A population of 1136 HPV DNA-HR positive women: expression of p16(INK4a)/Ki67 Dual-Stain Cytology and cytological diagnosis. Histological correlations and cytological follow up.

OBJECTIVE: The objectives of this study were to evaluate, in a selected HR-HPV positive population, the clinical performance of the p16/ki67 immunostaining in all the cytological diagnoses, as a reflex test of triage HPV-cytology, and assess the usefulness of p16/ki67-staining to classify CIN1 according to its risk of progression/regression in order to plan a personalized follow-up. METHODS: Our analysis was in consecutive cases of 1136 women aged 25-64 years, asymptomatic, HR-HPV DNA HC2 tested positive in a HPV-screening program, from February to December 2011. All the women had a cervical sample, in the Thin Prep, used for cytological diagnosis and for pI6/Ki67 dual- staining. Histological correlations were 442. We studied the follow-up of two years of 387 cases, especially the biological behaviour of 316 low-grade lesions. RESULTS: pI6/Ki67 dual-staining increases the VPP CIN2+ and NPV CIN2+, especially in atrophy/dystrophy, in ASC-US and LSIL. In follow-up of 387 cases, 71 CIN2+ and 316 CIN1, 69 CIN2+, after surgical treatment, had a negative follow up; two cases of CIN2 (p16/ki67-) without invasive treatments, had a spontaneous regression. Among the 316 CIN1, progression was observed in 10 women (4 pI6/Ki67 + and 6 pI6/Ki67 -); regression in 260 women (64 p16/Ki67 + and 196 p16/Ki67-); 46 women had a persistent LSIL (9 pI6/Ki67 + and 37 p16/Ki67-). It seems no significant differences in the biological behaviour in relation to the expression of the two biomarkers. CONCLUSIONS: pI6/Ki67 immunostaining increases sensitivity of cytology in some diagnostic categories. After follow up of two years, a personalized and adequate treatment does not seem still possible. Further studies and trials are required to improve the management of the cervical lesions in HPV-based screening strategies.

Prognostic value of subclassification of T2 tumours in patients with gastric cancer.

BACKGROUND: This study was designed to evaluate the prognostic value of tumour stage T2 subcategorization (T2a and T2b) in patients with gastric carcinoma. METHODS: Clinicopathological details of a prospective series of patients who had radical resection of gastric adenocarcinoma in a single institution were analysed. Univariable and multivariable survival analyses were performed with the log rank test and Cox's model respectively. RESULTS: Of 373 evaluable patients, 49 (13.1 per cent) had a T2a and 143 (38.3 per cent) a T2b tumour. At a median follow-up of 35.5 months, the 5-year overall survival rate was 73 and 31.1 per cent for patients with T2a and T2b lesions respectively (P < 0.001). On multivariable analysis, T stage remained an independent prognostic factor. Compared with T1a, the mortality risk for patients with T1b (hazard ratio (HR) 1.00; P = 0.992) and T2a (HR 0.97; P = 0.916) tumours was similar; by contrast, the risk of death associated with T2b (HR 1.81; P = 0.031) and T3 (HR 1.89; P = 0.038) lesions was significantly greater than for T1a tumours. CONCLUSION: Subclassification of T2 tumours should be undertaken routinely in order to stratify patients with gastric cancer more accurately in terms of their mortality risk.

Clinical impact of false-negative sentinel lymph nodes in breast cancer.

AIMS: To evaluate the incidence of false-negative (FN) sentinel lymph node (SLN) cases, their correlation with a series of clinico-pathologic parameters and their impact on adjuvant treatment indications and on clinical axillary relapse in the setting of a multicentric clinical trial comparing SLN biopsy with axillary lymph node dissection (ALND). METHODS: A series of 697 patients with primary breast cancer < or = 3 cm were randomized to SLN biopsy associated with ALND (ALND arm) or to SLN biopsy followed by ALND only if the SLN was metastatic (SLN arm). The FN SLN rate was assessed in the ALND arm. A series of 11 clinico-pathological parameters were tested for a possible association with FN results. The indications for adjuvant treatments were evaluated by considering both the FN nodal stages, as indicated by the SLN, and the true positive axillary status, as indicated by completion ALND. The occurrence of clinically evident axillary recurrences was evaluated in the two arms. RESULTS: The FN rate was 16.7%. Of the clinico-pathologic parameters tested, only a tumour size < or = 2 cm and the presence of a single metastatic axillary node was significantly associated with a risk of FN (p = 0.033 and p = 0.018, respectively). The FN SLN would have led to different adjuvant therapy indications in 12/18 cases. At 56 months, no clinically evident axillary nodal recurrences were present in the ALND arm patients, whereas one case of axillary recurrence was detected in the SLN arm patients. CONCLUSIONS: FN SLN biopsy is not uncommon, especially in the presence of a small primary tumour with a single nodal metastasis. An FN finding can lead to less than optimal adjuvant treatment. However, the clinical impact of FN in terms of axillary recurrence at 56 months was minimal.

Extended lymphadenectomy (D2) in patients with early gastric cancer.

AIMS: To investigate the survival benefit of extended lymphadenectomy (D2) in EGC patients in one European Institution. METHODS: A review was made of our prospective gastric database from January 1980 to December 2001. Of 527 patients with primary gastric adenocarcinoma, 119 with EGC underwent potentially curative resection (R0) with D2 lymphadenectomy. RESULTS: There were two post-operative deaths. Of the 117 evaluable cases, 96 were classified as N0 and 21 as N+, with metastases in the perigastric lymph nodes (level 1) in 13, and beyond this site (level 2) in eight. Five-year survival was 85.9 and 83.0% in N0 and N+ patients, respectively. During a median follow-up of 90 months, five of the eight patients with level 2 metastases died of recurrent disease and three were alive. The estimated survival benefit for 119 patients with EGC was 2.5% (3/119 cases). CONCLUSIONS: In patients with EGC, metastases to level 2 are rare. Our results indicate that D2 lymphadenectomy has a limited survival benefit and that in these cases a less extensive lymphadenectomy (D1) could be performed.

D2 or non D2-lymphadenectomy in gastric cancer

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Detection and quantitation of morphine in fixed tissues and formalin solutions.

The study reports the results of the detection and quantitation of morphine in tissues fixed in formalin and in the formalin solutions in which the same tissues were fixed. Toxicological analyses were performed on formalin-fixed liver and kidney samples from five cases of opiate poisoning and on the formalin solutions (10% buffered pH 7) in which the samples were preserved. Analyses carried out at the time of autopsy on body fluids and tissues allowed identification of opiate as the cause of death and its quantitation. Tissue samples were preserved in formalin solutions for 12 weeks before analysis. The mean levels of recovery of morphine in fixed tissues were 36.29% in liver, 29.41% in kidney, 74.93% in formalin from liver, and 42.17% in formalin from kidney. Results indicated that this particular toxic substance shows good stability even in biological specimens subjected to chemical fixation.

Analytical detection and quantitation of strychnine in chemically fixed organ tissues.

This study reports the results of the detection and quantitation of strychnine in formalin-fixed tissues and in the formalin solutions in which the tissues were fixed. The toxicological analyses were performed on formalin-fixed liver and kidney samples and formalin solutions (10% buffered pH 7) in which the same samples from a case of acute strychnine poisoning were preserved. The analyses carried out at the time of autopsy on body fluid and tissues (bile, 2.40 mg/L; stomach contents, 14.2 mg; liver, 6.68 mg/kg; kidney, 2.68 mg/kg) allowed the identification of this substance as cause of death. The tissue samples were preserved in formalin solutions for 8 weeks. The analyses performed on formalin-fixed tissues (liver and kidney) and on formalin solutions, in which the same tissues were preserved, permitted the detection and quantitation of strychnine (liver, 1.59 mg/kg; formalin from the liver, 1.80 mg/L; kidney, 0.98 mg/kg; formalin from the kidney, 1.11 mg/L). The results indicate that this particular toxic substance also shows good stability in biological specimens subjected to chemical fixation.

PCR analysis of the short tandem repeat (STR) system HUMVWA31. Allele and genotype frequencies in an Italian population sample.

A population study in a sample of 211 unrelated individuals from 2 cities in North and Central Italy was carried out to investigate the short tandem repeat (STR) system HUMVWA31. Separation of PCR- amplified DNA fragments was performed by high-resolution horizontal denaturing polyacrylamide gel electrophoresis (PAGE) followed by silver staining. The 7 common alleles were found, together with a new smaller allele. Distribution of the observed genotypes did not deviate from Hardy-Weinberg (H-W) equilibrium. The power of discrimination for this locus was 0.93 and the chance of exclusion was 0.61. Good agreement was found between the allele frequencies in 2 Italian population samples and previous studies on Caucasians. The results of this study suggest that this STR system may be a useful tool in forensic investigations.

PCR typing of the locus D17S30 (YNZ22 VNTR) in an Italian population sample.

A sample of 202 subjects living in 2 Italian provinces (Ancona and Parma) was tested for YNZ22 polymorphism by the polymerase chain reaction (PCR). After amplification, the phenotypes were separated by agarose gel electrophoresis, stained with ethidium bromide and identified by comparison with a molecular weight marker. No heterogeneity was found between the 2 populations. Alleles, pooled in 4 groups to calculate the Hardy-Weinberg (H-W) equilibrium, showed good accordance between observed and expected values. The power of discrimination (PD) was 0.95 and the chance of exclusion was 0.69. The allele comparison with previous studies on Caucasians showed no significant difference.

Heterotopic gastric (fundic) mucosa in the duodenum.

Twenty cases of heterotopic fundic mucosa in the duodenum are reported. The patients had several small polyps ranging from one to three mm tightly grouped to form a plaque in a limited zone of the duodenal bulb. In some cases the polyps were separated from one another. They were round or conical and manifested a frosted-glass appearance with a pale-pink or redded coloration. In two cases a whitish solitary polyp of five mm was located in the 2nd part of the duodenum. Biopsies obtained from the polyps revealed them to be composed of fundal mucosa, thus representing a particular form of heterotopia, other then the steroid-induced type, and that of patients undergoing regular dialysis for uraemia. The different clinical and morphological data in the various forms of fundal heterotopia are discussed.

Morphological changes of the gastroduodenal mucosa in regular dialysis uraemic patients.

An endoscopic and biopsy study of the upper gastrointestinal tract in 102 patients receiving regular dialysis treatment (RDT) for chronic renal failure, showed prominent hypertrophic folds and a peculiar pale-grey or pale-pink colour of the gastric mucosa in most cases. Gastric erosions occurred in 11 cases and gastric ulcer in two. Duodenal erosions were found in 13 cases, eight of which were associated with hyperplasia of Brunner's glands. Duodenal ulcer occurred in one case. The histological findings were compared with those in 100 subjects with an endoscopically normal gastro-duodenal tract. In most cases of the RDT group the fundal area was enlarged at the expense of the antrum, fundal glands and/or isolated parietal cells often spreading within the duodenal mucosa. In most cases the duodenal bulb showed hyperplasia of Brunner's glands and heterotopic gastric surface epithelium. The frequency of the mucosal changes differs significantly in the two groups of subjects. Gastric hyperplastic changes in RDT are probably due to the trophic action of hypergastrinemia which is of common occurrence in such a condition, and can account for gastric acid hypersecretion. Acid hypersecretion, in turn, can account for the duodenal changes and gastroduodenal lesions.

Changes in the mucosa of the stomach and duodenum during immunosuppressive therapy after renal transplantation.

Upper gastrointestinal endoscopic examination of 40 patients on immunosuppressive therapy after successful kidney transplantation revealed a duodenal ulcer in four cases and duodenal erosions in six. Between four and six biopsies were collected from the antral and the fundal mucosa in each case and from the duodenal mucosa in 29. Antral superficial gastritis was found in 13 cases and fundal superficial gastritis in three. In the fundus, heterotopic calcifications were seen in eight cases and cytomegalovirus inclusion bodies in two. Parietal cells were increased in number and reached the pyloric zone in 34 cases, whilst they spread within the duodenal mucosa in 12. Multinucleate parietal cells were of common occurrence and in some cases showed mitotic figures. Duodenitis was found in 16 cases and in duodenal mucosal cells cytomegalovirus inclusion bodies were seen in nine cases. Biopsy evidence of hyperplasia of Brunner's glands was encountered in 26 cases. Of 20 patients tested for gastric acid secretion, hypersecretion occurred in 14 and normal secretion in six. Endoscopic and histological changes relate to the secretory pattern. Cytomegalovirus inclusion bodies relate to immunosuppressive therapy. An inverse temporal relationship exists between heterotopic calcification and the duration of renal transplant. Steroids seem to be responsible for gastroduodenal changes in transplanted patients.