Kepal N. Patel, M.D.

Impact of the 2009 American Thyroid Association guidelines on the choice of operation for well-differentiated thyroid microcarcinomas
Ogilvie, Jennifer B; Patel, Kepal N; Heller, Keith S
2010 Dec;148(6):1222-1227, Surgery
BACKGROUND: The 2009 ATA Guidelines state 'lobectomy alone may be sufficient treatment for small (<1 cm), low risk, unifocal, intrathyroidal papillary carcinomas in the absence of . . . nodal metastases.' We determined how often these criteria are satisfied, and whether tumor size alone can dictate operative management. METHODS: Medical records of 346 patients with well-differentiated thyroid cancer (WDTC) who underwent thyroidectomy from January 1, 2007 to November 10, 2009, were reviewed. There were 130 patients with tumors </=1 cm and negative lateral nodes. Pathology reports were reviewed to identify adverse features including multifocality, extrathyroidal extension, vascular invasion, and central node metastases. RESULTS: Eighty-four percent underwent total thyroidectomy and 16% central node dissection. All but 2 patients had papillary cancer. Sixty-one percent with cancers 6-10 mm (group 1) had adverse pathologic features compared with 32% with cancers <6 mm (group 2). Multifocality was most common: 55% in group 1 versus 32% in group 2 (P = .004). Positive central nodes were identified in 23% of group 1 versus 4% of group 2 (P = .004). Of patients in group 1, 88% had positive or suspicious fine-needle aspiration biopsy (FNAB) preoperatively. CONCLUSION: We recommend that total thyroidectomy be considered as the initial operation for thyroid tumors 6-10 mm in size in which the preoperative FNAB is diagnostic or suspicious for WDTC
— id: 115280, year: 2010, vol: 148, page: 1222, stat: Journal Article,

Spry2 expression correlates with BRAF mutation in thyroid cancer
Xu, Lizhong; Zhou, Jun Liang; Cohen, Michael; Bar-Sagi, Dafna; Patel, Kepal N
2010 Dec;148(6):1282-1287, Surgery
BACKGROUND: BRAF mutations activate the mitogen-activated protein kinase pathway and often confer an aggressive thyroid cancer (TC) phenotype. Spry2 is an inducible negative feedback regulator of the mitogen-activated protein kinase (MAPK) pathway. The aim of this study was to investigate the role of Spry2 in TC. METHODS: TC cell lines were analyzed for Spry2 expression and MAPK pathway activation. Cells were treated with MEK inhibitor and Spry2 small hairpin RNA. Cells were analyzed for Spry2 expression and MEK/ERK phosphorylation (pMEK, pERK). Thirty human papillary TCs were analyzed for mitogen-activated protein kinase pathway activating mutations and Spry2 expression. RESULTS: Increased baseline pMEK levels and Spry2 expression was found in BRAF V600E mutant (BRAF+) cells. MEK inhibition in BRAF+ cells showed decreased Spry2 expression and decreased pMEK/pERK levels. From our tissue samples, 10 papillary TCs had BRAF mutation, and increased Spry2 expression was found only in BRAF+ tumors. CONCLUSION: Spry2 expression correlates with BRAF status in vitro and in human tissue. Spry2 may serve as a negative feedback regulator of the mitogen-activated protein kinase pathway in BRAF+ TC. Increased Spry2 expression may serve as a surrogate marker of mitogen-activated protein kinase pathway activation with prognostic and therapeutic implications
— id: 115281, year: 2010, vol: 148, page: 1282, stat: Journal Article,

Tall cell variant of papillary thyroid carcinoma without extrathyroid extension: biologic behavior and clinical implications
Ghossein, Ronald A; Leboeuf, Rebecca; Patel, Kepal N; Rivera, Michael; Katabi, Nora; Carlson, Diane L; Tallini, Giovanni; Shaha, Ashok; Singh, Buvanesh; Tuttle, R Michael
2007 Jul;17(7):655-661, Thyroid
BACKGROUND: The tall cell variant (TCV) is a histologic subtype of papillary thyroid carcinoma (PTC) that is more aggressive than 'classical' PTC. Most authors believe that TCV's worse prognosis is related to older age at presentation, larger tumor size, and high frequency of extrathyroid tumor extension (ETE). To assess the biologic and clinical behavior of TCV without ETE, we performed a detailed comparative clinicopathologic analysis of classical PTC and TCV without ETE. METHODS: TCV was defined as a PTC harboring >50% tall cells, while classical PTC was restricted to those tumors containing >1% papillae and <30% tall cells. Microscopic analysis and chart review identified 62 cases of TCV and 83 classical PTC without ETE. These patients were analyzed for various pathologic, imaging, and clinical parameters including outcome. RESULTS: There was no statistical difference between TCV and classical PTC in relation to age, gender, tumor size, risk stratification, type of therapy, and length of follow-up. TCV displayed more invasion of the tumor capsule and more often infiltrated into the thyroid capsule (p = 0.047 and 0.0004, respectively). Among patients with microscopically assessable regional lymph node (LN), 33 of 49 (67.3%) patients with TCV had LN metastasis at presentation, while only 24 of 60 (40%) classical PTC had positive nodes (p = 0.004). In multivariate analysis, histologic subtype (TCV vs. classical PTC) was the only independent factor associated with LN metastases (p = 0.007). In patients with adequate follow-up, 4 of 62 (6.5%) classical PTC and 7 of the 47 (14.9%) TCV had thyroid cancer recurrence (p = 0.202). TCV recurred at a distant site (3 of 47, 6.4%) while none of the 62 classical PTC developed distant metastases (p = 0.077). CONCLUSION: TCV without ETE is biologically a more aggressive tumor than classical PTC without ETE independent of age, gender, and tumor size
— id: 74369, year: 2007, vol: 17, page: 655, stat: Journal Article,

Implications for clinical staging of metastatic cutaneous squamous carcinoma of the head and neck based on a multicenter study of treatment outcomes
Andruchow, Jennifer L; Veness, Michael J; Morgan, Gary J; Gao, Kan; Clifford, Anthony; Shannon, Kerwin F; Poulsen, Michael; Kenny, Lizbeth; Palme, Carsten E; Gullane, Patrick; Morris, Christopher; Mendenhall, William M; Patel, Kepal N; Shah, Jatin P; O'Brien, Christopher J
2006 Mar 1;106(5):1078-1083, Cancer
BACKGROUND: Cutaneous squamous cell carcinoma (SCC) of the head and neck is a common cancer that has the potential to metastasize to lymph nodes in the parotid gland and neck. Previous studies have highlighted limitations with the current TNM staging system for metastatic skin carcinoma. The aim of this study was to test a new staging system that may provide better discrimination between patient groups. METHODS: A retrospective multicenter study was conducted on 322 patients from three Australian and three North American institutions. All had metastatic cutaneous SCC involving the parotid gland and/or neck and all were treated for cure with a minimum followup time of 2 years. These patients were restaged using a newly proposed system that separated parotid disease (P stage) from neck disease (N stage) and included subgroups of P and N stage. Metastases involved the parotid in 260 patients (149 P1; 78 P2; 33 P3) and 43 of these had clinical neck disease also (22 N1; 21 N2). Neck metastases alone occurred in 62 patients (26 N1; 36 N2). Ninety percent of patients were treated surgically and 267 of 322 received radiotherapy. RESULTS: Neck nodes were pathologically involved in 32% of patients with parotid metastases. Disease recurred in 105 (33%) of the 322 patients, involving the parotid in 42, neck in 33, and distant sites in 30. Parotid recurrence did not vary significantly with P stage. Disease-specific survival was 74% at 5 years. Survival was significantly worse for patients with advanced P stage: 69% survival at 5 years compared with 82% for those with early P stage (P = 0.02) and for those with both parotid and neck node involvement pathologically: 61% survival compared with 79% for those with parotid disease alone (P = 0.027). Both univariate and multivariate analysis confirmed these findings. Clinical neck involvement among patients with parotid metastases did not significantly worsen survival (P = 0.1). CONCLUSIONS: This study, which included a mixed cohort of patients from six different institutions, provides further information about the clinical behavior of metastatic cutaneous SCC of the head and neck. The hypothesis that separation of parotid and neck disease in a new staging system is supported by the results. The benefit of having subgroups of P and N stage is uncertain, but it is likely to identify patients with unfavorable characteristics that may benefit from further research
— id: 74364, year: 2006, vol: 106, page: 1078, stat: Journal Article,

Poorly differentiated and anaplastic thyroid cancer
Patel, Kepal N; Shaha, Ashok R
2006 Apr;13(2):119-128, Cancer control
BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic (undifferentiated) thyroid carcinoma (ATC) comprise a small subset of thyroid tumors that are associated with a poor prognosis and account for a significant portion of the morbidity and mortality related to thyroid cancer. Since management strategies vary between these two entities, it is important for clinicians to be able to differentiate PDTC from ATC. METHODS: We reviewed the literature on PDTC and ATC and compared clinical and histopathologic features important in defining the disease process. RESULTS: Both PDTC and ATC display aggressive behavior with increased locoregional and distant disease. In most cases, patients are older and have large, locally advanced tumors. PDTC may represent an intermediate entity in the progression of well-differentiated thyroid carcinoma to ATC. The use of surgical management may be curative or palliative and differs between PDTC and ATC. The roles of radiotherapy and chemotherapy have not been well described. CONCLUSIONS: PDTC and ATC are rare diseases that carry a poor prognosis. Recognition of their different clinicopathologic features is important to the optimal management of these tumors
— id: 74366, year: 2006, vol: 13, page: 119, stat: Journal Article,

Genetic considerations in thyroid cancer
Patel, Kepal N; Singh, Bhuvanesh
2006 Apr;13(2):111-118, Cancer control
BACKGROUND: Recent molecular studies have described a number of abnormalities associated with the progression and dedifferentiation of thyroid carcinoma. These distinct molecular events are often associated with specific stages of tumor development. A better understanding of the mechanisms involved in thyroid cancer pathogenesis may help to translate these discoveries toward improvements in patient care. METHODS: We reviewed the literature on the molecular pathogenesis of thyroid cancer and compared clinical, histopathologic, and genetic features important in defining the disease process. RESULTS: The progression of thyroid cancer from well-differentiated to poorly differentiated and undifferentiated carcinoma represents a biological continuum. Specific genetic events serve as early initiating and late triggering events. Poorly differentiated thyroid carcinomas occupy an intermediate position in this progression model. CONCLUSIONS: With sophisticated genetic tools generating a wealth of information, we have gained better insight into the mechanisms driving thyroid tumor progression. Recognition of these features is crucial to the management of patients with thyroid cancer. Novel treatments are being designed based on our enhanced understanding of this disease process
— id: 74365, year: 2006, vol: 13, page: 111, stat: Journal Article,

Staphylococcal liver abscess and acute cholecystitis in a patient with Crohn's disease receiving infliximab
Patel, Tushar R; Patel, Kepal N; Boyarsky, Andrew H
2006 Jan;10(1):105-110, Journal of gastrointestinal surgery
We present an unusual case of empyema of the gallbladder associated with a pyogenic liver abscess in a patient with Crohn's disease on Infliximab. It manifested by weakness, weight loss, and vague abdominal pain, which eventually localized to the right upper quadrant 4 days prior to admission. Diagnostic evaluation, which included ultrasonography and computed tomography, revealed cholelithiasis, gallbladder wall thickening, and a low-attenuation, complex mass in the left hepatic lobe. Cholecystectomy and open drainage of the liver abscess were successfully performed. There are few reports of intrahepatic abscess associated with Crohn's disease. The relationship between acute cholecystitis and Crohn's disease has also been documented. However, this report documents the unusual complication of pyogenic liver abscess secondary to acute cholecystitis in the unique population of Crohn's disease patients on Infliximab
— id: 74363, year: 2006, vol: 10, page: 105, stat: Journal Article,

Squamous cell carcinoma related oncogene/DCUN1D1 is highly conserved and activated by amplification in squamous cell carcinomas
Sarkaria, Inderpal; O-charoenrat, Pornchai; Talbot, Simon G; Reddy, Pabbathi G; Ngai, Ivan; Maghami, Ellie; Patel, Kepal N; Lee, Benjamin; Yonekawa, Yoshihiro; Dudas, Maria; Kaufman, Andrew; Ryan, Russell; Ghossein, Ronald; Rao, Pulivarthi H; Stoffel, Archontoula; Ramanathan, Y; Singh, Bhuvanesh
2006 Oct 1;66(19):9437-9444, Cancer research
Chromosomal amplification at 3q is common to multiple human cancers, but has a specific predilection for squamous cell carcinomas (SCC) of mucosal origin. We identified and characterized a novel oncogene, SCC-related oncogene (SCCRO), which is amplified along the 3q26.3 region in human SCC. Amplification and overexpression of SCCRO in these tumors correlate with poor clinical outcome. The importance of SCCRO amplification in malignant transformation is established by the apoptotic response to short hairpin RNA against SCCRO, exclusively in cancer cell lines carrying SCCRO amplification. The oncogenic potential of SCCRO is underscored by its ability to transform fibroblasts (NIH-3T3 cells) in vitro and in vivo. We show that SCCRO regulates Gli1--a key regulator of the hedgehog (HH) pathway. Collectively, these data suggest that SCCRO is a novel component of the HH signaling pathway involved in the malignant transformation of squamous cell lineage
— id: 74367, year: 2006, vol: 66, page: 9437, stat: Journal Article,

MUC1 plays a role in tumor maintenance in aggressive thyroid carcinomas
Patel, Kepal N; Maghami, Ellie; Wreesmann, Volkert B; Shaha, Ashok R; Shah, Jatin P; Ghossein, Ronald; Singh, Bhuvanesh
2005 Dec;138(6):994-1001, Surgery
BACKGROUND: We recently identified MUC1 as a target driving selection for 1q21 amplification and validated it as an independent marker of aggressive behavior in thyroid cancer (TC). The aims of this study were to determine whether TC cell lines retain MUC1 expression patterns that are seen in primary tumors, assess the role of MUC1 in tumor maintenance, and develop a virally delivered anti-MUC1 RNA interference (RNAi) that is effective in decreasing MUC1 expression in vitro. METHODS: Fifteen TC cell lines were screened for MUC1 protein expression. Cell lines with varying MUC1 protein levels were treated with anti-MUC1 monoclonal antibody to assess cell viability. A recombinant retroviral short hairpin RNAi delivery system against MUC1 was developed. Efficacy and optimal dosing of short hairpin RNA against MUC1 was determined. RESULTS: MUC1 expression patterns in TC cell lines were found to be similar to that seen in primary tumors. Treatment with anti-MUC1 antibody resulted in a significant decrease in cell viability in MUC1 over-expressing cell lines. MUC1-779 RNAi construct showed excellent infection efficiency and reproducible silencing. CONCLUSION: These data offer functional evidence that implicates MUC1 over-expression as a key molecular event in the pathogenesis of aggressive TC. Retrovirally delivered anti-MUC1 RNAi is effective in silencing MUC1 and merits further investigation to establish therapeutic efficacy and safety in anticipation of potential clinical application
— id: 74362, year: 2005, vol: 138, page: 994, stat: Journal Article,

Neck dissection: past, present, future
Patel, Kepal N; Shah, Jatin P
2005 Jul;14(3):461-77, vi, Surgical oncology clinics of North America
— id: 74358, year: 2005, vol: 14, page: 461, stat: Journal Article,

Locally advanced thyroid cancer
Patel, Kepal N; Shaha, Ashok R
2005 Apr;13(2):112-116, Current opinion in otolaryngology & head & neck surgery
PURPOSE OF REVIEW: The purpose of this review is to summarize existing literature with respect to locally advanced thyroid cancer and define the intricacies of preoperative evaluation, surgical management of involved sites and postoperative treatment. RECENT FINDINGS: Locally invasive thyroid cancer is an uncommon disease process, which carries significant morbidity and mortality. Current treatment modalities include appropriate surgery, radioactive iodine treatment and external beam radiation therapy. Proper evaluation of the extent of disease, with complete gross tumor removal, is paramount in managing this difficult problem. Surgical treatment is still the mainstay for locally advanced thyroid cancer. SUMMARY: Little progress has been made in advancing the treatment of locally advanced thyroid cancer. Patient identification, evaluation and proper surgical management with adjuvant therapy, still remain the most effective course of treatment. Aggressive surgical treatment including removal of all gross tumor and still preserving vital structures along with adjuvant therapy is likely to offer the best results. There is a very high incidence of locoregional and distant failure in this group of patients. The understanding and recognition of histopathological variations, such as poorly differentiated thyroid cancer is also important. New molecular markers are needed to help identify and predict aggressive tumor behavior
— id: 74356, year: 2005, vol: 13, page: 112, stat: Journal Article,

Pathology quiz case 2. Cutaneous angiosarcoma
Patel, Kepal N; Shaha, Ashok R
2004 Dec;130(12):1439, 1440-1, Archives of otolaryngology, head & neck surgery
— id: 74354, year: 2004, vol: 130, page: 1439, 1440, stat: Journal Article,

Genome-wide profiling of papillary thyroid cancer identifies MUC1 as an independent prognostic marker
Wreesmann, Volkert B; Sieczka, Elizabeth M; Socci, Nicholas D; Hezel, Michael; Belbin, Thomas J; Childs, Geoffrey; Patel, Snehal G; Patel, Kepal N; Tallini, Giovanni; Prystowsky, Michael; Shaha, Ashok R; Kraus, Dennis; Shah, Jatin P; Rao, Pulivarthi H; Ghossein, Ronald; Singh, Bhuvanesh
2004 Jun 1;64(11):3780-3789, Cancer research
Clinicopathological variables used at present for prognostication and treatment selection for papillary thyroid carcinomas (PTCs) do not uniformly predict tumor behavior, necessitating identification of novel prognostic markers. Complicating the assessment is the long natural history of PTC and our rudimentary knowledge of its genetic composition. In this study we took advantage of differences in clinical behavior of two distinct variants of PTC, the aggressive tall-cell variant (TCV) and indolent conventional PTC (cPTC), to identify molecular prognosticators of outcome using complementary genome wide analyses. Comparative genome hybridization (CGH) and cDNA microarray (17,840 genes) analyses were used to detect changes in DNA copy number and gene expression in pathological cPTC and TCV. The findings from CGH and cDNA microarray analyses were correlated and validated by real-time PCR and immunohistochemical analyses on a series of 100 cases of cPTC and TCV. Genes identified by this approach were evaluated as prognostic markers in cPTC by immunohistochemistry on tissue arrays. CGH identified significant differences in the presence (76 versus 27%; P = 0.001) and type of DNA copy number aberrations in TCV compared with cPTC. Recurrent gains of 1p34-36, 1q21, 6p21-22, 9q34, 11q13, 17q25, 19, and 22 and losses of 2q21-31, 4, 5p14-q21, 6q11-22, 8q11-22, 9q11-32, and 13q21-31 were unique to TCV. Hierarchical clustering of gene expression profiles revealed significant overlap between TCV and cPTC, but further analysis identified 82 dysregulated genes differentially expressed among the PTC variants. Of these, MUC1 was of particular interest because amplification of 1q by CGH correlated with MUC1 amplification by real-time PCR analysis and protein overexpression by immunohistochemistry in TCV (P = 0.005). Multivariate analysis revealed a significant association between MUC1 overexpression and treatment outcome, independent of histopathological categorization (P = 0.03). Analysis of a validation series containing a matched group of aggressive and indolent cPTCs confirmed the association between MUC1 overexpression and survival (relative risk, 2.3; 95% confidence interval, 1.1-5.5; P = 0.03). Our data suggest that MUC1 dysregulation is associated with aggressive behavior of PTC and may serve as a prognostic marker and potential therapeutic target in this disease
— id: 74350, year: 2004, vol: 64, page: 3780, stat: Journal Article,