Premature mortality trends in 183 countries by cancer type, sex, WHO region, and World Bank income level in 2000-19: a retrospective, cross-sectional, population-based study.

BACKGROUND: Cancer is a leading cause of mortality worldwide. By 2040, over 30 million new cancers are predicted, with the greatest cancer burden in low-income countries. In 2015, the UN passed the Sustainable Development Goal 3.4 (SDG 3.4) to tackle the rising burden of non-communicable diseases, which calls for a reduction by a third in premature mortality from non-communicable diseases, including cancer, by 2030. However, there is a paucity of data on premature mortality rates by cancer type. In this study, we examine annual rates of change for cancer-specific premature mortality and classify whether countries are on track to reach SDG 3.4 targets. METHODS: This is a retrospective, cross-sectional, population-based study investigating premature mortality trends from 2000-19 using the WHO Global Health Estimates data. All cancers combined and thirteen individual cancers in 183 countries were examined by WHO region, World Bank income level, and sex. The risk of premature mortality was calculated for ages 30-69 years, independent of other competing causes of death, using standard life table methods. The primary objective was to compute average annual rate of change in premature mortality from 2000 to 2019. Secondary objectives assessed whether this annual rate of change would be sufficient to reach SDG 3.4. targets for premature mortality by 2030. FINDINGS: This study was conducted using data retrieved for the years 2000-19. Premature mortality rates decreased in 138 (75%) of 183 countries across all World Bank income levels and WHO regions, however only eight (4%) countries are likely to meet the SDG 3.4 targets for all cancers combined. Cancers where early detection strategies exist, such as breast and colorectal cancer, have higher declining premature mortality rates in high-income countries (breast cancer 48 [89%] of 54 and colorectal cancer 45 [83%]) than in low-income countries (seven [24%] of 29 and four [14%]). Cancers with primary prevention programmes, such as cervical cancer, have more countries with declining premature mortality rates (high-income countries 50 [93%] of 54 and low-income countries 26 [90%] of 29). Sex-related disparities in premature mortality rates vary across WHO regions, World Bank income groups, and by cancer type. INTERPRETATION: There is a greater reduction in premature mortality for all cancers combined and for individual cancer types in high-income countries compared with lower-middle-income and low-income countries. However, most countries will not reach the SDG 3.4 target. Cancers with early detection strategies in place, such as breast and colorectal cancers, are performing poorly in premature mortality compared with cancers with primary prevention measures, such as cervical cancer. Investments toward prevention, early detection, and treatment can potentially accelerate declines in premature mortality. FUNDING: WHO.

Series on the Lancet Oncology Commission on Global Cancer Surgery: Introduction-Intent and Content.

BACKGROUND: Surgery plays a key role in the multi-disciplinary cancer care pathway. Nearly 80% of patients with solid tumors will require surgical intervention during the course of their disease. Unfortunately, the vast majority of these patients do not have access to safe, timely, high-quality, and affordable cancer surgical care. The first Lancet Oncology Commission on Global Cancer Surgery shone a light on this grave situation and outlined some strategies to address them. The second Lancet Oncology Commission on Global Cancer Surgery (TLO- II) was conceived to continue the work of its predecessor by developing a roadmap of practical solutions to propel improvements in cancer surgical care globally. METHODS: The Commission was developed by involving approximately 50 cancer care leaders and experts from different parts of the world to ensure diversity of input and global applicability. RESULTS: The Commission identified nine solutional domains that are considered essential to deliver safe, timely, high-quality, and affordable cancer surgical care. These nine domains were further refined to develop solutions specific to each of the six World Health Organization regions. Based on the above solutions, we developed eight action items that are intended to propel improvements in cancer surgical care on the global stage. CONCLUSIONS: The second Lancet Oncology Commission on Global Cancer Surgery builds on the first Commission by developing a pragmatic roadmap of practical solutions that we hope will ensure access to safe, timely, high-quality, and affordable cancer surgical care for everyone regardless of their socioeconomic status or geographic location.

Cancer surgery on the global stage: Updates and progress.

Over 5 billion people lack access to basic surgical procedures, and it is estimated, the number of surgical procedures needed for cancer care will increase by 5 million from 2018 to 2040. The greatest increase in demand will occur in low- and middle-income countries. In this article, we highlight progress made in surgical cancer care globally and gaps that still needs to be addressed. We highlight political support, workforce progress and shortages, impact of the COVID-19 pandemic, and the importance of high value cancer care.

PI3K/Akt/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment.

In the last decade, pathway-specific targeted therapy has revolutionized colorectal cancer (CRC) treatment strategies. This type of therapy targets a tumor-vulnerable spot formed primarily due to an alteration in an oncogene and/or a tumor suppressor gene. However, tumor heterogeneity in CRC frequently results in treatment resistance, underscoring the need to understand the molecular mechanisms involved in CRC for the development of novel targeted therapies. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin (PI3K/Akt/mTOR) signaling pathway axis is a major pathway altered in CRC. The aberrant activation of this pathway is associated with CRC initiation, progression, and metastasis and is critical for the development of drug resistance in CRC. Several drugs target PI3K/Akt/mTOR in clinical trials, alone or in combination, for the treatment of CRC. This review aims to provide an overview of the role of the PI3K/Akt/mTOR signaling pathway axis in driving CRC, existing PI3K/Akt/mTOR-targeted agents against CRC, their limitations, and future trends.

Global Cancer Surgery: pragmatic solutions to improve cancer surgery outcomes worldwide.

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Education of the cancer surgical workforce: Gaps, priorities, and strategies.

Cancer is a leading cause of noncommunicable disease-related mortality. The predicted number of new cancer cases will increase from 19.3 million in 2020 to 30.2 million by 2040. To mitigate the cancer burden, it is critical to build capacity of the cancer workforce, especially in systems with limited resources. We provide a global overview of gaps and implementation strategies that can increase the quality and quantity of the global surgical cancer workforce.

Inequities in cancer surgical research capacity in the global south and strategies to address them.

Globally, cancer is a leading cause of premature mortality and incidence is rising rapidly. To mitigate the cancer burden establishing research programs that are country and/or region specific will inform evidence-based cancer control policies and programs. However inequities in surgical cancer research in the global south exist and in this article we discuss gaps and potential solutions through frameworks focusing on research training, building infrastructure, economic strategies, and research ethics.

Global trends in the incidence and mortality of pancreatic cancer based on geographic location, socioeconomic status, and demographic shift.

BACKGROUND: Pancreatic cancer (PC) is a lethal malignancy with a significantly rising rate of incidence and mortality. This study aims to describe the influence of geography, socioeconomic development (based on the Human Development Index [HDI]), gender, and demographic shift on the temporal trends in the global burden of PC. METHODS: Data (2020-2040) relating to the incidence, mortality of PC, and demographic shifts based on continents and HDI areas were extracted from GLOBOCAN 2020. RESULTS: PC was associated with a higher socioeconomic status. Asia contributed to the majority of the burden, led by China. Advanced age (≥65 years) contributed to the majority of the burden in all socioeconomic regions except in Medium HDI and Low HDI countries, where the younger population (<65 years) contributed more. Females contributed to a higher burden in certain countries. Future trends for 2040 showed a >60% increase in the incidence and mortality of PC with an associated demographic shift. CONCLUSION: The global burden of PC is expected to rise significantly over the next few decades regardless of geography, socioeconomic development, age, and gender. Advance knowledge of this data can help to formulate strategies and public health policies to specifically target countries and populations at risk.

Global epidemiological trends and variations in the burden of gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is a rare but lethal malignancy with a dismal prognosis. The aim of this study is to analyze the burdens and trends of GBC across the world based on geography, socioeconomic development (based on human development index [HDI]), and gender. METHODS: GLOBOCAN 2020 database was used to extract data (2020-2040) relating to the incidence and mortality of GBC across the world. RESULTS: Asia had the highest burden of GBC with India and China contributing to majority of the absolute burden. The burden of GBC by age standardized rate was highest in Latin America (Bolivia and Chile) and Southeast Asia (Bangladesh and Nepal). Medium HDI countries had a higher mortality rate compared to very high HDI countries. Females had a higher predilection for GBC across different regions and socioeconomic groups. GBC burden is expected to significantly increase across the world by 2040 with variable trends across different regions, age groups, and genders. CONCLUSION: The global burden of GBC will significantly increase over the next two decades with marked regional and demographic variations. The results of this study will empower national and global health leaders to develop policies to address the increasing burden of this lethal malignancy.

Colorectal cancer: Review of signaling pathways and associated therapeutic strategies.

Tumor profiling and targeted therapy revolutionized the treatment strategies of metastatic colorectal cancer (mCRC) in the last decade. The heterogeneity of CRC tumors plays a critical role in the development of treatment resistance, which underscores the need to understand the molecular mechanism involved in CRC to develop novel targeted therapeutic strategies. This review provides an overview of the signaling pathways driving CRC, the existing targeted agents, their limitations, and future trends.

Factors associated with pathologic complete response following neoadjuvant chemoradiation and esophagectomy for carcinoma of esophagus and gastroesophageal junction.

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze factors associated with pathologic complete response (pCR) following neoadjuvant chemoradiation (NCRT) and esophagectomy for carcinoma of the esophagus (EC) and gastroesophageal junction (GEJ). METHODS: Patients with EC and GEJ tumors who received NCRT and underwent esophagectomy between January 2010 to March 2021 were included. Univariate and multivariate analyses were performed to evaluate the factors associated with pCR by comparing the patients who achieved pCR (pCR group) with those who did not achieve pCR (non-pCR group). RESULTS: A total of 321 patients were included in the study, with squamous cell carcinoma (SCC) accounting for the majority of cases (76%). One hundred and sixty (49.8%) patients had pCR. SCC histology and pretreatment radiographic node-negative status (cN0) were associated with pCR. Patients in the pCR group had significantly better overall and disease-free survival compared with patients in the non-pCR group. CONCLUSIONS: SCC histology and pretreatment radiographic node-negative status were associated with pCR. For patients with tumors of EC and GEJ who received NCRT and underwent esophagectomy, pCR was associated with improved prognosis compared with those not achieving pCR.

Global Forum of Cancer Surgeons: Cancer Surgery During the COVID-19 Pandemic: Impact and Lessons Learned.

BACKGROUND: The purpose of this article is to summarize the opinions of the surgical oncology leaders from the Global Forum of Cancer Surgeons (GFCS) about the global impact of COVID-19 pandemic on cancer surgery. METHODS: A panel session (virtual) was held at the annual Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care to address the impact of COVID-19 on cancer surgery globally. Following the virtual meeting, a questionnaire was sent to all the leaders to gather additional opinions. The input obtained from all the leaders was collated and analyzed to understand how cancer surgeons from across the world adapted in real-time to the impact of COVID-19 pandemic. RESULTS: The surgical oncology leaders noted that the COVID-19 pandemic led to severe disruptions in surgical cancer care across all domains of clinical care, education, and research. Several new changes/protocols associated with increased costs were implemented to deliver safe care. Leaders also noted that preexisting disparities in care were exacerbated, and the pandemic had a detrimental effect on well-being and financial status. CONCLUSIONS: The COVID-19 pandemic has led to severe disruptions in surgical cancer care globally. Leaders of the GFCS opined that new strategies need to be implemented to prepare for any future catastrophic events based on the lessons learned from the current events. The GFCS will embark on developing such a roadmap to ensure that surgical cancer care is preserved in the future regardless of any catastrophic global events.

Radical surgery for de novo gallbladder carcinoma-Single-center analysis of prognostic factors and survival outcomes from an endemic region.

BACKGROUND AND OBJECTIVE: Gallbladder cancer (GBC) is an aggressive malignancy where curative resection is possible in few and survival is poor. There are limited data on outcomes in patients with de novo GBC from endemic regions undergoing surgery for curative intent. We report survival outcomes in this group of patients from a region with high incidence of disease. METHODS: We reviewed the records of all GBC patients (2014-2018) and included those who underwent radical cholecystectomy (RC) for de novo GBC. Univariable and multivariable analyses were performed to identify factors influencing recurrence and survival. RESULTS: A total of 649 patients with GBC were evaluated for surgery and curative intent surgery was attempted in 246 (38%) patients. Of these 246 patients, RC was performed in 115 patients, with histologically confirmed de novo GBC. Locally advanced disease (≥stage IIIB) was present in 52 (45.2%) patients. Median time to recurrence and overall survival (OS) were 31 and 36 months, respectively. Lymph node positivity (p = 0.005) and grade significantly influenced OS on multivariable analysis. CONCLUSION: Satisfactory survival outcomes are possible after RC for de novo GBC. Extended resections performed in high volume centers combined with appropriate adjuvant treatment can offer significant survival benefits, with acceptable morbidity and mortality rates.

The Role of Personal Accomplishment in General Surgery Resident Well-being.

OBJECTIVE: To investigate the association of personal accomplishment (PA) with the other subscales, assess its association with well-being outcomes, and evaluate drivers of PA by resident level. BACKGROUND: Most studies investigating physician burnout focus on the emotional exhaustion (EE) and depersonalization (DP) subscales, neglecting PA. Therefore, the role of PA is not well understood. METHODS: General surgery residents were surveyed following the 2019 American Board of Surgery In-Training Examination regarding their learning environment. Pearson correlations of PA with EE and DP were assessed. Multivariable logistic regression models assessed the association of PA with attrition, job satisfaction, and suicidality and identified factors associated with PA by PGY. RESULTS: Residents from 301 programs were surveyed (85.6% response rate, N = 6956). Overall, 89.4% reported high PA, which varied by PGY-level (PGY1: 91.0%, PGY2/3: 87.7%, PGY4/5: 90.2%; P = 0.02). PA was not significantly correlated with EE (r = -0.01) or DP (r = -0.08). After adjusting for EE and DP, PA was associated with attrition (OR 0.60, 95%CI 0.46-0.78) and job satisfaction (OR 3.04, 95%CI 2.45-3.76) but not suicidality (OR 0.72, 95%CI 0.48-1.09). Although the only factor significantly associated with PA for interns was resident cooperation, time in operating room and clinical autonomy were significantly associated with PA for PGY2/3. For PGY4/5s, PA was associated with time for patient care, resident cooperation, and mentorship. CONCLUSION: PA is a distinct metric of resident well-being, associated with job satisfaction and attrition. Drivers of PA differ by PGY level and may be targets for intervention to promote resident wellness and engagement.

Management of Locally Advanced Pancreatic Cancer: Results of an International Survey of Current Practice.

OBJECTIVE: The aim of this study was to investigate surgeon preferences for the management of patients with locally advanced pancreatic cancer (LAPC). BACKGROUND: Select patients with LAPC may become candidates for curative resection following neoadjuvant therapy, and recent reports of survival are encouraging. Yet the optimal management approach remains unclear. METHODS: An extensive electronic survey was systematically distributed by email to an international cohort of pancreas surgeons. Data collected included practice characteristics, management preferences, attitudes regarding contraindications to surgery, and 6 clinical vignettes of patients that ultimately received a margin negative resection (with detailed videos of post-neoadjuvant imaging) to assess propensity for surgical exploration if resection status is not known. RESULTS: A total of 153 eligible responses were received from 4 continents. Median duration of practice is 12 years (interquartile range 6-20) and 77% work in a university setting. Most surgeons (86%) are considered high volume (>10 resections/yr), 33% offer a minimally-invasive approach, and 50% offer arterial resections in select patients. Most (72%) always recommend neoadjuvant chemotherapy, and 65% prefer FOLFIRINOX. Preferences for the duration of chemotherapy varied widely: 39% prefer ≥2 months, 43% prefer ≥4 months, and 11% prefer ≥6 months. Forty-one percent frequently recommend neoadjuvant radiotherapy, and 53% prefer 5 to 6 weeks of chemoradiation. The proportion of surgeons favoring exploration following neoadjuvant varied extensively across 5 vignettes of LAPC, from 14% to 53%. In a vignette of oligometastatic liver metastases, 31% would offer exploration if a favorable therapy response is observed. CONCLUSIONS: In an international cohort of pancreas surgeons, there is substantial variation in management preferences, perceived contraindications to surgery, and the propensity to consider exploration in LAPC. These results emphasize the importance of a robust and nuanced multidisciplinary discussion for each patient, and suggest an evolving concept of "resectability."

Comprehensive Characterization of the General Surgery Residency Learning Environment and the Association With Resident Burnout.

OBJECTIVES: To characterize the learning environment (ie, workload, program efficiency, social support, organizational culture, meaning in work, and mistreatment) and evaluate associations with burnout in general surgery residents. BACKGROUND SUMMARY DATA: Burnout remains high among general surgery residents and has been linked to workplace exposures such as workload, discrimination, abuse, and harassment. Associations between other measures of the learning environment are poorly understood. METHODS: Following the 2019 American Board of Surgery In-Training Examination, a cross-sectional survey was administered to all US general surgery residents. The learning environment was characterized using an adapted Areas of Worklife survey instrument, and burnout was measured using an abbreviated Maslach Burnout Inventory. Associations between burnout and measures of the learning environment were assessed using multivariable logistic regression. RESULTS: Analysis included 5277 general surgery residents at 301 programs (85.6% response rate). Residents reported dissatisfaction with workload (n = 784, 14.9%), program efficiency and resources (n = 1392, 26.4%), social support and community (n = 1250, 23.7%), organizational culture and values (n = 853, 16.2%), meaning in work (n = 1253, 23.7%), and workplace mistreatment (n = 2661, 50.4%). The overall burnout rate was 43.0%, and residents were more likely to report burnout if they also identified problems with residency workload [adjusted odds ratio (aOR) 1.60, 95% confidence interval (CI) 1.31-1.94], efficiency (aOR 1.74; 95% CI 1.49-2.03), social support (aOR 1.37, 95% CI 1.15-1.64), organizational culture (aOR 1.64; 95% CI 1.39-1.93), meaning in work (aOR 1.87; 95% CI 1.56-2.25), or experienced workplace mistreatment (aOR 2.49; 95% CI 2.13-2.90). Substantial program-level variation was observed for all measures of the learning environment. CONCLUSIONS: Resident burnout is independently associated with multiple aspects of the learning environment, including workload, social support, meaning in work, and mistreatment. Efforts to help programs identify and address weaknesses in a targeted fashion may improve trainee burnout.

Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma: Propensity-Matched Analysis of Postoperative Complications Using ACS-NSQIP.

BACKGROUND: The use of neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) is increasing. While there is an association between NAT and improved post-pancreatectomy complication rates in limited patient populations, the strength of the relationship and its applicability to a broader and modern pancreatectomy cohort remains unclear. METHODS: We used the 2014-2018 American College of Surgeons National Surgical Quality Improvement Project to evaluate NAT use for PDAC patients undergoing pancreatectomy. We also used propensity score matching techniques to compare 30-day postoperative outcomes, including clinically relevant postoperative pancreatic fistula (CR-POPF) and delayed gastric emptying (DGE), between patients selected for NAT versus upfront surgery. RESULTS: Patients receiving NAT were more likely to undergo vascular resections (33% vs. 16%, p < 0.001), have perioperative transfusions (18% vs. 12%, p < 0.001), and undergo longer procedures. Rates of CR-POPF (6%, vs. 10%, p < 0.001), DGE (11% vs. 13%, p = 0.016), postoperative percutaneous drainage (9% vs. 12%, p < 0.001), and SSI (15% vs. 18%, p < 0.001) were lower for patients selected for NAT. The association of NAT with CR-POPF remained statistically significant (adjusted odds ratio 0.52, 95% CI 0.42-0.66) after adjustment for operative technique, gland texture, and need for vascular resection for patients undergoing pancreaticoduodenectomy, but not for patients undergoing distal pancreatectomy. CONCLUSIONS: Among PDAC patients undergoing resection, selection for NAT is associated with fewer CR-POPFs, postoperative procedural interventions, and infectious complications, particularly for patients undergoing pancreaticoduodenectomy. These associations should be considered in discussions of multidisciplinary treatment sequencing for patients with PDAC.

Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

Neoadjuvant therapy for pancreas cancer: Global perspective and optimal care pathways in low to middle-income countries.

Surgery remains the only curative intent treatment modality for localized pancreatic adenocarcinoma. Even in those who can undergo successful margin negative resection, the ability to deliver adjuvant chemotherapy is suboptimal for various reasons, resulting in poor outcomes. The delivery of "standard of care" intensive modern neoadjuvant therapies can be challenging in low to-middle-income countries (LMICs) with limited resource. This article reviews the constraints in delivering neoadjuvant therapies in LMICs and strategies to improve its implementation.