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The aim of this study was to compare the 2-year outcomes of de novo versus postendovascular lesion treatment of femoropopliteal occlusions included in a national, multicenter, observational, prospective registry based on the treatment of critical Limb-threatening IschaeMia with infragenicular Bypass adopting in situ SAphenous VEin technique (LIMBSAVE) registry.From January 2018 to December 2019, 541 patients from 43 centers have been enrolled in the LIMBSAVE registry. Of these patients, 460 were included in the present study: 341 (74.1%) with de novo lesions (DN group) and 119 (25.9%) with postendovascular treatment lesions (PE group). Initial outcome measures were assessed at 30 days after treatment. Furthermore, at the 2-year follow-up, the estimated outcomes of primary patency, primary-assisted patency, secondary patency, and limb salvage were analyzed with Kaplan-Meier curves and compared between groups with the log-rank test.Both groups were homogeneous in terms of demographic data, preoperative risk factors, and clinical presentation. However, compared with DN group, more patients in PE group had a great saphenous vein diameter of less than 3 mm (11.1% vs 21%; P = .007). Intraoperatively, both groups showed similar distal anastomosis sites: below-the-knee popliteal artery (63% DN group, 66.4% PE group) and tibial vessel (37% DN group, 33.6% PE group) (P = .3). The overall mean duration of follow-up was 11.6 months (range, 1-24 months). At the 2-year follow-up, there were no differences between the two groups in terms of primary patency (66.3% DN group vs 74.1% PE group; P = .9), primary-assisted patency (78.2% DN group vs 79.5% PE group; P = .2), secondary patency (85.1% DN group vs 91.4% PE group; P = .2), and limb salvage (95.2% DN group vs 95.1% PE group; P = .9).The LIMBSAVE registry did not show a worsening of overall patency and limb salvages rates at the 2-year follow-up in patients undergoing in situ saphenous bypass after a failed endovascular approach for long femoropopliteal occlusive disease. This finding is in contrast with what has been published in literature.

The aim was to demonstrate contemporary outcomes of in situ saphenous vein bypass using a valvulotome.Analysis of two year outcomes of a multicentre registry based on the treatment of critical Limb Ischaemia with infragenicular Bypass adopting in situ SAphenous VEin technique (LIMBSAVE). Between January 2018 and December 2019, 541 patients in 43 centres were enrolled. In all patients an innovative valvulotome was used. Early outcomes were assessed. Two year outcomes according to Kaplan-Meier curves in terms of patency and limb salvage were evaluated. Associations between patient and procedure variables were analysed with univariable and multivariable analyses.In all cases, a valvulotome was able to lyse the valves. Vein injury due to the in situ technique was 3.5%. Thirty day mortality and major amputation rates were 3% and 0.9%, respectively. Mean follow up was 12.1 months. Two year estimated primary patency, primary assisted patency, secondary patency, and limb salvage were 69.1%, 81.4%, 86.5%, and 94.5%, respectively. Multivariable analysis showed an association between pre-operative vein diameter3 mm and lower primary patency (hazard ration [HR] 14.3, p.001), primary assisted patency (HR 9.4, p = .002), secondary patency (HR 7.2, p = .007), and limb salvage (HR 7.8, p = .005) rates. Distal anastomosis to a tibial or foot vessel was also associated with lower primary patency (HR 4.8, p = .033), and primary assisted patency (HR 6, p = .011) rates. Use of a suprafascial tributary collateral as a graft was associated with lower primary patency (HR 6.7, p = .013), and primary assisted patency (HR 4.2, p = .042) rates.Vein diameter3 mm, distal anastomosis on a tibial or foot vessel, and use of a suprafascial tributary collateral as a graft were significantly associated with loss of patency and limb loss during follow up.

Purpose: The efficacy and safety of endovascular aneurysm repair (EVAR), in patients outside instruction for use (IFU), is very challenging and widely debated. The aim of this study was to evaluate the placement of the Treovance® abdominal aorta stent-graft in patients with hostile proximal necks considered outside IFU. Materials and Methods: Between May 2013 and August 2014, 5 patients with outside IFU underwent EVAR with the Treovance® stent-graft. Technical and clinical successes were evaluated. All 5 patients underwent clinical and imaging follow-up. Results: Technical and clinical successes were achieved in all 5 patients without adjunctive endovascular procedures or surgical conversion. During the mean follow-up of 21 months, no type I/III endoleaks, stent-graft migration nor kinking/occlusion were observed. In all 5 patients, a reduction of the proximal neck angle was observed. Conclusion: In our small series of selected outside IFU patients, EVAR with the Treovance® stent-graft was technically feasible and safe, with satisfactory short-term follow-up results, when performed by experienced operators. Long-term follow-up will be necessary to confirm the durability of our preliminary promising results.

A major problem in treating patients with peritoneal spread from colorectal cancer is that at diagnosis wide peritoneal involvement often precludes all curative attempts. A possible solution is to identify those patients at risk for peritoneal metastases and intervene early to prevent locoregional disease spread before it develops and, thus, to improve outcome. We analyzed long-term results from a previous study and compared outcomes in 25 patients with advanced colon cancer considered at high risk for peritoneal spread (pT3/pT4 and mucinous or signet ring cell histology) prospectively included and managed with a proactive surgical approach including target organ resection for peritoneal spread plus hyperthermic intraperitoneal chemotherapy (HIPEC) and in 50 retrospectively well-matched controls who underwent standard surgical resection during the same period and in the same hospital by different surgical teams. At 48 months after the study closed, peritoneal metastases and local recurrence developed significantly less often in proactively managed patients than in controls (4 vs 28 %) (p

Background & Aims: The role of desmoplasia in colorectal carcinoma progression is unclear and the presence of collagen stroma may represent a barrier against cancer diffusion and vascular invasion or a stroma to build up and support the tumor. The aim of this study was to evaluate the effect of desmoplastic response on long-term survival of patients who underwent radical resection for colorectal carcinoma. Methods: The study included 429 patients who underwent radical colorectal resection for cancer with a median follow-up period of 72.8 months. Results: At univariate analysis significant associations were observed between desmoplasia and histologic type, parietal infiltration, growth pattern, and staging. No associations were found between desmoplasia and the other clinical and histologic parameters. The multivariate analysis stratified for tumor stage revealed that the factor showing the most favorable influence on time to death was desmoplasia. The presence of desmoplasia was likely to decrease the failure rate to a third of the rate experienced by patients without desmoplasia. Parietal infiltration was associated with an increased risk for a shortened time to death. Conclusions: Our results favor the view that desmoplasia is a protective factor for survival in patients with colorectal carcinoma. This finding is consistent with the hypothesis that desmoplasia may prevent cancer invasiveness by building a barrier against tumor diffusion.

The role of surgery in the treatment of primary gastric lymphoma has been recently re-evaluated. We report the results of a series of 37 operated patients for primary gastric lymphoma (PGL). All patients underwent gastrectomy with D2 lymphadenectony and bilateral liver biopsies. Postoperative histopathological classification was compared to preoperative staging data. No mortality and low morbidity were observed in this series of patients. We found a high incidence of mixed grading of tumors and a relatively high incidence of lymph node metastases in low grade lymphoma. Relying on preoperative biopsies and imaging techniques could lead to preoperative staging inaccuracy and therefore to inappropriate treatment planning. For these reasons we advocate systematic primary surgery in PGL. Surgery could be useful for staging purposes and seems to be curative in stage IE.

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.

observed (Fig. 3). The presented case shows theimportance of team work and selection of the optimalirradiation technique in determining diagnosis, tumorstaging, and treatment of the patient. After histologi-cal classification, high-grade primary breast lympho-mas should be treated with combinationchemotherapy with or without radiation similar tosystemic lymphomas of a similar histological type.Reports on breast lymphoma treatment include fewor no details about the target volume and applied irra-diation technique and usually mention only the totalradiation dose. The delivery of radiotherapy was a sig-nificant predictor of improved overall survival in ourcase.

BACKGROUND Numerous studies have investigated locoregional immune responses and long term survival in patients with various types of cancer; few have focused on patients with lung carcinoma. The current study was designed to assess the prognostic value of immunomorphologic changes in locoregional lymph nodes and lymphocytic infiltration of primary tumor (LI) in patients who undergo resection for bronchogenic carcinoma. METHODS In a retrospective analysis, immune responses in locoregional lymph nodes and at primary tumor sites were studied histologically in 172 selected patients. Lymph node morphology was studied according to the system of Cottier et al. Sinus histiocytosis and paracortical lymphoid cell hyperplasia were considered to be cellular immune responses, and follicular hyperplasia of the cortical area was considered to be a humoral reaction. LI was classified with Black's method. The survival rate was estimated by using the Kaplan–Meier product-limit method. The log rank test and the Cox proportional-hazards model were used to determine statistical significance in univariate and multivariate survival analyses. RESULTS Among the 172 patients, 35.5% had no evident response in regional lymph nodes, 19.8% had a marked cellular response, 11% had a marked humoral response, and 33.7% had a mixed cellular and humoral response. LI was intense in 36.6% of patients and was absent or scarcely evident in 63.4%. A lymph node cellular response and marked LI improved long term survival rates even in patients with regional lymph node metastases. Multivariate analysis identified two independent variables that had high prognostic value: lymph node immunoreactivity and LI. CONCLUSIONS Lymph node immunoreactivity and LI significantly influence long term survival after curative surgery for patients with carcinoma of the lung and may be useful in stratifying patients for prospective trials of adjuvant treatment, including immunotherapy. Cancer 2000;89:2038–45. © 2000 American Cancer Society.

The study compared the outcome in patients with advanced colonic cancer at high risk of peritoneal metastases (mucinous or signet-ring cell) without peritoneal or systemic spread, treated with standard colectomy or a more aggressive combined surgical approach. The study included patients with colonic cancer with clinical T3/T4, any N, M0, and mucinous or signet ring cell histology. The 25 patients in the experimental group underwent hemicolectomy, omentectomy, bilateral adnexectomy, hepatic round ligament resection, and appendectomy, followed by HIPEC. The control group comprised 50 patients treated with standard surgical resection during the same period in the same hospital by different surgical teams. Outcome data, morbidity, peritoneal recurrence rate, and overall, and disease-free survival, were compared. Peritoneal recurrence developed in 4% of patients in the experimental group and 22% of controls without increasing morbidity ( 𝑃 < 0 . 0 5 ). Actuarial overall survival curves disclosed no significant differences, whereas actuarial disease-free survival curves showed a significant difference between groups (36.8 versus 21.9 months, 𝑃 < 0 . 0 1 ). A more aggressive preventive surgical approach combined with HIPEC reduces the incidence of peritoneal recurrence in patients with advanced mucinous colonic cancer and also significantly increases disease-free survival compared with a homogeneous control group treated with a standard surgical approach without increasing morbidity.

Clinicopathologic data from 59 patients with primary gastric non-Hodgkin’s lymphoma (NHL) were reviewed. Lymphomas in 13 patients were limited to the gastric wall, in the remaining cases nodes or adja

The diagnosis, treatment and follow up of oncologic patients require multidisciplinary working groups made up of a dedicated team of physicians. Over the last decade the multidisciplinary treatment of oncologic diseases has become increasingly integrated and decreasingly sequential. The aim of cooperation is to provide quality treatment and produce new knowledge through both basic and clinical research and medical education.

Background: Colorectal cancer (CRC) metastasis is enhanced in patients with venous embolization increasing the risk of recurrence and therefore mortality rate. Several evidences indicate that stage II patients have an abrupt recurrence within five years from surgery. This fact, led us to investigate the role played by different histological variables on CRC invasiveness. Aim :T o demonstrate if quantitative and qualitative desmoplastic response and lymphocytic infiltration are prognostic factor involved in the recurrence of CRC within five years from surgery, considering possible clinical and therapeutical implications. Methods: Thirty-four patients with CRC underwent colectomy and the UICC-TNM classification was applied for disease staging. Histological variables were semi-quantitatively evaluted. Qualitative evaluation of desmoplasia was obtained with the hematoxillin-eosin method. Results: Survival rate arose 88% at stage II, at five years of follow-up, and the 12% not treated with adiuvant chemotherapy developed metastasis. Desmoplasia is strongly associated with venous neoplastic invasiveness (OR: 21.93; 95%CI: 1.012-475.26, p = 0.02), and therefore, with mortality rate (OR: 14.33; 95%CI: 0.67-304, p = 0.04). Moreover, mortality rate was significantly higher in patients with immature desmoplasia compare to mature stromal tissue (OR: 15.61, 95%CI: 0.69-343.38, p= 0.04). Conclusions: These observations should prompt a future evaluation of desmoplasia to extent more suitably the use of adjuvant chemotherapy in II stage patients. Further clinical trials are needed to determine if these findings will be able to reduce mortality rate, in stage II CRC patients.

Pleomorphic hyalinizing angiectatic tumours are rare stromal lesions histologically resembling both neurilemoma and malignant fibrous histiocytoma and occurring in the subcutaneous soft tissue of the lower and upper limbs and, less frequently, in the chest wall. The case reported here is one of 22 cases published in the medical literature and describes a pleomorphic hyalinizing angiectatic tumour which was localized in a body cavity and developed in the pelvis. The present report is the first of its kind to date. A 53-year-old asymptomatic woman was treated via an open laparotomy. The lesion arising from the left mesorectal tissue was entirely resected. The postoperative course was uneventful and the patient was discharged on postoperative day 3. The patient is still disease-free 58 months after the operation. A review of the literature shows that pleomorphic hyalinizing angiectatic tumours are locally aggressive. A 20% recurrence rate has also been observed in long-term follow-up. These patients should therefore be treated by wide local excision and require long-term surveillance.

This study investigated the changes, if any, in the level of expression of a well defined panel of cell proliferation, differentiation and apoptosis markers between the primary breast tumor and the corresponding synchronous lymph node metastasis from a population of patients with a comparable disease status, in terms of clinical features, and natural history.Ninety pure invasive ductal carcinomas with 10 or more axillary lymph nodes involved and without evidence of distant metastasis were included in this study. Primary tumor and corresponding metastatic lymph node tissue specimens were evaluated for the expression of Cyclin B1, MMP1 metalloproteinase, ICAM-1, RARbeta, Ki67, ER, PgR, p53, bcl-2 and c-erbB2 by immunohistochemistry using standard methods. The bivariate Pearson correlation analysis demonstrated a close relationship between primary and matching corresponding metastatic node. A high grade of correlation has been maintained even when staining results where categorized as positive/negative according to each one marker cut-off level of staining expression. We report the most extensive immunohistochemical analysis of biological determinants in a well defined population of patients with invasive ductal carcinomas and involvement of 10 or more axillary nodes and no distant metastasis. We found a close correlation between the primary tumor and corresponding metastatic node in terms of the expression of all 10 of the markers investigated in this study. The not complete concordance observed could be explained by the gene expression modulation by extrinsic factors and by the microenvironment in which the cancer cells reside.

A small but significant excess of deaths for tumors of the digestive system has been described in Crohn's disease. In a study analyzing all cancers of the small intestine within a defined population, Crohn's disease was the major underlying factor for cancer of the small intestine. Areas of the small intestine containing strictures are unusually prone to malignant transformation. We report the rare case of a patient in whom surgery for intestinal occlusion disclosed Crohn's disease of the distal ileum complicated by two adenocarcinomas arising within distinct areas of the inflamed bowel.

The aim of the study was to compare the resultsof ultrasonography (US) and laparoscopy in a series of210 patients referred to our institution for thediagnosis of widespread liver diseases. Among 205 patients, laparoscopy revealed cirrhosis in114, chronic widespread disease in 70 (chronicpersistent hepatitis in 21, chronic active hepatitis in28, steatosis in 14, acute hepatitis in 5, fibrosis in 2), and absence of liver disease in 21. Four ofthese cases had minor complications. A corroborativediagnosis was obtained in 122 patients (59.5%). Overallsensitivity of US was 84% with a low specificity due to the high rate of false negatives. Fromthe results of this study we conclude that laparoscopyis a safe and essential diagnostic tool in the finaldiagnosis of widespread liver diseases and that US is not a reliable screening method becauseof its incidence of false negatives.

Objective Pre-operative staging of rectal cancer should identify patients with extrarectal spread, who might benefit from pre-operative radiotherapy, and patients with minimal sphincteral involvement, who can avoid permanent colostomy. The aim of this study was to assess the accuracy of Magnetic Resonance Imaging (MRI) to predict tumour stage and sphincter status. Patients and methods Thirty-three patients with a rectal tumour were pre-operatively assessed by MRI with a phased-array coil. Imaging results were correlated with the final pathological findings. Results The overall accuracy of pre-operative staging with MRI was 88% (k = 0.75) for extramural tumour invasion and 59% (k = 0.26) for lymph node metastases. MRI correctly evaluated the infiltration of the anal sphincters in 87% of patients (7 of 8 patients with low rectal tumour). Conclusion MRI provides the surgeon with valuable information regarding extramural tumour spread and sphincteral involvement, enabling appropiate selection of patients for pre-operative adjuvant therapy or sphincter-saving surgery.

Adrenomedullin (ADM) is a new potent vasorelaxant peptide identified originally in extracts of pheochromocytoma, and is widely distributed within the tissue. Although histopathological studies have demonstrated the presence of ADM-immunoreactivity (ir-ADM) in some human neuroendocrine tumors (such as insulinoma, pituitary adenoma, and gastrointestinal neuroendocrine tumors), data on the presence of ADM in normal and pathological parathyroid gland are not available. Plasma AM concentrations were recently reported to be elevated in patients with PHP (primary hyperparathyroidism). The aim of our study was to determine tissue distribution of ir-AM in 34 patients with PHP (27 female and 7 male, mean age 50 +/- 6 years) undergoing surgery. Six normal parathyroid samples incidentally found during thyroidectomy for neoplastic diseases and ten sections of human rectus abdominis muscle tissue were used as controls (C). Adenomatous parathyroids were found in 22 PHP and hyperplastic parathyroids in twelve PHP patients. Four hyperplastic parathyroids were found in three PHP patients and three parathyroids in 10 PHP patients. Eight parathyroids revealed a prevalent diffuse growth pattern and four showed a prevalent nodular growth pattern. Immunohistochemical ADM expression was seen in seven of twelve (58.3 %) hyperplastic parathyroids and in fourteen of twenty-two (66.6 %) adenomatous glands. Parathyroid chief cells showed strong cytoplasmatic staining, whereas oncocytic cells showed a faintly aspecific cytoplasmatic staining. Normal parathyroids were negative for ir-ADM. In conclusion, we found the presence of ADM in parathyroid chief cells of PHP patients using immunohistochemistry in our study.

Myofasciitis syndrome encompasses a group of disorders characterized by chronic inflammation and/or fibrosis of the subcutaneous septa and muscular fascia. We report on a patient in whom myositis was diagnosed in the areas previously irradiated for papillary thyroid carcinoma and anal canal carcinoma respectively 21 and 3 years after radiotherapy. We are not able to explain why myopathy developed at the same time in two different sites at a different interval from the two radiotherapic schemes. We can suppose that the patient developed a subclinical regional myopathy after the first radiotherapic scheme. Radiation induced heritable mutations within surviving cells that were unable to tolerate the second damage by systemic chemotherapy. It is unclear how radiosensitization correlates with an ability to reactivate latent effects in normal tissue. Physicians using chemotherapic radiosensitizers should be aware of their potential to induce a delayed form of radiosensitization. We report this case to encourage physicians to be alert to the knowledge of the clinical, histologic and morphologic characteristics of radiation myositis in order to distinguish it from an infectious or immune fasciitis or myositis.

Although relatively little is known about the molecular mechanisms underlying tumor progression, recently CD44 glycoproteins and the c-Met receptor tyrosine kinase have been identified as potentially important components of the metastatic cascade. CD44 is a family of transmembrane receptors generated from a single gene by alternative splicing and differential glycosylation. Important biological processes involving CD44 glycoproteins include cell adhesion, lymphocyte homing, hematopoiesis, tumor progression and metastasis. The precise mechanism via which CD44 promotes tumorigenesis have not yet been elucidated. We evaluated the expression of adhesion molecule CD44 variant 6 in pulmonary metastases from colorectal carcinomas and its correlation with clinicopathological parameters. Twenty patients were randomly selected from the patients who had undergone a resection of pulmonary metastasis from colorectal cancer. Formalin-fixed, paraffin-embedded archival specimens of tumor tissues and adjacent normal mucosa from these patients were the subjects of the present study. Immunoreactivity for CD44 was quantified. Specimens were considered positive if almost 25% of the neoplastic cells were stained. CD44 v6 expression was related to the interval between colon resection and metastases diagnosis, the number of pulmonary metastases, and the survival after lung resection. No statistical correlation was found between CD44 v6 positivity and disease-free interval after colon resection, number of metastases or 2-year survival after lung resection. Probably CD44 v6 is necessary and sufficient to confer metastatic potential to carcinoma cells increasing the migration capacity and participating in invasion via changes in adhesion to the extracellular ligands, but is not necessary to modify the clinical history of the metastases. Therefore the evaluation of CD44 v6 expression in lung metastases does not influence the therapeutic scheme.

Primary hyperparathyroidism is the clinical result of parathyroid adenoma or hyperplasia, rarely of carcinoma. Clinical, serologic, and radiologic data are unable to discriminate a single parathyroid adenoma from an enlarged hyperplastic gland. Morphologic features also overlap in adenoma and small hyperplastic gland. Studying immunohistochemical expression of fatty acid synthase (FAS), p53, Ki67 and bcl-2, we found that among 21 adenomas 19 (90.5%) were positive for FAS, 12 (57.2%) for Ki67, 11 (52.4%) for p53, and 16 (76.2%) for bcl-2; among 12 hyperplasias, 12 (100%) were positive for FAS, 6 (50%) for KI67, 8 (66.7%) for p53, and 8 (66.7%) for bcl-2. Statistical analysis showed that FAS was associated with parathormone (PTH) (P =.001), Ki67 (P =.01), and p53 (P =.01). Moreover, FAS was associated with hyperplastic (P =.0001) and adenomatous glands (P =.0001). Ki67 was associated with both adenomatous (P =.02) and hyperplastic glands (P =.005). P53 protein were associated only with hyperplastic glands (P =.01). The different occurrence of p53 in parathyroids adenoma and hyperplasia may enable a different management and follow-up of the patients with primary hyperparathyroidism, stratifing them into two groups. The first, with a "false" adenoma having a high risk of relapse, may necessitate exams like serum calcium levels, PTH concentrations, urinary calcium levels for 24 hours, kidney functional tests, and radiology and ultrasound every 3 to 6 months, whereas the second with "true" adenoma, at low risk of relapse, may be checked less frequently with serum calcium levels and PTH concentrations.

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.

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.

As recently shown, angiogenesis is the most reliable marker of breast cancer invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue specimens. We have used technetium-99m sestamibi, a marker of regional blood flow in other organs that often but not always images breast cancer, to assess the invasiveness of this tumour. Nineteen patients, ten with nodal metastases and nine without any metastases, were studied with 99mTc-sestamibi scintigraphy before operation. Angiogenesis was quantitatively assessed by immunohistochemical staining of endothelia for factor VIII. All the node-positive (N+) patients at surgical revision showed a positive 99mTc-sestamibi scan of the primary tumour and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive tumours showed more than 135 microvessels/mm2 and one showed 99 microvessels/mm2; by contrast there were 71.6 +/- 12.1 microvessels/mm2 in the nine N- and sestamibi-negative tumours. Our study suggests that 99mTc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour.

Twenty-three patients with cirrhosis (alcoholic, post-hepatitic and cryptogenetic), who underwent hepatic venous catheterization and hepatic biopsy, were included in a histopathologic study to identify morphologic features correlated with the values of corrected sinusoidal pressure. The alterations in acinar architecture were investigated by histomorphometry and could be described as: a) multiacinar fibrosis with partial persistence of normal afferent and efferent vascular structures; b) complex acinar fibrosis with partial persistence of afferent structures alone; and c) simple acinar and subacinar fibrosis with almost complete disappearance of normal vascular structures. A significant negative correlation (p0.05) was found between corrected sinusoidal pressure values and the percentage of portal spaces not involved in the process of bridging fibrosis, indicated as "residual portal spaces". Residual portal space evaluation can therefore be suggested as an easily quantifiable morphologic feature indicative of portal pressure.

The purpose of this study was to investigate the effect of long-term misoprostol administration, at non-antisecretory doses, on N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-induced gastric carcinogenesis. The incidence of gastric carcinomas and precancerous lesions was evaluated in 50 male 250-g Sprague-Dawley rats after 52 weeks of continuous oral administration of MNNG (120 mg/l; n = 20), MNNG plus misoprostol (2 mg kg-1 day-1; n = 20) or tap water (n = 10) (experiment 1), and in 30 rats treated with MNNG for 30 weeks followed by tap water (n = 15) or by misoprostol (n = 15) for 22 weeks; a third group (n = 10) received tap water only for 52 weeks (experiment 2). After sacrifice, gastric mucosal lesions were macroscopically evaluated and their histology obtained. MNNG consumption was comparable in all groups (6.5 +/- 1.1 mg rat-1 day-1). Misoprostol consumption was 180 +/- 0.25 mg kg-1 day-1 rat-1. In experiment 1 the incidence of gastric carcinomas was 60% in the MNNG group and 25% in the group treated with MNNG plus misoprostol (P less than 0.05). Cytotoxic and hyperplastic gastric mucosal lesions were also significantly reduced by misoprostol. In experiment 2 the incidence of carcinomas was 31% and 38.6% respectively. Misoprostol significantly decreased the incidence of gastric cancer formation when given from the beginning of the experiment. By contrast, when administered after 30 weeks of MNNG treatment it did not interfere with experimental gastric cancer formation. Exogenous prostaglandins are able to prevent the early MNNG-induced gastric mucosal lesions, thus interfering with gastric carcinogenesis.

An increased number of interphasic nucleolar organizer regions containing ribosomal cistrons associated with argyrophilic proteins (AgNORs) has been described in human malignant tumor cells. In this study variations in AgNOR numbers have been compared with changes of cell kinetics, evaluated by the mitotic count (MC) and bromodeoxyuridine labeling index (BrdU LI), during gastric carcinogenesis induced with N-methyl-N'-nitro-N-nitrosoguanidine (NG) in rats. Significant differences (2 P0.005) in AgNOR mean numbers, evaluated in the antral isthmic cells, in MC mean values and BrdU LI, evaluated in the whole antral cellular population, were found when comparing areas of acute gastritis, atrophy and hyperplasia in NG-treated rats with the normal mucosa in controls. No differences were observed in MC and BrdU LI between normal antrum and carcinoma cells which showed an AgNORs mean number lower than in the isthmic cells of controls (2 P0.005). Moreover, significant correlations were found comparing changes in AgNOR numbers with MC (r = 0.89, P0.001) and BrdU LI (r = 0.66, P0.001) in different lesions. These data show that evaluation of AgNOR numbers does not allow the identification of malignant cells in NG-induced gastric carcinoma. However AgNOR quantification seems to be a reliable index of cell kinetics and related well with the cellular dividing fraction.

The current study was performed on 71 cases of human female breast cancer and compares the results of five morphologic methods developed for the detection of estrogen receptors (ER), progesterone receptors (PgR), lectin Peanut agglutinin (PNA) binding sites, monoclonal antibody Ki-67 immunoreactivity, and the mean number of argyrophilic nucleolar organizer regions (Ag-NOR). All the parameters were evaluated on serial cryostat sections representative of a closely related, if not identical, neoplastic population. A significant positive correlation was found between the occurrence of estrogen, progesterone, and peanut receptors and between Ki-67 immunoreactivity, mean number of NOR, and mitotic index. Furthermore, ER, PgR, and PNA receptors showed a significant, inverse correlation with Ki-67 immunoreactivity, mitotic index, and mean number of Ag-NOR. These results provide further data that support the hypothesis that (1) progesterone and PNA receptors are estrogen-induced and indicate a metabolic response of the target cells to functioning estrogen receptors; (2) the mean number of NOR reflects the cell kinetics of the tumor; and (3) metabolic differentiation of neoplastic cells is inversely correlated to the proliferation index.

The management of patients affected or at risk for the Lynch Syndromes must focus upon its natural history, early age of onset, predilection for the proximal Colon, excess of synchronous and metachronous Colon cancer, and autosomal dominant mode of inheritance (Lynch Syndrome I). In addition, predisposition to carcinoma of the endometrium, ovary, stomach, pancreas, and other anatomic sites are integral features of the Lynch Syndrome II counterpart [Lynch H.T., 1985, 1988, 1988a]. The absence of biomarkers for the genotype and/ or premonitory signs, such as multiple colonic adenomatous polyps, as occurs in the familial adenomatous polyposis (FAP) syndrome, makes the job of the diagnostician a vexing one [Cristofaro G., 1988, 1989].

The behaviour of silver-binding Nucleolar Organizer Regions (Ag-NORs) in interphasic nuclei was investigated in six cases of normal colonic mucosa, six cases each of mild, moderate and severely dysplastic colonic adenomatous polyps and six cases of colonic adenocarcinomas. The silver-stained dots were counted directly from slides using a 100X oil-immersion lens and from micrographs of the same fields using an image analyzer at a final magnification of 1,700X. The mean number of argyrophilic dots and the mean nuclear area occupied by argyrophilic proteins increased progressively from mild to severe dysplasia to adenocarcinoma with both methods. The Ag-NORs technique has a predictive value only when a suitable number of cells are examined because a wide overlap between the ranges of different parameters does not allow to consider the Ag-NOR method as a marker of malignant transformation in a single cell.

The study was initiated to evaluate the effect of N-methyl-N-nitro-N-nitrosoguanidine (NG) on gastric intraluminal prostaglandin release during a 30-day treatment period and to investigate the effect of a stable prostaglandin E1 analogue (misoprostol) on NG-induced gastric mucosal damage during the same time period. Samples of gastric juice (1 h) were obtained from 40 male Sprague-Dawley rats with chronic gastric fistulas, in basal conditions and after 5, 15 and 30 days of continuous oral administration of NG (120 mg/l) or tap water. Aliquots of gastric juice were titrated with 0.1 M NaOH. Other aliquots were extracted with ethyl acetate and subjected to specific radioimmunoassay for prostaglandin E2. The severity of gastric mucosal lesions was evaluated in 60 rats after 5 days and 30 days of continuous oral administration of NG (120 mg/l) or NG plus misoprostol (200 micrograms/kg-1/day-1) or tap water, and a histological study was carried out. Administration of NG induced a significant decrease of gastric intraluminal prostaglandin E2 concentration at 15 and 30 days. Oral administration of misoprostol, at non-antisecretory doses, protected the rats against NG-induced gastric mucosal damage. Prostaglandins may be involved in the early phases of experimental gastric carcinogenesis.

It was previously reported that a neonatal injection of 7,12-dimethylbenz (a) anthracene (DMBA) in mice induces a reduction both of the primary immune response to sheep red blood cells (SRBC) and, later in life, of delayed hypersensitivity. In this study we investigated the secondary immune response to SRBC in Swiss mice injected at birth with 100 μg of DMBA. Groups of DMBA treated and control animals were sacrificed respectively 30, 50, 75, 100, 150 and 200 days after treatment with the carcinogen. They were given a priming i.p. injection of 4 × 108 SRBC in saline 20 days before sacrifice and a booster of SRBC 48 h before killing. The numbers of indirect spleen plaque forming cells and the hemagglutinin titers after reduction with 2-mercaptoethanol were determined at the time of sacrifice. It has been constantly found that animals given carcinogen at birth show a depressed secondary response, regardless of the presence of tumors. The present results fit well with our previously reported observations showing a constantly depressed immune response after neonatal DMBA treatment, and further suggest the existence of a relationship between immunodepression and the high rate of tumors that DMBA induces. The results are also discussed in relation to others studies indicating a direct action of leukemia viruses on undifferentiated B-lymphocytes of marrow origin, in view of the suggested activation of a latent lymphoma virus by DMBA.

The effects of ALS (anti-lymphocyte serum) and NRS (normal rabbit serum) treatments on the development of malignant lymphoma, lung, subcutaneous and skin tumors induced in mice by 7,12-dimethylbenz (a) anthracene (DMBA) are described. Groups of Charles-River mice, injected at birth with a dose of 100 μg of DMBA, received a single injection of ALS or NRS at the same time as DMBA administration or 10, 20, 30, 40 and 50 days after birth. Incidence, latency, histology and spread of the tumors were studied in all groups. It was found that both ALS and NRS increased tumor incidence and shortened their latency period. Malignant lymphomas were the main tumors whose latency was shortened either by ALS or NRS treatment. In addition ALS treatment apparently increased dissemination of DMBA induced lymphoma in bone marrow.

The effect of adding cetylpyridinium chloride to the fixative on the preservation of sulphated glycosaminoglycans (SGs) was studied in human normal colonic mucosa. SGs were visualized at the ultrastructural level through the application of Spicer's High Iron Diamine (HID) technique followed by a post-fixation with potassium ferrocyanide-reduced osmium tetroxide. SGs were mainly localized in basement membranes of epithelium and capillary wall and along collagen fibers. The morphology of the reactive sites depended on the presence of cetylpyridinium chloride, SGs being granular in absence of the salt and more or less elongated when cetylpyridinium chloride was added to the fixative. We suggest that the use of cetylpyridinium chloride during fixation may help to preserve SG molecule at the ultrastructural level.

The histochemical and ultrastructural features of an adenosquamous carcinoma of the stomach have been studied. Both the adenomatous and the squamous component of the tumour showed malignant characteristics. Elements which were considered as undifferentiated cells on light microscopy showed ultrastructural features of poorly differentiated squamous cells. No intermediate cells, sharing squamous and glandular aspects, were found by electron microscopical examination. The adenomatous component exhibited histochemical and ultrastructural features of the intestinal type of gastric carcinoma and the mucosa surrounding the tumour showed a colonic type of intestinal metaplasia. A possible histogenesis from a totipotential undifferentiated cell is considered.

Peanut lectin reactivity was examined in normal fundic glands from human gastric samples, both at light- and electron-microscopic levels, using a peroxidase conjugate. Positive reaction was observed in the glycocalyx of parietal cell secretory canaliculi as well as in the mucous globules of mucous cells and in the luminal cell coat of chief cells. The presence of terminal galactose in the canalicular glycocalyx may be connected with the peculiar function of hydrochloric acid secretion. Peroxidase-labelled peanut lectin is proposed as a marker for visualizing the secretory canaliculus of parietal cells.

AIM: To investigate β-catenin expression in patients with intestinal metaplasia, and to look for a possible relationship between β-catenin expression and either epithelial proliferation values or Helicobacter pylori (H pylori) infection. METHODS: Twenty patients with complete type intestinal metaplasia were studied. β-catenin expression and epithelial cell proliferation in antral mucosa were assessed using an immunohistochemical analysis. H pylori infection was detected by histology and a rapid urease test. RESULTS: Reduced β-catenin expression on the surface of metaplastic cells was detected in 13 (65%) out of 20 patients. Moreover, in eight (40%) patients intranuclear expression of β-catenin was found. When patients were analyzed according to H pylori infection, the prevalence of both β-catenin reduction at the cell surface and its intranuclear localization did not significantly differ between infected and uninfected patients. Cell proliferation was higher in patients with intranuclear β-catenin expression as compared to the remaining patients, although the difference failed to reach the statistical significance (36 ± 8.9 vs 27.2 ± 11.4, P = 0.06). On the contrary, a similar cell proliferation value was observed between patients with reduced expression of β-catenin on cell surface and those with a normal expression (28.1 ± 11.8 vs 26.1 ± 8.8, P = 0.7). H pylori infection significantly increased cell proliferation (33.3 ± 10.2% vs 24.6 ± 7.4%, respectively, P = 0.04). CONCLUSION: Both cell surface reduction and intranuclear accumulation of β-catenin were detected in intestinal metaplasia. The intranuclear localization of β-catenin increases cell proliferation. H pylori infection does not seem to play a direct role in β-catenin alterations, whilst it significantly increases cell proliferation.

A total of 35 patients (age range 35-78 years) with gastric tumors on the lesser curve, or in the antro-pyloric region, underwent angio-CT in the prone position after filling the stomach with 500 ml of water and intravenous administration of glucagon. The films were reviewed by three radiologists independently, staging each tumor according to the TNM classification preoperatively. The overall accuracy of tumor staging ranged between 66-77 %, overstaging between 17-25 %, and understaging between 3-8.5 %. The diagnostic sensitivity, specificity, and accuracy for serosal invasion ranged between 90 and 100, 76 and 84, and 80-88 %, respectively, and the overall accuracy for N staging was 46, 48, and 51 % for the three observers. If, however, N1 and N2 tumors were considered as a single group, N-stage accuracy increased, ranging between 63 and 77 %. The "K test" for analyzing the interobserver agreement was 60 %, i. e., the diagnostic results are reproducible. Water filling of the stomach optimizes visualization of the gastric wall on contrast-enhanced CT. The prone position and drug-induced hypotony allows for good distension without any disturbing artifact reduction obscuring the lower gastric body.

Introduction Ganglioneuromas are rare benign peripheral neuroblastic tumors characterized by hyperplasia of ganglion cells, nerve fibers, and supporting cells. They are not usually localized in the colon. Case presentation A 61-year-old Caucasian man was admitted to our department for colon cancer screening. A colonoscopy revealed a lipoma of 5cm in diameter, two micropolyps of less than 1cm, and one sessile polyp of 0.6cm in diameter. The polyps were removed with hot biopsy forceps. A histological examination revealed two hyperplastic polyps and one ganglioneuroma polyp. A follow-up colonoscopy showed no signs of recurrence after 16 months. Conclusions Although a few cases of lipomas associated with ganglioneuromatous syndrome have been reported, the association of an intestinal lipoma with an isolated ganglioneuroma polyp has not been described. The implications of this association are unknown.

A villous adenoma of the duodenum was studied histologically and histochemically by semi-thin sections using glycol-methacrylate as embedding medium. All the four epithelial cell types which are present in normal duodenal mucosa (absorptive columnar, goblet, Paneth, endocrine) were found in the tumour, as well as undifferentiated elements. Neutral and acid non-sulphated mucins were detected. Cell type distribution and mucin production varied according to the degree of differentiation. Foci of gastric metaplasia were observed. A possible histogenesis from crypt base stem cell is considered.