Surgical decisions and quality of life after gastrectomy for gastric cancer: update from Asian studies

Gastric cancer (GC) remains the fifth most frequent cancer and fourth in cancer-related deaths^[1]. Surgery still represents the mainstay of curative treatment for GC. With improvements in long-term survival, the importance of quality of life (QOL) as an outcome measure has been refocused as a consideration of academic interest. Some GC patients who have received gastrectomy suffer from distinct, subjective symptoms (such as nausea, reflux, early satiety, and diarrhea). These symptoms are called postgastrectomy syndromes (PGS) which impair the QOL of patients. Various surgical factors, such as the extent of resection, degree of lymph node dissection, and reconstruction methods are involved in the severity of QOL. Thus, a key goal of surgical decision-making is to better achieve good symptomatic control and better QOL. Many kinds of modified gastrectomy (such as gastrectomy preserving the bursa, pylorus, vagal nerve, and omentum) and anastomotic procedures (such as jejunal interposition and jejunal pouch interposition), have been performed from the perspective of patient's QOL^[2].

The prevalence of GC differs among regions worldwide, with more than 50% of cases occurring in Eastern Asia, especially in Japan, South Korea, and China^[3]. Japan and Korea have emerged as leaders in the global efforts to prevent, diagnose, and treat GC, setting an example for Chinese doctors to learn from. Much attention has been paid to the ability of surgery to cure GC in these countries. There are some differences in GC between these countries. More than 80% of patients are diagnosed at an advanced stage in China^[4]. With national programs for GC screening, the rate of diagnosis and treatment of early GC in Japan and Korea is relatively high^[5,6]. Japan, Korea, China, and other Asian countries have been paying attention to the QOL after GC surgery for a long time^[7−9]. Many instruments evaluating the QOL of GC patients have been developed and more attention to surgical factors has been given to this by these countries^[10,11].

In the last three decades, interest has significantly increased in the creation and validation of QOL questionnaires specific to GC surgery, particularly in Asian nations. Nonetheless, the understanding of the interpretation and practical application of QOL measurements related to GC surgery remains limited^[12]. Incorporation of these results into surgical decisions is frequently underused. In this article, the most common GC QOL metrics are summarized and previous Asian studies further reviewed to provide an update on the different surgical decisions made related to postgastrectomy QOL.

To identify the current status of QOL of GC surgery in Asia, a systematic search was carried out on PUBMED for publications from the past 30 years. Search terms included the MESH terms 'stomach neoplasms', 'surgery', and 'quality of life', and the following free text searches: gastric cancer, stomach cancer, gastric neoplasm, gastric malignancy, stomach malignancy, life quality, and health related quality of life, were made in several combinations. Only English language articles stating the QOL of GC surgery from Asian countries were included in the analysis. The frequency of use of QOL survey metrics was determined by the number of articles obtained through the query. These metrics were categorized into three groups: low-frequency, moderate-frequency, and high-frequency. The low-frequency category included metrics that were mentioned in less than five articles. The moderate-frequency category included metrics mentioned in 5−10 articles. Finally, the high-frequency category included metrics mentioned in more than 10 articles.

Many instruments have been developed that purport to measure QOL. Assessment of postoperative QOL for GC generally includes several conceptual domains of QOL: systemic symptoms, gastrointestinal symptoms, social and mental health, and overall functioning. This is important in determining the broad health-related implications of GC and postoperative QOL^[13]. Detailed descriptions of QOL assessment instruments for GC surgery are summarized in Table 1.

Gastrointestinal Symptom Rating Scale (GSRS)

The GSRS scale, which was created and validated in Sweden in 1988, is a rating scale used to assess various gastrointestinal symptoms. The GSRS is a specific tool for diseases, comprising of 15 items categorized into five symptom clusters that illustrate reflux, abdominal pain, indigestion, diarrhea, and constipation. The scale of GSRS adopts a Likert-type format with seven points, where 1 indicates the absence of bothersome symptoms and 7 represents highly troublesome symptoms. Studies have provided evidence demonstrating the reliability and validity of the GSRS, while reference values for the general population can be found^[14,26].

Quality of Life Questionnaire(QLQ)-C30 and QLQ-STO22

The European Organization for Research and Treatment of Cancer (EORTC) developed the QLQ-C30 in 1993, a self-administered structured questionnaire comprising 30 items that primarily focused on physical symptoms. It is suitable for self-administration and can be used across various cultural settings. The domains addressed in the questionnaire encompass physical, role, cognitive, emotional, and social functions. Furthermore, it also incorporates symptom domains including fatigue, pain, as well as nausea and vomiting. The questionnaire also assesses global health and QOL and consists of six single items addressing dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties^[15].

In 2001, alongside the QLQ-C30, a gastric-cancer specific instrument called QLQ-STO22 was developed^[16]. QLQ-STO22 explores five domains: dysphasia, pain/discomfort, dietary restrictions, upper gastrointestinal symptoms, and specific emotional problems. However, there are a few considerations to be made. Firstly, since 2001, treatment strategies have significantly evolved, with precision medicine and minimally invasive surgery becoming more prominent. Secondly, the development of the STO22 did not involve specialists and patients from East Asia. Hence, the original version might not adequately address the QOL concerns specific to East Asian patients. As a result, it might not accurately assess the Health-Related Quality of Life of patients currently undergoing treatment. To address this, the EORTC QOL group has collaborated with the EORTC Gastrointestinal Tract Cancer Group and the Japan Clinical Oncology Group (JCOG) to update STO22^[27].

Functional Assessment of Cancer Therapy-General (FACT-G)and FACT-Gastric (FACT-GA)

The measurement instrument FACT-G was created to assess the QOL in cancer patients who are undergoing therapy. It consists of 27 items which are rated on a scale ranging from 0 to 4. The subscales of the instrument encompass physical well-being, social/family well-being, emotional well-being, functional well-being, and overall QOL^[18].

A modified version of FACT-G, known as FACT-GA, was introduced in 2004 specifically for evaluating QOL in patients with GC. The FACT-GA module comprises 19 items focused on GC, which complement the existing 28-item FACT-G core questionnaire. When combined, these two questionnaires result in a total of 47 items. Additionally, the 19-item subscale within FACT-GA (referred to as GCS) explores symptoms related to GC and adverse effects associated with its treatment^[19,20]. To gather information on QOL-related aspects from the past week, FACT-GA items are presented as statements for patients to recall (similar to QLQ-STO22). While QLQ-30 and QLQ-STO22 prioritize functional aspects, FACT-GA places more emphasis on social and emotional issues^[19].

Gastrointestinal Quality of Life Index (GIQLI) scale

First published in 1995, the GIQLI questionnaire underwent development and validation in Germany as a measure of QOL specifically designed for individuals with various gastrointestinal (GI) disorders. Comprising a total of 36 items, this questionnaire delves into diverse aspects such as GI and non-GI symptoms, physical functionality, psychological state, and social well-being. It is important to note that this survey does not differentiate between specific GI ailments and exhibits limited specificity when used with cancer patients. Over time, despite its widespread applicability, the GIQLI tool has gradually been supplanted by more cancer-specific indicators among GC patients^[28].

Dysfunction After Upper Gastrointestinal Surgery for Cancer (DAUGS32)

DAUGS32 is a questionnaire developed in 2005 by Japanese scholars. It consists of 32 items and is specifically designed to identify post-operative gastrointestinal dysfunction issues. Unlike other questionnaires like STO-22 and FACT-GA, DAUGS32 solely focuses on gastrointestinal symptoms such as reflux, gastric dumping, digestive difficulties, nausea and vomiting, and lower gastrointestinal symptoms. It does not include a more general cancer QOL questionnaire^[22−24]. The questionnaire has been validated to measure the QOL in patients who have undergone upper gastrointestinal surgery for cancer.

Postgastrectomy Syndrome Assessment Scale (PGSAS-45)

The Japan Postgastrectomy Syndrome Working Party (JPSWP) was established to closely examine the symptoms and lifestyle changes experienced by patients who have undergone gastrectomy. One of the main outcomes of the JPSWP's research is the development of a new questionnaire called the Postgastrectomy Syndrome Assessment Scale (PGSAS)-45. The extensive questionnaire consists of 45 questions, featuring eight questions derived from the 8-Item Short-Form Health Survey (SF-8), 15 questions from the GSRS, and 22 clinically significant questions chosen by the JPSWP. These 22 selected items cover various aspects of postgastrectomy symptoms, dumping syndrome, dietary intake, social activity, and satisfaction with daily life.

The PGSAS-45 questionnaire is particularly useful in evaluating the impact of different types of gastrectomy or reconstructive procedures on the QOL of post-operative patients. It is expected that this questionnaire will be increasingly used in the future. Currently, there have been several studies conducted in Japan using this scale to assess the QOL of patients with early GC^[29−42]. These studies have shown that the main differences in QOL are related to issues such as diet-related distress, esophageal reflux, body mass changes, dietary dissatisfaction, work dissatisfaction, and dissatisfaction with daily life. However, it should be noted that there is a lack of research specifically focusing on the use of the PGSAS-45 questionnaire for evaluating gastrectomized patients with advanced stages of the disease^[42]. Additionally, the questionnaire has only been validated in Asian patients. Therefore, further studies are needed to fully explore its effectiveness and applicability in different patient populations and stages of gastrectomy.

Korean Quality of Life in Stomach Cancer Patients Study Group (KOQUSS-40)

The KOrean QUality of life in Stomach cancer patients Study group (KOQUSS) was formed in January 2016 with the goal of developing a method to assess the QOL of GC patients who have undergone gastrectomy. In 2020, a questionnaire called KOQUSS-40 was released, which was based on methods used for EORTC QLQ-C30 and QLQ-STO22^[11]. The KOQUSS-40 comprises 40 questions categorized into 11 distinct domains. These questions particularly address symptoms experienced after gastrectomy, such as difficulty digesting food, trouble swallowing, acid reflux, dumping syndrome, alterations in bowel habits, constipation, psychological concerns, and anxieties related to cancer. It is important to note that the validity and applicability of the questionnaire have only been assessed in Korean patients with stage I GC who have successfully recovered from surgery. Patients who have undergone chemoradiotherapy and have different symptoms are not included in the questionnaire.

Patient Reported Outcomes Measurement Information System (PROMIS)

The National Institutes of Health (NIH) developed the PROMIS program in 2004. This program consists of a standardized collection of patient-reported outcomes (PROs), which encompass physical, mental, and social aspects of health. With its extensive catalog of over 300 items, most of which employ five-option response scales, ranging from 1 (not at all) to 5 (very much)^[25], PROMIS has gained significant recognition as a valuable tool for assessing the well-being of patients diagnosed with GI cancers^[43]. By utilizing PROMIS, healthcare professionals can gauge the extent of health impairment caused by the underlying disease before surgical intervention, monitor the degree of post-operative recovery, and determine the duration required for full recuperation^[44,45].

Adequate surgical resection with adequate lymphadenectomy is the only potentially curative method in GC treatments. Pre-operative evaluation identifying clinical stage, location, size, and histological type affects the strategy regarding the extent of resection. Meanwhile, the postoperative QOL should be under consideration before surgeons determine the surgical decision. Reducing resection extent can theoretically mitigate PGS by preserving gastric function and physiology and may translate to better QOL in appropriate GC patients. Table 2 shows recent studies that assessed the relationship between the extent of gastrectomy and QOL in Asia.

TG vs PG in proximal gastric cancer

The incidence of proximal gastric cancer (PGC), especially proximal early GC has been increasing worldwide^[53]. Total gastrectomy (TG) has been used as a standard operation in advanced GC for cancers of the upper one-third of the stomach. However, for early proximal GC, proximal gastrectomy (PG), as a functional preservation surgery, was at one point a popular form of resection to obtain better postoperative QOL^[54−56]. Esophagogastrostomy anastomosis was recommended for large residual stomach volume, while jejunal pouch anastomosis was recommended for small residual stomach volume, which can improve postoperative QOL of PG patients^[32,57]. Most studies concerning PG and QOL were from Japan. A Japanese nationwide multi-institutional study found that PG had fewer symptoms of diarrhea and vomiting, less weight loss, and no additional meals were required, which could reduce the incidence of postoperative PGS^[33]. However, reflux esophagitis and anastomotic stenosis are still reported in PG^[49,58].

PPG vs DG in middle-third gastric cancer

Pylorus-preserving gastrectomy (PPG) was initially devised for resection of gastric ulcers and recently applied to middle-third early GC patients to maintain pyloric function and improve QOL. Several studies from Japan and China showed that PPG can provide better QOL than DG, with less incidence of diarrhea and vomiting, less body weight loss, and no need for supplementary feeding^[36,37,52]. In a retrospective trial, it was recommended to retain sufficient proximal residual stomach to allow patients to achieve higher postoperative QOL when PPG was performed^[35].

Open vs minimally invasive surgery

During the period of minimally invasive surgical techniques, both laparoscopic-assisted gastrectomy and totally laparoscopic gastrectomy have been emphasized due to their anticipated minimal invasiveness and comparable oncological results when contrasted with traditional open gastrectomy. The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) group, Japan Clinical Oncology Group, and the Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) group performed separately or jointly launched several randomized trials assessing QOL of minimally invasive gastrectomy, such as JCOG0912, KLASS-01, CLASS-08 (NCT04351321), and CKLASS-01. However, to date most QOL outcomes have not been reported.

In various postgastrectomy symptoms, such as fatigue, pain, dietary restrictions, dysphagia, reflux, and body image, laparoscopic-assisted distal gastrectomy (LADG) usually demonstrates superior performance compared to open distal gastrectomy in nonrandomized studies^[59−62]. Multiple retrospective studies indicated that the laparoscopic approach, when performed independently, outperformed the approach that involved laparoscopic assistance in terms of QOL. A Korean prospective randomized study could not find significant differences in QOL scores at 2 weeks and 3 months after surgery between laparoscopic distal gastrectomy (TLDG) and LADG, incorporating QLQ-C30 STO22^[63]. However, a recent study from China showed that LADG generally out-performs TLDG in body image^[64]. To explore the total laparoscopic approach in patient's QOL, KLASS designed a multicentre prospective study (KLASS07 trial)^[65]. In a propensity-score matched analysis from Korea, total laparoscopic total gastrectomy resulted in improved quality of life regarding dysphagia, pain, eating, and odynophagia compared to laparoscopic-assisted total gastrectomy (LATG) for patients^[66]. Compared with the LATG group, elderly patients aged ≥ 70 years had lower nausea and vomiting scores and higher satisfaction with their body image^[64]. Table 3 shows recent studies that assessed laparoscopic gastrectomy compared with open surgery.

To prevent PGS, various procedures for total gastrectomy have been introduced. These procedures bear minimal dissimilarities. Based on their fundamental features, they can be categorized as reconstruction methods with or without pouch construction, and reconstruction methods with or without preservation of the duodenal passage^[71]. The Japanese Gastric Cancer Association's 6^th edition of the guideline recommends several effective techniques for restoring the digestive system, including Roux-en-Y esophagojejunostomy, jejunal interposition, and the newly introduced double-tract method. However, it should be noted that the functional advantages of pouch reconstruction are yet to be determined^[72]. Creating a gastric substitute pouch that can simulate the reservoir function could reduce the rate of dumping symptoms. Recent meta-analysis revealed pouch-based methods markedly reduced the risk of dumping syndrome, esophagitis, heartburn, and food intake disturbance and nutritional outcomes^[73−75]. Recently a Japanese multi-institutional cross-sectional study investigated the usefulness of jejunal pouch creation using PGSAS-45. Three pouch-creation procedures: total gastrectomy with jejunal pouch interposition (TGJPR), total gastrectomy with Roux-en-Y oral pouch (TGJPI), and total gastrectomy with Roux-en-Y aboral pouch (TGJPY) were analyzed. Patients with TGJPR and TGJPI reported a significantly higher QOL compared to those in the TGJPY group. Additionally, utilizing an oral pouch during TG may enhance postoperative QOL and alleviate the symptoms associated with PGS^[76].

Reconstruction for distal gastrectomy

Radical distal gastrectomy is the main therapeutic approach for tumors located in the distal part of the stomach. After this surgical procedure, four principal reconstruction choices can be considered: Billroth-I (BI), Billroth-II (BII), Roux-en-Y (RY), and uncut Roux-en-Y (URY). These alternatives provide different approaches to reconstructing the gastrointestinal tract. BI, which is frequently used, is simple and can provide a physiological route for food digestion and absorption. In advanced-stage patients, the volume of residual stomach is sometimes small, and BI reconstruction may lead to tension during anastomosis, BII and RY are more commonly adopted. BII is a less complex procedure compared to RY gastrojejunostomy, although it is frequently linked to bile reflux and the development of gastritis caused by reflux. RY is used for the prevention of alkaline reflux gastritis, esophagitis, and dumping syndrome through a complex anastomosis. The URY is a modified technique based on the BII operation with Braun anastomosis to reduce gastric residue and decrease reflux.

Several retrospective studies have compared BI against RY reconstruction, and each method has its advantages. It was reported that BI had less body weight reduction, and RY had a lower incidence of residual gastritis and esophageal reflux symptoms^[29,77−82]. An optimal technique for digestive tract reconstruction has not yet been established. When BI was performed, the Kocher maneuver may increase meal-related discomfort and diminish the quality of ingestion and impart a negative effect on QOL^[30]. When RY was performed, the size of the residual stomach, and the length and route of the Roux limb significantly affects the QOL^[31]. RCT trials revealed that RY and BII are comparable in terms of postoperative QOL and nutritional status^[68,83]. It was indicated that URY has the potential to decrease occurrences of gastric stasis, gastritis, and bile reflux, while also enhancing the postoperative quality of life for patients based on a study involving 200 Chinese patients^[84]. A multicenter phase III study with a larger population from China is ongoing comparing QOL as a secondary outcome between BII and URY^[85].

Over the past 30 years, there has been growing interest in developing and the validation of QOL questionnaires suitable for GC surgery, especially in Asian countries. Reducing resection extent can mitigate PGS by preserving gastric function and physiology and may translate to better QOL in appropriate GC patients. Patients may benefit from minimally invasive surgery and have better QOL, however prospective randomized controlled studies are still needed.