Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

Gastric cancer in Africa:Current management and outcomes

Gastric cancer is the fourth most common cancer and second most common cause of cancer death worldwide. Globally, gastric cancer poses a significant public health burden - both economically and socially. In 2008, the economic burden from premature cancer deaths and disability was $895 billion and gastric cancer was the second highest cancer responsible for healthy life lost. With the expected increase in cancer deaths and non-communicable diseases, these costs are expected to rise and impact patient care. World Health Organization, estimates a 15% increase in non-communicable disease worldwide, with more than 20% increase occurring in Africa between 2010 and 2020. Mali, West Africa, is ranked 15th highest incidence of gastric cancer worldwide at a rate of 20.3/100000, yet very scarce published data evaluating etiology, prevention or management exist. It is understood that risk factors of gastric cancer are multifactorial and include infectious agents (Helicobacter pylori, Epstein-Barr virus), genetic, dietary, and environmental factors (alcohol, smoking). Interestingly, African patients with gastric cancer are younger, in their 3rd-4th decade, and present at a late stage of the disease. There is sparse data regarding gastric cancer in Africa due to lack of data collection and under-reporting, which impacts incidence and mortality rates. Currently, GLOBOCAN, an International Agency for Research on Cancer resource, is the most comprehensive available resource allowing comparison between nations. In resource limited settings, with already restricted healthcare funding, data is needed to establish programs in Africa that increase gastric cancer awareness, curtail the economic burden, and improve patient management and survival outcomes.

Pancreaticoduodenectomy and pancreaticoduodenectomy combined with superior mesentericportal vein resection for elderly cancer patients

BACKGROUND： There is an increasing frequency of pancreaticoduodenectomy（PD） and PD with superior mesenteric-portal vein（SMPV） resection in elderly cancer patients. The study aimed to investigate the safety and the survival benefits of PD and PD with SMPV resection in patients under or over 70 years of age.METHODS： We divided 296 patients who had undergone PD and PD with SMPV resection into two groups according to their ages： under or over 70 years old. The clinical data were compared between the two groups.RESULTS： Preoperative comorbidity rate was higher in elder patients than in younger patients（P=0.001）. The elder patients were more likely to have postoperative complications（P=0.003）.Specifically, complications above grade III were more likely to occur in the elderly patients（P=0.030）. Multivariable analysis showed that age（adjusted OR=2.557, P=0.015） and hypertension（adjusted OR=2.443, P=0.019） were independent predictors of postoperative complications. There was no significant difference in the mortality rates between the two groups（P=0.885）. In the PD with SMPV resection series, elderly patients were more likely to have postoperative complications（P=0.063）, but this difference was not statistically significant.There was no difference in the survival rate of patients with pancreatic ductal adenocarcinoma between the two groups.Operation type（PD vs PD with SMPV resection） did not affect the survival of patients.CONCLUSIONS： Age affects postoperative complication in patients undergoing either PD or PD with SMPV resection.However, extensive experience and advanced perioperative management lower the complication rate to an acceptablelimit. Hence it is safe and worthwhile to perform PD for elderly patients. Because of low numbers in the SMPV subset, we could not conclude whether PD with SMPV resection is feasible in elderly patients.

Incidental gallbladder cancer during laparoscopic cholecystectomy:Managing an unexpected finding

AIM:To evaluate the impact of incidental gallbladder cancer on surgical experience.METHODS:Between 1998 and 2008 all cases of cholecystectomy at two divisions of general surgery,one university based and one at a public hospital,were retrospectively reviewed.Gallbladder pathology was diagnosed by history,physical examination,and laboratory and imaging studies [ultrasonography and computed tomography(CT)].Patients with gallbladder cancer(GBC) were further analyzed for demographic data,and type of operation,surgical morbidity and mortality,histopathological classification,and survival.Incidental GBC was compared with suspected or preoperatively diagnosed GBC.The primary endpoint was diseasefree survival(DFS).The secondary endpoint was the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention.RESULTS:Nineteen patients(11 women and eight men) were found to have GBC.The male to female ratio was 1:1.4 and the mean age was 68 years(range:45-82 years).Preoperative diagnosis was made in 10 cases,and eight were diagnosed postoperatively.One was suspected intraoperatively and confirmed by frozen sections.The ratio between incidental and nonincidental cases was 9/19.The tumor node metastasis stage was:pTis(1),pT1a(2),pT1b(4),pT2(6),pT3(4),pT4(2);five cases with stageⅠa(T1 a-b);two with stageⅠb(T2 N0);one with stage Ⅱa(T3 N0);six with stage Ⅱb(T1-T3 N1);two with stage Ⅲ(T4 Nx Nx);and one with stage Ⅳ(Tx Nx Mx).Eighty-eight percent of the incidental cases were discovered at an early stage(≤Ⅱ).Preoperative diagnosis of the 19 patients with GBC was:GBC with liver invasion diagnosed by preoperative CT(nine cases),gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum(one case),porcelain gallbladder(one case),gallbladder adenoma(one case),and chronic cholelithiasis(eight cases).Every case,except one,with a T1b or more advanced invasion underwent Ⅳb + Ⅴ wedge liver resection and pericholedochic/hepatoduodenal lymphadenectomy.One patient with stage T1b GBC refused further surgery.Cases with Tis and T1a involvement were treated with cholecystectomy alone.One incidental case was diagnosed by intraoperative frozen section and treated with cholecystectomy alone.Six of the nine patients with incidental diagnosis reached 5-year DFS.One patient reached 38 mo survival despite a port-site recurrence 2 years after original surgery.Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5-year DFS.CONCLUSION:Laparoscopic cholecystectomy does not affect survival if implemented properly.Reoperation should have two objectives:R0 resection and clearance of the lymph nodes.