Systematic Pelvic Lymph Node Dissection Research Articles

Hypertension and hyperglycaemia are positively correlated with local invasion of early cervical cancer.

Metabolic disorders are involved in the development of numerous cancers, but their association with the progression of cervical cancer is unclear. This study aims to investigate the association between metabolic disorders and the pathological risk factors and survival in patients with early cervical cancer. Patients with FIGO IB1 (2009) primary cervical cancer who underwent radical hysterectomy and systematic pelvic lymph node dissection at our institution from October 2014 to December 2017 were included retrospectively. Clinical data regarding the metabolic syndrome and surgical pathology of the patient were collected. The correlations between metabolic disorders (hypertension, hyperglycemia, and obesity) and clinicopathological characteristics as well as survival after surgery were analyzed. The study included 246 patients with clinical IB1 cervical cancer, 111 (45.1%) of whom had at least one of the comorbidities of hypertension, obesity, or hyperglycemia. Hypertension was positively correlated with parametrial invasion and poorly differentiated histology; hyperglycemia was positively correlated with stromal invasion; obesity was negatively associated with lymph node metastasis; but arbitrary disorder did not show any correlation with pathologic features. Hypertension was an independent risk factor for parametrial invasion (OR=6.54, 95% CI: 1.60-26.69); hyperglycemia was an independent risk factor for stromal invasion (OR=2.05, 95% CI: 1.07-3.95); and obesity was an independent protective factor for lymph node metastasis (OR=0.07, 95% CI: 0.01-0.60). Moreover, the patients with hypertension had a significantly lower 5-year OS rate (70.0% vs. 95.3%, P<0.0001) and a significantly lower 5-year PFS rate than those without hypertension (70.0% vs. 91.2%, P=0.010). Hypertension and hyperglycemia are positively associated with local invasion of early cervical cancer, which need to be verified in multi-center, large scale studies.

Sentinel lymph node in cervical cancer: time to move forward.

In early-stage cervical cancer, lymph node status is of paramount importance to determine the best therapeutic strategy and is one of the most important prognostic factors of survival. According to main international guidelines, pelvic full lymphadenectomy is recommended for lymph node staging. Sentinel lymph node (SLN) biopsy is an accurate method for the assessment of lymph nodal involvement and has been suggested instead of systematic pelvic lymph node dissection (PLND). The SLN technique requires a learning-curve to be well performed. Combined detection with technetium-99 and blue dye has been widely used but the recent introduction of indocyanine green (ICG) is of growing interest since it could improve SLN detection. SLN biopsy offers a more accurate anatomical staging by finding potential metastatic nodes outside of usual lymphadenectomy areas. SLN biopsy improves the diagnostic value of lymph node staging with ultrastaging and detection of low-volume nodal metastases [isolated tumor cells (ITCs) and micrometastases]. Appropriate selection of patient and minimal training combined with some simple rules may guarantee a low false negative rate. Several studies have shown that SLN mapping in these patients is feasible, with excellent detection rates and sensitivity. Less-radical lymph node dissection decreases the associated morbidity of PLND, especially the risk of lower-limb lymphoedema, which severely affects patient quality of life. Some points are still subject to debate such as the low accuracy of intraoperative SLN status assessment by frozen section and the impact of micrometastasis on prognosis. Although international guidelines consider SLN biopsy as an alternative to PLND, SLN biopsy alone is not the gold-standard yet due to lack of prospective evidence on long-term oncological safety. The 3 ongoing prospective trials SENTIX, PHENIX and SENTICOL III will most probably give an answer to these issues.

Pathological factors associated with non-sentinel lymph node metastasis in early stage cervical cancer.

To analyze the predictive factors for non-sentinel lymph node (non-SLN) metastasis in early-stage cervical cancer. We analyzed a series of 113 patients who underwent sentinel lymph node (SLN) mapping for cervical cancer. The SLNs were examined by immunohistochemistry (IHC) when the hematoxylin-eosin stain was negative. The overall bilateral detection rate was 81.5%, with a median of two SLNs resected. The study ultimately included 92 patients with SLNs that were mapped who had also undergone systematic pelvic lymph node dissection. Thirteen (14.1%) patients had positive SLNs, with a median of one positive SLN. Regarding the size of SLN metastasis, one (1.1%) had isolated tumor cells (ITC), seven (7.6%) had micrometastases, and five(5.4%) had macrometastases. Notably, 46.1% (6/13) had lymph node metastases detected only after IHC. Five (38.5%) cases had positive non-SLNs, with a median count of one positive lymph node. Parametrial invasion was the only risk factor for positive non-SLN (p = .045). Regarding the size of SLN metastasis, non-SLN involvement was present in the only case with ITC (1/1), 42.9% (3/7) of cases with micrometastases, and in 20% (1/5) with macrometastases. Our data suggest that parametrial invasion correlates with the risk of non-SLN metastasis in cervical cancer.

The diagnostic accuracy of fluorodeoxyglucose-positron emission tomography/computed tomography and sentinel node biopsy in the prediction of pelvic lymph node metastasis in patients with endometrial cancer: A retrospective observational study.

According to the sentinel node biopsy (SNB), systematic pelvic lymph node dissection (PLND) may not be needed for patients with early-stage endometrial cancer. On the other hand, imaging technology including fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) has been developing worldwide. The aim of this study was to evaluate the combined diagnostic accuracy of FDG PET/CT and SNB in the prediction of pelvic lymph node metastasis in endometrial cancer patients.One hundred twenty-one patients with endometrial cancer underwent FDG PET/CT before hysterectomy and received SNB followed by systematic PLND. Univariate and multivariate analyses were performed to compare the diagnostic accuracy of FDG PET/CT and SNB in the prediction of pelvic node metastasis to the ultimate histologic status.FDG PET/CT had lower sensitivity (36.8% versus 57.9%, P = .1) and a higher specificity (96.4% versus 84.8%, P < .01) than SNB. The kappa statistics of FDG PET/CT and SNB were 0.37 (95% CI, 0.15–0.59) and 0.72 (95% CI, 0.53–0.90), respectively. The sensitivity of SNB was significantly higher than that of FDG PET/CT in all hemi-pelvises (HPs) in which the short axis of the largest metastatic lymph node was <5 mm in diameter (72.7% versus 18.2%, P = .01). In contrast, the sensitivity of FDG PET/CT was higher than that of SNB in all HPs in which the short axis of the largest metastatic lymph node was ≥5 mm in diameter (62.5% versus 37.5%, P = .2); however, the difference was not statistically significant. When the combined diagnosis of FDG PET/CT and SNB was made, the sensitivity and specificity were 84.2% and 82.1%, respectively.SNB was more useful for detecting lymph node metastasis than FDG PET/CT, especially in patients with small metastatic lymph nodes. The combined diagnosis of FDG PET/CT and SNB improves the sensitivity; PET-positive nodes should be dissected regardless of SNB status and HPs in which SNB was not detected should be dissected systematically regardless of FDG PET/CT status.

Which is better for predicting pelvic lymph node metastases in patients with cervical cancer: Fluorodeoxyglucose-positron emission tomography/computed tomography or a sentinel node biopsy? A retrospective observational study.

Systematic pelvic lymph node resection may not be needed for patients with cervical cancer, especially in the early stage, if the pre- or intraoperative diagnosis of lymph node status is correct. The aim of this study was to evaluate the diagnostic accuracy of pelvic lymph node metastasis for fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) and sentinel node biopsy (SNB) of cervical cancer patients.Forty-eight patients with cervical cancer were imaged with FDG PET/CT before radical hysterectomy and underwent an SNB followed by systematic pelvic lymph node dissection. The diagnostic accuracy for predicting pelvic node metastases for FDG PET/CT and SNB compared with the ultimate histologic status was analyzed.Among 96 hemi-pelvises (HPs) in 48 patients, pelvic lymph node metastases were obtained in 12 HPs. The sensitivity of pelvic node metastases for FDG PET/CT and SNB was 8.3% and 75.0%, respectively. The specificity for FDG PET/CT and SNB was 97.6% and 94.0%, respectively. The negative predictive value for FDG-PET/CT and SNB was 88.2% and 100%, respectively.SNB is more suitable for detecting pelvic node metastases than FDG PET/CT. The omission of systematic pelvic lymphadenectomy should be considered based on the findings of SNB, not FDG PET/CT.

Is it time to consider the sentinel lymph node mapping the new standard in endometrial cancer

In the march issue of Lancet Oncology , Rossi et al . published the results of a prospective multicenter validation trail on robotic indocyanine green (ICG) sentinel lymph node (SLN) mapping in endometrial cancer (EC): the FIRES trial (1). In this trial, at 18 institutions, 340 patients with EC underwent a robotic ICG SLN mapping followed by a systematic pelvic lymph node dissection in every case and by a para-aortic lymph node dissection in 58% of the cases. The median number of SLNs and of total nodes removed was 2 and 19 respectively. We believe that this is a landmark trial that may lead to changes in the management recommendations for EC. The prospective multicentre design and the strong validation data derived from its large cohort of patients and the thoroughness of the lymphadenectomy represent its major strengths.

Cost-effectiveness of sentinel node biopsy and pathological ultrastaging in patients with early-stage cervical cancer.

The objective of this study was to determine the cost-effectiveness of radical hysterectomy (RH) and sentinel lymph node biopsy (SLNB) for the management of early-stage cervical cancer (stage IA2-IB1). A simple decision tree model was developed to follow a simulated cohort of patients with early-stage cervical cancer treated with RH and 1 of 3 lymph node assessment strategies: systematic pelvic lymph node dissection (PLND), SLNB using technetium 99 (Tc99) and blue dye, and SLNB using Tc99 only. SLNB using indocyanine green (ICG) was used as an exploratory strategy. Relevant studies were identified to extract the probability data and utility parameters and to estimate quality-adjusted life-years (QALYs) and absolute life-years (ALYs). Only direct medical costs were modeled, and the time horizon for the study was 5 years. SLNB using Tc99 and blue dye cost $21,089 and yielded 4.54 QALYs and 4.90 ALYs. PLND cost $22,353 and yielded 4.47 QALYs and 4.91 ALYs. SLNB using blue dye and Tc99 was the most cost-effective strategy when ALYs were considered with an incremental cost-effectiveness ratio (ICER) of $144,531. When QALYs were considered, the SLNB technique using Tc99 and blue dye dominated all other strategies. SLNB using ICG cost $20,624 and yielded 4.90 ALYs and 4.54 QALYs. It was clinically superior to and less expensive than all other strategies when QALYs were the outcome of interest and had an ICER of $221,171 per ALY in comparison with RH plus PLND. SLNB using Tc99 and blue dye with ultrastaging is considered the most cost-effective strategy with respect to 5-year progression-free survival and morbidity-free survival. Although it was included only as an exploratory strategy in this study, SLNB with ICG has the potential to be the most cost-effective strategy. Cancer 2017;123:1751-1759. © 2017 American Cancer Society.

A novel therapeutic strategy for chylous ascites after gynecological cancer surgery: a continuous low-pressure drainage system

Postoperative chylous ascites is an unusual complication following retroperitoneal surgery. A search of the English literature showed only 44 cases of chylous ascites following gynecological cancer surgery. The treatment is primarily conservative, but surgical treatment is considered in resistant cases. We developed a novel non-surgical therapeutic strategy for postoperative chylous ascites. We report a case of severe chylous ascites following pelvic lymph node dissection for gynecological cancer. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washing, and systematic pelvic lymph node dissection were performed for a stage II G1 endometrioid adenocarcinoma (FIGO 2009). Forty-one days after surgery, the patient was readmitted due to massive ascites. Repeated paracentesis and a low-fat diet were only partially effective. Fifty-one days after surgery, we started paracentesis with a continuous low-pressure drainage system. Nine days later, there was no further fluid drainage. The patient was asymptomatic and without recurrent disease at follow-up 3 months later. Pelvic lymph node dissection may cause postoperative chylous ascites. Paracentesis with a continuous low-pressure drainage system can be an effective conservative treatment for postoperative chylous ascites.

Neoadjuvant chemotherapy plus radical surgery followed by chemotherapy in locally advanced cervical cancer.

5093 Background: The aim of this study is to evaluate the efficacy, in terms of overall survival and progression free survival, and safety of adjuvant chemotherapy after neoadjuvant chemotherapy followed by radical surgery both in patients with and without node metastases. Methods: Between June 2000 to May 2007, all patients with diagnosis of locally advanced cervical cancer referred to the Division of Gynecologic Oncology of the University Campus Bio-Medico of Rome were elegible for this protocol.All enrolled patients received 3 cycles of platinum-based chemotherapy every 3 weeks according to the scheme cisplatin 100 mg/mq and paclitaxel 175 mg/mq. After neoadjuvant chemotherapy all patients with stable or progression to treatment were excluded from the protocol, all other were submitted classical radical hysterectomy and bilateral systematic pelvic lymph node dissection, and after to adjuvant treatment with 6 cycles of platinum based chemotherapy with cisplatin 100 mg/mq and paclitaxel 175 mg/mq. Results: 110 patients with local advanced cervical cancer received the treatment with neoadjuvant chemotherapy followed by radical surgery and adjuvant chemotherapy.Our study focused on clinical and operative data , in terms of overall survival and disease free survival at 5 and 3 years. 5-year OS of our series was 78% at five years and 86% at 3-years, with encouraging results also in subgroup with and without node mestastases. Conclusions: The adjuvant chemotherapy regimen after neoadjuvant chemotherapy and radical surgery rappresents a valid treatment option for patients with locally advanced cervical cancer without lymph node involvement, both in terms of overall survival than in terms of disease-free interval, the results have also confirmed the validity of this approach in lymph node metastases, with a complication rate lower than the standard radio-chemotherapy regime.

Cervical Mullerian Adenosarcoma with heterologous sarcomatous overgrowth: a fourth case and review of literature

BackgroundUterine sarcomas are relatively rare tumors that account for approximately 1-3% of female genital tract malignancies and between 4-9% of uterine cancers. Less than 8% of all cases are Mullerian adenosarcoma, a distinctive uterine neoplasm characterized by a benign, but occasionally atypical, epithelial and a malignant, usually low-grade, stromal component, both of which should be integral and neoplastic constituents of the tumor. Mullerian adenosarcoma with sarcomatous overgrowth (MASO) is a very aggressive variant, associated with post-operative recurrence, metastases, even when diagnosed in early stage.Case PresentationWe present a fourth MASO case derived from uterine cervix in a 72-year-old woman with metrorrhagia and a polypoid mass protruding through the cervical ostium. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, systematic pelvic lymph node dissection, omental biopsy and appendectomy were performed. Surgery treatment was associated with adjuvant whole-pelvis radiation (45 Gy) and adjuvant chemotherapy (cisplatin/ifosfamide). After nine months of follow up, the patient was free of tumor.ConclusionsThe rarity of MASO of the cervix involves a management difficult. Most authors recommend total abdominal hysterectomy, usually accompanied by bilateral salpingo-oophorectomy. There is no common agreement on staging by lymphadenectomy during primary surgery and adjuvant chemo-radio therapy.

Role of Sentinel Lymph Node Biopsy in Cervical Cancer: Pro

Sentinel lymph node biopsy in cervical cancer is used to reduce the morbidity of a full lymph node dissection while improving the pickup rate of metastatic lymph nodes. The higher detection rate achieved can be explained by the following: the identification of the sentinel lymph node in an aberrant location which would not be routinely included in a systematic pelvic lymph node dissection, the sentinel lymph node is completely excised, and the routine use of ultrastaging. The higher detection rate achieved through sentinel lymph node biopsy can identify additional patients who could potentially benefit from adjuvant therapy therefore, in our view the gold standard of lymph node assessment in early stage cervical cancer has shifted and sentinel lymph node biopsy has taken the place of a complete lymphadenectomy.

Lymph node detection by MRI before and after a systematic pelvic lymphadenectomy

Objective Pelvic lymphadenectomy is considered the gold standard to diagnose and possibly treat lymphatic metastases in gynaecological cancer patients. The aim of this study is to evaluate whether all presurgical MRI detected lymph nodes were removed during the systematic pelvic lymph node dissection (PLND) in cervical cancer patients. Methods 21 consecutive cervical cancer patients who were scheduled to undergo a PLND were evaluated by a MRI scan prior to surgery and 6 weeks afterwards. All patients had tumour metastasis negative lymph nodes at histopathological examination. Results On average, 10 pelvic lymph nodes (range 5–17) per patient were detected by presurgical MRI. Postsurgical MRI scans showed that on average 1 (range 0–3) pelvic node per patient was not removed by surgery. In total, 14% of the presurgical MR detected nodes were not removed by surgery (31/225). Approximately half of all lymph nodes that remained after surgery were located in the obturator region. In spite of the remaining nodes, surgery and histopathological examination did detect more nodes than MRI: on average 21 lymph nodes per patient (range 9–59) were removed. Another 2 lymph nodes (range 0–6 per patient) were judged to be newly developed after surgery. Conclusion Although surgery was able to remove many more lymph nodes than those detected by presurgical MRI, 14% of presurgical MRI detected lymph nodes were not removed by PLND. The value of MRI prior to surgery for the detection of pathological lymph nodes is a subject of further research.

Author reply

We thank Drs. Barranger and Darai for their letterconcerning our recent article in Cancer.1 However, we would like to clarify several points regarding their comments. With regard to the false-negative rate, the value of this index is limited by the procedures used to identify metastasis in the lymph nodes. For example, in our study, the false-negative rate was 0% when using classic histologic techniques. However, with the use of serial sectioning and immunohistochemical techniques on all sentinel and nonsentinel lymph nodes, the false-negative rate in the same population was found to be 12.5% (3 of 24 patients). In addition, Drs. Barranger and Darai recently published an article2 in which a procedure (serial sectioning and immunohistochemistry with an anticytokeratin antibody) similar to the one we used was performed. They found a false-negative rate of 0% in 18 cervical carcinoma patients in whom the sentinel lymph node was identified. However, their study has several limitations. First, the number of patients evaluated was only 18, whereas our study was based on 29 patients. Also, when closely examining their inclusion criteria, it appears that eight patients with advanced cervical tumors were included in the study by Drs. Barranger and Darai. These eight patients were treated first with chemoradiotherapy before undergoing the sentinel lymph node procedure. The value of the sentinel lymph node procedure after neoadjuvant treatment was not evaluated, and in our opinion these eight patients should not be included in a study evaluating the sentinel lymph node procedure. Lastly, the mean number of lymph nodes retrieved after a full systematic pelvic lymph node dissection was 10.5 per patient in their study, but it was nearly twice as high (19.4 per patient) in our study. We can assume that Drs. Barranger and Darai may have missed some lymph nodes that may have been involved by metastatic cells. Therefore, in our opinion, Drs. Barranger and Darai should not state that, in patients with cervical carcinoma, the sentinel lymph node procedure is reliable based on a study of only 10 patients. To define the value of the sentinel lymph node procedure precisely, a multicentric study with a minimum of 100 patients should be performed, in which the patients are evaluated with serial sectioning and immunohistochemistry of the sentinel and the nonsentinel lymph nodes. This type of study is currently underway in France involving not only our center but the team of Drs. Barranger and Darai as well. We hope that this study will define clearly the value of the sentinel lymph node procedure in patients with early cervical carcinoma. Patrice Mathevet M.D., Ph.D.*, * Department of Gynecology, Hospital Edouard Herriot, Lyon, France.

The role of pelvic lymphadenectomy and radical cystectomy for lymph node positive bladder cancer. The memorial sloan-kettering cancer center experience

The impact of pelvic lymph node dissection (PLND) on the survival of patients with lymph node positive bladder cancer is controversial. The authors retrospectively analyzed the long term and disease free survival among 140 patients with lymph node positive disease having radical cystectomy and bilateral PLND at the Memorial Sloan-Kettering Cancer Center between 1980 and 1988. They also sought to identify prognostic variables for recurrence and survival. Of the 140 patients, 36 (25.7%) were found to be tumor free, with 22 (15.7%) followed longer than 5 years. Regression analysis identified P-category as the only prognostic parameter influencing survival. Patients with tumors confined to the bladder (< or = P3a) had a 52.6% 5-year survival rate compared with 23.4% among those with extravesical (> or = P3b) tumors. N-category was a significant predictor for recurrence but not survival. As judged from this analysis, radical cystectomy and a systematic PLND alone can provide favorable outcome in some patients with regional nodal metastases from bladder cancer. The survival advantage is most pronounced in patients with low stage primary tumors. Stage migration and patient selection may have biased these findings.