Development of a ratio of emergent to total hernia repairs as a surgical capacity metric.

INTRODUCTION: Non-communicable diseases including surgical conditions are gaining attention in developing countries. Despite this there are few metrics for surgical capacity. We hypothesized that (a) the ratio of emergent to total hernia repairs (E/TH) would correlate with per capita health care expenditures for any given country, and (b) the E/TH is easy to obtain in resource-poor settings. METHODS: We performed a systematic review to identify the E/TH for as many countries as possible (Prospero registry CRD42013004645). We screened 1285 English language publications since 1990; 23 met inclusion criteria. Primary data was also collected from Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. A total of 13 countries were represented. Regression analysis was used to determine the correlation between per capita health care spending and the E/TH. RESULTS: There is a strong correlation between the log values of the ratio emergent to total groin hernias and the per capita health care spending that is robust across country income levels (R(2) = 0.823). Primary data from KCH was easily obtained and demonstrated a similar correlation. CONCLUSIONS: The ratio of emergent to total groin hernias is a potential measure of surgical capacity using data that is easily attainable. Further studies should validate this metric against other accepted health care capacity indicators. Systematic review registered with Prospero (CRD42013004645).

The role of seizure disorders in burn injury and outcome in Sub-Saharan Africa.

Patients with epilepsy have higher incidence and severity of burn injury. Few studies describe the association between epilepsy and burns in low-income settings, where epilepsy burden is highest. The authors compared patients with and without seizure disorder in a burn unit in Lilongwe, Malawi. The authors conducted a retrospective study of patients admitted to the Kamuzu Central Hospital burn ward from July 2011 to December 2012. Descriptive analysis of patient characteristics and unadjusted and adjusted analyses of risk factors for mortality were conducted for patients with and without seizure disorder. Prevalence of seizure disorder was 10.7% in the study population. Adults with burns were more likely to have seizure disorder than children. Flame injury was most common in patients with seizure disorder, whereas scalds predominated among patients without seizure disorder. Whereas mortality did not differ between the groups, mean length of stay was longer for patients with seizure disorder, 42.1 days vs 21.6 days. Seizure disorder continues to be a significant risk factor for burn injury in adults in Malawi. Efforts to mitigate epilepsy will likely lead to significant decreases in burns among adults in Sub-Saharan Africa and must be included in an overall burn prevention strategy in our environment.

Application of SIRS criteria to a paediatric surgical population in Malawi.

INTRODUCTION: Little is known regarding systemic inflammatory response syndrome (SIRS) criteria and mortality in developing countries. We evaluated the utility of the SIRS criteria to predict death among a paediatric surgical population in Lilongwe, Malawi. METHODS: Age, SIRS variables (temperature, heart rate, systolic blood pressure, respiratory rate and leucocyte count), diagnosis, surgical procedure and outcome were analysed for paediatric surgical patients during 2012. Age-specific criteria for SIRS variables were then applied to the data. RESULTS: Using published SIRS criteria, temperature was the only variable that correlated with mortality. When norms for an African population were used, leucocyte count also correlated with mortality. DISCUSSION: With the exception of temperature, published SIRS criteria were not predictive of mortality. Leucocyte count became predictive of death using norms specific to an African population. SIRS and its component data are a worthwhile area of future prospective research in developing countries.

Pediatric surgical care in Lilongwe, Malawi: outcomes and opportunities for improvement.

BACKGROUND: One of the objectives of the Millennium Development Goals is to improve child health. We describe the burden of pediatric surgical disease at a tertiary hospital in Malawi. METHODS: We conducted a retrospective analysis of a pediatric surgery database at Kamuzu Central Hospital in Malawi for the calendar year 2012. Variables included patient demographics, admission diagnosis, primary surgery and outcome. RESULTS: A total of 1170 pediatric patients aged 0-17 years were admitted to the surgical service during the study period. The mean age was 6.9 years, and 62% were male. Trauma was the most common indication for admission (51%, n = 596), and 67% (n = 779) of all patients were managed non-operatively. Neonates and patients managed non-operatively had a significantly increased risk of mortality. CONCLUSION: Only a third of patients admitted to the pediatric surgery service underwent surgery. More than half of patients with congenital anomalies did not undergo surgical intervention. Importantly, patients who underwent surgery had a survival advantage.

Validating a verbal autopsy tool to assess pre-hospital trauma mortality burden in a resource-poor setting.

OBJECTIVES: To present the validation of a verbal autopsy (VA) tool using inpatient deaths in order to ultimately assess the burden of adult pre-hospital trauma mortality in Lilongwe, Malawi. METHODS: A WHO VA tool was administered at the Kamuzu Central Hospital (KCH) morgue in Lilongwe to family members of inpatient deceased. Two physicians assigned cause of death as 'trauma' or 'non-trauma' as well as a standard VA cause of death based on the VA tool. These assignments were compared to the 'gold standard' of physician review of hospital records using a kappa statistic. RESULTS: The VA method had near-perfect agreement with the hospital record in determining 'trauma' vs. 'non-trauma'. There was moderate agreement when comparing types of death, for example cardiovascular vs. infectious disease, and limited agreement when comparing specific causes of death. CONCLUSION: This VA tool can accurately ascertain trauma-related mortality with almost perfect agreement. The next step is to assess pre-hospital trauma mortality burden using the VA tool to determine whether hospital records underestimate the burden of trauma in the community.

Delivery of operative pediatric surgical care by physicians and non-physician clinicians in Malawi.

BACKGROUND: Specialized pediatric surgeons are unavailable in much of sub-Saharan Africa. Delegating some surgical tasks to non-physician clinical officers can mitigate the dependence of a health system on highly skilled clinicians for specific services. METHODS: We performed a case-control study examining pediatric surgical cases over a 12 month period. Operating surgeon was categorized as physician or clinical officer. Operative acuity, surgical subspecialty, and outcome were then compared between the two groups, using physicians as the control. RESULTS: A total of 1186 operations were performed on 1004 pediatric patients. Mean age was 6 years (±5) and 64% of patients were male. Clinical officers performed 40% of the cases. Most general surgery, urology and congenital cases were performed by physicians, while most ENT, neurosurgery, and burn surgery cases were performed by clinical officers. Reoperation rate was higher for patients treated by clinical officers (17%) compared to physicians (7.1%), although this was attributable to multiple burn surgical procedures. Physician and clinical officer cohorts had similar complication rates (4.5% and 4.0%, respectively) and mortality rates (2.5% and 2.1%, respectively). DISCUSSION: Fundamental changes in health policy in Africa are imperative as a significant increase in the number of surgeons available in the near future is unlikely. Task-shifting from surgeons to clinical officers may be useful to provide coverage of basic surgical care.

A case of acute necrotizing pancreatitis: Practical and ethical challenges of a North-South partnership.

INTRODUCTION: The Departments of Surgery at the University of North Carolina (UNC) and Kamuzu Central Hospital (KCH) in Lilongwe, Malawi, formed a partnership of service, training, and research in 2008. We report a case of recurrent pancreatitis leading to pancreatic necrosis treated at KCH. PRESENTATION OF CASE: A 42 year-old male presented to KCH with his fourth episode of abdominal pain, nausea and vomiting. He had tachycardia, guarding, rebound tenderness, and free fluid on abdominal ultrasonography. He underwent laparotomy and had fat saponification with pancreatic necrosis. A large drain was placed, he was given antibiotics, and he recovered. He had normal lipids, no gallstones, and did not consume alcohol. He was encouraged to seek further evaluation with endoscopic retrograde cholangiopancreatography or computed tomography in South Africa, however this was prohibitively expensive. DISCUSSION: This case illustrates the limitations that are often faced by surgeons visiting developing countries. What we consider standard resources and treatment algorithms in managing necrotizing pancreatitis in developed countries (such as serum lipase and percutaneous interventions) were not available. CONCLUSION: Visiting surgeons and trainees must be both familiar with local resource limitations and aware of the implications of such limitations on patient care. To support training and promote advances in health care, local surgeons and trainees should understand optimal treatment strategies regardless of their particular resource limitations. North-South partnerships are an excellent means to uphold our professional obligation to humanity, promote health care as a right, and shape the future of health care in developing countries.

Cancer Treatment in Malawi: A Disease of Palliation.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Survival after burn in a sub-Saharan burn unit: challenges and opportunities.

BACKGROUND: Burns are among the most devastating of all injuries and a major global public health crisis, particularly in sub-Saharan Africa. In developed countries, aggressive management of burns continues to lower overall mortality and increase lethal total body surface area (TBSA) at which 50% of patients die (LA50). However, lack of resources and inadequate infrastructure significantly impede such improvements in developing countries. METHODS: This study is a retrospective analysis of patients admitted to the burn center at Kamuzu Central Hospital in Lilongwe, Malawi between June 2011 and December 2012. We collected information including patient age, gender, date of admission, mechanism of injury, time to presentation to hospital, total body surface area (TBSA) burn, comorbidities, date and type of operative procedures, date of discharge, length of hospital stay, and survival. We then performed bivariate analysis and logistic regression to identify characteristics associated with increased mortality. RESULTS: A total of 454 patients were admitted during the study period with a median age of 4 years (range 0.5 months to 79 years). Of these patients, 53% were male. The overall mean TBSA was 18.5%, and average TBSA increased with age--17% for 0-18 year olds, 24% for 19-60 year olds, and 41% for patients over 60 years old. Scald and flame burns were the commonest mechanisms, 52% and 41% respectively, and flame burns were associated with higher mortality. Overall survival in this population was 82%; however survival reduced with increasing age categories (84% in patients 0-18 years old, 79% in patients 19-60 years old, and 36% in patients older than 60 years). TBSA remained the strongest predictor of mortality after adjusting for age and mechanism of burn. The LA50 for this population was 39% TBSA. DISCUSSION: Our data reiterate that burn in Malawi is largely a pediatric disease and that the high burn mortality and relatively low LA50 have modestly improved over the past two decades. The lack of financial resources, health care personnel, and necessary infrastructure will continue to pose a significant challenge in this developing nation. Efforts to increase burn education and prevention in addition to improvement of burn care delivery are imperative.

The burden of surgical diseases on critical care services at a tertiary hospital in sub-Saharan Africa.

In many developing countries, including those of sub-Saharan Africa, care of the critically ill is poorly developed. We sought to elucidate the characteristics and outcomes of critically ill patients in order to better define the burden of disease and identify strategies for improving care. We conducted a cross sectional observation study of patients admitted to the intensive care unit at Kamuzu Central Hospital in 2010. Demographics, patient characteristics, clinical specialty and outcome data was collected for the 234 patients admitted during the study period. Older age and admission from trauma, general surgery or medical services were associated with increased mortality. The lowest mortality was among obstetrical and gynaecology patients. Use of the ventilator and transfusions were not associated with increased mortality. Patients with head injuries had the highest mortality rate. Rationing of critical care resources, using admitting diagnosis or scoring tools, can maximize access to critical care services in resource-limited settings. Furthermore, improvements of critical care services will be central to future efforts to reduce surgical morbidity and mortality and improving outcomes in all critically ill patients.

Prevalence of HIV and Disease Outcomes on the Medical and Surgical Wards at Kamuzu Central Hospital, Lilongwe, Malawi.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Epidemiology of pediatric injury in Malawi: burden of disease and implications for prevention.

PURPOSE: Pediatric injuries pose a significant health burden in sub-Saharan Africa, though historic data are too scarce to appreciate the extent of the problem. The purpose of this study is to utilize a comprehensive database to describe the epidemiology of pediatric injuries at a tertiary hospital in Malawi. METHODS: Data were prospectively collected on patients presenting to the emergency department for treatment of injuries from 2008 to 2010 (n = 23,625). The subset of pediatric patients (n = 7233) underwent cross-sectional analysis to examine demographics, injury environment, timing and mechanisms. RESULTS: Pediatric patients, (0-16 years) comprised 30.6% of all trauma patients. Mean age was 7.2 years. Falls were the most common injury (43%), followed by burns (11.1%), pedestrian road traffic injuries (9.7%), foreign bodies (7.5%), and assaults (7.2%). Statistically significant differences in injury pattern were observed between gender, age groups and season. After logistic regression, predictors of fall included male gender, home setting, and rainy season, whereas predictors of burn included female gender, age 0-5 yrs, home setting, and cold season. Predictors of pedestrian injury included age 6-10 yrs, female, and roadside setting. Predictors of foreign body ingestion included age 0-5 yrs, female gender, home setting, and daytime, and predictors of assault include male gender, age 11-16 yrs, nighttime hours. All predictors were statistically significant (p < 0.05). CONCLUSIONS: This study revealed patterns of injury based upon age, gender, location, and season. Our results may prove useful to stakeholders in injury prevention for designing, evaluating, and implementing programs to improve public safety in children in Malawi and similar resource poor nations.

Under-reporting of road traffic mortality in developing countries: application of a capture-recapture statistical model to refine mortality estimates.

Road traffic injuries are a major cause of preventable death in sub-Saharan Africa. Accurate epidemiologic data are scarce and under-reporting from primary data sources is common. Our objectives were to estimate the incidence of road traffic deaths in Malawi using capture-recapture statistical analysis and determine what future efforts will best improve upon this estimate. Our capture-recapture model combined primary data from both police and hospital-based registries over a one year period (July 2008 to June 2009). The mortality incidences from the primary data sources were 0.075 and 0.051 deaths/1000 person-years, respectively. Using capture-recapture analysis, the combined incidence of road traffic deaths ranged 0.192-0.209 deaths/1000 person-years. Additionally, police data were more likely to include victims who were male, drivers or pedestrians, and victims from incidents with greater than one vehicle involved. We concluded that capture-recapture analysis is a good tool to estimate the incidence of road traffic deaths, and that capture-recapture analysis overcomes limitations of incomplete data sources. The World Health Organization estimated incidence of road traffic deaths for Malawi utilizing a binomial regression model and survey data and found a similar estimate despite strikingly different methods, suggesting both approaches are valid. Further research should seek to improve capture-recapture data through utilization of more than two data sources and improving accuracy of matches by minimizing missing data, application of geographic information systems, and use of names and civil registration numbers if available.

An observational study addressing the anatomic basis of mesosigmoidopexy as a rational treatment of non-gangrenous sigmoid volvulus.

Sigmoid volvulus is a common cause of bowel obstruction. We describe mesosigmoidopexy, an accepted surgical technique for the management of non-gangrenous sigmoid volvulus, and provide anatomic correlations supporting the therapy. Mesosigmoidopexy should be considered as a rational alternative to resection and anastomosis when operating on non-gangrenous sigmoid volvulus.

An Observational Study of the Etiology, clinical presentation and outcomes associated with peritonitis in Lilongwe, Malawi.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The role of the anatomy of the sigmoid colon in developing sigmoid volvulus: a case-control study.

Sigmoid volvulus is a common condition throughout much of the world. To this date, there are no adequately controlled clinical trials examining the role of anatomy in sigmoid volvulus. Therefore, the objective of this study was to determine if the anatomic dimensions of the sigmoid colon differ in sigmoid volvulus compared to controls. This prospective case-control study was conducted at Kamuzu Central Hospital, Lilongwe, Malawi. Cases included individuals 18 years or older with surgically confirmed sigmoid volvulus, while controls included individuals undergoing surgery for reasons unrelated to the descending or sigmoid colon, or rectum. Intraoperative measurements of the sigmoid colon were taken, including mesosigmoid root width and mesosigmoid length. A total of 26 cases and 12 controls were enrolled. When compared to controls, the mesosigmoid of cases had a greater length and maximal width; however, mesosigmoid root width was similar between groups. These findings support the assertion that sigmoid volvulus is due to a long and wide mesosigmoid that rotates on a constant mesosigmoid root width. This is the first adequately controlled trial examining anatomy in sigmoid volvulus and provides strong evidence that refines prior hypotheses regarding the anatomic basis of sigmoid volvulus.

Activation and involvement of Ral GTPases in colorectal cancer.

Current approaches to block KRAS oncogene function focus on inhibition of K-Ras downstream effector signaling. We evaluated the antitumor activity of selumetinib (AZD6244, ARRY-142886), a potent and selective MEK1/2 inhibitor, on a panel of colorectal carcinoma (CRC) cells and found no inhibition of KRAS mutant CRC cell anchorage-independent growth. Although AKT activity was elevated in KRAS mutant cells, and PI3K inhibition did impair the growth of MEK inhibitor-insensitive CRC cell lines, concurrent treatment with selumetinib did not provide additional antitumor activity. Therefore, we speculated that inhibition of the Ral guanine exchange factor (RalGEF) effector pathway may be a more effective approach for blocking CRC growth. RalGEFs are activators of the related RalA and RalB small GTPases and we found activation of both in CRC cell lines and patient tumors. Interfering RNA stable suppression of RalA expression reduced CRC tumor cell anchorage-independent growth, but surprisingly, stable suppression of RalB greatly enhanced soft agar colony size and formation frequency. Despite their opposing activities, both RalA and RalB regulation of anchorage-independent growth required interaction with RalBP1/RLIP76 and components of the exocyst complex. Interestingly, RalA interaction with the Exo84 but not Sec5 exocyst component was necessary for supporting anchorage-independent growth, whereas RalB interaction with Sec5 but not Exo84 was necessary for inhibition of anchorage-independent growth. We suggest that anti-RalA-selective therapies may provide an effective approach for KRAS mutant CRC.

A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease. For patients with localized PDAC, surgery is the best option, but with a median survival of less than 2 years and a difficult and prolonged postoperative course for most, there is an urgent need to better identify patients who have the most aggressive disease. METHODS AND FINDINGS: We analyzed the gene expression profiles of primary tumors from patients with localized compared to metastatic disease and identified a six-gene signature associated with metastatic disease. We evaluated the prognostic potential of this signature in a training set of 34 patients with localized and resected PDAC and selected a cut-point associated with outcome using X-tile. We then applied this cut-point to an independent test set of 67 patients with localized and resected PDAC and found that our signature was independently predictive of survival and superior to established clinical prognostic factors such as grade, tumor size, and nodal status, with a hazard ratio of 4.1 (95% confidence interval [CI] 1.7-10.0). Patients defined to be high-risk patients by the six-gene signature had a 1-year survival rate of 55% compared to 91% in the low-risk group. CONCLUSIONS: Our six-gene signature may be used to better stage PDAC patients and assist in the difficult treatment decisions of surgery and to select patients whose tumor biology may benefit most from neoadjuvant therapy. The use of this six-gene signature should be investigated in prospective patient cohorts, and if confirmed, in future PDAC clinical trials, its potential as a biomarker should be investigated. Genes in this signature, or the pathways that they fall into, may represent new therapeutic targets. Please see later in the article for the Editors' Summary.

Hospital-based injury data in Malawi: strategies for data collection and feasibility of trauma scoring tools.

Injury is a major cause of morbidity and mortality in developing countries. Utilizing a partnership between Kamuzu Central Hospital (KCH) and the University of North Carolina Departments of Surgery, we describe an approach to injury surveillance, examine the utility of trauma scoring systems, and outline steps necessary before such scoring systems can be reliably instituted in a resource-constrained setting.