Value of sentinel node mapping in cancer of the cervix

Objectives

To compare the relative value of two methods of detection for the sentinel lymphatic nodes (SLNs): colorimetric with Isosulfan blue (ISB) and radio-isotopic with Technetium-99 (Tc99), and to evaluate the concept of the SLN mapping applied to cervical cancer.

Methods

From October 2000 to December 2006, radical surgery was planned in 211 patients who presented early-stage cancer of the cervix. Both ISB and Tc99 were used to detect the SLNs. In all cases, we proceeded with laparoscopy for the identification and removal of the SLNs, followed by a complete pelvic lymphadenectomy with or without para-aortic node sampling. The SLNs were sent for frozen section (1 level) and were ultra-staged (6 levels) for final pathology. Detection rate, sensitivity and negative predictive value (NPV) were calculated.

Results

Among the 211 patients, ISB (n = 152) identified at least 1 SLN in 92.8% of the cases. With Tc99 (n = 166), the detection rate of SLN increased to 96.9%. When both techniques were used together (n = 107), Tc99 was significantly better than ISB by 7.8% (p = 0.0094) and at least 1 SLN (hot and/or blue) was found in 99.1% of the cases. In 16.7% of patients, a SLN was located in aberrant sites, including 3.8% in the para-aortic area. Thirty-three out of the 211 patients (15.6%) had lymph node metastases. When considering only the 181 patients with bilateral SLNs identified, the NPV of SLN is 100% after ultra staging on final pathology and 94.2% on frozen section (FS).

Conclusion

Sentinel node mapping is feasible using laparoscopy. The radio-isotopic technique adds significantly to the rate of detection. The main benefits of SLN mapping in cervical cancer are the detection of micro-metastases on ultra staging which might be missed on routine pathological evaluation, and identification of aberrant drainage sites. However, the current frozen section techniques lack sensitivity to identify very small metastases and need refinement. SLN mapping should become the standard of care in the modern management of cervical cancer and complete pelvic lymphadenectomy could be avoided when bilateral SLNs are detected in patients with lesions less than 2 cm.     

Isthmocervical labelling and SPECT/CT for optimized sentinel detection in endometrial cancer: Technique,experience and results

Objective

We evaluated the clinical feasibility of a new injection technique for sentinel detection in endometrial carcinoma (EC), transcervical subepithelial injection into the isthmocervical region of the myometrium. We compared detection of sentinel lymph nodes (SLN) by single photon emission computed tomography with CT (SPECT/CT) with planar lymphoscintigraphy.

Methods

This is a unicentric prospective study. In all patients, transcervical injection of 10 MBq Technetium-99m-nanocolloid was performed into the isthmocervical myometrium without anaesthesia. After 40 (30–60) min, lymphoscintigraphy and SPECT/CT were performed. Patent blue was administered before surgery. The number and localisation of SLN detected in SPECT/CT and lymphoscintigraphy were recorded and compared to the SLN and non-SLN dissected intra-operatively.

Results

Between August 2008 and March 2012, 31 patients with EC were enrolled. The new transcervical injection of labelling substances led to high intra-operative (90.3%) detection rates, pelvic bilateral (57%), para-aortic (25%). SPECT/CT significantly identified more SLN than lymphoscintigraphy (mean 2.2 (1–8) to 1.3 (1–7)) in more patients (29/31 (93.5%) to 21/31 (68%), p < 0.01). If SLN were identified in one hemi-pelvis, the histological evaluation of the SLN correctly predicted lymph node (LN) metastases for this basin which led to sensitivity 100%, negative predictive value (NPV) 100%, and false negative results 0%.

Conclusion

Transcervical SLN marking in combination with SPECT/CT is easily applicable and leads to high physiologic detection rates in pelvic and para-aortic lymphatic drainage areas. Non-affected SLN truly predicted a non-affected LN basin. Combining both methods SLN dissection may be a safe and feasible staging technique for clinical routine in EC.     

The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes

Objective

To determine the false-negative rate of a surgical sentinel lymph node (SLN) mapping algorithm that incorporates more than just removing SLNs in detecting metastatic endometrial cancer.

Methods

A prospective database of all patients who underwent lymphatic mapping for endometrial cancer was reviewed. Cervical injection of blue dye was used in all cases. The surgical algorithm is as follows: 1) peritoneal and serosal evaluation and washings; 2) retroperitoneal evaluation including excision of all mapped SLNs and suspicious nodes regardless of mapping; and 3) if there is no mapping on a hemi-pelvis, a side-specific pelvic, common iliac, and interiliac lymph node dissection (LND) is performed. Paraaortic LND is performed at the attendings' discretion. The algorithm was retrospectively applied.

Results

From 9/2005 to 4/2011, 498 patients received a blue dye cervical injection for SLN mapping. At least one LN was removed in 95% of cases (474/498); at least one SLN was identified in 81% (401/498). SLN correctly diagnosed 40/47 patients with nodal metastases who had at least one SLN mapped, resulting in a 15% false-negative rate. After applying the algorithm, the false-negative rate dropped to 2%. Only one patient, whose LN spread would not have been caught by the algorithm, had an isolated positive right paraaortic LN with a negative ipsilateral SLN and pelvic LND.

Conclusions

Satisfactory SLN mapping in endometrial cancer requires adherence to a surgical SLN algorithm and goes beyond just the removal of blue SLNs. Removal of any suspicious node along with side-specific lymphadenectomy for failed mapping are an integral part of this algorithm. Further validation of the false-negative rate of this algorithm is necessary.     

Preoperative pelvic lymphoscintigraphy is of limited usefulness for sentinel lymph node detection in cervical cancer

Objectives

To analyze concordance between preoperative lymphoscintigraphy and intraoperative lymphatic mapping (ILM) for sentinel lymph node identification using technetium 99m-labeled-dextran 500 (99m-Tc) and patent blue dye in patients with early cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy, as well as to evaluate sentinel lymph node (SLN) detection.

Study design

Forty-seven patients underwent surgical treatment for cervical cancer. For SLN identification, 99m-Tc and blue patent were injected into the cervix on the eve and day of surgery, respectively. Preoperative pelvic lymphoscintigraphy was performed in all patients after 99m-Tc injection. Concordance between preoperative lymphoscintigraphy and ILM was evaluated.

Results

Of the 56 patients who underwent preoperative lymphoscintigraphy, 43 (81.13%) had at least one lymph node identified. Bilateral lymph nodes were identified in 21 (37.5%) patients. Sentinel lymph nodes detected on ILM had been previously found on preoperative lymphoscintigraphy in 66.7%, 67.2% and 0% in the right, left and central locations, respectively. In 14 patients (25%), only one lymph node was identified on preoperative lymphoscintigraphy, but more than one sentinel lymph node was detected on intraoperative mapping. In nine (16.1%) patients, lymphoscintigraphy showed only unilateral lymph nodes, but ILM identified bilateral sentinel lymph nodes.

Conclusion

The combination of patent blue and radionuclide techniques produced excellent results for SLN detection in cervical cancer. Preoperative lymphoscintigraphy does not offer any advantage over ILM for SLN identification.     

Initial failure site according to primary treatment with or without para-aortic lymphadenectomy in endometrial cancer

Objective

The objective of this study was to compare the initial failure sites in patients with endometrial cancer who underwent surgical treatment including pelvic lymphadenectomy with or without para-aortic lymphadenectomy.

Methods

A retrospective chart review was carried out for 657 endometrial cancer patients with no residual disease after initial treatments including lymphadenectomy at two tertiary centers between 1987 and 2004. Surgical treatment at one institute included pelvic lymphadenectomy (PLX) without para-aortic lymphadenectomy (PALX), while surgical treatment including PLX + PALX was routinely performed at the other institute. We identified patients with recurrence and evaluated initial failure sites. Rates of recurrence in the respective sites were compared according to the type of lymphadenectomy.

Results

Of the 657 patients, 103 (15.7%) suffered recurrence. There was no significant difference between the rate of intrapelvic recurrence in the PLX alone group and that in the PLX + PALX group (4.7% vs. 2.9%, p = 0.22). The rate of extrapelvic recurrence in the PLX alone group was significantly higher than that in the PLX + PALX group (16.1% vs. 6.2%, p < 0.0001), and the rate of para-aortic node (PAN) recurrence in the PLX alone group was also significantly higher than that in the PLX + PALX group (5.1% vs. 0.6%, p = 0.0004). In the analysis of patients who received adjuvant chemotherapy, the rate of PAN recurrence in the PLX alone group was significantly higher than that in the PLX + PALX group (9.5% vs. 1.3%, p = 0.0036).

Conclusion

PAN recurrence was a failure pattern peculiar to the PLX alone group. Adjuvant chemotherapy might not be able to replace surgical removal as a treatment for metastatic lymph nodes.     

Sentinel lymph node biopsy in the management of early-stage cervical carcinoma

Objectives

We aimed to determine the sentinel lymph node detection rates, accuracy in predicting the status of lymph node metastasis, and if pathologic ultrastaging improves the detection of micrometastases and isolated tumor cells at the time of primary surgery for cervical cancer.

Methods

A prospective, non-randomized study of women with early-stage (FIGO stage IA1 with lymphovascular space involvement — IIA) cervical carcinoma was conducted from June 2003 to August 2009. All patients underwent an intraoperative intracervical blue dye injection. Patients who underwent a preoperative lymphoscintigraphy received a 99 m Tc sulfur colloid injection in addition. All patients underwent sentinel lymph node (SLN) identification followed by a complete pelvic node and parametrial dissection. SLN were evaluated using our institutional protocol that included pathologic ultrastaging.

Results

SLN mapping was successful in 77 (95%) of 81 patients. A total of 316 SLN were identified, with a median of 3 SLN per patient (range, 0-10 SLN). The majority (85%) of SLN were located at three main sites: the external iliac (35%); internal iliac (30%); and obturator (20%). Positive lymph nodes (LN) were identified in 26 (32%) patients, including 21 patients with positive SLN. Fifteen of 21 patients (71%) had SLN metastasis detected on routine processing. SLN ultrastaging detected metastasis in an additional 6/21 patients (29%). Two patients had grossly positive LN at exploration, and mapping was abandoned. Three of 26 (12%) patients had successful SLN mapping; however, the SLN failed to identify the metastatic LN. Of these 3 false negative cases, 2 patients had a metastatic parametrial node as the only positive LN with multiple negative pelvic nodes including negative SLN. One patient with stage IA1 disease and lymphovascular invasion had unilateral SLN mapping and a metastatic common iliac LN identified on completion lymphadenectomy of the contralateral side that did not map. The 4 (5%) patients with unsuccessful mapping included 1 who had grossly positive nodes identified at the time of laparotomy; the remaining 3 occurred during each surgeon's initial SLN mapping learning phase.

Conclusion

SLN mapping in early-stage cervical carcinoma yields high detection rates. Ultrastaging improves micrometastasis detection. Parametrectomy and side-specific lymphadenectomy (in cases of failed mapping) remain important components of the surgical management of selected cases.     

Detection of sentinel lymph nodes in patients with endometrial cancer undergoing robotic-assisted staging: a comparison of colorimetric and fluorescence imaging

Objective

To retrospectively compare results from lymphatic mapping of pelvic sentinel lymph nodes (SLN) using fluorescence near-infrared (NIR) imaging of indocyanine green (ICG) and colorimetric imaging of isosulfan blue (ISB) dyes in women with endometrial cancer (EC) undergoing robotic-assisted lymphadenectomy (RAL). A secondary aim was to investigate the ability of SLN biopsies to increase the detection of metastatic disease.

Methods

Thirty-five patients underwent RAL with hysterectomy. One mL ISB was injected submucosally in four quadrants of the cervix, followed by 0.5 mL ICG [1.25 mg/mL] immediately prior to placement of a uterine manipulator. Retroperitoneal spaces were dissected for colorimetric detection of lymphatic pathways. The da Vinci^® camera was switched to fluorescence imaging and results recorded. SLN were removed for permanent analysis with ultra-sectioning, H&E, and IHC staining. Hysterectomy with RAL was completed.

Results

Twenty-seven (77%) and 34 (97%) of patients had bilateral pelvic or aortic SLN detected by colorimetric and fluorescence, respectively (p = 0.03). Considering each hemi-pelvis separately, 15/70 (21.4%) had “weak” uptake of ISB in SLN confirmed positive with fluorescence imaging. Using both methods, bilateral detection was 100%. Ten (28.6%) patients had lymph node (LN) metastasis, and 9 of these had SLN metastasis (90% sensitivity, one false negative SLN biopsy). Seven of nine (78%) SLN metastases were ISB positive and 100% were ICG positive. Twenty-five had normal LN, all with negative SLN biopsies (100% specificity). Four (40%) with LN metastasis were detected only by IHC and ultra-sectioning of SLN.

Conclusions

Fluorescence imaging with ICG detected bilateral SLN and SLN metastasis more often than ISB, and the combination resulted in 100% bilateral detection of SLN. Ultra-sectioning/IHC of SLN increased the detection of lymph node metastasis.     

Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer

Objective

Retrospective and perspective series have shown the feasibility of sentinel lymph-node (SLN) identification of pelvic nodes in endometrial cancer using a cervical injection of tracers. We designed a perspective study to assess the detection rate and diagnostic accuracy of the SLN procedure by means of hysteroscopic injection of a radiolabeled tracer in endometrial cancer patients.

Methods

Patients with endometrial cancer underwent hysteroscopic technetium injection. SLN assessment was performed intraoperatively. A systematic pelvic and paraaortic dissection was carried out thereafter. SLNs were examined by standard and immunochemistry methods. The primary endpoint was estimation of sensitivity and negative predictive value (NPV) of sentinel-node biopsy.

Results

From 2005 to 2010, 80 consecutive patients entered the study. No severe complications occurred during or after the injection or during surgical SLN biopsy. At least one SLN was detected in 76 of the 80 eligible patients. Fifty nine patients were evaluable according to the study protocol. Ten of these patients (17%) had node metastases. Thirty-three patients (56%) had SLN in the para-aortic area. NPV was 98% (95% CI 89.4-100) and sensitivity 90% (55.5-99.8).

Conclusions

SLN detection for endometrial cancer patients has a high sensitivity and NPV when injection is carried out by hysteroscopy. The occurrence of a 56% of sentinel node in paraaortic area may suggest a better sensitivity in this area using hysteroscopic injection compared to cervical injection.     

Twelve-year experience with laparoscopic radical hysterectomy and pelvic lymphadenectomy in cervical cancer

Objectives

This study aims to evaluate the morbidity, oncological outcome, and prognostic factors of cervical cancer patients treated with laparoscopic radical hysterectomy and pelvic lymphadenectomy (LRH).

Methods

Patients with cervical cancer undergoing LRH at the First People's Hospital of Foshan between August 1998 and March 2010 were enrolled in this study. The medical records were reviewed.

Results

A total of 240 patients were identified. According to FIGO stage, the number of patients with stage Ia2, Ib1, Ib2, IIa, and IIb was 2, 163, 34, 35, and 6, respectively. The conversion rate was 1.25%. Intraoperative and postoperative complications occurred in 7.08% and 9.16% patients, respectively. Other medical problems included 74 cases (30%) of bladder dysfunction. Excluding the lost cases, the median follow-up of 221 cases was 35 months, and 5-year survival rate for Ia2, Ib1, Ib2, IIa was 100%, 82%, 66%, 60%, respectively. Univariate analysis showed factors impacting the survival rate were FIGO stage > Ib1, non-squamous histologic type, deep cervical stromal invasion, and lymph node metastasis (P = 0.027, 0.023, 0.007, 0.000). The Cox-proportional hazards regression analysis indicated that only lymph node metastasis (OR = 3.827, P = 0.000) was independent of poor prognostic factor. The 5-year survival rates in Ib1 were 88% with negative lymph nodes and 59% with positive lymph nodes (P = 0.000).

Conclusions

Our data demonstrate that LRH can be performed in stage Ia2-Ib1 or less advanced node negative cervical cancer patients without compromising survival. The feasibility of LRH for more advanced patients needs further investigations.     

A comparative detail analysis of the learning curve and surgical outcome for robotic hysterectomy with lymphadenectomy versus laparoscopic hysterectomy with lymphadenectomy in treatment of endometrial cancer: a case-matched controlled study of the first one hundred twenty two patients

Goal

To determine the learning curve and surgical outcome for the first one hundred twenty-two robotic hysterectomy with lymphadenectomy patients in comparison to the first one hundred twenty-two patients who underwent the same procedure laparoscopically.

Materials and methods

An analysis of the first 122 patients who underwent a robotic assisted hysterectomy with lymphadenectomy (RHBPPALND) was compared to the first 122 patients who underwent a total laparoscopic hysterectomy with lymphadenectomy (LHBPPALND). The learning curve of the surgical procedure was determined by measuring operative time with respect to chronological order of each patient who had undergone their respective procedure. Number of lymph nodes, estimated blood loss, days of hospitalization, and complications of all patients were also analyzed and compared.

Results

The learning curve of the surgical procedure was determined by measuring operative time with respect to chronological order of each patient who had undergone their respective procedure. Data were analyzed for mean age, body mass index, operative time, estimated blood loss, lymph node retrieval and complications for both surgical procedures. The mean operative time was 147.2 ± 48.2 and 186.8 ± 59.8 for RHBPPALND and LHBPPALND respectively. The mean EBL was statistically significant at 81.1 ± 45.9 and 207.4 ± 109.4 for RHBPPALND and LHBPPALND respectively. The total number of pelvic and aortic lymph nodes was 25.1 ± 12.7 for RHBPPALND and 43.1 ± 17.8 for LHBPPALND. The number of pelvic lymph node was 19.2 ± 9.0 and 24.7 ± 11.9 for RHBPPALND and LHBPPALND. The days of hospitalization of RHBPPALND and LHBPPALND were 1.5 ± 0.9 and 3.2 ± 2.3. The number of intraoperative complications for RHBPPALND, and LHBPPALND was 1 and 7, respectively.

Conclusion

Robotic hysterectomy with lymphadenectomy has a faster learning curve in comparison to laparoscopic hysterectomy with lymphadenectomy. The adequacy of surgical staging was comparable between the two surgical methods. RHBPPALND is associated with shorter hospitalization, less blood loss and less intraoperative and major complications, and lower rate of conversion to open procedure.     

Establishing a sentinel lymph node mapping algorithm for the treatment of early cervical cancer

Objective

To establish an algorithm that incorporates sentinel lymph node (SLN) mapping to the surgical treatment of early cervical cancer, ensuring that lymph node (LN) metastases are accurately detected but minimizing the need for complete lymphadenectomy (LND).

Methods

A prospectively maintained database of all patients who underwent SLN procedure followed by a complete bilateral pelvic LND for cervical cancer (FIGO stages IA1 with LVI to IIA) from 03/2003 to 09/2010 was analyzed. The surgical algorithm we evaluated included the following: 1. SLNs are removed and submitted to ultrastaging; 2. any suspicious LN is removed regardless of mapping; 3. if only unilateral mapping is noted, a contralateral side-specific pelvic LND is performed (including inter-iliac nodes); and 4. parametrectomy en bloc with primary tumor resection is done in all cases. We retrospectively applied the algorithm to determine how it would have performed.

Results

One hundred twenty-two patients were included. Median SLN count was 3 and median total LN count was 20. At least one SLN was identified in 93% of cases (114/122), while optimal (bilateral) mapping was achieved in 75% of cases (91/122). SLN correctly diagnosed 21 of 25 patients with nodal spread. When the algorithm was applied, all patients with LN metastasis were detected; with optimal mapping, bilateral pelvic LND could have been avoided in 75% of cases.

Conclusions

In the surgical treatment of early cervical cancer, the algorithm we propose allows for comprehensive detection of all patients with nodal disease and spares complete LND in the majority of cases.     

Evaluation of a novel single-port robotic platform in the cadaver model for the performance of various procedures in gynecologic oncology

Objectives

The purpose of this protocol was to evaluate the feasibility and reproducibility of a dedicated da Vinci® single-port robotic platform in cadavers for the performance of various gynecologic oncology procedures.

Methods

Three fresh frozen female cadavers were used to evaluate the feasibility, reproducibility, and to develop the correct docking of the robotic column and trocars. Procedures performed in this training protocol included (hysterectomy, bilateral salpingo-oophorectomy, modified radical hysterectomy, six pelvic lymph node dissections, and one para-aortic node dissection). A data set was collected for each procedure, operative times were compared between cases and procedures by use of Wilcoxon rank sum test, a p-value < 0.05 was considered significant.

Results

All the procedures were technically successful with no need of additional ports or conversions to a standard laparoscopy. The median time of port insertion and BMI was 6 min range (4-10) and 33 min range (25-56) respectively. The median time for a left and right pelvic lymph node dissection was 22 min range (22-23) and 28 min range (26-38) respectively. There was significant difference in operating times for symmetrical procedures (pelvic lymphadenectomy), p = 0.049.

Conclusion

This preliminary data demonstrates that the performance of various oncology procedures using the new da Vinci® single-site robotic platform is feasible, and more importantly, reproducible in the cadaver model.     

A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial cancer

Objective

The study objective was to compare the ability to detect sentinel lymph nodes (SLNs) in women with endometrial cancer (EC) or complex atypical hyperplasia (CAH) using fluorometric imaging with indocyanine green (ICG) versus colorimetric imaging with isosulfan blue (ISB).

Methods

Women underwent SLN mapping, with either ISB or ICG, during robotic-assisted total laparoscopic hysterectomy (RA-TLH) from September 2012 to March 2014. SLNs were submitted for permanent pathologic analysis. Completion lymphadenectomy and ultrastaging were performed according to institutional protocols.

Results

RA-TLH and SLN mapping was performed in 71 women; 64 had EC (64) and 7 had CAH. Age, body mass index (BMI), stage and tumor characteristics were similar in the ICG versus the ISB cohorts. Overall, SLNs were identified bilaterally (62.0%), unilaterally (21.1%), or neither (16.9%), and in 103 of 142 hemi-pelvises (72.5%). The mean number of SLNs retrieved per hemipelvis was 2.23(SD 1.7). SLNs were identified in the hypogastric (76.8%), external iliac (14.2%), common iliac (4.5%) and paraaortic (4.5%) regions. ICG mapped bilaterally in 78.9% of women compared with 42.4% of those injected with ISB (p = 0.02). Five women (7%) had positive lymph nodes, all identified by the SLN protocol (false negative rate: 0%). On multivariate analysis, BMI was negatively correlated with bilateral mapping success (p = 0.02). When stratified by dye type, the association with BMI was only significant for ISB (p = 0.03).

Conclusions

Fluorescence imaging with ICG may be superior to colorimetric imaging with ISB in women undergoing SLN mapping for endometrial cancer. SLN mapping success is negatively associated with increasing patient BMI only when ISB is used.     

Randomized comparison of near-infrared fluorescence lymphatic tracers for sentinel lymph node mapping of cervical cancer

Objective

Near-infrared fluorescence imaging using indocyanine green (ICG) has recently been introduced as a novel technique for sentinel lymph node (SLN) mapping in early-stage cervical cancer. Although preclinical research has shown that ICG adsorbed to human serum albumin (ICG:HSA) improves its performance, the need for HSA has not yet been confirmed in cervical cancer patients. The current randomized study aims to determine whether ICG:HSA offers advantages over using ICG alone.

Methods

Eighteen consecutive early-stage cervical cancer patients scheduled to undergo pelvic lymphadenectomy were included. Prior to surgery, 1.6 mL of 500 μM ICG:HSA or 500 μM ICG alone was injected transvaginally in 4 quadrants around the tumor. The Mini-FLARE imaging system was used for intraoperative NIR fluorescence detection and quantitation.

Results

SLNs were identified intraoperatively in 78% of the patients. Patient and tumor characteristics were equally distributed over both treatment groups. No significant difference in signal-to-background ratio (9.3 vs. 10.1, P = .72) or average number of detected SLNs (2.9 vs 2.7, P = .84) was found between the ICG:HSA group and the ICG alone group, respectively.

Conclusions

In conclusion, this double-blind, randomized trial showed no advantage of ICG:HSA over ICG alone for the SLN procedure in early-stage cervical cancer. Further optimization is required to improve the intraoperative detection rate.     

Uterine leiomyosarcomas: Tumor size, mitotic index, and biomarkers Ki67, and Bcl-2 identify two groups with different prognosis

Background

Prognostic factors for uterine leiomyosarcomas are not well established. Although most tumors are associated with poor prognosis even when apparently confined to the uterus (stage I), some cases that exhibited morphologic features of malignancy had prolonged survival.

Methods

Using tissue microarrays of 84 uterine leiomyosarcomas, we investigated conventional clinico-pathologic parameters, including International Federation of Gynecology and Obstetrics (FIGO) stage, together with expression of Ki67, p53, p16, and Bcl-2, attempting to distinguish leiomyosarcomas with different prognosis. The rate of CD163 immunoreactive tumor macrophages was also investigated.

Results

Tumor size and mitotic index were significant prognostic factors by univariate (p = 0.018 and p = 0.003, respectively) and multivariate (p = 0.006 and p = 0.001) analyses. Of the biomarkers investigated, only Ki67 immunoreaction was significant by univariate analysis and was associated with adverse prognosis (p = 0.01). However, combination of tumor size, mitotic index, Ki67, and Bcl-2 worked even better. Using these 4 parameters, unsupervised hierarchical clustering identified 2 groups of tumors with different prognosis (p = 0.001): group 1 consisted mostly of smaller leiomyosarcomas (< 10 cm) with mitotic index < 20 MF/10 HPF, negative Ki67, and positive or negative Bcl-2 immunostaining. These tumors were associated with better prognosis. In contrast, group 2 leiomyosarcomas which were mostly ≥ 10 cm in diameter had higher mitotic index (≥ 20 MF/10 HPF), and were positive for Ki67 and negative for Bcl-2 had worse prognosis. Also, the number of CD163-macrophages was greater in group 2 than group 1 (p = 0.007).

Conclusions

Tumor size and mitotic index are morphologic predictors of malignancy in uterine leiomyosarcomas. Combination of tumor size, mitotic index, Ki67, and Bcl-2 protein expression allows distinguishing 2 groups of leiomyosarcomas with different survival. Leiomyosarcomas associated with poor outcome had a higher number of CD163 stromal macrophages.     

The insulin resistant subphenotype of polycystic ovary syndrome: clinical parameters and pathogenesis

Objective

This study was undertaken to compare clinical and biochemical characteristics of the insulin resistant (IR) and non-IR subphenotypes of polycystic ovary syndrome (PCOS).

Study design

Infertile PCOS women were classified as IR (n = 32) or non-IR (n = 46) on the basis of fasting glucose and insulin levels. The incidence of acanthosis nigricans (AN), hirsutism, and ovulation in response to clomiphene citrate (CC) was compared between the 2 groups, along with serum levels of gonadotropins, and sex steroids. Blood samples from 28 PCOS patients and 8 controls were analyzed by enzymatic immunoassay for autophosphorylated insulin receptor (APIR) and total insulin receptor (TIR) content.

Results

Insulin resistance was associated with obesity (odds ratio [OR] = 3.5, P < .05), AN (OR = 6.0, P < .05), hirsutism (OR = 3.1, P < .05), and resistance to CC (OR = 5.0, P < .05). Mean levels of LH, LH/FSH ratios, and testosterone were lower in women with IR (11.5 ± 6.8 mIU/mL, 2.0 ± 1.0, and 56.6 ± 29.0 ng/dL, respectively) compared with women without IR (15.0 ± 13.4 mIU/mL, 2.4 ± 1.5, and 72.5 ± 29.8 ng/dL, respectively) (P < .05). Mean APIR/TIR ratios in IR women were lower than in non-IR women (P < .05 at 100 nmol/L of insulin) and controls (P < .01 at 1, 10 and 100 nmol/L insulin).

Conclusion

Patients with IR are more likely to be obese and have AN, hirsutism, resistance to CC, and lower LH, LH/FSH ratios, and testosterone levels. Furthermore, IR patients appear to have defective autophosphorylation of the insulin receptor, a key element in insulin action, and a possible mechanism for IR in PCOS.     

Sentinel lymph node biopsy in endometrial cancer: meta-analysis of 26 studies

Objective

The validity of the sentinel lymph node (SLN) procedure for the assessment of nodal status in patients with endometrial cancer is unclear. We aimed to assess the diagnostic performance of this procedure.

Methods

We searched the PubMed and Embase databases for studies published before June 1, 2011. Eligible studies had a sample size of at least 10 patients, and reported the detection rate and/or sensitivity of the SLN biopsy.

Results

We identified 26 eligible studies, which included 1101 SLN procedures. The overall weighted-mean number of harvested SLNs was 2.6. The detection rate and the sensitivity were 78% (95% confidence interval [CI] = 73%-84%) and 93% (95% CI = 87%-100%), respectively. Significant between-study heterogeneity was observed in the analysis of the detection rate (I-squared statistic, 80%). The use of pericervical injection was correlated with the increase of the detection rate (P = 0.031). The hysteroscopic injection technique was associated with the decrease of the detection rate (P = 0.045) and the subserosal injection technique was associated with the decrease of the sensitivity (P = 0.049), if they were not combined with other injection techniques. For the detection rate, significant small-study effects were noted (P < 0.001).

Conclusions

Although SLN biopsy has shown good diagnostic performance in endometrial cancer, such performance should be interpreted with caution because of significant small study effects. Current evidence is not yet sufficient to establish the true performance of SLN biopsy in endometrial cancer.     

Tracer injection sites and combinations for sentinel lymph node detection in patients with endometrial cancer

Objective

The aim of the present study was to clarify the most effective combination of injected tracer types and injection sites in order to detect sentinel lymph nodes (SLNs) in early endometrial cancer.

Patients and methods

The study included 100 consecutive patients with endometrial cancer treated at Tohoku University Hospital between June 2001 and December 2012. The procedure for SLN identification entailed either radioisotope (RI) injection into the endometrium during hysteroscopy (55 cases) or direct RI injection into the uterine cervix (45 cases). A combination of blue dye injected into the uterine cervix or uterine body intraoperatively in addition to preoperative RI injection occurred in 69 of 100 cases. All detected SLNs were recorded according to the individual tracer and the resultant staging from this method was compared to the final pathology of lymph node metastases including para-aortic nodes.

Results

SLN detection rate was highest (96%) by cervical RI injection; however, no SLNs were detected in para-aortic area. Para-aortic SLNs were detected only by hysteroscopic RI injection (56%). All cases with pelvic lymph node metastases were detected by pelvic SLN biopsy. Isolated positive para-aortic lymph nodes were detected in 3 patients. Bilateral SLN detection rate was high (96%; 26 of 27 cases) by cervical RI injection combined with dye.

Conclusion

RI injection into the uterine cervix is highly sensitive in detection of SLN metastasis in early stage endometrial cancer. It is a useful and safe modality when combined with blue dye injection into the uterine body.     

Para-aortic lymphadenectomy for primary fallopian tube cancer

Objective

To investigate the topography of lymph node spread and the need for para-aortic lymphadenectomy in primary fallopian tube cancer (PFTC).

Methods

Twenty-six women were diagnosed with PFTC at Cheil General Hospital and Women's Healthcare Center, Seoul, Korea, between March 1992 and November 2009. Of the 26 patients, we retrospectively analyzed 15 patients who underwent complete staging surgery, including bilateral pelvic and para-aortic lymphadenectomy.

Results

The median follow-up period was 57.9 months (range, 3-185 months) and the 5-year survival rate was 86.3%. Five (33.3%) patients were diagnosed with FIGO stage I, 1 (6.7%) with stage II, and 9 (60%) with stage III cancer. The median number of lymph nodes removed was 53.8 (range, 18-106 nodes). Four (26.7%) patients had nodal involvement: 2 patients with para-aortic lymph node involvement and 2 patients with both pelvic and para-aortic lymph node involvement. None of the patients was positive for pelvic lymph nodes alone.

Conclusion

A comprehensive para-aortic lymphadenectomy was necessary for accurate staging in PFTC.     

Laparoscopic Sentinel Node Mapping in Endometrial Cancer After Hysteroscopic Injection of Indocyanine Green

Study Objective

To report the detection rate (DR) of sentinel lymph nodes (SLNs) in endometrial cancer (EC) patients after hysteroscopic injection of indocyanine green (ICG) and laparoscopic near-infrared (L-NIR) fluorescence mapping.