Clinical impact (cost-effectiveness) of qualifying atypical squamous cells of undeterminate significance (ASCUS) in cases favoring a reactive or dysplastic process.

The cost-effectiveness of qualifying ASCUS cases into two different subcategories, favoring a reactive (ASCUS-R) or dysplastic process (ASCUS-S), was evaluated at the Centro per lo Studio e la Prevenzione Oncologica of Florence in a prospective study. The study determined the positive predictive value (PPV) for histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2) or more (CIN>) severe lesion of the two ASCUS subgroups. ASCUS-S had a PPV (10.78%) comparable to low-grade squamous intraepithelial lesions (LSIL) (11.40%). For ASCUS-R cases, the recommendation of 6-mo repeat cytology prompting colposcopy in cases of persistent ASCUS or more severe cytology was also effective, as it selected a subgroup with a relatively high PPV (10.34%). The cost-effectiveness of a protocol based on ASCUS qualification was compared with two other possible options for nonqualified ASCUS cases: immediate colposcopy and colposcopy in persistent ASCUS at 6-mo repeat cytology. The detection rate of CIN2> was substantially higher using ASCUS qualification (35.9 vs 14.8 or 17.1). The cost per ASCUS subject was euro 24.99, 27.11, or 25.14 and that per CIN2> detected was euro 697, 1,831 or 1,470 for the three options, respectively. The evidence that ASCUS detection option implies a higher detection rate of CIN2> and subsequently a lower cost per CIN2> detection must be considered with caution and deserves confirmation by other comparative studies.

Achalasia.

AIM: Achalasia is a disease of unknown etiology resulting from degeneration of the esophageal Auerbach submucous plexus. This degeneration makes normal relaxation of the cardia during swallowing impossible leading to dysphagia, chest pain and regurgitation of varying degree. Until 15 years ago the main conservative treatment for achalasia was dilatation of the cardia with the Starck apparatus. Such approach to achalasia was usually reported as fairly effective, but complicated by an exceedingly high rate of perforation. This led most centers to replace the Starck procedure with pneumatic or hydrostatic balloon dilators. The aim of our study was to evaluate safety, early and late results of the Starck procedure. METHODS: Our report is based on the retrospective analysis of 21 patients [male/female: 12/9, mean age 46 years (range-65)] who underwent 52 Starck procedures for esophageal achalasia. The effectiveness of the Starck procedure was assessed according to the scale of Vantrappen and Hellemans. RESULTS: After the scheduled 2 Starck sessions, an excellent result was seen in 10 patients (50%), a good result in 8 (40%); 2 patients (10%) showed a poor result. One month after the last Stark procedure 1 patient (5%) experienced gastroesofageal reflux easily managed with protein pump inhibitors. During or after dilations no major complications were observed. CONCLUSIONS: The Starck procedure, now replaced by the new Rigiflex pneumatic dilator, resulted effective and safe in experienced hands.

Systemic nitric oxide production and renal function in nonazotemic human cirrhosis: a reappraisal.

OBJECTIVES: Several studies in human cirrhosis have demonstrated increased nitric oxide (NO) production. In experimental animals, intracerebroventricular administration of NO donors causes a marked depression of the endogenous dopaminergic activity, a function known to be physiologically recruited and exerting a natriuretic function in patients with compensated cirrhosis. The aim of this study is to evaluate the interaction between the systemic plasma levels of NO, the endogenous dopaminergic activity and the main parameters of renal function in patients with liver cirrhosis of differing degrees of severity. METHODS: A total of 21 patients (11 with preascitic and 10 with nonazotemic diuretic-free ascitic cirrhosis) and 10 healthy control subjects underwent the following tests: a) basal plasma renin activity (PRA) and aldosterone levels; b) renal clearances of sodium, potassium, inulin, para-minohippurate and lithium (the latter being a measure of the fluid delivery to the distal nephron); c) NO systemic plasma levels measured through paramagnetic resonance spectroscopy as nitrosylhemoglobin complexes; d) endogenous dopaminergic activity, evaluated by means of the incremental prolactin and aldosterone plasma levels after dopaminergic blockade with i.v. metoclopramide. RESULTS: NO plasma values and endogenous dopaminergic activity, although significantly increased with respect to healthy controls, were not different in the two groups of patients. The plasma NO/PRA ratio was significantly higher in the group of compensated patients with respect to ascitic cirrhotics (respectively, 18.3 +/- 11.8 vs 3.5 +/- 2.6 A.U./ng/ml/h, p < 0.001). Compared with compensated cirrhotics, patients with ascites showed significantly lower values of glomerular filtration rate (GFR) and renal plasma flow (RPF). Interestingly, GFR values were substantially the same in the ascitic patients and the control subjects. Compensated patients displayed a significant positive correlation between metoclopramide-induced incremental aldosterone plasma levels (i.e., endogenous dopaminergic tone) and fractional excretion of sodium (r = 0.58; p < 0.05). In the group of compensated patients, NO levels correlated inversely with creatinine plasma concentrations (r = -0.85; p < 0.001) and directly with inulin clearance (r = 0.65; p < 0.05). CONCLUSIONS: These data show that, at least in compensated cirrhotic patients, the stimulation of systemic NO production and the increased dopaminergic function may be mechanisms preventing renal perfusion, GFR, and fractional excretion of sodium from precocious reductions.

Renal tubular events following passage from the supine to the standing position in patients with compensated liver cirrhosis: loss of tubuloglomerular feedback.

BACKGROUND AND AIMS: Patients with preascitic liver cirrhosis display significant renal sodium retention in the upright posture and an exaggerated natriuresis during recumbency. To date, intrarenal sodium handling in these patients has not been studied using lithium clearance and fractional excretion techniques during recumbency and orthostatism. METHODS: Ten patients with preascitic (Child-Pugh A) liver cirrhosis and 10 healthy subjects underwent the following measurements during recumbency and then after four hours of standing: (a) active renin and aldosterone plasma levels; and (b) renal clearance of creatinine, sodium, potassium, and lithium (an index of fluid delivery to the loop of Henle). RESULTS: Unlike the control group, in the upright posture patients had significantly lower values of lithium clearance and fractional excretion compared with recumbency (21.6 (8.6) v 30.5 (10.2) ml/min (p<0.03) and 12.8 (4.4)% v 20.8 (4.9)% (p<0.01), respectively). Our patients showed maintenance of the glomerular-tubular balance-that is, the correlation between creatinine clearance and proximal tubular reabsorption of fluid-during both recumbency and in the upright posture (r=0.96, p<0.001; r=0.97, p<0.001, respectively). In contrast, patients displayed tubuloglomerular feedback only in the supine position. This was demonstrated by the observation of a negative correlation between lithium fractional excretion (a measure of the fractional delivery of sodium to the distal nephron) and filtered sodium load only in recumbency (r=-0.73; p< 0.03) and not during standing (r=0.22; p> 0.05). CONCLUSIONS: This study suggests that both the reduction in fluid and sodium delivery to the distal nephron and loss of tubuloglomerular feedback (the mechanism increasing glomerular filtration rate when the distal tubule is reached by a reduced sodium load) contribute towards the tendency to sodium retention in compensated cirrhosis during prolonged upright posture.

p53 evaluation in gastric mucosa of patients with chronic Helicobacter pylori infection.

Gastric cancer is often associated with p53 over-expression and Helicobacter pylori (HP) infection. In this study we have investigated the production of the p53 protein and mutation of its gene in precancerous gastric lesions with HP infection. For this purpose 130 patients who underwent endoscopy for dyspepsia were enrolled in the study. To assess p53 production and mutation of the p53 gene we employed an immunoluminometric assay and polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) analysis, respectively. Histologically, 52 of the 130 enrolled patients showed intestinal metaplasia type I (IM) (90.4% of these were also HP positive), 47 had HP-related gastritis and 31 were normal. p53 cytosol levels were significantly higher in patients with IM or HP-related gastritis than in normal patients (p = 0.0137 and p = 0.0411, respectively). All DNAs extracted from gastric mucosa samples with higher p53 values and examined for p53 mutations by PCR-SSCP analysis were characterized by a normal run. Our data indicate, that irreversible genetic changes in the p53 protein has not yet occurred in morphologically non-neoplastic gastric mucosa with IM and HP-related chronic gastritis. In conclusion, the increase in p53 cytosolic levels found in our study is due to an increased production of the wild-type protein probably related to an inflammatory response induced by HP infection.

Analysis of false-negative and underreported smears in the Florence district screening program for cervical carcinoma.

AIMS AND BACKGROUND: To review false-negative or underreported (reactive changes, squamous or glandular atypia) smears performed in women developing histologically proven CIN2 or more severe lesions within 24 months and evaluate error causes. The study setting was the Florence District cervical cancer population-based screening: about 60,000 women age 25-60 years screened per year. METHODS: 118 false-negative or underreported cases were identified at screening files-cancer Registry matching, and the original smears were reviewed by six independent readers to judge smear adequacy and error type. RESULTS: Sampling errors (reported as inadequate, negative or less severe than CIN1 at review) accounted for 74% and screening/interpretation errors (reported as CIN1 or more severe at review) accounted for 26% of studied cases. Screening/interpretation errors were more likely ascribed to misinterpretation and underreporting than to misperception of cellular abnormalities. CONCLUSIONS: Quality control should above all address the problem of sampling adequacy. Due to the rarity of misperceived abnormalities (true screening errors), manual or automated rescreening of negative smears would not be an effective procedure for quality control.

Analysis of the causes of false negative cytology reports on breast cancer fine needle aspirates.

Forty-six (2.9%) false negative reports were recorded among adequate fine needle aspirates from 1609 consecutive histologically proven carcinomas, observed from 1991 to 1993. False negatives were more frequent among younger women (< 40 years = 7.1; 40-49 years = 4.0; 50-59 years = 3.6; 60-69 years = 1.7; > 69 years = 1.5%), lobular invasive subtypes (5.4%), and smaller tumours (pT1a = 4.2; pT1b = 7.6; pT1c = 1.9; pT2 = 2.1; pT3-4 = 1.5%). The latter findings is probably ascribable to better differentiation and less precise sampling of small non-palpable tumours. No significant association was found between the false negative rate and the sampler's or reader's skill and experience. The former finding may be ascribed to the wide use of sonography guided aspiration, even for palpable masses, and the latter to the fact that readers were highly experienced and undergo periodic quality control of individual performance. False negatives were reclassified at reviews as true false negatives, reading errors or inadequates in 27, 11, and eight cases, respectively. The observed findings suggest that in most cases cytological faults were due to the absence of cytological atypia in cells sampled from well differentiated tumours, rather than to misinterpretation or sampling from adjacent normal tissues.

[Palliative biliary-digestive bypass with a Kehr tube for neoplastic surgical cholestatic jaundice]. / Bypass bilio-digestivo palliativo con tubo di Kehr per ittero colostatico chirurgico neoplastico.

The authors, in some rare cases of surgical neoplastic icterus operation, had to adopt a technique of biliary-digestive bypass with prosthesis on account of the technical-anatomical and general conditions of the patients. That prosthesis has been made out of the typical Keher's duct which can be generally found in every general surgery. The above mentioned authors describe the operations they have carried out, their directions and the results of six cases which have been treated with a technique similar to Kron's.

Routine colposcopic survey of patients with squamous atypia. A method for identifying cases with false-negative smears.

Routine colposcopy was performed on 376 women with cervical squamous atypia (originally reported as "inflammatory atypia"). Colposcopy showed no abnormalities in 240 cases and a lesion in 136 cases; the latter were sampled by colposcopy-guided biopsy. The biopsy samples showed evidence of human papillomavirus (HPV) infection and/or grade I cervical intraepithelial neoplasia (CIN I) in 42 cases (11.1%), CIN II in 4 cases (1.1%) and CIN III in 5 cases (1.3%); the other 85 biopsied cases were histologically negative. Most cases of HPV/CIN I (35 of 42) and all of the cases of CIN II-III occurred in women under the age of 40. The detection rates were 4.4% for CIN II-III in women under the age of 40, 4.0% for HPV/CIN I in women 40 and older and 17.2% for HPV/CIN I in women under the age of 40 (P less than .001). It thus appears that women under the age of 40 who show cytologic evidence of squamous atypia would benefit from colposcopic examination.

"Nonclassic" cytologic signs of cervical condyloma. A case-control study.

The association between "nonclassic" cytologic signs of condyloma and human papillomavirus (HPV) infection in women with negative Papanicolaou smears was analyzed via a case-control study. The cytologic signs considered were mild koilocytosis, mild dyskeratosis, binucleation or multinucleation, cleared cytoplasm and nuclear hyperchromatism. The Papanicolaou smears of 166 cases that showed colposcopic and histologic evidence of HPV infection (but whose smears lacked the classic cytologic signs of condyloma) and 166 controls that were negative colposcopically were randomly admixed and blindly reviewed by a panel of cytologists. A significant association to HPV infection was observed for all of the nonclassic signs studied, but multivariate analysis showed a weakly independent association only for mild koilocytosis. The sensitivity (0.46) and the specificity (0.87) of these nonclassic signs were not satisfactory. The utility of selecting women with negative Papanicolaou smears for colposcopy on the basis of these signs is discussed.

Colposcopic survey of Papanicolaou test-negative cases with hyperkeratosis or parakeratosis.

A colposcopic survey was performed in 269 consecutive women with negative cytology showing hyperkeratosis or parakeratosis. A colposcopy-guided biopsy specimen of cervical abnormalities was taken in 88 cases, and human papillomavirus infection (HPV) was detected histologically in 25 cases. No cervical intraepithelial neoplasia (CIN) was detected. The detection rate of HPV was not significantly different from that observed in a consecutive series of 1073 Papanicolaou test-negative subjects self-referred for colposcopy. Colposcopic screening of subjects showing hyperkeratosis or parakeratosis with otherwise negative smears is not recommended because it does not allow detection of cytologically false-negative CIN.

Percutaneous transhepatic cholangioscopy with a 2.8 mm fiberscope.

The authors describe their initial experience with a 2.8 mm (8.5F) fiberscope. The instrument, used to refine interventional radiology maneuvers of the intra- and extra-hepatic bile ducts, caused no additional discomfort to the 18 patients treated. The fiberscope permitted differentiation between different causes of biliary stenosis in the few cases where doubt persisted after percutaneous cholangiography. Brushing was also performed wherever necessary. The color, and thus the composition, of bile duct stones could also be determined. This has helped us to plan the therapy with methyl-tert-butyl-ether (MTBE) in patients with cholesterol stones. Compared with traditional fiberscopes (diameter of 5mm or more) the new instrument is easier to use, and allows more peripheral ducts to be reached, but is expensive and has a smaller field of view and fewer possibilities for therapeutic applications.

[Methyl-ter-butyl ether (MTBE) therapy of cholesterol biliary calculosis. First long-term controls (up to 22 months)]. / Trattamento con metil-ter-butil etere (MTBE) della calcolosi biliare colesterinica. Primi controlli a distanza (fino a 22 mesi).

The results and clinical and instrumental examinations of 12 patients at least 6 months after MTBE treatment for cholesterine biliary calculosis are presented. No recurrence of stones or alterations to the biliary ways or duodenal mucosa attributable to MTBE were encountered.

[Percutaneous transhepatic cholangioscopy with an 8.5 French endoscopic catheter. Technic and preliminary results]. / Colangioscopia percutanea transepatica con catetere endoscopico 8,5 French. Tecnica e risultati preliminari.

The authors describe their preliminary personal experience in bile duct endoscopy with a very small diameter catheter (8.5 F) much less traumatic than traditional choledochoscope (15 F). The CE can be reutilized after sterilization; an angiographic guide wire up to 0.042" can be introduced in the operating channel. The CE was used in 3 patients with uncertain cholangiographic diagnosis. Instrument introduction is facilitated when simple technical manoeuvres are followed; there were no difficulties in report interpretation. An experienced interventional radiologist and an endoscopist are needed to handle the instrument. Cytologic sample, biopsy and gallstone lithotomy instruments will increase diagnostic and therapeutic possibilities of the system: for this a wider CE use in the immediate future to complete interventional radiology manoeuvres can be expected.

[Percutaneous pancreato-gastrostomy in the treatment of pancreatic pseudocysts. Presentation of 2 cases]. / La pancreato-gastrostomia percutanea nel trattamento delle pseudocisti pancreatiche. Presentazione di 2 casi.

The authors describe a new method for the treatment of pancreatic pseudocysts using a personal technique: the percutaneous pseudocystogastrostomy. Under US and fluoroscopy guidance at first a percutaneous drainage is introduced in the pseudocyst using a transgastric approach. For seven days the drainage catheter is flushed with antibiotic solution (Rifocin), then under fluoroscopy and endoscopy guidance doubled pig-tail catheter is placed with its curlend ends in the lumen of the stomach and pseudocyst respectively. After 60 days the double pig-tail catheter is removed endoscopically. Two patients with pancreatic pseudocysts were treated successful by this method. No complications or recurrences were observed.

Methyl-TER-butyl ether (MTBE) and endoscopic sphincterotomy. A possible solution for dissolving gallstones.

MTBE was instilled in 6 cases of lithiasis (1 intrahepatic, 5 giant common bile duct stones following EPT). The nasobiliary route (3 cases) and a percutaneous biliary drain (3 cases) were used for this purpose. Complete stone dissolution was achieved in four cases. In the other two, volume reduction was sufficient to allow spontaneous elimination after EPT. A full clinical recovery was obtained in all cases. Further investigation is required in cases of intrahepatic and common bile duct stones when their removal by EPT is not enough to lead to clinical resolution. Follow-up is indispensable.

[Clinical evaluation of chemical cholelitholysis using methyl tertiary butyl ether in lithiasis of the bile ducts]. / Valutazione clinica della colelitolisi chimica con MTBE nella litiasi delle vie biliari.

Personal experience is reported in the treatment of calculosis of the biliary ways using MTBE and injected through percutaneous biliary drainage catheters placed surgically or endoscopically in 11 patients in whom surgery appeared to be contraindicated or particularly dangerous. In 10 out of the 11 cases chemical cholelitholysis was successful and the technique is therefore proposed as a valid alternative to surgery in ductal cholelitholysis when sphincterotomy and endoscopic removal of the stones cannot cure the conditions.