Bio

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


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

Professional Education


  • 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)

Research & Scholarship

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

Clinical Trials


  • Molecular Genetic and Pathological Studies of Anal Tumors Recruiting

    Study the Genetics of Anal Cancer

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  • Capecitabine, Oxaliplatin, and Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Stage I Rectal Cancer Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Oxaliplatin may make tumor cells more sensitive to radiation therapy. Giving capecitabine and oxaliplatin together with radiation therapy before surgery may shrink the tumor so it can be removed. PURPOSE: This phase II trial is studying how well giving capecitabine and oxaliplatin together with radiation therapy works in treating patients who are undergoing surgery for stage I rectal cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Moe Jalali, (650) 724 - 4023.

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  • Early Removal of Urinary Catheters in Patients After Rectal Surgery: a Prospective Study Recruiting

    Recent national surgical quality guidelines (Surgical Care Improvement Project, National Hospital Inpatient Quality Measures)state that removal of urinary catheters should occur by post-operative day two for all surgical patients. These guidelines exclude neither patients who have undergone rectal surgery nor those with epidural analgesic catheters. The common practice among most colorectal surgeons is to leave urinary catheters in for three to five days for patients who have undergone rectal operations, due to concern for urinary retention. This study aims to explore the outcomes of following the national surgical guidelines for early urinary catheter removal, especially with regards to urinary retention and urinary tract infection.

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  • Parastomal Reinforcement With Strattice Not Recruiting

    The purpose of this study is to compare the clinical outcomes of patients undergoing surgery for a permanent abdominal wall ostomy with and without placement of Strattice fascial inlay, as measured by postoperative occurence of parastomal hernia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Moe Jalali, (650) 724 - 4023.

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  • Perfusion CT as a Predictor of Treatment Response in Patients With Rectal Cancer Recruiting

    Recent advances in computed tomography (CT) technology have made CT perfusion imaging feasible for the assessment of tumor perfusion in solid tumors of the abdomen. CT perfusion has shown promising results in serving as a noninvasive method of predicting response to therapy in cancer patients. CT perfusion parameters have also been found to correlate with immunohistologic markers of angiogenesis in a number of solid tumors, suggesting a possible role for CT perfusion as a noninvasive biomarker of tumor angiogenesis. The goals of the investigators study are twofold: first, to determine the relationship between baseline CT perfusion characteristics of rectal cancers and their response to treatment, and second, to determine if perfusion CT can be used to subsequently monitor tumor response to treatment. The investigators hope to enroll those patients with locally advanced rectal cancer undergoing standard CT for pre-treatment planning, integrating CT perfusion imaging into the current abdomen/pelvis imaging protocol with close clinical and radiologic follow-up after treatment to determine response to therapy and time to disease progression.

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  • Safety Study of Cetuximab in Combination With Oxaliplatin, Capecitabine, and Radiation Therapy Followed by Surgery for Locally-advanced Rectal Cancer Not Recruiting

    1. To determine the MTD and DLTs of oxaliplatin and capecitabine when combined with C225 and radiotherapy (Phase I) 2. To determine the pathologic response rate of C225 in combination with this neoadjuvant cytotoxic regimen (Phase II)

    Stanford is currently not accepting patients for this trial. For more information, please contact Heidi Kaiser, (650) 724 - 0079.

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  • Effect of Celecoxib on Perioperative Inflammatory Response in Colon Cancer Not Recruiting

    The proposed study aims to investigate how the administration of a drug known to reduce inflammation in humans, Celecoxib, will effect the peri-operative inflammatory response of a patient undergoing primary tumor resection surgery for colon cancer. The proposed project is an exploratory study, and will use data from blood samples and tumor samples to attempt to elucidate the immune and inflammatory response in colon cancer patients undergoing primary resection of their tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Julia McNeal, (650) 723 - 9433.

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  • Assessment of Health Related Quality of Life in Patients Treated for Rectal Cancer Not Recruiting

    Treatment of rectal cancer often consists of surgical resection of the tumor. Chemotherapy and/or radiotherapy are frequently given before or after surgery. In this study, we wish to learn if there are differences in the treatment effectiveness or in the quality of life of patients based on their type of treatment (e.g. Radiotherapy and chemotherapy before or after surgery). Information from this questionnaire collected from you and other patients may help improve the quality of life of rectal cancer patients in the future. Medical information on your tumor, treatment received, and side effects will be compiled and maintained in a database to learn more about outcomes of treatment for rectal cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Moe Jalali, (650) 724 - 4023.

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  • QOL & Functional Outcomes After Combined Modality Tx for Anal CA: Comparison of Conventional vs IMRT Not Recruiting

    The purpose of this study is show that intensity-modulated radiotherapy (IMRT), as compared with conventional radiotherapy, improves the precision of tumor targeting and reduces the acute and late effects of radiation toxicity when used to treat anal cancer. Results from this work will provide a basis for incorporating the use of IMRT to treat anal cancer in future treatment protocols.

    Stanford is currently not accepting patients for this trial. For more information, please contact Moe Jalali, (650) 724 - 4023.

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Teaching

2013-14 Courses


Publications

Journal Articles


  • Mechanical Bowel Preparation in Intestinal Surgery: A Meta-Analysis and Review of the Literature JOURNAL OF GASTROINTESTINAL SURGERY Pineda, C. E., Shelton, A. A., Hernandez-Boussard, T., Morton, J. M., Welton, M. L. 2008; 12 (11): 2037-2044

    Abstract

    Despite several meta-analyses and randomized controlled trials showing no benefit to patients, mechanical bowel preparation (MBP) remains the standard of practice for patients undergoing elective colorectal surgery.We performed a systematic review of the literature of trials that prospectively compared MBP with no MBP for patients undergoing elective colorectal resection. We searched MEDLINE, LILACS, and SCISEARCH, abstracts of pertinent scientific meetings and reference lists for each article found. Experts in the field were queried as to knowledge of additional reports. Outcomes abstracted were anastomotic leaks and wound infections. Meta-analysis was performed using Peto Odds ratio.Of 4,601 patients (13 trials), 2,304 received MBP (Group 1) and 2,297 did not (Group 2). Anastomotic leaks occurred in 97(4.2%) patients in Group 1 and in 81(3.5%) patients in Group 2 (Peto OR = 1.214, CI 95%:0.899-1.64, P = 0.206). Wound infections occurred in 227(9.9%) patients in Group 1 and in 201(8.8%) patients in Group 2 (Peto OR = 1.156, CI 95%:0.946-1.413, P = 0.155).This meta-analysis demonstrates that MBP provides no benefit to patients undergoing elective colorectal surgery, thus, supporting elimination of routine MBP in elective colorectal surgery.In conclusion, MBP is of no benefit to patients undergoing elective colorectal resection and need not be recommended to meet "standard of care."

    View details for DOI 10.1007/s11605-008-0594-8

    View details for Web of Science ID 000260282200037

    View details for PubMedID 18622653

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

    Abstract

    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

    Abstract

    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

  • High-resolution anoscopy targeted surgical destruction of anal high-grade squamous intraepithelial lesions: A ten-year experience DISEASES OF THE COLON & RECTUM Pineda, C. E., Berry, J. M., Jay, N., Palefsky, J. M., Welton, M. L. 2008; 51 (6): 829-835

    Abstract

    This study was designed to determine whether high-resolution anoscopy and targeted surgical destruction of anal high-grade squamous intraepithelial lesions is effective in controlling high-grade squamous intraepithelial lesions while preserving normal tissues.Retrospective review of 246 patients with high-grade squamous intraepithelial lesions treated with high-resolution anoscopy-targeted surgical destruction from 1996 to 2006, with at least one follow-up at a minimum two months with physical examination, high-resolution anoscopy, cytology, and biopsy when indicated.Lesions were extensive in 197 patients (81 percent); 207 (84 percent) were men, and 194 (79 percent) were immunocompromised (HIV or other). Persistent disease occurred in 46 patients (18.7 percent), requiring planned staged therapy; 10 required surgery. Recurrent high-grade squamous intraepithelial lesions occurred in 114 patients (57 percent) at an average 19 (range, 3-92) months; 26 of these required surgery. All other patients were retreated in-office with high-resolution anoscopy-directed therapies. Complications were seen in nine patients (4 percent). Despite treatment, three patients progressed to invasive cancer (1.2 percent). At their last visit, 192 patients (78 percent) had no evidence of high-grade squamous intraepithelial lesions.High-resolution anoscopy-targeted destruction combined with office-based surveillance and therapy is effective in controlling high-grade squamous intraepithelial lesions and is superior to reports of expectant management or traditional mapping procedures.

    View details for DOI 10.1007/s10350-008-9233-4

    View details for Web of Science ID 000256428500005

    View details for PubMedID 18363070

  • High resolution anoscopy in the planned staged treatment of anal squamous intraepithelial lesions in HIV-negative patients JOURNAL OF GASTROINTESTINAL SURGERY Pineda, C. E., Berry, J. M., Jay, N., Palefsky, J. M., Welton, M. L. 2007; 11 (11): 1410-1415

    Abstract

    Anal dysplasia (low-grade squamous intraepithelial lesions, LSIL; high-grade squamous intraepithelial lesions, HSIL) is a challenging disease for the surgeon. We reviewed 42 patients that underwent high-resolution anoscopy (HRA)-targeted surgical therapy of anal dysplasia in the past 10 years. Patients were followed up in the Anal Neoplasia Clinic with physical examination, cytology, HRA, and biopsy if indicated. Patients with disease amenable to local therapy were treated with office-based HRA-directed therapies. There were 30 men (mean age 39 years, range 21-63) and 12 women (mean age 50 years, range 31-71) included in the study. HSIL was present in 33, with four undergoing planned staged treatment due to circumferential disease. HSIL recurred in 45%, and most were re-treated successfully in-office. Progression to HSIL was seen in one patient with LSIL and to squamous cell carcinoma in one patient with HSIL despite therapy. No patients with LSIL had dysplasia at last follow-up. Minor complications occurred in three patients. HRA-targeted surgical therapy coupled with surveillance and re-treatment with office-based therapies offered an effective method in controlling anal dysplasia in the immunocompetent patient. Morbidity is minimal, and our progression to cancer rate is low (2.4%).

    View details for DOI 10.1007/s11605-007-0262-4

    View details for Web of Science ID 000249979900007

    View details for PubMedID 17710507

  • 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

    Abstract

    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

    Abstract

    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

    Abstract

    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

    Abstract

    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 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
  • Anal Cartography in the Treatment of Anal Bowen?s Disease and High-Grade Squamous Intraepithelial Lesions Submitted Dis Colon Rectum Welton ML 2002
  • 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

    Abstract

    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

    Abstract

    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

    Abstract

    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

    Abstract

    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

  • Management of anal squamous intraepithelial lesions. Clinics in colon and rectal surgery Pineda, C. E., Welton, M. L. 2009; 22 (2): 94-101

    Abstract

    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

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