Immunohistochemical/histochemical double staining method in the study of the columnar metaplasia of the oesophagus.

Intestinal metaplasia in Barrett's oesophagus (BO) represents an important risk factor for oesophageal adenocarcinoma. Instead, few and controversial data are reported about the progression risk of columnar-lined oesophagus without intestinal metaplasia (CLO), posing an issue about its clinical management. The aim was to evaluate if some immunophenotypic changes were present in CLO independently of the presence of the goblet cells. We studied a series of oesophageal biopsies from patients with endoscopic finding of columnar metaplasia, by performing some immunohistochemical stainings (CK7, p53, AuroraA) combined with histochemistry (Alcian-blue and Alcian/PAS), with the aim of simultaneously assess the histochemical features in cells that shows an aberrant expression of such antigens. We evidenced a cytoplasmic expression of CK7 and a nuclear expression of Aurora A and p53,  both in goblet cells of BO and in non-goblet cells of CLO, some of which showing mild dysplasia. These findings suggest that some immunophenotypic changes are present in CLO and they can precede the appearance of the goblet cells or can be present independently of them, confirming the conception of BO as the condition characterized by any extention of columnar epithelium. This is the first study in which a combined immunohistochemical/histochemical method has been applied to Barrett pathology.

Barium study associated with water siphon test in gastroesophageal reflux disease and its complications.

PURPOSE: The aim of this study was to evaluate the role of digital cineradiography associated with the water siphon test (WST) in the diagnosis of gastroesophageal reflux and to compare the results with oesophageal motility study, pH monitoring and endoscopy associated with biopsy and histology. MATERIALS AND METHODS: One hundred and sixty consecutive patients underwent digital cineradiography with WST, motility study, pH monitoring and endoscopy with biopsy. The presence of gastroesophageal reflux, oesophagitis, Barrett's oesophagus and intestinal metaplasia was evaluated. RESULTS: WST vs. pH monitoring showed sensitivity of 71%, specificity of 31%, positive predictive value (PPV) of 53% and negative predictive value (NPV) of 50%; when middle-proximal refluxes only were considered, sensitivity decreased to 45% and specificity increased to 55%. Furthermore, the association between reflux and oesophagitis demonstrated by the chi-square (chi(2)) test proved to be statistically significant both for WST and pH monitoring, whereas the association between reflux and Barrett's oesophagus was not significant for either WST or for pH monitoring. With regard to intestinal metaplasia, WST (middle-proximal refluxes) showed higher sensitivity (64% vs. 58%) and specificity (63% vs. 51%) than pH monitoring, whereas the statistical association between reflux and metaplasia proved to be significant for WST but not for pH monitoring. CONCLUSIONS: WST is a simple, inexpensive and reliable test that might be useful in the diagnosis of gastroesophageal reflux disease (GERD). A positive WST might be an additional indication for endoscopy with biopsy.

Aurora-A overexpression as an early marker of reflux-related columnar mucosa and Barrett's oesophagus.

BACKGROUND: The development of oesophageal adenocarcinoma is generally closely associated with the presence of a specialised intestinal-type epithelium such as that found in Barrett's oesophagus (BO). A particular histological condition is when the distal oesophagus showing cardiac and/or fundic mucosa without intestinal metaplasia cannot be defined as 'Barrett's mucosa' [condition that we call 'columnar-lined oesophagus' (CLO)] and up till now, there has been no agreement in literature about the management of this condition. Aurora-A overexpression leads to centrosome amplification, chromosomal instability and aneuploidy in mammalian cells. PATIENTS AND METHODS: A prospective study was carried out on 28 consecutive patients who presented columnar mucosa above the gastro-oesophageal junction (GOJ) at endoscopy. As controls, two more biopsies were obtained, one on the normal-appearing squamous oesophagus above the GOJ, as far as possible from the columnar mucosa (controls A), and one taken 1 cm below the GOJ (controls B). The Aurora-A and p53 expression levels were analysed respectively by Quantitative Real Time PCR and immunohistochemistry. RESULTS: Twelve patients were affected by BO (43%) while the other 16 patients (57%) had a CLO. Nine of 28 (32%) cases were focally positive for p53 immunostaining. All the BO/CLO samples were positive for the Aurora-A transcript with regard to controls. Furthermore, 13 of 28 (46%) cases showed overexpression (above the median for the whole group). CONCLUSION: Due to the low number of cases, we are not at present able to state that statistically significant quantitative differences in Aurora-A messenger RNA expression exist between CLO and BO cases with and without dysplasia and p53-positive immunostaining. Further studies on a larger number of cases with a follow-up period are necessary in order to establish the risk of progression and the correct management of these subjects.

Gastrointestinal stromal tumors (GISTs): focus on histopathological diagnosis and biomolecular features.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are believed to originate from a neoplastic transformation of the intestinal pacemaker cells (interstitial cells of Cajal) normally found in the bowel wall or their precursors. Although the microscopic features have been known for a long time, the defining characteristic of GIST is the presence of the cell-surface antigen CD117 (KIT), which is demonstrated by immunohistochemistry. KIT, which is a growth factor transmembrane receptor, is the product of the proto-oncogene c-kit (chromosome 4). Surgical removal remains the only curative treatment for patients with GISTs. Tumor size, mitotic index, anatomic location, tumor rupture and disease-free interval are the classic characteristics used to predict the clinical course of patients who undergo complete gross resection. Most GISTs express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. Imatinib mesylate is a rationally designed, molecularly specific oral anticancer agent that selectively inhibits several protein tyrosine kinases central to the pathogenesis of human cancer and which has demonstrated remarkable clinical efficacy in patients with chronic myeloid leukemia and malignant GISTs. More recently Sunitinib, a new KIT/PDGFRA kinase inhibitor, has been tested in patients with GIST resistant to imatinib, with promising results.

Aberrant methylation within RUNX3 CpG island associated with the nuclear and mitochondrial microsatellite instability in sporadic gastric cancers. Results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Gastric cancer (GC) development is a multistep process, during which numerous alterations accumulate in nuclear and mitochondrial DNA. A deficiency of repair machinery brings about an accumulation of errors introduced within simple repetitive microsatellite sequences during replication of DNA. Aberrant methylation is related to microsatellite instability (MSI) by the silencing of the hMLH1 gene. The aim of this study is to investigate a possible relationship between the RUNX3 promoter methylation, nuclear microsatellite instability (nMSI) and mitochondrial microsatellite instability (mtMSI), in order to clarify its biological role in GC. PATIENTS AND METHODS: nMSI and mtMSI were evaluated in a consecutive series of 100 GC patients. For the analysis of the nMSI, we followed the National Cancer Institute guidelines. mtMSI was assessed by analyzing a portion of the displacement-loop region. The aberrant methylation of RUNX3 was analyzed in 40 GC patients by methylation-specific PCR. RESULTS: Overall, 55% of GC demonstrated methylation of the RUNX3 promoter; 82% of GC was classified as stable microsatellite instability, 5% as low-level microsatellite instability and 13% as high-level microsatellite instability (MSI-H); mtMSI was detected in 11% of GC. A significant association was found between mtMSI and tumor-node-metastasis staging, furthermore an interesting association between MSI-H status, mtMSI and RUNX3 methylation. CONCLUSION: These data suggest that RUNX3 is an important target of methylation in the evolution of mtMSI and nMSI-H GC.

Gastric adenomas: relationship between clinicopathological findings, Helicobacter pylori infection, APC mutations and COX-2 expression.

Gastric adenomas are rare neoplastic growths characterized by localized polypoid proliferations of dysplastic epithelium that tend to progress to infiltrating adenocarcinoma. Therefore, the identification of molecular markers that could reliably recognize adenomas at risk of progression is advocated in the clinical management. In this study we investigated, in a series of gastric adenoma specimens from an area at high risk of gastric cancer, the relationship between clinicopathological characteristics of adenoma and Helicobacter pylori infection, APC mutational status, and COX-2 and the down-stream enzyme mPGES1 expression. Helicobacter pylori infection, detected in 24%, and 33% by histology and PCR analyses, respectively, did not show any relationship with growth pattern, localization, size, dysplasia grade and presence of synchronous cancer. Pathogenetic mutations of MCR region (codons 1269-1589) of the APC gene were detected only in one case corresponding to a single, small size, low grade, H. pylori-negative adenoma. The expression of COX-2 largely matched that of mPGES(1). Both were overexpressed in 79% of cases showing a relationship with high-grade dysplasia, size >10 mm and presence of a synchronous carcinoma. In conclusion, COX-2 may play a key role in the development and progression of gastric adenoma and could be an attractive target in the management of gastric adenoma at major risk of cancer development.

Weekly docetaxel as II line therapy in non-small cell lung cancer: an interim analysis of a phase II study.

To evaluate the efficacy and toxicity of weekly docetaxel (D) as II line treatment in non-small cell lung cancer (NSCLC), in November 1999, we started a phase II study on advanced (stages IIIB-IV) NSCLC patients pre-treated with at least one platinum-based chemotherapy regimen with or without radiotherapy. The schedule consisted of D 40 mg/m(2), weekly for 6 weeks, followed by a rest period of 2 weeks, for three cycles or until progression. Eligibility criteria were: histopathologic diagnosis of NSCLC; age

DNA aneuploidy and high proliferative activity but not K-ras-2 mutations as independent predictors of clinical outcome in operable gastric carcinoma: results of a 5-year Gruppo Oncologico dell'Italia Meridonale (GDIM) prospective study.

BACKGROUND: The prognostic value of DNA ploidy, S-phase fraction (SPF) and K-ras-2 mutations in gastric carcinoma (GC) has not yet been clearly defined. The aim of this study was to clarify the association between biomolecular variables, tumor characteristics, and clinical outcome in GC patients. METHODS: Resected specimens from a consecutive series of 69 patients with GC who underwent potentially curative surgery were studied prospectively. DNA ploidy and SPF were assessed by flow cytometry on multiple frozen tumor samples, whereas K-ras-2 mutations were detected by polymerase chain reaction followed by single-strand conformation polymorphism. All the patients involved in this study were followed up for a mean of 95 months. RESULTS: DNA aneuploidy was present in 72% of the cases (50 of 69), whereas 10% of these (5 out of 50) showed multiclonality. Mutations of K-ras-2 were detected in 8% of the tumors (5 of 63). Both DNA ploidy and SPF were associated with TNM stage (American Joint Committee on Cancer [AJCC] staging system) and node status. Moreover, DNA aneuploidy was significantly related to high SPF. K-ras-2 mutations were not associated with clinicopathologic variables or flow cytometric indicators. At univariate analysis, advanced TNM stage, node involvement, diffuse histotype, depth of invasion, DNA aneuploidy, and high SPF proved to be significantly related to quicker tumor relapse and to shorter overall patient survival. With multivariate analysis, DNA aneuploidy, high SPF, and depth of invasion were related to risk of tumor relapse and patient death, whereas diffuse histotype was independently related to patient risk of tumor relapse. CONCLUSIONS: DNA ploidy and SPF, when associated with clinicopathologic staging, might be useful for the identification of GC patients who have different risks for death or relapse of disease.

[Use of mechanical staplers in biliopancreatic diversion intervention]. / L'impiego delle suturatrici meccaniche nell'intervento di diversione biliopancreatica (BPD).

The use of mechanical staplers in general surgery and in particularity in biliopancreatic diversion (BPD) has led to a marked reduction in the duration of surgery, thus requiring shorter anesthesia times. In obese subjects this also serves to reduce the risks related to their particular clinical and metabolic conditions. The authors report their experience in 53 patients; in 26 cases automatic linear staplers were used to create the ileal-duodenal and gastric tomy only, whereas the entero-entero anastomosis and gastro-entero anastomosis were performed manually using a biliopancreatic diversion technique. In the remaining 27 cases the operation was performed exclusively using automatic staplers. The paper then examines the complications arising from the use of mechanical staplers, dividing them into early and late. Among the first were two episodes of GEA hemorrhage (7.4%) and an asymptomatic fistula again of the GEA (3.7%). The late complications only included two stenoses (7.4%) of the GEA, both resolved using endoscopic pneumatic dilation.

[Care of the patient after biliopancreatic diversion (BPD) surgery]. / L'assistenza al paziente operato di diversione biliopancreatica (BPD).

The authors report their experience in the care of severely obese patients undergoing biliopancreatic diversion (BPD) surgery. The success of this surgical technique not only depends on its correct application but also on correct postoperative management, both immediately and over time. After a short summary of the methods of management used immediately after surgery, the authors focus in greater detail on the most frequent complications in this type of surgery: these are divided into early and late. Among the former, the authors discuss thromboembolic disease, the most severe complications and bronchopneumonia disorders. The authors illustrate the methods of treating both as well as therapies for their prevention. The most frequent and potentially dangerous late complications are examined in detail: protein malnutrition, sideropenic anemia and diarrhea. Lastly, the authors underline the need for a constant rather than episodic approach to the problem of severe obesity since, in their opinion, only continuous and long term application ensures the best results with the fewest complications.

[Organization of a center for prevention and treatment of obesity]. / Organizzazione di un Centro per la prevenzione e cura dell'obesità.

Obesity, a pathology with a multifactorial etiopathogenesis currently has an incidence of around 6% in the adult population in Italy. Considering that this disease provokes a statistically significant reduction of life expectancy, there is an evidence need to create structures which can deal with this problem. For this purpose, the Centre for the prevention and cure of obesity was set up by the Department of Surgery and Anatomy at the University of Palermo in 1990. It makes use of the specialist skills of experts in internal medicine, dieticians, cardiologists, psychologists and surgeons. In particular the authors give a detailed description of the diagnostic iter used and the methods of follow-up adopted for patients undergoing biliopancreatic diversion (BPD) surgery. In conclusion, the authors emphasize the need for a multidisciplinary approach to this pathology since this is the only way of minimizing complications arising during BPD surgery and obtaining the best results.

[Surgical treatment of hemorrhoids using Milligan-Morgan technique. Survey of 366 cases]. / La terapia chirurgica delle emorroidi secondo Milligan-Morgan. Revisione casistica su 366 casi.

After a careful review of the Author's own case list and of the literature on this subject, Milligan-Morgans' technique is assessed and compared with different surgical techniques as far as early and late complications are concerned. The Authors conclude that the Milligan-Morgan technique is to be preferred because of its simplicity, safety and flexibility, particularly if associated with sphincterectomy, with or without rhagade, in order to prevent the cicatricial scars.

[Staging of gastric carcinoma and consequential therapeutic protocols]. / La stadiazione del carcinoma dello stomaco e protocolli terapeutici consequenziali.

The Authors examine the most recent diagnostic methods of studying gastric carcinoma illustrating their limits and peculiarities. It is underlined that only an integrated use of these diagnostic methods may allow a right staging of the disease, which is very important for a correct therapeutic approach. After a review of the literature the Authors discuss on the extent gastric resection and lymphadenectomy must have to be considered radical and, at the same time, curative.

[The use of the TA-55 mechanical suturing device in the closure of the cecostomy. The authors' experience]. / L'uso della suturatrice meccanica TA-55 nella chiusura della ciecostomia. Esperienza personale.

The authors confirm the actuality and validity of decompressive cecostomy in emergency treatment of large bowel obstructions. Taking into account that staplers have substantially reduced the rate of complications and inconvenient of gastrointestinal surgery, their use of cecostomy closure is proposed. Advantages obtained with this technique, namely lack of infections and incisional hernias, are underlined.

[Use of BICAP by endoscopic route in the palliative treatment of neoplastic stenosis of the esophagus]. / L'impiego del BICAP per via endoscopica nel trattamento palliativo delle stenosi neoplastiche dell'esofago.

Over the years the palliative treatment of neoplastic stenosis of the esophagus in patients who cannot be operated has seen a variation of endoscopic methods which aimed to reopen the alimentary canal either using simple dilatation, or the insertion of endoprostheses, or sclerosing injection or antiblastic therapy, or lastly using disobstructive laser therapy. In particular, the use of Neodymium YAG laser in endoscopic therapy for the deobstruction of neoplastic esophageal stenosis is currently widely used. More recently deobstruction of the stenosis may also be achieved using bipolar diathermocoagulation with BICAP following esophageal dilatation. Recent comparative studies of the use of BICAP and laser therapy in the treatment of neoplastic esophageal stenosis have tended to reveal the complementary characteristics of the two techniques. The present paper reports the Authors' experience in this respect which has been satisfactory with regard to both methods, in line with the findings of other studies. In the study of two groups of 8 patients treated with BICAP and laser therapy respectively, recanalisation was obtained in 100% of cases with good functional results in 75% of patients treated with BICAP and 87.5% of those receiving laser therapy. The time interval between one treatment session and the next in relation to the efficacy of the therapy was similar in both methods and ranged from a minimum of 4 weeks to a maximum of 12 weeks. Complications were scarce in both groups.

[The value and limits of the follow-up in patients operated on for breast carcinoma. Our experience]. / Validità e limiti del follow-up delle pazienti operate per carcinoma mammario. Nostra esperienza.

The aim of follow-up is essentially that of diagnosing possible recidivation at a relatively early and practically asymptomatic stage in order to optimise the results of appropriate treatment and to improve both the overall survival rate and the patient's quality of life. In spite of the correct and systematic planning of controls, the authors underline that in their experience only 64.7% of relapses are diagnosed during the asymptomatic phase. However, the authors have confirmed that the expectation of relapse has a barely significant influence on survival. After five years of first receiving treatment, 83% of patients with relapses diagnosed in a symptomatic phase had died, compared to 81.7% of those with relapses diagnosed during the asymptomatic phase. In conclusion, in spite of the fact that it is possible to obtain early diagnosis of recidivation during follow-up, it is equally true that this has no influence at all on the survival rate. However, irrespective of these results, the authors maintain that it is useful to follow patients undergoing breast surgery through a periodic follow-up to evaluate the evolution of disease and acquire an increasingly precise and definite knowledge of its natural history. The authors put forward a protocol for follow-up in which patients are divided into groups on the basis of lymph node status and pre- or postmenopause.

[Value of rectosigmoidoscopy in the secondary prevention of carcinoma of the colon and rectum. Results of a study of ours carried out in elderly patients]. / Il valore della rettosigmoidoscopia nella prevenzione secondaria del carcinoma del colon-retto. Risultati di un nostro studio condotto su pazienti anziani.

Secondary prevention is undoubtedly a vital consideration in the early diagnosis of cancer of the large bowel. The examination of asymptomatic subjects considered to be at high risk of colorectal carcinomas will improve the prognosis for this tumour by identifying lesions at an early stage or, even better, pathologies considered precancerous. Rectosigmoidoscopy was therefore employed on a sample of asymptomatic geriatrics, at high risk because of their age. The examination of 245 elderly people revealed various asymptomatic conditions (haemorrhoids, rhagades, polyps, etc.) and, more importantly, 4 cases (1.6%) of rectosigmoid tumours, 2 of them Dukes stage A and 2 polyps in the initial phase of degeneration into malignancy. The paper concludes by emphasising the value of mass screening of the elderly and indeed of other high risk groups using a flexible rectosigmoidoscope, in the hope of identifying early-stage tumours or precancerous lesions with a view to reducing the incidence of colorectal carcinoma and therefore significantly improving the prognosis for that condition.