%0 Book Section %A Schnitzler, Margaret %T Management Challenges Following Rectal Cancer Treatment %B When Cancer Crosses Disciplines: A Physician's Handbook %D 2010 %C London, UK %I Imperial College Press %V %N %P 465-486 %@ 139871848163645 %E Girgis, Afaf %X %Z FOR Codes: 111204 %0 Journal Article %~ Pubmed %A Shanley, S %A Fung, C %A Milliken, J %A Leary, J %A Barnetson, R %A Schnitzler, M %A Kirk, J %T Breast cancer immunohistochemistry can be useful in triage of some HNPCC families. %B Familial cancer %D 2009 %V 8 %N 3 %P 251-5 %@ 1573-7292 %X Immunohistochemistry of tumour samples is increasingly used in the triage of families where hereditary non-polyposis colorectal cancer (HNPCC) due to mismatch repair defects is suspected. Usually, this is undertaken in tumours that are a recognised part of the spectrum of HNPCC-related cancers e.g. colon or endometrial cancers. Although breast cancers are not classed as part of this spectrum, this study examined the extent to which some breast tumours do arise by the mismatch repair pathway in these families. This may have clinical utility in families where an individual with a 'classic HNPPC-related' tumour is not available for evaluation. Immunohistochemistry of a breast tumour may identify an individual in whom germline mutation testing is worthwhile. %Z FOR Codes: 111202 %0 Journal Article %~ Pubmed %A Warusavitarne, Janindra %A McDougall, Fiona %A de Silva, Keshani %A Barnetson, Rebecca %A Messina, Marinella %A Robinson, Bruce %A Schnitzler, Margaret %T Restoring TGFbeta function in microsatellite unstable (MSI-H) colorectal cancer reduces tumourigenicity but increases metastasis formation. %B International journal of colorectal disease %D 2009 %V 24 %N 2 %P 139-44 %@ 1432-1262 %X TGFbeta is an important cell growth regulator which may have a role in metastasis formation. Microsatellite unstable (MSI-H) colon cancer serves as a unique model to demonstrate this as most MSI-H colon cancers have a mutation in the transforming growth factor beta receptor II (TGFbetaRII) gene and a low metastatic rate. %Z FOR Codes: 110323 %0 Journal Article %~ Pubmed %A Warusavitarne, Janindra %A Schnitzler, Margaret %T The role of chemotherapy in microsatellite unstable (MSI-H) colorectal cancer. %B International journal of colorectal disease %D 2006 %V 22 %N 7 %P 739-48 %@ 0179-1958 %X High-frequency microsatellite instability (MSI-H) is an alternate pathway of colorectal carcinogenesis, which accounts for 15% of all sporadic colorectal cancers. These tumours arise from mutations in the DNA mismatch repair system and thus have different responses to chemotherapeutic agents compared to microsatellite stable (MSS) cancers. %0 Journal Article %~ Pubmed %A Warusavitarne, Janindra %A Ramanathan, Palaniappan %A Kaufman, Anthony %A Robinson, Bruce %A Schnitzler, Margaret %T 5-fluorouracil (5FU) treatment does not influence invasion and metastasis in microsatellite unstable (MSI-H) colorectal cancer. %B International journal of colorectal disease %D 2006 %V 21 %N 7 %P 625-31 %@ 0179-1958 %X Microsatellite instability is a recognised pathway of colorectal carcinogenesis responsible for about 15% of all sporadic colorectal cancers. Recent evidence has suggested that these tumours may not have the same response as microsatellite stable colon cancers to 5-fluorouracil (5FU)-based chemotherapy. The response to 5FU in four microsatellite unstable (MSI-H) cell lines was examined by cell viability assays and invasion assays. Flow cytometry was used to assess the effect of 5FU on MSI-H cell lines. In vivo response to 5FU was assessed by intraperitoneal injection of 5FU or control to 80 nude mice that had received intrasplenic injections of an MSI-H cell line KM12C prior to commencing treatment. There was inhibition of cell growth in MSI-H cell lines when treated with 5FU. There was no difference in invasiveness in the MSI-H cell lines when treated with 5FU. Primary tumours formed in 27 of the untreated and 25 of the 5FU treated mice (p=NS). There was a 36% reduction in splenic weight in those mice treated with 5FU (p<0.03). Metastases formed in 5 of the untreated and 9 of the treated mice (p=0.12). 5FU treatment of MSI-H tumours results in a reduction in growth but does not result in a reduction in invasion or metastasis. %Z FOR Codes: 111204 %0 Journal Article %~ Pubmed %A MacPherson, Ross D %A Reeve, Simon A %A Stewart, Tanya V %A Cunningham, Anna E S %A Craven, Mary L %A Fox, Greg %A Schnitzler, Margaret %T Effective strategy to guide pathology test ordering in surgical patients. %B ANZ Journal of Surgery %D 2005 %V 75 %N 3 %P 138-43 %@ 1445-1433 %X BACKGROUND: Ordering of pathology testing by junior medical staff is often a haphazard process with little regard to the appropriateness of test ordering. The aim of the present study was to reduce ordering of inappropriate pathology tests in surgical patients attending the pre-admission clinic (PAC) through the introduction of a protocol-based test ordering system and to create an environment where such improvement can be sustained. METHODS: This is a prospective study with a retrospective control group. Three cohorts of patients attending the PAC were included. Group I (n = 700) attended prior to the introduction of the test protocols (April-June 2002) and acted as a control group. Group II (n = 720) attended after the protocol introduction (April-June 2003), and group III (n = 763) attended during the subsequent 3-month period from July to August 2003. The study examined the numbers of patients in each group who were ordered any of eight standard pathology tests. The average number of tests per patient, and cost of tests per patient were also ascertained. RESULTS: Following the introduction of pathology test protocols, the ordering of all but one of the eight tests was statistically significantly reduced. In particular, ordering of coagulation studies was reduced from 22.5% to 13.8% and electrolytes, urea and creatinine from 65.2% to 48.25% of patients (both P < 0.0001). Average number of tests performed per patient declined from 2.48 to 1.88, representing a savings of 10.33 dollars per patient (a decrease from 42.22 dollars to 31.89 dollars) and a projected annualized cost saving in excess of 26,000 dollars. CONCLUSIONS: Provided that certain preliminary guidelines are followed, these protocols can reduce pathology test ordering in any pre-admission Service. %0 Journal Article %~ Pubmed %A Barnetson, Rebecca %A Eckstein, Robert %A Robinson, Bruce %A Schnitzler, Margaret %T There is no increase in frequency of somatic mutations in metastases compared with primary colorectal carcinomas with microsatellite instability. %B Genes, chromosomes & cancer %D 2003 %V 38 %N 2 %P 149-56 %@ 1045-2257 %X This study investigates the molecular features of metastasis in sporadic colon carcinomas with high-level microsatellite instability (MSI-H). DNA from 51 regions from 10 MSI-H metastatic carcinomas and 26 corresponding metastases was analyzed for mutations in TGFBRII, IGFIIR, BAX, MSH3, MSH6, and TCF4, which are associated with MSI-H carcinomas. In addition, 10 metastatic and 10 non-metastatic MSI-H carcinomas and 10 metastatic microsatellite-stable (MSS) carcinomas were examined for expression of vascular endothelial growth factor (VEGF) and mutant TP53. The frequency of microsatellite instability and somatic mutations was not significantly increased in the metastases compared with the that of primary carcinomas. Although significantly fewer MSI-H carcinomas expressed VEGF (P < 0.01) and mutant TP53 (P < 0.005) than MSS carcinomas, there was no difference in VEGF and mutant TP53 expression in metastatic and non-metastatic MSI-H carcinomas. In conclusion, metastasis does not appear to be associated with an increase in somatic mutation rate in any of the genes examined in MSI-H colon carcinomas. Furthermore, VEGF and TP53 expression did not appear to be involved in metastasis in MSI-H colon carcinomas. %Z FOR Codes: 111203 %0 Journal Article %~ Pubmed %A Shannon, Catherine %A Kirk, Judy %A Barnetson, Rebecca %A Evans, Justin %A Schnitzler, Margaret %A Quinn, Michael %A Hacker, Neville %A Crandon, Alex %A Harnett, Paul %T Incidence of microsatellite instability in synchronous tumors of the ovary and endometrium. %B Clinical Cancer Research %D 2003 %V 9 %N 4 %P 1387-92 %@ 1078-0432 %X PURPOSE: Families with hereditary nonpolyposis colorectal cancer (HNPCC) have an increased lifetime risk of endometrial (40%) and ovarian (10%) carcinomas. Endometrial and ovarian carcinomas from members of these families frequently display a mutator phenotype as manifest by high levels of microsatellite instability (MSI-H). Microsatellite instability (MSI) occurs in 17-32% of sporadic endometrial carcinomas and 3-17% of sporadic ovarian carcinomas. We hypothesized that there might be a higher rate of MSI in tumors from women with synchronous primary carcinomas of the ovary and endometrium. EXPERIMENTAL DESIGN: We identified 52 cases of synchronous tumors of the ovary and endometrium from the databases of four gynecological oncology units. Archival material and clinical data were available on 45 of these patients. We examined DNA extracted from ovarian and endometrial tumor tissue for MSI using DNA extracted from normal tissue of that patient as a germ-line DNA control. MSI was assessed using a panel of five standard microsatellite markers: D2S123, D5S346, D17S250, BAT25, and BAT26. MSI-H was defined by more than two markers being positive. Low-level MSI (MSI-L) was defined as one or two markers positive and microsatellite stable (MSS) was defined as no markers positive. RESULTS: The 45 patients had a median age at diagnosis of 53 years. Of a total of 134 samples analyzed, only three samples (3.3%) were MSI-H. No patient had high levels of MSI in both ovarian and endometrial tumors. One ovarian carcinoma had five of five markers positive with the corresponding endometrial carcinoma being MSI-L. Two endometrial carcinomas were MSI-H, and the corresponding ovarian carcinomas were MSI-L and MSS, respectively. Seven ovarian tumors and seven endometrial tumors were MSI-L. The majority of patients had early-stage ovarian carcinoma [International Federation of Gynecology and Obstetrics (FIGO) stage I, 44.4%; stage II, 26.7%; and stage III, 26.6%]. Eighty-two % of the endometrial primaries were FIGO stage I. Progression-free survival was significantly better for patients with synchronous primaries than those presenting with ovarian carcinoma alone [adjusted hazards ratio, 1.94; P = 0.023; 95% confidence interval, 1.096-3.44]. CONCLUSION: Synchronous primary carcinomas of the ovary and endometrium are unlikely to be part of the HNPCC syndrome unless the family history is in keeping with the modified Amsterdam criteria. %Z FOR Codes: 111299 %0 Journal Article %~ Pubmed %A Tobin, Peter J %A Dodds, Helen M %A Clarke, Stephen %A Schnitzler, Margaret %A Rivory, Laurent P %T The relative contributions of carboxylesterase and beta-glucuronidase in the formation of SN-38 in human colorectal tumours. %B Oncology reports %D 2003 %V 10 %N 6 %P 1977-9 %@ 1021-335X %X Irinotecan (CPT-11) is a prodrug that is used to treat metastatic colorectal cancer. It is activated to the topoisomerase poison SN-38 by carboxylesterases. SN-38 is subsequently metabolised to its inactive glucuronide, SN-38G, which can however be reactivated to SN-38 by beta-glucuronidase. The purpose of this study was to examine the role of carboxylesterases and beta-glucuronidase in the in vitro production of SN-38 in human colorectal tumours. The production of SN-38 from CPT-11 and SN-38G was measured by HPLC in human colorectal tumour homogenates. Carboxylesterase and beta-glucuronidase activities were found to be lower in tumour tissues compared to matched normal colon mucosa samples. In colorectal tumour, beta-glucuronidase and carboxylesterase-mediated SN-38 production rates were comparable at clinically relevant concentrations of SN-38G and CPT-11, respectively. Therefore, tumour beta-glucuronidase may play a significant role in the exposure of tumours to SN-38 in vivo, particularly during prolonged infusions of CPT-11. %Z FOR Codes: 111299 %0 Journal Article %A Hatzidis, WT %A Solomon, MJ %A Schnitzler, M %A Cartmill, JA %A Loder, P %A Chapuis, PH %T Does the caseload of the pathologist influence the minimum and extended data set of pathology variables reported for rectal adenocarcinoma? %B Colorectal Disease %D 2000 %C %I Blackwell Science Ltd %V 21 %N %P 26-30 %@ 1462-8910 %X %0 Journal Article %A Barnetson, RA %A Symons, P %A Robinson, BG %A Schnitzler, M %T Genetic analysis of multiple sporadic colon carcinomas from a single patient %B International Journal of Colorectal Disease %D 2000 %C %I Springer-Verlag %V 15 %N %P 83-86 %@ 0179-1958 %X