Search

Objective: Selection of the optimal treatment strategy for patients with rectal cancer requires appropriate investigation, but published guidelines provide no clear consensus. We examined the current practice pattern for the investigation of primary rectal cancer by general surgeons in the province of Ontario, Canada. Methods: A telephone interview was completed by 124 surgeons in Ontario who manage patients with rectal cancer, who indicated the investigations they routinely perform in assessment before treatment. An exploratory cluster analysis was used to identify surgeon-related variables that predicted the pattern of investigation; these were tested in univariate and multivariate analyses. Results: Cluster analysis identified 3 distinct groups of surgeons based on patterns of test usage. Univariate analysis showed that the use of chest radiography, computed tomography of the abdomen and pelvis, and ultrasound of the abdomen varied significantly with the surgeon's subspecialty training, practice location and years in practice. Regression analysis confirmed that each of these 3 variables independently predicted the pattern of preoperative investigation. There were no significant predictors of the use of colonoscopy, sigmoidoscopy or carcinoembryonic antigen level. Over half of surgeons reported that they would have ordered additional imaging tests but did not because of lack of availability. The perceived desirability of additional tests, endorectal ultrasound in particular, varied with training. Conclusions: The current practice pattern for the preoperative investigation of primary rectal cancer by general surgeons varies significantly with specific surgeon-related variables, with potential impact on the management and outcome of patients with rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Mammary ductoscopy allows direct visualization of ductal epithelium using a fibreoptic microendoscope. As the first centre in Canada to apply ductoscopy to surgical practice, we report our experience with this technology.Methods: Between 2004 and 2008, 65 women with pathologic nipple discharge underwent ductoscopy before surgical duct excision under general anesthetic. Prospective data collection included cannulation and complication rates, procedure length and lesion visualization rate compared with preoperative ductography, if performed. In addition, we classified the endoscopic appearance according to Makita and colleagues and correlated it with surgical pathology.Results: It took longer than 6 months to overcome technical problems before the routine use of ductoscopy in the operating room. The ductoscope was easy to use: we achieved cannulation in 63 of 66 breast ducts (95%) and we visualized a lesion in 52 of 63 breast ducts (83%). The mean procedure length was 5.1 minutes, with no complications. Lesions seen on ductography were seen endoscopically 30 of 33 (91%) times. All 3 malignancies were seen: invasive carcinoma in 1 of 62 (1.6%) and in situ disease in 2 of 62 (3.2%) patients. Surgeons found ductoscopy helpful in defining the extent of duct excision. Except for the "polypoid solitary" class, which accurately predicted a papilloma (23/23), we found poor correlation between Makita and colleague's endoscopic classification and final pathology.Conclusion: Ductoscopy is feasible, safe and practical. Our surgeons routinely use it to identify the location and extent of duct excision without ordering preoperative ductography. Identifying pathology based on the endoscopic appearance is unreliable unless the lesion is solitary and polypoid. [ABSTRACT FROM AUTHOR]

Background: Visualization of cancer during breast conserving surgery (BCS) remains challenging; the BCS reoperation rate is reported to be 20-70% of patients. An urgent clinical need exists for real-time intraoperative visualization of breast carcinomas during BCS. We previously demonstrated the ability of a prototype imaging device to identify breast carcinoma in excised surgical specimens following 5-aminolevulinic acid (5-ALA) administration. However, this prototype device was not designed to image the surgical cavity for remaining carcinoma after the excised lumpectomy specimen is removed. A new handheld fluorescence (FL) imaging prototype device, designed to image both excised specimens and within the surgical cavity, was assessed in a clinical trial to evaluate its clinical utility for first-in-human, real-time intraoperative imaging during index BCS., Results: The imaging device combines consumer-grade imaging sensory technology with miniature light-emitting diodes (LEDs) and multiband optical filtering to capture high-resolution white light (WL) and FL digital images and videos. The technology allows for visualization of protoporphyrin IX (PpIX), which fluoresces red when excited by violet-blue light. To date, n = 17 patients have received 20 mg kg bodyweight (BW) 5-ALA orally 2-4 h before imaging to facilitate the accumulation of PpIX within tumour cells. Tissue types were identified based on their colour appearance. Breast tumours in sectioned lumpectomies appeared red, which contrasted against the green connective tissues and orange-brown adipose tissues. In addition, ductal carcinoma in situ (DCIS) that was missed during intraoperative standard of care was identified at the surgical margin at <1 mm depth. In addition, artifacts due to the surgical drape, illumination, and blood within the surgical cavity were discovered., Conclusions: This study has demonstrated the detection of a grossly occult positive margin intraoperatively. Artifacts from imaging within the surgical cavity have been identified, and potential mitigations have been proposed., Trial Registration: ClinicalTrials.gov Identifier: NCT01837225 (Trial start date is September 2010. It was registered to ClinicalTrials.gov retrospectively on April 23, 2013, then later updated on April 9, 2020, to reflect the introduction of the new imaging device.)., (© 2024. The Author(s).)

Background: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery., Methods: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness., Discussion: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients., Trial Registration: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021)., (© 2024. The Author(s).)

Aims: To make recommendations on managing the surveillance of patients with stage I, II, III or resectable IV melanoma who are clinically free of disease following treatment with curative intent., Materials and Methods: This guideline was developed by Ontario Health's (Cancer Care Ontario's) Program in Evidence-Based Care and the Melanoma Disease Site Group (including seven medical oncologists, four surgical oncologists, three dermatologists, one radiation oncologist and one patient representative). The MEDLINE, EMBASE, Cochrane Library, PROSPERO databases and the main relevant guideline websites were searched. Internal and external reviews were conducted, with final approval by the Program in Evidence-Based Care and the Melanoma Disease Site Group. The Grading of Recommendations, Assessment, Development and Evaluation approach was followed, and the Modified Delphi method was used., Results: Based on the current evidence (eight eligible original study papers and four relevant guidelines) and the clinical opinions of the authors of this guideline, the initial recommendations were made. To reach 75% agreement for each recommendation, the Melanoma Disease Site Group (16 members) voted twice and one recommendation was voted on three times. After a comprehensive internal and external review process (including national and international reviewers), 12 recommendations, three weak recommendations and six qualified statements were ultimately made., Conclusions: After a systematic review, a comprehensive internal and external review process and a consensus process, the current guideline has been created. The guideline authors believe that this guideline will help clinicians, patients and policymakers make well-informed healthcare decisions that will guide them in clinical melanoma surveillance and ultimately assist in improving patient outcomes., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Targeted screening programs for patients at high risk for anal squamous-cell carcinoma have been proposed; however, the evidence in support of screening remains unclear., Objective: This study aimed to determine whether screening high-risk patients (predominantly those living with HIV) detected squamous-cell carcinoma at an earlier stage compared to the routine practice of not screening., Design: This is a cohort study., Settings: This study was conducted at a quaternary care center in Canada., Patients: Included patients were at least 18 years old with a pathologic diagnosis of invasive anal squamous-cell carcinoma between 2002 and 2022., Interventions: Patients diagnosed through a high-risk screening program were compared to those who did not undergo screening., Main Outcome Measures: The primary outcome was clinical stage at presentation, categorized as T1N0M0 vs other. Secondary outcomes included treatments received, treatment failure, and overall survival., Results: A total of 612 patients with anal squamous-cell carcinoma were included, with 26 of those patients diagnosed through a screening program. Patients with screen-detected cancers had greater odds of presenting with T1N0M0 tumors compared to unscreened patients (18 [69.2%] vs 84 [14.3%]; adjusted OR 9.95; 95% CI, 3.95-25.08). A propensity score-matched sensitivity analysis found similar results (OR 11.13; 95% CI, 4.67-26.52). Screened patients had greater odds of treatment with wide local excision alone, as opposed to any combination of chemotherapy, radiation therapy, and surgery (3 [12.5%] vs 18 [3.2%]; OR 4.38; 95% CI, 1.20-16.04). There were no statistically significant differences in treatment failure or overall survival between groups., Limitations: The small number of screened patients limits the power of the analysis., Conclusions: Screening for anal squamous-cell carcinoma among high-risk populations detects cancers at an earlier stage. Patients with screen-detected cancers also had a greater likelihood of being candidates for wide local excision alone, which may have spared them the morbidity associated with chemoradiotherapy or abdominoperineal resection. See Video Abstract., Cnceres De Ano En Pacientes Previamente Detectados Por Cribado Versus No Detectados Estadio Del Tumor Y Resultados Del Tratamiento: ANTECEDENTES:Se han propuesto programas de cribado dirigidos a pacientes con alto riesgo de carcinoma anal de células escamosas; sin embargo, la evidencia a favor de la detección sigue sin estar clara.OBJETIVO:Este estudio tuvo como objetivo determinar si el cribado de pacientes de alto riesgo (predominantemente aquellos que viven con el VIH) detectó el carcinoma de células escamosas en una etapa más temprana en comparación con la práctica habitual de no cribado.DISEÑO:Este es un estudio de cohortes.CONFIGURACIÓN:Este estudio se realizó en un centro de atención cuaternaria en Canadá.PACIENTES:Los pacientes incluidos tenían al menos 18 años con un diagnóstico patológico de carcinoma de células escamosas anal invasivo entre 2002 y 2022.INTERVENCIONES:Los pacientes diagnosticados mediante un programa de cribado de alto riesgo se compararon con aquellos que no se sometieron a cribado.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el estadio clínico en la presentación, categorizado como T1N0M0 versus otro. Los resultados secundarios incluyeron los tratamientos recibidos, el fracaso del tratamiento y la supervivencia general.RESULTADOS:Se incluyeron un total de 612 pacientes con carcinoma anal de células escamosas, con 26 de esos pacientes diagnosticados a través de un programa de cribado. Los pacientes con cánceres detectados mediante cribado tenían mayores probabilidades de presentar tumores T1N0M0 en comparación con los pacientes no cribados (18 [69.2%] frente a 84 [14.3%]; razón de probabilidad ajustada 9.95; intervalo de confianza del 95 % 3.95 -25.08). Un análisis de sensibilidad emparejado por puntaje de propensión encontró resultados similares (odds ratio 11.13; intervalo de confianza del 95% 4.67 -26.52; p < 0.001). Los pacientes examinados tenían mayores probabilidades de recibir tratamiento con escisión local amplia sola, en comparación con cualquier combinación de quimioterapia, radiación y cirugía (3 [12.5%] frente a 18 [3.2%]; razón de probabilidad 4.38; intervalo de confianza del 95 % 1.20 -16.04). No hubo diferencias estadísticamente significativas en el fracaso del tratamiento o la supervivencia global entre los grupos.LIMITACIONES:El pequeño número de pacientes evaluados limita el poder del análisis.CONCLUSIONES:La detección del carcinoma anal de células escamosas entre las poblaciones de alto riesgo detecta los cánceres en una etapa más temprana. Los pacientes con cánceres detectados mediante cribado también tenían una mayor probabilidad de ser candidatos para una escisión local amplia sola, lo que puede haberles evitado la morbilidad asociada con la quimiorradioterapia o la resección abdominoperineal. (Traducción --Dr. Aurian Garcia Gonzalez )., (Copyright © The ASCRS 2023.)

Background: Maintaining and improving quality of life (QOL) are important goals of anal cancer management. This disease is generally curable, with many long-term survivors., Objective: Long-term QOL after chemoradiation for patients with anal cancer was evaluated., Design: This was a prospective cohort study., Settings: This study used data from a prospective study of patients with anal cancer who were treated with chemoradiation between 2008 and 2013., Patients: Patients with anal cancer who were treated with image-guided intensity-modulated radiation therapy were included., Interventions: English-speaking patients completed European Organization for Research and Treatment of Cancer cancer-specific (C30) and site-specific (CR29) QOL questionnaires at baseline, at end of radiation, at 3 and 6 months, and then annually., Main Outcomes Measures: Long-term QOL was evaluated clinically (a change in score of ≥10 points was considered clinically significant) and statistically (using repeated-measurement analysis) by comparing the subscale scores at 1, 2, and 3 years with baseline scores. Subanalysis compared patients who received a radiation dose of 45 to 54 Gy versus 63 Gy., Results: Ninety-six patients were included (median follow-up of 56.5 months). The symptom and functional scales showed a clinically significant decline at the end of treatment with improvement by 3 months after treatment. There was a long-term statistically significant decline in dyspnea, body image, bowel embarrassment, fecal incontinence, and hair loss, and there was long-term statistically and clinically significant worsening of impotence. Higher radiation dose (63 Gy) was not associated with significantly worse QOL., Limitations: Limitations included single-institution, single-arm study design, and lack of dose reconstruction (ie, analyses were based on prescribed, rather than delivered, dose)., Conclusions: Patients with anal cancer treated with chemoradiation reported recovery of overall QOL to baseline levels. Specific symptoms remained bothersome, emphasizing the need to address and manage the chemoradiation-induced symptoms, during treatment and in the long term. See Video Abstract at http://links.lww.com/DCR/B905., Impacto De La Quimiorradiacin Definitiva En Cambios En La Calidad De Vida De Los Pacientes Con Cncer Anal Resultados a Largo Plazo De Un Estudio Prospective: ANTECEDENTES:Mantener y mejorar la calidad de vida son objetivos importantes del tratamiento del cáncer anal, ya que esta enfermedad generalmente es curable, con muchos sobrevivientes a largo plazo.OBJETIVO:Se evaluó la calidad de vida a largo plazo después de la quimiorradiación en pacientes con cáncer anal.DISEÑO:Este fue un estudio de cohorte prospectivo.ENTORNO CLINICO:Utilizamos datos de un estudio prospectivo en pacientes con cáncer anal tratados con quimiorradiación entre 2008-2013.PACIENTES:Los pacientes con cáncer anal fueron tratados con radioterapia de intensidad modulada guiada por imágenes.INTERVENCIONES:Los pacientes de habla inglesa completaron los cuestionarios de calidad de vida específicos de cáncer (C30) y específicos del sitio (CR29) de la Organización Europea para la Investigación y el Tratamiento del Cáncer al inicio, al final de la radiación, 3 y 6 meses, y luego anualmente.PRINCIPALES MEDIDAS DE RESULTADOS:Se evaluó a largo plazo la calidad de vida clínicamente (un cambio en la puntuación de ≥10 puntos se consideraron clínicamente significativo) y estadísticamente (usando análisis de medición repetida) comparando las subescalas de puntuación al 1, 2, y 3 años. Con puntuaciones de referencia. El subanálisis comparó pacientes que recibieron 45-54 Gy versus 63 Gy.RESULTADOS:Se incluyeron un total de 96 pacientes (mediana de seguimiento: 56,5 meses). La mayoría de las escalas funcionales y de síntomas mostraron una disminución clínicamente significativa al final del tratamiento con una mejoría a los 3 meses posteriores al tratamiento. Hubo una disminución estadísticamente significativa a largo plazo en disnea, imagen corporal, vergüenza intestinal, incontinencia fecal y pérdida de cabello; y hubo un empeoramiento a largo plazo estadística y clínicamente significativo en impotencia. La dosis de radiación más alta (63 Gy) no se asoció con una calidad de vida significativamente peor.LIMITACIONES:Institución única, diseño de estudio de un solo brazo y falta de recomposición de la dosis (es decir, los análisis se basan en la dosis prescrita, en lugar de la administrada).CONCLUSIÓNES:Los pacientes con cáncer anal tratados con quimiorradiación reportaron una recuperación de la QOL en general a los niveles de base. Síntomas específicos siguieron siendo molestos, lo que enfatiza la necesidad de resolver y tartar los síntomas inducidos por la quimiorradiación no solo durante el tratamiento, sino a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B905. (Traducción- Dr. Francisco M. Abarca-Rendon)., (Copyright © The ASCRS 2022.)

Background: Anal adenocarcinoma is a rare clinical entity for which the optimal management is not defined., Objective: This study aimed to describe the multidisciplinary management and outcomes of patients with anal adenocarcinoma., Design: This is a retrospective cohort study., Setting: This study was conducted at a quaternary cancer center., Patients: Men and women with anal adenocarcinoma treated between 1995 and 2016 were selected., Interventions: Fifty-two patients were treated with either chemoradiotherapy or trimodality therapy including radiation therapy, chemotherapy, and surgical resection., Main Outcome Measures: Local failure, regional failure, and distant metastasis rates were estimated using the cumulative incidence method. The Kaplan-Meier method was used to estimate progression-free survival and overall survival. The multivariable Cox proportional hazards model was used to evaluate the clinical predictors of outcome., Results: There was a higher 5-year rate of local failure in patients treated with chemoradiotherapy compared with trimodality therapy (53% vs 10%; p < 0.01). The 5-year incidence of distant metastases was 29% (trimodality therapy) versus 30% (chemoradiotherapy; p = 0.9); adjuvant chemotherapy did not reduce the incidence of distant metastases (p = 0.8). Five-year overall survival was 73% (trimodality therapy) versus 49.4% (chemoradiotherapy; p = 0.1). On multivariable analysis, factors associated with worse overall survival were treatment with chemoradiotherapy, cT3-4 category disease, and node-positive disease., Limitations: This study is limited by its small sample size and retrospective nature., Conclusions: Although treatment may continue to be tailored to individual patients, better outcomes with a trimodality therapy approach were observed. See Video Abstract at http://links.lww.com/DCR/B708.ADENOCARCINOMA ANAL: UNA ENTIDAD POCO FRECUENTE EN NECESIDAD DE UN MANEJO MULTIDISCIPLINARIO., Antecedentes: El adenocarcinoma anal es una entidad clínica poco frecuente por lo que aún no se define el manejo óptimo., Objetivo: Describir el manejo multidisciplinario y los resultados de los pacientes con adenocarcinoma anal., Diseo: Estudio de cohorte retrospectivo., Entorno Clinico: Centro de cáncer cuaternario., Pacientes: Hombres y mujeres con adenocarcinoma anal tratados entre 1995 y 2016., Intervenciones: Cincuenta y dos pacientes fueron tratados con quimiorradioterapia o terapia trimodal que incluyó: radioterapia, quimioterapia y resección quirúrgica., Principales Medidas De Valoracion: Se estimaron las tasas de falla local, falla regional y metástasis a distancia mediante el método de incidencia acumulada. Se utilizó el método de Kaplan-Meier para estimar la supervivencia libre de progresión y la supervivencia global. Los riesgos proporcionales de multivariable Cox se utilizaron para evaluar los predictores clínicos de los resultados., Resultados: Hubo una mayor tasa de falla local a cinco años en pacientes tratados con quimiorradioterapia en comparación con terapia trimodal (53% vs 10%; p < 0,01). La incidencia a cinco años de metástasis a distancia fue del 29% (terapia trimodal) versus 30% (quimiorradioterapia) (p = 0,9); la quimioterapia adyuvante no redujo la incidencia de metástasis a distancia (p = 0,8). La supervivencia global a cinco años fue del 73% (terapia trimodal) versus 49,4% (quimiorradioterapia); p = 0,1. En el análisis multivariable, los factores asociados con una peor supervivencia general fueron el tratamiento con quimiorradioterapia, enfermedad de categoría cT3-4 y enfermedad con ganglios positivos., Limitaciones: Este estudio está limitado por su pequeño tamaño de muestra y su naturaleza retrospectiva., Conclusiones: Aunque el tratamiento puede seguir adaptándose a pacientes individuales, se observaron mejores resultados con un enfoque TTM. Conslute Video Resumen en http://links.lww.com/DCR/B708. (Traducción- Dr. Francisco M. Abarca-Rendon)., (Copyright © The ASCRS 2021.)

Background: Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS., Methods: Fifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology., Results: In the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed., Conclusions: This is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device., Trial Registration: Clinicaltrials.gov identifier NCT01837225 . Registered 23 April 2013., (© 2021. The Author(s).)

Certain population groups are known to have higher than average anal cancer risk, namely persons living with HIV (PLHIV), men who have sex with men (MSM), women diagnosed with human papillomavirus (HPV)-related gynecological precancerous lesions or cancer, solid organ transplant recipients (SOTRs) and patients with autoimmune diseases. Our aim was to provide robust and comparable estimates of anal cancer burden across these groups. Summary incidence rates (IRs), as cases per 100 000 person-years (py), were calculated by fixed-effects meta-analysis. IRs were 85 (95% confidence interval [CI] = 82-89) for HIV-positive MSM (n = 7 studies; 2 229 234 py), 32 (95% CI = 30-35) for non-MSM male PLHIV (n = 5; 1626 448 py) and 22 (95% CI = 19-24) for female PLHIV (n = 6; 1 472 123 py), with strong variation by age (eg, from 16.8 < 30 years to 107.5 ≥ 60 years for HIV-positive MSM). IR was 19 (95% CI = 10-36) in HIV-negative MSM (n = 2; 48 135 py). Anal cancer IRs were much higher after diagnosis of vulvar (IR = 48 [95% CI = 38-61]; n = 4; 145 147 py) than cervical (9 [95% CI = 8-12]; n = 4; 779 098 py) or vaginal (IR = 10 [95% CI = 3-30]; n = 4; 32 671) cancer, with equivalent disparity after respective precancerous lesions. IR was 13 (95% CI = 12-15) in SOTRs (n = 5; 1 946 206 py), reaching 24.5 and 49.6 for males and females >10 years after transplant. Anal cancer IRs were 10 (95% CI = 5-19), 6 (95% CI = 3-11) and 3 (95% CI = 2-4) for systemic lupus erythematosus, ulcerative colitis and Crohn's disease, respectively. In conclusion, a unifying anal cancer risk scale, based upon comprehensive meta-analysis, can improve prioritization and standardization in anal cancer prevention/research initiatives, which are in their public health infancy., (© 2020 International Agency for Research on Cancer (IARC/WHO); licensed by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

Aneurysmal fibrous histiocytoma is an uncommon variant of cutaneous fibrous histiocytomas with a local recurrence rate of 19%. We present a case of aneurysmal fibrous histiocytoma in a 20-year-old female with a regional lymph node metastasis and subsequent satellite nodule. The patient initially presented with a 1-month history of two palpable nodules in left lower anterior shoulder and left axilla. Needle core biopsies from both lesions revealed an atypical spindle cell neoplasm with a differential diagnosis of aneurysmal fibrous histiocytoma and angiomatoid fibrous histiocytoma. The axillary dissection confirmed a metastatic deposit in 1 out of 22 lymph nodes. At 6 months a satellite nodule arose between the resection scar and the axilla histopathologically demonstrating a cellular spindle cell nodule at the dermis subcutaneous junction with large, blood-filled pseudovascular spaces lined by histiocytes. The periphery of the lesion showed collagen trapping without a lymphoplasmacytic infiltrate. The lesional cells were diffusely positive for CD10 and focally for CD68 and Illumina RNA fusion panel sequencing was negative. Herein we present this case of metastatic aneurysmal fibrous histiocytoma with review of the literature and discussion of biology, cytogenetic alterations, and differential diagnosis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Gender preference among patients seeking medical care is an issue that is not well understood. It warrants exploration, particularly for patients undergoing sensitive physical exams. In a recent IJHPR article, Groutz et al. reported a survey study that explored patient preferences in selecting a breast surgeon. They found that a third of patients preferred a female surgeon for their breast examination. However, surgical ability was the primary factor in selecting a surgeon for their breast surgery. This commentary discusses these findings in the context of patient-centered care and issues of gender equality in medical education.Gender equality is considered an important societal movement in achieving human rights for everyone based on their ability, rather than their gender and opportunity. This commentary argues that the goal of gender equality is why women should be encouraged to enter surgical professions, recognizing that patient preferences will be shaped by societal norms. Gender preferences for the performance of sensitive physical examinations by some patients are likely multifactorial and they warrant more exploration to deliver ideal patient centered care.

Purpose: Patterns of failure and long term outcomes were prospectively evaluated following tumor factors-stratified radiation dose for anal/perianal cancer., Methods: Between 2008-2013, patients with anal/perianal squamous cell carcinoma were accrued to an institutional REB-approved prospective study. All patients were treated with image-guided intensity-modulated radiation therapy (IG-IMRT). Radiation dose selection (27-36 Gy for elective target, and 45-63 Gy for gross target) was based on tumor clinico-pathologic features. Chemotherapy regimen was 5-fluorouracil/mitomycin-C (weeks 1&5). Local [LF], regional failure [RF], distant metastasis [DM], overall- [OS], disease-free [DFS], colostomy-free survival [CFS] and late toxicity were analyzed., Results: Overall, 101 patients were evaluated; median follow-up: 56.5 months; 49.5% male; 34.7% T3/4-category, and 35.6% N+. Median radiation dose was 63 Gy. The most common acute grade ≥3 toxicities were skin (41.6%) and hematological (30.7%). Five-year OS, DFS, CFS, LF, RF, DM rates were 83.4%, 75.7%, 74.7, 13.9%, 4.6% and 5% respectively. Five-year LF for patients with T1-2 and T3-4 disease were 0% and 39.2% respectively. All LF ( n = 14, after 63 Gy, in tumors ≥5 cm) were in the high dose volume except one marginal to the high dose volume. All RF ( n = 4) were within elective dose volume except one within the high dose volume. On multivariable analysis, T3/4-category predicted for poor DFS, CFS and OS. The overall late grade ≥3 toxicity was 36.2% (mainly anal [20%])., Conclusions: Individualized radiation dose selection using IG-IMRT resulted in good long term outcomes. However, central failures remain a problem for locally advanced tumors even with high dose radiation (63 Gy/7weeks)., Competing Interests: CONFLICTS OF INTEREST No related potential conflict of interest

Palliative care has long been described in medical literature but only recently is being discussed in the surgical domain. Mounting evidence suggests that early integration of palliative care improves patient outcomes and this is especially true of oncology patients. Thus, the pendulum is swinging toward recognizing that palliative care and active disease management are not mutually exclusive but rather synergistic in modern surgical oncology. Here we use a patient vignette to demonstrate the new challenges and possibilities in modern surgical oncology, we then discuss the historic perspective of palliative care and describe how the paradigm is shifting. Finally, we introduce a model that may be beneficial in conceptualizing this new way of thinking about and integrating palliative care into surgical oncology., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development.

Introduction: Regional lymph node dissection (rlnd) for melanoma with nodal metastasis is a specialized procedure that is associated with improved disease-specific survival in selected patients. Furthermore, there is evidence that a higher lymph node retrieval rate (lnrr) is associated with improved local control. Currently, no consensus has been reached on the definition of an adequate lnrr. A minimum lnrr has been proposed as a quality assessment parameter that has to be validated., Methods: We conducted a retrospective cohort analysis at the Princess Margaret Cancer Centre (University Health Network, Toronto, ON). The lnrrs for all patients who underwent rlnd for malignant cutaneous melanoma during 2000-2010 were recorded. Indications for rlnd were a positive sentinel lymph node biopsy or clinical lymphadenopathy (palpable or radiologically detected)., Results: Of the 207 identified rlnds, 146 (70.5%) were subsequent to a positive sentinel lymph node biopsy, and 61 (29.5%) were performed for clinical lymphadenopathy. The median lnrr was 24 nodes (range: 9-47 nodes; 10th percentile: 14 nodes) for axillary rlnd, 12 nodes (range: 5-30 nodes; 10th percentile: 8 nodes) for inguinal rlnd, and 16 nodes (range: 10-21 nodes; 10th percentile: 11 nodes) for ilioinguinal rlnd. The results were similar when comparing patients with positive sentinel lymph nodes and those with clinical lymphadenopathy, and the same surgical techniques were used in both groups., Conclusions: The lnrrs at our institution are similar to rates reported at other tertiary-care melanoma centres. A minimum acceptable lnrr can be considered a quality assessment parameter in the surgical management of melanoma with nodal metastasis.

Objectives: Educational demands coupled with restricted hours reduce residents' availability to provide care at academic hospitals. Physician assistants (PAs) may address this issue. This study assessed the effect of PAs on patient discharges, resident workload, and resident perceptions of PAs on a surgical team., Methods: Two PAs were employed on teams caring for complex surgical patients. Measures included time of discharge order entry, hours residents spent on the electronic medical record (EMR), and resident opinions of PA effectiveness., Results: The teams with PAs had a 0.5% late discharge and 16% early discharge rate. Junior residents with a PA on the team spent fewer hours on the EMR. Residents reported PAs significantly improved their rotation and quality care., Conclusions: PAs reduce resident workload and improve care on surgical teams in a tertiary hospital.

Background: Utilization of breast reconstruction (BR) is low in many jurisdictions. We studied the geographical and surgical workforce factors that contribute to access and use of BR using a small area analysis approach with a geographical unit of analysis., Methods: We linked administrative data from Ontario Canada to calculate the age-standardized rates for immediate BR (IBR) (same time as mastectomy) between 2002 and 2011, and delayed BR (DBR) (within 3 years of mastectomy) for each county. The influence of plastic surgeon access on variation in county rates of BR was examined using Poisson random effects models., Results: 12,663 women underwent mastectomy in Ontario; 2,948 had BR within 3 years (23.3%). Over 50% of the counties had no access to any plastic surgeon. County IBR rates ranged from 0 to 21.5%; plastic surgeon access explained 46% of geographic variation (p<0.0001). IBR rates in counties with very low, low, and moderate access to plastic surgeons were significantly less than counties with high access (relative rate [RR] 0.48 [95% confidence interval (CI) 0.35-0.66], RR 0.61 [CI 0.43-0.87] and RR 0.70 [CI 0.52-0.96], respectively) after adjusting for age and county socioeconomic characteristics. For DBR, while there was less geographic variation, very low access counties demonstrated reduced rates (RR 0.60 [CI 0.47-0.76])., Interpretation: Geographic access to a plastic surgeon is a major determinant of BR. Targeted interventions for regions without high access to plastic surgeons may improve overall rates and reduce geographic disparities in care, particularly for IBR.

Purpose: A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer., Methods and Materials: From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicity was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation., Results: Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus-positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were significantly better at 12 months than at baseline. Multiple dose-volume parameters correlated moderately with diarrhea, skin, and hematologic toxicity scores., Conclusion: IMRT reduces acute grade 3 + hematologic and gastrointestinal toxicities compared with reports from non-IMRT series, without compromising locoregional control. The reported QOL scores most relevant to acute toxicities returned to baseline by 3 months after treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Breast cancer is managed by a multidisciplinary team with a goal for the timely provision of high quality care. Given radiation oncologist (RO) time constraints, an opportunity arises for task delegation of breast seroma target delineation to an advanced practice clinical specialist radiation therapist (CSRT) with clinical and technical expertise to facilitate treatment planning. To explore this further, we quantitatively evaluated the variability in post-surgical seroma delineation between the CSRT and ROs., Methods: Specialized site specific training was provided to the CSRT, who, with 7 ROs, independently contoured the seroma and graded its clarity, using the cavity visualization score (CVS), for 20 patients with clinical stage Tis-2N0 breast tumors. The conformity indices were analyzed for all possible pairs of delineations. The estimated "true" seroma contour was derived from the RO contours using the simultaneous truth and performance level estimation algorithm. Generalized kappa coefficient and center of mass metrics were used to examine the performance level of the CSRT in seroma delineations., Results: The CVS of the CSRT correlated well with the mean RO-group CVS, (Spearman ρ = 0.87, P < .05). The mean seroma conformity index for the RO group was 0.61 and 0.65 for the CSRT; a strong correlation was observed between the RO and CSRT conformity indices (Spearman ρ = 0.95, P < .05). Almost perfect agreement levels were observed between the CSRT contours and the STAPLE RO consensus contours, with an overall kappa statistic of 0.81 (P < .0001). The average center of mass shift between the CSRT and RO consensus contour was 1.69 ± 1.13 mm., Conclusions: Following specialized education and training, the CSRT delineated seroma targets clinically comparable with those of the radiation oncologists in women with early breast tumors suitable for accelerated partial breast or whole breast radiotherapy following lumpectomy. This study provides support for potential task delegation of breast seroma delineation to the CSRT in our current multidisciplinary environment. Further study is needed to assess the impact of this role expansion on radiotherapy system efficiency., (Copyright © 2012 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Systematic optimisation of a poorly soluble lead series of isoxazole-3-carboxamides was conducted. Substitution of the 4-position with specific polar functionality afforded the requisite balance of potency, solubility and physicochemical properties. Compound 21a was found to be efficacious in the rat Capsaicin Hargreaves assay following oral administration., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We report an expansion of the structure-activity relationship (SAR) of a novel series of indole-3-heterocyclic CB1 receptor agonists. Starting from the potent but poorly soluble lead, 1, a rational approach was taken in order to balance solubility, hERG activity and potency while retaining the desired long duration of action within the mouse tail flick test. This led to the discovery of compound 38 which successfully progressed into clinical development., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Optimization of a water soluble, moderately potent lead series of isoxazole-3-carboxamides was conducted, affording a compound with the requisite balance of potency, solubility and physicochemical properties for in vivo use. Compound 8e was demonstrated to be efficacious in a rat model of inflammatory pain, following oral administration., (Copyright © 2011. Published by Elsevier Ltd.)

Novel 3-(1H-indol-3-yl)-1,2,4-oxadiazoles and -thiadiazoles were synthesized and found to be potent CB1 cannabinoid receptor agonists. The oral bioavailability of these compounds could be dramatically improved by optimization studies of the side chains attached to the indole and oxadiazole cores, leading to identification of a CB1 receptor agonist with good oral activity in a range of preclinical models of antinociception and antihyperalgesia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Optimisation of a screening hit incorporating both TRPV1 activity and solubility was conducted. Substitution of the isoxazole-3-carboxamide with the bespoke 1S, 3R-3-aminocyclohexanol motif afforded the requisite balance of potency and solubility. Compounds 32 and 40 were found to have antihyperalgesic effects in the rat CFA Hg assay and induce a mechanism based hyperthermia., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Novel indole-3-heterocycles were designed and synthesized and found to be potent CB1 receptor agonists. Starting from a microsomally unstable lead 1, a bioisostere approach replacing a piperazine amide was undertaken. This was found to be a good strategy for improving stability both in vitro and in vivo. This led to the discovery of 24, which had an increased duration of action in the mouse tail flick test in comparison to the lead 1., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

We report the technical feasibility of autofluorescence ductoscopy in the ex-vivo setting. The current imaging algorithm for visualizing tumor tissue against the normal tissue background, although developed and optimized for other organs, appears to provide discrimination between intraductal tumor and normal ductal tissue. Point fluoroscopy is also performed. Although the optical "geometry" for this is different, the findings are consistent with the imaging observations.

The surgical management of lymph nodes continues to be important in melanoma since effective systemic therapies are not available. Controversy exists around the significance of the early detection and management of microscopically positive lymph nodes detected by sentinel lymph node biopsy and this is the subject of current surgical clinical trials. Complete lymphadenectomy is recommended for lymph node metastases. The importance of proper surgical technique is discussed.

Malignant bowel obstruction (MBO) is a common and distressing outcome particularly in patients with bowel or gynaecological cancer. Radiological imaging, particularly with CT, is critical in determining the cause of obstruction and possible therapeutic interventions. Although surgery should be the primary treatment for selected patients with MBO, it should not be undertaken routinely in patients known to have poor prognostic criteria for surgical intervention such as intra-abdominal carcinomatosis, poor performance status and massive ascites. A number of treatment options are now available for patients unfit for surgery. Nasogastric drainage should generally only be a temporary measure. Self-expanding metallic stents are an option in malignant obstruction of the gastric outlet, proximal small bowel and colon. Medical measures such as analgesics according to the W.H.O. guidelines provide adequate pain relief. Vomiting may be controlled using anti-secretory drugs or/and anti-emetics. Somatostatin analogues (e.g. octreotide) reduce gastrointestinal secretions very rapidly and have a particularly important role in patients with high obstruction if hyoscine butylbromide fails. A collaborative approach by surgeons and the oncologist and/or palliative care physician as well as an honest discourse between physicians and patients can offer an individualised and appropriate symptom management plan.

The management of patients with malignant bowel obstruction (MBO) can be one of the most challenging aspects of advanced cancer care, and as a result, their symptoms are often palliated poorly, especially near the end of life. The term MBO encompasses a heterogeneous clinical syndrome,defined as obstructive symptoms due to the presence of intra-abdominal neoplastic disease. Radiological imaging, particularly with computed tomography, is critical in determining the cause of obstruction and possible therapeutic interventions. Options include laparotomy with or without a stoma, decompression with a stent, or aggressive medical therapy. Surgical decision-making involves the selection of the intervention most likely to relieve symptoms and improve quality of life for a particular patient at that particular point along his or her disease course. Although MBO is a relatively common dilemma encountered in clinical practice, there are no simple treatment guidelines or algorithms to follow. Instead, each patient must be assessed individually to devise a treatment plan that best balances the advantages and disadvantages of the intervention, considering the patient's prognosis, tumor biology, and-most importantly-his or her goals of care, as determined through an honest discourse between physician and patient. This review outlines a surgical framework for clinicians managing patients with MBO.

Background: Symptomatic malignant ascites is a problem for patients with advanced intra-abdominal malignancy. Although the goal of paracentesis, the most common therapeutic intervention, is symptom palliation, the best method of assessing symptom improvement is unknown. The aim of this study was to assess the ability of existing symptom and quality-of-life questionnaires to detect change in symptoms after paracentesis., Methods: Patients with symptomatic ascites completed four questionnaires before and 24 hours after paracentesis. These tests were Edmonton Symptom Assessment System-Ascites Modification (ESAS:AM), Memorial Symptom Assessment Scale-Short Form, European Organization for the Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), and the EORTC Core Quality of Life Questionnaire, 26-item pancreatic cancer module (QLQ-PAN26). Sensitivity, validity, reliability, and responsiveness of the questionnaires were evaluated., Results: Sixty-one patients completed the baseline and 44 the follow-up questionnaire. Most patients had ovarian (41%) or gastrointestinal cancer (25%); Eastern Cooperative Oncology Group performance status was 2 (26%) and 3 (49%). Patients reported major symptoms at baseline; symptom scores were highest for the clinically recognized symptoms of ascites. Most patients (78%) reported that their symptoms improved after paracentesis. All questionnaires showed strong sensitivity, validity, and reliability. Subscales that included the most distressing symptoms were most responsive; great improvement was seen in abdominal bloating (42% to 54%), anorexia (20% to 37%), dyspnea (33% to 43%), insomnia (29% to 31%), fatigue (14% to 17%), and mobility (25%). The amount of fluid removed (median, 3.5 L; range, .3% to 9.7 L) did not correlate with symptom improvement (r = .29, P = -.10)., Conclusions: Paracentesis provides symptom relief that can be measured by existing questionnaires. For future clinical trials of symptomatic ascites, the QLQ-C30 and the ESAS:AM together, or the QLQ-C30 with the addition of the QLQ-PAN26 ascites and abdominal pain subscales could be used.

Background: Sentinel lymph node biopsy (SLNB) is a widely accepted alternative to axillary lymph node dissection in invasive breast cancer. Its role in ductal carcinoma-in-situ (DCIS) is unclear. The purpose of this study was to determine factors associated with the subsequent diagnosis of invasive disease and to determine the role of SLNB when performing a mastectomy for DCIS., Methods: A retrospective study was conducted of all mastectomies performed on patients with a preoperative diagnosis of DCIS between 2000 and 2005 at a single tertiary-care institution., Results: Ninety mastectomies for DCIS were included, 54 (60%) of which were performed with concurrent SLNB. Of 44 patients diagnosed preoperatively with DCIS by core biopsy only, 34 patients (63%) had a concurrent SLNB, while 10 patients (28%) were treated with mastectomy alone (P < .01). Overall, 30 patients (33%) had invasive disease, 22 of whom received concurrent SLNB. Seven SLNB patients (13%) had positive SLNs. On univariate analysis, multifocality (P = .03), multicentricity (P = .01), comedonecrosis (P = .01), and diagnosis by core biopsy (P < .001) were associated with invasive disease on pathology. On multivariate analysis, comedonecrosis (P = .04) and diagnosis by core biopsy (P < .01) were independent predictors for invasion. There was no statistically significant predictor for sentinel lymph node metastasis., Conclusions: Approximately one-third of patients with DCIS treated with mastectomy at our institution later had invasive disease, and factors associated with invasion have been identified. On the basis of our results, routine SLNB is recommended in this patient population.

Advance care planning is a process to help people to formulate and communicate their preferences regarding future care during critical illness. Reviews of the advance care planning process in its current form have been disappointing. Improvements in care at the end of life and palliative care are necessary for the provision of modern medical care. Medical research has led to many improvements at the physiological and technological levels. It is only by applying the same rigour of scientific study and research ethics that improvements in the advance care planning process can be made.

This article reviews the management of isolated recurrences after primary treatment of breast cancer. These recurrences may occur within the breast after breast-conserving surgery, on the chest wall after mastectomy, or in the axilla. While often a marker of concurrent or future metastatic disease, local management with curative intent is advocated if the recurrence is isolated at presentation. Systemic therapy at this time (readjuvant) may well have benefit and should be more thoroughly investigated. Changes in breast cancer management, including sentinel lymph node biopsy, neoadjuvant chemotherapy, hormonal therapy and partial breast irradiation, may change the implications and management of isolated local breast, chest wall and axillary recurrences.

Background: We attempted to determine factors contributing to the extent of initial curative resection for colon cancer in a population-based cohort. Total abdominal colectomy with ileorectal anastomosis (TAC-IR) may be considered for young patients or those with a colorectal cancer family history to prevent metachronous lesions and facilitate surveillance., Methods: All Ontario patients newly diagnosed with colon cancer over 12 months beginning in July 1997 were staged at the time of surgery. The extent of resection was compared with variables, including familial risk obtained from the Ontario Familial Colon Cancer Registry., Results: Complete staging was possible for 86% of patients. A total of 1223 patients had a potentially curative resection: 17%, 46%, and 36% were stage I, II, and III, respectively. Patients were more likely to receive a TAC-IR if they were < or = 50 years old (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8-6.6), if they had a synchronous lesion (OR, 28.37; 95% CI, 12.2-61.2), or if they were at a teaching hospital (OR, 2.8; 95% CI, 1.6-4.7), but not if they had a family history (OR,.7; 95% CI,.3- 1.5)., Conclusions: Young age, teaching hospital, and multiple cancers but not family history were important factors for performing a TAC-IR.

Background: Quality end-of-life care is an increasing concern for the public and the medical profession. Surgical textbooks could serve as an important educational and reference resource to improve this care., Methods: Four general surgical textbooks were scored for helpful information on death and dying for eight surgical diseases. For each disease, nine content domains related to care of the dying patient were evaluated. Three texts included a chapter on cancer that was evaluated separately., Results: Disease epidemiology, prognosis/prevention, progression, and medical interventions were generally well discussed in all textbooks. However, little helpful information was provided with regards to breaking bad news/advanced care planning, mode of death, treatment decision-making, effect on family/surgeon, and symptom management. Cancer chapters also addressed only a few of these concerns., Conclusion: Death and the dying patient are sufficiently frequent in surgical practice that it would be appropriate to increase the amount of information provided.

Two types of procedure may be indicated in incurable patients. The first is palliative, in which the goal of intervention is relief of symptoms. The second type is supportive, where the procedure is a technical intervention done as part of a multidisciplinary treatment plan. The most minimally invasive but effective procedure is chosen. Procedures are categorized by the type of symptom the procedure is intended to relieve. This article emphasizes the principles involved in patient selection and outcome assessment in order to identify areas where more research is needed.

Cancer influences hepatic amino acid metabolism in the host. To further investigate this relationship, the effects of an implanted fibrosarcoma on specific amino acid transport activities were measured in periportal (PP)- and perivenous (PV)-enriched rat hepatocyte populations. Na(+)-dependent glutamate transport rates were eightfold higher in PV than in PP preparations but were relatively unaffected during tumor growth. System N-mediated glutamine uptake was 75% higher in PV than in PP preparations and was stimulated up to twofold in both regions by tumor burdens of 9 +/- 4% of carcass weight compared with hepatocytes from pair-fed control animals. Excessive tumor burdens (26 +/- 7%) resulted in hypophagia, loss of PV-enriched system N activities, and reduced transporter stimulation. Conversely, saturable arginine uptake was enhanced fourfold in PP preparations and was induced twofold only after excessive tumor burden. These data suggest that hepatic amino acid transporters are differentially influenced by cancer in a spatial and temporal manner, and they represent the first report of reciprocal zonal enrichment of system N and saturable arginine uptake in the mammalian liver.

The Ontario Familial Colon Cancer Registry (OFCCR) is a novel registry that collects family history information, epidemiologic data, blood samples and tumour specimens from a population-based sample of colorectal cancer patients and their families. Families are classified as either high familial risk, intermediate familial/other risk or low (sporadic) risk for colorectal cancer. Obtaining high response rates in genetic family studies is especially challenging because of both the time commitment required and issues of confidentiality. The first-year response rate was 61%, resulting in 1,395 participating probands. In an attempt to assess potential response bias, we compared participants with non-participants. The age and sex of participants did not differ from non-participating probands; however, cases in rural areas were somewhat more likely to participate. To date, 57% of 1,587 relatives participated; females were more likely to participate, and relatives of low familial risk were least likely to participate. The OFCCR is an excellent resource that will facilitate the study of genetic and environmental factors associated with colorectal cancer.

Background: The hepatic uptake of amino acids is increased in both sepsis and cancer, and this response appears to be both global and essential in the catabolic host. Because immunocompromised cancer patients are susceptible to episodes of gram-negative sepsis, we examined the capacity of hepatocytes from normal and tumor-influenced livers to respond to the additional challenge of endotoxemia via increases in the Na+-dependent uptake of glutamine and zwitterionic amino acids by System N and System A, respectively., Materials and Methods: Fischer 344 rats were implanted with methylcholanthrene-induced fibrosarcomas. Control rats were sham-operated and pair-fed. Animal pairs (tumor burden = 8-32% carcass weight) were injected intraperitoneally with either Escherichia coli endotoxin (10 mg/kg) or PBS, and after 4 h, hepatocytes were isolated from the livers of the animals via collagenase perfusion and placed in primary culture. Three hours later, amino acid transport rates were measured using radiolabeled glutamine for System N and alpha-methylaminoisobutyric acid (MeAIB), a nonmetabolizable substrate specific for System A., Results: Cancer-independent of tumor size-and endotoxin each elicited similar 1.5- to 2-fold inductions of System N activity. When combined, their effects were additive rather than synergistic. In contrast, endotoxin induced an insignificant increase in System A activity, whereas cancer stimulated this carrier 2-fold in either the absence or the presence of endotoxin., Conclusions: The primary glutamine and alanine carriers in hepatocytes are differentially influenced during catabolic states, and the tumor-influenced liver is competent to further increase glutamine uptake in response to additional catabolic insults., (Copyright 1998 Academic Press.)

Background: Calcification occurs in 12-27% of hepatic colorectal metastases, but its clinical significance and its influence on prognosis are unknown., Methods: All patients diagnosed with colorectal liver metastases at the Ottawa Regional Cancer Center in 1991 (n = 97), as well as those enrolled in chemotherapy trials in 1990-1992 (n = 51), were entered into a retrospective cohort study. Thirty-six patients were excluded due to inadequate follow-up. In the remaining 112, abdominal CT scans and/or ultrasound examinations were used to determine the presence of calcification. Charts were reviewed for variables, including primary tumour pathology, amount of liver involvement by tumour (< 25%, 25-50%, > 50%), and the chemotherapeutic agents received, and were subjected to multivariate and regression analysis. End point was survival in months or to December 1993 (median follow up 24 months)., Results: Patients with calcification (n = 31) (28%) were compared to those who did not have calcifications (n = 81). The groups were comparable with respect to sex, age, time to calcification, time to metastases, and treatment type. Calcification occurred independent of the degree of tumour differentiation, the presence of mucinous adenocarcinoma, or the hepatic tumour burden. Nine patients with calcified metastases (30%) had calcification at presentation. Biopsies showed calcification next to viable tumour cells with an absence of an inflammatory reaction. Survival was improved with better primary tumour differentiation and less tumour burden. The presence of calcification had a statistically highly significant improvement in survival (P < 10(-6), relative risk = .19) independent of other variables., Conclusions: The presence of calcification within a colorectal liver metastasis appears to imply a significantly better prognosis.