The pathology of ductal-type pancreatic carcinomas and pancreatic intraepithelial neoplasia: Insights for clinicians

The phenotypic classification of pancreatic neoplasms is based on their cellular lineage. Thus, tumors with a ductal, acinar, and endocrine phenotype can be distinguished. Most pancreatic neoplasms show a ductal phenotype and can be classified as ductal adenocarcinomas. Less common tumors with a ductal phenotype are the variants of ductal adenocarcinoma, intraductal papillary mucinous neoplasm (including colloid carcinoma), mucinous cystic neoplasm, medullary carcinoma, and other rare tumors. Ductal adenocarcinomas most likely develop from ductal proliferative lesions arising in the pancreatic duct system. A recently adopted classification system for these lesions distinguishes between three grades of pancreatic intraepithelial neoplasia (PanIN). Molecular studies have revealed that PanIN-2 and PanIN-3 lesions represent a distinct step toward invasive carcinoma.     

Mechanisms of Action and Resistance of Somatostatin Analogues for the Treatment of Hepatocellular Carcinoma: A Message Not Well Taken

Somatostatin (SST) acts as an inhibitory peptide of various secretory and proliferative processes. Apart from neuroendocrine tumors, where SST analogues have an established role, they have been tested in other tumors such as hepatocellular carcinoma (HCC) in the view of the fact that chemotherapy is not working. Several positive reports have been published. Approximately 40% of patients respond with improved survival and an impressive quality of life. A usual misunderstanding in trial designs is that, although SST is not a rescue drug, selection of patients is inappropriate, with mostly moribund patients being recruited. SST analogues do not seem to work in 60% of HCCs and this has been linked to the presence of SST receptors (SSTR) in the tumor, while several resistance mechanisms might be involved. Future management should engage more specific SST analogues targeted to a tumor with a known SSTR map. The use of somatostatin analogues as an adjunct therapy in combination with other treatment modalities should also be investigated.     

Identification of hemoglobin Q India (α 1–64 Asp–His) through ARMS-PCR. First report from Pakistan

Various hemoglobinopathies have been reported from Pakistan excepting the rare ones like hemoglobin Q India. Our purpose of study was to identify the mutation (α 1 64 aspartate to histidine) through amplification restriction mutation system-polymerase chain reaction (ARMS-PCR) in patients where hemoglobin Q has been detected via high performance liquid chromatography (HPLC) and also to evaluate the cost effectiveness of the two technologies. All patients irrespective of age and gender who underwent HPLC for identification of their hemoglobin variant during January 1, 2006 to January 30, 2007 were studied. The blood samples with unknown peak at a retention time of 4.7 min were evaluated at the molecular level. Analysis of HPLC tracings of 11,008 subjects over a thirteen-month period identified ten individuals with hemoglobin Q. Male to female ratio was 1:1.5 and their age was variable ranging from 1 to 49 (mean 22.8) years. The mean hemoglobin level was 11.3 g/dl while MCV (fl) and MCH (pg) were 73.0 and 20.8 respectively. HPLC showed an unknown peak of 17.7% which was detected as Hb Q. ARMS based PCR showed Hb Q specific product of 370 bp and also an amplified product of 766 bp as the control fragment in these samples. This is the first ever report that documents the presence of Hb Q India (α 64 Asp to His) in Pakistani population. We recommend that HPLC be used as a useful screening tool especially in developing countries where PCR facilities may not be accessible.     

Effect of Acarbose on Vascular Disease in Patients with Abnormal Glucose Tolerance

INTRODUCTION: Excessive postprandial (pp) glucose excursion in people with IGT and type 2 diabetes is associated with a cascade of proatherogenic events. Acarbose, a potent competitive inhibitor of alpha-glucosidases of the small intestine specifically reduces pp hyperglycemia with an average reduction of HbA1c by 0.8% in Cochrane metaanalysis. This is associated with pleiotropic effects on a broad spectrum of cardiovascular (CV) risk factors: reduction of overweight, lowering of blood pressure, triglycerides, hsCRP, fibrinogen and other biomarkers of low grade inflammation. RESULTS AND DISCUSSION: Flow mediated vasodilation was improved and progression of intima media thickness was reduced by acarbose. In the STOP-NIDDM trial in people with IGT acarbose decreased the incidence of diabetes by 36%. The STOP-NIDDM trial with CV events as secondary objective is the only intervention trial in people with IGT so far with a significant benefit for CV disease inclusive hypertension. In a metaanalysis of controlled studies (MeRIA) in patients with type 2 diabetes, treatment with acarbose was associated with a 64% lower rate of myocardial infarction and 35% less CV events. CONCLUSION: Thus results so far available prove that acarbose is an effective and safe drug to treat abnormal glucose tolerance. They suggest that acarbose can help to control a broad spectrum of CV risk factors and may prevent CV disease.     

Multilocular cystic renal cell carcinoma: an experience of clinical management for 31 cases

In order to increase our knowledge and understanding about multilocular cystic renal cell carcinoma (MCRCC), including diagnosis, surgical management, pathologic and prognostic characteristics, clinical data of patients who suffered with MCRCC were reviewed retrospectively. From 1998 to 2005, among 770 patients diagnosed with renal cell carcinoma (RCC) at our institute, 31 cases (4.0%) were identified as MCRCC. The average age of patients suffered with RCC and MCRCC was 58.1 ± 3.6 and 45.9 ± 2.7, respectively (P < 0.01), whereas the gender ratio of male to female in RCC and MCRCC is 2.12:1 and 2.88:1(P < 0.01). Surprisingly, 28 of those 31 renal masses (90.3%) were first discovered on the radiographic image, and the size of tumors in maximum diameter ranged from 1.7 to 11.0 cm (mean 4.1 ± 2.2 cm). All those patients were treated with open nephrectomy, including 21 radical and 10 partial. The stages of tumor were classified as pT1N0M0, pT2N0M0, and pT3bN0M0 following the 1997 criteria of tumor-node-metastasis (TNM) classification in the number of 27(87.1%), 3(9.7%) and 1(3.2%), respectively. By contrast, according to the tumor nuclear grading system, those tumors were classified as Grades 1 and 2 in 13 (42%) and 18 patients (58%), respectively. Only 29 cases from those patients have been followedup for a period of 9 to 81 months so far (mean 32.6 ± 11), while no tumor recurrence occurred except for 1 case who died of causes other than MCRCC. In general, MCRCC is a frequent subtype of RCC in the clinic. A nephron-sparing procedure should be considered in the preoperative plan when a complex multicystic renal mass with enhanced density is observed.     

The Effect of Processing on Liver Biopsy Core Size

OBJECTIVES: Liver biopsy is a valuable clinical tool, but for the interpretation to be meaningful a certain core size should be obtained. This study examines the changes the liver biopsy core undergoes during processing steps. METHODS: A total of 61 consecutive percutaneous liver biopsies were obtained between November 2004 and April 2005. The needle type utilized was the 16-gauge automatic tru-cut. A measurement was made while each liver biopsy core specimen resided in the cartridge, then a measurement was made with the core placed on the tray, and a final measurement was made after the pathologist received the formalin-fixed specimen. RESULTS: The mean size of the biopsy core in the cartridge measured 15 +/- 2 mm, compared to a mean size on the tray of 19.6 +/- 3.5 mm, and a mean size after fixation of 18.3 mm. All mean sizes were statistically different from one another. The compressive effect of the cartridge was 23%. The shrinkage effect of formalin fixation was 7%. CONCLUSIONS: The liver biopsy core size changes significantly through the processing steps. It is imperative that the operator is aware of these changes so that appropriate decisions are made. As an example, if the operator underestimates the core size when measured in the cartridge, a second pass may be completed when in fact adequate tissue had been obtained on the first pass.     

Update on therapeutic options for <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-related diseases

Triple therapy including clarithromycin, amoxicillin, and a proton pump inhibitor (PPI) has been recommended as the treatment of choice for Helicobacter pylori eradication. This regimen is now challenged by an increasing level of clarithromycin resistance that jeopardizes the treatment success. When clarithromycin resistance has been detected, or when its rate is known to be high in the geographic area, this drug cannot be used. It can be replaced by metronidazole, the resistance of which has a limited clinical relevance. Another option is to prescribe tetracycline and metronidazole with a PPI or ranitidine bismuth citrate. New antibiotics such as levofloxacin or rifabutin can also be used in combination with amoxicillin and a PPI. Probiotics can be added to all of these regimens to improve compliance by decreasing adverse events. But some authors advocate a quadruple therapy as a first-line treatment. Solutions to improve the limitations of this last regimen are now being proposed. Clarification of the controversial treatment indications such as gastroesophageal reflux disease or prevention of nonsteroidal anti-inflammatory drug gastroduodenal symptoms has been made. The question of prevention of gastric carcinoma by H. pylori eradication remains unanswered.