Para-aortic Lymphadenectomy Group Research Articles

Comparison Between Transperitoneal and Extraperitoneal Laparoscopic Paraaortic Lymphadenectomy in Gynecologic Malignancies

Study ObjectiveTwo validated laparoscopic approaches for para-aortic lymphadenectomy (PAL) exist: the transperitoneal and the extraperitoneal. The aim of this study was to compare the surgical outcomes of both approaches. DesignA retrospective review of all patients who underwent laparoscopic PAL for a gynecologic malignancy between January 2008 and October 2013. SettingUniversity Hospital. PatientsTwo patients groups were compared: transperitoneal (n = 51) and extraperitoneal (n = 21). InterventionsParaaortic lymphadenectomy. Measurements and Main ResultsThe χ2 test, Fisher's exact test, or Student's t-test were used for univariate analysis and a stepwise logistic regression for multivariate analysis. The threshold of statistical significance was set at 0.05. All patient characteristics were similar between the 2 groups (p > .05 for all variables). There was only 1 (1.3%) conversion to laparotomy encountered in the transperitoneal PAL group and 3 conversions from extraperitoneal to transperitoneal PAL (14.2%). In 1 case of extraperitoneal PAL, the procedure was abandoned because of inadequate equipment (body mass index 48 kg/m2). The mean duration of surgery was longer in the transperitoneal group: 200 min (35–360) versus 125.6 min (45–180) in the extraperitoneal group (p = .001). The mean number of harvested lymph nodes was higher in the transperitoneal group: 17 (4–37) versus 13 (3–25) in the extraperitoneal group (p = .029). There was no difference in postoperative course and complications between both groups in multivariate analysis. ConclusionsIn nonobese patients, the extraperitoneal PAL is associated with shorter surgical duration, whereas the transperitoneal approach was associated with a higher number of harvested lymph nodes. As a result of improved ergonomy, the transperitoneal approach enables laparoscopic management of operative complications.

Chylous Ascites After Laparoscopic Lymph Node Dissection in Gynecologic Malignancies

Study ObjectiveTo evaluate the clinical presentation, epidemiology, risk factors, and treatment of chylous ascites after laparoscopic lymphadenectomy to treat gynecologic malignancies. DesignRetrospective study with review of outcomes (Canadian Task Force classification II-3). SettingUniversity research hospital. PatientsFrom November 2009 to December 2012, 997 patients underwent laparoscopic lymphadenectomy to treat gynecologic malignancies at our hospital. InterventionsPostoperative chylous ascites resolved with continuous drainage and dietary restriction or fasting. Measurements and Main ResultsNine of 997 patients (0.9%) developed chylous ascites postoperatively. Mean age of these 9 patients was 47.5 years. Median time from operation to development of chylous ascites was 4 days (range, 2–9 days). Chylous ascites developed on either day 1 in 6 patients, day 2 in 2 patients, and day 8 in 1 patient, after food intake. We found that postoperative chylous ascites was associated more with para-aortic lymphadenectomy than with pelvic lymphadenectomy (overall incidence, 0.9%; 4.08% in the para-aortic lymphadenectomy group vs 0.35% in the pelvic lymphadenectomy group). In all patients, chylous ascites resolved with conservative treatment. Median time to resolution was 7 days (range, 3–9 days). Drainage tubes were removed within 9 days after treatment. ConclusionsThe incidence of chylous ascites after laparoscopic lymphadenectomy was 0.9%. Para-aortic lymphadenectomy was associated with postoperative chylous ascites. Chylous ascites was successfully treated with conservative management. An abdominal drainage tube can be a simple and effective approach and should be considered in the treatment of chylous ascites.

Recent advances in research on epigenetic alterations and clinical significance of para-aortic lymphadenectomy in endometrial cancer: an introduction

Endometrial cancer is the most frequent cancer of the female reproductive organs in industrialized countries. In 2012, the numbers of new cases and deaths from endometrial cancer in the US were estimated to be 47,130 and 8,010, respectively [1]. The incidence of endometrial cancer is also increasing steadily in Japan, where the estimated number of new cases in 2007 was 9,104 [2] and the number of deaths in 2011 was 2,034 [3]. Endometrial cancer is a surgically staged disease and post-operative therapy is offered to patients with a high risk of recurrence according to the extent and aggressiveness of the tumor. Current topics in endometrial cancer include: the therapeutic significance of lymphadenectomy, the role of epigenetic alterations, and revision of the International Federation of Gynecology and Obstetrics staging criteria (FIGO 2008) for this disease. There was a paradigm shift in the treatment strategy for endometrial cancer after the introduction of a surgical staging system (FIGO 1988) that replaced the older clinical staging system. The newer paradigms of extended-surgical staging containing lymphadenectomy with more restricted use of adjuvant therapy and the older paradigm of simple hysterectomy bilateral salpingo-oophorectomy with more frequent use of adjuvant radiotherapy need to be compared prospectively in terms of survival benefits, quality of life, and cost of treatment [4]. Several issues regarding surgical staging need to be clarified. They include: how should suitable patients for complete lymphadenectomy be selected and what is the optimal extent of lymphadenenctomy? The therapeutic significance of lymphadenectomy has long been a matter of great debate. In 1964, Lewis suggested a therapeutic effect of pelvic lymphadenectomy in nodepositive patients [5]. He employed pelvic lymphadenectomy because endometrial cancer often recurred at the pelvic side wall after conventional hysterectomy and bilateral salpingo-oophorectomy, which suggested inadequate primary surgery. Retrospective studies suggest a therapeutic significance for lymphadenectomy, which is a function of removed lymph node count (thoroughness) and area of dissection (pelvic only versus pelvic and para-aortic lymphadenectomy) [6–8]. However, two prospective randomized controlled trials (RCTs) that intended to prove the therapeutic role of pelvic lymphadenectomy failed to show any survival advantage of pelvic lymphadenectomy versus no lymphadenectomy [9, 10]. However, there has been some criticism about the design of these trials because para-aortic lymphadenectomy was not included in the study arm. A retrospective cohort study which compared pelvic lymphadenectomy with combined pelvic and paraaortic lymphadenectomy revealed survival improvement in the pelvic and para-aortic lymphadenectomy group if this treatment was offered to intermediate-/high-risk endometrial cancer patients [11]. Based on these findings, discussions have begun about the design of future clinical trials to validate the therapeutic significance of lymphadenectomy. Topics for discussion include the eligibility of patients (all patients or selected patients at some risk of nodal metastasis), extent of lymphadenectomy (area: pelvic alone versus pelvic plus para-aortic, thoroughness: number of nodes removed), and type of experimental design (RCT versus cohort study). The difficulties and pitfalls of RCTs for validating surgical procedures have often been addressed [12–16]. These include the participating surgeons’ expertise in experimental N. Sakuragi (&) Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, North 15, West 7, Kitaku, Sapporo 060-8638, Japan e-mail: sakuragi@med.hokudai.ac.jp

Efficacy of Para-Aortic Lymphadenectomy in Ovarian Cancer: A Retrospective Study

Objective: The prognostic impact for ovarian cancer treatment of employing a systematic para-aortic and pelvic lymphadenectomy is still poorly defined. The purpose of this study was to evaluate the therapeutic efficacy of adding a para-aortic lymphadenectomy (PA) to the pelvic lymphadenectomy (PL), as compared with solely the pelvic lymphadenectomy. Materials and Methods: A retrospective study of patient outcomes was conducted of ovarian cancer patients who underwent optimal debulking surgery, concurrent with either PA + PL or PL alone, between 2000 and 2009 at our Osaka General Medical Center. Results: One hundred twenty-one patients with ovarian cancer underwent surgery. Forty-four patients (36%) underwent optimal debulking surgery (all residual disease was 1 cm) concurrent with lymphadenectomy. Seventeen patients underwent PA + PL (PA group), and 27 patients underwent PL alone (PL group). There were no significant differences in terms of overall survival (OS; hazard ratio [HR] = 0.49; 95% CI, 0.13 to 1.82; p = 0.29) and progression-free survival (PFS; HR = 0.62; 95% CI, 0.19 to 2.00; p = 0.40) between the PA group and the PL group. Both OS and PFS also failed to show significant differences, even when comparing them among 26 cases of FIGO stage I cases. Conclusions: Our data failed to show any prognostic improvement for ovarian cancer by adding para-aortic lymphadenectomy to the standard pelvic lymphadenectomy regimen.

Novel para‐aortic lymphadenectomy technique for gynecological malignancies prevents postoperative bowel obstruction

The aim of this study was to evaluate the effect of our novel technique on the prevention of postoperative ileus in patients undergoing systematic para-aortic lymphadenectomy (PALN). PALN was performed in 135 gynecological cancer patients (67 with ovarian cancer, 58 with endometrial cancer, 8 with serous surface papillary adenocarcinoma (SSPC) and 2 with fallopian tube cancer) between 2006 and 2011. To prevent postoperative ileus, we performed our novel technique wherein the small bowel and colon are released from pressure and soaked in 2 L of physiological saline for 1 min every 20 min during the lymphadenectomy. We indicated our novel PALN technique and retrospectively analyzed the outcomes of the surgical procedure in terms of the surgical data, and postoperative incidence of gastrointestinal dysfunction in patients with gynecological malignancies. The mean blood loss was 641.2 ± 800.3 mL in the PALN group and 313.9 ± 278.9 mL in the pelvic lymphadenectomy (PLN) without PALN group (P < 0.0001). There was no difference in the first passage of flatus between the PALN group and the PLN group (1.8 ± 0.7 days vs 1.6 ± 0.7 days). The mean time to tolerance of a regular diet was significantly longer in the PALN group than in the PLN group (P < 0.0001), whereas the incidence of vomiting was similar in both groups. Surprisingly, there were no cases of postoperative ileus in either group. Our novel technique is a safe and effective way to prevent the incidence and decrease the severity of postoperative ileus after PALN for gynecological malignancies.

Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis

In response to findings that pelvic lymphadenectomy does not have any therapeutic benefit for endometrial cancer, we aimed to establish whether complete, systematic lymphadenectomy, including the para-aortic lymph nodes, should be part of surgical therapy for patients at intermediate and high risk of recurrence. We selected 671 patients with endometrial carcinoma who had been treated with complete, systematic pelvic lymphadenectomy (n=325 patients) or combined pelvic and para-aortic lymphadenectomy (n=346) at two tertiary centres in Japan (January, 1986-June, 2004). Patients at intermediate or high risk of recurrence were offered adjuvant radiotherapy or chemotherapy. The primary outcome measure was overall survival. Overall survival was significantly longer in the pelvic and para-aortic lymphadenectomy group than in the pelvic lymphadenectomy group (HR 0.53, 95% CI 0.38-0.76; p=0.0005). This association was also recorded in 407 patients at intermediate or high risk (p=0.0009), but overall survival was not related to lymphadenectomy type in low-risk patients. Multivariate analysis of prognostic factors showed that in patients with intermediate or high risk of recurrence, pelvic and para-aortic lymphadenectomy reduced the risk of death compared with pelvic lymphadenectomy (0.44, 0.30-0.64; p<0.0001). Analysis of 328 patients with intermediate or high risk who were treated with adjuvant radiotherapy or chemotherapy showed that patient survival improved with pelvic and para-aortic lymphadenectomy (0.48, 0.29-0.83; p=0.0049) and with adjuvant chemotherapy (0.59, 0.37-1.00; p=0.0465) independently of one another. Combined pelvic and para-aortic lymphadenectomy is recommended as treatment for patients with endometrial carcinoma of intermediate or high risk of recurrence. If a prospective randomised or comparative cohort study is planned to validate the therapeutic effect of lymphadenectomy, it should include both pelvic and para-aortic lymphadenectomy in patients of intermediate or high risk of recurrence. Japanese Foundation for Multidisciplinary Treatment of Cancer, and the Japan Society for the Promotion of Science.

Meta-analysis of safety and efficacy on paraaortic lymphadenectomy in gastric cancer

To evaluate the safety and efficacy of paraaortic lymphadenectomy in gastric cancer with meta-analysis. Randomized controlled trial comparing D(2)/D(3) and D(2)/D(3) plus paraaortic lymphadenectomy in gastric cancer were identified by two investigators after search strategy was established. Seven randomized controlled trials with 1446 cases were included in this meta-analysis. Fixed effect model or random model was separately used to evaluate the safety and efficacy of paraaortic lymphadenectomy in gastric cancer. Total complication rate in the D(2)/D(3) plus paraaortic lymphadenectomy group was significantly higher than that in the D(2)/D(3) group (RR 1.34, 95% CI 1.03-1.75, P=0.03), while surgery associated complication between the two groups was almost the same. Lymphorrhea and severe diarrhea was more common in the D(2)/D(3) plus paraaortic lymphadenectomy (RR 16.23 and 9.56, 95% CI 1.99-131.98 and 1.70-53.67, respectively). Anastomotic leak, pancreatic fistula, abdominal abscess, ileus, postoperative bleeding and wound infection were similar. There were no advantages in operating time, amount of blood transfusion, in-hospital stay, reoperation, recurrence and 5-year survival favoring the paraaortic lymphadenectomy group except intra-operative blood loss and rate of blood transfusion (WMD 202.95, 95% CI 116.80-289.10; RR 1.93, 95% CI 1.20-3.10). Paraaortic lymphadenectomy is associated with increased total complication without altering postoperative recurrence and survival. Strict large-scale multicenter controlled trials with long-term follow-up are required.

Effects of super-extended paraaortic lymphadenectomy (PAL) on biological responses in totally gastrectomized patients with T3 or T4 gastric cancer.

BACKGROUND: In Japan, much attention has recently been paid to super-extended paraaortic lymphadenectomy (PAL) for the treatment of advanced gastric cancer. However, it has been reported that PAL is associated with increased morbidity and mortality, as compared to conventional extended lymphadenectomy (D2 or D3). Therefore, an analysis of the effects of PAL on perioperative changes in the biological responses of patients essential for determining the potential utility of this procedure.METHODS: The current non-randomized prospective study included evaluations of perioperative changes in parameters of surgical stress (series I; serum levels of antidiuretic hormone, interleukin-6, trypsin, and phospholipase A(2)) and immunocompetence (series II; phytohemagglutinin- and concanavalin A-induced blastogenesis, activity of natural killer cells and the ratio of CD4 cells to CD8 cells) in patients with advanced gastric cancer (T3 or T4), comparing groups treated with D3 plus PAL ( n = 12) and D3 ( n = 13), and a control group with early gastric cancer ( n = 16) treated with D1 lymphadenectomy (perigastric N1 nodes) between April 1995 and April 1997.RESULTS: The duration of surgery and the amount of blood lost were longer and greater in the D3 plus PAL group than in the D3 and D1 groups. D3 plus PAL and D3 were associated with significant postoperative increases in parameters of surgical stress, as well as with significant postoperative immunosuppression, compared to results with D1. However, there were no significant differences in the respective parameters between the D3 plus PAL and D3 groups.CONCLUSIONS: Our results indicate that there are no essential differences in patients' biological responses between D3 plus PAL and D3 lymphadenectomy. It appears that PAL-associated morbidity can be minimized by very careful manipulation during the dissection of paraaortic lymph nodes.