[Show abstract][Hide abstract] ABSTRACT: Aim There is a high burden of oesophageal cancer in Malawi with dismal outcomes. It is not known whether environmental factors are associated with oesophageal cancer. Without knowing this critical information, prevention interventions are not possible. The purpose of this analysis was to explore environmental factors associated with oesophageal cancer in the Malawian context. Methods A hospital-based case-control study of the association between environmental risk factors and oesophageal cancer was conducted at Kamuzu Central Hospital in Lilongwe, Malawi and Queen Elizabeth Central Hospital in Blantyre, Malawi. Ninety-six persons with squamous cell carcinoma and 180 controls were enrolled and analyzed. These two groups were compared for a range of environmental risk factors, using logistic regression models. Unadjusted and adjusted odds ratios and 95% confidence intervals (CI) were calculated. Results Firewood cooking, cigarette smoking, and use of white maize flour all had strong associations with squamous cell carcinoma of the oesophagus, with adjusted odds ratios of 12.6 (95% CI: 4.2-37.7), 5.4 (95% CI: 2.0-15.2) and 6.6 (95% CI: 2.3-19.3), respectively. Conclusions Several modifiable risk factors were found to be strongly associated with squamous cell carcinoma. Research is needed to confirm these associations and then determine how to intervene on these modifiable risk factors in the Malawian context.
Preview · Article · Oct 2015 · Malawi medical journal: the journal of Medical Association of Malawi
[Show abstract][Hide abstract] ABSTRACT: Aim Review the literature from 1990 to 2013 to determine known anatomic sites, risk factors, treatments, and outcomes of head and neck squamous cell carcinoma (HNSCC) in sub-Saharan Africa. Methods Using a systematic search strategy, literature pertaining to HNSCC in sub-Saharan Africa was reviewed and patient demographics, anatomic sites, histology, stage, treatment, and outcomes were abstracted. The contributions of human immunodeficiency virus (HIV), human papillomavirus (HPV) and behavioural risk factors to HNSCC in the region were assessed. Results Of the 342 papers identified, 46 were utilized for review, including 8611 patients. In sub-Saharan Africa, the oropharyngeal/oral cavity was found to be the most common site, with 7750 cases (90% of all cases). Few papers distinguished oropharyngeal from oral cavity, making identification of possible HPV-associated oropharyngeal squamous cell carcinoma (SCC) difficult. SCC of the nasopharynx, nasal cavity, or paranasal sinuses was identified in 410 patients (4.8% of all cases). Laryngeal SCC was found in 385 patients (4.5% of all cases), and only 66 patients (0.8% of all cases) with hypopharyngeal SCC were identified. In 862 patients with data available, 43% used tobacco and 42% used alcohol, and reported use varied widely and was more common in laryngeal SCC than that of the oropharyngeal/oral cavity. Toombak and kola nut use was reported to be higher in patients with HNSCC. Several papers reported HIV-positive patients with HNSCC, but it was not possible to determine HNSCC prevalence in HIV-positive compared to negative patients. Reports of treatment and outcomes were rare. Conclusions The oropharyngeal/oral cavity was by far the most commonly reported site of HNSCC reported in sub-Saharan Africa. The roles of risk factors in HNSCC incidence in sub-Saharan Africa were difficult to delineate from the available studies, but a majority of patients did not use tobacco and alcohol.
Preview · Article · Oct 2015 · Malawi medical journal: the journal of Medical Association of Malawi
[Show abstract][Hide abstract] ABSTRACT: The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs.
[Show abstract][Hide abstract] ABSTRACT: Background:
It is unclear whether bone invasion in small oral cavity squamous cell carcinomas (OCSCC) results in worse prognosis.
Two hundred fifty-four patients with OCSCC were identified and divided into 3 cohorts: (1) ≤4 cm with no bone invasion; (2) ≤4 cm with bone invasion; and (3) ≥4 cm or other factors (eg, skin invasion, deep muscle invasion) that would qualify for American Joint Committee on Cancer (AJCC) T4 classification aside from bone invasion. Depth of bone invasion (none, cortical, or medullary) was also recorded.
Cohorts 1 and 2 had similar outcomes. Cohort 3 had lower rates of regional control (p = .04), disease-specific survival (DSS; p < .01), and overall survival (OS; p < .01). On multivariate analysis, margin status and medullary bone invasion were associated with worse outcomes.
Bone invasion does not seem to significantly influence outcomes in patients with small primary tumors treated with surgery/radiation. Medullary bone invasion seems to result in reduced rates of control and survival.
[Show abstract][Hide abstract] ABSTRACT: Aim:
Description of pathologic causes of cervical lymphadenopathy at Kamuzu Central Hospital.
The evaluation of cervical lymphadenopathy is a common diagnostic challenge facing clinicians. Previously at Kamuzu Central Hospital (KCH) tuberculosis (TB) was reported to be the most common cause of cervical lymphadenopathy However, no recent study has assessed this common diagnostic challenge in Malawi, particularly since the beginning of the HIV epidemic and the subsequent scale-up of antiretroviral therapy.
We conducted a cross-sectional study of all cervical lymph node specimens from the KCH pathology laboratory between 1 July 2011 and 28 February 2013 and describe patient age, gender, and pathologic diagnoses.
Our search of the KCH pathology database yielded 179 cases. Of these, 143 (77%) were histologic specimens (open biopsy or core needle samples) while 34 (23%) were cytology specimens. The age range was from 0 to 76 years with a mean of 30 (SD: 19). In adults, the most common diagnosis was malignancy (n=41, 35%), while in children 15 cases each of malignancy and benign masses were diagnosed. Only 6 cases (5%) of TB were diagnosed in adults, and 4 cases (6%) of TB were diagnosed in children.
Our study shows more malignancy and much less TB than a prior study of cervical lymphadenopathy at KCH. With the successful initiaion of the KCH Pathology Laboratory in 2011, we recommend biopsy or FNA early in the workup of cervical lymphadenopathy to prevent long delays in diagnosis and treatment of curable cancers.
No preview · Article · Mar 2014 · Malawi medical journal: the journal of Medical Association of Malawi
[Show abstract][Hide abstract] 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).
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).
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.
IPNs at staging in patients with HNSCC do not affect prognosis and should neither influence initial treatment planning nor the frequency of posttreatment surveillance.
[Show abstract][Hide abstract] 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.
Full-text · Article · Dec 2013 · Tropical Medicine and Health
[Show abstract][Hide abstract] ABSTRACT: Nasal fractures are usually diagnosed by clinical examination, with or without the support of imaging studies. While plain-film radiography lacks sensitivity and specificity for diagnosing nasal fractures, and computed tomography (CT) is not always practical or cost-effective, ultrasonography (US) may be useful in this regard. The criteria by which adult nasal fractures are reliably identified on US must be clear. We conducted a preliminary prospective, controlled, observational study to define the appearance of nasal fractures on US. We used US to image 12 patients with a clinical or radiologic (CT or x-ray) diagnosis of nasal fracture. All patients presented within 2 weeks of their injury. For comparison purposes, we also obtained US images from 12 control subjects who had no history of nasal trauma or surgery. We found that we could confidently diagnose nasal fractures on lateral-view US on the basis of a disruption of bone continuity and/or displacement of fracture segments. However, our findings were not as consistent with dorsal-view US, and we do not believe it is adequate for diagnosis. We conclude that lateral US can be used to detect nasal fractures in adults, but further studies are needed to assess its sensitivity, specificity, cost-effectiveness, and practicality.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
Full-text · Article · Jul 2013 · Otolaryngology Head and Neck Surgery
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
No preview · Article · Jun 2013 · World Journal of Oncology
[Show abstract][Hide abstract] 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.
No preview · Article · Dec 2012 · Clinical lymphoma, myeloma & leukemia
[Show abstract][Hide abstract] 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.
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.
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.
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.
[Show abstract][Hide abstract] 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.
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.
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).
The risk of subclinical nodal disease is low for patients with an isolated LR after chemoradiotherapy.
No preview · Article · Jul 2012 · American journal of clinical oncology
[Show abstract][Hide abstract] 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.
Full-text · Article · Jun 2012 · British Journal of Cancer