Advances,breakthroughs,and challenges in gastric cancer surgery

Hayun Kim ,Sungsoo Park

1Department of Medicine,Korea University College of Medicine,Seoul 02841,South Korea;2 Division of Foregut Surgery,Korea University College of Medicine;Center for Obesity and Metabolic Diseases,Korea University Anam Hospital;Gut &Metabolism Laboratory,Korea University College of Medicine,Seoul 02841,South Korea

Abstract Gastric cancer (GC) remains a substantial health burden worldwide,ranking fifth in incidence and third in mortality among all cancer types.Surgeons have persistently attempted to address this growing burden through surgical management of GC encompassing various aspects of surgery,including advances in surgical techniques and tools for minimally invasive surgery,novel technology for real-time image-guided surgery,and function-preserving and oncometabolic surgeries,aimed at improving patients’ quality of life.The current perspective discusses the five most critical dimensions of the recent technical improvements and conceptual changes in GC surgery.We recommend further exploration of long-term benefits of these advancements,identification of breakthrough solutions to address current challenges,and delivery of the best quality of care.

Keywords: Gastric cancer surgery;minimally invasive surgery;function preserving surgery;oncometabolic surgery;quality of life

Introduction

Gastric cancer (GC) accounts for a substantial burden worldwide,being the fifth highest in incidence,the highest in East Asia,including China,Korea,and Japan,and the third highest in mortality among all cancer types (1).Over the years,surgeons have tackled the burden of GC,including integrating technology and basic science into clinical medicine to improve surgical skills or technology,enhance patient satisfaction,and promote a better quality of life (QoL).As a result,the 5-year survival rate of GC has increased in the range of 5%-20% in the past 20 years (2),and conceptual changes in treatment have been adopted to include previously excluded patients eligible for GC treatment.

However,the clinical outcomes of these advancements have not been clarified for global use,and more information is needed to determine whether these advances have long-term benefits for aggressive incorporation into standard patient care.This article encompasses five most important advances in GC surgery and prospects for each advancement (Figure 1).

Technical improvement in minimally invasive surgery (MIS)

Since the paradigm of GC surgery has shifted from extended to MIS,there has been significant improvement in the surgeon’s skill to the point where what was done with a multiport approach is now achievable with a reduced-port method.An increasing number of cases of reduced-port surgery have been reported worldwide;however,randomized trials are yet to be conducted to validate the efficacy and long-term benefits of reduced-port surgery (3,4).Current limitations,such as a small surgical field,minimal manipulation,and restraints on mobility have been addressed by the development of novel tools.A group of surgeons recently reported the feasibility of using an articulating bipolar vessel sealer in robot-assisted singleport gastrectomy,which was expected to overcome the limitations of manipulation in a restricted surgical field (5).The articulating tool has been shown to provide good configuration in the direction of dissection,and the learning curve was rapid,leading to comparable results between the use of articulating tools and conventional laparoscopic tools.With the simultaneous development of technology and surgical techniques,reduced-or single-port surgery is expected to improve cosmetic outcomes while maintaining oncological safety.However,reduced-or single-port surgery is not likely to be incorporated into relatively complex procedures,such as function-preserving surgery.Further investigation is needed to prove the direct association between a reduced number of entry ports or wound size and postoperative QoL in cancer patients.

Improving QoL with function-preserving surgery

The incidence and survival rates of early gastric cancer(EGC) show a geographical variation between Western and Eastern countries,with the highest incidence in East Asia and a higher survival rate of up to 97.4% in Korea (6).This has led surgeons to focus on preserving postoperative stomach function and optimizing patient’s QoL.Functionpreserving surgery,including pylorus-preserving gastrectomy (PPG) and proximal gastrectomy (PG),with novel reconstruction methods following gastrectomy,has been actively incorporated into GC surgery to minimize the extent of gastric resection and maximize stomach function preservation.

Initially introduced for peptic ulcer treatment,PPG has expanded into EGC surgery to reduce postoperative bile regurgitation or dumping syndrome and improve QoL (7).Short-term outcomes of a randomized clinical trial in Korea (KLASS-04) showed favorable functional outcomes and comparable complication rates in patients who underwent laparoscopic PPG in comparison to laparoscopic distal gastrectomy (8).However,a Japanese group recently reported in a long-term follow-up study a 15.6% incidence rate of severe reflux esophagitis after PPG(9).A consensus for evaluating the negative impact of the short-and long-term side effects (e.g.,delayed gastric emptying and gastroesophageal reflux disease) of PPG will need to be reached before this procedure can be used as a standard approach for GC surgery.

To tackle reflux after PPG,PG was introduced during EGC surgery.A meta-analysis and retrospective study has shown that laparoscopic proximal gastrectomy (LPG) with double tract reconstruction (DTR) has lower rates of reflux symptoms than laparoscopic total gastrectomy (10,11),while another retrospective study comparing LPG with DTR and LPG with double flap reconstruction (DFR)showed similar surgical outcomes,including operation time,blood loss,and number of dissected lymph nodes,as well as complications and nutritional outcomes 1 year after surgery (12).However,alterations in normal physiology raise concerns about the oncological safety and nutritional risks of this procedure;for example,a retrospective study in Japan recently reported a 5.7% and 11.4% of cumulative 5-and 10-year incidence rates,respectively,in patients with GC who underwent PG with DFR (13).Long-term outcomes after PG are needed to evaluate whether the postoperative benefits of QoL outweigh the oncologic safety.

Real-time image-guided surgery

With the development of imaging technology,surgeons can now navigate surgery with enhanced visualization of anatomical structures,in addition to anatomical knowledge.Indocyanine green fluorescence imaging (ICG-FI) is widely used in various surgical procedures and has broadened its applications in GC surgery.A study comparing patients with or without ICG-FI for LG reported less blood loss,a shorter operation time,and shorter hospital stay in the ICG-FI group.Measurements by ICG-FI enable noninvasive evaluation of gastric stump perfusion,prediction of anastomosis leakage,and detection of lymph nodes,which are expected to improve resection margin accuracy for oncologic gastrectomy (14).

Hyperspectral imaging (HSI) is a newly developed noninvasive,non-contrast imaging technique that allows the visualization of wavelength differences between cancerous and non-cancerous tissues that cannot be detected by the human eye.Preliminary results have reported the feasibility of HIS as a helpful surgical tool for assessing tissue perfusion of the gastric sleeve during esophageal resection surgery (15),and several retrospective studies have been designed to validate the feasibility of a modified HSI camera for MIS (16).However,this method is still in the experimental stage,and further studies on the feasibility of GC surgery and substantial cost reduction are needed for clinical application.

Conceptual change in chemotherapy opens doors for treatment in advanced GC patients

Current guidelines recommend palliative chemotherapy for patients with stage IV unresectable GC or distant metastases.An increasing number of studies have reported extended survival in patients who underwent intensive chemotherapy and subsequent curative R0 resection.This“conversion gastrectomy” allows patients ineligible for surgical management to benefit from surgery,which lead to prolonged survival.A retrospective CONVO-GC-1 study in China,Korea,and Japan reported a median survival time of 36.7 months in 1,206 patients who underwent surgery after chemotherapy with curative intent (17).Several retrospective studies in Japan have reported favorable overall survival in patients who underwent conversion surgery for advanced GC with peritoneal metastasis (PM),with a low complication rate and extended survival compared with patients who only received chemotherapy(18,19).However,chemotherapy regimens differ between countries and institutions,and the pathophysiology of stage IV GC includes various modes of metastasis.Despite efforts to create a standardized criterion,challenges remain in identifying resectable tumors and designing a randomized clinical trial in a heterogeneous patient population.

Peritoneal recurrence is one of the most common causes of treatment failure in patients with GC.Hyperthermic intraperitoneal chemotherapy (HIPEC) was introduced to treat and prevent gastric PM.Although HIPEC with cytoreductive surgery tends to show prolonged survival and reduced PM,recommendations for HIPEC are limited to patients with resectable tumors and reports on mortality and morbidity are heterogeneous (20).Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was proposed as an alternative to HIPEC,and several studies reported an overall survival ranging from an average of 15.4 to 19.1 months (21,22).To enhance pharmacological properties by improving drug delivery and reducing the overall procedure time,electrostatic precipitation PIPAC(ePIPAC) for patients with PM has been investigated in a retrospective study that reported the feasibility and safety of the technique (23).

Oncometabolic surgery — multi-disease treatment in a single operation

Obesity is a well-known risk factor for GC (24),and type 2 diabetes mellitus (T2DM) is a risk factor for cancer and non-cancer mortality.Thus,glycemic control is necessary to ensure patient survival and QoL after GC surgery.Based on the idea of treating GC and achieving T2DM in a single procedure,the term “oncometabolic surgery” was first coined by a group of surgeons in South Korea (25) and has since been incorporated into clinical practice.Jejunal bypass was performed after curative gastrectomy,followed by standard lymphadenectomy to mimic the metabolic effects of gastric bypass surgery.The postoperative results showed effective glycemic control comparable to conventional metabolic surgery for morbid obesity.Due to adaptation from a malabsorptive procedure,postoperative management requires a multidisciplinary approach with lifelong surveillance for nutritional deficiencies,including iron deficiency anemia,vitamin B12 deficiency,and hypoalbuminemia.

Various modifications have been made to oncometabolic surgery,such as a long-limb Roux-en-Y reconstruction,to enhance the T2DM remission rates and prevent relapse.Pilot data showed that the postoperative T2DM remission rates were higher than the nationwide average T2DM remission rate in Korean patients who underwent conventional gastrectomy.Based on the finding that the biliopancreatic limb length of the Roux-en-Y gastric bypass plays a key role in improving glycemic control (26),current ongoing randomized controlled trials are focusing on whether the elongation of the biliopancreatic limb (e.g.,Korean STARDOM trial) or alimentary limb (e.g.,Korean KLASS-09 trial) for long-limb Roux-en-Y reconstruction after gastrectomy is more efficient in postoperative glycemic control in patients with GC.These studies are expected to obtain meaningful data on long-term results.The Diabetes Prediction scoring system (DP score) was developed using nationwide Korean data and validated using machine learning methods to predict the probability of T2DM remission after gastrectomy for cancer to refine the patient selection criteria for GC surgery (27).More clinical assessment tools are needed to establish indications for oncometabolic surgery.

Conclusions

We have reached a point where the surgical management of GC encompasses all aspects of surgery,including advances in surgical techniques,novel technology,and improving patient QoL.More investigation and long-term outcomes of large-scale randomized control trials will be needed to find a breakthrough for the current challenges and provide the best quality of care.

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.