Lymphadenectomy For Gastric Cancer Research Articles

The Prognosis of Patients Operated on for Gastric Cancer in Relation to the Percentage of Lymph Nodes Invaded by Tumour

Introduction : In evaluating the type of gastrectomy and lymphadenectomy for gastric cancer, adequate prognosis has been dependant on the retrieval of at least 15 lymph nodes. We propose an alternative method in which the prognostic value is evaluated, according to whether or not more than 20% of the retrieved lymph nodes are invaded by tumour.Materials & Methods : Sixty-five patients (36 men, 29 women) with a median age of 69 years (mean age 68.9 ± 12.1 years) were evaluated, who were operated upon between 1985 and 1999 for gastric cancer by gastrectomy with either D1 or D2 lymphadenectomy.Results : The average number of retrieved lymph nodes was 10.4 ± 8.6. In 51 patients (78.5%) less than 15 and in 14 patients (21.5%) 15 or more lymph nodes were retrieved, according to the TNM guidelines. In our study, there is a statistically significant difference in prognosis between patients with less than 20% and those with more than 20% of the retrieved lymph nodes invaded by tumour, irrespective of the total number of lymph nodes resected. Conclusion : Gastric cancer patients in whom less than 20% of the retrieved lymph nodes are invaded, have a significantly better prognosis compared with patients in whom 20% or more of the lymph nodes retrieved are invaded by tumour, irrespective of the total number of retrieved lymph nodes.

The beginning of a new era: East meets West more comfortably regarding lymphadenectomy for gastric cancer — Japan will finally drop the surgery-alone arm in its pursuit of a multimodal treatment strategy

The beginning of a new era: East meets West more comfortably regarding lymphadenectomy for gastric cancer — Japan will finally drop the surgery-alone arm in its pursuit of a multimodal treatment strategy

Techniques and complications of laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer

Aim Recently, LADG has become a viable alternative for the treatment of patients with early gastric cancer. Surgeons who are seeking to undertake, or currently practicing LADG, are concerned about unpredictable intraoperative events that occur during LADG. The aims of this study were to investigate intraoperative and postoperative complications in laparoscopy-assisted distal gastrectomy (LADG) with more than D1 + β lymphadenectomy for gastric cancer. Materials and methods Of 219 patients who underwent laparoscopy-assisted gastrectomy for gastric cancer by a single surgeon between April 2003 and January 2006, 128 patients were enrolled in this study. The operative procedure was divided into five steps. Various intraoperative complications, such as bleeding and perigastric organ injuries, that occurred during different operative steps were investigated by reviewing videotapes. Results A total of 839 events of bleeding were encountered during the procedure with a mean of 6.6 per patient. The mean number of bleeding during each step was significantly different and more bleedings occurred during steps II and IV ( P < 0.0001). Sixteen cases of complications other than bleeding occurred in 15 patients (11.7%), and they were all managed properly without conversion or reoperation. Postoperative morbidity and mortality rates were 15.6 and 0.7%, respectively. Conclusion LADG with more than D1 + β lymphadenectomy is a technically feasible and acceptable surgical modality for gastric cancer. Intraoperative bleeding was found to be the most common complication during LADG for gastric cancer, and more bleedings occurred during steps II and IV.

Clinical Outcome after D1 vs D2–3 Gastrectomy for Treatment of Gastric Cancer

Clinical benefit from extended lymphadenectomy for gastric cancer remains controversial as a considerable variation exists between results of different studies. 562 patients were treated at HUCH between 1987-2003, whereof 223 underwent gastrectomy with curative intent. Of these, 114 patients underwent subtotal/total gastrectomy with D1 (standard) lymphadenectomy and 109 patients had D2-3 (extended) lymph node dissection. The clinical outcome of these patients was analysed retrospectively. The incidence of surgical complications was 33.0% in D2-3 and 16.8% in D1 lymphadenectomy groups (p = 0.008). Abscess was the most common complication (11.0%) among D2-3 operated patients and haemorrhage (4.4%) in D1 group. Hospital mortality was 3.7% in D2-3 and 1.8% in D1 group (p = 0.438). The only statistically significant factor influencing the rate of complications was D2-3 lymphadenectomy (OR 2.620, 95% C.I. 1.375 to 4.991). D2-3 was associated with a longer postoperative hospital stay and operation time, greater blood loss and increased need for blood transfusions compared to D1. The 5-year survival was not statistically different between lymphadenectomy groups. It is justified to perform a D2-3 gastrectomy in Europe with a acceptable postoperative mortality but with a significant morbidity. Further studies are needed to assess the value of extended lymphadenectomy in gastric cancer.

Standard D2 versus extended D2 (D2+) lymphadenectomy for gastric cancer: an interim safety analysis of a multicenter, randomized, clinical trial

Background A multicenter, randomized, clinical trial was initiated to evaluate the possible benefits of extended D2 (D2+) lymphadenectomy after potentially curative resection of gastric cancer. Methods Standard D2 lymphadenectomy was defined according to the Japanese Gastric Cancer Association classification. D2+ lymph node dissection additionally included the removal of para-aortic nodes. Results Of 781 patients screened, 275 were randomized to standard D2 (n = 141) or extended D2+ (n = 134) lymphadenectomy. The overall morbidity rates were comparable in D2 (27.7%; 95% confidence interval [CI], 20.3–35.1) and D2+ (21.6%; 95% CI, 13.7–29.5) groups ( P = .248). Pre-existing cardiac disease, splenectomy, and excessive blood loss were identified as risk factors for overall and nonsurgical complications. Postoperative mortality rates were 4.9% (95% CI, 1.4–8.5) and 2.2% (95% CI, 0–4.7), respectively ( P = .376). Conclusions The interim safety analysis failed to show any significant difference with regard to the extent of lymph node dissection. The surgical outcome was not different between the 2 surgeries.

37 ORAL Extended (D2) and superextended (D3) lymphadenectomy for gastric cancer. Postoperative outcome and risk factors for complications

37 ORAL Extended (D2) and superextended (D3) lymphadenectomy for gastric cancer. Postoperative outcome and risk factors for complications

Complications after Extended (D2) and Superextended (D3) Lymphadenectomy for Gastric Cancer: Analysis of Potential Risk Factors

Very few studies from Western centers have compared D2 and D3 dissection in the surgical treatment of gastric cancer. The aim of the prospective observational study reported here was to analyze the postoperative outcome and potential risk factors for complications following D2 and D3 lymphadenectomy. A total of 330 consecutive patients, of which 251 submitted to D2 lymphadenectomy and 79 were treated by D3 lymphadenectomy, were enrolled in the study. Twenty potential risk factors for morbidity and mortality were studied by means of univariate and multivariate analysis. Overall morbidity and mortality rates were 34% (111 patients) and 4% (14 patients), respectively. Abdominal abscess, anastomotic leakage, pleuropulmonary diseases and pancreatitis were the most commonly observed complications. No differences in morbidity, surgical morbidity, mortality rates and mean hospital stay between D2 and D3 lymphadenectomy were found. Multivariate analysis revealed that American Society of Anesthesiologists' (ASA) class II/III versus class I, perioperative blood transfusions, and low albumin serum levels were independent predictors of postoperative complications. Age, surgical radicality (R1/R2 vs. R0) and low albumin serum levels independently predicted mortality. Mortality rate was .5% in the 203 patients aged 75 years or younger who underwent curative surgery. Most of deaths were observed in patients older than 75 years with low albumin serum levels or treated by non-curative surgery. D2 lymphadenectomy represents a feasible procedure associated to acceptable morbidity and mortality rates. In specialized centers, D3 lymphadenectomy may be performed without increasing the risk of postoperative complications and associated deaths in carefully selected patients. These techniques should be avoided in subgroups of patients with a high risk of postoperative mortality.

Lymph node counts in the upper abdomen: Anatomical basis for lymphadenectomy in gastric cancer

The number of regional lymph nodes was determined in sites relevant to lymphadenectomy in gastric cancer in 30 cadavers. Tissue was cleared by dissolving fatty tissue, thus making lymph nodes with a diameter of at least 1 mm visible. All lymph node stations indicated by the Japanese Research Society for Gastric Cancer were studied. In stations 1-11 (corresponding with R2 resection) an average of 27 nodes (range 17-44 nodes) was found, whereas stations 1-16 (corresponding with R3 resection) showed an average of 43 nodes (range 25-64 nodes). These values are higher than those usually obtained from lymphadenectomy for gastric cancer. Striking individual differences in the total number of lymph nodes and the number of single stations was observed. The number of lymph nodes in these investigations are the normal anatomical values and serve as quality control of lymph node dissection in gastric carcinoma.

Low Maruyama Index Surgery for Gastric Cancer: Blinded Reanalysis of the Dutch D1‐D2 Trial

A quantitative estimate of residual nodal disease after gastric cancer surgery, the Maruyama index of unresected disease (MI), proved to be a strong independent predictor of survival in a large U.S. adjuvant chemoradiation study in which surgical undertreatment was frequent. Data from the Dutch D1-D2 Lymphadenectomy Trial permit an opportunity to assess the prognostic value of this variable in a cohort with lower-stage disease treated with minimum D-1 lymphadenectomy and no adjuvant chemoradiation. Blinded to survival, and excluding those cases with missing information, the MI was calculated for 648 of the original 711 patients treated with curative intent. Survival was assessed by log-rank and multivariate Cox regression analysis. All patients have been followed for a minimum of 11 years. Overall Dutch trial findings were not affected by the absence of 63 cases with incomplete data. As expected, the median MI was 26, much lower than in the previous U.S. study. In contrast to the D level, MI < 5 proved to be a strong predictor of survival by both univariate and multivariate analysis. The MI was an independent predictor of both overall survival [P = 0.016; hazard ratio (HR) = 1.45; 95% confidence interval (CI) 1.07-1.95] and relapse risk (P = 0.010; HR = 1.72; 95% CI 1.14-2.60). A strong dose-response reaction with respect to the MI and survival was also observed. We conclude that in this trial low-MI surgery is associated with enhanced survival, whereas outside of certain subgroups routine D2 lymphadenectomy is not. This observation suggests that surgeons might have more of an impact on patient survival by achieving a low-MI operation than a particular D level. A compelling dose-response effect reveals that the MI is a quantitative yardstick for assessing the adequacy of lymphadenectomy in gastric cancer.

Clinical significance of sentinel lymph node detection by combining the dye-directed and radioguided methods in gastric cancer

To investigate the feasibility and accuracy of detection of sentinel lymph nodes (SLN) with combining the dye-directed and radioguided methods in gastric cancer and assess its potential role in determining the rational extent of lymphadenectomy in gastric cancer surgery. Twenty-six patients of gastric cancer diagnosed as T(1)-T(3) were enrolled in this study. Endoscopic injection submucosally of (99m)Tc labeled sulfur colloid solution was performed around the primary tumor 2 - 4 h before operation. Immediately after laparotomy, patent blue violet was injected into subserosal layer adjacent to the tumor. SLNs were defined as blue stained nodes or(and) those containing 10 times more radioactivity than surrounding tissue with a gamma probe. Standard radical gastrectomy with lymphadenectomy (D(2) or D(3)) was performed in most of the patients, however, limited surgery was performed in early gastric cancer (EGC) when a rapid frozen examination indicated negative SLNs. All resected nodes were examined postoperatively by routine HE stain and those negative SLNs were examined with further cytokeratin immunohistochemistical staining. The diagnostic accuracy, sensitivity, negative predictive value and false-negative rate of regional lymph node status on the basis of SLN status were calculated respectively. SLNs were dectected in 25 of 26 patients with a successful detection rate of 96%. The number of SLNs ranged from 1 to 6, with a mean value of 3.2 per case. The SLNs of gastric cancer were only found in N(1) area in 50% of the cases, and only in N(2) or N(3) in 12%. The incidence of metastasis was significantly higher in SLNs than in non-SLNs (35% vs 7%). The diagnostic accuracy, sensitivity, negative predictive value and false-negative rate were 96%, 94%, 7/8 and 6% respectively. Complete analysis of SLN upstaged 2/7 of patients of gastric cancer. The SLN concept is validated in gastric cancer. Combined-agent SLN mapping is an accurate diagnostic procedure for detecting lymph node metastasis in patients with gastric cancer and may indicate rational extent of lymphadenectomy for gastric cancer.

Complications of gastrectomy with lymphadenectomy in gastric cancer

Currently, gastrectomy and extended lymphadenectomy (LN) is the treatment of choice for gastric cancer. Although a survival rate benefit of D2 LN compared to D1 LN has been shown, the D2 LN procedure is not fully employed, due to possible higher morbidity and mortality rates. These higher rates are being questioned in more recent series, in which D1 and D2 LN complication rates have been similar. The aim of this study was to analyze the immediate postoperative complications of patients submitted to total or subtotal gastrectomy with D1 or D2 LN (according to the Japanese guidelines for gastric cancer) at the Gastrointestinal Surgery Division of the Medical School of São Paulo University, between January 2001 and April 2003. One hundred consecutive patients were studied; 61 were men and 39, women. Total gastrectomy was performed in 52 patients (13 with D1 LN and 39 with D2 LN), and subtotal gastrectomy was performed in 48 (11 with D1 LN and 37 with D2 LN). Total or subtotal gastrectomy with D1 or D2 LN was performed according to the tumor extent and histological classification (Lauren's diffuse or intestinal type), considering the patient's general condition and the gastric cancer stage. Roux-en-Y reconstruction was performed in almost all patients. No difference was observed regarding complications and mortality related to the extent of the gastrectomy. Although morbidity was higher in the D1 group, no significant difference was observed. Mortality was higher in the D1 group, and this was probably related to their poor surgical condition and more advanced tumors. According to these results, it appears that total or subtotal gastrectomy with D2 LN in gastric cancer treatment, performed according to the Japanese guidelines, can be considered a safe procedure, with acceptable morbidity and mortality, when performed by a trained surgical team.

Lymphatic mapping and sentinel node biopsy using 99mTc tin colloid in gastric cancer.

The aim of this study was to determine the feasibility of sentinel lymph node (SLN) biopsy in patients with gastric cancer for the assessment of regional lymph node status. SLN is the first draining node from the primary lesion, and it is the first site of lymph node metastasis in malignancy. SLN mapping and biopsy are of great significance in the determination of the extent of lymphadenectomy, allowing patients with gastric cancer to have a better quality of life without jeopardizing survival. The SLN biopsy was performed in 46 consecutive patients having gastric cancer with a preoperative imaging stage of T1/T2, N0, or M0. Three hours prior to each operation, Tc tin colloid (2.0 mL, 1.0 mCi) was endoscopically injected into the gastric submucosa around the primary tumor. Subsequently, serial lymphoscintigraphy was performed using a dual-head gamma camera. After the SLN biopsy had been performed using a gamma probe, all patients underwent radical gastrectomy (D2 or D2+alpha). The SLN was cut and immediately frozen-sectioned. A paraffin block was then produced for permanent hematoxylin-eosin staining and immunohistochemistry (IHC). SLNs were successfully identified in 43 of 46 patients (success rate, 93.5%). On average, 2 (range, 1-8) SLNs were identified per patient. The positive predictive value, negative predictive value, sensitivity, and specificity of SLN biopsy were 100% (11 of 11), 93.8% (30 of 32), 84.6% (11 of 13), and 100% (30 of 30), respectively. SLNs were located at the level I lymph nodes in 38 (88.4%), the level I+II nodes in 2 (4.7%), and the level II nodes in 3 (7.0%). No micrometastases of SLNs was found on IHC for cytokeratin. SLN biopsy using a radioisotope in patients with gastric cancer is a technically feasible and accurate technique, and it is a minimally invasive approach in the assessment of patient nodal status.

The Minimal Range of a Lymphadenectomy in Gastric Cancer according to an Analysis of Sentinel Lymph Node and Solitary Lymph Node Metastasis

Purpose: The incidence of nodal metastases is as low as 2 to in early gastric cancer, so there is a trend to lessen the extent of surgery. In addition, the adequate range for a lymphadenectomy is controversial, especially in early gastric cancer. In this study, we tried to find the minimal range for a lymphadenectomy by analyzing sentinel-node and solitary lymph-node metastases in gastric cancer. Materials and Methods: The total of 78 patients who underwent a curative gastrectomy with a D2 lymphadenectomy for early gastric cancer between 2000 and 2002 in the Department of Surgery, Yonsei University, Seoul, Korea, were included for the evaluation of sentinel-node metastases.. After a laparotomy, 25 mg of indocyanine green was mixed in 5 ml of normal saline, and all the dye was injected into the subserosal layer around the primary tumor. All nodes stained within 5 minutes were marked. In addition, a total of 141 patients, who underwent a curative gastrectomy between 1997 and 2001 at the Department of Surgery, Yonsei University, Seoul, Korea, were analyzed for solitary lymph- node metastases. Results: Among the 78 patients, sentinel nodes were detected in 69 patients (). The sentinel nodes in 60 cases () were located in the perigastric area. However, 9 cases () had sentinel nodes in the N2 group. In the 141 cases that had a solitary metastatic node, 125 cases () demonstrated the metastatic lymph node in the perigastric area, and 16 cases () showed that the metastatic node in the N2 group. Conclusion: Taken together, removal of a perigastric lymph node could miss early metastases in gastric cancer, so a D1 lymphadenectomy should not be the minimal range of dissection if a lymphadenectomy is necessary.

Sentinel Node Biopsy in Gastric Cancer: Preliminary Results

Background: Extent of lymphadenectomy in gastric cancer is one of the still unresolved and ongoing questions. Whether extensive procedures lead to better survival remains controversial. The detection of sentinel node could become a helpful method to define the desirable extent of lymph node dissection for each particular patient. Material and methods: Prospective, single-centre, clinical trial. Sentinel node is identified using vital blue dye. After performance of D2 lymphadenectomy, the pathologist minutely investigates all lymphatic nodes by histological and imunohistochemistry techniques.Results: During a period of 36 months, an attempt to localise the sentinel node for biopsy was made in 22 patients. The successful rate of sentinel node detection with a good relation between metastatic involvement of the sentinel node and other nodes was 56% (13 out of 22 patients). All these patients suffered from small tumours and early stage of the disease. In large tumours and advanced stages, blue dye stained the tissue around the tumour diffusely rendering the identification of true sentinel node impossible. Fresh frozen section of the sentinel node resulted in two patients in a false negative outcome because of micrometastatic involvement.Conclusions: Sentinel node biopsy in gastric cancer using vital staining is a feasible method. Reliable results were seen in early stage of the disease. Fresh frozen section of sentinel node has probably a low sensitivity for detection of micro-metastases.

Survival benefit of extended D2 lymphadenectomy in gastric cancer with involvement of second level lymph nodes: a longitudinal multicenter study.

The survival benefit of extended lymphadenectomy in the surgical treatment of gastric cancer is still being debated. The aim of this longitudinal multicenter study was to evaluate long-term survival in a group of patients with involvement of second level lymph nodes, which would not have been removed in the case of a limited lymphadenectomy. Results were compared with those in patients with involvement of first level lymph nodes. Between 1991 and 1997, 451 patients with primary gastric cancer underwent curative resection with extended lymphadenectomy at three surgical departments in Italy according to the rules of the Japanese Research Society for Gastric Cancer. In 451 cases treated by extended lymphadenectomy, morbidity and mortality rates were 17.1% and 2%, respectively. In 126 patients (27.9%) (group A), metastases were found in lymph node stations 7 to 12; 109 patients (24.2%) had metastases confined to the first level (group B). Lymph node stations 7 and 8 showed the highest incidence of metastases in the second level (17.1% and 12.4%, respectively). A significant difference in 5-year survival was observed between group A and group B (32% vs. 54%; P =.0005). This difference disappeared when cases were stratified according to the number of positive lymph nodes. By multivariate analysis, only the number of positive lymph nodes (relative risk, 1.8; P <.0001) and the depth of invasion (relative risk, 2.1; P <.0001), but not the level of involved nodes, showed to be independent predictors of poor prognosis. Japanese-type extended lymphadenectomy yields low morbidity and mortality rates if performed in specialized centers. This procedure could provide a good probability of long-term survival, even for patients with involvement of regional lymph nodes.

Lymphadenectomy in gastric cancer: prognostic role and therapeutic implications

Aims: Surgeons involved in the treatment of gastric cancer are interested in the extent of lymphadenectomy as the latter may not only influence the reliability of the tumour, node and metastasis classification but also be relevant for the long-term oncological outcome. The purpose of the study was to evaluate the prognostic role of the number of resected lymph nodes (as an indicator of the scope of lymphadenectomy) and of the number of metastatic lymph nodes on the long-term mortality for all causes and to provide clinicians with estimates of predictive survival probabilities. Methods: The study involved 615 cancer patients subjected to a curative (R0) subtotal or total gastrectomy in a randomized Italian trial. According to the trial protocol, a D2 lymphadenectomy had been advised. The number of resected and metastatic lymph nodes was analysed as a continuous variable in multiple Cox models. Results: There was no difference in operative mortality (about 1.8%) according to the number of lymph nodes in the specimen (≤15, 16–25, >25). The risk of long-term death for all causes tended to decrease with increasing number of resected lymph nodes up to about 25, and then could be considered stable for wider lymphadenectomies. An increasing risk of death for all causes was associated with an increasing number of metastatic lymph nodes; the risk could be considered stable for more than 20 metastatic lymph nodes. Conclusions: A lymphadenectomy including more than 25 lymph nodes is suggested, provided that there is a low risk of operative mortality.

18 P Safety, efficacy and long term prognosis of extended D2 and D3 lymphadenectomy for gastric cancer

18 P Safety, efficacy and long term prognosis of extended D2 and D3 lymphadenectomy for gastric cancer

Lymphadenectomy in gastric cancer: our experience with 180 cases

We have reviewed our experience with 180 gastric cancer patients who underwent extended and complete node dissection (D2) (that is with N1-N2 dissection), performed unroutinely and only when clinical and instrumental criteria warranted it. Our purpose was to assess the eventual presence of a significant difference between the prognosis of our patients and the prognosis of patients surgically treated elsewhere with extended and routine lymph node dissection (D2) or with more extended lymph node dissection (D4); the latter should give a better prognosis by providing R0 (absence of residual tumor) conditions. Since clinical and pathological staging presents margins of error not only for the prognosis but also for the type and intensity of the treatment (which are bound to fundamental processes of cellular life: proliferation, differentiation and death), it may be helpful to compare the mortality and prognosis of our patients.

Gastric Cancer Nodal Metastases: Biologic Significance and Therapeutic Considerations

Stage migration as well as marked variation in stage distribution confounds the direct comparison of survival rates associated with varying degrees of lymphadenectomy for gastric cancer. Data from prospective randomized trials document increased mortality and morbidity associated with D-2 lymphadenectomy. Evidence for improved survival with D-2 lymphadenectomy comes from retrospective and prospective nonrandomized studies that have yet to be validated by any prospective randomized trial. Although it is of value for accurate staging, D-2 lymphadenectomy has yet to be proven therapeutically superior to D-1 resection.

Lymphadenectomy for gastric cancer in clinical trials: update.

The controversy over the value of extended lymph node dissection for treatment of gastric cancer is fiercely debated. Whereas Japanese surgeons claim that the superior survival rates in their series are due to extensive resection (D2 resection), many Western authorities believe that their results only reflect differences in the prevalence of prognostic factors, inconsistencies between Japanese and Western staging systems, and the phenomenon of "stage migration," which occurs with extensive resection. Two small randomized prospective trials from Hong Kong and Cape Town showed a tendency toward high morbidity with extensive lymph node dissection but no survival benefit. In contrast, the recently completed prospective German Gastric Carcinoma Study demonstrated a clear survival advantage with D2 resection for tumor stages II and IIIa with no increase in perioperative morbidity or mortality. The long-term results of the still ongoing randomized MRC and Dutch trials are therefore eagerly awaited.