Correa-Cote J, Morales-Uribe C, Sanabria A. Laparoscopic management of gastric gastrointestinal stromal tumors. World J Gastrointest Endosc 2014; 6(7): 296-303
Corresponding Author of This Article
Alvaro Sanabria, MD, MSc, PhD, FACS, Department of Surgery, School of Medicine, Universidad de Antioquia-Hospital Pablo Tobon Uribe-San Vicente de Paul. Medellin, Carrera 51d Nº 62-29, Medellin 050010, Colombia. firstname.lastname@example.org
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Endosc. Jul 16, 2014; 6(7): 296-303 Published online Jul 16, 2014. doi: 10.4253/wjge.v6.i7.296
Laparoscopic management of gastric gastrointestinal stromal tumors
Juan Correa-Cote, Carlos Morales-Uribe, Alvaro Sanabria
Juan Correa-Cote, Carlos Morales-Uribe, Alvaro Sanabria, Department of Surgery, School of Medicine, Universidad de Antioquia-Hospital Pablo Tobon Uribe-San Vicente de Paul. Medellin, Medellin 050010, Colombia
ORCID number: $[AuthorORCIDs]
Author contributions: Correa-Cote J, Morales-Uribe C and Sanabria A contributed equally to this work; Correa-Cote J and Morales-Uribe C designed the research; Correa-Cote J, Morales-Uribe C and Sanabria A performed the research, analyzed the data; and wrote the paper.
Correspondence to: Alvaro Sanabria, MD, MSc, PhD, FACS, Department of Surgery, School of Medicine, Universidad de Antioquia-Hospital Pablo Tobon Uribe-San Vicente de Paul. Medellin, Carrera 51d Nº 62-29, Medellin 050010, Colombia. email@example.com
Received: November 4, 2013 Revised: April 7, 2014 Accepted: May 28, 2014 Published online: July 16, 2014
Gastrointestinal stromal tumors (GISTs) are the most frequent gastrointestinal tumors of mesodermal origin. Gastric GISTs represent approximately 70% of all gastrointestinal GISTs. The only curative option is surgical resection. Many surgical groups have shown good results with the laparoscopic approach. There have not been any randomized controlled trials comparing the open vs laparoscopic approach, and all recommendations have been based on observational studies. The experience obtained from gastric laparoscopic surgery during recent decades and the development of specific devices have allowed the treatment of most gastric GISTs through the laparoscopic approach.
Core tip: Gastrointestinal stromal tumors (GISTs) are the most frequent gastrointestinal tumors of mesodermal origin. Gastric GISTs represent approximately 70% of all gastrointestinal GISTs. The only curative option is surgical resection. Many surgical groups have shown good results with the laparoscopic approach. There have not been any randomized controlled trials comparing the open vs laparoscopic approach, and all recommendations have been based on observational studies. The experience obtained from gastric laparoscopic surgery during recent decades and the development of specific devices have allowed the treatment of most gastric GISTs through the laparoscopic approach.
Citation: Correa-Cote J, Morales-Uribe C, Sanabria A. Laparoscopic management of gastric gastrointestinal stromal tumors. World J Gastrointest Endosc 2014; 6(7): 296-303
Gastrointestinal stromal tumors (GISTs) are the most frequent gastrointestinal tumors of mesodermal origin, and gastric GISTs represent approximately 70% of all gastrointestinal GISTs. These tumors are derived from the interstitial cells of Cajal, and have been shown to harbor gain of function mutations in the cell-surface KIT receptor in approximately 90% or in the platelet-derived growth factor receptor α (PDGFRA) in 8%.
Most tumors are limited to the primary organ, and less than 2% of tumors present lymph node metastasis. GISTs can also metastasize to the peritoneum and infrequently present hematogenous metastasis to other intra-abdominal viscera, lung, pleura, bone and brain.
Most patients are asymptomatic; the tumors are usually found as an incidental finding in 4%-39% of cases[6-11]. In most surgical series, the most frequent symptoms are gastrointestinal bleeding (14%-68%), abdominal pain (16.1%-45%), abdominal mass (3.3%-21%), early satiety (36%), anemia (19.4%-77%), weight loss (11%), bowel obstruction (3.6%), liver metastasis (3.6%), dyspeptic symptoms (9.7%) and dysphagia (9%)[6-10]. There is a clear relationship between tumor size and symptoms, smaller tumores are generally asymptomatic.
The diagnosis is usually made by endoscopy or abdominal imaging. During endoscopy, it is possible to see gastric lumen narrowing associated with normal protruded mucosa, although in larger tumors, the mucosa can show ulcers due to local ischemia[12,13]. The ideal method for diagnosis is endoscopic ultrasonography (EUS), which can define the size, vascular pattern and form of the tumor and differentiate between an extra-luminal compression and a submucous growth. GISTs are hypoechoic tumors located at the fourth layer, although some reports have shown tumors located at the third layer. However, the imaging of these tumors is not sensitive (43%), which necessitates histologic evaluation. EUS also helps guide fine needle aspiration biopsies, showing better performance than biopsies under normal endoscopy. The sensitivity of FNAB guided by EUS increases by 10% if a pathologist makes an immediate examination of the adequacy of the sample. In some series, preoperative diagnosis was only possible 52.3%.
Computed tomography (CT) is necessary for preoperative stratification. CT can usually show intra- or extraluminal tumors with different morphologic patterns according to size. Larger tumors can show irregular margins and heterogeneous internal density, and if the diameter is larger than 6 cm, the tumors are usually accompanied by central necrosis. Magnetic resonance imaging (MRI) is recommended in cases of simultaneous liver metastasis because of the possibility of conducting a combined resection. PET-CT can be useful in patients with undetermined findings on CT or MRI. However, there is not a good correlation between imaging findings and malignancy.
A differential diagnosis with other submucous tumors such as leiomyoma, leiomyosarcoma, schwannoma, granular cell tumors, heterotopic pancreatic tissue, lipoma, neurofibroma, Kaposi tumors and non-functional adrenal tumors should be performed[16,17]. Immunohistochemistry for GIST detection is very useful and shows positivity for CD117 (95% of GISTs). Only 2% are usually related to PDGFRA mutations[16,18]. Other helpful tests are CD34 that is positive in 70% of the cases and vimentin.
The only curative option is surgical resection, which can be offered to patients with good functional status and non-metastatic resectable tumors, although in some cases, a metastasis resection surgery can be performed in association with resection of the primary tumor. Surgical principles for resection include total extracapsular resection, avoiding tumor fracture or bleeding, which are associated with recurrence and peritoneal sarcomatosis. There are no recommended margins, because microscopic margins status doesn´t correlate with survival as does the mitotic count and tumor size. Wedge resection is a good option for tumors located in the anterior wall or greater curve. For tumors located at the antrum wedge resection can produce a stenosis, so formal gastric resections are favored. Wider margins have not shown any oncologic advantage, and lymph node dissection has not been indicated. The National Comprehensive Cancer Network (NCCN) guidelines suggest that tumors smaller than 1 cm that do not fulfill high risk endosonographic criteria (irregular borders, cystic spaces, ulcer of echogenic heterogeneous focus) can be observed during endoscopic follow-up at each 6-12-mo interval. Most larger tumors need adjuvant treatment with imatinib mesylate to avoid recurrence.
Open surgical resection was the standard of treatment until two decades ago. Many surgical groups have shown good results with the laparoscopic approach. Although NCCN guidelines suggest that laparoscopic resection is indicated in tumors less than 2 cm, many surgeons have reported a safe excision of tumors > 5 cm and other up to 10 cm[24-26]. Lukaszczry and Pretez in 1992 were the first to report a successful laparoscopic resection of a gastric GIST.
The laparoscopic techniques can be divided into different subtypes: transgastric resections, endoscopy-assisted laparoscopic resections, wedge resections, partial gastrectomy and hand-assisted laparoscopic resections. The surgical approach depends on tumor size and location (Figure 1). Privette et al proposed a classification system based on tumor location as a guideline to choose the best surgical approach. Trocars and operating tables are organized in a similar manner to any other hiatus procedures, with the surgeon located between the legs. A 12-15 mmHg pneumoperitoneum is established, and a 30° camera and a liver retractor are useful. Before resection, it is mandatory to review the abdominal cavity to rule out peritoneum or liver metastasis. If the surgeons suspect solid organ metastasis, the use of intraoperative ultrasound with biopsy can help in the operative decision. Assistance by endoscopy during the surgical procedure is useful for locating the tumor and guiding resection, and staining with ink could help delineate the resection margins.
Figure 1 Surgical approach according to gastrointestinal stromal tumor localization.
Tumors located at the fundus and at the anterior and posterior walls can be resected by partial gastrectomy or wedge resection. In cases of small tumors, the greater curve is mobilized, ligating the gastroepiploic vessels with an ultrasonic scalpel or a thermal device. The gastric wall is elevated with sutures placed in the seromuscular layer around the tumor to obtain a complete resection with a linear mechanical stapler, guaranteeing macroscopic margins. In cases of larger tumors, the gastric wall is directly opened and the tumor is resected, maintaining a free margin with a late direct closure using a continuous suture. In cases where tumors are located in the posterior wall, an anterior gastrotomy is made exactly above the tumor, usually assisted by endoscopy. The tumor is resected by the techniques described, with a late closure of the anterior wall with a continuous suture[11,26].
For tumors located at the antrum or at the prepyloric area, partial gastrectomy is recommended due to the high risk of stenosis and delayed stomach emptying when wedge resections are used. In these cases, the greater and lesser curves are dissected to obtain retrogastric access. The duodenum is sectioned just distal to the pylorus with a linear mechanical stapler, and the proximal section is also made with a mechanical stapler; this is usually assisted by endoscopy. Finally, a Roux-en-Y anastomosis is made.
Tumors located at the esophagogastric junction are infrequent and represent less than 5% of all tumors. Some authors have recommended enucleation of these tumors based on the high morbidity (6%-24%) and mortality (0%-1.5%) with classical resections and due to the lack of advantage in prognosis and survival. However, the best surgical approach is still debated. The enucleation is made through an anterior gastrotomy, and in these cases, a submucous infiltration with epinephrine is recommended to avoid bleeding and perforation. The use of devices such as an ultrasonic scalpel or an electrocautery has been recommended[10,28].
Some authors have varied the surgical technique using transgastric trocars and endoscopy-assisted insufflation. In these cases, smaller tumors can even be extracted by the mouth using endoscopy. For larger tumors, other authors have suggested a hand-assisted technique because it allows for better exploration and easier handling and dissection of the tumor[12,13]. Others have also shown good results with the single-port approach or dissections without insufflation. In all cases, the use of a bag is recommended for the extraction of the tumor to avoid recurrence and metastasis at the port insertion sites[30,31].
Until now, there have not been any randomized controlled trials comparing the open vs laparoscopic approach, and all recommendations have been based on observational studies. Actual recommendations are based on outcomes related to surgical technique (intact specimen, free margins) and prognosis (operative complications, recurrence, cancer free survival) reported from these observational studies. Tables 1 and 2 show the results of comparative and non-comparative published series.
Table 1 Non-comparative series of laparoscopic resection of gastric gastrointestinal stromal tumor.
GLA: Gasless laparoscopy-assisted; PG: Wedge resection or partial gastrectomy; DG: Distal gastrectomy; TransG: Transgastric gastrectomies; TotGas: Total gastrectomy; OS: Open surgery; AR: Anatomic resections; NAR: Non-anatomic resections; LOS: Length of stay; NS: Not specified; LAP/END: Laparoendoscopic resection; LAP-HA: Laparoscopic hand-assisted; RG: Remnant gastrectomy; Prox Gas: Proximal gastrectomy; SSI: Surgical site infection.
Recently, Koh et al published a systematic review of eleven observational studies comparing laparoscopic vs open resection with evaluation of short and long term outcomes. In their study, which included 381 patients in the laparoscopic group and 384 patients in the open group, the laparoscopic approach showed a lower frequency of minor complications (OR = 0.517; 95%CI: 0.277-0.965), lower length of stay [mean difference -3.421 d (-4.737 to -2.104)], shorter time to the initiation of oral diet [mean difference -1.887 d (-2.785 to -0.989)] and lower intraoperative bleeding [mean difference -86.508 mL (-141.184 to -31.831 mL)]. They could not find any statistically significant differences in reoperation rate, operative time, positive margins, local recurrence, cancer free survival and overall survival. However, comparisons showed that most high risk tumors were treated with open gastrectomy, introducing a selection bias.
The rate of conversion to open surgery is 0%-31%, and this cannot be considered a complication but rather an intraoperative decision to obtain better tumor control when the surgeon is faced with adverse intraoperative conditions.
Follow-up is mandatory in all patients, even in the absence of malignancy. Patients should be reviewed every 3-6 mo during the first 5 years. An annual endoscopy and CT are recommended to rule out local recurrence. The survival rate of patients with early tumors is greater than 90%. A size larger than 10 cm, a high mitotic rate and intraoperative rupture are risk factors for recurrence.
The experience obtained from gastric laparoscopic surgery during recent decades and the development of specific devices have allowed the treatment of most gastric GISTs through the laparoscopic approach. As with all surgical techniques, the laparoscopic approach must be applied in select patients with particular characteristics based on functional status, tumor size, location and surgeons’ experience. The case series presented in this review support laparoscopic resection as a safe and effective alternative, with similar rates of complications, but with lower pain and an early recovery. It is important to realize that tumor size by itself is not an adequate factor to contraindicate the laparoscopic approach and that other factors should be considered in the decision.
P- Reviewers: Mello ELR, Nezhat FR, Rodrigo L S- Editor: Song XX L- Editor: A E- Editor: Zhang DN
Raut CP, Morgan JA, Ashley SW. Current issues in gastrointestinal stromal tumors: incidence, molecular biology, and contemporary treatment of localized and advanced disease.Curr Opin Gastroenterol. 2007;23:149-158.
Lai IR, Lee WJ, Yu SC. Minimally invasive surgery for gastric stromal cell tumors: intermediate follow-up results.J Gastrointest Surg. 2006;10:563-566.
Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.Science. 1998;279:577-580.
Vassos N, Agaimy A, Hohenberger W, Croner RS. Extraabdominal lymph node metastasis in gastrointestinal stromal tumors (GIST).J Gastrointest Surg. 2011;15:1232-1236.
Wu Y, Zhu X, Ding Y. Diagnosis and treatment of gastrointestinal stromal tumors of the stomach: report of 28 cases.Ann Clin Lab Sci. 2007;37:15-21.
Catena F, Di Battista M, Fusaroli P, Ansaloni L, Di Scioscio V, Santini D, Pantaleo M, Biasco G, Caletti G, Pinna A. Laparoscopic treatment of gastric GIST: report of 21 cases and literature’s review.J Gastrointest Surg. 2008;12:561-568.
Wu JM, Yang CY, Wang MY, Wu MH, Lin MT. Gasless laparoscopy-assisted versus open resection for gastrointestinal stromal tumors of the upper stomach: preliminary results.J Laparoendosc Adv Surg Tech A. 2010;20:725-729.
Berindoague R, Targarona EM, Feliu X, Artigas V, Balagué C, Aldeano A, Lahoud A, Navines J, Fernandez-Sallent E, Trias M. Laparoscopic resection of clinically suspected gastric stromal tumors.Surg Innov. 2006;13:231-237.
Hwang SH, Park do J, Kim YH, Lee KH, Lee HS, Kim HH, Lee HJ, Yang HK, Lee KU. Laparoscopic surgery for submucosal tumors located at the esophagogastric junction and the prepylorus.Surg Endosc. 2009;23:1980-1987.
De Vogelaere K, Hoorens A, Haentjens P, Delvaux G. Laparoscopic versus open resection of gastrointestinal stromal tumors of the stomach.Surg Endosc. 2013;27:1546-1554.
Ponsaing LG, Kiss K, Loft A, Jensen LI, Hansen MB. Diagnostic procedures for submucosal tumors in the gastrointestinal tract.World J Gastroenterol. 2007;13:3301-3310.
Sakamoto H, Kitano M, Kudo M. Diagnosis of subepithelial tumors in the upper gastrointestinal tract by endoscopic ultrasonography.World J Radiol. 2010;2:289-297.
Kalkmann J, Zeile M, Antoch G, Berger F, Diederich S, Dinter D, Fink C, Janka R, Stattaus J. Consensus report on the radiological management of patients with gastrointestinal stromal tumours (GIST): recommendations of the German GIST Imaging Working Group.Cancer Imaging. 2012;12:126-135.
Chourmouzi D, Sinakos E, Papalavrentios L, Akriviadis E, Drevelegas A. Gastrointestinal stromal tumors: a pictorial review.J Gastrointestin Liver Dis. 2009;18:379-383.
Ponsaing LG, Kiss K, Hansen MB. Classification of submucosal tumors in the gastrointestinal tract.World J Gastroenterol. 2007;13:3311-3315.
Chung SD, Chueh JS, Yu HJ. Laparoscopic resection of gastric gastrointestinal stromal tumors presenting as left adrenal tumors.World J Gastroenterol. 2012;18:96-98.
Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up.Am J Surg Pathol. 2005;29:52-68.
DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival.Ann Surg. 2000;231:51-58.
Roggin KK, Posner MC. Modern treatment of gastric gastrointestinal stromal tumors.World J Gastroenterol. 2012;18:6720-6728.
Silberhumer GR, Hufschmid M, Wrba F, Gyoeri G, Schoppmann S, Tribl B, Wenzl E, Prager G, Laengle F, Zacherl J. Surgery for gastrointestinal stromal tumors of the stomach.J Gastrointest Surg. 2009;13:1213-1219.
Nguyen SQ, Divino CM, Wang JL, Dikman SH. Laparoscopic management of gastrointestinal stromal tumors.Surg Endosc. 2006;20:713-716.
Demetri GD, Benjamin RS, Blanke CD, Blay JY, Casali P, Choi H, Corless CL, Debiec-Rychter M, DeMatteo RP, Ettinger DS. NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)--update of the NCCN clinical practice guidelines.J Natl Compr Canc Netw. 2007;5 Suppl 2:S1-29; quiz S30.
De Vogelaere K, Van Loo I, Peters O, Hoorens A, Haentjens P, Delvaux G. Laparoscopic resection of gastric gastrointestinal stromal tumors (GIST) is safe and effective, irrespective of tumor size.Surg Endosc. 2012;26:2339-2345.
Privette A, McCahill L, Borrazzo E, Single RM, Zubarik R. Laparoscopic approaches to resection of suspected gastric gastrointestinal stromal tumors based on tumor location.Surg Endosc. 2008;22:487-494.
Novitsky YW, Kercher KW, Sing RF, Heniford BT. Long-term outcomes of laparoscopic resection of gastric gastrointestinal stromal tumors.Ann Surg. 2006;243:738-45; discussion 745-7.
Lukaszczyk JJ, Preletz RJ. Laparoscopic resection of benign stromal tumor of the stomach.J Laparoendosc Surg. 1992;2:331-334.
Koh YX, Chok AY, Zheng HL, Tan CS, Chow PK, Wong WK, Goh BK. A systematic review and meta-analysis comparing laparoscopic versus open gastric resections for gastrointestinal stromal tumors of the stomach.Ann Surg Oncol. 2013;20:3549-3560.
Fujimoto Y, Nakanishi Y, Yoshimura K, Shimoda T. Clinicopathologic study of primary malignant gastrointestinal stromal tumor of the stomach, with special reference to prognostic factors: analysis of results in 140 surgically resected patients.Gastric Cancer. 2003;6:39-48.
Joensuu H, Vehtari A, Riihimäki J, Nishida T, Steigen SE, Brabec P, Plank L, Nilsson B, Cirilli C, Braconi C. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts.Lancet Oncol. 2012;13:265-274.
Choi SM, Kim MC, Jung GJ, Kim HH, Kwon HC, Choi SR, Jang JS, Jeong JS. Laparoscopic wedge resection for gastric GIST: long-term follow-up results.Eur J Surg Oncol. 2007;33:444-447.
Ronellenfitsch U, Staiger W, Kähler G, Ströbel P, Schwarzbach M, Hohenberger P. Perioperative and oncological outcome of laparoscopic resection of gastrointestinal stromal tumour (GIST) of the stomach.Diagn Ther Endosc. 2009;2009:286138.
Tagaya N, Mikami H, Kubota K. Laparoscopic resection of gastrointestinal mesenchymal tumors located in the upper stomach.Surg Endosc. 2004;18:1469-1474.
Karakousis GC, Singer S, Zheng J, Gonen M, Coit D, DeMatteo RP, Strong VE. Laparoscopic versus open gastric resections for primary gastrointestinal stromal tumors (GISTs): a size-matched comparison.Ann Surg Oncol. 2011;18:1599-1605.
Kim KH, Kim MC, Jung GJ, Kim SJ, Jang JS, Kwon HC. Long term survival results for gastric GIST: is laparoscopic surgery for large gastric GIST feasible?World J Surg Oncol. 2012;10:230.
Nishimura J, Nakajima K, Omori T, Takahashi T, Nishitani A, Ito T, Nishida T. Surgical strategy for gastric gastrointestinal stromal tumors: laparoscopic vs. open resection.Surg Endosc. 2007;21:875-878.
Otani Y, Furukawa T, Yoshida M, Saikawa Y, Wada N, Ueda M, Kubota T, Mukai M, Kameyama K, Sugino Y. Operative indications for relatively small (2-5 cm) gastrointestinal stromal tumor of the stomach based on analysis of 60 operated cases.Surgery. 2006;139:484-492.