Evaluation of endometrial carcinoma on magnetic resonance imaging.

Our aims were to assess diagnostic performance of T2-weighted (T2W) and dynamic gadolinium-enhanced T1-weighted (T1W) magnetic resonance imaging (MRI) in the preoperative assessment of myometrial and cervical invasion by endometrial carcinoma and to identify imaging features that predict nodal metastases. Two radiologists retrospectively reviewed MR images of 96 patients with endometrial carcinoma. Tumor size, depth of myometrial and cervical invasion, and nodal enlargement were recorded and then correlated with histology. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the identification of any myometrial invasion (superficial or deep) were 0.94, 0.50, 0.93, 0.55 on T2W and 0.92, 0.50, 0.92, 0.50 on dynamic T1W, and for deep myometrial invasion were 0.84, 0.78, 0.65, 0.91 on T2W and 0.72, 0.88, 0.72, 0.88 on dynamic T1W. The sensitivity, specificity, PPV and NPV for any cervical invasion (endocervical or stromal) were 0.65, 0.87, 0.57, 0.90 on T2W and 0.50, 0.90, 0.46, 0.92 on dynamic T1W, and for cervical stromal involvement were 0.69, 0.95, 0.69, 0.95 on T2W and 0.50, 0.96, 0.57, 0.95 on dynamic T1W. Leiomyoma or adenomyosis were seen in 73% of misdiagnosed cases. Sensitivity and specificity for the detection of nodal metastases was 66% and 73%, respectively. Fifty percent of patients with cervical invasion on MRI had nodal metastases. In conclusion, MRI has a high sensitivity for detecting myometrial invasion and a high NPV for deep invasion. MRI has a high specificity and NPV for detecting cervical invasion. Dynamic enhancement did not improve diagnostic performance. MRI may allow accurate categorization of cases into low- or high-risk groups ensuring suitable extent of surgery and adjuvant therapy.

Surgical morbidity associated with radical trachelectomy and radical hysterectomy.

OBJECTIVES: To examine intra-operative, short and longer term morbidity associated with Radical Trachelectomy (RT) within our cohort of patients, compared with conventional Radical Hysterectomy (RH). METHODS: A retrospective case note review comprising 29 RT and 50 RH patients. Patients who required adjuvant treatment were excluded. Operative data, short-term and long-term complications were recorded. Long-term problems were included only if they had been of persistent nature. RESULTS: The median age and follow up period for the RH group were 40 years and 60 months and for RT group 30.5 years and 25 months. There were significant differences between RH and RT groups in median operative time (260 versus 187 min), blood loss (1000 versus 400 ml), transfusion requirement (75% versus 12%), analgesic requirement (8 versus 3.5 days) and hospital stay (11 versus 6 days). Bladder hypotonia requiring prolonged catheterisation was more frequent in RH group (P = 0.004). There was no apparent difference in psychosexual problems between the two groups (17 versus 16%). Complications of deep dyspareunia (P = 0.009), excessive vaginal discharge (P = 0.01), and upper thigh parasthesia (P = 0.05) were noted to be significantly higher in the RT group. Specific problems encountered in the RT group included; dysmenorrhea (24%), irregular menstruation (17%), recurrent candidiasis (14%), cervical suture problems (14%), isthmic stenosis (10%) and prolonged amenorrhea (7%). CONCLUSION: RT is associated with less operative and short-term morbidity compared with conventional RH. In addition to specific complications associated with RT, in our experience, there are long-term morbidities that are not as commonly observed in RH.

Can MRI rule out bladder and rectal invasion in cervical cancer to help select patients for limited EUA?

OBJECTIVES: Although invasion of the bladder or rectum is rare in cervical carcinoma, endoscopic assessment of both organs is part of the standard FIGO clinical staging system, with associated increase in cost and risk of complications. Our objective was to evaluate whether MRI could be used to select patients who did not require invasive staging of the bladder or rectum. METHODS: Two observers, blinded to the results of cystoscopy and endoscopic examination of the rectum, retrospectively reviewed the MR images of 112 patients with cervical carcinoma. A 5-point invasion score was used to determine bladder and rectal invasion (1 = no invasion, 5 = definite invasion). A confidence score of 3 or above was used to identify patients with possible bladder or rectal involvement. The results of cystoscopy and endoscopic examination of the rectum were recorded and correlated with the MR findings. RESULTS: MRI was negative for both bladder and rectal invasion in 94/112 patients. Cystoscopy and endoscopic examination of the rectum were confirmed to be normal in all 94 cases. MRI identified 12 patients with possible rectal invasion, 2 confirmed at endoscopy. MRI identified 14 patients with possible bladder invasion, one confirmed at cystoscopy. Using a low threshold cut-off score of >3 to predict invasion resulted in a 100% negative predictive value (NPV) in detection of bladder and rectal invasion. CONCLUSION: The absence of bladder or rectal invasion can be diagnosed with sufficient confidence using an MRI scoring system to safely obviate the need for invasive cystoscopic or endoscopic staging in the majority of patients with cervical cancer. This could potentially lead to a reduction in staging costs and morbidity.

Elevated tumour markers prior to complete tumour removal in patients with pseudomyxoma peritonei predict early recurrence.

OBJECTIVE: To assess the potential value of pre-operative CEA, CA 125 and CA 19-9 in identifying Pseudomyxoma peritonei (PMP) patients at risk of recurrence following complete cytoreductive surgery and intraperitoneal chemotherapy. METHOD: Between March 1996 and October 2001, 35 patients, with documented pre-operative tumour marker measurements, underwent complete cytoreduction. Outcome in the 32 survivors was recorded. RESULTS: Median age was 53 years (range: 32-74). There were 17[53%] females. In 9/32[28%] all tumour markers were normal. The most common abnormality was elevated CEA level in 14/32[44%]. Median follow up was 23 months (range: 11-74). Recurrence was detected in 8/32[25%]. The 2-year recurrence free interval was 53% in those with elevated CEA compared with 94% with normal CEA. The 2-year disease free intervals were 100% in 9 patients with normal preop markers compared with 66% for the group with at least one abnormal marker. CONCLUSION: PMP patients with elevated CEA, or more than one abnormal serum tumour maker, are at risk of developing recurrent disease.

Assessment of the depth of myometrial invasion in stage I endometrioid endometrial cancer using pancytokeratin immunohistochemistry.

BACKGROUND: There is a strong correlation between disease mortality and the depth of myometrial invasion in stage I endometrial cancer (EC). Current assessment of the depth of invasion relies on light microscopy. Tumor cells can evade detection by light microscopy if they are vastly outnumbered by myometrial cells. Immunohistochemical (IHC) techniques against pancytokeratins (PCKs) have a great potential in the detection of such isolated cells. OBJECTIVES: To investigate the application of IHC techniques in the identification of isolated infiltrating tumor cells within myometrium and assess its significance in clinically stage I EC. METHODS: A single representative tissue block containing the deepest myometrial invasion by the tumor was selected for 90 patients with stage I EC. Sections from each block were immunostained in accordance with established streptavidin-biotin peroxidase method using a mouse monoclonal antikeratin clone AE1/AE3. Myometrium was re-examined to identify deeper myometrial invasion that had escaped detection on hematoxylin and eosin (H&E) section. The clinical records were reviewed, and following data were collected: age, race, parity, presentation, associated medical disorders (obesity, diabetes, and hypertension), use of tamoxifen or hormone replacement therapy, menopausal state, recurrence, and survival. RESULTS: Of 90 cases, deeper myometrial invasion was detected on IHC sections in seven cases (7.7%). In five of these seven cases, isolated tumor cells surrounded by inflammatory cells were noted 0.2-1.2 mm deeper within the myometrium than that detected by H&E staining. In the remaining two cases, the deeper extension seen was the result of examining serial levels through the tumor block; in these cases, deeper infiltration should have been apparent on H&E sections. Follow-up data was available in 72 of the 90 cases. A trend was noted between the presence of isolated tumor cells deeper within myometrium on IHC and tumor recurrence (P = 0.056). The 2-year recurrence-free survival was 40% for the group with IHC evidence of deeper invasion compared with 89% for the group without (P = 0.005). Similarly, analysis of cause-specific and overall survival revealed significant differences between the two groups (P = 0.038 and P = 0.026, respectively). CONCLUSIONS: In this study, we have shown that it is possible to identify deeper level of myometrial invasion by tumor cells using an IHC technique. IHC-detected deeper invasion is an uncommon event and may be a feature of more aggressive tumors with greater potential for recurrence and lower survival.

Clinical value of immunohistochemically detected lymphovascular invasion in endometrioid endometrial cancer.

INTRODUCTION: Lymphovascular Invasion (LVSI) of tumour cells is marked as an important step in the process of tumour metastases and is an important prognostic factor in Endometrial Cancer (EC). Currently, the standard method for assessing LVSI is light microscopic examination of H&E stained sections. Tumour cells within lymphovascular spaces can evade detection on H&E staining if they are present in very small numbers or surrounded by a greater number of circulating cells. Dual immunostaining for epithelial and endothelial cell markers cell markers has been shown to increase detection rate of LVSI significantly. OBJECTIVES: To investigate the clinical significance of LVSI as detected by H&E (LVSI-H&E) and immunohistochemically (LVSI-IHC) in clinically stage I endometrioid EC patients. Methods. Single representative section of 90 patients with stage I endometriod EC were immunostained in accordance with established streptavidin-biotin peroxidase method using a mouse monoclonal pancytokeratin (PCK), clone AE1/AE3 and CD31 endothelial cell marker. The H&E sections and their corresponding immunostained sections were re-examined to identify LVSI. Clinical records were available on 72 patients. The following data were collected: age, race, parity, presentation, associated medical disorders (obesity, diabetes and hypertension), use of Tamoxifen or HRT, menopausal state, recurrence and survival. RESULTS: Overall, LVSI was present in 45 (50%) cases and absent in 45 (50%) cases on IHC, as compared with 17 (19%) and 73 (81%) cases, respectively, on H&E. Statistical analysis revealed significant association between LVSI-H&E and depth of myometrial invasion (P < 0.0001). The median follow-up period was 161 months (range 5-207 months). During the follow-up period, six of 14 cases with evidence of LVSI-H&E presented with recurrence as opposed to six of 58 patients with no evidence (OR = 6.26, 95%: CI = 1.3-30.6). There was a significant association between tumour recurrence rate and LVSI-H&E (P = 0.01). The 5-year recurrence-free survival was 54% for the group with H&E evidence of LVSI (95%: CI = 44-64%) compared with 89% for the group without (95%: CI = 82-97%). There was a significant difference in the recurrence-free survival between the two groups (Chi-square = 6.96, P = 0.008). In contrast, LVSI-IHC was found to be significantly associated only with high-grade tumours (P = 0.01) and survival analysis revealed no statistically significant association with recurrence or survival. CONCLUSIONS: LVSI-H&E in stage I EC remains an important predictive factor of recurrent disease and reduced disease-free interval. Immunohistochemically detected LVSI is a common event, associated with tumour grade and appears to be of no statistically significant clinical value.

Detection of tumour lymphovascular space invasion using dual cytokeratin and CD31 immunohistochemistry.

BACKGROUND: Lymphovascular space invasion (LVSI) is an important step in the complex process of tumour metastasis. Various methods have been used in the past to improve the histological detection of LVSI. AIMS: To develop a sensitive immunohistochemical method for the detection of LVSI. METHODS: Paraffin wax blocks from 108 patients who had undergone hysterectomy for stage I endometrial cancer were retrieved. Dual immunostaining for pancytokeratin and the CD31 endothelial cell marker was carried out on 4 micro m sections cut from these bocks and compared with conventional haematoxylin and eosin staining. RESULTS: The detection rate for LVSI increased threefold compared with conventional haematoxylin and eosin staining in the test group. CONCLUSION: This finding suggests that LVSI is a much more common phenomenon than previously thought and questions current understanding of tumour metastasis.