Clinical Focus

  • Cancer > GI Oncology
  • Anal Cancer
  • Basal / Squamous Cell Carcinomas
  • Basal / Squamous Cell Carcinomas - Surgery
  • Carcinoid Tumors
  • Carcinoid Tumors - Surgery
  • Colon and Rectal Surgery
  • Colorectal Cancer
  • Colorectal Cancer - Surgery
  • Gastrointestinal Cancers
  • Gastrointestinal Cancers - Surgical Oncology
  • Inflammatory Bowel Disease
  • Rectal Cancer
  • Rectal Cancer - Surgery

Academic Appointments

Honors & Awards

  • Best Basic Science Paper, National Meeting of American Society of Colon & Rectal Surgeons (1999)
  • Distinguished Physician Award, Crohn's and Colitis Foundation of America (1998)
  • Young Researcher Award, Research Foundation of the American Society of Colon & Rectal Surgeons (1998)
  • Alpha Omega Alpha, UCLA School of Medicine (1984)
  • Phi Kappa Phi, UC Davis (1979)

Professional Education

  • Board Certification: General Surgery, American Board of Surgery (1992)
  • Residency:UCLA Medical Center (1992) CA
  • Board Certification: Colon and Rectal Surgery, American Board of Colon and Rectal Surgery (1994)
  • Fellowship:Barnes - Jewish Hospital (1993) MO
  • Internship:UCLA Medical Center (1985) CA
  • Medical Education:UCLA School of Medicine (1984) CA
  • B.S. (Honors), UC Davis, Human Development (1979)
  • M.D., UCLA, Medicine (1984)

Current Research and Scholarly Interests

Clinical research focused on the diagnosis, prevention and treatment of anal cancer and its precursor lesions. Clinical trials of ablative therapy for High-grade Squamous Intraepithelial Lesions (HSIL) of the anus and perianal tissues as a means for preventing anal cancer.
Basic science work in collaboration with Ronald Davis and Hanlee Ji focused on the molecular genetic and pathologic studies of anal cancers using moecular inversion probe genomic technology

2016-17 Courses

All Publications

  • Rendezvous EndoSeel Technique for Non-operative Closure of Anastomotic Leak After Ileoanal Pouch Operation DIGESTIVE DISEASES AND SCIENCES Thosani, N., Sethi, S., Hovsepian, D., Kochar, R., Welton, M., Banerjee, S. 2015; 60 (12): 3545-3548

    View details for DOI 10.1007/s10620-015-3657-1

    View details for Web of Science ID 000364563600009

    View details for PubMedID 25868632

  • Prevalence of Anal Dysplasia in Patients With Inflammatory Bowel Disease. Clinical gastroenterology and hepatology Shah, S. B., Pickham, D., Araya, H., Kamal, A., Pineda, C. E., Ghole, S., Shih, L., Kong, C., Pai, R., Welton, M. 2015; 13 (11): 1955-61 e1


    Although the prevalence of anal dysplasia is higher in some immunosuppressed populations, the prevalence in patients with inflammatory bowel disease (IBD) is unknown. We examined the prevalence of abnormal anal cytology among IBD patients, and its relation to the human papilloma virus (HPV).Adults with IBD and age-matched healthy controls (HC) were recruited. IBD patients were categorized as nonimmunosuppressed (IBD-N) or immunosuppressed (IBD-I). Anal Papanicolaou tests were performed for HPV testing and classification by a cytopathologist as follows: negative, atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, cancer, or unsatisfactory.A total of 270 subjects (100 IBD-I, 94 IBD-N, and 76 HC) were recruited. ASC-US were detected in 19 subjects, with a trend toward a higher prevalence among IBD subjects compared with HC (8.8% vs 2.6%; P = .10). The prevalence did not differ with respect to immunosuppression. Crohn's disease (CD) subjects had a higher prevalence of ASC-US compared with others with IBD (P = .02). Among those with CD, female sex and disease duration longer than 10 years were risk factors. There were no cases of low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, or anal cancer in the cohort. HPV was present in 5.3% and 1.5% of subjects with and without ASC-US, respectively (P = .26).Although there was a trend toward abnormal anal Papanicolaou tests in IBD subjects compared with HC, there was no difference based on immunosuppression. The presence of HPV did not correlate with abnormal anal cytology. Risk factors associated with this increased trend include female CD subjects and those with a longer duration of CD. number: NCT01860963;

    View details for DOI 10.1016/j.cgh.2015.05.031

    View details for PubMedID 26044314

  • Controversies in the management of anal high-grade squamous intraepithelial lesions. Minerva chirurgica Pineda, C. E., Welton, M. L. 2008; 63 (5): 389-399


    Anal squamous dysplasia is recognized as a spectrum of disease that ranges from low-grade intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions (HSIL) to invasive anal squamous cell carcinoma (SCC). Recent reports have shown a significant increase in both the incidence and prevalence of both HSIL and anal SCC, particularly in immunocompromised patients and in men who have sex with men. These lesions are associated with chronic infection with the human papillomavirus. The natural history is unknown, yet reports of untreated patients have shown progression rates of up to 50% in high risk patients. There are controversies as to the optimal management of patients with HSIL. However, there is evidence that screening of high-risk patients with anal cytology is useful in identifying those that require further evaluation. Examination of the anorectal region is enhanced with the use of high resolution anoscopy. Treatment modalities vary in terms of morbidity and success rates. Wide local excision is associated with significant morbidity. Newer therapies such as topical immunomodulation, photodynamic therapy and therapeutic vaccines have been proposed, but long-term follow-up is unavailable. High resolution anoscopy can be used in the office or in the operating room to direct therapy. Using a comprehensive approach of cytology and office-based and/or operating room procedures directed with high resolution anoscopy results in clearance of HSIL in up to 80% of patients, malignant progression in 1%, and less morbidity than wide local excision.

    View details for PubMedID 18923350

  • Diagnostic problems in anal pathology ADVANCES IN ANATOMIC PATHOLOGY Longacre, T. A., Kong, C. S., Welton, M. L. 2008; 15 (5): 263-278


    Anal squamous cell carcinoma and its precursor lesions are increasing in incidence in the United States and Europe. This trend predates human immunodeficiency virus/acquired immune deficiency syndrome and has been associated with persistent high-risk human papilloma virus (HPV) genotype infection, previous lower genital tract dysplasia/carcinoma, high frequency anoreceptive intercourse, heavy cigarette smoking, immunosuppression in solid organ transplant and immune disorders, and human immunodeficiency virus seropositivity. Screening protocols for at-risk patients are under active investigation and pathologists are often asked to assess anal canal and perianal biopsies for the presence of dysplasia and/or invasive carcinoma. Because underdiagnosis and overdiagnosis of anal cancer and precancer may lead to inappropriate treatment, it is important for the pathologist to be aware of current screening strategies, specific risk lesions, and the role of pathology in initial diagnosis and evaluation of anal biopsy and/or resection specimens. Standardized histologic criteria and uniform terminology should be used for reporting all anal canal and perianal squamous intraepithelial lesions. HPV subtyping, anal cytology, and recently identified biomarkers, such as p16 and Becton Dickinson ProEx C may provide additional information in problematic cases, but it is important to be aware of the limitations of these assays. HPV has been linked to all the major histologic subtypes of anal carcinoma (eg, basaloid, cloacogenic, transitional, etc.) and this association is strongest for anal canal lesions. With the possible exception of the microcystic pattern, histologic subtype does not seem to predict prognosis; and anal squamous cell carcinomas should be classified as either keratinizing or nonkeratinizing. Poorly differentiated squamous cell carcinomas have a worse prognosis and should be distinguished from poorly differentiated adenocarcinoma, melanoma, and neuroendocrine tumors. Very well differentiated squamous cell carcinoma with pushing margins (so-called giant condyloma of Buschke and Lowenstein) should be classified as verrucous carcinoma; this tumor shows aggressive local infiltration but does not metastasize. As all anal condylomata may harbor foci of high-grade dysplasia or invasive carcinoma, careful sectioning and complete histologic examination is required.

    View details for Web of Science ID 000259172900002

    View details for PubMedID 18724100

  • Role of human papillomavirus in squamous cell metaplasia-dysplasia-carcinoma of the rectum AMERICAN JOURNAL OF SURGICAL PATHOLOGY Kong, C. S., Welton, M. L., Longacre, T. A. 2007; 31 (6): 919-925


    Primary colorectal squamous cell carcinoma (SCC) and squamous dysplasia are uncommon and little is known about their pathogenesis. Most have been reported in association with ulcerative colitis and other chronic disease states. Although cervical and anal SCC have been strongly linked to human papillomavirus (HPV) infection, the role of HPV in rectal squamous carcinoma has not been well-examined. We evaluated 3 cases of primary rectal SCC for the presence of high-risk HPV by immunohistochemistry for p16(INK4A), in situ hybridization, and polymerase chain reaction. HPV type 16 was detected by polymerase chain reaction in all cases. In addition, all cases exhibited diffuse strong reactivity for p16(INK4A) and punctate nuclear staining by Ventana HPVIII in situ hybridization. The presence of HPV 16 in all three cases suggests that high-risk HPV infection is a risk factor for rectal SCC, particularly in patients with underlying chronic inflammatory disease processes or altered immune status. Further studies are warranted to determine if SCC occurring more proximal in the colon are also HPV-dependent or occur via another, HPV-independent pathway.

    View details for Web of Science ID 000246872500014

    View details for PubMedID 17527081

  • Transperineal repair of persistent rectovaginal fistulas using an acellular cadaveric dermal graft (AlloDerm (R)) DISEASES OF THE COLON & RECTUM Shelton, A. A., Welton, M. L. 2006; 49 (9): 1454-1457


    A number of surgical techniques have been described to treat rectovaginal fistulas. Recurrent or persistent fistulas after previous repair can be particularly difficult to treat. We report a novel technique used to successfully repair rectovaginal fistulas after failed mucosal advancement flap procedures using a transperineal-layered closure with an interposed graft of acellular cadaveric dermis (Alloderm).

    View details for DOI 10.1007/s10350-006-0619-x

    View details for Web of Science ID 000240516100026

    View details for PubMedID 16897332

  • The etiology and epidemiology of anal cancer. Surgical oncology clinics of North America Welton, M. L., Sharkey, F. E., Kahlenberg, M. S. 2004; 13 (2): 263-275


    The anatomic definitions for anal cancer (canal versus margin) are made based on the relationship of the tumor to the anal verge. This method had led to confusion for some providers. A modification in the terminology is proposed that includes intra-anal, perianal, and skin as categories. The cause of anal carcinoma remains to be fully elucidated, and HPV seems to play a central role in this process. The incidence of anal cancers has increased, which is related to the evolution of HIV and AIDS, and their treatment. The accurate pathologic analysis of anal tumors is complex and is significantly aided by close communication between clinician and pathologist.

    View details for PubMedID 15137956

  • Expression and endocytosis of VEGF and its receptors in human colonic vascular endothelial cells AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Wang, D. F., Lehman, R. E., Donner, D. B., Matli, M. R., Warren, R. S., Welton, M. L. 2002; 282 (6): G1088-G1096


    Normal human colonic microvascular endothelial cells (HUCMEC) have been isolated from surgical specimens by their adherence to Ulex europaeus agglutinin bound to magnetic dynabeads that bind alpha-L-fucosyl residues on the endothelial cell membrane. Immunocytochemistry demonstrated the presence of a range of endothelial-specific markers on HUCMEC, including the von Willebrand factor, Ulex europaeus agglutinin, and platelet endothelial cell adhesion molecule-1. The growing cells form monolayers with the characteristic cobblestone morphology of endothelial cells and eventually form tube-like structures. HUCMEC produce vascular endothelial growth factor (VEGF) and express the receptors, kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase, through which VEGF mediates its actions in the endothelium. VEGF induces the tyrosine phosphorylation of KDR and a proliferative response from HUCMEC comparable to that elicited from human umbilical vein endothelial cells (HUVEC). On binding to HUCMEC or HUVEC, (125)I-labeled VEGF internalizes or dissociates to the medium. Once internalized, (125)I-labeled VEGF is degraded and no evidence of ligand recycling was observed. However, significantly less VEGF is internalized, and more is released to the medium from HUCMEC than HUVEC. Angiogenesis results from the proliferation and migration of microvascular, not large-vessel, endothelial cells. The demonstration that microvascular endothelial cells degrade less and release more VEGF to the medium than large-vessel endothelial cells identifies a mechanism permissive of the role of microvascular cells in angiogenesis.

    View details for DOI 10.1152/ajpgi.00250.2001

    View details for Web of Science ID 000175620100021

    View details for PubMedID 12016135

  • Anal Cartography in the Treatment of Anal Bowen?s Disease and High-Grade Squamous Intraepithelial Lesions Submitted Dis Colon Rectum Welton ML 2002
  • Anal Bowen?s Disease and High Grade Squamous Intraepithelial Lesions are Histologically and Immunohistochemically Indistinguishable Submitted Dis Colon Rectum Welton ML, merhauser A, Litle VL, Leavenworth J, Darraugh T, Palefsky JM 2002
  • Screening for Anal Cancer in Women. Journal of lower genital tract disease Moscicki, A., Darragh, T. M., Berry-Lawhorn, J. M., Roberts, J. M., Khan, M. J., Boardman, L. A., Chiao, E., Einstein, M. H., Goldstone, S. E., Jay, N., Likes, W. M., Stier, E. A., Welton, M. L., Wiley, D. J., Palefsky, J. M. 2015; 19 (3): S26-41


    The incidence of anal cancer is higher in women than men in the general population and has been increasing for several decades. Similar to cervical cancer, most anal cancers are associated with human papillomavirus (HPV), and it is believed that anal cancers are preceded by anal high-grade squamous intraepithelial lesions (HSIL). Our goals were to summarize the literature on anal cancer, HSIL, and HPV infection in women and to provide screening recommendations in women.A group of experts convened by the American Society for Colposcopy and Cervical Pathology and the International Anal Neoplasia Society reviewed the literature on anal HPV infection, anal SIL, and anal cancer in women.Anal HPV infection is common in women but is relatively transient in most. The risk of anal HSIL and cancer varies considerably by risk group, with human immunodeficiency virus-infected women and those with a history of lower genital tract neoplasia at highest risk compared with the general population.While there are no data yet to demonstrate that identification and treatment of anal HSIL leads to reduced risk of anal cancer, women in groups at the highest risk should be queried for anal cancer symptoms and required to have digital anorectal examinations to detect anal cancers. Human immunodeficiency virus-infected women and women with lower genital tract neoplasia may be considered for screening with anal cytology with triage to treatment if HSIL is diagnosed. Healthy women with no known risk factors or anal cancer symptoms do not need to be routinely screened for anal cancer or anal HSIL.

    View details for DOI 10.1097/LGT.0000000000000117

    View details for PubMedID 26103446

  • Equivocal Effect of Intraoperative Fluorescence Angiography on Colorectal Anastomotic Leaks DISEASES OF THE COLON & RECTUM Kin, C., Vo, H., Welton, L., Welton, M. 2015; 58 (6): 582-587


    Intraoperative fluorescence angiography is beneficial in several surgical settings to assess tissue perfusion. It is also used to assess bowel perfusion, but its role in improving outcomes in colorectal surgery has not been studied.The purpose of this work was to determine whether intraoperative angiography decreases colorectal anastomotic leaks.This was a case-matched retrospective study in which patients were matched 1:1 with respect to sex, age, level of anastomosis, presence of a diverting loop ileostomy, and preoperative pelvic radiation therapy.The study was conducted at an academic medical center.Patients who underwent colectomy or proctectomy with primary anastomoses were included.The intraoperative use of fluorescence angiography to assess perfusion of the colon for anastomosis was studied.Anastomotic leak within 60 days and whether angiography changed surgical management were the main outcomes measured.Case matching produced 173 pairs. The groups were also comparable with respect to BMI, smoking status, diabetes mellitus, surgical indications, and type of resection. In patients who had intraoperative angiography, 7.5% developed anastomotic leak, whereas 6.4% of those without angiography did (p value not significant). Univariate analysis revealed that preoperative pelvic radiation, more distal anastomosis, surgeon, and diverting loop ileostomy were positively associated with anastomotic leak. Multivariate analysis demonstrated that level of anastomosis and surgeon were associated with leaks. Poor perfusion of the proximal colon seen on angiography led to additional colon resection before anastomosis in 5% of patients who underwent intraoperative angiography.The retrospective study design with the use of historical control subjects, selection bias, and small sample size were limitations to this study.Intraoperative fluorescence angiography to assess the perfusion of the colon conduit for anastomosis was not associated with colorectal anastomotic leak. Perfusion is but one of multiple factors contributing to anastomotic leaks. Additional studies are necessary to determine whether this technology is beneficial for colorectal surgery.

    View details for DOI 10.1097/DCR.0000000000000320

    View details for Web of Science ID 000354100400011

    View details for PubMedID 25944430

  • Progression of anal high-grade squamous intraepithelial lesions to invasive anal cancer among HIV-infected men who have sex with men INTERNATIONAL JOURNAL OF CANCER Berry, J. M., Jay, N., Cranston, R. D., Darragh, T. M., Holly, E. A., Welton, M. L., Palefsky, J. M. 2014; 134 (5): 1147-1155


    The incidence of anal cancer is elevated in human immunodeficiency virus (HIV)-infected men-who-have-sex-with-men (MSM) compared to the general population. Anal high-grade squamous intraepithelial lesions (HSIL) are common in HIV-infected MSM and the presumed precursors to anal squamous cell cancer; however, direct progression of HSIL to anal cancer has not been previously demonstrated. The medical records were reviewed of 138 HIV-infected MSM followed up at the University of California, San Francisco, who developed anal canal or perianal squamous cancer between 1997 and 2011. Men were followed up regularly with digital anorectal examination (DARE), high-resolution anoscopy (HRA) and HRA-guided biopsy. Although treatment for HSIL and follow-up were recommended, not all were treated and some were lost to follow-up. Prevalent cancer was found in 66 men. Seventy-two HIV-infected MSM developed anal cancer while under observation. In 27 men, anal cancer developed at a previously biopsied site of HSIL. An additional 45 men were not analyzed in this analysis due to inadequate documentation of HSIL in relation to cancer location. Of the 27 men with documented progression to cancer at the site of biopsy-proven HSIL, 20 men progressed from prevalent HSIL identified when first examined and seven men from incident HSIL. Prevalent HSIL progressed to cancer over an average of 57 months compared to 64 months for incident HSIL. Most men were asymptomatic, and cancers were detected by DARE. Anal HSIL has clear potential to progress to anal cancer in HIV-infected MSM. Early diagnosis is facilitated by careful follow-up. Carefully controlled studies evaluating efficacy of screening for and treatment of HSIL to prevent anal cancer are needed.

    View details for DOI 10.1002/ijc.28431

    View details for Web of Science ID 000328246700014

    View details for PubMedID 23934991

  • Predictors of postoperative urinary retention after colorectal surgery. Diseases of the colon & rectum Kin, C., Rhoads, K. F., Jalali, M., Shelton, A. A., Welton, M. L. 2013; 56 (6): 738-746


    : National quality initiatives have mandated the earlier removal of urinary catheters after surgery to decrease urinary tract infection rates. A potential unintended consequence is an increased postoperative urinary retention rate.: The aim of this study was to determine the incidence and risk factors for postoperative urinary retention after colorectal surgery.: This was a prospective observational study.: A colorectal unit within a single institution was the setting for this study.: Adults undergoing elective colorectal operations were included.: Urinary catheters were removed on postoperative day 1 for patients undergoing abdominal operations, and on day 3 for patients undergoing pelvic operations. Postvoid residual and retention volumes were measured.: The primary outcomes measured were urinary retention and urinary tract infection.: The overall urinary retention rate was 22.4% (22.8% in the abdominal group, 21.9% in the pelvic group) and was associated with longer operative time and increased perioperative fluid administration. Mean operative time for those with retention was 2.8 hours and, for those without retention, the mean operative time 2.2 hours (abdominal group 2 hours vs 1.4 hours, pelvic group 3.9 hours vs 3.1 hours, p ≤ 0.02). Patients with retention received a mean of 2.7L during the operation, whereas patients without retention received 1.8L (abdominal group 1.9L vs 1.4L, pelvic group 3.6L vs 2.2L, p < 0.01). In the abdominal group, patients with and without retention also received different fluid volumes on postoperative days 1 (2.2L vs 1.7L, p = 0.004) and 2 (1.6L vs 1L, p = 0.05). Laparoscopic abdominal group had a 40% retention rate in comparison with 12% in the open abdominal group (p = 0.004). Age, sex, preoperative radiation therapy, preoperative prostatism, preoperative diagnosis, and level of anastomosis were not associated with retention. The urinary tract infection rate was 4.9%.: The lack of documentation of preoperative urinary function was a limitation of this study.: The practice of earlier urinary catheter removal must be balanced with operative time and fluid volume to avoid high urinary retention rates. Also important is increased vigilance for the early detection of retention.

    View details for DOI 10.1097/DCR.0b013e318280aad5

    View details for PubMedID 23652748

  • p16 Is Superior to ProEx C in Identifying High-grade Squamous Intraepithelial Lesions (HSIL) of the Anal Canal AMERICAN JOURNAL OF SURGICAL PATHOLOGY Bala, R., Pinsky, B. A., Beck, A. H., Kong, C. S., Welton, M. L., Longacre, T. A. 2013; 37 (5): 659-668


    Although the incidence of human papillomavirus (HPV)-associated anal neoplasia is increasing, interobserver and intraobserver reproducibility in the grading of biopsy specimens from this area remains unacceptably low. Attempts to produce a more reproducible grading scheme have led to the use of biomarkers for the detection of high-risk HPV (HR-HPV). We evaluated the performance of standard morphology and biomarkers p16, ProEx C, and Ki-67 in a set of 75 lesions [17 nondysplastic lesions, 23 low-grade squamous intraepithelial lesions (LSIL)/condyloma, 20 high-grade squamous intraepithelial lesions (HSIL), 15 invasive squamous cell carcinomas] from the anal and perianal region in 65 patients and correlated these findings with HPV subtype on the basis of a type-specific multiplex real-time polymerase chain reaction assay designed to detect HR-HPV. A subset of cases with amplifiable HPV DNA was also sequenced. HSIL was typically flat (15/20), and only a minority (4/20) had koilocytes. In contrast, only 1 LSIL was flat (1/23), and the remainder were exophytic. The majority of LSIL had areas of koilocytic change (20/23). HR-HPV DNA was detected in the majority (89%) of invasive carcinomas and HSIL biopsies, 86% and 97% of which were accurately labeled by strong and diffuse block-positive p16 and ProEx C, respectively. LSIL cases, however, only infrequently harbored HR-HPV (13%); most harbored low-risk HPV (LR-HPV) types 6 and 11. Within the LSIL group, p16 outperformed ProEx C, resulting in fewer false-positive cases (5% vs. 75%). Ki-67 was also increased in HR-HPV-positive lesions, although biopsies with increased inflammation and reactive changes also showed higher Ki-67 indices. These data suggest that strong and diffuse block-positive nuclear and cytoplasmic labeling with p16 is a highly specific biomarker for the presence of HR-HPV in anal biopsies and that this finding correlates with high-grade lesions.

    View details for DOI 10.1097/PAS.0b013e31828706c0

    View details for Web of Science ID 000317663100005

    View details for PubMedID 23552383

  • Do Hospitals that Serve a High Percentage of Medicaid Patients Perform Well on Evidence-based Guidelines for Colon Cancer Care? Journal of health care for the poor and underserved Rhoads, K. F., Ngo, J. V., Ma, Y., Huang, L., Welton, M. L., Dudley, R. A. 2013; 24 (3): 1180-1193


    Background. Previous work suggests hospitals serving high percentages of patients with Medicaid are associated with worse colon cancer survival. It is unclear if practice patterns in these settings explain differential outcomes. Hypothesis: High Medicaid hospitals (HMH) have lower compliance with evidence-based care processes (examining 12 or more lymph nodes (LN) during surgical staging and providing appropriate chemo-therapy). Methods. Retrospective analysis of stage I-III colon cancers from California Cancer Registry (1996-2006) linked to discharge abstracts and hospital profiles predicted hospital compliance with guidelines and trends in compliance over time. Results. Cases (N=60,000) in 439 hospitals analyzed. High Medicaid hospital settings had lower odds of compliance with the 12 LN exam (ORHMH0.91, CIHMH[0.85, 0.98]) and with the delivery of appropriate chemotherapy (ORHMH0.76, CIHMH[0.67, 0.86]). Conclusions. High Medicaid hospital status is associated with poor performance on evidence-based colon cancer care. Policies to improve the quality of colon cancer care should target these settings.

    View details for DOI 10.1353/hpu.2013.0122

    View details for PubMedID 23974390

  • Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features MODERN PATHOLOGY Chang, D. T., Pai, R. K., Rybicki, L. A., DiMaio, M. A., Limaye, M., Jayachandran, P., Koong, A. C., Kunz, P. A., Fisher, G. A., Ford, J. M., Welton, M., Shelton, A., Ma, L., Arber, D. A., Pai, R. K. 2012; 25 (8): 1128-1139


    Recent literature suggests an increasing incidence of colorectal carcinoma in young patients. We performed a histologic, molecular, and immunophenotypic analysis of patients with sporadic early-onset (≤40 years of age) colorectal carcinoma seen at our institution from the years 2000-2010 and compared these tumors to a cohort of consecutively resected colorectal carcinomas seen in patients >40 years of age. A total of 1160 primary colorectal adenocarcinomas were surgically resected for the years 2000 through 2010. Of these, 75 (6%) were diagnoses in patients ≤40 years of age of which 13 (17%) demonstrated abnormalities in DNA mismatch repair, 4 (5%) were in patients with known germline genetic disorders (two patients with familial adenomatous polyposis, one patient with juvenile polyposis, and one patient with Li-Fraumeni syndrome), and three patients (4%) had long-standing chronic inflammatory bowel disease. The sporadic early-onset colorectal carcinoma group comprised a total of 55 patients (55/1160, 5%) and were compared with a control group comprising 73 consecutively resected colorectal carcinomas with proficient DNA mismatch repair in patients >40 years of age. For the early-onset colorectal carcinoma group, most cases (33/55, 60%) were diagnosed between the age of 35 and 40 years of age. Compared with the control group, the early-onset colorectal carcinoma group was significantly different with respect to tumor location (P<0.007) with 80% (44/55 cases) identified in either the sigmoid colon (24/55, 44%) or rectum (20/55, 36%). Morphologically, early-onset colorectal carcinomas more frequently displayed adverse histologic features compared with the control colorectal carcinoma group such as signet ring cell differentiation (7/55, 13% vs 1/73, 1%, P=0.021), perineural invasion (16/55, 29% vs 8/73, 11%, P=0.009) and venous invasion (12/55, 22% vs 4/73, 6%, P=0.006). A precursor adenomatous lesion was less frequently identified in the early-onset colorectal carcinoma group compared with the control group (19/55, 35% vs 39/73, 53%, P=0.034). Of the early-onset colorectal carcinomas, only 2/45 cases (4%) demonstrated KRAS mutations compared with 11/73 (15%) of the control group colorectal adenocarcinomas harboring KRAS mutations, although this difference did not reach statistical significance (P=0.13). BRAF V600E mutations were not identified in the early-onset colorectal carcinoma group. No difference was identified between the two groups with regard to tumor stage, tumor size, number of lymph node metastases, lymphatic invasion, tumor budding, mucinous histology, or tumor-infiltrating lymphocytes. Both groups had similar recurrence-free (P=0.28) and overall survival (P=0.73). However, patients in the early-onset colorectal carcinoma group more frequently either presented with or developed metastatic disease during their disease course compared with the control colorectal carcinoma group (25/55, 45% vs 18/73, 25%, P=0.014). In addition, 8/55 patients (15%) in the early-onset colorectal carcinoma group developed local recurrence of their tumor while no patients in the control colorectal carcinoma group developed local recurrence (P<0.001), likely due to the increased incidence of rectal carcinoma in the patients with early-onset colorectal carcinoma. Our study demonstrates that colorectal carcinoma is not infrequently diagnosed in patients ≤40 years of age and is not frequently the result of underlying Lynch syndrome or associated with other cancer-predisposing genetic conditions or chronic inflammatory conditions. These tumors have a striking predilection for the distal colon, particularly the sigmoid colon and rectum and are much more likely to demonstrate adverse histologic factors, including signet ring cell differentiation, venous invasion, and perineural invasion.

    View details for DOI 10.1038/modpathol.2012.61

    View details for Web of Science ID 000307222200008

    View details for PubMedID 22481281

  • Orthovoltage Intraoperative Radiotherapy for Locally Advanced and Recurrent Colorectal Cancer DISEASES OF THE COLON & RECTUM Daly, M. E., Kapp, D. S., Maxim, P. G., Welton, M. L., Tran, P. T., Koong, A. C., Chang, D. T. 2012; 55 (6): 695-702


    Locally advanced and recurrent colorectal cancers pose a significant therapeutic challenge. Orthovoltage intraoperative radiotherapy provides one potential means of improving disease control at the time of surgery.This study sought to analyze outcomes and identify prognostic factors of patients treated with orthovoltage intraoperative radiotherapy for locally advanced or recurrent colorectal cancer.This study is a retrospective chart review conducted at a tertiary medical center.Between January 1990 and July 2009, 55 patients underwent intraoperative radiotherapy to a total of 61 sites for locally advanced (n = 14) or recurrent (n = 41) cancers of colon (n = 18) or rectum/rectosigmoid junction (n = 37).Median dose was 12 Gy (range, 7.5-20 Gy). Among locally advanced rectal/rectosigmoid cases, surgery included abdominoperineal resection (n = 3) or low anterior resection (n = 9). Seven treated sites had gross residual (R2) disease, 28 had pathologic or clinical microscopic residual disease (R1), and 15 were complete resections (R0). Treated sites included sacrum (n = 22), anterior pelvis/pelvic sidewall (19), sacrum and sidewall (n = 1), aortic bifurcation (n = 2), vaginal cuff (n = 2), psoas (n = 3), perivesicular region (n = 2), and other (n = 10).Outcomes measures included in-field local control, locoregional control, overall survival, and grade ≥3 toxicity.At a median follow-up of 27 months (range, 4-237) among living patients, 2-year Kaplan-Meier estimates of in-field local control, locoregional control, and overall survival were 69%, 51%, and 59%. Margin status predicted for improved locoregional control (p = 0.01) and overall survival (p = 0.01). Seventeen patients (31%) developed a grade 3 to 5 toxicity following surgery with intraoperative radiotherapy.This study was limited by its retrospective nature and relatively small sample size.Local control with intraoperative radiotherapy for locally advanced and recurrent colorectal cancers is good despite the high risk of residual disease. Among carefully selected patients, multimodality regimens including intraoperative radiotherapy may permit long-term survival.

    View details for DOI 10.1097/DCR.0b013e31824d464c

    View details for Web of Science ID 000304368500011

    View details for PubMedID 22595850

  • Intensity-Modulated Radiation Therapy Versus Conventional Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal CANCER Bazan, J. G., Hara, W., Hsu, A., Kunz, P. A., Ford, J., Fisher, G. A., Welton, M. L., Shelton, A., Kapp, D. S., Koong, A. C., Goodman, K. A., Chang, D. T. 2011; 117 (15): 3342-3351


    The purpose of this study was to compare outcomes in patients with anal canal squamous cell carcinoma (SCCA) who were treated with definitive chemoradiotherapy by either intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (CRT).Forty-six patients who received definitive chemoradiotherapy from January 1993 to August 2009 were included. Forty-five patients received 5-fluorouracil with mitomycin C (n = 39) or cisplatin (n = 6). Seventeen (37%) were treated with CRT and 29 (63%) with IMRT. The median dose was 54 Gy in both groups. Median follow-up was 26 months (CRT) and 32 months (IMRT). T3-T4 stage (P = .18) and lymph node-positive disease (P = .6) were similar between groups.The CRT group required longer treatment duration (57 days vs 40 days, P < .0001), more treatment breaks (88% vs 34.5%, P = .001), and longer breaks (12 days vs 1.5 days, P < .0001) than patients treated with IMRT. Eleven (65%) patients in the CRT group experienced grade >2 nonhematologic toxicity compared with 6 (21%) patients in the IMRT group (P = .003). The 3-year overall survival (OS), locoregional control (LRC), and progression-free survival were 87.8%, 91.9%, and 84.2%, respectively, for the IMRT groups and 51.8%, 56.7%, and 56.7%, respectively, for the CRT group (all P < .01). On multivariate analysis, T stage, use of IMRT, and treatment duration were associated with OS, and T stage and use of IMRT were associated with LRC.The use of IMRT was associated with less toxicity, reduced need for treatment breaks, and excellent LRC and OS compared with CRT in patients with SCCA of the anal canal.

    View details for DOI 10.1002/cncr.25901

    View details for Web of Science ID 000293103800008

    View details for PubMedID 21287530

  • Pathological response after chemoradiation for T3 rectal cancer. Colorectal disease Chennupati, S. K., Kamaya, A., Fisher, G. A., Ford, J. M., Kunz, P., Itakura, H., Welton, M. L., Shelton, A., Van Dam, J., Koong, A. C., Chang, D. T. 2010; 12 (7 Online): e24-30


    The aim of this study was to investigate the effect of preoperative chemoradiotherapy (CRT) on nodal disease in locally advanced rectal adenocarcinoma.Thirty-two patients staged uT3N0 and 27 patients staged uT3N1 rectal adenocarcinoma who underwent pre-CRT staging using endoscopic ultrasound or rectal protocol CT were included. The median radiation dose was 50.4 Gy (range: 45-50.4 Gy) at 1.8 Gy per fraction and all patients received concurrent 5-FU or capecitabine-based chemotherapy. Low anterior resection or abdomino-perineal resection occurred at a median of 46 days (range: 27-112 days) after CRT.Eleven of 32 uT3N0 patients (34.4%) and 13 of 26 uT3N1 patients (50.0%) had ypN+ (P = 0.29). For patients with uT3N0, 10 of 20 (50.0%) with ypT2-3 and 1 of 12 (8.3%) with ypT0-1 were ypN+ (P = 0.02). For patients with uT3N1, 12 of 20 (60.0%) with ypT2-3 and 1 of 6 (16.7%) with ypT0-1 were ypN+ (P = 0.16). Overall, the ypN+ rate was 11.1% in the ypT0-yT1 group compared with 55.0% in the ypT2-yT3 group (P = 003). Among patients with uT3N0 disease, the ypN+ rate in patients who had surgery > 46 days vs 46 days vs 46 days vs

    View details for DOI 10.1111/j.1463-1318.2009.02013.x

    View details for PubMedID 19614668

  • Pathological response after chemoradiation for T3 rectal cancer COLORECTAL DISEASE Chennupati, S. K., Kamaya, A., Fisher, G. A., Ford, J. M., Kunz, P., Itakura, H., Welton, M. L., Shelton, A., Van Dam, J., Koong, A. C., Chang, D. T. 2010; 12 (7): E24-E30
  • Intensity Modulated Radiation Therapy vs. Conventional Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Bazan, J. G., Hara, W., Kunz, P., Fisher, G. A., Ford, J. M., Welton, M. L., Koong, A., Shelton, A., Goodman, K. A., Chang, D. T. ELSEVIER SCIENCE INC. 2010: S300–S301
  • Management of anal squamous intraepithelial lesions. Clinics in colon and rectal surgery Pineda, C. E., Welton, M. L. 2009; 22 (2): 94-101


    Anal squamous intraepithelial lesions include both low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and are caused by chronic infection with the human papillomavirus (HPV). The disease is increasing in both incidence and prevalence, especially among patients with the following risk factors: homosexual men, acquired or iatrogenic immunosuppression, and presence of other HPV-related diseases. Although the natural history of the disease is unknown, there is significant evidence that untreated HSIL progresses to squamous cell carcinoma in 11% of patients and in up to 50% of patients with extensive disease and immunosuppression. Anal cytology and reflex HPV DNA testing are used to screen for disease, particularly among patients with the aforementioned risk factors. Evaluation of the patient should include physical examination and high-resolution anoscopy (HRA) to evaluate for disease above and below the dentate line. Intervention is warranted and this can be achieved in many ways. The treatment option associated with the best outcomes is ablation directed with HRA, which can be performed in the office or in the operating room with minimal morbidity. This strategy is effective in patients with both low-volume and high-volume disease and is associated with a malignant progression rate of 0.4% in patients with treated HSIL.

    View details for DOI 10.1055/s-0029-1223840

    View details for PubMedID 20436833

  • Anal cancer and its precursors in HIV-positive patients: perspectives and management. Surgical oncology clinics of North America Berry, J. M., Palefsky, J. M., Welton, M. L. 2004; 13 (2): 355-373


    Anal cancer is an increasing problem among HIV-infected persons. Although patients are living longer and with better quality of life because of treatment with HAART, they remain at risk for invasive anal cancer and its precursor, anal HSIL. Given the substantial numbers of patients with anal HSIL, further studies need to be done to determine the efficacy and optimal mode of treatment of HSIL, to define the optimal method for screening patients at risk, to define the best way to follow up patients with documented HSIL to ensure early detection, to define prognostic factors for progression to invasive cancer, and to determine the progression rate of HSIL to invasive cancer. Although patients with good functional status and immunologic function seem to do relatively well with standard CMT for anal cancer, there are less fortunate patients who experience substantial morbidity from therapy and have a poorer outcome. It is difficult to draw definitive conclusions about the therapy of HIV-positive patients with anal cancer based on the available literature because of the retrospective nature of the analyses, the small number of patients, and the heterogeneity of the patients reported with regard to tumor size, pretreatment immunologic status, and the variety of treatments received by patients in some series. Identifying patients who develop invasive anal cancer as early as possible will improve results to some degree, but prospective, controlled, multi-institutional trials evaluating the treatment of anal cancer in HIV-infected persons are required to accurately define ways to improve outcome with less morbidity. The results of ongoing therapeutic HPV vaccine trials are eagerly awaited. Improvement may come by the following, determining ways to more accurately stage patients, such as endoanal ultrasound, sentinel lymph node sampling, or positron emission tomography scans; defining the role of cisplatin and whether it is indeed less toxic and equally or more effective; consideration of continuous protracted infusion of low-dose 5-FU; the optimum use of growth factors; and an evaluation of the role of conformal radiotherapy or the use of radio-protectants, such as amifostine. Meanwhile, the best way to treat anal cancer in HIV-infected persons may be to prevent it from occurring by screening persons at risk and treating HSIL, or at a minimum, following up patients carefully and detecting cancers, if they occur, at the earliest possible time.

    View details for PubMedID 15137962

  • Rectourethral fistulae: The perineal approach JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Visser, B. C., McAninch, J. W., Welton, M. L. 2002; 195 (1): 138-143

    View details for Web of Science ID 000176600100018

    View details for PubMedID 12113539

  • Local therapy for rectal cancer SURGICAL ONCOLOGY-OXFORD Visser, B. C., Varma, M. G., Welton, M. L. 2001; 10 (1-2): 61-69


    In selected patients with early rectal cancer, local therapy is an effective alternative to radical resection and offers minimal morbidity and the avoidance of a colostomy. Several techniques are described: transanal excision, dorsal approaches (York-Mason or Kraske procedures), transanal endoscopic microsurgery, endocavitary radiation, and transanal fulguration. Among these, transanal excision is favored for the low rate of complications, promising outcomes, and ability to secure tissue for pathology. Patients with T1 lesions with favorable histologic features may undergo local excision alone, while those with T2 lesions require adjuvant chemoradiation. The data currently available do not support the use of local therapy with curative intent for tumors that are advanced (T3 or T4), poorly differentiated, or have other negative pathologic characteristics. In carefully selected patients for local excision, local recurrence and survival rates are similar to traditional radical resection. Following local excision, patients require close observation for recurrence. Most patients with local recurrence can be salvaged by radical resection, though the long-term outcome is unknown.

    View details for Web of Science ID 000172659200006

    View details for PubMedID 11719030