Serrated polyps - a concealed but prevalent precursor of colorectal cancer.

Serrated polyps have long been considered to lack malignant potential but accumulating data suggest that these lesions may cause up to one-third of all sporadic colorectal cancer. Serrated polyps are classified into three subtypes, including sessile serrated adenomas/polyps (SSA/Ps), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). SSA/P and TSA harbour malignant potential but TSA represents only 1-2%, wheras SSA/P constitute up to 20% of all serrated lesions. HPs are most common (80%) of all serrated polyps but are considered to have a low potential of developing colorectal cancer. Due to their subtle appearence, detection and removal of serrated polyps pose a major challenge to endoscopists. Considering that precancerous serrated polyps are predominately located in the right colon could explain why interval cancers most frequently appear in the proximal colon and why colonoscopy is less protective against colon cancer in the proximal compared to the distal colon. Despite the significant impact on colorectal cancer incidence, the aetiology, incidence, prevalence, and natural history of serrated polyps is incompletely known. To effectively detect, remove, and follow-up serrated polyps, endoscopists and pathologists should be well-informed about serrated polyps. This review highlights colorectal serrated polyps in terms of biology, types, diagnosis, therapy, and follow-up.

Evaluation of immune cell markers in tumor tissue treated with radioimmunotherapy in an immunocompetent rat colon carcinoma model.

BACKGROUND: Immune cells within the tumor can act either to promote growth or rejection of tumor cells. The aim of the present study was to evaluate immune cell markers (number and localization) within the tumor before and during rejection due to radioimmunotherapy, to determine whether there is a change in markers related to rejection and/or tolerance of the tumor cells. METHODS: Thirty immunocompetent rats were inoculated with syngeneic rat colon carcinoma cells and 13-14 days later 21 of these rats were treated with 400 MBq/kg of (177)Lu-DOTA-BR96 monoclonal antibodies. The treated animals were sacrificed and dissected 1, 2, 3, 4, 6, and 8 days post-injection in groups of three animals per day (6 animals on day 8); while the nine untreated animals were sacrificed and dissected on day 0. Paraffin sections were used for immunohistochemical staining of CD2, CD3, CD8α, CD68, and CD163 antigens. Positive cells were counted within: vital tumor cell areas, necrotic areas, granulation tissue surrounding and between the tumor cell areas. The change in the number of positive cells over time in tumors treated with radioimmunotherapy in the same location was evaluated with linear regression models. The number of positive cells in various locations and the number of various antigen-positive cells within the same location were also evaluated over time using box plots. RESULTS: There were a higher number of cells expressing immune cell markers in granulation tissue compared with vital tumor cell areas. Cells expressing markers decreased during radioimmunotherapy, and T-cell markers decreased more than macrophage markers in tumors treated with radioimmunotherapy. The expression of CD8α was higher than that of the other T-cell markers evaluated (CD3 and CD2), which could be explained by the additional expression of CD8α by natural killer (NK) cells and a subset of dendritic cells (DCs). The expression of CD68 (all macrophages, DCs, and neutrophils) tended to be higher than that of CD163 (pro-tumor macrophages). CONCLUSIONS: In this model, we demonstrated a higher number of positive cells for immune cell markers related to augmenting the immune rejection than immune tolerance of tumor cells in tumors and a decrease in markers during radioimmunotherapy.

[Serrated polyps is a hidden but common cause of colorectal cancer]. / Sågtandande polyper en dold men vanlig orsak till kolorektal cancer.

The concept that serrated polyps can cause colorectal cancer is relatively new and not very well-known. Serrated polyps are difficult to identify and treat endoscopically. This together with the fact that premalignant serrated polyps are mainly located in the proximal colon might help explain why colonoscopy is less effective against right-sided compared to left-sided colorectal cancers and why interval cancers usually appear in the proximal colon. In fact, serrated polyps may cause up to one third of all sporadic colorectal cancers. In spite of this, the aetiology, incidence, prevalence and natural history of serrated polyps remains elusive. Endoscopists and pathologists must have a good understanding of serrated polyps in order to effectively diagnose, treat and follow up these lesions. This review focuses on the pathophysiology, types, work-up, treatment and follow-up of serrated polyps in the colon and rectum.

Cystic neuroendocrine tumor in the pancreas detected by endoscopic ultrasound and fine-needle aspiration: a case report.

BACKGROUND: Pancreatic neuroendocrine tumors are typically solid neoplasms but in very rare cases present as cystic lesions. The diagnosis of cystic tumors in the pancreas is extremely difficult and the use of endoscopic ultrasound and fine-needle aspiration might be helpful in the work-up of patients with cystic neuroendocrine tumors in the pancreas. CASE PRESENTATION: A 78-year-old Caucasian man was admitted with a history of epigastric pain. Laboratory tests were normal. The patient underwent transabdominal ultrasound, computed tomography and magnetic resonance cholangiopancreatography demonstrating an unclear cystic mass in the head of the pancreas. The patient was referred for endoscopic ultrasound. Endoscopic ultrasound showed a hypoechoic lesion (42 × 47 mm) in the head of the pancreas with regular borders and large cystic components. The main pancreatic duct was normal without any connection to the cystic process. The lesion underwent fine-needle aspiration (22 Gauge). Cytological examination demonstrated cohesive groups of plasmacytoid cells staining positively for synaptophysin and chromogranin A, which is suggestive of a neuroendocrine tumor. CONCLUSIONS: Differential diagnosis of cystic lesions in the pancreas is very difficult with conventional radiology, such as computed tomography and magnetic resonance imaging. This unusual case with a pancreatic cystic neuroendocrine tumor highlights the clinical importance of endoscopic ultrasound in the work-up of patients with unclear lesions in the pancreas.

Change in cell death markers during (177)Lu-mAb radioimmunotherapy-induced rejection of syngeneic rat colon carcinoma.

PURPOSE: To monitor cell death in tumors during the rejection process after treatment with an antibody radiolabeled with a ß-emitter. METHODS: Tumors during rejection after treatment with (177)Lu-labeled antibody BR96 and after administration of unlabeled BR96 were compared with untreated tumors from the same immunocompetent syngeneic rat tumor model. Cell death was monitored with the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical staining of activated caspase-3 and γH2AX. These data were evaluated together with histopathological morphology, BR96-binding antigen expression, and (177)Lu radioactivity distribution imaged by digital autoradiography. RESULTS: The untreated tumors showed staining for all the markers, mainly in and around the necrotic areas. One to 2 days p.i. large areas were stained with anti-γH2AX, followed by a slight decrease. Staining of activated caspase-3 was intense and extensive 1-2 days p.i., while found in and around necrotic areas 3-8 days p.i. TUNEL staining was similar to activated caspase-3 staining 1-2 days p.i. but more extensive than activated caspase-3 staining 3-4 days p.i. Digital autoradiography revealed activity concentration in granulation tissue from 1 day p.i. CONCLUSION: Following radioimmunotherapy in an immunocompetent syngeneic colon carcinoma model, tumor cells did not only die through caspase-3-dependent apoptosis, but also by other mechanisms.

Dendritic fibromyxolipoma adherent to the median nerve in the forearm.

We describe a 65-year-old woman with a tumour adherent to the median nerve in the left forearm that was found to be a dendritic fibromyxolipoma, a distinctive benign soft tissue lesion possibly related to a myxoid spindle cell lipoma; it is a solitary fibrous tumour that may be mistaken for a sarcoma. The tumour was successfully excised with no complications.

Human papillomavirus type-specific risk of cervical cancer in a population with high human immunodeficiency virus prevalence: case-control study.

There are limited data on human papillomavirus (HPV) type-specific cervical cancer risk among human immunodeficiency virus (HIV)-positive women. Previous studies have suggested that HPV 16 would be relatively less important as a causative agent among HIV-positive compared with HIV-negative women. This study investigates HPV type-specific cervical cancer risk in a population in which HIV is endemic. At the Central Hospital, Maputo, Mozambique, 221 cervical cancer cases and 203 hospital-based controls were consecutively enrolled. HPV typing from cervical samples, HIV testing and recording of socio-demographic factors were performed. Logistic regression modelling was used to assess HPV type-specific risk and effect modification between HIV and HPV infection. Infection with HPV 16, 18 and 'high-risk non-HPV 16/18 types' (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) was associated with cervical cancer in both crude and adjusted analyses. HPV 16 and 18 were the most common types detected in cancer biopsies among both HIV-negative and HIV-positive women. There was no significant evidence of effect modification between any HPV type and HIV infection, and there were no significant differences in the HPV type-specific prevalence when cervical cancers among HIV-positive and HIV-negative women were compared. Within the limitations of the study, the relative importance of different HPV types in cervical carcinogenesis appears not to be modified greatly by HIV infection, suggesting that HPV vaccines might not need to be type-specifically modified to be suitable for populations where HIV is endemic.

Breast tomosynthesis: Accuracy of tumor measurement compared with digital mammography and ultrasonography.

BACKGROUND: Mammographic tumor size measurement can be difficult because breast structures are superimposed onto a two-dimensional (2D) plane, potentially obscuring the tumor outline. Breast tomosynthesis (BT) is a 3D X-ray imaging technique in which low-dose images are acquired over a limited angular range at a total dose comparable to digital mammography (DM). These low-dose images are used to mathematically reconstruct a 3D image volume of the breast, thus reducing the problem of superimposed tissue. PURPOSE: To investigate whether breast cancer size can be more accurately assessed with breast tomosynthesis than with digital mammography and ultrasonography (US), by reducing the disturbance effect of the projected anatomy. MATERIAL AND METHODS: A prototype BT system was used. The main inclusion criterion for BT examination was subtle but suspicious findings of breast cancer on 2D mammography. Sixty-two women with 73 breast cancers were included. BT, DM, and US sizes were measured independently by experienced radiologists without knowledge of the pathology results, which were used as reference. RESULTS: The tumor outline could be determined in significantly more cases with BT (63) and US (60) than DM (49). BT and US size correlated well with pathology (R=0.86 and R=0.85, respectively), and significantly better than DM size (R=0.71). Accordingly, staging was significantly more accurate with BT than with DM. CONCLUSION: The study indicates that BT is superior to DM in the assessment of breast tumor size and stage.

Dietary supplementation with carbonate increases expression of ornithine decarboxylase and proliferation in gastric mucosa in a rat model of gastric cancer.

Dietary factors play essential roles in gastric carcinogenesis. We recently found that dietary supplementation with NaHCO(3) significantly increased the development of gastric cancer in a rat gastric stump model. Here, we analysed nontransformed gastric mucosa for expression of the cancer-related proteins cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC), and we examined the relationship between expression levels of those proteins and mucosal proliferation. Research has shown that COX-2 is upregulated in gastric mucosal inflammation and is strongly associated with gastrointestinal cancer. ODC is the key enzyme in polyamine synthesis and a regulator of cell proliferation. We performed gastric resections on 48 Wistar rats to induce spontaneous gastric cancer; half of these animals were given a normal diet, and the other half received a diet supplemented with NaHCO(3). Twenty-four unoperated rats served as a control group. The surgical procedure per se led to a significant rise in mucosal expression of COX-2 and an associated increase in cell proliferation. However, the COX-2 level in gastric mucosa was not further affected by dietary supplementation of carbonate. Interestingly, nontransformed gastric mucosa in the operated rats receiving a carbonate-supplemented diet showed a pronounced increase in ODC expression that was strongly correlated with a further enhanced cell proliferation. These results indicate that carbonate ions, which represent a major constituent of intestinal reflux into the stomach, increase the expression of ODC and thereby enhance cell proliferation in nontransformed mucosa, and consequently elevate the risk of gastric cancer.

Human papillomavirus genotypes in cervical cancers in Mozambique.

The distribution of human papillomavirus (HPV) types in cervical cancers is essential for design and evaluation of HPV type-specific vaccines. To follow up on a previous report that HPV types 35 and 58 were the dominant HPV types in cervical neoplasia in Mozambique, the HPV types in a consecutive case series of 74 invasive cervical cancers in Mozambique were determined. The most common worldwide major oncogenic HPV types 16 and 18 were present in 69 % of cervical cancers, suggesting that a vaccine targeting HPV-16 and -18 would have a substantial impact on cervical cancer also in Mozambique.

PACAP is expressed in secretory granules of insulin and glucagon cells in human and rodent pancreas. Evidence for generation of cAMP compartments uncoupled from hormone release in diabetic islets.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an islet neuropeptide with potent insulinotropic action. The current study investigates PACAP expression in normal human and rat pancreatic islets, and whether it is altered in diabetic state. To that end, PACAP immunoreactivity was studied by immunofluorescence methods enhanced by the catalyzed reporter deposition (CARD) technique. Insulin and cyclic adenosine monophosphate (cAMP) generation induced by PACAP were investigated in islets isolated from the spontaneously diabetic Goto-Kakizaki (GK) rat. PACAP immunoreactivity was observed in virtually all insulin and glucagon cells in both species, but not in somatostatin or pancreatic polypeptide (PP) cells; this co-localization pattern was unaltered in diabetic pancreata. In normal human pancreas, PACAP was further localized ultrastructurally to the secretory granules of insulin and glucagon cells. PACAP significantly potentiated glucose-stimulated insulin release in isolated islets of normal but not of GK rats. PACAP failed to enhance cAMP generation in normal islets, but induced approximately 5-folds exaggeration in the diabetic islets. In conclusion, using improved immunocytochemistry techniques and electron microscopy (EM), PACAP was shown to be expressed both in normal and diabetic islet cells and localized to secretory granules of insulin and glucagon cells. Furthermore, the insulinotropic action of PACAP was markedly impaired in diabetic islets in spite of exaggerated cAMP response.

Intermediate thyroid carcinoma in humans and ultimobranchial tumors in bulls: A comparative morphological and immunohistochemical study.

The intermediate type of thyroid carcinoma in humans has been defined as having characteristics of both follicular and parafollicular cell carcinoma. The ultimobranchial (UB) body in mammals is believed to harbor stem cells capable of developing both follicular and parafollicular cells. Hyperplastic and neoplastic lesions of the UB remnants and of the parafollicular cell system frequently occur in bulls. Such lesions, found in 64 individuals (6%) derived from an autopsy material of 1,101 bulls, have been compared structurally and immunohistochemically with 18 human cases of thyroid carcinoma of the intermediate type, in order to define their possible biological relationship. UB changes in bulls formed a continuum ranging from hyperplastic nodules to gross tumors. They contained all epithelial components present in the normal UB remnants in cattle: UB cysts and tubules and solid nests of small basophilic immature cells, which were immunocytochemically indifferent, as wellas mature follicular and neuroendocrine cells. The indifferent cell component dominated in most bull tumors; a minority were mainly formed by mature follicular or parafollicular cells. Human tumors resembled the bull UB tumors structurally and immunohistochemically, although generally the degree of maturation was higher in human tumors. A few were mainly formed by indifferent immature cells and contained typical UB cysts and tubules. One bull tumor and one human tumor contained amyloid. UB changes in bulls were invariably associated with a marked hyperplasia of the parafollicular cell system, in some cases even with tumor development. A similar hyperplasia, but without neoplastic change, was found in 4 of 11 human cases in which nontumorous thyroid parenchyma was available for examination.The findings suggest that intermediate thyroid carcinoma rather than medullary carcinoma is the human equivalent to the bull UB tumors. It is concluded that although both the medullary and the intermediate type of carcinoma appear to be histogenetically related to the UB body, the former shows evidence of a pure parafollicular cell differentiation, whereas the latter develops both follicular and parafollicular, as well as intermediate, cell forms and sometimes also immature structures of the type seen in UB remnants of the adult human thyroid gland.