Perineal stapled prolapse resection (PSPR) in elderly patients for external rectal prolapse: early experience.

BACKGROUND: Full-thickness rectal prolapse in frail elderly patients is often treated by a perineal approach with considerable attendant morbidity. We report our preliminary results of the perineal stapled prolapse resection (PSPR) technique for resection of full-thickness external rectal prolapse using a new reloadable Contour(®) Transtar™ stapler (Ethicon Endo-Surgery) device. METHODS: Fourteen elderly high-risk patients with an external prolapse up to 10 cm in length were treated between April 2010 and October 2011, and operative factors, outcome and recurrence rates were assessed. RESULTS: There were no intraoperative difficulties and no perioperative morbidity. The median operating time was 35 min (range 25-45 min) with a median hospital stay of 3 days (range 3-5 days). Four patients developed early recurrence over a median follow-up of 32 months (range 25-41 months). CONCLUSIONS: PSPR is safer, faster and easier to perform than other conventional perineal prolapse procedures and is suitable for elderly, high-risk patients for whom an abdominal approach under general anesthesia is not advisable.

CF102 an A3 adenosine receptor agonist mediates anti-tumor and anti-inflammatory effects in the liver.

The Gi protein-associated A(3) adenosine receptor (A(3) AR) is a member of the adenosine receptor family. Selective agonists at the A(3) AR, such as CF101 and CF102 were found to induce anti-inflammatory and anti-cancer effects. In this study, we examined the differential effect of CF102 in pathological conditions of the liver. The anti-inflammatory protective effect of CF101 was tested in a model of liver inflammation induced by Concanavalin A (Con. A) and the anti-cancer effect of CF102 was examined in vitro and in a xenograft animal model utilizing Hep-3B hepatocellular carcinoma (HCC) cells. The mechanism of action was explored by following the expression levels of key signaling proteins in the inflamed and tumor liver tissues, utilizing Western blot (WB) analysis. In the liver inflammation model, CF102 (100 µg/kg) markedly reduced the secretion of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase in comparison to the vehicle-treated group. Mechanistically, CF102 treatment decreased the expression level of phosphorylated glycogen synthase kinase-3ß, NF-κB, and TNF-α and prevented apoptosis in the liver. This was demonstrated by decreased expression levels of Fas receptor (FasR) and of the pro-apoptotic proteins Bax and Bad in liver tissues. In addition, CF102-induced apoptosis of Hep-3B cells both in vitro and in vivo via de-regulation of the PI3K-NF-κB signaling pathway, resulting in up-regulation of pro-apoptotic proteins. Taken together, CF102 acts as a protective agent in liver inflammation and inhibits HCC tumor growth. These results suggest that CF102 through its differential effect is a potential drug candidate to treat various pathological liver conditions.

Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment.

OBJECTIVE: Studies have suggested that rheumatoid arthritis (RA) and osteoarthritis (OA) share common characteristics. The highly selective A(3) adenosine receptor agonist CF101 was recently defined as a potent antiinflammatory agent for the treatment of RA. The purpose of this study was to examine the effects of CF101 on the clinical and pathologic manifestations of OA in an experimental animal model. METHODS: OA was induced in rats by monosodium iodoacetate, and upon disease onset, oral treatment with CF101 (100 microg/kg given twice daily) was initiated. The A(3) adenosine receptor antagonist MRS1220 (100 microg/kg given twice daily) was administered orally, 30 minutes before CF101 treatment. The OA clinical score was monitored by knee diameter measurements and by radiographic analyses. Histologic analyses were performed following staining with hematoxylin and eosin, Safranin O-fast green, or toluidine blue, and histologic changes were scored according to a modified Mankin system. Signaling proteins were assayed by Western blotting; apoptosis was detected via immunohistochemistry and TUNEL analyses. RESULTS: CF101 induced a marked decrease in knee diameter and improved the changes noted on radiographs. Administration of MRS1220 counteracted the effects of CF101. CF101 prevented cartilage damage, osteoclast/osteophyte formation, and bone destruction. In addition, CF101 markedly reduced pannus formation and lymphocyte infiltration. Mechanistically, CF101 induced deregulation of the NF-kappaB signaling pathway, resulting in down-regulation of tumor necrosis factor alpha. Consequently, CF101 induced apoptosis of inflammatory cells that had infiltrated the knee joints; however, it prevented apoptosis of chondrocytes. CONCLUSION: CF101 deregulated the NF-kappaB signaling pathway involved in the pathogenesis of OA. CF101 induced apoptosis of inflammatory cells and acted as a cartilage protective agent, which suggests that it would be a suitable candidate drug for the treatment of OA.

IB-MECA, an A3 adenosine receptor agonist prevents bone resorption in rats with adjuvant induced arthritis.

OBJECTIVES: The anti-inflammatory effect of adenosine is partially mediated via the A3 adenosine receptor (A3AR), a Gi protein associated cell surface receptor. The highly selective A3AR agonist, IB-MECA was earlier shown to prevent the clinical and pathological manifestations of arthritis in experimental animal models of collagen and adjuvant induced arthritis (AIA). In this study we tested the effect of IB-MECA on the prevention of bone resorption in AIA rats and looked at the molecular mechanism of action. METHODS: Rats with AIA were treated orally twice daily with IB-MECA starting upon onset of disease and the clinical score was evaluated every other day. At study termination the foot, knee and hip region of both vehicle and IB-MECA treated animals were subjected to histomorphometric analysis. Western blot analysis was carried out on paw protein extracts. RESULTS: IB-MECA ameliorated the clinical manifestations of the disease and reduced pannus and fibrosis formation, attenuated cartilage and bone destruction and decreased the number of osteoclasts. In cell protein extracts derived from paw of AIA rats, A3AR was highly expressed in comparison to naïve animals. In paw extracts derived from IB-MECA treated AIA rats, down-regulation of the A3AR protein expression level was noted. PI3K, PKB/Akt, IKK, NF-kappaB, TNF-alpha and RANKL were down-regulated whereas caspase 3 was up-regulated. CONCLUSION: IB-MECA, a small highly bioavailable molecule, induces modulation of proteins which control survival and apoptosis resulting in the amelioration of the inflammatory process and the preservation of bone mass in AIA rats.

Inhibition of primary colon carcinoma growth and liver metastasis by the A3 adenosine receptor agonist CF101.

Adenosine is a purine nucleoside that acts as a regulatory molecule by binding to specific G-protein-coupled A1, A(2A), A(2B), and A3 cell surface receptors. We have recently demonstrated that adenosine inhibits tumour cell growth and concomitantly stimulates bone marrow cell proliferation via activation of the A3 adenosine receptor (A3AR). In the present study, we show that a synthetic agonist to the A3AR, CF101, at the low nanomolar concentration range, inhibits HCT-116 human colon carcinoma cell growth. This effect was reversed by the selective A3AR antagonist MRS1523, demonstrating the specificity of the response. CF101 (given orally) was efficacious in inhibiting the development of primary tumours in xenograft and syngeneic models in which mice were inoculated subcutaneously with human HCT-116 or murine CT-26 colon carcinoma cells, respectively. Moreover, CF101 suppressed (50%, P<0.01) colon cancer liver metastases in syngeneic mice inoculated to the spleen with CT-26 cells. The mechanism of action entailed upregulation of interleukin-12 production in the CF101-treated groups and potentiation of NK cell activity. In the HCT-116 xenograft model in which a combined therapy of CF101 and 5-fluorouracyl (5-FU) was examined, an additive antitumour effect was demonstrated. Moreover, CF101 prevented the 5-FU-induced myelotoxicity, resulting in normal values of white blood cell and neutrophil counts. We conclude that the A3AR agonist CF101, a small orally bioavailable molecule, exerts systemic anticancer, antimetastatic, and myeloprotective effects in colon carcinoma-bearing mice, and may serve as an adjuvant treatment to enhance the chemotherapeutic index and prevent myelotoxicity.

An immunocytochemical approach to the demonstration of intracellular processing of mast cell carboxypeptidase.

Newly synthesized secretory proteins are transported from the rough endoplasmic reticulum to the Golgi complex where they can undergo posttranslational modification and are then packaged for secretion by concentration within membrane-bound very small progranules that fuse to form large immature granules. The contents of these vesicles are thought to be then processed, forming mature secretory granules. After acquiring their mature appearance, the secretory granules reside in the cytoplasm until they are secreted. In this study, we raised antibodies against the first 15 N-terminal amino acids of mast cell pro-carboxypeptidase and the last 14 C-terminal amino acids of mast cell carboxypeptidase. Immunohistochemical localization of the two peptides was carried out in human breast tissue and rat tissue (ear, skin, peritoneum, and tongue). In all cases, both epitopes were demonstrated only in mast cell secretory granules. However, mast cells from 3-week-old rats were more positive for the pro-enzyme compared to 3-month-old rats. Human mast cells in breast tissues were mostly negative for the pro-enzyme and positive for the carboxypeptidase. On the basis of these observations, it seems that posttransitional modification of the pro-enzyme to form the active enzyme occurs in the mast cell secretory granules.

A new rapid technique for the fixation of thyroid gland surgical specimens.

One of the main diagnostic problems in thyroid pathology is to distinguish between follicular adenoma and follicular carcinoma. Thorough sampling of the nodule's capsule is recommended in order to identify capsular invasion. However, during the hardening of the tissue, by the usual fixatives the capsule shrinks and rolls downwards and sometimes the capsule separates from the remaining tissue. The present work evaluates the use of "Lymph Node Revealing Solution" (LNRS) for the rapid fixation (2h) of different thyroid lesions as compared to that of formalin. Fifty-one unselected consecutive cases of thyroid nodules, which included various benign and malignant lesions, were examined. Each specimen was cut in two equal parts; one was fixed in LNRS, the other in formalin. Fixation in LNRS for 2 hours gave adequate results in sectioning and staining of the tissue, and excellent immunostains. Its advantage over formalin is the conservation of the natural relationship between the capsule and the rest of the tissue, on the same plane, as well as the short time required for the final diagnosis.

Nucleolar organizer regions in conjunctival nevi and melanomata.

The objective of this study was to compare the argyrophil nucleolar organizer region (Ag-NOR) counts of conjunctival nevi and melanomata and to compare the efficacy of this method in their differential diagnosis. Nine histologically diagnosed conjunctival nevi and three conjunctival malignant melanomas were studied. Representative sections were stained using the AgNOR technique. Fifty cells of each melanocytic lesion were randomly selected without knowing their histologic diagnosis. The AgNORs were visualized at a magnification of x1000. They consisted of clusters >1 micron in diameter and of satellites <1 micron in diameter, which were counted and recorded for each cell separately. The mean AgNOR count for the nevi was 1.12 clusters and 1.72 satellites per cell, while the count for the melanomas was 1.6 clusters and 6.8 satellites per cell. These results are statistically significant. There was no overlap between the number of AgNOR clusters and satellites in conjunctival nevi and melanomas, indicating that the AgNOR count might be a useful tool in distinguishing benign from malignant conjunctival melanocytic lesions.

Lymph node revealing solution: a new method for lymph node sampling: results in gastric adenocarcinoma.

Staging of gastric carcinoma depends on exact lymph node status. However, very small nodes are not easily found as they are obscured by the surrounding adipose tissue. The purpose of the present study was to demonstrate the usefulness of a Olymph node revealing solutionO (LNRS) in gastric cancer. The perigastric adipose tissue of ten OproblematicO cases of gastric carcinoma, in which <10 lymph nodes were found using the traditional method, was immersed in LNRS for 6-12 h. Subsequently, the lymph nodes stood out as white chalky nodules. They were excised and processed routinely. The traditional method yielded a total of 30 lymph nodes with a mean size of 6.69 +/- 3.43 mm. The LNRS revealed 89 additional nodes with a mean size of 3.03 +/- 3.43 mm, which was significantly smaller. The Node (N) stage was changed in four cases from Nx to N0, in one case from N1 to N2, and in one case from N0 to N2. LNRS seems to be the technique of choice for staging of patients with gastric adenocarcinoma in whom <10 lymph nodes were found with the traditional method and accurate staging was not possible.

Asymptomatic postmenopausal intrauterine fluid accumulation: characterization and significance.

OBJECTIVES: The aims of the study were to characterize those postmenopausal women who develop intrauterine fluid accumulation and to evaluate its significance. METHODS: All asymptomatic postmenopausal women who were referred for routine transvaginal ultrasonographic examination between 1 January 1995 and 31 March 1996 were included in the study. Demographic and ultrasonographic parameters were recorded on a prospectively created computerized database. When intrauterine fluid accumulation was identified, the women was referred for endometrial sampling. RESULTS: A total of 1175 consecutive, asymptomatic postmenopausal women were evaluated; intrauterine fluid accumulation was identified sonographically in 166 (14.1%). Women with intrauterine fluid accumulation were older, had experienced more years since the menopause, and had smaller uterine volume indices, thinner endometria and smaller indices of ovarian area, compared to those without intrauterine fluid accumulation (all at a significant level of p < 0.0005). The prevalences of hormone replacement therapy use were 6.6% in the 'accumulating fluid' women and 43% in the 'non-accumulating fluid' group (p < 0.0005). Of the 166 women with intrauterine fluid accumulation, 91 had an endometrial biopsy, of which 70% were insufficient for evaluation and 30% were normal on histology. CONCLUSION: Postmenopausal intrauterine fluid accumulation is a common, mostly benign phenomenon that typically occurs in the late postmenopausal age subgroups. It may be postulated that it represents part of the atrophic mechanism that takes place at this stage of life. Hormone replacement therapy appears to be a 'protection' against this phenomenon.

The clinical and histological features of transitional cell carcinoma of the bladder with microcysts: analysis of 12 cases.

OBJECTIVE: To describe the clinical course and histological features of transitional cell carcinoma (TCC) of the bladder with microcysts. PATIENTS AND METHODS: Among 940 patients with bladder TCC diagnosed at our institution during a 5 year period. 12 (1.2%; eight men and four women, mean age 71.1 years, range 52-85) were diagnosed histologically as having microcystic TCC. Sections of the tumours were stained with haematoxylin and eosin, periodic acid-Schiff and Alcian blue and clinical data obtained from the patients' records. RESULTS: Of the 12 patients with bladder TCC with microcysts, three had tumours confined to the epithelium, six had tumour invasion of the lamina propria and three had muscle invasion. One patient had low-grade TCC and 11 had high-grade TCC; six patients had a second primary tumour; three had a colon carcinoma, one a villous adenoma of the caecum, one a locally advanced carcinoma of the prostate and the last a squamous cell carcinoma of the uterine cervix. CONCLUSIONS: Microcystic TCC was associated with high-stage and high-grade bladder tumours and with other primary tumours, especially of the colon. Screening these patients for asymptomatic tumours of the colon is suggested.

Brush cytology and biopsy in the diagnosis of colorectal cancer. A comparison.

OBJECTIVE: To determine the usefulness of brush cytology of colorectal lesions as compared to biopsy examination. STUDY DESIGN: One hundred brushing cytologies and biopsies were performed on patients who underwent colonoscopic examination for different symptoms. The cytologic smears were classified into five cytologic diagnostic categories. The histologic diagnoses were adenocarcinoma, adenoma and nonneoplastic lesion. RESULTS: Twenty-six cases were cytologically positive for malignant cells, and all were histologically diagnosed as adenocarcinoma. Nineteen cases were suspicious for malignancy on cytology; histologically, eight of them showed adenocarcinoma. Two other cases proved to be adenocarcinoma in subsequent biopsies. Nine cases were adenomas, with severe dysplasia in five of them. Fourteen cases that were cytologically negative with minimal glandular atypia showed seven adenomas and seven nonneoplastic lesions on biopsy. Forty cases negative for malignant cells showed 19 adenomas and 21 nonspecific changes in the biopsy examination. CONCLUSION: Colonoscopic brushing cytodiagnosis is a sensitive technique for the detection of colorectal cancer. The combination of brushing cytology and biopsy improves the accuracy of diagnosis.

[Late solitary metastases of breast origin presenting as primary colonic carcinoma].

The case of a 72-year-old woman with 2 solitary metastases to the colon of breast origin with mimicked primary colonic cancer is presented. The primary breast lesion was an infiltrating duct carcinoma and the metastases to the colon were discovered 6 years later. Some of the regional lymph nodes draining the colon were infiltrated by tumor, probably originating from the 2 colonic metastases. This is an unusual condition that has not as yet yet been reported.

Nucleolar organizer regions in breast cytology material.

OBJECTIVE: To evaluate the presence of nucleolar organizer regions (NORs) by the argyrophil NOR (AgNOR) technique on scrape cytology on breast lumps. STUDY DESIGN: The study group consisted of 112 breast lumps that were sent for frozen section and included fibrocystic disease (52 cases), fibroadenomas (15 cases) and carcinomas (45 cases). Scrape cytology was performed on each case, and the number of AgNOR dots was recorded for 50 cells and the mean value calculated. RESULTS: The mean AgNOR counts were statistically significantly higher in malignant lesions in comparison to either fibroadenomas or fibrocystic changes. CONCLUSION: The AgNOR technique could be of use in cytologic material as an adjunct to fine needle aspiration of breast lesions.

Acid mucin and high molecular weight cytokeratin in prostatic lesions: evaluation of a combined histochemical and immunohistochemical stain.

OBJECTIVE: To evaluate the presence of acid mucins and high molecular weight cytokeratin (KER) in prostatic lesions using a combined histochemical and immunohistochemical stain consisting of Alcian blue at pH 2.5(AB) with a strept-avidin-biotin complex (SAB) staining for KER (SAB-KER). MATERIALS AND METHODS: Sections were obtained from archival paraffin blocks which included 20 cases of prostatic carcinoma, 30 cases of benign hyperplasia, and five cases of basal cell hyperplasia. Sections were stained for mucosubstances using the AB stain, for KER using SAB-KER and by both AB and SAB-KER, the combined stain (CS). RESULTS: With the CS stain KER, which is present in the prostatic basal cells, was not detected in malignant glands and in 60% of these cases intraluminal blue-stained acidic mucin was seen. On the other hand, all benign hyperplastic prostatic glands were devoid of intraluminal acidic mucin and showed staining for KER of their basal cells. Areas of basal cell hyperplasia were strongly positive for KER and intraluminal acidic mucin was seen in one case. Each of the stains separately gave similar results to the CS method but the contrast between the areas of carcinoma and hyperplasia was accentuated by the CS, and small foci of carcinoma were easily detected. CONCLUSION: The combined AB+SAB-KER stain is quicker to perform and allows the simultaneous appraisal of acid mucin and KER.

Systemic distribution of beta 2-microglobulin-derived amyloidosis in patients who undergo long-term hemodialysis. Report of seven cases and review of the literature.

A search for visceral amyloid deposits was performed on autopsy material from 20 patients who had been receiving long-term hemodialysis treatment for 4 to 21 years. Visceral amyloid was found in seven patients who had undergone hemodialysis for more than 10 years. Histochemically, the amyloid was permanganate sensitive, and immunohistochemically, it stained positively for beta 2-microglobulin. The amyloid was found mainly in the wall of blood vessels, in the form of subendothelial nodules, bulging into the vessel's lumen. The amount of amyloid increased with increasing years of hemodialysis treatment. The organs most frequently involved were the heart, gastrointestinal tract, and lungs. Smaller deposits were seen in medium blood vessels of all other visceral organs. Only the spleen was "resistant" to amyloid deposition; the reason for this splenic resistance is unknown. A similar organ distribution was found in the 19 previously reported autopsy cases. Clinically, one patient experienced a perforation of the small intestine, probably related to the narrowing of the intestinal blood vessels by amyloid deposits, and this patient died of peritonitis.