Iliac-hepatic arterial bypass for compromised collateral flow during modified Appleby operation for advanced pancreatic cancer

Involvement of the celiac trunk and common hepatic artery are two of the most common forms of vascular invasion by tumours of the distal pancreas, and until recently this finding was considered a contra-indication to resection. We described a modified Appleby operation for locally advanced distal pancreatic cancer with compromised hepatic collateral flow that needed hepatic arterial revascularization, successfully accomplished by left external iliac-hepatic arterial bypass with Dacron prosthesis. Patient recovery was uneventful and he was discharged on the 10th postoperative day. Postoperative angio-CT disclosed a patent arterial bypass. Patient is well and asymptomatic 13 months after operation. At the time of this writing, postoperative CT scan showed no evidence of disease and CA 19-9 level is normal. There is a well established rationale to perform extended resection of pancreatic carcinomas that compromise vascular structures. Modified Appleby procedure can safely be performed, has oncological advantages to palliative procedures and provides relief of pain but is reserved for selected patients. Preservation of hepatic arterial flow has utmost importance to avoid hepatobiliary complications as liver necrosis, liver abscess, gallbladder necrosis or cholecystitis. In this case, hepatic revascularization was particularly challenging, but was successfully accomplished by left external iliac-hepatic arterial bypass. To our knowledge this type of arterial bypass has never been described so far in the English literature and its description may be important for surgeons dealing with advanced pancreatic cancer. (C) 2009 Elsevier Ltd. All rights reserved.

Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of a2b1 Integrin and E-Cadherin Function

In our previous studies we have described that ST3Gal III transfected pancreatic adenocarcinoma Capan-1 and MDAPanc-28 cells show increased membrane expression levels of sialyl-Lewis x (SLex) along with a concomitant decrease in α2,6-sialic acid compared to control cells. Here we have addressed the role of this glycosylation pattern in the functional properties of two glycoproteins involved in the processes of cancer cell invasion and migration, α2β1 integrin, the main receptor for type 1 collagen, and E-cadherin, responsible for cell-cell contacts and whose deregulation determines cell invasive capabilities. Our results demonstrate that ST3Gal III transfectants showed reduced cell-cell aggregation and increased invasive capacities. ST3Gal III transfected Capan-1 cells exhibited higher SLex and lower α2,6-sialic acid content on the glycans of their α2β1 integrin molecules. As a consequence, higher phosphorylation of focal adhesion kinase tyrosine 397, which is recognized as one of the first steps of integrin-derived signaling pathways, was observed in these cells upon adhesion to type 1 collagen. This molecular mechanism underlies the increased migration through collagen of these cells. In addition, the pancreatic adenocarcinoma cell lines as well as human pancreatic tumor tissues showed colocalization of SLex and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of α2β1 integrin and E-cadherin appear to influence the functional role of these two glycoproteins supporting the role of these glycans as an underlying mechanism regulating pancreatic cancer cell adhesion and invasion

Cryptosporidiosis of the biliary tract mimicking pancreatic cancer in an AIDS patient

Diarrhea caused by Cryptosporidium sp is frequent in patients with AIDS, but involvement of other organs of the digestive tract is uncommon. We report a case of Cryptosporidium-associated obstruction of the biliary tract mimicking cancer of the head of the pancreas in a 43-year-old woman with AIDS.

Avaliação in vitro da eficácia de produtos homeopáticos contendo momordica charantia através de bioensaios

Homeopathic medicines have been used for over two hundred years without the examination of their effects on in vivo and in vitro assays, due to the peculiarity of homeopathic preparations, the high dilution, which creates a challenge for the use of usual analytical techniques of quality control of medicine.Although there is scarcity of literature and variety of experiments, recently there have been some studies with few in vitro assays which have shown positive responses when evaluating the mechanism of action of homeopathic medicines which are able to act on a specific system.The present study aims to evaluate the efficacy of homeopathic products containing Momordica charantia through bioassays.Homeopathic products were tested by the MTT to assess cytotoxicity in RAW 264.7 (macrophage-like cells) and in tumor cells HeLa (human cervical adenocarcinoma cells), CHO K1 (Chinese hamster ovary cells), PANC-1 (human pancreas cancer cells) and PC-3 (human prostate cancer cells), dosage of inflammatory mediators NO, TNF-α and IL-6 released by RAW 264.7 cells, analysis of the death process and cell cycle changes of PC-3 by flow cytometry. The data demonstrate that homeopathic products of Momordica charantia did not show cytotoxicity to RAW 264.7, increased the production of inflammatory mediators by RAW 264.7 synergistically with LPS, showed cytotoxicity to PC-3 with change in its cell cycle inhibiting its proliferation, being the 30CH the most potent sample. Correlation studies were conducted in order to evaluate the possible in vitro applicable models to the quality control of homeopathic products with Momordica charantia. The data showed that the best applicable models in assessing the quality are the MTT to assess cytotoxicity in RAW 264.7 and PC-3 in 24 hours for Momordica charantia fruit products and dosage of NO production by RAW 264.7 with and without LPS

Robotic Resection of Intraductal Neoplasm of the Pancreas

Background: Minimally invasive techniques have been revolutionary and provide clinical evidence of decreased morbidity and comparable efficacy to traditional open surgery. Computer-assisted surgical devices have recently been approved for general surgical use. Aim: The aim of this study was to report the first known case of pancreatic resection with the use of a computer-assisted, or robotic, surgical device in Latin America. Patient and Methods: A 37-year-old female with a previous history of radical mastectomy for bilateral breast cancer due to a BRCA2 mutation presented with an acute pancreatitis episode. Radiologic investigation disclosed an intraductal pancreatic neoplasm located in the neck of the pancreas with atrophy of the body and tail. The main pancreatic duct was enlarged. The surgical decision was to perform a laparoscopic subtotal pancreatectomy, using the da Vinci (R) robotic system (Intuitive Surgical, Sunnyvale, CA). Five trocars were used. Pancreatic transection was achieved with vascular endoscopic stapler. The surgical specimen was removed without an additional incision. Results: Operative time was 240 minutes. Blood loss was minimal, and the patient did not receive a transfusion. The recovery was uneventful, and the patient was discharged on postoperative day 4. Conclusions: The subtotal laparoscopic pancreatic resection can safely be performed. The da Vinci robotic system allowed for technical refinements of laparoscopic pancreatic resection. Robotic assistance improved the dissection and control of major blood vessels due to three-dimensional visualization of the operative field and instruments with wrist-type end-effectors.

Metabolic activation of aromatic amines by human pancreas

Epidemiologic studies have suggested that aromatic amines (and nitroaromatic hydrocarbons) may be carcinogenic for human pancreas, Pancreatic tissues from 29 organ donors (13 smokers, 16 non-smokers) were examined for their ability to metabolize aromatic amines and other carcinogens, Microsomes showed no activity for cytochrome P450 (P450) 1A2-dependent N-oxidation of 4-aminobiphenyl (ABP) or for the following activities (and associated P450s): aminopyrine N-demethylation and ethylmorphine N-demethylation (P450 3A4); ethoxyresorufin O-deethylation (P450 1A1) and pentoxyresorufin O-dealkylation (P450 2B6); p-nitrophenol hydroxylation and N-nitrosodimethylamine N-demethylation (P450 2E1); lauric acid omega-hydroxylation (P450 4A1); and 4-(methylnitrosamino)-1-(3-pyridyl-1-butanol) (NNAL) and 4-(methylnitrosamino)1-(3-pyridyl)-1-butanone (NNK) alpha-oxidation (P450 1A2, 2A6, 2D6). Antibodies were used to examine microsomal levels of P450 1A2, 2A6, 2C8/9/18/19, 2E1, 2D6, and 3A3/ 4/5/7 and epoxide hydrolase. Immunoblots detected only epoxide hydrolase at low levels; P450 levels were <1% of liver. Microsomal benzidine/prostaglandin hydroperoxidation activity was low. In pancreatic cytosols and microsomes, 4-nitrobiphenyl reductase activities were present at levels comparable to human liver. The O-acetyltransferase activity (AcCoA-dependent DNA-binding of [H-3]N-hydroxy-ABP) of pancreatic cytosols was high, about two-thirds the levels measured in human colon. Cytosols showed high activity for N-acetylation of p-aminobenzoic acid, but not of sulfamethazine, indicating that acetyltransferase-1 (NAT1) is predominantly expressed in this tissue. Cytosolic sulfotransferase was detected at low levels. Using P-32-post-labeling enhanced by butanol extraction, putative arylamine-DNA adducts were detected in most samples. Moreover, in eight of 29 DNA samples, a major adduct was observed that was chromatographically identical to the predominant ABP-DNA adduct, N-(deoxyguanosin-8-yl)-ABP. These results are consistent with a hypothesis that aromatic amines and nitroaromatic hydrocarbons may be involved in the etiology of human pancreatic cancer.

Acinar cell carcinoma of the pancreas: is the absence of neuroendocrine component related to a more malignant behavior?

Background/Aims: Acinar cell carcinomas are uncommon malignant tumors of the pancreas, accounting for 1-2% of all the cases of exocrine pancreatic tumor. Some authors have estimated acinar cell tumors to be as aggressive as ductal adenocarcinoma of the pancreas whereas other series showed acinar cell tumors to have a favorable clinical outcome. This discrepancy in prognosis may be related to the cellular components of the tumor. Methodology: With the aim to evaluate the possible relationship between the presence of neuroendocrine differentiation and behavior of these tumors, the authors reviewed all patients presenting acinar cell carcinoma of the pancreas in the last 5 years with emphasis in the immunohistochemical evaluation. Results: Four patients presented neuroendocrine differentiation on immunohistochemical evaluation and had a more benign outcome. Two patients without neuroendocrine component had a disseminated disease at presentation. This data suggests that this tumor is less aggressive than ductal adenocarcinoma and even with nodal involvement, long term survival after complete resection can be achieved. Conclusions: It is possible that the absence of neuroendocrine component may be related to a less favorable outcome and adjuvant therapy may be necessary. Due to the rarity of this pancreatic tumor, this relationship remains to be confirmed with a multicentric study including a larger number of patients.

Frequency and prognostic relevance of cancer testis antigen 45 expression in multiple myeloma

Objective. This study aims to analyze the expression of cancer testis antigen 45 (CT45) in normal tissues and in plasma cell disorders and to identify possible associations with clinical data and prognosis in multiple myeloma (MM) patients. Materials and Methods. Expression of CT45 was studied in 20 normal tissues (testis, placenta, skeletal muscle, bladder, lung, spleen, heart, brain and fetal brain, thymus, uterus, stomach, mammary gland, pancreas, prostate, small intestine, kidney, adrenal gland, spinal cord, colon, and one pool of 10 normal bone marrow samples) and bone marrow aspirates from 3 monoclonal gammopathies of undetermined significance, 5 solitary plasmacytomas, 61 newly diagnosed MM patients and MM cell line U266 by reverse transcriptase polymerase chain reaction. Results. CT45 was positive in 3 of 20 (15%) normal tissues tested: lung, brain (both fetal and adult), and spinal cord. Among monoclonal gammopathies, CT45 was positive in 2 of 5 (40%) solitary plasmacytomas bone marrow aspirates, 10 of 61 (16%) MM bone marrow aspirates, and in the U266 MM cell line. Conclusions. We did not find associations between bone marrow histology and CT45 expression. However, we demonstrated for the first time that positive expression of CT45 was associated with poor prognostic (international Staging System) and poor outcomes in MM patients, meaning that CT45-positive cases presented seven times more chance of worse evolution than the negative ones. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

Human trypsinogen in colorectal cancer

Trypsinogen (TRY), the precursor to the serine protease trypsin, is found in the pancreas and mediates digestive proteolysis in the small intestine. Differential display of cDNAs expressed by human colorectal tumor tissues compared with adjacent normal colonic mucosa identified an isoform of TRY (TRY2) up-regulated in colorectal cancers. Northern blot analysis of RNA isolated from a series of 28 malignant colon tumors and corresponding normal mucosa showed that TRY transcripts were up-regulated 2- to 33-fold in 29% of tumors. Further, TRY mRNA was expressed in 6 colorectal cancer cell lines, with highest levels detected in the metastatic tumor lines SW620 and HT29. Immunostaining for TRY protein expression showed intense immunoreactivity in the supranuclear cytoplasm of colon tumors in 16% of tissue specimens. To evaluate the relative contributions of 2 isoforms of TRY, TRY1 and TRY2, to total TRY mRNA expression, a semiquantitative multiplex RT-PCR assay was developed. TRY2 mRNA was detected in all 6 colorectal tumor cell lines, whereas TRY1 mRNA was expressed only in the metastatic tumor lines, showing that the high levels of TRY expression in the metastatic tumor lines are likely due to up-regulation of TRY1. Evaluation of TRY1 and TRY2 mRNA expression by multiplex RT-PCR in a series of 20 colon tumor tissues representative of the range of tumor progression showed that TRY2 mRNA was expressed much more commonly than TRY1 mRNA in normal mucosa (26% vs. 6%) as well as in primary tumor tissues (65% vs. 15%). These data demonstrate that TRY2 is the dominant TRY in colon tissue and suggest that up-regulation of TRY1 expression in colon tumors may be associated with a metastatic phenotype. (C) 2001 Wiley-Liss, Inc.

Cryptosporidiosis of the biliary tract mimicking pancreatic cancer in an AIDS patient

Diarrhea caused by Cryptosporidium sp is frequent in patients with AIDS, but involvement of other organs of the digestive tract is uncommon. We report a case of Cryptosporidium-associated obstruction of the biliary tract mimicking cancer of the head of the pancreas in a 43-year-old woman with AIDS.

The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development.

Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers and a lifelong neutralizing Ab response. We show that removal of the draining lymph node after establishment of the germinal center reaction led to complete loss of neutralizing Abs despite comparable infection levels in peripheral lymphocytes. Importantly, in the absence of neutralization, only the exocrine organs mammary gland, salivary gland, pancreas, and skin showed strikingly increased infection, resulting in accelerated mammary tumor development. Induction of stronger neutralization did not influence chronic infection levels of peripheral lymphoid organs but strongly inhibited mammary gland infection and virus transmission to the next generation. Taken together, we provide evidence that a tight equilibrium in virus neutralization allows limited infection of exocrine organs and controls cancer development in susceptible mouse strains. These experiments show that a strong neutralizing Ab response induced after infection is not able to control lymphoid MMTV infection. Strong neutralization, however, is capable of blocking amplification of mammary gland infection, tumor development, and virus transmission to the next generation. The results also indicate a role of neutralization in natural resistance to MMTV infection.

Cruciferous vegetables and cancer risk in a network of case-control studies.

Background Cruciferous vegetables have been suggested to protect against various cancers, though the issue is open to discussion. To further understand their role, we analyzed data from a network of case-control studies conducted in Italy and Switzerland. Patients and methods The studies included a total of 1468 cancers of the oral cavity/pharynx, 505 of the esophagus, 230 of the stomach, 2390 of the colorectum, 185 of the liver, 326 of the pancreas, 852 of the larynx, 3034 of the breast, 367 of the endometrium, 1031 of the ovary, 1294 of the prostate, 767 of the kidney, and 11 492 controls. All cancers were incident, histologically confirmed; controls were subjects admitted to the same network of hospitals as cases for a wide spectrum of acute nonneoplastic conditions. Results The multivariate odds ratio (OR) for consumption of cruciferous vegetables at least once a week as compared with no/occasional consumption was significantly reduced for cancer of the oral cavity/pharynx (OR = 0.83), esophagus (OR = 0.72), colorectum (OR = 0.83), breast (OR = 0.83), and kidney (OR = 0.68). The OR was below unity, but not significant, for stomach (OR = 0.90), liver (OR = 0.72), pancreatic (OR = 0.90), laryngeal (OR = 0.84), endometrial (OR = 0.93), ovarian (OR = 0.91), and prostate (OR = 0.87) cancer. Conclusion This large series of studies provides additional evidence of a favorable effect of cruciferous vegetables on several common cancers.

N-3 fatty acids, cancer and cachexia: a systematic review of the literature.

Use of n-3 fatty acids (FA) has been reported to be beneficial for cancer patients. We performed a systematic review of the literature in order to issue recommendations on the clinical use of n-3 FA in the cancer setting. A systematic search was performed in MEDLINE, EMBASE, Cochrane and Healthstar databases. We selected clinical trials or prospective observational studies including patients with cancer and life expectancy >2 months, in which enteral supplements with n-3 FA were administered. Parameters evaluated individually were clinical (nutritional status, tolerance, survival and hospital stays), biochemical (inflammatory mediators), and functional (functional status, appetite and quality of life (QoL)). Seventeen studies met the inclusion criteria; eight were of high quality. The panel of experts established the following evidence: (1) oral supplements with n-3 FA benefit patients with advanced cancer and weight loss, and are indicated in tumours of the upper digestive tract and pancreas; (2) the advantages observed were: increased weight and appetite, improved QoL, and reduced post-surgical morbidity; (3) there is no defined pattern for combining different n-3 FA, and it is recommended to administer > 1.5 g/day; and (4) better tolerance is obtained administering low-fat formulas for a period of at least 8 weeks. All the evidences were grade B but for 'length of treatment' and 'advantage of survival' it was grade C. Our findings suggest that administration of n-3 FA (EPA and DHA) in doses of at least 1.5 g/day for a prolonged period of time to patients with advanced cancer is associated with an improvement in clinical, biological and QoL parameters.

European cancer mortality predictions for the year 2013.

Background Estimated cancer mortality statistics were published for the years 2011 and 2012 for the European Union (EU) and its six more populous countries. Patients and methods Using logarithmic Poisson count data joinpoint models and the World Health Organization mortality and population database, we estimated numbers of deaths and age-standardized (world) mortality rates (ASRs) in 2013 from all cancers and selected cancers. Results The 2013 predicted number of cancer deaths in the EU is 1 314 296 (737 747 men and 576 489 women). Between 2009 and 2013, all cancer ASRs are predicted to fall by 6% to 140.1/100 000 in men, and by 4% to 85.3/100 000 in women. The ASRs per 100 000 are 6.6 men and 2.9 women for stomach, 16.7 men and 9.5 women for intestines, 8.0 men and 5.5 women for pancreas, 37.1 men and 13.9 women for lung, 10.5 men for prostate, 14.6 women for breast, and 4.7 for uterine cancer, and 4.2 and 2.6 for leukaemia. Recent trends are favourable except for pancreatic cancer and lung cancer in women. Conclusions Favourable trends will continue in 2013. Pancreatic cancer has become the fourth cause of cancer death in both sexes, while in a few years lung cancer will likely become the first cause of cancer mortality in women as well, overtaking breast cancer.

European cancer mortality predictions for the year 2014.

BACKGROUND: From most recent available data, we projected cancer mortality statistics for 2014, for the European Union (EU) and its six more populous countries. Specific attention was given to pancreatic cancer, the only major neoplasm showing unfavorable trends in both sexes. PATIENTS AND METHODS: Population and death certification data from stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukemias and total cancers were obtained from the World Health Organisation database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected 2014 numbers of deaths by age group were obtained by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS: In the EU in 2014, 1,323,600 deaths from cancer are predicted (742,500 men and 581,100 women), corresponding to standardized death rates of 138.1/100,000 men and 84.7/100,000 women, falling by 7% and 5%, respectively, since 2009. In men, predicted rates for the three major cancers (lung, colorectum and prostate cancer) are lower than in 2009, falling by 8%, 4% and 10%, respectively. In women, breast and colorectal cancers had favorable trends (-9% and -7%), but female lung cancer rates are predicted to rise 8%. Pancreatic cancer is the only neoplasm with a negative outlook in both sexes. Only in the young (25-49 years), EU trends become more favorable in men, while women keep registering slight predicted rises. CONCLUSIONS: Cancer mortality predictions for 2014 confirm the overall favorable cancer mortality trend in the EU, translating to an overall 26% fall in men since its peak in 1988, and 20% in women, and the avoidance of over 250,000 deaths in 2014 compared with the peak rate. Notable exceptions are female lung cancer and pancreatic cancer in both sexes.