Experience of a single academic institution with the National Accreditation Program for Rectal Cancer and the resulting improvement in care.

AIM: The American College of Surgeons Committee on Cancer developed the National Accreditation Program for Rectal Cancer (NAPRC) to reduce variations in rectal cancer care, standardize clinical practice and encourage multidisciplinary approaches. The aim of this study was to analyse if accreditation achieved a higher quality of care at one hospital. METHOD: The University of California Davis Medical Center was accredited in 2019. A retrospective review of rectal adenocarcinoma patients was performed between the years 2013 and 2018. Patients presenting from 2013 to 2015 were discussed at a gastrointestinal tumour board while patients in 2018 had an accredited rectal cancer tumour board. Patients from 2016 to 2017 were excluded as the programme was still developing. Compliance to the NAPRC standards was compared between the cohorts. RESULTS: One hundred and thirty patients were evaluated, 88 (68%) in the prerectal tumour board cohort and 42 (32%) in the rectal tumour board cohort. The prerectal tumour board cohort often failed to meet attendance standards. All patients in the rectal tumour board cohort met all criteria. Similarly, clinical service compliance improved in the rectal tumour board cohort for 13 metrics, 10 of which were statistically significant. Although a high proportion of patients in both groups experienced quality surgery, i.e. complete total mesorectal excision and negative margins, the lack of complete pathological reporting in the prerectal tumour board cohort limited analysis. CONCLUSION: Multidisciplinary rectal cancer tumour boards are associated with improved compliance with recommended care by the NAPRC. Patients discussed at a rectal cancer tumour board were more likely to receive appropriate staging, coordinated care and have better clinical documentation.

Analysis of Patterns of Compliance with Accreditation Standards of National Accreditation Program for Rectal Cancer.

BACKGROUND: We identified commonly deficient standards across rectal cancer programs that underwent accreditation review by the National Accreditation Program for Rectal Cancer to evaluate for patterns of noncompliance. STUDY DESIGN: With the use of the internal database of the American College of Surgeons, programs that underwent accreditation review from 2018 to 2020 were evaluated. The occurrence and frequency of noncompliance with the standards, using the 2017 standards manual, were evaluated. Programs were further stratified based on the year of review, annual rectal cancer volume, and Commission on Cancer classification. RESULTS: A total of 25 programs with annual rectal cancer volume from 14 to more than 200 cases per year underwent accreditation review. Only 2 programs achieved 100% compliance with all standards. Compliance with standards ranged from 48% to 100%. The 2 standards with the lowest level of compliance included standard 2.5 and standard 2.11 that require all patients with rectal cancer to be discussed at a multidisciplinary team meeting before the initiation of definitive treatment and within 4 weeks after definitive surgical therapy, respectively. Patterns of noncompliance persisted when programs were stratified on the basis oof the year of survey, annual rectal cancer volume, and Commission on Cancer classification. The corrective action process allowed all programs to ultimately become successfully accredited. CONCLUSION: During this initial phase of the National Accreditation Program for Rectal Cancer accreditation, the majority of programs undergoing review did not achieve 100% compliance and went through a corrective action process. Although the minimal multidisciplinary team meeting attendance requirements were simplified in the 2021 revised standards, noncompliance related to presentation of all patients at the multidisciplinary team meeting before and after definitive treatment highlights the need for programs seeking accreditation to implement optimized and standardized workflows to achieve compliance.

Measuring Rectal Cancer Tumor Height: Concordance Between Clinical Examination and MRI.

BACKGROUND: Rectal cancer is categorized into categories on the basis of tumor height measurements. Tumor height is used to guide initial treatment and determines the eligibility for clinical trials. OBJECTIVE: This study aimed to determine the concordance between tumor heights measured by MRI and by clinical examination. DESIGN: This was an institutional review board-approved retrospective analysis of MRI and the clinical measurements of tumor height. SETTING: This study was conducted at a single university center that was accredited by the Commission on Cancer National Accreditation Program for Rectal Cancer. PATIENTS: Ninety-five patients who were treated between 2015 and 2019 and who had an MRI and clinical evaluation were included. MAIN OUTCOME MEASUREMENTS: The mean difference of tumor height between MRI and clinical examination was calculated. Secondary outcomes were to assess whether position in the rectum, age, BMI, or sex would affect the difference and how the measurements would change eligibility for rectal cancer trials. RESULTS: Tumor height measurement by MRI and clinical examination had a good correlation, with r = 0.89 and p < 0.001. The mean absolute difference of measurement of tumor height was 1.56 cm. Higher tumors had a larger absolute difference between measurements. Body mass index was significantly associated with the difference in measurements. The discordance in measurements led to a change in eligibility for clinical trials for 38.9% of patients. Clinical trial eligibility was not significantly associated with tumor height category, sex, or patient age. LIMITATIONS: This study was conducted at a single center with retrospective methodology. CONCLUSIONS: Although MRI and clinical measurements showed a strong correlation, nearly 40% of our patients had a change in clinical trial eligibility depending on measurement modality. We suggest that trial investigators be consistent in establishing measurement technique as their inclusion criterion. See Video Abstract at http://links.lww.com/DCR/B756. MEDICIN DE LA ALTURA DEL TUMOR DE CNCER DE RECTO CONCORDANCIA ENTRE EL EXAMEN CLNICO Y LA RESONANCIA MAGNTICA: ANTECEDENTES:El cáncer de recto se clasifica en categorías basadas en las mediciones de la altura del tumor. La altura del tumor se usa para guiar el tratamiento inicial y determina la elegibilidad para los ensayos clínicos.OBJETIVO:Determinar la concordancia entre la altura de los tumores medida por resonancia magnética (RMN) y por examen clínico.DISEÑO:Este fue un análisis retrospectivo aprobado por el IRB de la resonancia magnética y las mediciones clínicas de la altura del tumor.AJUSTE:Esto se llevó a cabo en un único centro universitario que fue acreditado por el Programa Nacional de Acreditación del Cáncer de Recto de la Comisión de Cáncer.PACIENTE:Se incluyeron 95 pacientes que fueron atendidos entre 2015 y 2019 y que tuvieron una resonancia magnética y evaluación clínica.PRINCIPALES MEDIDAS DE RESULTADOS:Se calculó la diferencia media de la altura del tumor entre la resonancia magnética y el examen clínico. Los resultados secundarios fueron evaluar si la posición en el recto, la edad, el índice de masa corporal (IMC) o el sexo afectarían la diferencia y cómo las mediciones cambiarían la elegibilidad para los ensayos de cáncer de recto.RESULTADOS:La medición de la altura del tumor por resonancia magnética y el examen clínico tuvo una buena correlación con r = 0,89 y p < 0,001. La diferencia absoluta media de medición de la altura del tumor fue de 1,56 cm. Los tumores más altos tenían una diferencia absoluta más grande entre las mediciones. El IMC se asoció significativamente con la diferencia en las mediciones. La discordancia en las mediciones llevó a un cambio en la elegibilidad para los ensayos clínicos para el 38,9% de los pacientes. La elegibilidad para ensayos clínicos no se asoció significativamente con la categoría de altura del tumor, el sexo o la edad del paciente.LIMITACIONES:Se realizó en un solo centro con metodología retrospectiva.CONCLUSIONES:Aunque la resonancia magnética y las mediciones clínicas mostraron una fuerte correlación, casi el 40% de nuestros pacientes tuvieron un cambio en la elegibilidad para los ensayos clínicos según la modalidad de medición. Sugerimos que los investigadores del ensayo sean coherentes al establecer la técnica de medición como criterio de inclusión. Consulte Video Resumen en http://links.lww.com/DCR/B756.

Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.

Size Criteria Is Not Sufficient in Selecting Patients for Local Excision Versus Radical Excision for Rectal Neuroendocrine Tumors >2 cm: A National Cancer Database Analysis.

BACKGROUND: Patients with rectal neuroendocrine tumors >2 cm often undergo radical surgery, despite limited data supporting this practice. Five- and 10-year survival rates for these patients have been reported previously as 74.8% and 58.6%. OBJECTIVE: Overall survival was compared between local excision and radical surgery and pN0 and pN1 within the radical surgery subgroup for rectal neuroendocrine tumors >2 cm. Factors independently associated with survival were identified. DESIGN: A retrospective, nationwide, multivariate regression analysis was performed. SETTINGS: Data are from the National Cancer Database (2004-2013). PATIENTS: Patients with rectal neuroendocrine tumors >2 cm, excluding stages T4 and M1, were included. MAIN OUTCOME MEASURES: Outcome measures were overall survival and independent risk factors for overall survival based on multivariate regression analysis. RESULTS: Each group had 178 patients. After local excision, 5- and 10-year overall survival rates were 88% and 72% vs 51% and 42% after radical surgery (p < 0.001). A multivariate Cox proportional hazards model showed similar survival (p = 0.96). Tumor factors independently associated with survival were nodal metastasis (HR = 2.01 (95% CI, 1.01-3.97)), poorly differentiated tumors (HR = 4.82 (95% CI, 1.65-14.01)), and undifferentiated tumors (HR = 9.91 (95% CI, 2.77-35.49)). After radical surgery, patients with and without nodal metastasis had 5-year survival rates of 44% vs 59% (unadjusted p = 0.09; adjusted p = 0.11), with insufficient 10-year survival data. LIMITATIONS: The study is a retrospective analysis and includes only Commission on Cancer-accredited hospitals. Long-term follow-up was limited. Lymphovascular invasion was missing for a majority of patients analyzed. CONCLUSIONS: Local excision for select patients with rectal neuroendocrine tumors >2 cm is a viable alternative to radical surgery. Nodal status and tumor grade independently predict survival and should be factored into surgical intervention selection. In higher-risk patients selected for radical surgery, survival was similar between the pN0 and pN1 groups, possibly indicating a benefit of radical surgery for these patients. See Video Abstract at http://links.lww.com/DCR/B455. EL CRITERIO DE TAMAO NO ES SUFICIENTE PARA SELECCIONAR PACIENTES PARA LA ESCISIN LOCAL VERSUS ESCISIN RADICAL PARA TUMORES NEUROENDOCRINOS RECTALES CM ANLISIS DE UNA BASE DE DATOS NACIONAL DE CANCER: ANTECEDENTES:Los pacientes con tumores neuroendocrinos rectales >2 cm a menudo se someten a cirugía radical, a pesar de los datos limitados que respaldan esta práctica. La supervivencia a cinco y diez años para estos pacientes se había informado anteriormente como 74,8% y 58,6%, respectivamente.OBJETIVO:Se comparó la supervivencia global entre escisión local y cirugía radical, y pN0 y pN1 dentro del subgrupo de cirugía radical para tumores neuroendocrinos rectales >2 cm. Se identificaron factores asociados de forma independiente con la supervivencia.DISEÑO:Se realizó un análisis retrospectivo de regresión multivariante a nivel nacional.AJUSTE:Los datos provienen de la Base de Datos Nacional sobre el cáncer (2004-2013).PACIENTES:Pacientes con tumores neuroendocrinos rectales > 2 cm, excluyendo los estadios T4 y M1.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas de resultado fueron la supervivencia general y los factores de riesgo independientes para la supervivencia general según el análisis de regresión multivariante.RESULTADOS:Cada grupo tuvo 178 pacientes. Después de la escisión local, la supervivencia global a cinco y diez años fue del 88% y 72% frente al 51% y el 42% después de la cirugía radical (p <0,001). Un modelo multivariado de riesgos proporcionales de Cox mostró una supervivencia similar (p = 0,96). Los factores tumorales asociados de forma independiente con la supervivencia fueron metástasis ganglionares (HR = 2,01; IC, 1,01-3,97), tumores pobremente diferenciados (HR = 4,82, IC, 1,65-14,01) y tumores indiferenciados (HR = 9,91, IC, 2,77-35,49). Después de la cirugía radical, los pacientes con y sin metástasis ganglionar tuvieron una supervivencia a cinco años del 44% frente al 59%, respectivamente (p no ajustado = 0,09; p ajustado = 0,11), con datos insuficientes de supervivencia a diez años.LIMITACIONES:El estudio es un análisis retrospectivo e incluye solo hospitales acreditados por la Comisión de Cáncer. El seguimiento a largo plazo fue limitado. La mayoría de los pacientes analizados no tenían invasión linfovascular.CONCLUSIONES:La escisión local para pacientes seleccionados con tumores neuroendocrinos rectales >2 cm es una alternativa viable a la cirugía radical. El estado ganglionar y el grado del tumor predicen de forma independiente la supervivencia y deben tenerse en cuenta en la selección de la intervención quirúrgica. En los pacientes de mayor riesgo seleccionados para cirugía radical, la supervivencia fue similar entre los grupos pN0 vs. pN1, lo que posiblemente indica un beneficio de la cirugía radical para estos pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B455.

Trends in flap reconstruction of pelvic oncologic defects: Analysis of the national inpatient sample.

BACKGROUND: Flap reconstruction of radiated pelvic oncologic defects decreases perineal wound-healing complications. How widely and how often reconstructions are performed, and how technical mastery and improved perioperative care has affected outcomes, is unknown. Our objective is to 1) provide a comprehensive evaluation of national trends in flap reconstruction of pelvic oncologic defects and 2) compare complications and length of stay (LOS) in patients with/without reconstruction. METHODS: The National Inpatient Sample (NIS) database was queried (1998-2014) for patients diagnosed with cancer, primarily of the rectum and anus, who underwent abdominoperineal resection (APR) or pelvic exenteration (PE). Differences in complications and LOS were compared between patients with flap reconstruction versus primary closure. Regional and hospital outcomes were also analyzed. RESULTS: The cohort included 117,923 adult patients; 3,673 (3.1%) underwent flap reconstruction. Flap reconstruction rates increased from 0.8% in 1998 to 9.8% in 2014. Extirpative procedures decreased 37.4% from 1998 to 2014. Flap reconstruction decreased risk of wound breakdown (OR 0.87; p = 0.0029) and need for secondary closure of dehiscence (OR 0.82; p = 0.0023) between periods 1998-2009 and 2010-2014. Median LOS was higher for flap patients (median [IQR] of 9.8 [7.2,14.8] vs. 7.9 [6.1-11.0; p < 0.0001) and decreased over time. CONCLUSIONS: The use of flap reconstruction for pelvic oncologic defects increased from 1998 to 2014, with a reduction in LOS. Following flap reconstruction, overall complications are higher, but wound breakdown and dehiscence requiring reclosure are decreasing, suggesting technique maturation. We anticipate flap reconstruction rates will increase with further improvement in patient outcomes.

Blood-based biomarkers of human papillomavirus-associated cancers: A systematic review and meta-analysis.

BACKGROUND: Despite the significant societal burden of human papillomavirus (HPV)-associated cancers, clinical screening interventions for HPV-associated noncervical cancers are not available. Blood-based biomarkers may help close this gap in care. METHODS: Five databases were searched, 5687 articles were identified, and 3631 unique candidate titles and abstracts were independently reviewed by 2 authors; 702 articles underwent a full-text review. Eligibility criteria included the assessment of a blood-based biomarker within a cohort or case-control study. RESULTS: One hundred thirty-seven studies were included. Among all biomarkers assessed, HPV-16 E seropositivity and circulating HPV DNA were most significantly correlated with HPV-associated cancers in comparison with cancer-free controls. In most scenarios, HPV-16 E6 seropositivity varied nonsignificantly according to tumor type, specimen collection timing, and anatomic site (crude odds ratio [cOR] for p16+ or HPV+ oropharyngeal cancer [OPC], 133.10; 95% confidence interval [CI], 59.40-298.21; cOR for HPV-unspecified OPC, 25.41; 95% CI, 8.71-74.06; cOR for prediagnostic HPV-unspecified OPC, 59.00; 95% CI, 15.39-226.25; cOR for HPV-unspecified cervical cancer, 12.05; 95% CI, 3.23-44.97; cOR for HPV-unspecified anal cancer, 73.60; 95% CI, 19.68-275.33; cOR for HPV-unspecified penile cancer, 16.25; 95% CI, 2.83-93.48). Circulating HPV-16 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41-72.57). In 3 cervical cancer case-control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid. CONCLUSIONS: HPV-16 E6 antibodies and circulating HPV-16 DNA are the most robustly analyzed and most promising blood-based biomarkers for HPV-associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type-specific, high-risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high-risk HPV types. Further investigation of blood-based microRNA expression profiling appears indicated.

Trends in Primary Surgical Resection and Chemotherapy for Metastatic Colorectal Cancer, 2000-2016.

BACKGROUND: When, whether, and in whom primary tumor resection (PTR) for patients with metastatic colorectal cancer (CRC) is indicated remains unknown. With advances in multiagent systemic chemotherapy, PTR may be undertaken less frequently. The aim of this study was to obtain estimates of changes in the utilization of PTR and chemotherapy for metastatic CRC. METHODS: Patients diagnosed with metastatic CRC between 2000 and 2016 were identified from Surveillance Epidemiology, and End Results (SEER) registry. Multivariable logistic regression defined odds of undergoing PTR. The analysis was also stratified by primary site (colon vs. rectum), age (younger than 50 vs. 50 y and older), and whether patients also underwent resection of metastatic sites (yes vs. no). The secondary endpoint of interest was the receipt of any chemotherapy, also assessed by multivariable logistic regression. RESULTS: Among 99,835 patients with metastatic CRC, 55,527 (55.7%) underwent PTR. The odds of undergoing PTR decreased with a later year of diagnosis, with patients diagnosed in 2016 being 61.1% less likely to undergo surgery than those diagnosed in 2000 (adjusted odds ratio=0.39, 95% confidence interval: 0.36-0.42, P<0.0001; absolute percentage: 62.3% to 43.8%). Similar trends by year for PTR were observed among each of the subgroups, although patients with colon primary, young adults (age younger than 50 y), and patients also undergoing metastasectomy were more likely to undergo PTR (P<0.001 for all). In contrast, the odds of receiving chemotherapy increased dramatically with a later year of diagnosis (adjusted odds ratio=2.21, 95% confidence interval: 2.04-2.40, P<0.0001). CONCLUSIONS: From 2000 to 2016, there was a sharp decline in the rate of PTR for patients with metastatic CRC, while the use of chemotherapy increased over the same period. Prospective studies are needed to define the optimal local treatment for patients with metastatic CRC.

Effect and Safety of Radiation Therapy Boost to Extramesorectal Lymph Nodes in Rectal Cancer.

PURPOSE: In rectal cancer, the presence of extramesorectal/lateral pelvic lymph node (LPN) is associated with higher risk of locoregional and distant recurrences. LPNs are not typically resected during a standard total mesorectal excision (TME) procedure, and the optimal management for these patients is controversial. We assessed the safety and efficacy of adding a radiation therapy boost to clinically positive LPN during neoadjuvant chemoradiation therapy for rectal cancer. METHODS AND MATERIALS: We analyzed nonmetastatic, lymph node positive rectal adenocarcinoma patients treated with neoadjuvant chemoradiation therapy followed by TME between May 2011 and February 2018. Patients without LPN involvement received external beam radiation therapy (45 Gy in 25 fractions) to the primary tumor and regional draining lymph node basins followed by a boost (5.4 Gy in 3 fractions) to gross disease. Patients with clinically positive LPN that would not be removed during TME received an additional boost (up to a total dose between 54.0 and 59.4 Gy) to the involved LPNs. We compared locoregional control, overall survival, progression-free survival, and treatment-related toxicity between these 2 groups. RESULTS: Fifty-three patients were included in this analysis with median follow-up of 30.6 months for the LPN- group (n = 41) and 19.9 months for the LPN+ group (n = 12). There was no difference in 3-year overall survival (90.04% vs 83.33%, P = .890) and progression-free survival (80.12% vs 80.21%, P = .529) between the 2 groups. We did not observe any LPN recurrences. There were no differences in rates of acute grade 3+ or chronic toxicities. CONCLUSIONS: Despite the well-documented negative prognostic effect of LPN metastasis, we observed promising outcomes for LPN+ patients treated with an additional radiation boost. Our results suggest that radiation therapy boost to clinically involved, unresected LPN is an effective treatment approach with limited toxicity. Additional studies are needed to optimize treatment strategies for this unique patient subset.

Historical review of Lynch syndrome / Revisão histórica da síndrome de Lynch

Lynch syndrome was formerly known as Hereditary Nonpolyposis Colorectal Cancer. Currently, these two nomenclatures each have their unique definitions and are no longer used interchangeably. The history of hereditary nonpolyposis colorectal cancer was first recognized formally in the literature by Henry Lynch in 1967. With advances of molecular genetics, there has been a transformation from clinical phenotype to genotype diagnostics. This has led to the ability to diagnose affected patients before they manifest with cancer, and therefore allow preventative surveillance strategies. Genotype diagnostics has shown a difference in penetrance of different cancer risks dependent on the gene containing the mutation. Surgery is recommended as prevention for some cancers; for others they are reserved for once cancer is noted. Various surveillance strategies are recommended dependent on the relative risk of cancer and the ability to intervene with surgery to impact on survival. Risk reduction through aspirin has shown some recent promise, and continues to be studied. (AU)

A síndrome de Lynch era anteriormente conhecida como "câncer colorretal hereditário não polipose". Atualmente, essas duas nomenclaturas têm, cada uma, sua própria definição original e já não são empregadas de forma intercambiável. O histórico de câncer colorretal hereditário não polipose foi formalmente reconhecido pela primeira vez na literatura por Henry Lynch em 1967. Com os avanços da genética molecular, verificou-se uma mudança do fenótipo clínico para o diagnóstico genotípico. Esse fato levou à capacidade de diagnosticar pacientes afetados antes que o câncer se manifestasse, e, portanto, à utilização de estratégias preventivas de rastreamento. O diagnóstico genotípico mostrou a diferença na penetrância de diferentes riscos de câncer dependendo do gene que contem a mutação. A cirurgia é recomendada para a prevenção de alguns tipos de câncer; para outros, ela é reservada quando há o aparecimento da doença. Várias estratégias de rastreamento são recomendadas, dependendo do risco relativo de câncer, bem como a capacidade para intervir com a cirurgia objetivando um impacto na sobrevivência. A redução do risco através do uso de aspirina recentemente mostrou ser promissor e continua a ser estudada. (AU)

Tandem sequence of phenol oxidation and intramolecular addition as a method in building heterocycles.

A tandem phenol oxidation-Michael addition furnishing oxo- and -aza-heterocycles has been developed. Dirhodium caprolactamate [Rh(2)(cap)(4)] catalyzed oxidation by T-HYDRO of phenols with alcohols, ketones, amides, carboxylic acids, and N-Boc protected amines tethered to their 4-position afforded 4-(tert-butylperoxy)cyclohexa-2,5-dienones that undergo Brønsted acid catalyzed intramolecular Michael addition in one-pot to produce oxo- and -aza-heterocycles in moderate to good yields. The scope of the developed methodology includes dipeptides Boc-Tyr-Gly-OEt and Boc-Tyr-Phe-Me and provides a pathway for understanding the possible transformations arising from oxidative stress of tyrosine residues. A novel method of selective cleavage of O-O bond in hindered internal peroxide using TiCl(4) has been discovered in efforts directed to the construction of cleroindicin F, whose synthesis was completed in 50% yield over just 3 steps from tyrosol using the developed methodology.

Dirhodium-catalyzed phenol and aniline oxidations with T-HYDRO. Substrate scope and mechanism of oxidation.

Dirhodium caprolactamate, Rh(2)(cap)(4), is a very efficient catalyst for the generation of the tert-butylperoxy radical from tert-butyl hydroperoxide, and the tert-butylperoxy radical is a highly effective oxidant for phenols and anilines. These reactions are performed with 70% aqueous tert-butyl hydroperoxide using dirhodium caprolactamate in amounts as low as 0.01 mol % to oxidize para-substituted phenols to 4-(tert-butyldioxy)cyclohexadienones. Although these transformations have normally been performed in halocarbon solvents, there is a significant rate enhancement when Rh(2)(cap)(4)-catalyzed phenol oxidations are performed in toluene or chlorobenzene. Electron-rich and electron-poor phenolic substrates undergo selective oxidation in good to excellent yields, but steric influences from bulky para substituents force oxidation onto the ortho position resulting in ortho-quinones. Comparative results with RuCl(2)(PPh(3))(3) and CuI are provided, and mechanistic comparisons are made between these catalysts that are based on diastereoselectivity (reactions with estrone), regioselectivity (reactions with p-tert-butylphenol), and chemoselectivity in the formation of 4-(tert-butyldioxy)cyclohexadienones. The data obtained are consistent with hydrogen atom abstraction by the tert-butylperoxy radical followed by radical combination between the phenoxy radical and the tert-butylperoxy radical. Under similar reaction conditions, para-substituted anilines are oxidized to nitroarenes in good yield, presumably through the corresponding nitrosoarene, and primary amines are oxidized to carbonyl compounds by TBHP in the presence of catalytic amounts of Rh(2)(cap)(4).

Challenging cases encountered in colorectal cancer screening for Lynch syndrome reveal novel findings: nucleolar MSH6 staining and impact of prior chemoradiation therapy.

Many pathology laboratories have developed specific screening protocols to detect patients with Lynch syndrome. With recent recommendations to test all patients with newly diagnosed colorectal cancer for Lynch syndrome, the volume of testing will increase, and the most economic and reliable screening test will prevail. Although the detection of microsatellite instability by polymerase chain reaction and the detection of loss of the mismatch repair proteins by immunohistochemistry can each be used as a screening tool, each methodology has its strengths and weaknesses. During the time of our study, we used both polymerase chain reaction and immunohistochemistry to screen for Lynch syndrome in colorectal cancer specimens. We encountered 21 cases that posed significant interpretive challenges. A previously unpublished pattern of nucleolar MSH6 staining and potential spurious results induced by chemoradiation therapy are described. We feel that it is important to report these cases so that potential pitfalls in screening for Lynch syndrome can be avoided.

Performance of the revised Bethesda guidelines for identification of colorectal carcinomas with a high level of microsatellite instability.

CONTEXT: Criteria for microsatellite instability (MSI) testing to rule out hereditary nonpolyposis colorectal cancer were recently revised and include parameters such as age and specific histologic features that can be identified by the pathologist, triggering reflex MSI testing. OBJECTIVE: To review the performance of the revised Bethesda guidelines to identify MSI-positive colorectal cancers. DESIGN: Seventy-five patients with colorectal cancer were included; 68 patients younger than 50 years and 7 patients between 50 and 60 years were selected based on histopathologic criteria. Microsatellite instability testing with the National Cancer Institute--recommended panel and immunohistochemistry for hMLH1 and hMSH2 were performed. Tumors were classified into microsatellite instability high (MSI-H), low (MSI-L), or stable (MSS) categories. RESULTS: Overall, 17 (23%) of 75 colorectal cancer cases were classified as MSI-H, including 13 patients younger than 50 years and 4 patients between 50 and 60 years. Among the MSI-H tumors, 10 (59%) were characterized by loss of hMLH1 and 6 (35%) were hMSH2 negative. Histologic features suggestive of MSI-H phenotype were present in 80% of MSI-H and 35% of MSS/MSI-L tumors. The number of positive lymph nodes was higher in MSS/MSI-L adenocarcinomas (P = .04). CONCLUSIONS: By selecting for age and histologic features, we detected MSI-H tumors in approximately one quarter of colorectal cancer cases meeting the revised Bethesda guidelines and identified 17 MSI-H cases, whereas only 8 would have been recognized by the prior guidelines. These data indicate that reflex testing requested by pathologists based on the revised Bethesda guidelines increases the detection of MSI-H and potential hereditary nonpolyposis colorectal cancer cases.

Metastatic adenocarcinoma of the colon presenting as a mass in the mandible.

BACKGROUND: Metastatic adenocarcinoma of the colon is a frequently encountered medical situation. Metastasis to the mandible from adenocarcinoma of the colon is very unusual and rarely reported. We report the case of a 73-year-old man with metastatic adenocarcinoma to the mandible. METHODS: The patient was referred for evaluation of a mass of 2 months' duration in the right parotid gland. He gave a history of watery bowel movements of unknown duration. Physical examination revealed a 7- x 6-cm hard mass, which seemed to be fixed to the right mandible. A CT scan revealed a destructive process involving the ramus and condyle of the right mandible that invaded the pterygopalatine fossa, pterygoid muscles, and middle cranial fossa. CT scans of the abdomen and pelvis revealed a 5-cm mass in the sigmoid colon with metastases to the liver. RESULTS: A biopsy of the mass in the mandible was performed, and metastatic adenocarcinoma of colonic origin was diagnosed. Colonoscopy and biopsy of the colonic mass substantiated that the sigmoid colon was the primary site of the cancer. Because the patient had disseminated disease, he declined treatment, and he died shortly thereafter. CONCLUSIONS: Although rare, metastatic adenocarcinoma from the colon to the mandible and parotid area should be included in the differential diagnosis of masses in this area. After analysis of our case and a review of the literature, we conclude that metastasis from adenocarcinoma of the colon is quite rare and represents incurable disseminated disease.

Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications.

OBJECTIVE: To review the epidemiology and characteristics of patients who died or underwent colectomy secondary to fulminant Clostridium difficile colitis. SUMMARY BACKGROUND DATA: In patients with C. difficile colitis, a progressive, systemic inflammatory state may develop that is unresponsive to medical therapy; it may progress to colectomy or death. METHODS: The authors reviewed 2,334 hospitalized patients with C. difficile colitis from January 1989 to December 2000. Sixty-four patients died or underwent colectomy for pathologically proven C. difficile colitis. RESULTS: In 2000, the incidence of C. difficile colitis in hospitalized patients increased from a baseline of 0.68% to 1.2%, and the incidence of patients with C. difficile colitis in whom life-threatening symptoms developed increased from 1.6% to 3.2%. Forty-four patients required a colectomy and 20 others died directly from C. difficile colitis. Twenty-two percent had a prior history of C. difficile colitis. A recent surgical procedure and immunosuppression were common predisposing conditions. Lung transplant patients were 46 times more likely to have C. difficile colitis and eight times more likely to have severe disease. Abdominal computed tomography scan correctly diagnosed all patients, whereas 12.5% of toxin assays and 10% of endoscopies were falsely negative. Patients undergoing colectomy for C. difficile colitis had an overall death rate of 57%. Significant predictors of death after colectomy were preoperative vasopressor requirements and age. CONCLUSIONS: C. difficile colitis is a significant and increasing cause of death. Surgical treatment of C. difficile colitis has a high death rate once the fulminant expression of the disease is present.