Bio

Clinical Focus


  • Cancer > GI Oncology
  • Rectal Cancer
  • Colon and Rectal Surgery
  • Colorectal Cancer
  • Crohn's Disease
  • Colorectal Cancer - Surgery
  • Gastrointestinal Cancers
  • Gastrointestinal Cancers - Surgical Oncology
  • Inflammatory Bowel Diseases
  • Ulcerative Colitis
  • Laparoscopic colorectal surgery
  • Minimally Invasive Surgical Procedures

Academic Appointments


Administrative Appointments


  • Clinical Director Medical Informatics, Stanford University Hospital and Clinics (2006 - Present)

Honors & Awards


  • Phi Beta Kappa, University of Colorado (1987)
  • Alpha Omega Alpha, University of Wisconsin (1991)
  • Resident Research Award, University of Minnesota (1998)

Professional Education


  • Residency:UCSF General Surgery Residency (1996) CA
  • Internship:UCSF General Surgery Residency (1992) CA
  • Board Certification: General Surgery, American Board of Surgery (1997)
  • Board Certification: Colon and Rectal Surgery, American Board of Colon and Rectal Surgery (1999)
  • Fellowship:University of Minnesota (1998) MN
  • Fellowship, University of Minnesota, Colon and Rectal Surgery (1998)
  • Residency, UCSF, General Surgery (1996)
  • Medical Education:University of Wisconsin Medical School (1991) WI
  • M.D., University of Wisconsin, Medicine (1991)
  • B.A., University of Colorado, Molecular Biology (1987)

Community and International Work


  • Community Medical Advisory Committee

    Topic

    Inflammatory Bowel Disease

    Partnering Organization(s)

    Crohn's & Colitis Foundation of America

    Populations Served

    Patients and families with Crohn's Disease and Ulcerative Colitis

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


Multimodality treatment of rectal cancer
Sphincter preserving procedures for rectal cancer
Laparoscopic colon and rectal surgery
Surgical education

Teaching

2019-20 Courses


Publications

All Publications


  • Fragility of Life: Recurrent Intestinal Perforation Due to Vascular Ehlers-Danlos Syndrome DIGESTIVE DISEASES AND SCIENCES Sceats, L. A., Sukerkar, P. A., Raghavan, S. S., Shandiz, A., Shelton, A., Kin, C. 2019; 64 (8): 2120–23
  • TB or Not TB: Crohn's Disease, Peritoneal Tuberculosis, or Both? DIGESTIVE DISEASES AND SCIENCES Miller, M., Kim-Nhien Vu, Zemek, A., Shelton, A., Kin, C. 2019; 64 (6): 1432–35
  • Effects of Colorectal Surgery Classification on Reported Postoperative Surgical Site Infections JOURNAL OF SURGICAL RESEARCH Kethman, W. C., Shelton, E. A., Kin, C., Morris, A. M., Shelton, A. A. 2019; 236: 340–44
  • Effects of Colorectal Surgery Classification on Reported Postoperative Surgical Site Infections. The Journal of surgical research Kethman, W. C., Shelton, E. A., Kin, C., Morris, A. M., Shelton, A. A. 2019; 236: 340–44

    Abstract

    BACKGROUND: Current procedural terminology (CPT) for colon and rectal surgery lacks procedural granularity and misclassification rates are unknown. However, they are used in performance measurement, for example, in surgical site infection (SSI). The objective of this study was to determine whether American College of Surgeons National Surgical Quality Improvement Program (NSQIP) abstraction methods accurately classify types of colorectal operations and, by extension, reported SSI rates.MATERIALS AND METHODS: This was a retrospective study conducted at a single tertiary care center. The colectomy- and proctectomy-targeted NSQIP database from January 2011 to July 2016 was used to perform a semiautomated reclassification (SAR) of all colectomy and proctectomy cases performed by colorectal surgeons. The primary outcome was the difference in perioperative SSI rates by case classification method.RESULTS: Thousand sixty-three patients underwent a colectomy or proctectomy during the study period with a mean age of 55.7 (SD=16.7) years. Use of the NSQIP classification scheme resulted in 849 colectomy and 214 proctectomy cases. Use of the SAR method resulted in 650 colectomy cases and 413 proctectomy cases (P<0.001), a 23.4% reclassification of colectomy cases. The group of cases classified as colectomy by SAR had a lower rate of deep/organ space infections than those classified as colectomy by NSQIP (4.5% versus 7.1%, P=0.034).CONCLUSIONS: These findings highlight the challenges of CPT code-based patient classification and subsequent outcomes analysis. Expanding the CPT system to more accurately represent colorectal operations would allow for more representative reported outcomes, thus enabling benchmarking and quality improvement.

    View details for PubMedID 30694775

  • Sigmoid Volvulus. JAMA Baiu, I., Shelton, A. 2019; 321 (24): 2478

    View details for DOI 10.1001/jama.2019.2349

    View details for PubMedID 31237646

  • Fragility of Life: Recurrent Intestinal Perforation Due to Vascular Ehlers-Danlos Syndrome. Digestive diseases and sciences Sceats, L. A., Sukerkar, P. A., Raghavan, S. S., Esmaeili Shandiz, A., Shelton, A., Kin, C. 2019

    View details for PubMedID 30656563

  • TB or Not TB: Crohn's Disease, Peritoneal Tuberculosis, or Both? Digestive diseases and sciences Miller, M., Vu, K., Zemek, A., Shelton, A., Kin, C. 2018

    View details for PubMedID 30334111

  • Surgical and molecular characterization of primary and metastatic disease in a neuroendocrine tumor arising in a tailgut cyst COLD SPRING HARBOR MOLECULAR CASE STUDIES Erdrich, J., Schaberg, K. B., Khodadoust, M. S., Zhou, L., Shelton, A. A., Visser, B. C., Ford, J. M., Alizadeh, A. A., Quake, S. R., Kunz, P. L., Beausang, J. F. 2018; 4 (5)
  • Surgical and molecular characterization of primary and metastatic disease in a neuroendocrine tumor arising in a tailgut cyst. Cold Spring Harbor molecular case studies Erdrich, J., Schaberg, K., Khodadoust, M. S., Zhou, L., Shelton, A. A., Visser, B. C., Ford, J. M., Alizadeh, A. A., Quake, S. R., Kunz, P. L., Beausang, J. F. 2018

    Abstract

    Neuroendocrine tumors arising from tailgut cysts are rare but increasingly reported entity with gene expression profiles that may be indicative of the gastrointestinal cell of origin. We present a case report describing the unique pathological and genomic characteristics of a tailgut cyst neuroendocrine tumor that metastasized to liver. The histologic and immunohistochemical findings were consistent with a well-differentiated neuroendocrine tumor. Genomic testing indicates a germline frame-shift in BRCA1 and a few somatic mutations of unknown significance. Transcriptomic analysis suggests an enteroendocrine L-cell in the tailgut as a putative cell-of-origin. Genomic profiling of a rare neuroendocrine tumor and metastasis provides insight into its origin, development and potential therapeutic options.

    View details for PubMedID 30087100

  • Deep Immune Profiling of an Arginine-Enriched Nutritional Intervention in Patients Undergoing Surgery JOURNAL OF IMMUNOLOGY Aghaeepour, N., Kin, C., Ganio, E. A., Jensen, K. P., Gaudilliere, D. K., Tingle, M., Tsai, A., Lancero, H. L., Choisy, B., McNeil, L. S., Okada, R., Shelton, A. A., Nolan, G. P., Angst, M. S., Gaudilliere, B. L. 2017; 199 (6): 2171–80
  • The Prognostic Significance of Pretreatment Hematologic Parameters in Patients Undergoing Resection for Colorectal Cancer AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Kozak, M. M., von Eyben, R., Pai, J. S., Anderson, E. M., Welton, M. L., Shelton, A. A., Kin, C., Koong, A. C., Chang, D. T. 2017; 40 (4): 405–12
  • Deep Immune Profiling of an Arginine-Enriched Nutritional Intervention in Patients Undergoing Surgery. Journal of immunology (Baltimore, Md. : 1950) Aghaeepour, N., Kin, C., Ganio, E. A., Jensen, K. P., Gaudilliere, D. K., Tingle, M., Tsai, A., Lancero, H. L., Choisy, B., McNeil, L. S., Okada, R., Shelton, A. A., Nolan, G. P., Angst, M. S., Gaudilliere, B. L. 2017

    Abstract

    Application of high-content immune profiling technologies has enormous potential to advance medicine. Whether these technologies reveal pertinent biology when implemented in interventional clinical trials is an important question. The beneficial effects of preoperative arginine-enriched dietary supplements (AES) are highly context specific, as they reduce infection rates in elective surgery, but possibly increase morbidity in critically ill patients. This study combined single-cell mass cytometry with the multiplex analysis of relevant plasma cytokines to comprehensively profile the immune-modifying effects of this much-debated intervention in patients undergoing surgery. An elastic net algorithm applied to the high-dimensional mass cytometry dataset identified a cross-validated model consisting of 20 interrelated immune features that separated patients assigned to AES from controls. The model revealed wide-ranging effects of AES on innate and adaptive immune compartments. Notably, AES increased STAT1 and STAT3 signaling responses in lymphoid cell subsets after surgery, consistent with enhanced adaptive mechanisms that may protect against postsurgical infection. Unexpectedly, AES also increased ERK and P38 MAPK signaling responses in monocytic myeloid-derived suppressor cells, which was paired with their pronounced expansion. These results provide novel mechanistic arguments as to why AES may exert context-specific beneficial or adverse effects in patients with critical illness. This study lays out an analytical framework to distill high-dimensional datasets gathered in an interventional clinical trial into a fairly simple model that converges with known biology and provides insight into novel and clinically relevant cellular mechanisms.

    View details for PubMedID 28794234

  • Pulmonary Crohn's Disease DIGESTIVE DISEASES AND SCIENCES Regalia, K., Shelton, A., Berry, G., Triadafilopoulos, G., Cartwright, C. A. 2017; 62 (1): 64-67

    View details for DOI 10.1007/s10620-015-3993-1

    View details for Web of Science ID 000392312200011

    View details for PubMedID 26685911

  • Gastrointestinal Mucormycosis Requiring Surgery in Adults with Hematologic Malignant Tumors: Literature Review SURGICAL INFECTIONS Forrester, J. D., Chandra, V., Shelton, A. A., Weiser, T. G. 2015; 16 (2): 194-202

    Abstract

    Gastrointestinal mucormycosis is associated with high mortality rates. Appropriate and early antifungal therapy and prompt surgical intervention are essential.Case report and literature review.Nineteen case reports were reviewed describing adults with hematologic malignant tumors who developed intestinal mucormycosis and underwent surgery. The overall survival rate was 50%.Intestinal mucormycosis is an infection associated with a high mortality rate although adults with underlying hematologic malignant have improved outcomes compared with other groups.

    View details for DOI 10.1089/sur.2013.232

    View details for Web of Science ID 000352360400015

    View details for PubMedID 25405775

  • The Prognostic Significance of Pretreatment Hematologic Parameters in Patients Undergoing Resection for Colorectal Cancer. American journal of clinical oncology Kozak, M. M., von Eyben, R., Pai, J. S., Anderson, E. M., Welton, M. L., Shelton, A. A., Kin, C., Koong, A. C., Chang, D. T. 2015: -?

    Abstract

    The prognostic value of several hematologic parameters, including platelet, lymphocyte, and neutrophil counts, has been studied in a variety of solid tumors. In this study, we examined the significance of inflammatory markers and their prognostic implications in patients with colorectal cancer (CRC).Patients with stage I-III CRC who underwent surgical resection at the Stanford Cancer Institute between 2005 and 2009 were included. Patients were excluded if they did not have preoperative complete blood counts performed within 1 month of surgical resection, underwent preoperative chemotherapy or radiation, had metastatic disease at diagnosis, or had another previous malignancy. We included 129 eligible patients with available preoperative complete blood counts in the final analysis.A preoperative neutrophil-to-lymphocyte ratio of>3.3 was significantly associated with worse disease-free (DFS) and overall survival (OS) (P=0.009, 0.003), as was a preoperative lymphocyte-to-monocyte ratio of ≤2.6 (P=0.01, 0.002). Preoperative lymphopenia (P=0.002) was associated with worse OS but not DFS (P=0.09). In addition, preoperative thrombocytosis was associated with worse DFS (P=0.006) and OS (P=0.010). Preoperative leukocytosis was associated with worse OS (P=0.048) but not DFS (P=0.49). Preoperative hemoglobin was neither associated with OS (P=0.24) or DFS (P=0.15).Pretreatment lymphopenia, thrombocytosis, a decreased lymphocyte-to-monocyte ratio, and an elevated neutrophil-to-lymphocyte ratio independently predict for worse OS in patients with CRC.

    View details for PubMedID 25756348

  • Gastrointestinal Mucormycosis Initially Manifest as Hematochezia from Arterio-Enteric Fistula DIGESTIVE DISEASES AND SCIENCES Cloyd, J. M., Brown, J., Sinclair, T., Jenks, D., Desai, J., Longacre, T., Chandra, V., Shelton, A. 2014; 59 (12): 2905-2908
  • Assigning a team-based pager for on-call physicians reduces paging errors in a large academic hospital. Joint Commission journal on quality and patient safety / Joint Commission Resources Shieh, L., Chi, J., Kulik, C., Momeni, A., Shelton, A., DePorte, C., Hopkins, J. 2014; 40 (2): 77-82

    Abstract

    As complexity of care of hospitalized patients has increased, the need for communication and collaboration among members of the team caring for the patient has become increasingly important. This often takes the form of a nurse's need to contact a patient's physician to discuss some aspect of care and modify treatment plans. Errors in communication delay care and can pose risk to patients. This report describes the successful implementation of a standardized team-based paging system at an academic center. Results showed a substantial improvement in nurses' perceptions of knowing how to contact the correct physician when discussion of the patient's care is needed. This improvement was found across multiple medical and surgical specialties and was particularly effective for services with the greatest communication problems.

    View details for PubMedID 24716330

  • Outcomes of repeat colonoscopy in patients with polyps referred for surgery without biopsy-proven cancer GASTROINTESTINAL ENDOSCOPY Friedland, S., Banerjee, S., Kochar, R., Chen, A., Shelton, A. 2014; 79 (1): 101-107

    Abstract

    Despite advances in endoscopic treatment, many colonic adenomas are still referred for surgical resection. There is a paucity of data on the suitability of these lesions for endoscopic treatment.To analyze the results of routine repeat colonoscopy in patients referred for surgical resection of colon polyps without biopsy-proven cancer.Retrospective review.University hospital.Patients referred to a colorectal surgeon for surgical resection of a polyp without biopsy-proven cancer.Repeat colonoscopy.The rate of successful endoscopic treatment.There were 38 lesions in 36 patients; 71% of the lesions were noncancerous and were successfully treated endoscopically. In 26% of the lesions, previous removal was attempted by the referring physician but was unsuccessful. The adenoma recurrence rate was 50%, but all recurrences were treated endoscopically and none were cancerous. Two patients were admitted for overnight observation. There were no major adverse events.Single center, retrospective.In the absence of biopsy-proven invasive cancer, it is appropriate to reevaluate patients referred for surgical resection by repeat colonoscopy at an expert center.

    View details for DOI 10.1016/j.gie.2013.06.034

    View details for Web of Science ID 000328736700018

    View details for PubMedID 23916398

  • 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

    Abstract

    : 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

  • Endoscopic management of nonlifting colon polyps. Diagnostic and therapeutic endoscopy Friedland, S., Shelton, A., Kothari, S., Kochar, R., Chen, A., Banerjee, S. 2013; 2013: 412936-?

    Abstract

    Background and Study Aims. The nonlifting polyp sign of invasive colon cancer is considered highly sensitive and specific for cancer extending beyond the mid-submucosa. However, prior interventions can cause adenomas to become nonlifting due to fibrosis. It is unclear whether nonlifting adenomas can be successfully treated endoscopically. The aim of this study was to evaluate outcomes in a referral practice incorporating a standardized protocol of attempted endoscopic resection of nonlifting lesions previously treated by biopsy, polypectomy, surgery, or tattoo placement. Patients and Methods. Retrospective review of patients undergoing colonoscopy by one endoscopist at two hospitals found to have nonlifting lesions from prior interventions. Lesions with biopsy proven invasive cancer or definite endoscopic features of invasive cancer were excluded. Lesions ≥ 8 mm were routinely injected with saline prior to attempted endoscopic resection. Polypectomy was performed using a stiff snare, followed by argon plasma coagulation (APC) if necessary. Results. 26 patients each had a single nonlifting lesion with a history of prior intervention. Endoscopic resection was completed in 25 (96%). 22 required snare resection and APC. 1 patient had invasive cancer and was referred for surgery. The recurrence rate on follow-up colonoscopy was 26%. All of the recurrences were successfully treated endoscopically. There was 1 postprocedure bleed (4%), no perforations, and no other complications. Conclusions. The majority of adenomas that are nonlifting after prior interventions can be treated successfully and safely by a combination of piecemeal polypectomy and ablation. Although recurrence rates are high at 26%, these too can be successfully treated endoscopically.

    View details for DOI 10.1155/2013/412936

    View details for PubMedID 23761952

    View details for PubMedCentralID PMC3666422

  • 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 PubMedID 22481281

  • Free transverse rectus abdominis myocutaneous flap reconstruction of a massive lumbosacral defect using superior gluteal artery perforator vessels MICROSURGERY Gaster, R. S., Bhatt, K. A., Shelton, A. A., Lee, G. K. 2012; 32 (5): 388-392

    Abstract

    Despite significant advances in reconstructive surgery, the repair of massive lumbosacral defects poses significant challenges. When the extent of soft tissue loss, tumor resection, and/or radiation therapy preclude the use of traditional local options, such as gluteal advancement flaps or pedicled thigh flaps, then distant flaps are required. We report a case of a 64-year-old male who presented with a large sacral Marjolin's ulcer secondary to recurrent pilonidal cysts and ulcerations. The patient underwent wide local composite resection, which resulted in a wound measuring 450 cm(2) with exposed rectum and sacrum. The massive defect was successfully covered with a free transverse rectus abdominis myocutaneous flap, providing a well-vascularized skin paddle and obviating the need for a latissimus flap with skin graft. The free-TRAM flap proved to be a very robust flap in this situation and would be one of our flaps of choice for similar defects.

    View details for DOI 10.1002/micr.21981

    View details for Web of Science ID 000306178000009

    View details for PubMedID 22473859

  • Single-cell dissection of transcriptional heterogeneity in human colon tumors NATURE BIOTECHNOLOGY Dalerba, P., Kalisky, T., Sahoo, D., Rajendran, P. S., Rothenberg, M. E., Leyrat, A. A., Sim, S., Okamoto, J., Johnston, D. M., Qian, D., Zabala, M., Bueno, J., Neff, N. F., Wang, J., Shelton, A. A., Visser, B., Hisamori, S., Shimono, Y., Van De Wetering, M., Clevers, H., Clarke, M. F., Quake, S. R. 2011; 29 (12): 1120-U11

    Abstract

    Cancer is often viewed as a caricature of normal developmental processes, but the extent to which its cellular heterogeneity truly recapitulates multilineage differentiation processes of normal tissues remains unknown. Here we implement single-cell PCR gene-expression analysis to dissect the cellular composition of primary human normal colon and colon cancer epithelia. We show that human colon cancer tissues contain distinct cell populations whose transcriptional identities mirror those of the different cellular lineages of normal colon. By creating monoclonal tumor xenografts from injection of a single (n = 1) cell, we demonstrate that the transcriptional diversity of cancer tissues is largely explained by in vivo multilineage differentiation and not only by clonal genetic heterogeneity. Finally, we show that the different gene-expression programs linked to multilineage differentiation are strongly associated with patient survival. We develop two-gene classifier systems (KRT20 versus CA1, MS4A12, CD177, SLC26A3) that predict clinical outcomes with hazard ratios superior to those of pathological grade and comparable to those of microarray-derived multigene expression signatures.

    View details for DOI 10.1038/nbt.2038

    View details for PubMedID 22081019

  • 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 PubMedID 21287530

  • Fulminant Clostridium difficile Colitis in a Post-Liver Transplant Patient DIGESTIVE DISEASES AND SCIENCES Lee, M., Shelton, A. A., Concepcion, W. L., Bonham, C. A., Daugherty, T. J. 2010; 55 (9): 2459-2462

    View details for DOI 10.1007/s10620-010-1318-y

    View details for Web of Science ID 000280595500006

    View details for PubMedID 20635145

  • 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

  • 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

    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 Web of Science ID 000208355900003

  • Mechanical Bowel Preparation in Intestinal Surgery: A Meta-Analysis and Review of the Literature 49th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract/Digestive Disease Week Pineda, C. E., Shelton, A. A., Hernandez-Boussard, T., Morton, J. M., Welton, M. L. SPRINGER. 2008: 2037–44

    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

  • SIR 2008 annual meeting film panel case: Castleman disease complicated by follicular dendritic cell sarcoma 33rd Annual Meeting of the Society-of-Interventional-Radiology (SIR) Sze, D. Y., Shelton, A. A. ELSEVIER SCIENCE INC. 2008: 1141–44

    View details for DOI 10.1016/j.jvir.2008.04.015

    View details for Web of Science ID 000258168100003

    View details for PubMedID 18656005

  • Section 20.3. Laparoscopic Management of Intestinal Endometriosis NEZHAT'S OPERATIVE GYNECOLOGIC LAPAROSCOPY AND HYSTEROSCOPY, 3RD EDITION Shelton, A. A., Nezhat, C., Nezhat, F., Nezhat, C. 2008: 529–36
  • Dartos muscle interposition flap for the treatment of rectourethral fistulas DISEASES OF THE COLON & RECTUM Varma, M. G., Wang, J. Y., Garcia-Aguilar, J., Shelton, A. A., McAninch, J. W., Goldberg, S. M. 2007; 50 (11): 1849-1855

    Abstract

    Rectourethral fistula is a rare complication of pelvic surgery, trauma, or inflammation. The many techniques for repairing these fistulas vary in their success rates. Our goal was to describe the use of a dartos muscle interposition flap for repair of these fistulas.We performed a retrospective review of eight patients who underwent repair of a rectourethral fistula with a dartos muscle interposition flap. We describe the success rate and patient-related factors that may have affected success. The technique of dartos muscle interposition is described and compared with other previously described techniques.Six of eight patients had healing of their fistulas documented by follow-up cystogram.Dartos muscle interposition is a straightforward technique that can result in successful fistula repair but should not be used in patients with risk factors for poor wound healing, such as an immunocompromised state or previous radiation therapy.

    View details for DOI 10.1007/s10350-007-9032-3

    View details for Web of Science ID 000250785500013

    View details for PubMedID 17828402

  • Phenotypic characterization of human colorectal cancer stem cells PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Dalerba, P., Dylla, S. J., Park, I., Liu, R., Wang, X., Cho, R. W., Hoey, T., Gurney, A., Huang, E. H., Simeone, D. M., Shelton, A. A., Parmiani, G., Castelli, C., Clarke, M. F. 2007; 104 (24): 10158-10163

    Abstract

    Recent observations indicate that, in several types of human cancer, only a phenotypic subset of cancer cells within each tumor is capable of initiating tumor growth. This functional subset of cancer cells is operationally defined as the "cancer stem cell" (CSC) subset. Here we developed a CSC model for the study of human colorectal cancer (CRC). Solid CRC tissues, either primary tissues collected from surgical specimens or xenografts established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, were disaggregated into single-cell suspensions and analyzed by flow cytometry. Surface markers that displayed intratumor heterogeneous expression among epithelial cancer cells were selected for cell sorting and tumorigenicity experiments. Individual phenotypic cancer cell subsets were purified, and their tumor-initiating properties were investigated by injection in NOD/SCID mice. Our observations indicate that, in six of six human CRC tested, the ability to engraft in vivo in immunodeficient mice was restricted to a minority subpopulation of epithelial cell adhesion molecule (EpCAM)(high)/CD44+ epithelial cells. Tumors originated from EpCAM(high)/CD44+ cells maintained a differentiated phenotype and reproduced the full morphologic and phenotypic heterogeneity of their parental lesions. Analysis of the surface molecule repertoire of EpCAM(high)/CD44+ cells led to the identification of CD166 as an additional differentially expressed marker, useful for CSC isolation in three of three CRC tested. These results validate the stem cell working model in human CRC and provide a highly robust surface marker profile for CRC stem cell isolation.

    View details for DOI 10.1073/pnas.0703478104

    View details for Web of Science ID 000247363000044

    View details for PubMedID 17548814

    View details for PubMedCentralID PMC1891215

  • 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

  • Sexually transmitted parasitic diseases. Clinics in colon and rectal surgery Shelton, A. A. 2004; 17 (4): 231-234

    Abstract

    An increasing number of diseases are recognized as being sexually transmitted. The majority of these are bacterial or viral in nature; however, several protozoan and nematode infections can also be transmitted by sexual activity. For most of these diseases, the primary mode of transmission is nonsexual in nature, but sexual activity that results in fecal-oral contact can lead to transmission of these agents. Two parasitic diseases commonly transmitted by sexual contact are amebiasis and giardiasis. The management of these conditions is discussed.

    View details for PubMedID 20011264

  • The pelvic floor in health and disease WESTERN JOURNAL OF MEDICINE Shelton, A. A., Welton, M. L. 1997; 167 (2): 90-98

    Abstract

    Normal pelvic floor function involves a set of learned and reflex responses that are essential for the normal control and evacuation of stool. A variety of functional disturbances of the pelvic floor, including incontinence and constipation, are not life threatening, but can cause significant distress to affected patients. Understanding the normal anatomy and physiology of the pelvic floor is essential to understanding and treating these disorders of defecation. This article describes the normal function of the pelvic floor, the diagnostic tools available to investigate pelvic floor dysfunction, and the etiology, diagnosis, and management of the functional pelvic floor disorders that lead to incontinence and constipation.

    View details for Web of Science ID A1997XU74200004

    View details for PubMedID 9291746