Minimally Invasive Surgery for Gastric Cancer: The Future Standard of Care

Laparoscopy-assisted distal gastrectomy for gastric cancer was first reported by Kitano et al. in 1991. Laparoscopic wedge resection (LWR) and intragastric mucosal resection (IGMR) were quickly adapted for gastric cancer limited to the mucosal layer and having no risk of lymph node metastasis. Following improvements in endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), the use of LWR and IGMR for these indications decreased, and patients with gastric cancer, including those with a risk of lymph node metastases, were more likely to be managed with laparoscopic gastrectomy (LG) with lymph node dissection. Many retrospective comparative trials and randomized-controlled trials (RCT) have confirmed that LG is safe and feasible, and that short-term outcomes are better than those of open gastrectomy (OG) in patients with early gastric cancer (EGC). However, these trials did not include a satisfactory number of patients to establish clinical evidence. Thus, additional multicenter randomized-controlled trials are needed to delineate significantly quantifiable differences between LG and OG. As laparoscopic experience has accumulated, the indications for LG have been broadened to include older and overweight patients and those with advanced gastric cancer. Moreover, advanced techniques, such as laparoscopy-assisted total gastrectomy, laparoscopy-assisted proximal gastrectomy, laparoscopy-assisted pylorus-preserving gastrectomy (PPG), and extended lymph node dissection (D2) have been widely performed.     

Laparoscopic surgery for gastric cancer: indications and limitations]

Gastric cancer has been successfully treated by both endoscopic and open surgery, while early-stage gastric cancer with some risk of lymph node metastasis is managed with laparoscopic surgery. The principle of treatment of gastric cancer is to perform a complete resection of the lesion with safe and appropriate procedures based on disease stage. Three types of laparoscopic surgery have been reported: laparoscopy-assisted distal gastrectomy (LADG); laparoscopic local resection with the use of aT-fastener; and intragastric mucosal resection. In local resection, there is a possibility that past of the lesion or lymph node metastases may remain. D2 lymph node dissection requires a longer operative time and technical difficulties causing postoperative complications may be encountered. At present, LADG is the preferred choice of treatment in patients with early-stage gastric cancers due to the acceptable length of surgery and simple lymph node harvesting. For the wider application of minimally invasive surgery, numerous advances in operative procedures, including hand-assisted surgery and sentinel node navigation surgery, are required, along with technical developments for more accurate diagnosis to offer ideal treatment for each stage of gastric cancer.     

内镜黏膜下剥离术联合腹腔镜前哨淋巴结活检术治疗早期胃癌26例分析

目的 探讨内镜黏膜下剥离术（ESD）联合腹腔镜前哨淋巴结活检术治疗早期胃癌的可行性和临床疗效。方法 回顾性分析2009年3月至2013年8月期间在江南大学附属医院行ESD联合腹腔镜前哨淋巴结活检术治疗的26例早期胃癌患者的临床资料。对这些患者先行腹腔镜前哨淋巴结活检术,如冰冻病理学检查结果提示有淋巴结转移,则行腹腔镜下胃癌D2根治术;如提示无淋巴结转移,则行ESD。结果 本组26例患者共检出SLN 95枚,（3.7±1.4）枚/例,（1～6枚/例）;有2例患者因SLN阳性而行腹腔镜辅助远端胃癌根治术,24例患者行ESD。26例患者术后随访时间5～46个月,中位随访时间22个月。ESD术后无病生存率（DFS）为91.7% （22/24）,局部复发率为4.2% （1/24）;总体DFS为96.2% （25/26）。结论 ESD治疗早期胃癌是安全、可行的,联合腹腔镜胃癌前哨淋巴结活检术更符合肿瘤根治原则。     

Sentinel node mapping during laparoscopic distal gastrectomy for gastric cancer

Background The goal of this study was to evaluate the feasibility and accuracy of sentinel node (SN) mapping with endoscopic submucosal blue dye injection during laparoscopic distal gastrectomy for gastric cancer. Methods Thirty-four patients affected by gastric adenocarcinoma without gross clinical serosal invasion and distant metastasis were prospectively enrolled. At the start of the surgery, 2 ml of 2% patent blue was endoscopically injected into the submucosal layer at four points around the site of the primary tumor. Sentinel nodes were defined as nodes that were stained by the blue dye within 5–10 min after the dye injection. After identification and removal of sentinel lymph nodes, each patient underwent laparoscopic distal gastrectomy with D1 (n = 2) or D2 (n = 32) lymphadenectomy. Results Of the 34 patients, 14 had positive nodules (41%). SNs were detectable as blue nodes in 27 (80%) of 34 patients. The mean number of dissected lymph nodes per patient was 31 ± 10 (range = 16–64) and the mean number of blue nodes was 1.5 (range = 1–4). Only five (sensitivity 36%) of 14 N(+) patients had at least one metastatic lymph node among the SNs identified. In these 14 patients the sentinel node was traced in 12 cases. Sentinel node status diagnosed the lymph node status with 74% accuracy. In early gastric cancer (n = 18), three patients had lymph node metastasis. These early gastric cancer patients with nodal metastases had at least one metastatic lymph node among the SNs identified (sensitivity 100%). Conclusions Blue dye SN mapping during laparoscopic distal gastrectomy seems to be a feasible and accurate diagnostic tool for detecting lymph node metastasis in patients with early-stage gastric cancer in which the accuracy of the method was 100%. However, in more advanced gastric cancer the results are not satisfactory. Validation of this method requires further studies on technical issues, including selection of the tracers.     

Sentinel node concept and its application for cancer surgery

The sentinel node is the first lymph node that drains a primary tumor. A negative sentinel lymph node accurately predicts the absence of metastasis to any other regional lymph nodes. A higher rate of feasibility, sensitivity, specificity, and diagnostic accuracy in sentinel lymph node mapping has been demonstrated of cancer of the breast, penis, and vulva and in malignant melanoma. Intraoperative endoscopic lymphatic mapping, which we developed for gastric cancer in 1994, was also useful in accurately predicting nodal status in 163 early-stage gastric cancer patients: the rate of sensitivity, specificity, and accuracy was 91%, 100%, and 98%, respectively. Therefore if the sentinel lymph node biopsy is free of metastasis, limited surgery such as wedge resection, segmental resection, pylorus-preserving gastrectomy, or proximal gastrectomy is indicated. The tumor-free sentinel lymph node allows dissection of regional lymph nodes to be avoided and results in an improved quality of life in postoperative patients. In addition, sentinel lymph node biopsy has the advantages of enhancing staging accuracy, detecting micrometastases, and identifying variations in the regional lymphatic basin. Further progress may change the mode of nodal dissection and the indications for adjuvant chemotherapy for cancer.     

Surgical treatment of early gastric cancer

Around half the cases of gastric cancer are found in the early stage in Japan. With an expected good prognosis, many treatment options have been developed to maintain a good quality of life of the patients after the treatment. Gastric cancer is diagnosed with endoscopy, and the depth of invasion is diagnosed with endoscopy and endoscopic ultrasound. One of the new treatments is endoscopic submucosal dissection. Improvements in surgical treatment are minimizing lymph node dissection, reconstruction methods, laparoscopy-assisted surgery, and sentinel node navigation surgery. Minimizing lymph node dissection for early gastric cancer is well described in the Guidelines for Gastric Cancer Treatments. Pylorus-preserving gastrectomy, jejunal interposition, pouch reconstruction, and Roux-en-Y reconstruction after distal gastrectomy are improvements in reconstruction after gastrectomy. More and more surgeons start laparoscopy-assisted gastrectomy with lymph node dissection. Even with these improvements, the 5-year survival of early gastric cancer is more than 90% in Japan. Further improvements would be possible in the future.     

Current status of laparoscopic gastrectomy for cancer in Japan

Because of the increased incidence of early gastric cancer in Japan, minimally invasive laparoscopic approaches to gastric malignancies have been under development since 1991. Laparoscopic local resection of the stomach, i.e., laparoscopic wedge resection (LWR) and intragastric mucosal resection (IGMR), is used to treat mucosal cancer without lymph node metastasis. Laparoscopy-assisted distal gastrectomy (LADG) is used to treat early gastric cancer with risk factors for regional lymph node metastasis. A survey conducted by the Japan Society for Endoscopic Surgery showed that 1428 LWRs, 260 IGMRs, and 2600 LADGs were performed between 1991 and 2001 in departments of endoscopic surgery in Japan. Laparoscopic gastrectomy for gastric cancer is still under development in Japan. According to short-term results reported by a small group of surgeons, laparoscopic approaches to gastric cancer provide for minimal invasion, early recovery, and decreased morbidity and mortality. If the advantages can be confirmed in one or more multicenter randomized control studies of the long-term outcome of patients undergoing laparoscopic gastrectomy for gastric cancer, the procedure should come into wide acceptance and use.     

双镜联合治疗早期胃癌的临床体会

目的:探讨胃镜、腹腔镜双镜联合治疗早期胃癌的安全性与可行性。方法:回顾分析近6年双镜联合治疗78例早期胃癌患者的临床资料。胃体、远端胃肿瘤非溃疡患者行内镜黏膜下剥离术,近端胃及胃体、远端胃肿瘤合并溃疡患者行双镜联合下腹腔镜胃楔形切除术。标本送快速病理检查。结果:为早期胃癌浸润至黏膜下层及肌层、伴有脉管癌栓、肿瘤直径>20 mm、低分化腺癌(包括印戒细胞癌)的30例患者行腹腔镜胃癌D2根治术,5例近贲门或幽门部位肿瘤患者行单纯胃大部切除术,43例患者仅行内镜黏膜下剥离术或单纯胃楔形切除术。根治患者术后淋巴结转移占全部病例的11.5%,术后均无并发症发生,患者痊愈出院。结论:双镜联合治疗早期胃癌安全、患者创伤小、康复快、疗效确切,更加体现了微创优势,避免了部分患者不必要的根治切除甚至全胃切除的痛苦,值得临床推广。     

Indication for and outcome of laparoscopy-assisted Billroth I gastrectomy

BACKGROUND: Since 1991, laparoscopy-assisted Billroth I gastrectomy has been used for patients with early gastric cancer. The aim of this study was to clarify the outcome of 40 patients who underwent this operation and to examine the indications based on a retrospective histological study of 248 resected cases of early gastric cancer. METHODS: Operating time, blood loss, length of skin incision, and postoperative hospital stay and complications were examined using the operation records and medical charts. The presence or absence of lymph node metastasis, tumour size, site, gross type, histological type, depth of invasion, presence or absence of ulceration, and status of lymph node metastasis were investigated in 248 early gastric cancers. RESULTS: The mean operating time was 3 h and 48 min and the mean length of skin incision was 5.8 cm. Although one patient who had suffered from chronic bronchitis developed pneumonia and wound dehiscence, no other patients had a postoperative complication. The mean hospital stay after operation was 16 days and all patients were alive without recurrence at a median follow-up of 21 months. The incidence of lymph node metastasis in early gastric cancer was 2 per cent (three of 130) in mucosal cancers and 14 per cent (17 of 118) in submucosal cancers. These lesions could have been completely resected by laparoscopy-assisted gastrectomy. CONCLUSION: All 40 patients were treated successfully by laparoscopy-assisted Billroth I gastrectomy without significant complications and with no recurrences to date. Pathological study of conventionally resected stomach and lymph nodes confirmed that laparoscopy-assisted Billroth I gastrectomy would be a safe and useful operation for most early gastric cancers.     

腹腔镜辅助胃癌根治术(附48例报告)

目的:探讨腹腔镜辅助胃癌根治术的安全性与手术疗效。方法:回顾分析48例腹腔镜胃癌根治切除术的临床资料,评价其手术时间、术中出血量、术后住院时间、并发症发生率、中转开腹率及淋巴结清扫数量。结果:3例中转开腹,45例成功完成腹腔镜手术。远端胃切除、全胃切除、近端胃切除手术时间平均(170.5±15.2)min、(220.3±20.1)min、(180.8±53.7)min。术中出血量:(125.6±19.5)ml、(320.2±31.7)ml、(178.4±24.8)ml。淋巴结清扫数量:(23.8±8.2)、(25.7±4.6)、(22.5±9.1)。术后住院时间:(7.5±2.1)d、(8.9±6.4)d、(7.2±3.7)d。术后随访3~24个月,7例复发转移(包括中转开腹2例),术后发生并发症6例。结论:腹腔镜辅助胃癌根治术是治疗进展期胃癌安全、可行且近期疗效良好的手术方法。随着腹腔镜器械的改进,术者手术经验的积累、操作技术的熟练及对胃癌生物学特性的进一步认识,合理地将腹腔镜同其他内窥镜技术联合起来,腹腔镜胃癌根治术会得到更好地开展与推广,适应证将不断扩展。     

Modern treatment of early gastric cancer: review of the Japanese experience

BACKGROUND: Recently, detections of early gastric cancer (EGC) have been increasing, and the treatment strategies for gastric cancer have been changing. To demonstrate recent clinical experience of EGC in Japan and to assess modern strategies for the treatment of EGC, we investigated the English-language literature of the past 10 years through computer searches. METHODS: This article intends to provide gastric surgeons with recent Japanese experience of the treatment for EGC. In a search for modern treatments of EGC, we selected 100 papers published in well-known medical journals, and focused on the following items of EGC: (1) prognostic factors, (2) endoscopic treatment, (3) surgical procedures, and (4) Japanese guidelines. RESULTS: The most important factor influencing the survival of patients with EGC is the status of lymph node metastasis. The incidence of lymph node metastasis is 1-3% for mucosal cancers and 11-20% for submucosal cancers. Endoscopic mucosal resection (EMR) is a technique for the treatment of EGC, and the recent indication includes the tumors confined to the mucosa up to 3 cm in size or those invading the superficial submucosa. Surgical procedures include conventional Billroth I gastrectomy, limited resections, and laparoscopic surgery. Laparoscopic wedge resection using the lesion-lifting method and laparoscopy-assisted distal gastrectomy provide less pain, faster recovery and shorter hospital stay. Guidelines for the treatment of gastric cancer proposed by the Japanese Gastric Cancer Association show that patients with mucosal cancer can be managed by EMR or distal gastrectomy, whereas patients with submucosal cancer are candidates for distal gastrectomy with lymph node dissection. CONCLUSION: Although the prognosis of patients with EGC depends on the presence or absence of lymph node metastasis, most are successfully treated by modern endoscopic or surgical techniques. Laparoscopic surgery and limited resections will contribute to the better quality of life of patients with EGC.     

New Sentinel Node Mapping Technologies for Early Gastric Cancer

The sentinel node (SN) concept has revolutionized the surgical staging of both melanoma and breast cancer over the past two decades. The application of this concept can yield benefits for patients by preventing various complications related to unnecessary prophylactic regional lymph node dissection in patients with cancer-negative SNs. Clinical application of SN mapping in patients with early gastric cancer has been a controversial issue for years. However, a recent meta-analysis and a prospective multicenter trial of SN mapping for early gastric cancer have shown acceptable SN detection rates and accuracy of determination of lymph node status. For early stage gastric cancer such as cT1N0M0, for which a better prognosis can be achieved through conventional surgical approaches, the establishment of individualized, minimally invasive treatments that may retain the patients’ quality of life should be the next surgical challenge. Although there are many unresolved technical issues, laparoscopic SN biopsy with laparoscopic minimized gastrectomy or endoscopic mucosal resection/endoscopic submucosal dissection has the potential to achieve this goal.     

Less invasive surgery for early gastric cancer based on the low probability of lymph node metastasis

BACKGROUND: Less invasive treatment is the current trend in many surgical fields. Most patients with early gastric cancer do not have lymph node metastasis. Thus extensive resection of the stomach and extended lymph node dissection do not appear to be necessary. METHODS: In a retrospective study, 890 consecutive patients with early gastric cancer who had undergone standard gastrectomy were assessed for depth of invasion, gross appearance, and maximum diameter of the tumor to examine the possibility of limiting the extent of lymph node dissection. A variety of limited gastrectomies have been developed and now include endoscopic mucosal resection, wedge resection, segmental gastrectomy, limited proximal gastrectomy, and distal hemigastrectomy. RESULTS: A retrospective study revealed that extensive lymph node dissection did not improve the survival of patients with early gastric cancer. Endoscopic mucosal resection was suitable for cancers of the depressed type of less than 1 cm in diameter and the elevated type of less than 2 cm in diameter. Wedge, segmental, or limited proximal gastrectomy was suitable for the elevated type of 2 to 3 cm in diameter. The elevated type of more than 3 cm in diameter and the depressed type of 1 to 3 cm in diameter sometimes involved metastasis to group 1 nodes. The depressed type of more than 3 cm in diameter sometimes involved metastasis to group 2 nodes. Thus such cases should be treated by gastrectomy with dissection of potentially metastatic lymph nodes. CONCLUSIONS: Limitation of the extent of gastrectomy and lymph node dissection may be possible, depending on the gross appearance and size of the tumor.     

Technique and assessment of sentinel lymph node biopsy usefulness in laparoscopy-assisted distal gastrectomy

Background Recently, some studies have suggested that sentinel node biopsy also can be applied to gastric cancer. The authors apply sentinel lymph node biopsy in laparoscopy assisted distal gastrectomy to perform it as safe limited surgery. Limited surgery is a procedure in which the extent of lesion resection and lymph node dissection is reduced. The authors demonstrate that intraoperative diagnosis of lymph node metastasis is useful in this respect. Methods The study was conducted with 38 patients (29 men and 9 women) who had a preoperative diagnosis of T1 tumor invasion. The patients had a mean age of 66.2 years. Patent blue (1%) was injected submucosally into four or five different sites around the primary tumor at 1 ml per site. Blue-stained lymphatics and lymph nodes could be seen by turning over the greater omentum and the lesser omentum extraperitoneally. If blue nodes were found, biopsy was performed. Results The mean number of blue nodes dissected was 2.5 ± 1.9. Intraoperative identification and biopsy of blue nodes could be performed for 35 (92.1%) of the 38 patients. Of the 35 patients in whom blue nodes were identified, 4 (9.7%) had metastases in blue nodes confirmed by intraoperative frozen-section diagnosis. Intraoperative frozen-section diagnosis was negative for blue node metastasis in 31 patients. Postoperative permanent section diagnosis also showed no evidence of lymph node metastasis in these 31 patients (100% accuracy, 0% false-negative rates). Conclusions The reported method allows observation of blue-stained lymphatics up to 2 h after patent blue injection. Sentinel node biopsy was performed in laparoscopy assisted distal gastrectomy, making it technically equivalent to open gastrectomy. Sentinel node biopsy can serve as a method to determine the appropriate use of laparoscopy assisted distal gastrectomy for management of T1 gastric cancer.     

Laparoscopic surgery for gastroduodenal disease

Since 1990, laparoscopic surgery for gastrointestinal disease has been accepted worldwide because it is minimally invasive, associated with less pain, and results in early recovery. For the surgical management of gastroesophageal reflux and perforated peptic ulcer, laparoscopic procedures are recognized as the standard. Laparoscopic gastrectomies for cancer have developed since 1991. Laparoscopic wedge resection and intragastric mucosal resection are performed for the treatment of early gastric cancer without the risk of lymph node metastasis. For early gastric cancer with the risk of perigastric lymph node metastasis, laparoscopy-assisted Billroth-I gastrectomy with D1 lymph node dissection has been successfully performed. Thus, laparoscopic approaches play an important role in the management of gastroduodenal disease.     

Function-Preserving Gastrectomy for Early Gastric Cancer

The number of early gastric cancer (EGC) cases has been increasing because of improved diagnostic procedures. Applications of function-preserving gastric cancer surgery may therefore also be increasing because of its low incidence of lymph node metastasis, excellent survival rates, and the possibility of less-invasive procedures such as laparoscopic gastrectomy being used in combination. Pylorus-preserving gastrectomy (PPG) with radical lymph node dissection is one such function-preserving procedure that has been applied for EGC, with the indications, limitations, and survival benefits of PPG already reported in several retrospective studies. Laparoscopy-assisted proximal gastrectomy has also been applied for EGC of the upper third of the stomach, although this procedure can be associated with the 2 major problems of reflux esophagitis and carcinoma arising in the gastric stump. In the patient with EGC in the upper third of the stomach, laparoscopy-assisted subtotal gastrectomy with a preserved very small stomach may provide a better quality of life for the patients and fewer postoperative complications. Finally, the laparoscopy endoscopy cooperative surgery procedure combines endoscopic submucosal dissection with laparoscopic gastric wall resection, which prevents excessive resection and deformation of the stomach after surgery and was recently applied for EGC cases without possibility of lymph node metastasis. Function-preserving laparoscopic gastrectomy is recommended for the treatment of EGC if the indication followed by accurate diagnosis is strictly confirmed. Preservation of remnant stomach sometimes causes severe postoperative dysfunctions such as delayed gastric retention in PPG, esophageal reflux in PG, and gastric stump carcinoma in the remnant stomach. Moreover, these techniques present technical difficulties to the surgeon. Although many retrospective studies showed the functional benefit or oncological safety of function-preserving gastrectomy, further prospective studies using large case series are necessary.     

Laparoscopic Local Resection Based on Sentinel Node Evaluation for Early Gastric Cancer: A Preliminary Report

We previously reported that lymphatic mapping using isosulfan blue can be used to identify sentinel nodes (SNs). This study was undertaken to evaluate the feasibility of using the SN technique in treating early gastric cancer and to explore its usefulness for minimal invasive surgery. Twenty-three patients with early gastric cancer who underwent SN biopsy were retrospectively evaluated. Based on SN evaluation, individualized surgery was performed in five patients with T1N0M0 gastric cancer. When pathological examination of frozen sections revealed metastasis in SNs, we performed a standard D2 gastrectomy. Laparoscopic local resection was applied when the SN biopsy was negative. Our results showed that the success rate with SN biopsy in early gastric cancer was 100%, as were the accuracy, sensitivity, and specificity. All five patients with early gastric cancer had SNs negative for metastases both by frozen section and by postoperative pathology. Thus, all these patients underwent laparoscopic local resection without extended lymphadenectomy. We conclude that SN biopsy is a useful tool to individualize the operative procedure, and laparoscopic local resection can be safely performed using SN guidance in selected patients with early gastric cancer.     

早期胃癌前哨淋巴结临床研究进展

内镜切除和腹腔镜手术是早期胃癌治疗的主要手段,结合前哨淋巴结（SLN）示踪技术被认为是能在保证肿瘤根治前提下达到保留胃功能、改善病人生活质量的手段。但由于胃癌淋巴结转移途径的特殊性,早期胃癌SLN导航手术（SNNS）一直存在争议。随着SLN引流区概念的提出,早期胃癌SNNS的根治性得到更好的保证。尤其是SENORITA研究结果的发表,早期胃癌SNNS的安全性和有效性得到进一步证实。SLN引流区清扫联合腹腔镜或内镜手术将成为有效的早期胃癌治疗手段。     

Surface gastric cancer. Lymphatic metastases

We present 10 cases of early gastric carcinoma with lymph node invasion in a series of 40 cases early gastric cancer operated between 1974 and 1984 in our unit. Two tumours were mucosal and 8 were submucosal. One tumour was polypoid, 5 were superficiel and 4 were ulcerated. The mean number of invaded lymph nodes was 2.7. We performed a total gastrectomy in two patients and a distal gastrectomy in the other eight patients. Two patients died 26 and 27 months after the operation. The others are alive and tumour free. We believe that early gastric cancer must be treated aggressively by means of total or partial gastrectomy with resection of the N1 and N2 lymph node chains, when ever possible.     

胃镜病理活检诊断高级别上皮内瘤变的临床探讨

目的 评价胃高级别上皮内瘤变（HIN）这一概念在临床应用中的价值和不足.方法 回顾性分析经胃镜活检病理诊断为HIN的45例患者的临床和病理资料,并与术后病理诊断结果进行对比研究.结果 本组患者33例接受远端胃大部切除术,3例行近端胃大部分切除术,7例行全胃切除术,2例行内镜黏膜切除术.术后病理结果显示,15例（33.3%）维持HIN的诊断：14例（31.1%）为早期胃癌,16例（35.6%）为进展期胃癌,其中40.0%（12/30）伴有局部淋巴结转移.术前胃镜活检显示直径大于或等于3 cm、伴有溃疡或具有低分化癌特点的HIN病灶.术后多提示为癌（P〈0.05）.对于胃癌患者,具有上述特征者多为进展期胃癌,易发生淋巴结转移（P〈0.05）.结论 术前采用胃镜病理活检对HIN作出诊断应慎重;当HIN病灶直径大于或等于3 cm、伴有溃疡或具有低分化癌特点时,建议选择积极的根治性手术治疗.