Carol G Shores

University of North Carolina at Chapel Hill, North Carolina, United States

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Publications (60)169.86 Total impact

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    ABSTRACT: Description of pathologic causes of cervical lymphadenopathy at Kamuzu Central Hospital.
    Malawi medical journal: the journal of Medical Association of Malawi 03/2014; 26(1):16-9. · 0.27 Impact Factor
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    ABSTRACT: The World Health Organization (WHO) recommends HIV Counseling and Testing (HCT) in a range of clinical settings. We describe the characteristics of patients diagnosed with HIV on the medical and surgical wards at a tertiary care hospital in Malawi. Under the universal opt-out HCT protocol we characterized the number of new HIV/AIDS infections and associated clinical features among hospitalized surgical and medical patients diagnosed during the course of admission. All 2985 and 3959 medical and surgical patients, respectively, admitted between April 2012 and January 2013 were screened for HCT. 62% and 89% of medical and surgical patients, respectively, had an unknown status on admission and qualified for testing. Of the patients with an unknown status, a new HIV diagnosis was made in 20% and 7% of medical and surgical patients, respectively. Of the newly diagnosed patients with a CD4 count recorded, 91% and 67% of medical and surgical patients, respectively, had a count less than 350, qualifying for ART by Malawi ART guidelines. Newly HIV-diagnosed medical and surgical patients had an inpatient mortality of 20% and 2%, respectively. While newly diagnosed HIV-positive medical patients had high inpatient mortality and higher rates of WHO stage 3 or 4 conditions, surgical patients presented with less advanced HIV, though still meeting ART initiation guidelines. The medical inpatient wards are an obvious choice for implementing voluntary counseling and testing (VCT), but surgical patients present with less advanced disease and starting treatment in this group could result in more years of life gained.
    Tropical Medicine and Health 12/2013; 41(4):163-70.
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    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV), no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical) consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR. For potential clinical use the signatures are complimentary to classification by HPV infection status as well as the putative high risk marker CCND1 copy number gain. A molecular etiology for the subtypes is suggested by statistically significant chromosomal gains and losses and differential cell of origin expression patterns. Model systems representative of each of the four subtypes are also presented.
    PLoS ONE 07/2013; 8(2):e56823. · 3.53 Impact Factor
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    ABSTRACT: Objective To investigate ERCC1 protein expression and its relationship to clinical factors and treatment outcomes in patients with head and neck squamous cell carcinoma (HNSCC).DesignCase series.SettingTertiary care academic center.SubjectsOne hundred and seventy-six patients diagnosed with HNSCC and treated with intent to cure between 2002 and 2008 were analyzed with respect to clinical data and tumor pathology.Main Outcome MeasuresTissue microarrays were constructed from tumor blocks and immunohistochemical staining for ERCC1 performed. ERCC1 expression status was dichotomized into high and low using the Allred score. Clinical characteristics of patients with high versus low ERCC1 expression were compared. Distributions of overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method.ResultsOf 176 patients, ERCC1 showed baseline nuclear staining in 148 patients (84.1%). Lower staining intensity ERCC1 expression was prominent in parabasal cells in the lower half of the epithelium, while at high staining intensity, ERCC1 expression was present throughout the epithelium. The median H-score was 50. No significant differences in age, gender, smoking status, tumor site, or stage were seen between the high and low ERCC1 expression groups. Expression of ERCC1 stratified by tumor site correlates with OS. Patients with oropharyngeal HNSCC and high ERCC1 expression (H-score > 120) were more likely to survive (P < .01) and remain disease free when compared to non-oropharyngeal squamous cell carcinoma (SCCa) patients with high ERCC1 expression despite treatment modality and human papillomavirus virus (HPV) status.Conclusion Patients with oropharyngeal SCCa and high ERCC1 expression may have better outcomes despite HPV status.
    Otolaryngology Head and Neck Surgery 07/2013; · 1.73 Impact Factor
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    ABSTRACT: To identify the patterns of local failure for sinonasal malignancies treated with radiation therapy (RT). We retrospectively identified 79 patients with sinonasal malignancies treated between 2000 and 2011. The median follow-up was 34 months (7-137). Fifty patients (63%) had surgery and RT with or without chemotherapy, and 29 (37%) received definitive chemoradiation therapy. Twenty-six of 79 patients (33%) failed locally; 11 had persistent disease and 15 had local recurrence (LR). The patients with LR had at least a 3-month disease-free interval posttreatment. Imaging of the 15 LR was registered to the treatment planning computed tomography. Failures were categorized as in-field, marginal, or out-of-field if >95%, 20%-95%, or <20% of the LR was within the 95% prescription isodose line, respectively. Of the 15 patients with LR, 7 were in-field, 2 were marginal, and 6 were out-of-field. For 3 patients, treatment plans were not retrievable; however, it was apparent from clinical records that 2 had in-field LR and 1 had an out-of-field LR (untreated contralateral maxillary sinus). No patient with a marginal or out-of-field recurrence had more than 39% of their recurrent tumor volume within 95% of the prescribed dose. Coverage of the LR by 54 Gy and 45 Gy was suboptimal in 7/7 and 5/7 patients with LR, respectively. Marginal and out-of-field LR were predominantly above the pretreatment tumor location and at the level of or superior to the eyes. Sinonasal malignancies failed marginally or out-of-field in 53% (8/15) of LR and 31% (8/26) of all local failures. The anatomic location of these marginal and out-of field LR are predominately at, or superior to, the level of the eyes. This pattern of failure may be directly related to efforts to minimize RT to the optic structures and the degree of difficulty of skull base operations.
    Practical radiation oncology. 07/2013; 3(3):e113-20.
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    ABSTRACT: BACKGROUND: The purpose of this study was to determine whether indeterminate pulmonary nodules (IPNs) at staging are predictive of lung metastasis, primary lung carcinoma, or survival in patients with advanced head and neck squamous cell carcinoma (HNSCC). METHODS: One hundred ten patients with IPN at staging who had follow-up imaging and 100 patients without IPN were identified from an HNSCC database. The primary endpoints were lung progression-free survival (PFS) and overall survival (OS). RESULTS: Two-year lung PFS for the IPN and No-IPN cohorts were 66% versus 61% (p = .92) and the OS for these cohorts were 71% versus 68% (p = .77). Within the IPN cohort, level IV/V lymph node involvement (odds ratio = 4.34; p = .03), hypopharynx primary (odds ratio = 21.5; p = .005), and race (odds ratio = 9.29; p = .001) were independent predictors of developing lung malignancy. CONCLUSION: IPNs at staging in patients with HNSCC do not affect prognosis and should neither influence initial treatment planning nor the frequency of posttreatment surveillance. © 2013 Wiley Periodicals, Inc. Head Neck, 2013.
    Head & Neck 06/2013; · 2.83 Impact Factor
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    ABSTRACT: Worldwide, new cancer cases will nearly double in the next 20 years while disproportionately affecting low and middle income countries (LMICs). Cancer outcomes in LMICs also remain bleaker than other regions of the world. Despite this, little is known about cancer epidemiology and surgical treatment in LMICs. To address this we sought to describe the characteristics of cancer patients presenting to the Surgery Department at Kamuzu Central Hospital in Lilongwe, Malawi. We conducted a retrospective review of adult (18 years or older) surgical oncology services at Kamuzu Central Hospital in Lilongwe, Malawi from 2007 - 2010. Data obtained from the operating theatre logs included patient demographics, indication for operative procedure, procedure performed, and operative procedures (curative, palliative, or staging). Of all the general surgery procedures performed during this time period (7,076 in total), 16% (406 cases) involved cancer therapy. The mean age of male and female patients in this study population was 52 years and 47 years, respectively. Breast cancer, colorectal cancer, gastric cancer, and melanoma were the most common cancers among women, whereas prostate, colorectal, pancreatic, and, gastric were the most common cancers in men. Although more than 50% of breast cancer operations were performed with curative intent, most procedures were palliative including prostate cancer (98%), colorectal cancer (69%), gastric cancer (71%), and pancreatic cancer (94%). Patients with colorectal, gastric, esophageal, pancreatic, and breast cancer presented at surprisingly young ages. The paucity of procedures with curative intent and young age at presentation reveals that many Malawians miss opportunities for cure and many potential years of life are lost. Though KCH now has pathology services, a cancer registry and a surgical training program, the focus of surgical care remains palliative. Further research should address other methods of increasing early cancer detection and treatment in such populations.
    World journal of oncology. 06/2013; 4(3):142-146.
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    ABSTRACT: Background: It is unclear whether bone invasion in small oral cavity squamous cell carcinomas (OCSCC) results in worse prognosis. Methods: 254 OCSCC were identified and divided into 3 cohorts: 1) ≤ 4 cm with no bone invasion, 2) ≤ 4 cm with bone invasion, 3) ≥4 cm or other factors (e.g. skin invasion, deep muscle invasion, etc.) that would qualify for AJCC T4 classification aside from bone invasion. Depth of bone invasion (none, cortical, medullary) was also recorded. Results: Cohorts 1 and 2 had similar outcomes. Cohort 3 had lower rates of RC (p = 0.04), DSS (p < 0.01), and OS (p < 0.01). On multivariate analysis, margin status and medullary bone invasion were associated with worse outcomes. Conclusions: Bone invasion does not appear to significantly influence outcomes in patients with small primaries treated with surgery/radiation. Medullary bone invasion appears to result in reduced rates of control and survival. Head Neck, 2013.
    Head & Neck 04/2013; · 2.83 Impact Factor
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    ABSTRACT: Despite increasing cancer burden in Malawi, pathology services are limited. We describe operations during the first 20 months of a new pathology laboratory in Lilongwe, with emphasis on cancer diagnoses. We performed a cross-sectional study of specimens from the Kamuzu Central Hospital pathology laboratory between July 1, 2011 and February 28, 2013. Patient and specimen characteristics, and final diagnoses are summarized. Diagnoses were categorized as malignant, premalignant, infectious, other pathology, normal or benign, or nondiagnostic. Patient characteristics associated with premalignancy and malignancy were assessed using logistic regression. Of 2772 specimens, 2758 (99%) with a recorded final diagnosis were included, drawn from 2639 unique patients. Mean age was 38 years and 63% were female. Of those with documented HIV status, 51% had unknown status, and 36% with known status were infected. Histologic specimens comprised 91% of cases, and cytologic specimens 9%. Malignant diagnoses were most common overall (n = 861, 31%). Among cancers, cervical cancer was most common (n = 117, 14%), followed by lymphoma (n = 91, 11%), esophageal cancer (n = 86, 10%), sarcoma excluding Kaposi sarcoma (n = 75, 9%), and breast cancer (n = 61, 7%). HIV status was known for 95 (11%) of malignancies, with HIV prevalence ranging from 9% for breast cancer to 81% for cervical cancer. Increasing age was consistently associated with malignancy [bivariable odds ratio 1.24 per decade increase (95% CI 1.19-1.29) among 2685 patients with known age; multivariable odds ratio 1.33 per decade increase (95% CI 1.14-1.56) among 317 patients with known age, gender, and HIV status], while HIV infection and gender were not. Despite selection and referral bias inherent in these data, a new pathology laboratory in Lilongwe has created a robust platform for cancer care and research. Strategies to effectively capture clinical information for pathologically confirmed cancers can allow these data to complement population-based registration.
    PLoS ONE 01/2013; 8(8):e70361. · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: Nucleoside analogues, including acyclovir, ganciclovir, and their precursors, have shown some efficacy against several Epstein-Barr virus (EBV)-associated diseases, including active EBV infection and posttransplantation lymphoproliferative disorder (PTLD). They have also been proposed as a possible treatment for EBV-associated malignancies, including endemic Burkitt lymphoma. The safety of nucleoside analogues in combination with chemotherapy in the developing world has not been studied and is necessary before any large scale efficacy trials are conducted. PATIENTS AND METHODS: Children 3-15 years old meeting inclusion criteria were assigned to a 3+3 dose escalation trial of combination valacyclovir (15 and 30 mg/kg, 3 times daily for 40 days) and cyclophosphamide (CPM) (40 mg/kg day 1, 60 mg/kg on days 8, 18, and 28) or CPM monotherapy. Subjects were monitored for clinical and laboratory toxicity and had EBV levels measured regularly. Dose-limiting toxicity (DLT) was our primary outcome. RESULTS: We found that the combination of valacyclovir and CPM was safe and did not lead to any DLT compared with CPM monotherapy. The most common side effects were vomiting, abdominal pain, and tumor site pain, which were similar in both arms. Patients with measurable serum EBV showed decreased loads over their treatment course. CONCLUSIONS: We recommend a phase II valacyclovir dose of 30 mg/kg 3 times daily for 40 days. We also observed that 6 of our 12 patients with presumed Burkitt lymphoma had measurable EBV viral loads that decreased over the course of their treatment, suggesting that phase II studies should investigate this correlation further. This study paves the way for a phase II efficacy trial of combined valacyclovir and CPM in the treatment of endemic Burkitt lymphoma.
    Clinical lymphoma, myeloma & leukemia 12/2012;
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    ABSTRACT: BACKGROUND: The exodus of health professionals including surgeons from sub-Saharan Africa has been well documented, but few effective, long-term solutions have been described. There is an increasing burden of surgical diseases in Africa attributable to trauma (road traffic injuries), burns, and other noncommunicable diseases such as cancer, increasing the need for surgeons. METHODS: We conducted a Descriptive analysis of surgical academic partnership between Kamuzu Central Hospital (KCH) Malawi, the University of Malawi-College of Medicine, the University of North Carolina in the United States, and Haukeland University Hospital, Norway, to locally train Malawian surgical residents in a College of Surgeons of East, Central and Southern Africa (COSECSA) approved program. RESULTS: The KCH Surgery Residency program began in 2009 with 3 residents, adding 3 general surgery and 2 orthopedic residents in 2010. The intention is to enroll ≥3 residents per year to fill the 5-year program and the training has been fully accredited by COSECSA. International partners have provided near-continuous presence of attending surgeons for direct training and support of the local staff surgeons, while providing monetary support in addition to the Malawi Ministry of Health salary. CONCLUSION: This collaborative, academic model of local surgery training is designed to limit brain drain by keeping future surgeons in their country of origin as they establish themselves professionally and personally, with ongoing collaboration with international colleagues.
    Surgery 10/2012; · 3.37 Impact Factor
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    ABSTRACT: OBJECTIVES/HYPOTHESIS:: To estimate the incidence of subclinical nodal disease at the time of isolated local recurrence (LR) after chemoradiotherapy for an initially staged N0 head and neck squamous cell carcinoma. METHODS:: We retrospectively reviewed 44 patients who underwent salvage surgery with or without elective neck dissection (END) for an isolated LR between 1997 and 2010. The incidence of subclinical nodal disease was determined from the pathology reports and from clinical neck failures. RESULTS:: Thirty patients received END. The overall incidence of subclinical nodal disease in patients with dissected necks was 10% (3/30 patients). The rate of regional control for the 14 observed necks was 100%. Three-year local control and overall survival rates for the END and non-END cohorts were 71% versus 73% (P=0.80) and 55% versus 64%, respectively (P=0.40). CONCLUSIONS:: The risk of subclinical nodal disease is low for patients with an isolated LR after chemoradiotherapy.
    American journal of clinical oncology 07/2012; · 2.21 Impact Factor
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    ABSTRACT: Recently, the management of head and neck squamous cell carcinoma (HNSCC) has focused considerable attention on biomarkers, which may influence outcomes. Tests for human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible. Tumours from familial melanoma syndromes have suggested that nuclear localisation of p16 might have a further role in risk stratification. We hypothesised p16 staining that considered nuclear localisation might be informative for predicting outcomes in a broader set of HNSCC tumours not limited to the oropharynx, human papilloma virus (HPV) status or by smoking status. Patients treated for HNSCC from 2002 to 2006 at UNC (University of North Carolina at Chapel Hill) hospitals that had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear and cytoplasmic staining. Human papilloma virus staining was also carried out using monoclonal antibody E6H4. p16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS). A total of 135 patients had sufficient sample for this analysis. Median age at diagnosis was 57 years (range 20-82), with 68.9% males, 8.9% never smokers and 32.6% never drinkers. Three-year OS rate and PFS rate was 63.0% and 54.1%, respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear, high cytoplasmic staining group (HN), low nuclear, low cytoplasmic staining group (LS) and high cytoplasmic, low nuclear staining group (HC). The HN and the LS groups had significantly better OS than the HC group with hazard ratios of 0.10 and 0.37, respectively, after controlling for other factors, including HPV status. These two groups also had significantly better PFS than the HC staining group. This finding was consistent for sites outside the oropharynx and did not require adjustment for smoking status. Different p16 protein localisation suggested different survival outcomes in a manner that does not require limiting the biomarker to the oropharynx and does not require assessment of smoking status.
    British Journal of Cancer 06/2012; 107(3):482-90. · 5.08 Impact Factor
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    ABSTRACT: BACKGROUND:: We evaluated whether classifying 1 side of a patients' neck as "high risk" would help in deciding the extent of neck dissection in patients with bilateral nodal disease. METHODS:: We conducted a retrospective review of 44 patients (88 heminecks) with head and neck squamous cell carcinoma who had bilateral nodal disease and received definitive chemoradiotherapy (CRT). For lateralized lesions (70%), the ipsilateral neck was designated as the "high-risk" neck. For midline lesions, pre-CRT and post-CRT computed tomography scans were used to stage each side of the neck (hemineck); the higher staged hemineck was designated as the "high-risk" neck. RESULTS:: Twenty-seven patients had died at the time of analysis. Patients had a median follow-up of 27.8 months (range, 6 to 150 mo). Two-year neck control and overall survival were 83% and 56%, respectively. Sixty-two heminecks (71%) were dissected. A total of 6/22 (27%) "low-risk" necks were positive after CRT if the "high-risk" neck was positive versus 0/22 if the "high-risk" neck was negative (P=0.02). CONCLUSIONS:: Identifying the more "high-risk" neck may be useful when deciding the extent of neck dissection after CRT. For patients with bilateral nodal disease treated with CRT, dissection of the "low-risk" hemineck may be omitted if the "high-risk" neck is pathologically negative.
    American journal of clinical oncology 03/2012; · 2.21 Impact Factor
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    ABSTRACT: Esophagogastroduodenoscopy (EGD) is a valuable tool for diagnosing and treating upper gastrointestinal disease. Prioritizing the use of EGD in resource-limited settings must be customized to local populations to maximize population benefit from the examination. Cross-sectional, retrospective review of EGD reports was conducted at Kamuzu Central Hospital (KCH), Lilongwe, Malawi. Esophageal tumors were defined as obstructive or nonobstructive and esophageal varices were graded on a scale of I to IV. Descriptive statistics were calculated and logistic regression performed for each disease state compared with all other reports. A total of 1,034 cases were reviewed (56% male; mean age (standard deviation), 44 (17) years). The most common indications were dysphagia (37%), hematemesis (21%), and epigastric pain (16%). The most common diagnoses were normal (36%), esophageal cancer (27%), and esophageal varices (17%). Eighty-six percent of esophageal tumors were obstructive and 45% of esophageal varices were grade III or IV. Normal examinations were more likely to be female, younger, and present with dyspepsia. Esophageal cancers were more likely to be male, older, present with dysphagia, and present from districts outside Lilongwe. Esophageal varices were more likely to present with hematemesis. EGD is a limited resource at KCH; patient selection should be guided by patient age and indication. The high burden of esophageal cancer and varices in Malawi suggests that therapeutic endoscopy would be beneficial.
    World Journal of Surgery 02/2012; 36(5):1074-82. · 2.23 Impact Factor
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    ABSTRACT: Report the prevalence and risk factors of liver metastasis in head and neck squamous cell carcinoma (HNSCC) while evaluating the utility of liver function tests (LFTs) in detection of such metastases. Case series with chart review. Tertiary referral center. Of 745 patients with newly diagnosed HNSCC (oral cavity, oropharynx, hypopharynx, larynx) treated at University of North Carolina hospitals from 1989 to 2005, 655 had sufficient data for analysis. Prevalence of liver metastasis was 3% (20/655) with 7 patients demonstrating early metastasis and 12 with late metastasis. Oropharyngeal and hypopharyngeal lesions constituted 65% of identified liver metastasis but only 39% of the study population. Patients with oropharyngeal lesions were most likely to develop liver metastasis (P = .047). Abnormal LFTs were seen in 26% of all patients. Overall sensitivity and specificity were 45% and 75%. Seventy-five percent of patients with liver metastasis had stage IV disease at diagnosis and were more likely to have abnormal LFTs than other stages (P = .048). In these patients, 2.2% (8/365) had liver metastases and abnormal LFTs, whereas 1.9% (7/365) had liver metastases and normal LFTs. Sensitivity for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase 0%, 10%, 20%, and 30%, respectively. Specificities ranged from 88.0% to 94.3%. Positive predictive values were poor, with the highest being 10.5%. Liver metastases are rare in HNSCC and often delayed in presentation. This study clearly reveals that LFTs do not reliably identify patients with liver metastasis and do not provide physicians with an adequate screening modality in this population.
    Otolaryngology Head and Neck Surgery 01/2012; 146(1):88-91. · 1.73 Impact Factor
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    ABSTRACT: Peritonitis is a life-threatening condition with a multitude of etiologies that can vary with geographic location. The aims of this study were to elucidate the etiology, clinical presentation and outcomes associated with peritonitis in Lilongwe, Malawi. All patients admitted to Kamuzu Central Hospital (KCH) who underwent an operation for treatment of peritonitis during the calendar year 2008 were eligible. Peritonitis was defined as abdominal rigidity, rebound tenderness, and/or guarding in one or more abdominal quadrants. Subjects were identified from a review of the medical records for all patients admitted to the adult general surgical ward and the operative log book. Those who met the definition of peritonitis and underwent celiotomy were included. 190 subjects were identified. The most common etiologies were appendicitis (22%), intestinal volvulus (17%), perforated peptic ulcer (11%) and small bowel perforation (11%). The overall mortality rate associated with peritonitis was 15%, with the highest mortality rates observed in solid organ rupture (35%), perforated peptic ulcer (33%), primary/idiopathic peritonitis (27%), tubo-ovarian abscess (20%) and small bowel perforation (15%). Factors associated with death included abdominal rigidity, generalized (versus localized) peritonitis, hypotension, tachycardia and anemia (p < 0.05). Age, gender, symptoms (obstipation, vomiting) and symptom duration, tachypnea, abnormal temperature, leukocytosis, hemoconcentration, thrombocytopenia and thrombocytosis were not associated with mortality (p = NS). There are several signs and laboratory findings predictive of poor outcome in Malawian patients with peritonitis. Tachycardia, hypotension, anemia, abdominal rigidity and generalized peritonitis are the most predictive of death (P < 0.05 for each). Similar to studies from other African countries, in our population the most common cause of peritonitis was appendicitis, and the overall mortality rate among all patients with peritonitis was 15%. Identified geographical differences included intestinal volvulus, rare in the US but the 2nd most common cause of peritonitis in Malawi and gallbladder disease, common in Ethiopia but not observed in Malawi. Future research should investigate whether correction of factors associated with mortality might improve outcomes.
    World Journal of Emergency Surgery 11/2011; 6(1):37. · 0.92 Impact Factor
  • Fuel and Energy Abstracts 10/2011; 81(2).
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    ABSTRACT: We evaluated X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) protein in head and neck squamous cell carcinoma (HNSCC) patients in association with outcome. XRCC1 protein expression was assessed by immunohistochemical (IHC) staining of pretreatment tissue samples in 138 consecutive HNSCC patients treated with surgery (n = 31), radiation (15), surgery and radiation (23), surgery and adjuvant chemoradiation (17), primary chemoradiation (51), and palliative measures (1). Patients with high XRCC1 expression by IHC (n = 77) compared with patients with low XRCC1 expression (n = 60) had poorer median overall survival (OS; 41.0 months vs. OS not reached, P = 0.009) and poorer progression-free survival (28.0 months vs. 73.0 months, P = 0.031). This association was primarily due to patients who received chemoradiation (median OS of high- and low-XRCC1 expression patients, 35.5 months and not reached respectively, HR 3.48; 95% CI: 1.44-8.38; P = 0.006). In patients treated with nonchemoradiation modalities, there was no survival difference by XRCC1 expression. In multivariable analysis, high XRCC1 expression and p16(INK4a)-positive status were independently associated with survival in the overall study population (HR = 2.62; 95% CI: 1.52-4.52; P < 0.001 and HR = 0.21; 95% CI: 0.06-0.71; P = 0.012, respectively) and among chemoradiation patients (HR = 6.02; 95% CI: 2.36-15.37; P < 0.001 and HR = 0.26; 95% CI: 0.08-0.92, respectively; P = 0.037). In HNSCC, high XRCC1 protein expression is associated with poorer survival, particularly in patients receiving chemoradiation. Future validation of these findings may enable identification of HNSCC expressing patients who benefit from chemoradiation treatment.
    Clinical Cancer Research 09/2011; 17(20):6542-52. · 7.84 Impact Factor
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    ABSTRACT: Although treatment paradigms have shifted to recommend primary chemoradiation therapy (CRT) for advanced head and neck squamous cell carcinoma, few studies include any significant number of patients with N3 (>6 cm) neck disease. The objective of this study was to determine if primary chemoradiation therapy has equivalent overall survival (OS) and disease-free survival (DFS) when compared to primary surgical resection in patients with N3 neck disease. Nonrandomized, single-institution, retrospective cohort study. Retrospective analysis of 100 patients treated for HNSCC with N3 neck disease between 1989 and 2009 was performed. Patients who received primary surgery had better OS and DFS than those who had primary chemoradiation (P = .047), with a 5-year OS of 68% (95% confidence interval [CI], 45%-84%) versus 32% (95% CI, 19%-45%), and a 5-year DFS of 64% (95% CI, 41%-80%) versus 32% (95% CI, 19%-45%). Neck dissection following primary treatment with CRT did not improve OS. For patients with nonoropharyngeal squamous cell carcinoma with N3 neck disease, those who underwent primary surgery (n = 14) had significantly better OS than those who had primary CRT (n = 32, P = .02). Patients with oropharyngeal disease had better outcomes than other sites regardless of treatment modality, with 5-year OS of 54% (95% CI, 38%-68%) versus 32% (95% CI, 17%-47%, P = .02), but there was no statistical difference between patients treated with primary surgery versus CRT. Patients with head and neck squamous cell cancer and N3 neck disease have at least equivalent survival with primary surgical treatment versus primary CRT. Primary surgical resection with appropriate adjuvant therapy should be considered for patients with resectable N3 disease, especially patients with nonoropharyngeal sites. Post-CRT neck dissections did not change the OS of patients with N3 disease.
    The Laryngoscope 09/2011; 121(9):1881-7. · 1.98 Impact Factor

Publication Stats

685 Citations
169.86 Total Impact Points

Institutions

  • 2004–2014
    • University of North Carolina at Chapel Hill
      • • Lineberger Comprehensive Cancer Center
      • • Department of Otolaryngology/Head and Neck Surgery
      North Carolina, United States
  • 2012
    • National Institutes of Health
      Maryland, United States
    • University of California, San Francisco
      San Francisco, California, United States
    • Kocaeli University
      Cocaeli, Kocaeli, Turkey
  • 2011
    • University of Pennsylvania
      • Department of Radiation Oncology
      Philadelphia, PA, United States