Evaluation of Laparoscopic Surgery in The Treatment of Gastric Gastrointestinal Stromal Tumors: A Systematic Review

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Review Article

Evaluation of Laparoscopic Surgery in The Treatment of Gastric Gastrointestinal Stromal Tumors: A Systematic Review

Corresponding author: Dr. Li-Bo Sun, Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospi- tal, Jilin University, No. 126, Xiantai Street, Changchun 130033, China. Tel: +86-13-514401922; Fax: +86-431-84641026; E-mail: sunlibo0431@sina.com

Abstract

Laparoscopic resection has been widely used in the management of gastric gastrointestinal stromal tumors (GISTs). Howev- er, larger gastric GISTs and tumors accompanied by adjacent organ invasion and/or recurrence make laparoscopic surgery difficult, or even impossible. The aim of this review was to evaluate the advantages and limitation of laparoscopy in the treatment of gastric GISTS. The current status of laparoscopy in the treatment of gastric GISTs was reviewed by collecting the last ten years reports that could be retrieved from PubMed, and those related to larger gastric GISTS were given much more attention. Most reports demonstrated that gastric GISTs < 5 cm in diameter could be successfully resected by laparoscopy with shorter time to recovery. For tumors > 5 cm, the potential benefits of laparoscopy remain unclear due to the fact that laparoscopy was generally less frequently performed on patients in this tumor group. Open resection is the common procedure of choice for larger gastric GIST, and for patients with local invasion, metastasis, and/or recurrence. It is concluded that laparoscopic surgery can provide better recovery for most lesser gastric GISTS, but larger tumor need more experienced surgeons to perform, and open approach is still an useful method in complicated conditions.

Keywords: Gastric gastrointestinal stromal tumor; Laparoscopy; Minimally invasive surgery; Open resection

Introduction

Gastrointestinal stromal tumors (GISTs) of the stomach are the most common mesenchymal tumors of the gastrointestinal tract and represent nearly 70% of all GISTs [1,2]. Surgical resection is considered to be the standard for effective management of gastric GISTs without distant metastasis [3-5]. Because most gastric GISTs are considered to be small (<5 cm) and extended lymphadenectomy is not necessary, laparoscopic resection has been widely consid-

ered as a safe and feasible procedure with reduced blood loss, smaller incision, fewer complications, quick recovery, and similar survival compared to open approach. [7-8]. However, for larger gastric GISTs, and tumors accompanied by adjacent organ involvement and recurrence, laparoscopy becomes difficult, and even impossible [9-11]. Here, recent clinical reports are reviewed in an effort to summarize the advantages and limitations of laparoscopic surgery in the treatment of gastric GISTs.

Advantages of laparoscopic surgery

Less bleeding

Objective criteria in the determination of the utility of laparoscopy for the treatment of gastric GISTs are degree of blood loss and size of incision, whereas other criteria, such as recovery of bowel function and length of hospital stay, are more subjective. One of the main advantages of lap- aroscopy in the management of gastric tumors, therefore, is the smaller size of surgical incision, which effectively leads to less bleeding and shorter recovery times. As most gastric GISTs are < 5 cm in size, a smaller incision can generally be made during removal of the tumor from the abdominal cavity [7-9,16]. Decreased blood loss has also been associ- ated with the use of the harmonic scalpel in gastrectomy performed with laparoscopy for gastric cancer. Careful dis- section of soft tissue with the harmonic scalpel significantly decreases the chance of bleeding that usually occurs during sharp dissection in open surgery [12,13]. Our previous study on open resections in gastric cancer and gastric GISTs similarly demonstrated that less blood loss occurred when the harmonic scalpel was used in combination with lapa- roscopy [14,15].

Enhanced vision of surgical field

Another significant advantage of laparoscopy is a larger and less obstructed view of the surgical field. The enhanced field of vision enables surgeons to avoid/manage small vessels, and therefore, lessens the chance of minor bleeding which is often generally ignored during open pro- cedures. The application of three-dimension (3D) high-defi- nition laparoscopy to the management of gastric GISTs has not yet been reported. However, high-definition laparosco- py in the resection of gastric cancer has been shown to pro- vide simulated 3D vision and enhanced depth perception, which facilitates more precise movements and decreases time in surgery [17]. Compared to 2D, simulated 3D vision improves the speed and accuracy of laparoscopic phantom tasks in laparoscopically naïve subjects [18]. High-defini- tion 3D vision also enables surgeons to be proficient at the technique more rapidly [19]. Outside of the minimally inva- sive nature of laparoscopy, superior vision may therefore be the main feature driving surgeons to select this approach for the removal of gastric GISTs.

Minimally invasive exploration

Intraoperative exploration is a primary reason to implement laparoscopy in the management of gastric GIST patients. When combined with endoscopy, endoscopic ul- trasound, and CT, laparoscopy is a minimally invasive pro- cedure [20,21] that can define tumor size, location, and re- lationship to adjacent tissue and organs. Such patient data are the basis for the selection of laparoscopic procedures, such as wedge resection or partial gastrectomy [22,23]. If the tumor is very small (< 2 cm), intraoperative endoscopy assistance is necessary or trans gastric resection is possible [24,25]. The possibility remains, however, that the switch to an open procedure, in the case of complicated tumor inva- sion, insufficient laparoscopic skill, or intraoperative com- plications, such as excessive bleeding, will be necessary. Finally, in the case of gastric GISTs with metastasis, laparos- copy can be used to obtain biopsies for pathologic diagnosis and molecular analysis in order to guide strategies for the potential use of targeted chemotherapeutic agents, such as imagine [21].

Quick recovery

Although randomized controlled trials have not been performed to directly compare outcomes from open and laparoscopic surgical approaches, and all current rec- ommendations are based on observational studies, most reports have concluded that laparoscopic resection of gas- tric GISTs results in less operative pain, earlier oral intake, similar postoperative morbidity, and a shorter hospital stay [7-9,12]. Smaller incisions and reduced bleeding are likely to be the basis for reduced pain and quick recovery follow- ing laparoscopic surgery in gastric GIST patients. In fact, it has been reported that the length of the laparotomy inci- sion is associated with 63% of the development of a more critical surgical complication and adhesion formation to the abdominal wall, and that postoperative adhesion was the main cause of small bowel obstruction [25,27]. Therefore, the size of incision is tightly correlated to the extent of post- operative bowel adhesion, and in turn, influences the recov- ery of bowel function. In addition, minimal bleeding during laparoscopy may reduce the release of a serosanguineous exudate that forms a fibrinous bridge between two organs, and the subsequent collagen deposition that contributes to the formation of a permanent adhesion [28].

Operation duration and complications

The duration of laparoscopy is generally longer or similar to open surgery for beginners [15,16], but may be shorter for experienced hands even though the tumours are larger than 5cm [29-33]. However, if the experienced oper-

ator preferred to choose hand sewing under laparoscopy, it might need longer times [34,35]. Another factor influencing the operation duration is the location of tumour, that cardia position generally need longer surgeries especially when hand dewing method is used [35,36]. The type of tumour re- section and gastrointestinal reconstruction can also decide the operation times. It can be imagined that gastrointesti- nal reconstruction after partial or total gastric resection requires more time compared to simple gastric wedge re- section, which is the same in both laparoscopic and open surgery [36,37].

As to complications, anastomotic leaks from staple line, end luminal bleeding, gastric retention, and wound infection, were less reported in the laparoscopic approach, which was similar with open surgery, and could be managed by conservative methods [31-36]. However, in one study, that laparoscopic surgery had a significantly lower complication was reported [37]. In this study, the overall complication oc- currence in the laparoscopic group was 5.9%, and 22.7% in the open surgery group. Of the complications, seven cases of pyrexia of unknown origin were only found in the open surgery group, and no pyrexia was found in the laparoscop- ic group, which showed some advantages of postoperative outcomes from laparoscopic surgery for gastric GISTs.

Oncological results

In the term of oncological results, most reports showed similar risk grade, recurrence, and overall surviv- al between laparoscopic and open surgery, no matter the tumor size is larger or smaller [1,2,22,29,30]. Tumor larger than 5 cm by laparoscopic approach could also get similar oncological results with open resection, even though larger tumor showed poorer behaviour. In addition, robot-assist- ed oncologic resection of gastric GISTS, including larger tumors, has been reported since 2009, with similar postop- erative tumor outcomes and survival, except the operation times seemed to be longer than general laparoscopic sur- gery, and patients number were relatively limited [38,39].

Limitations of laparoscopic surgery

Larger tumors

Most of the reports on laparoscopy for gastric GISTs limited the tumors to < or close to 5 cm. The guidelines from the NCCN and the Japanese Study Group on GIST recom- mend laparoscopy for gastric GIST tumors ≤ 5 cm [40,41]. However, laparoscopy performed on larger tumors has re-

cently been reported with similar duration of surgery, mor- bidity, and outcome, but shorter hospital stays, compared to open resections [32–34]. A smaller incision, however, is not feasible for the removal a gastric GIST > 10 cm. Larger gastric GISTs tend to result in high-risk surgeries where the chance of rupture increases, and patients have a poor prog- nosis. Furthermore, the frequency of switching to an open resection was increased if the size of the tumor was > 8 cm [34,42]. Larger tumors are usually associated with a rich blood supply, so that the field of vision can be easily blurred in laparoscopy, even though the amount of bleeding might be limited. Recent reports focusing on resection of larger tumors with laparoscopy are listed in Table 1. In most of the studies, however, the number of tumors > 5 cm was limit- ed [35,37,39,43]. Therefore, short time to recovery reflects the cases where tumors were < 5 cm rather than > 5 cm. In two reports focusing on gastric GISTs > 5 cm, tumor size in the laparoscopic group was still significantly smaller than in the open resection group, and more experienced laparo- scopic surgeons were required [33,34]. Tumor size > 7 cm usually is indicative of poor visualization and the possibil- ity of conversion to an open resection [34,44]. Therefore, whether resection by laparoscopy is a practical approach when tumor size is > 5 cm requires further evaluation, even if it is feasible by experienced hands. To avoid unnecessary conversion, the skill of the surgeon and tumor size and loca- tion should be fully evaluated before selecting laparoscopy.

Invasion of adjacent organs

It is not common for adjacent organs to be infiltrat- ed by gastric GISTs, but local organ invasion often occurs with larger gastric GISTs [45]. Gastric GISTs most frequently infiltrate the left lobe of the liver, spleen, and/or pancreas, and a combined organ resection is often necessary, even if the prognosis for these patients is poor [46]. Because of the difficulties of resection of adjacent organs with laparosco- py, most surgeons preferred open resection, when disease had spread. Local metastasis was also one of the primary reasons to switch the surgical approach from laparoscopy to open resection [34]. Distal pancreas is the most common site in cases with adjacent organ invasion by gastric GISTs, and splenectomy was performed simultaneously, with lon- ger duration of surgery, high postoperative morbidity, and a poor five-year survival [45,46]. Evaluation by CT scan pro- vides the most valuable information regarding adjacent or- gan invasion. If metastasis to liver, distal pancreas, or spleen is suspected, the surgeon should prepare for the possibility of an open procedure.

Recurrence

Larger tumor size, higher mitotic count, and symp- tomatic gastric GISTs are the main risk factors for recur- rence [47,48]. Until now, laparoscopy has not been re- ported for the treatment of recurrent gastric GISTs. Open resection accompanied by imagine targeted therapy was the main strategy reported for the treatment of recurrent gastric GISTs [49]. Preoperative imagine was recommended for unrespectable, recurrent gastric GISTs, and surgery was advocated for respectable recurrent cases following imag- ine treatment [50]. The role of debunking surgery in the treatment of recurrent gastric GISTs is debated, and further investigation is necessary [51].

In conclusion, gastrointestinal stromal tumors of the stom- ach < 5 cm in size could be successfully resected with lap- aroscopy with minimal invasion and quick recovery, but laparoscopy for larger gastric GISTs requires further evalu- ation. Open resection is suitable for patients with metasta- sis, recurrence, and local invasion.

Acknowledgments

The study was supported by the Science and Technology Agency of Jilin Province (Grant No. 20160101067JC).

Conflict of Interest

The authors declare that they have no conflict of interest.

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