INTRODUCTION:Despite advances in systemic therapy, metastatic gastric cancer is associated with a poor prognosis. As peritoneal disease is common, several studies looked at the potential benefits of hyperthermic intraperitoneal chemotherapy (HIPEC) in this context, with encouraging results. However, no Canadian data currently exists on the subject. MATERIALS AND METHODS:This study aims to report characteristics and outcomes of Canadian patients who underwent cytoreductive surgery and HIPEC (CRS-HIPEC) for gastric cancer associated with peritoneal disease or positive peritoneal cytology. This multicenter retrospective study included patients 18 years or older with gastric cancer associated with isolated peritoneal involvement who underwent CRS-HIPEC in five tertiary centers from 2016 to 2022. RESULTS:CRS-HIPEC was performed on 20 patients aged 34-69 years old, most of whom presented with poorly differentiated (90 %) adenocarcinoma, with synchronous peritoneal disease (95 %). Median PCI was 3 (0-13). The associated 90-day morbidity rate, defined as Clavien-Dindo grade III and above complications, was 10 %. At a mean follow-up of 23.3 months (range 4-48), 25 % of patients remained disease-free, with an estimated median overall survival of 24.2 months. CONCLUSION:CRS-HIPEC for gastric cancer can achieve longer term survival in highly selected patients with low-burden peritoneal disease or positive cytology. Ongoing randomized trials will further clarify patients' selection criteria and benefits of this approach.
PurposeWe report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM).MethodsIn this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS).Results451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc.ConclusionsOur analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS.
Abstract Purpose: We performed an integrated analysis of molecular classification systems proposed by The Cancer Genome Atlas (TCGA), the Asian Cancer Research Group (ACRG), and the tumor microenvironment (TME) score to identify which classification scheme(s) are most promising to pursue in subsequent translational investigations. Experimental Design: Supervised machine learning classifiers were created using 10-fold nested cross-validation for TCGA, ACRG, and TME subtypes and applied to 2,202 patients with gastric cancer from 11 separate publicly available datasets. Overall survival was assessed with a multivariable Cox proportional hazards model. A propensity score–matched analysis was performed to evaluate the subgroup effect of adjuvant chemotherapy on molecular subtypes. A public external cohort comprised of metastatic gastric cancer treated with immunotherapy was used to externally validate the molecular subtypes. Results: Classification models for TCGA, ACRG, and TME achieved an accuracy ± SD of 89.5% ± 0.04, 84.7% ± 0.04, and 89.3% ± 0.02, respectively. We identified the TME score as the only significantly prognostic classification system [HR, 0.54 (95% confidence interval [CI], 0.39–0.74); global Wald test P < 0.001]. In our subgroup analysis, patients who received adjuvant chemotherapy achieved greater survival with increasing TME score (HR, 0.47; 95% CI, 0.29–0.74; interaction P < 0.05). The combination of TME-high and microsatellite instability scores significantly outperformed microsatellite instability as a univariable predictor of immunotherapy response. Conclusions: We conclude that the TME score is a predominate driver of prognosis as well as chemotherapy- and immunotherapy-related outcomes in gastric cancer. This article provides a foundation for additional analyses and translational work.
BACKGROUND:Minimal literature exists on outcomes for Canadian patients with gastroesophageal adenocarcinoma (GEA). The objective of our study was to establish a prospective clinical database to evaluate demographic characteristics, presentation and outcomes of patients with GEA.METHODS:Patients diagnosed with GEA were recruited from Jan. 30, 2017, to Aug. 30, 2020. Data collected included demographic characteristics, presentation, treatment and survival. A multivariable model for overall survival in patients treated with curative intent was created using sex, lymph node status, resection margin status, age and tumour location as variables.RESULTS:A total of 122 patients with adenocarcinoma of the stomach or gastroesophageal junction were included. Median age was 65 years (interquartile range [IQR] 59-74), 70% of patients were male and 26% were born outside of Canada. Median follow-up time was 14.5 (IQR 8.0-31.0) months. Following staging computed tomography scanning, 88% of patients were deemed to have potentially resectable disease. Eighty-one (76%) received staging laparoscopy and 74 (61%) were treated with curativeintent surgery. Forty-six (62%) patients had nodal metastases. The median number of nodes harvested was 22 (IQR 18-30). The R0 resection margin rate was 82%. The 3-year overall survival for patients who received curative-intent treatment was 63% and 38% for all patients. On multivariable analysis, female sex (hazard ratio [HR] 3.88, p = 0.01), positive nodal status (HR 3.58, p = 0.02), positive margins (HR 3.11, p = 0.03) and tumour location (HR 3.00, p = 0.03) were associated with decreased overall survival.CONCLUSION:Many of the patients with GEA in this study presented with advanced disease, and only 61% were offered curative-intent surgery. A prospective multicentre national GEA database is now being established.
PURPOSE:Intensity modulated radiation therapy (IMRT) has confirmed its superiority in improving acute treatment-related toxicities in anal cancer, without compromising tumor control. However, the effect of IMRT on long-term quality of life (QOL) is poorly documented. The study prospectively evaluated the long-term patient-reported QOL after IMRT-based chemoradiation in anal cancer.METHODS AND MATERIALS:Fifty-eight patients treated with IMRT and concurrent 5 fluorouracil/mitomycin-C were enrolled in the study. A prespecified secondary endpoint was prospective evaluation of long-term QOL. Fifty-four patients underwent QOL evaluation at baseline, after treatment, and during follow-up until 60 months, with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) scales and the Colorectal Cancer-Specific Quality Of Life Questionnaire (QLQ-CR29) scales. The QOL scores at baseline and posttreatment periods were compared.RESULTS:For QLQ-C30, at 60 months, the mean scores of global health status, all functional scales, and all symptoms except diarrhea had improved, indicating normalization of QOL. Clinically and statistically significant improvements in the global health status (15.4; P = .003), role functioning (19.3; P = .0017), emotional functioning (18.9; P = .008), and social functioning (29.8; P ≤ .001) were observed. Diarrhea persisted as a concern over the years (P = .172). For European Organization for Research and Treatment of Cancer QLQ-CR29, rectal pain (-38.6; P = .001), mucous or blood discharge per rectum (-22.8; P = .005), and perianal soreness (-37.3; P ≤ .001) were improved both clinically and statistically. Clinically significant fecal leakage was reported by 16% of patients (5.6; P = .421). Volumes receiving 45 and 54 Gy were independent predictors for fecal incontinence. Clinically and statistically significant urinary incontinence occurred in 21% of patients (17.5; P = .014). Deterioration of dyspareunia was clinically significant (26.7; P = .099) at 60 months.CONCLUSIONS:Compared with historical data, IMRT is associated with reduced long-term effects on QOL. The majority of patients treated with IMRT experienced clinically significant recovery of function and improvement in QOL over 5 years after completion of treatment. Specific toxicities such as chronic diarrhea, fecal incontinence, and urinary and sexual dysfunction were primarily responsible for deterioration of the long-term QOL. Future research aimed at reducing such toxicities is needed to further improve long-term QOL in anal cancer.
An inadequate supply of fresh tissue is a major limitation of three-dimensional patient-derived gastric organoid research. We propose that tissue procurement for organoid culture could be increased by developing a cold storage shipment protocol for fresh surgical tissues. Sixty stomach specimens from C57BL/6J mice were resected, of which forty-five were stored in Hank’s Balanced Salt (HBSS), University of Wisconsin (UW), or Histidine-Tryptophan-Ketoglutarate (HTK) solutions for subsequent organoid culture. Stomachs were dissociated and processed into gastric organoids as fresh tissue or after transport at 4 °C for 24 or 48 h. All gastric organoid cultures were established and maintained for 10 passages. Cold storage for 24 or 48 h did not significantly affect organoid viability. Although cold storage was associated with decreased organoid growth rate, there were no differences in viability, cytotoxic dose response, or LGR5 and TROY stem cell gene expression compared to organoids prepared from fresh tissue. As a proof of concept, six human gastric cancer organoids were established after 24 or 48 h of storage. Patient-derived gastric organoids from mouse and human gastric tissue can be established after 48 h of cold ischemia. Our method, which only requires ice packs, standard shipping containers, and HBSS is feasible and reliable. This method does not affect the reliability of downstream dose–response assays and maintains organoid viability for at least 10 passages. The shipment of fresh tissue for organoid procurement could serve to enhance multicenter collaboration and achieve more elaborate or controlled organoid experimentation.
# 01. Operative classification of ventral abdominal hernias: new and practical classification {#article-title-2} Ventral hernias of the abdomen are defined as a noninguinal, nonhiatal defect in the fascia of the abdominal wall. Unfortunately, there is not currently a universal classification system
4049 Background: Multi-omics profiling of gastric cancer (GC) has produced numerous molecular classification systems. However, widespread clinical implementation and testing of molecular subtypes are currently limited. Here, we develop, validate and implement a custom Nanostring assay capable of allocating GC molecular subtypes to clinical specimens in a translational patient-derived organoid model. Methods: Using publicly available whole-transcriptome data, machine learning models were developed to predict GC molecular subtypes from 376 Cancer Genome Atlas (TCGA) and 1797 Tumour Microenvironment Score (TME) patients. Models were generated using feature selection with 10-fold nested cross-validation. GC biopsies from 10 local patients were preserved in paraffin (tumour) and established as an organoid culture (organoid). Gene expression was measured using Nanostring. The allocation of molecular subtypes was internally and externally validated using gold-standard reference features in public databases comprising 2202 GC patients and 10 tumour-organoid pairs, respectively. We evaluated the concordance of tumour-organoid molecular subtypes and explored the correlation between subtype scores and in-vitro chemotherapy response. Results: Classification models for TCGA (57 genes) and TME (50 genes) predicted subtypes with an accuracy ± standard deviation of 89.46% ± 0.04 and 89.33% ± 0.02, respectively. Subtype assignment of microsatellite instability (MSI) in reference to capillary electrophoresis was found to have 99.3% [95% CI 97.4-99.9, n = 277] internal and 100% [95% CI 83.2-100, n = 20] external accuracy. In reference to Epstein-Barr Virus (EBV) in-situ hybridization, EBV type internal and external accuracy was 98.7% [95% CI 97.4-99.5, n = 552] and 100% [95% CI 83.2-100, n = 20], respectively. TCGA Genomically Stable (GS) scores followed a previously characterized enrichment of diffuse-type histology compared to intestinal-type in internal and external cohorts (Dunn’s Test, p < 0.0001 and p < 0.05, n = 1471 and n = 15, respectively). Statistically similar subtype scores (Paired Wilcoxon, p > 0.05) were found for tumour-organoid pairs. Discordance occurred in three tumour-organoid pairs. In-vitro Drug Sensitivity Score was not statistically efficacious in any molecular subtype, but Pearson correlation identified increasing efficacy with increasing EBV and MSI scores. Conclusions: Patient-derived organoids generally recapitulate the molecular subtype of parent tumours; however, in specific cases, subtype discordance occurs. Although additional external validation is required, our 107 gene assay effectively captures multi-omics classification systems in GC and allows future inquiry into the prognostic and therapeutic implications of these molecular subtypes.
The inaugural Early-Age-Onset Colorectal Cancer Symposium was convened in June 2021 to discuss the implications of rapidly rising rates of early-age-onset colorectal cancer (EAO-CRC) in Canadians under the age of 50 and the impactful outcomes associated with this disease. While the incidence of CRC is declining in people over the age of 50 in Canada and other developed countries worldwide, it is significantly rising in younger people. Canadians born after 1980 are 2 to 2.5 times more likely to be diagnosed with CRC before the age of 50 than previous generations at the same age. While the etiology of EAO-CRC is largely unknown, its characteristics differ in many key ways from CRC diagnosed in older people and warrant a specific approach to risk factor identification, early detection and treatment. Participants of the symposium offered directions for research and clinical practice, and developed actionable recommendations to address the unique needs of these individuals diagnosed with EAO-CRC. Calls for action emerging from the symposium included: increased awareness of EAO-CRC among public and primary care practitioners; promotion of early detection programs in younger populations; and the continuation of research to identify unique risk factor profiles, tumour characteristics and treatment models that can inform tailored approaches to the management of EAO-CRC.
3 Background: Concurrent chemoradiation (CRT) with 2 doses of 5-fluorouracil (5-FU) and mitomycin C (MMC) is the standard of care for anal canal cancer (ACC) in North America while 1 dose of MMC is an acceptable practice. Given the lack of randomized data of 1 vs 2 doses of MMC on disease outcomes, we have conducted a population-based study to elucidate the impact of 1 vs. 2 doses of MMC on patterns of treatment failure (POF) and outcomes in ACC treatment. Zainab Al Habsi, Aswin Abraham, Mustafa Al Balushi, Gabriella Tankel, Karen Mulder, Heather Warkentin, Dan Schiller, Keith Tankel, Nawaid Usmani, Diane Severin, Kim Paulson, Hatim Karachiwala, Clarence Wong, Tirath Nijjar, Kurian Joseph. Methods: Data was collected from the provincial cancer registry of patients with stage I-III ACC who were treated with concurrent CRT from 2000 to 2018. Recurrence free survival (RFS), overall survival (OS), and ACC specific survival were calculated. Results: 428 patients with a median age of 58 years (29-88 years) were included in this analysis. 234 (54.7%) patients received 1 dose of MMC and 194 (45.3%) received 2 doses of MMC. At a median follow-up of 78.5 months (5-252 months), 89 (20.8%) patients developed disease recurrence: 44 (10.3%) loco-regionally, 39 (9.1%) distally and 6 (1.4%) had both local and distant recurrences. Cox Regression analysis showed that the dosage of MMC did not have an impact on overall recurrence (HR = 0.883, p = 0.561), whereas stage III was associated with increased risk for recurrence (HR = 5.238, p = 0.021). Subgroup analysis showed an association of stage IIIb and IIIc with recurrence (HR = 13.33, p = 0.008 and HR = 6.933, p = 0.011 respectively), but was not impacted by the use of 1 vs. 2 doses of MMC. The dosage of MMC did not show any association with local recurrence (HR = 1.136, p = 0.655) or distant recurrence (HR = 0.743, p = 0.267). However, in Stage IIIc patients, 2 doses of MMC showed a trend towards improved distant RFS (HR = 0.626,p = 0.084). Conclusions: Our analysis showed that the patterns of failure and the risk of loco-regional and distant failures were similar between patients who received 1 vs. 2 doses of MMC for stage groups I to IIIc. These finding support routine use of single dose of MMC along with 5FU and radiotherapy for definite chemoradiation. However, a trend towards better RFS was demonstrated with a second dose of MMC in patients with stage IIIc disease.
BACKGROUND AND PURPOSE:We prospectively assessed the contributions of PET to initial staging, early detection of treatment failures, and prognostication in patients with anal squamous cell carcinoma (ASCC). MATERIALS AND METHODS:Consecutive patients with ASCC referred for radical chemoradiotherapy (CRT) consented to undergo FDG-PET imaging pre-treatment and at 3 and 6 months post-treatment. Clinicopathologic data were collected and CT and PET imaging reviewed for contribution to staging and recurrence detection. Maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were assessed for association with progression-free survival (PFS), cause-specific survival (CSS), and overall survival (OS) using the Kaplan-Meier and Cox regression models. RESULTS:Between 2009 and 2016, 73 patients with clinical stages I-IIIB ASCC completed curative-intent CRT. Median follow-up was 48 months. 14 patients died and 18 patients experienced disease progression. 4-year PFS, CSS, and OS were 73%, 87%, and 84%, respectively. A pre-treatment MTV >35 cm3 predicted for worse PFS (p = 0.011) and CSS (p = 0.024) on univariate and multivariate analyses, employing an MTV definition of voxels ≥25% of SUVmax. Higher 6-month post-treatment SUVmax and SUVpeak predicted for worse PFS and OS (p ≤ 0.011). Pre-treatment SUVmax, SUVpeak, and TLG, and 3-month post-treatment SUVmax and SUVpeak did not significantly correlate with survival outcomes. CONCLUSIONS:Our findings support that pre-treatment MTV provides meaningful prognostic information, with suggestion that an MTV delineation threshold of voxels ≥25% of SUVmax is appropriate in the anal region. Post treatment, the combination of clinical examination and PET effectively detected all treatment failures. Higher 6-month post-treatment SUVmax and SUVpeak predicted worse PFS and OS; however, the optimal timing of post-treatment PET imaging remains unclear.
# 01. Laparoscopic splenectomy with management of intraoperative hemorrhage {#article-title-2} This video demonstrates a laparoscopic splenectomy for ITP with safe management of intraoperative hemorrhage. YouTube video link: [www.youtube.com/watch?v=6vYkOy3UePQ][1] # 02. Incisional hernia after
BACKGROUND: Local recurrence after breast conserving surgery is reported in 5‐10% of cases. This study aims to determine if preoperative MRI is associated with reduced IBTR rates in the longer term and evaluate IBTR rates of a high risk (TN and Her‐2 positive) subgroup in those receiving MRI or not.METHODS: Between 1999 and 2005, patients with invasive breast cancer undergoing BCS and radiation were identified. Primary endpoint was IBTR rate.RESULTS: The cohort consisted of 470 cases: 27% underwent MRI and 73% did not. Median follow‐up was 97 months. Overall 10‐year IBTR rate was 3.6%. There was no significant difference in IBTR rate at 10 years between those receiving MRI or not (1.6% vs. 4.2% (P = 0.37). The TN and Her‐2 positive combined subgroup had a higher IBTR rate than all others (9.8% vs. 1.7%, P = 0.001). In the group without MRI, the IBTR rate of the high risk group was 11.8% compared to 1.8% in the remainder (P = 0.002).CONCLUSION: With 10‐year follow‐up, there was no significant difference in IBTR rate whether preoperative MRI is performed versus not. The high risk population showed an increased IBTR rate, this was more marked in those who did not receive MRI.
Background and purpose Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced anal canal carcinoma, although treatment-related side effects can affect patient quality of life (QOL). The purpose was to prospectively evaluate the effects of Tomotherapy (HT) based CCRT on patient reported QOL in locally advanced anal cancer. Patients and Methods Fifty-four patients treated with HT and concurrent 5-fluorouracil/mitomycin-C underwent QOL evaluation at baseline, after treatment, and during follow-up with EORTC core (QLQ-C30) and colorectal (QLQ-CR29) questionnaires. The QOL scores at baseline and post-treatment were compared. Results All C30 functional symptoms, except emotional and cognitive functioning, were impaired end-of-treatment and recovered by 3 months follow-up. The majority of symptom scores were worse end-of-treatment but recovered by 3 months except for fecal incontinence (FI), diarrhea, urinary incontinence (UI), and dyspareunia which persisted. FI returned to baseline at 12 months while diarrhea, UI, and dyspareunia persisted. Conclusions Most impaired functions and symptoms following HT based CCRT were temporary and improved by 3 months post-therapy. Late complications affecting QOL were FI, sexual function, UI, and diarrhea. Our observations support routine use of IMRT and emphasize the significance of precise evaluation of sexual, urinary, and anorectal functions before starting CCRT and routine incorporation of QOL evaluations.
factors and systems engineering.Through the principles of human factors and system engineering, this study seeks to understand the relationship of radiation therapy associated hardware and software incidents, practitioners, their environment, and radiation technology.Methods and Materials: A retrospective analysis of incidents occurring from April 2013 September 2015 within a major metropolitan radiation therapy centre was performed.Radiation therapy (RT) related incidents were analyzed using two frameworks.Framework I classified incident types as software, hardware, or not applicable.Framework II applied the Human Factor Analysis and Classification System (HFACS), which was used to determine human and systematic attributes to incident causation.Results: One hundred and seventy-six incidents were identified to be RT-related.The application of Framework I indicated 44.89% and 15.34% involved the use of RT software and hardware respectively.A thematic analysis was completed using Framework II in relation to the classifications within Framework I.An examination of the major classes of software incidents showed, 26.70% of the total incidents were software transcription-related.A review of the major classes of hardware incidents identified 9.09% of total incidents were due to fault of the RT device and 5.11% were attributable to operator error.Conclusions: The addition of new technology and practices has the benefit of improved outcomes for patients.However, it also serves as a double edged sword that may potentially increase the risk of medical error and patient harm.Applying the principles of human factors and systems engineering provides an opportunity to identify incidents and leverage software and hardware design to potentially mitigate these errors, ultimately enhancing patient safety and quality of care.
Background: Invasive lobular carcinoma comprises 5-15% of all breast cancer cases, with its incidence gradually increasing. While it is uncommon for breast cancer to metastasize to the gastrointestinal tract, lobular carcinoma has a disproportionately higher incidence of spread to the gastrointestinal (GI) system in comparison to other types of breast cancer. To date, most studies of gastrointestinal metastatic lobular carcinoma have been case reports and small case series. Aim: This study is a review of all cases of lobular breast cancer with gastrointestinal metastases seen at a University affiliated Tertiary Cancer Institute over a five-year period, examining demographic, epidemiological, medical, and treatment factors that may have an association with the risk of GI metastases. Methods: This is a retrospective chart review of all patients seen at the Cross Cancer Institute in Edmonton, Alberta, Canada between 2005-2010, with lobular breast cancer spread to the gastrointestinal tract. The outcomes of interest were: age at diagnosis, receptor status, site of primary breast cancer, stage at initial presentation, pathology, hormone receptor status, site of gastrointestinal metastasis, time from diagnosis of breast primary to gastrointestinal metastasis, time from diagnosis to death, time to gastrointestinal metastasis to death, and treatment regimen for both primary and metastatic disease. Results: 343 consecutive cases of lobular breast cancer were reviewed, and 21(6%) were found to have GI metastases. The mean age at initial diagnosis of primary tumor was 63 years. The site of primary breast cancer was most commonly in the outer upper quadrant. Stage at presentation of the breast primary was: Stage 1A = 17%, Stage 1B/2A = 17%, Stage 2B = 22%, Stage 3A = 11%, Stage 3B = 6%, Stage 3C = 17%, and Stage 4 = 11%. Receptor status of the primary breast cancer was as follows: HER2+ = 5%, PR+ = 76%, ER+ = 90%. The mean age at time of diagnosis of metastatic disease was 67 years. The main presenting symptoms of GI metastatic disease were:: small bowel obstruction (12.5%), incidental finding on endoscopy (12.5%), and incidental finding on imaging (12.5%). Sites of gastrointestinal spread included the stomach (52%), peritoneum (14%), duodenum (4%), jejunum (4%), transverse colon (4%), and pancreas (4%). Five-year survival from initial diagnosis of lobular breast cancer averaged 46%. Five-year survival from diagnosis of gastrointestinal metastasis was 29%. Conclusions: Approximately 1 in 20 patients diagnosed with a primary breast cancer of lobular pathology will have metastatic spread to the GI tract, presenting approximately 4 years after their initial primary diagnosis. The most common presentation of metastatic disease is small bowel obstruction, with the most common site of spread being the stomach. There remains a paucity of data in the literature and our project is one of the first to further characterize these patients. Future research is needed in developing treatment regimens for these patients, as the 5-year survival is only approximately 1 in 4. Citation Format: Noah J Switzer, Andrew Lim, Lillian Du, Katia Tonkin, Dan Schiller. Case series of 21 patients with metastastic lobular breast carcinoma to the gastrointestinal tract [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-31.
22 Background: Gastric cancer (GC) has 70-75% mortality, attributable to delayed diagnosis. There is no standard screening in North America. Metabolomics is a systems biology approach to measure low molecular weight chemicals (metabolites) in body fluids or tissues to provide a phenotypic “fingerprint” of disease etiology. In this preliminary study it was hypothesized that metabolic profiling of urine samples using 1H-NMR spectroscopy could discriminate between resectable gastric adenocarcinoma (GC), benign gastric disease (BN), and healthy (HE) patients (pts). Methods: Midstream urine samples were collected, processed, and biobanked at -80°C, from 30 BN, 30 HE and 16 of 29 GC pts visiting three Edmonton clinics from August 2013 – January 2014. Thirteen of 29 samples were retrieved from a 2009-13 GC biobank. Samples were matched on age, gender and BMI. Using a validated standard operating procedure each sample was analyzed using high resolution 1H-NMR spectroscopy. Resulting spectral traces were converted into annotated and quantified metabolite profiles of 58 metabolites. Univariate and multivariate statistical analysis uncovered a disease specific biomarker profile. Partial Least Squares Discriminant Analysis (PLS-DA) developed a GC vs. HE discriminative model. A Receiver Operator Characteristic (ROC) curve was constructed. Results: There was no significant difference in metabolite profiles between GC and BN pts. However, univariate analysis revealed 13 metabolites that differed significantly between GC and HE (p<0.05). Correlation analysis, followed by PLS-DA produced a discriminative model with an area under ROC curve of 0.996, such that for a specificity of 100% the corresponding sensitivity was 93%. Conclusions: GC pts have a distinct urinary metabolite profile compared to HE controls; however in this study metabolic profiling was unable to discriminate GC from BN pts. This was probably due to sample size and phenotypic heterogeneity of BN patients. This preliminary study shows clinical potential for metabolic profiling for early GC detection.
OBJECTIVE:To quantify the time to diagnosis of anal cancer after onset of symptoms, to identify reasons for delays in diagnosis, and to identify the effect of delays on patient satisfaction.DESIGN:Retrospective questionnaire.SETTING:Cross Cancer Institute in Edmonton, Alta.PARTICIPANTS:Patients newly diagnosed with anal cancer on their first visit to the centre.MAIN OUTCOME MEASURES:Timeline from first symptoms to first access to medical care and to diagnosis, and patient satisfaction.RESULTS:Twenty-six patients completed the survey. Although most sought medical attention promptly, 19% waited for more than 6 months. At first visits after symptom onset, a rectal examination was performed in only 54% of patients, a diagnosis of hemorrhoids was given in 27% of patients, and further investigations were ordered in only 54% of patients. If a misdiagnosis of hemorrhoids was made, substantially more visits were required to diagnose the cancer. An average of 3.2 months after the first visit to a physician and 7.4 months after onset of symptoms was needed to obtain a diagnosis. Overall, 28% of patients believed there were no diagnostic delays and 40% of patients thought they were responsible for the delay. Overall, 72% of patients were satisfied with the care they received. Patients who were dissatisfied perceived the delay in diagnosis to be because no action was taken by a physician or the wait was too long for tests or referrals.CONCLUSION:To reduce delays in diagnosis, it might be important to educate relevant populations about symptoms of anal cancer. In addition, primary care physicians must maintain a high index of suspicion of anal cancer in high-risk populations. Finally, there must be a system-wide increase in access to further investigations through gastroenterologists and general surgeons.