerated and produces a very high response rate in the treatment of malignant pleural effusions.

Microautoradiography has been largely used to characterize the proliferative activity of colorectal mucosa. We used this technique in a large series of patients with polyps or cancer of the large bowel and in normal controls with the following objectives: (a) to define the normal pattern of cell replication in different tracts of the large bowel; (b) to compare the proliferative activity of colonic crypts in patients with colorectal cancer or polyps with that of controls; (c) to evaluate replicative activity of colorectal mucosa in the close vicinity and at distance from a neoplastic mass. Specimens of colorectal mucosa were taken during endoscopy (controls and polyps) or at surgery (cancer). During histological examination each intestinal hemicrypt was divided into five equal longitudinal compartments from the base to the surface and the labeled cells in each compartment were counted. In controls, total labeling index (ratio of labeled to total cells) and labeling index per crypt compartment showed only minor differences between the various large bowel tracts. Total labeling index tended to be higher in patients with polyps or cancer than in controls (13.5 +/- 0.4 and 12.5 +/- 0.4, respectively, versus 11.3 +/- 0.5). Labeling index per crypt compartment in the most superficial portions of the crypt (compartments 3 to 5) was significantly higher in the two groups of patients with tumors than in controls. This was particularly evident in the fifth compartment (the most superficial), in which labeled cells were observed in 15.8% (three subjects out of 19) of controls but in 71% (15 out of 21) and 87.5% (14 out of 16) of polyp and cancer patients, respectively. In patients with colorectal cancer there were not significant differences of cell proliferation between mucosal samples taken at various distances from the tumor margin; however, increased cell replication, especially in the most superficial portions of the crypt, has been observed. In conclusion, a significant upwards expansion of the proliferative zone of intestinal glands has been observed in patients with either polyps or cancer of the large bowel. In particular, labeling of the fifth compartment seems to possess the highest discriminatory power between subjects with or without intestinal neoplasms. Hyperproliferation of the entire colonic mucosa seems to be a common feature in patients with colorectal cancer.