Plasma and tissue prolactin detection in colon carcinoma.

Serum concentrations of prolactin, a trophic hormone produced by the pituitary gland, have been shown to be raised in certain group of patients with cancer. Prolactin was detected in 0-20% of the colon cancer by immunohistochemistry and in plasma in 6-53% of the patients. These conflicting results do not support the hypothesis of an ectopic prolactin production by colon carcinoma. The aim of this study was to confirm the reported incidence of hyper-prolactinemia in colorectal cancer and to find further evidence for an ectopic prolactin production by the tumor. Thirty consecutive patients with colon carcinoma were studied. Before surgery all the patients underwent blood sample collection to assay plasma prolactin levels. All patients underwent colectomy. All the neoplastic specimens were tested with antiprolactin antibody. In none of the patients were significantly high preoperative levels of plasma prolactin found. Prolactin immunostaining was not identified in any of the tumor specimens. We could not confirm previous reports of frequent hyperprolactinemia in patients with cancer. This is the first report in which the incidence of both hyperprolactinemia and prolactin positive immunostaining was 0%. Our study was unable to demonstrate the synthesis of prolactin by colorectal cancers. The tumor is unlikely to be the source of hormone production. Our results suggest that circulating prolactin levels cannot be used as prognostic marker in patients with colon cancer.

Prognostic impact of CD31 antigen expression in anal canal carcinoma.

BACKGROUND/AIMS: CD31 is a platelet endothelial cell adhesion molecule. Thus CD31 immunostaining of vascular endothelial cells can be used to measure degree of angiogenesis. As angiogenesis is necessary for tumor growth and metastasis, microvessels density could be a predictor of prognosis. The purpose of this study was to examine the relationship between CD31 value and standard pathologic parameters and prognosis of anal canal carcinoma. METHODOLOGY: Twenty-four patients with anal canal carcinoma were evaluated. Five-micron sections of formalin-fixed, paraffin-embedded tissue were tested with monoclonal anti-CD31 antibody. CD31 value is considered positive if more than 185 vessels/mm2 were counted. Pearson's chi 2 test was employed to test for association between CD31 value and clinicopathological variables. RESULTS: We found no correlation between CD31 value and histologic type, lymph node involvement, patients age and neoplastic relapse. Significant correlation was found between CD31 score and depth of parietal invasion. CONCLUSIONS: The relapse type could strengthen the hypothesis that increased vascularity promotes neoplastic dissemination. As angiogenesis could be used as prognostic indicator to determine patients who may be at higher risk for relapse, our results warrant further confirmation. Development of markers of angiogenic activity in anal canal carcinoma must be an integral part of proper clinical trials.

Analysis of a follow-up program for anal canal carcinoma.

The ideal follow-up program for anal canal cancer remains unclear and controversial. We hereby describe an extensive follow-up program for anal canal carcinoma in order to evaluate which examinations and which diagnostic techniques really had impact on survival and management. We evaluated 25 patients with anal canal carcinoma. Local excision (LE) was performed in 5 patients, radiochemotherapy (RCT) in 13, radiochemotherapy and local excision (RCTE) in 7. Mean follow-up time was 6.3 years (range 20 months-11 years). The follow-up program included clinical examination, serum tumor markers evaluation, transrectal ultrasonography (TRUS), anoscopy with either mucosal or by Tru-cut needle multiple biopsies, standard chest X-ray and hepatic-inguinal ultrasonography, endoanal magnetic resonance imaging and in some cases total-body skeletal scintigraphy. A large multicentered randomized and prospective trial is surely lacking and should be undertaken as soon as possible. Our results suggest that an effective local control, rather than a higher survival is the reachable goal at present for anal canal carcinomas. However, further steps should be made to achieve better results. After this experience we propose a more semplified follow-up protocol which consists in performing only rectal examination, endoscopy, Tru-cut needle biopsies and TRUS for local control and inguinal ultrasound and TC to evidence distant metastases.

Duodenal pancreatic heterotopy diagnosed by magnetic resonance cholangiopancreatography: report of a case.

We describe herein the case of a heterotopic pancreas that caused stenosis in the second portion of the duodenum. A 46-year-old man presented with upper abdominal pain and a 12-month history of intermittent vomiting. There was no history of melena, hematochezia, hematemesis, clay-colored stools, jaundice, or hepatitis and he did not describe any food dyscrasias, although fatty foods and alcohol seemed to make the symptoms worse. No specific medication or change in position relieved the pain. An initial diagnosis of chronic pancreatitis with multiple pseudocysts was made on the basis of elevated serum amylase and lipase levels, and abdominal ultrasonography and computed tomography (CT) findings. Medical treatment with octreotide was given for 8 weeks, but without any marked effect. Double-contrast barium examination and esophagogastroduodenoscopy were not diagnostic. Magnetic resonance (MR) cholangiopancreatography revealed findings indicative of cystic dystrophy of a heterotopic pancreas (CDHP), and an endoscopy supported this diagnosis. A pancreatoduodenectomy was performed and pathological examination confirmed a diagnosis of CDHP. In our opinion, MR cholangiopancreatography is the diagnostic tool of choice when CDHP is suspected.

Magnetic resonance imaging using endoanal coil in anal canal tumors after radiochemotherapy or local excision.

The ideal method for evaluation of anal canal tumors after radiochemotherapy and/or local excision remains controversial. Endoanal magnetic resonance imaging (EMRI) is a new, promising technique. The effectiveness of EMRI is reported in a study of 24 patients. Axial SET1-weighted and TSET2-weighted, sagittal and coronal T2-weighted sequences using Fat-suppression were acquired. In 4 cases, the low signal/noise ratio did not allow a diagnosis. In 6 cases, the lesion was not detected. Parietal hypo-intense thickening was detected in 14 patients, but it was not diagnostic for disease recurrence. In this study, EMRI showed 58.3% sensitivity and 41.6% specificity, thus it was not useful in the follow-up of anal tumors.

nm23-H1 protein expression in anal canal carcinoma: does it correlate with prognosis?

BACKGROUND AND OBJECTIVES: Anatomic extent is not the sole axis of classification of tumors and of tumor patients relevant to treatment planning and estimation of prognosis. This results in the need to demonstrate an improvement in prognostic assessment and choice of therapy achieved by consideration of factors other than TNM. nm23 protein does prevent tumor from metastasizing and may also play a role in the control of growth and development. The purpose of this study was to elucidate the clinical significance of nm23 expression in human anal canal carcinoma and to evaluate its influence on the outcome of patients after surgery or radiochemotherapy. METHODS: Twenty-two patients affected by anal canal carcinoma were evaluated. Each section was incubated with monoclonal antibody nm23 NDPK-A. Immunostaining was considered positive when at least 10% of the tumor cells were immunostained. RESULTS: nm23 immunoreactivity was detected in 6/22 (27.3%) tumors. No significant association was found between nm23 expression and prognosis. CONCLUSIONS: The mechanisms causing enhanced nm23-H1 expression in anal canal carcinoma are unknown. Although the level and expression were not correlated with prognosis, activation of nm23-H1 gene might be a prerequisite for oncogenesis in this type of tumor, while an alternate possibility is the modification of cellular characteristics in relation to proliferation and/or differentiation as a consequence of oncogenesis.

An unusual late radiotherapy-related complication requiring surgery in anal canal carcinoma.

We herein describe an unusual late radiation-related complication requiring surgery in a 60-year-old male affected by anal epidermoid carcinoma. The patient presented with obstructed defecation and ulcerated perianal lesions. The perianal biopsies were positive for anal squamous carcinoma. Transanal diagnostic investigations could not be performed because of anal stenosis. Computed tomography detected left inguinal lymphadenopathy and a nonhomogeneous presacral mass, infiltrating the rectal wall, the coccyx, and the sacrum. The patient underwent a colostomy, infusion of cisplatin and 5-fluorouracil, and irradiation of the pelvis, perianal region, and inguinal lymph nodes. In June 1997 the patient complained of the onset of continuous pain at the genitalia, and for penis necrosis he underwent penis amputation. The histologic examination was conclusive for postradiotherapy thrombosis. This complication could strengthen the hypothesis of vasculoconnective damage as the origin of long-term effects of radiotherapy. Probably the minimal dose in transit volume could not be achieved. Careful evaluation in choosing the treatment scheme is necessary if different options are available.

[Annular pancreas in adults: diagnostic considerations on a case]. / Il pancreas anulare nell'adulto: considerazioni diagnostiche su di un caso.

Annular Pancreas (AP) is a rare congenital anomaly that usually presents in childhood with symptoms referable to duodenal obstruction; nonetheless, this condition can manifest in adulthood with abdominal pain, pancreatitis, duodenal ulcer, pancreatic head mass. The Authors hereby discuss a case of AP observed in a 63 year-old patient in which EUS played a decisive role in achieving a certain diagnosis.

Immunohistochemical assessment of Ki-67 as prognostic cellular proliferation marker in anal canal carcinoma.

In order to define new prognostic factors useful for therapeutic decision-making, the Authors conducted a study on anal canal carcinomas in which Ki-67 proliferation index is correlated with pathological variables and clinical outcome. The Ki-67-detectable antigen is expressed in all stages of the cells cycle except G0. Thus, Ki-67 index can measure cell proliferation and it could be considered an indicator of prognosis. Thirty-one patients with anal canal carcinoma were evaluated. The specimens were formalin-fixed, paraffin-embedded and used for immunostaining of Ki-67 antigen. We found a significant correlation between Ki-67 score and depth of invasion and lymph node involvement. No correlation was found between high Ki-67 value and neoplastic relapse. These results suggest that Ki-67 positivity carries different significance in different cancers. Additional studies are required to ascertain whether more aggressive therapeutic procedures should be applied in the subset of patients with a high growth fraction.

Correlation between nm23-H1 overexpression and clinicopathological variables in human anal canal carcinoma.

To improve life expectancy prognostic factors other than TNM have been investigated. It is thought that nm23 protein may play a specific biological role in suppressing tumor metastasis. The purpose of this study was to elucidate the clinical significance of nm23 expression in human anal canal carcinoma. Immunostaining using anti-nm23 monoclonal antibody was performed in 22 anal canal tumors. The results were correlated with clinicopathological variables. Six cases out of 22 (27.3%) were nm23-positive. Significant association was found between nm23-H1 expression and depth of invasion, lymph node involvement and prognosis (p<0.05). There was no significant association between nm23-H1 expression, histologic type and age of the patients. nm23-H1 expression was not seen in our cases with metastasis and this may be related to nm23 gene alterations not being detectable by the monoclonal antibody used or to the presence of a subset of tumors in which nm23 gene abnormalities had not yet occurred at the time of tumor excision or biopsy. Overexpression of nm23-H1 protein in anal canal carcinoma may have implications for its metastatic potential. nm23-H1 expression would provide a more accurate evaluation of outcome for individual patients and thus improve treatment planning.

Human papillomavirus infection and p53 nuclear overexpression in anal canal carcinoma.

The product of HPV E6 and E7 genes is able to inactivate both the p53 and pRb proteins. The aim of this study was to evaluate the correlation among anal HPV infection and nuclear p53 overexpression. The Authors evaluated HPV DNA by PCR and p53 nuclear expression by immunohistochemistry in 12 cloacogenic and 6 squamocellular carcinoma. HPV DNA was detected in 71.4% of the squamocellular tumors and in 57.1% of the cloacogenic tumors. In squamocellular tumors HPV types 31-33 and 16 were found; in cloacogenic tumors type 16 alone was detected. Nuclear accumulation of p53 was found to be associated with the presence of HPV. There was no significant difference in parietal infiltration, lymph nodes involvement and prognosis between HPV+p53+ patients and HPV-p53- patients. Tumor aggressiveness is likely to be enhanced by factors other than HPV infection and p53 overexpression.

The prevalence of p53 immunoreactivity in anal canal carcinoma.

We examined the relationship between p53 expression and clinicopathologic parameters in anal carcinoma. p53 immunoreactivity was detected in 14/18 (77.7%) tumors. Significant association was found between p53 expression and depth of invasion. There was no significant association between p53 expression and histologic type, lymph node metastasis, age and prognosis. Possibly the genetic pathway to anal carcinoma involving p53 gene overexpression confer aggressive growth pattern, but it does not result in worse prognosis. The absence of correlation between p53 overexpression and prognosis could be explained by tumors negative for mutations having an excess of wild-type p53 protein.

Forecasting of hydrophilic contact lens tolerance by means of tear ferning test.

BACKGROUND: The ability of the tear ferning test to predict future hydrophilic contact lens tolerance was studied. METHODS: The tear ferning test (TFT) was performed on one randomly chosen eye of each of the 116 subjects who came to our contact lens clinic for hydrophilic contact lens application. The TFT was performed at the time of enrollment (TO) and then 1 month (T1), 3 months (T2) and 6 months (T3) after contact lens fitting. The specificity and the sensitivity of the TFT in identifying future contact lens tolerance was then studied. The statistical significance of the differences in behavior through the study period among the subjects with different pre-fitting TFT results was evaluated by means of survival curves. RESULTS: When only type I ferning was considered as a marker of good tear film conditions, the ability of the TFT to forecast contact lens tolerance had 78.95% sensitivity, 78.35% specificity and 78.45% diagnostic precision. The TFT showed sensitivity of 100%, specificity of 86.6% and diagnostic precision of 97.4% when performed after 1 month of contact lens wearing (T1). Survival curve analysis showed a statistically significant difference in behavior between the group of subjects with pre-fitting ferning type I and the other three groups (P < 0.001). CONCLUSION: The TFT appears to have good sensitivity and specific for prediction of contact lens tolerance in a clinical setting.

Trans anal full thickness tru-cut needle biopsies in anal canal tumors after conservative treatment.

After conservative treatment anal mucosal biopsies enable exclusion of neoplastic cells only on the endoluminal surface. We used transanal full thickness tru-cut needle biopsies in the follow-up of 11 anal tumors. Full thickness tru-cut needle biopsies showed malignant cells in the fibrous tissue in 3 patients and few cells with atypical nuclear features in another 2. All diagnostic exams resulted negative. Therefore, needle biopsies were helpful to diagnose neoplastic remainder. Multiple samples are necessary to reduce the false negative number. This method is simple, relatively inexpensive, easily repeatable and not burdened with complications.

An unusual location of cloacogenic carcinoma.

A 61 year-old female presented with abdominal pain, rectal bleeding, mucus discharge, tenesmus and constipation. Rectal examination and proctoscopy demonstrated rectal stenosis at 5 cm from the anal verge. Transrectal ultrasonography detected a capsulated lesion as a mesenchymal rectal tumor. Computed tomography and endorectal magnetic resonance detected a mesenchymal lesion in the lower-middle rectal thirds. Serum TPA, GICA, SCC and CYFRA were pathological. At surgery the tumour was fixed to the levator ani muscle with rectal folding. Frozen sections of the levator ani muscle biopsies revealed cloacogenic tumour. Abdominoperineal resection was performed. The rectal lesion was cloacogenic carcinoma at 9 cm from the dentate line (pT4 pN0; Ki67 35%; CD31 181 vessels/mm2). Adjuvant radio-chemotherapy was performed. The patient is alive and disease free at 19 months. Extra-anal cloacogenic tumours are an unusual finding. Perhaps cloacal cells were originally present in the rectal wall, but secondary rectal involvement by cloacal remnant from the levator ani muscle cannot be excluded.