The Significance of DNA Ploidy by Flow Cytometric Measurement in Pancreatic Cancer

The cellular DNA content of pancreatic cancer using formalin-fixed, paraffin-embedded specimens from 37 patients whose disease had been treated with surgical resection was determined by flow cytometry. Ploidy and cell cycle parameters were analysed and correlated with clinical and pathologic findings. There were 24 (64. 9%) diploid and 13 non-diploid pancreatic cancers. The median survival of the patients with diploid tumor was 14 months and that of the patients with non-diploid tumor was 8 months, but the difference did not have statistical significance (p=O. 078). And other cytometric parameters such as Gl phase fraction (p=O. 84), S phase fraction (0. 076), G2M phase fraction (p=O. 72), and proliferative index (p=O. 81) did not show any significant prognostic value. The patients with stage I (n=15) had 27 months of median survival, the patients with stage II (n=8) 7 months of median survival, the patients with stage III (n> 15) 9 months of median survival. The differences of survival by stage were the most significant among the parameters which were studied (p=O. 0003). The group which had lymph node metastasis (n> 11) showed 7 months of median survival and the group with negative lymph node (n=26) 12 months. The difference was also significant (p=O. 046). The other clinical parameters such as sex, the size of tumor, and the location of tumor did not have any influence on the prognosis of the pancreatic cancer patients in this study. Multivariate analysis by Weibull's model was used for prediction of survival time. Diploid versus non-diploid DNA content changed to less significant factor after adjustment for stage and lymph node. But the stage of the tumor remained a highly significant prognostic factor even after adjustment for ploidy and lymph node status

Clinical Comparison of Distal Pancreatectomy with or without Splenectomy

The spleen may be preserved during distal pancreatectomy (DP) for benign disease. The aim of this study was to compare the perioperative and postoperative courses of patients with conventional DP and spleen-preserving distal pancreatectomy (SPDP) for benign lesions or tumors with low-grade malignant potential occurred at the body or tail of the pancreas. A retrospective analysis was performed for the hospital records of all the patients undergoing DP and SPDP between January 1995 and April 2006. One-hundred forty-three patients underwent DP and 37 patients underwent SPDP. There were no significant differences in age, sex, indications of operation, estimated blood loss, operative time, and postoperative hospital stay between the two groups. Pancreatic fistula occurred in 21 (13.3%) patients following DP and in 3 (8.1%) following SPDP without a significant difference (p=0.081). Portal vein thrombosis occurred in 4 patients after DP. Splenic infarction occurred in one patient after SPDP. Overwhelming postosplenectomy infection was observed in one patient after DP. SPDP can be achieved with no increase in complication rate, operative time, or length of postoperative hospitalization as compared to conventional DP. Additionally, it has the advantage of reducing the risk of overwhelming postsplenectomy infection and postoperative venous thrombosis

Results of Hepatic Resections at S. N. U. H.: A Ten-year Experience

The medical records of 399 patients who underwent hepatic resection between January 1981 and December 1990 were reviewed. Information regarding the results of hepatic resection in terms of operative indication, operative procedure, operative morbidity and mortality, was abstracted. Until the end of 1990, a total of 402 hepatic resections were completed including 319 primary malignancies, 4 secondary malignancies, 2 gallbladder carcinomas, 42 intrahepatic cholelithiasis, 35 benign masses. Major hepatic resections were performed on 117 patients(29%). Of the 117 patients, 60(51%) had histologically proven liver cirrhosis. Minor hepatic resections were performed on 285 patients (71%). Sepsis was the most frequent complication, manifested primarily as wound infection(71 cases) or intra-abdominal infection(25 cases). Nonfatal hepatic failure occured in 9 patients with cirrhosis and 1 patient without cirrhosis. There were 38 operative deaths among 402 hepatic resections, for an overall operative mortality of 9.4 %. Twenty five of these patients died from hepatic failure after operation, accounting for 66 % of the total operative mortality. There has been an increasing frequency of hepatic resection during the last five years. Indications for resection increased from 87 to 195 resections for hepatocellular carcinoma. The cumulative data show a decrease in the complication rate and operative mortality. In the recent period, nonlethal postoperative complications have occured in 135 of 286 patients (47%). The overall survival rates in 172 patients with hepatocellular carcinoma excluding operative mortalities and palliative resections and reresections, were 71.0 %, 39.8%, 28.3% for 1, 3, and 5 years, respectively

Overexpression of p53, Mutation of hMLH1 and Microsatellite Instability in Gastric Carcinomas: Clinicopathologic Implications and Prognosis

Purpose: Mutated p53 is a tumor suppressor gene, hMLH1 is a mismatch repair gene, and hypermethylation of hMLH1 follows microsatellite instability (MSI). This research`s aim is to investigate mutated p53, inactivated hMLH1 and MSI in gastric cancer and their clinicopathologic implications. Methods: Between 2003 and 2007, 618 patients underwent curative radical gastrectomy for gastric cancer at Seoul National University Bundang Hospital in Korea. We reviewed their medical charts and the pathologic reports with immunohistochemistry for p53, hMLH1 and polymerase chain reaction for MSI in 509, 499, and 561 cases, respectively. These genetic markers were statistically compared with clinicopathologic features and postoperative survival. Results: The expression ratios of mutated p53, inactivated hMLH1, and MSI were 32.8%, 8.4%, and 8.7%, respectively. Mutation of p53 occurred more frequently in aged group (over 40), differentiated group (against the non-differentiated group), intestinal type, infiltrative type and positive lymph node metastasis group. Inactivated hMLH1 occurred more frequently in aged group, differentiated group, intestinal type and expanding growth type group. MSI was found more frequently in aged group, intestinal type and expanding growth type group. All three genetic markers had no significant associations with the 5-year survival. Conclusion: We identified significant relationships between mutated p53, inactivated hMLH1, and MSI with some clinicopathologic features of gastric cancer. However, there were no apparent relationships between p53, hMLH1, and MSI and prognosis.KU KB, 2007, J KOREAN SURG SOC, V72, P283WOERNER SM, 2006, CANCER BIOMARK, V2, P69LIU P, 2005, WORLD J GASTROENTERO, V11, P4904Lee HS, 2002, MODERN PATHOL, V15, P632Nakajima T, 2001, INT J CANCER, V94, P208Samowitz WS, 2001, AM J PATHOL, V158, P1517Rugge M, 2000, J CLIN PATHOL-MOL PA, V53, P207Wu MS, 2000, GENE CHROMOSOME CANC, V27, P403OH SH, 2000, J KOREAN SURG SOC, V59, P206Fleisher AS, 1999, CANCER RES, V59, P1090Leung SY, 1999, CANCER RES, V59, P159Monig SP, 1997, DIGEST DIS SCI, V42, P2463Thibodeau SN, 1996, CANCER RES, V56, P4836Starzynska T, 1996, CANCER, V77, P2005DosSantos NR, 1996, GASTROENTEROLOGY, V110, P38Peddanna N, 1995, ANTICANCER RES, V15, P2055TAMURA G, 1995, CANCER RES, V55, P1933SERUCA R, 1995, INT J CANCER, V64, P32CORREA P, 1994, CANCER RES, V54, pS1941BODMER W, 1994, NAT GENET, V6, P217RHYU MG, 1994, ONCOGENE, V9, P29UCHINO S, 1993, INT J CANCER, V54, P759TAHARA E, 1993, J CANCER RES CLIN, V119, P265CORREA P, 1992, CANCER RES, V52, P6735MARTIN HM, 1992, INT J CANCER, V50, P859HOLLSTEIN MC, 1991, CANCER RES, V51, P4102YONISHROUACH E, 1991, NATURE, V352, P345HARRIS AL, 1990, J PATHOL, V162, P5

Pulmonary Artery Embolotherapy in a Patient with Type I Hepatopulmonary Syndrome after Liver Transplantation

Although liver transplantation (LT) is the only effective treatment option for hepatopulmonary syndrome (HPS), the post-LT morbidity and mortality have been high for patients with severe HPS. We performed post-LT embolotherapy in a 10-year-old boy who had severe type I HPS preoperatively, but he failed to recover early from his hypoxemic symptoms after an LT. Multiple embolizations were then successfully performed on the major branches that formed the abnormal vascular structures. After the embolotherapy, the patient had symptomatic improvement and he was discharged without complications

Clinical Efficacy of Organ-Preserving Pancreatectomy for Benign or Low-Grade Malignant Potential Lesion

The clinical usefulness of organ-preserving pancreatectomy is not well established due to technical difficulty and ambiguity of functional merit. The purpose of this study is to evaluate the clinical efficacy of organ-preserving pancreatectomy such as duodenum-preserving resection of the head of the pancreas (DPRHP), pancreatic head resection with segmental duodenectomy (PHRSD), central pancreatectomy (CP) and spleen-preserving distal pancreatectomy (SPDP). Between 1995 and 2007, the DPRHP were performed in 14 patients, the PHRSD in 16 patients, the CP in 13 patients, and the SPDP in 45 patients for preoperatively diagnosed benign lesions or tumors with low-grade malignant potential. The clinical outcomes including surgical details, postoperative complications and long-term functional outcomes were compared between organ-preserving pancreatectomy and conventional pancreatectomy group. Major postoperative complications constituted the following: bile duct stricture (7.1% [1/14]) in DPRHP, delayed gastric emptying (31.2% [5/16]) in PHRSD, pancreatic fistula (21.4% [3/14]) in CP. There were no significant differences in postoperative complications and long-term functional outcomes between two groups. Organ-preserving pancreatectomy is associated with tolerable postoperative complications, and good long-term outcome comparing to conventional pancreatectomy. Organ-preserving pancreatectomy could be alternative treatment for benign or low-grade malignant potential lesion of the pancreas or ampullary/parapapillary duodenum

Presenilin 2 Is the Predominant γ-Secretase in Microglia and Modulates Cytokine Release

Presenilin 1 (PS1) and Presenilin 2 (PS2) are the enzymatic component of the γ-secretase complex that cleaves amyloid precursor protein (APP) to release amyloid beta (Aβ) peptide. PS deficiency in mice results in neuroinflammation and neurodegeneration in the absence of accumulated Aβ. We hypothesize that PS influences neuroinflammation through its γ-secretase action in CNS innate immune cells. We exposed primary murine microglia to a pharmacological γ-secretase inhibitor which resulted in exaggerated release of TNFα and IL-6 in response to lipopolysaccharide. To determine if this response was mediated by PS1, PS2 or both we used shRNA to knockdown each PS in a murine microglia cell line. Knockdown of PS1 did not lead to decreased γ-secretase activity while PS2 knockdown caused markedly decreased γ-secretase activity. Augmented proinflammatory cytokine release was observed after knockdown of PS2 but not PS1. Proinflammatory stimuli increased microglial PS2 gene transcription and protein in vitro. This is the first demonstration that PS2 regulates CNS innate immunity. Taken together, our findings suggest that PS2 is the predominant γ-secretase in microglia and modulates release of proinflammatory cytokines. We propose PS2 may participate in a negative feedback loop regulating inflammatory behavior in microglia

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration