Pietro Mingazzini

Prevention of Peritoneal Metastases from Colon Cancer in High-Risk Patients: Preliminary Results of Surgery plus Prophylactic HIPEC

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 < 0.05). 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 < 0.01). 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.

Correlation between genetic and biological aspects in primary non-metastatic breast cancers and corresponding synchronous axillary lymph node metastasis

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, RARβ, 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 comparative study of histopathology, hormone receptors, peanut lectin binding, ki-67 immunostaining, and nucleolar organizer region-associated proteins in human breast cancer

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.

Role of Desmoplasia in Recurrence of Stage II Colorectal Cancer within Five Years after Surgery and Therapeutic Implication

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: To 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.

Influence of cetylpyridinium chloride on the ultrastructural appearance of sulphated glycosaminoglycans in human colonic mucosa

SummaryThe 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 Spicers 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.

Is desmoplasia a protective factor for survival in patients with colorectal carcinoma

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.

Duodenal Pancreatic Heterotopy Diagnosed by Magnetic Resonance Cholangiopancreatography : Report of a Case

Abstract 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.

Visualization of the secretory canaliculi of human parietal cells with a peroxidase-labelled peanut lectin

SummaryPeanut 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.

Interphasic nucleolar organizer regions expression and cell kinetics evaluation during gastric carcinogenesis induced by nitrosoguanidine in the rat

SummaryAn 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 (2P< 0.005) 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 (2P< 0.005). Moreover, significant correlations were found comparing changes in Ag-NOR numbers with MC (r = 0.89,P<0.001) and BrdU LI (r = 0.66,P<0.001) 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.

Villous adenoma of the duodenum: cellular composition and histochemical findings

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.