Kaposi Sarcoma

Patients with invasive cancer, diagnosed between 1973 and 2014, were abstracted from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program^{22 ,23} . The overview and limitations of the database and the methods are described in the Supplementary information^{24 (link)–26} . SEER is a network of population-based incident tumor registries from geographically distinct regions in the US, covering 28% of the US population, including incidence, survival, and treatment (e.g. radiation therapy, surgery, and chemotherapy)^{22 ,23} . For the current analysis, the SEER18 registry was used. The SEER registry includes data on sex, age at diagnosis, race, marital status, and year of diagnosis. SEER does not code comorbidities, performance status, surgical pathology, margin status, doses, or chemotherapy agents. SEER*Stat 8.2.1 was used for analysis²² .
All patients with an invasive cancer diagnosis were included. Patients diagnosed only through autopsy or death certificate (<1.5% of patients) were excluded. Data were extracted for patients with more than 100,000 person-years or more of survival time; thus, certain uncommon and aggressive cancers were excluded, including Kaposi’s sarcoma, multiple myeloma, hepatobiliary cancer, male breast cancers, and mesotheliomas. Since certain cancers represent a heterogeneous group of disease (e.g. leukemia, lymphoma), these cancers were grouped for certain parts of the analysis, so they could be reported accurately.
Mortality codes in SEER are assigned from death certificates, completed by the doctor caring for the patient at the time of demise. Patients were considered to have committed suicide if the cause of death was coded as: suicide and self-inflicted injury (50220). Patients with other causes of death, including accident, homicide, and legal intervention were excluded from the present analysis. Survival time in SEER is measured in months, and the smallest nonzero value is 1 month, which was the minimum time to any event.
Notably, SEER does not code comorbidities or diagnoses associated with suicide, including suicidal ideation, previous suicide attempts, or use of anti-depressive medications. The observed associations between cancer and suicide may be confounded by psychiatric disorders and the use of medications, but we are unable to control for these factors in the current work. These are limitations of the analysis and limit the interpretability of the results.
For objective 1, we calculated standardized mortality ratios (SMRs), which provide the relative risk of death for patients with cancer as compared to all US residents, stratified by cancer subgroup^{3 (link),22 ,27} . Data were characterized with SMRs adjusted by age, race, and sex to the US population over the same time. Five-year age categories were used for standardization using SEER*Stat 8.2.1 and Microsoft Excel 15.0.4 (Microsoft, Redmond, WA)^{27 –29 (link)}.
For objective 2, odds ratios (ORs) with 95% CIs were calculated based on the number of observed events per patient subgroup. Further, the absolute and relative number of suicides per patient age group (at time of diagnosis) were calculated. We also performed a survival analysis using a Cox proportional hazards model to calculate hazard ratios (HRs), with the survival time being from diagnosis until suicide, and non-suicide deaths plus living patients being censored.

A timeline of events in the development of the laboratory is shown in Table 1. Unused space in an existing dermatology unit was donated by KCH. UNC resources were provided for renovations, including minor structural modifications, as well as installation of electricity, plumbing, and equipment totaling more than 200,000 US dollars. New equipment for the laboratory included stainless steel benches, sinks, Perspex safety cabinet, Leica tissue processor and embedding station, microtome, ultralow freezer, and Leica microscope equipped with digital camera and computer. An Aperio^TM virtual microscopy system was installed, so that UNC pathologists can provide long-distance consultation as needed. A weekly telepathology session is now held with participation of clinicians and pathologists both at UNC and in Malawi, to review specimens of interest. Support for these activities was provided by the US National Institutes of Health (NIH) through the Medical Education Partnership Initiative (MEPI), the AIDS Malignancy Consortium (AMC), and the Division of AIDS (DAIDS). Additional support was provided by the UNC Lineberger Compehensive Cancer Center, and the UNC Department of Pathology and Laboratory Medicine. KCH provides the majority of consumable supplies for ongoing operations.
The laboratory became operational in July 2011. Specimen review and laboratory direction are provided by Professor George Liomba, a senior Malawian pathologist trained in the United Kingdom. During the first 20 months of operations, Professor Liomba reviewed more than 70% of all specimens, and more than 95% of all specimens after joining the laboratory full-time in October 2012. Before then, specimens were sent to Professor Liomba in Blantyre where he was previously based before moving to Lilongwe. Volunteers from Pathologists Overseas additionally provided diagnostic interpretation during the early period. Malawian histology and cytology technicians were trained in Blantyre and also at the University of Witwatersrand in South Africa, and have returned home to staff the laboratory. Immunohistochemistry (IHC) is slowly being implemented (Table 2), to provide data which can be used for clinical decision making, as well as for research purposes and to support enrollment into clinical trials. UNC pathologists are able to provide real-time feedback on quality of the staining procedures as these are implemented in Malawi. During the period reported in this paper, pathologic diagnoses were based on morphology alone without the assistance of IHC, flow cytometry, or molecular diagnostic tools. Operating procedures, as well as quality assessment and control systems have been established, and include weekly telepathology review by UNC pathologists to ensure diagnostic accuracy. Systems for monitoring the frequency with which diagnoses are revised based on telepathology review are being developed, and these data are not currently available. However, anecdotally there has been a remarkable degree of consensus between Professor Liomba and UNC pathologists during telepathology sessions. Formal accreditation of the laboratory by DAIDS is now ongoing to support local participation in two phase III clinical trials for Kaposi sarcoma (KS), which are cosponsored by AMC and the AIDS Clinical Trials Group (ACTG). During the period reported, receipt of specimens was restricted to KCH and immediately adjacent clinics, but a timetable for receiving specimens from peripheral hospitals has been developed, as well as a fee schedule to allow revenue generation and ensure financial sustainability independent of external support.