Mahmoud A Khalifa

University of Toronto, Toronto, Ontario, Canada

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Publications (55)118.88 Total impact

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    ABSTRACT: Background:The histology and grade of endometrial cancer are important predictors of disease outcome and of the likelihood of nodal involvement. In most centres, however, surgical staging decisions are based on a preoperative biopsy. The objective of this study was to assess the concordance between the preoperative histology and that of the hysterectomy specimen in endometrial cancer.Methods:Patients treated for endometrial cancer during a 10-year period at a tertiary cancer centre were identified from a prospectively collected pathological database. All pathology reports were reviewed to confirm centralised reporting of the original sampling or biopsy specimens; patients whose biopsies were not reviewed by a dedicated gynaecological pathologist at the treating centre were excluded. Surgical pathology data including histology, grade, depth of myometrial invasion, cervical stromal involvement and lymphovascular space invasion (LVSI) as well as preoperative histology and grade were collected. Preoperative and final tumour cell type and grade were compared and the distribution of other high-risk features was analysed.Results:A total of 1329 consecutive patients were identified; 653 patients had a centrally reviewed epithelial endometrial cancer on their original biopsy, and are included in this study. Of 255 patients whose biopsies were read as grade 1 (G1) adenocarcinoma, 45 (18%) were upgraded to grade 2 (G2) on final pathology, 6 (2%) were upgraded to grade 3 (G3) and 5 (2%) were read as a non-endometrioid high-grade histology. Overall, of 255 tumours classified as G1 endometrioid cancers on biopsy, 74 (29%) were either found to be low-grade (G1-2) tumours with deep myometrial invasion, or were reclassified as high-grade cancers (G3 or non-endometrioid histologies) on final surgical pathology. Despite these shifts, we calculate that omitting surgical staging in preoperatively diagnosed G1 endometrioid cancers without deep myometrial invasion would result in missing nodal involvement in only 1% of cases.Conclusions:Preoperative endometrial sampling is only a modest predictor of surgical pathology features in endometrial cancer and may underestimate the risk of disease spread and recurrence. In spite of frequent shifts in postoperative vs preoperative histological assessment, the predicted rate of missed nodal metastases with a selective staging policy remains low.British Journal of Cancer advance online publication, 24 December 2013; doi:10.1038/bjc.2013.766
    British Journal of Cancer 12/2013; 110(3). DOI:10.1038/bjc.2013.766 · 5.08 Impact Factor
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    ABSTRACT: : The question whether the appendix should be removed at the time of surgery for apparent early-stage ovarian cancer is controversial. Removal of the appendix in the setting of mucinous histologic type is primarily driven by the existing challenge to distinguish between primary ovarian mucinous neoplasm and metastatic appendiceal carcinoma to the ovary. To evaluate the value of an appendectomy at the time of surgery for ovarian mucinous borderline tumors or carcinoma. A retrospective single institute-based study was conducted. We identified patients who were operated on by a gynecologic oncologist for an abnormal pelvic mass, which was diagnosed as mucinous adenocarcinoma or mucinous borderline tumor between January 2000 and December 2010. Cases were included in the study if an appendectomy was performed at the time of initial surgery. Seventy-seven cases meeting the inclusion criteria were identified. The ovarian mass of 11 patients (14%) was diagnosed as metastatic appendiceal carcinoma involving the ovary. Evidence of metastatic disease, abnormal-looking appendix, or pseudomyxoma peritonei, were identified at the time of surgery for all of these cases. The condition of 30 patients (39%) and 36 patients (47%) were diagnosed as mucinous borderline ovarian tumor and invasive or microinvasive mucinous ovarian carcinoma, respectively. Evidence of metastasis from the ovary to the appendix was not identified in any of the cases. Our data suggest that in cases of apparent early-stage mucinous ovarian borderline tumors and cancer, adding an appendectomy at the time of surgery is not warranted in the absence of a grossly abnormal appendix or evidence of metastatic disease.
    International Journal of Gynecological Cancer 07/2013; 23(7). DOI:10.1097/IGC.0b013e31829b7dca · 1.94 Impact Factor
  • American Journal of Clinical Pathology 05/2013; 139(5):694. DOI:10.1309/AJCPAKGFVRL8UXNX · 2.88 Impact Factor
  • Vlad Maksymov, Michael Hogan, Mahmoud A Khalifa
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    ABSTRACT: Assessment of a pancreaticoduodenectomy specimen by pathologists requires specialized knowledge of anatomy. Standardized assessment, description and documentation of the retroperitoneal margin are crucial for the accurate interpretation of studies evaluating adjuvant therapy for pancreatic cancer patients. Twenty-five patients who underwent a pancreaticoduodenectomy for pancreatic adenocarcinomas had their pathological specimens examined prospectively, using an anatomical-based mapping approach. All margins, including the bile duct, pancreatic neck, superior mesenteric artery, superior mesenteric vein and posterior surface of the uncinate process, were microscopically examined in their entirety. The assessment of an R1 margin in terms of distance was assessed in two ways: first defining it as a tumour at the margin or secondary as tumour within 1 mm (1 mm rule). If the existing College of American Pathologists recommendations were applied (assessing only the bile duct, pancreatic neck and superior mesenteric artery margins), a R1 status would be achieved in only 9 of 25 patients. Extending the examination by assessment and reporting of the entire retroperitoneal resection margin, including the Superior Mesenteric Vein margin and the Posterior surface of the uncinate process margin, increased the number of patients with a R1 resection to 14 out of 25. Applying the 1-mm rule further increased the number of patient with a R1 resection to 20 of 25 patients. The above findings illustrate that different approaches to the assessment and reporting of the retroperitoneal margin can change the results and adversely affect the final statistics used in pancreatic cancer studies and clinical trials.
    HPB 03/2013; 15(3):218-23. DOI:10.1111/j.1477-2574.2012.00561.x · 2.05 Impact Factor
  • Gynecologic Oncology 03/2012; 125:S75. DOI:10.1016/j.ygyno.2011.12.180 · 3.69 Impact Factor
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    ABSTRACT: A shift toward a disease-based therapy designed according to patterns of failure and likelihood of nodal involvement predicted by pathologic determinants has recently led to considering a selective approach to lymphadenectomy for endometrial cancer. Therefore, it became critical to examine reproducibility of diagnosing the key determinants of risk, on preoperative endometrial tissue samples as well as the concordance between preoperative and postresection specimens. Six gynaecologic pathologists assessed 105 consecutive endometrial biopsies originally reported as positive for endometrial cancer for cell type (endometrioid versus nonendometrioid), tumor grade (FIGO 3-tiered and 2-tiered), nuclear grade, and risk category (low risk defined as endometrioid histology, grade 1 + 2 and nuclear grade <3). Interrater agreement levels were substantial for identification of nonendometrioid histology (κ = 0.63; SE = 0.025), high tumor grade (κ = 0.64; SE = 0.025), and risk category (κ = 0.66; SE = 0.025). The overall agreement was fair for nuclear grade (κ = 0.21; SE = 0.025). There is agreement amongst pathologists in identifying high-risk pathologic determinants on endometrial cancer biopsies, and these highly correlate with postresection specimens. This is ascertainment prerequisite adaptation of the paradigm shift in surgical staging of patients with endometrial cancer.
    Obstetrics and Gynecology International 02/2012; 2012:414086. DOI:10.1155/2012/414086
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    Reda S Saad, Zeina Ghorab, Mahmoud A Khalifa, Mei Xu
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    ABSTRACT: CDX2 is a nuclear homeobox transcription factor that belongs to the caudal-related family of CDX homeobox genes. The gene encoding CDX2 is a nonclustered hexapeptide located on chromosome 13q12-13. Homeobox genes play an essential role in the control of normal embryonic development. CDX2 is crucial for axial patterning of the alimentary tract during embryonic development and is involved in the processes of intestinal cell proliferation, differentiation, adhesion, and apoptosis. It is considered specific for enterocytes and has been used for the diagnosis of primary and metastatic colorectal adenocarcinoma. CDX2 expression has been reported to be organ specific and is normally expressed throughout embryonic and postnatal life within the nuclei of epithelial cells of the alimentary tract from the proximal duodenum to the distal rectum. In this review, the authors elaborate on the diagnostic utility of CDX2 in gastrointestinal tumors and other neoplasms with intestinal differentiation. Limitations with its use as the sole predictor of a gastrointestinal origin of metastatic carcinomas are also discussed.
    11/2011; 3(11):159-66. DOI:10.4240/wjgs.v3.i11.159
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    ABSTRACT: Adult granulosa cell tumors are usually diagnosed at an early stage. However, most patients with advanced or recurrent disease will die of the disease due to limited treatment options. Data on the immunohistochemical characteristics of recurrent granulosa cell tumors are limited. The aim of this study was to compare the immunohistochemical profile of primary and recurrent adult granulosa cell tumors. Special emphasis is given to epidermal growth factor receptor expression because it represents a potential marker for targeted therapy with monoclonal antibodies.Inhouse granulosa cell tumor cases accessioned between 1999 and 2008 were retrieved and reviewed according to the WHO classification. Cases were studied by immunohistochemistry using a panel of 11 antibodies. Immunostaining was semiquantitatively recorded.We have studied 20 cases of primary and 20 cases of recurrent adult granulosa cell tumors from 31 patients. Immunohistochemistry showed that primary tumors were positive for inhibin in 100%, calretinin 100%, CD56 90%, CD99 40%, D2-40 35% and low molecular weight keratin 30%. Recurrences were positive for inhibin 90%, calretinin 85%, CD56 95%, CD99 65%, D2-40 55% and low molecular weight keratin 10%. Recurrences were positive for inhibin 90%, calretinin 85%, CD56 95%, CD99 65%, D2-40 55%, and low molecular weight keratin 10%. All primary and recurrent tumors were negative for melan-A, CD10, and epithelial membrane antigen. Epidermal growth factor receptor was positive in 65% of primary tumors and 85% of recurrences. Ki67 index was higher in recurrence specimens. The immunoprofile of primary and recurrent adult granulosa cell tumors is highly concordant. Similar to primary tumors, almost all recurrent cases exhibited evidence of sex cord lineage. The lack of specific markers emphasizes the need for evaluation using a panel of antibodies. Special attention should be paid when low molecular-weight keratin is used as part of a panel differentiating granulosa cell tumors from carcinomas, as a significant proportion of the former are positive. Although targeted therapies directed against epidermal growth factor receptor have not been tested yet in the setting of advanced or recurrent granulosa cell tumors, the high level of epidermal growth factor receptor expression is important as we step to an era of advanced biolabeled imaging techniques.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 11/2011; 31(1):80-90. DOI:10.1097/PGP.0b013e318224e089 · 2.07 Impact Factor
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    ABSTRACT: Undifferentiated carcinoma of the endometrium is a rare neoplasm, which, when involving the cervix, raises a question about its origin. Diffuse p16 positivity of uterine cancers is usually interpreted as a surrogate marker for high-risk human papilloma virus and favors cervical origin. In this study, we investigated the expression of cytokeratin 7 (CK7), monoclonal carcinoembryonic antigen (mCEA), estrogen receptor (ER), vimentin, and p16 in 28 cases of undifferentiated endometrial carcinoma, 20 high-grade endometrioid adenocarcinomas, and 50 cervical adenocarcinomas. Staining was considered positive when it was cytoplasmic for CK7, mCEA, and vimentin, nuclear for ER, and both nuclear and cytoplasmic for p16. Percentages of cells staining were recorded as follows: negative (0%-5%), 1+ (6%-25%), 2+ (26%-50%), 3+ (51%-75%), and 4+ (>75%). P16 was considered positive if it stained more than 75% of the tumor cells. Diffuse/strongly positive staining for p16 was seen in 40/50 (80%) cases of cervical adenocarcinoma and 14/28 (50%) cases of undifferentiated endometrial carcinoma. In high-grade endometrioid adenocarcinoma, staining was mainly patchy. CK7, mCEA, ER, progesterone receptor, and vimentin staining in undifferentiated endometrial carcinoma was as follows: 10/28 (36%), 4/28 (14%), 21/28 (75%), 23/28 (82%), and 26/28 (93%), respectively; for high-grade endometrioid carcinoma: 20/20 (100%), 1/20 (5%), 17/20 (85%), 18/20 (90%), and 19/20 (95%); for endocervical adenocarcinoma: 50/50 (100%), 45/50 (90%), 9/50 (18%), 8/50 (16%), and 6/50 (12%), respectively. Our data indicate that p16 may play a role in the tumorigenesis of a subset of undifferentiated endometrial carcinoma. In the setting of p16 positivity, undifferentiated endometrial carcinomas are more likely to be ER, progesterone receptor, and vimentin positive and mCEA negative when compared with endocervical adenocarcinomas. Distinction between undifferentiated endometrial carcinoma and endocervical adenocarcinoma, both of which can share diffuse p16 expression, should rely on detection of human papilloma virus in the latter.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 11/2011; 31(1):57-65. DOI:10.1097/PGP.0b013e318223118a · 2.07 Impact Factor
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    ABSTRACT: Recent studies questioned "classical" concepts in trauma care, including whether disseminated intravascular coagulation (DIC) occurs in trauma. The knowledge on trauma DIC is limited to few studies built on diagnosing DIC with laboratory-based scores. This study explores whether DIC diagnosed by the well-established ISTH (International Society for Thrombosis and Hemostasis) score is corroborated by anatomopathologic findings. Prospective observational cohort study of severely injured (ISS ≥ 16) patients. DIC was diagnosed by the ISTH score throughout the first 24 hours after trauma. All organs surgically removed within 24 hours of trauma were reviewed by two independent pathologists. All autopsy reports were reviewed. Of 423 patients enrolled, ∼11% had "overt DIC" and 85% had "suggestive of non-overt DIC" scores throughout the 24 hours after trauma. "Overt DIC" patients had higher mortality and worse bleeding, receiving more blood and plasma transfusions. One hundred and sixteen patients underwent surgery within 24 hours of trauma, and all 40 excised organs were reviewed by two pathologists. Twenty-seven autopsies reports were reviewed. No anatomopathologic evidence of DIC was identified in the first 24 hours, even after additional histochemical staining. d-dimer was universally elevated after trauma. Common DIC features: platelet count, fibrinogen, clotting time, and factor VIII drop were mostly absent. d-dimer has a disproportional participation in trauma DIC scores. Within 24 hours of trauma, most severely injured patients have DIC scores "suggestive for" or of "overt DIC" but no anatomopathologic evidence of DIC. Considering pathologic findings as the gold standard diagnosis, then DIC is exceptionally uncommon and the ISTH score should not be used for trauma.
    The Journal of trauma 11/2011; 71(5 Suppl 1):S441-7. DOI:10.1097/TA.0b013e318232e688 · 2.35 Impact Factor
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    ABSTRACT: Undifferentiated (anaplastic) carcinoma of the pancreas with osteoclast-like giant cells is exceedingly rare. The prognosis of undifferentiated carcinoma is worse than that of poorly differentiated ductal adenocarcinoma of the pancreas; however, undifferentiated carcinoma with osteoclast-like giant cells might have a more favorable prognosis. We report the case of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, showing an intraductal growth pattern with various degree of pancreas duct involvement in the different areas. As a result, we were able to demonstrate the entire spectrum of changes, ranging from the early, minimal intraluminal growth to the partial or complete occlusion of the branches of the main pancreatic duct, and finally invasion and formation of the large necrotic/degenerated cysts. Our findings support the epithelial origin of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells. In early stages, the affected pancreatic duct epithelium was intermingled with nonepithelial component and had an immunoprofile distinctive from the epithelial lining of the uninvolved (normal) pancreatic ducts. Distinctive immunoprofile (CK 5/6, p63 and p53 positive) of the epithelial component and p63 and p53 positivity of the nonepithelial component should be explained and further investigated in the similar cases. Our findings support prior assertions that undifferentiated carcinoma of the pancreas with osteoclast-like giant cells may develop from carcinoma in situ within the main pancreatic duct or its branches.
    JOP: Journal of the pancreas 01/2011; 12(2):170-6.
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    ABSTRACT: Hydatidiform moles are gestational diseases with abnormal development of the villous trophoblast and characterized by an excess of paternal to maternal genetic material. Complete moles are usually diploid and androgenetic, and are thought to develop after the fertilization of an "empty ovum" by either a haploid spermatozoon or two spermatozoa. We report a case of a complete mole in which fluorescence in situ hybridization (FISH) incidentally disclosed trisomy 13. Microsatellite genotyping showed a single allele at each of the markers tested on the chorionic villi, and comparison with parental peripheral blood specimens revealed that the markers were all of paternal origin. These results confirmed the paternal origin of all three copies of chromosome 13, and the isodisomy for each chromosome was consistent with duplication of a monospermic fertilization event and subsequent non-disjunction. To the best of our knowledge, this is the only case of an androgenetic complete mole with trisomy 13 described in the scientific literature. We present a review of the literature and hypothesize that the trisomy 13 in our case likely resulted from non-disjunction of chromosome 13.
    Pathology - Research and Practice 11/2010; 206(11):776-81. DOI:10.1016/j.prp.2010.02.013 · 1.56 Impact Factor
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    ABSTRACT: There are limited data evaluating the significance of lymphatic vessel density (LVD) as a prognostic marker in cervical adenocarcinoma. In this study, we investigated intratumoral and peritumoral LVD, using the lymphatic marker D2-40, as a prognostic marker in endocervical adenocarcinoma. Surgical specimens from 50 consecutive patients with endocervical adenocarcinoma treated with complete staging surgical procedures were reviewed. Selected tumor blocks were immunostained for D2-40 and CD31. Positively stained microvessels (MVs) were counted in densely vascular/lymphatic foci (hot spots) at 400x field in each specimen (0.17 mm). Results were expressed as the highest MV count identified within any single field. Both intratumoral CD31 MV and peritumoral D2-40 LVD showed significant correlation with depth of invasion (r=0.39, 0.37, respectively), percentage of circumferential involvement (r=0.36, 0.48, respectively), and lymphovascular invasion detected by D2-40 (r=0.45, 0.51, respectively; P<0.01). Only peritumoral D2-40 LVD showed a significant correlation with lymph node metastases (r=0.40; P<0.01), disease-free and overall survivals. Using univariate analysis, peritumoral D2-40 LVD showed significant correlation with lymphovascular invasion detected by D20-40 and lymph node metastases (P<0.05), which was maintained on multivariate analysis. D2-40 detected lymphovascular invasion in 16 of 50 (32%) cases, and showed a significant correlation with depth of invasion, lymph node metastases, involvement of parametrium (r=0.41, 0.38, 0.32, respectively; P<0.01), and disease-free survival. Our study showed that both angiogenesis and lymphangiogenesis play an important role in the progression of endocervical adenocarcinoma, and that peritumoral D2-40 LVD is an independent predictor of lymph node metastasis.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 07/2010; 29(4):386-93. DOI:10.1097/PGP.0b013e3181c3cd47 · 2.07 Impact Factor
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    ABSTRACT: We studied the expression of cytokeratin (CK) 7, CK20, CDX-2, and p16 in 119 cervical adenocarcinomas (65 usual type [50 invasive; 15 in situ], 37 intestinal type [21 invasive; 16 in situ], 10 endometrioid, 5 adenosquamous, and 2 signet-ring carcinomas) in comparison with 55 cases of rectal adenocarcinomas. The percentage of cells staining was considered negative if 0% to 5% stained; more than 5% was considered positive. For p16, staining of more than 50% was considered positive. CK7 was expressed in all cervical cases and in 12 rectal adenocarcinomas (22%). CK20 was expressed in 17 cervical adenocarcinomas (14.3%) and in 48 rectal adenocarcinomas (87%). CK20 immunostaining was diffuse in the majority of rectal tumors but focal in most cervical tumors. CDX-2 was expressed in all cases of rectal adenocarcinoma and in 46 cervical adenocarcinomas (38.7%): usual type, 10 (15%); intestinal type, 31 (84%); endometrioid type, 5 (50%); adenosquamous and signet-ring types, 0 (0%). CDX-2 is a marker for intestinal differentiation irrespective of a rectal or cervical origin. Therefore, it should not be used as the sole basis to confirm the colorectum as the primary origin in metastatic cases.
    American Journal of Clinical Pathology 10/2009; 132(4):531-8. DOI:10.1309/AJCP7E5ASGOENPFP · 2.88 Impact Factor
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    ABSTRACT: To compare the incidence of pelvic lymph node metastases in early stage cervical cancer patients undergoing sentinel lymph node biopsy (SLN) to a matched cohort undergoing pelvic lymphadenectomy. All patient data were entered prospectively into an ongoing cervical cancer database. Since April 2004, 87 patients with FIGO stage IA/B1 cervical cancer underwent SLN detection with identification of bilateral SLN. This cohort (cases) was compared to a matched group of patients who underwent complete pelvic lymphadenectomy (controls). The groups were matched 3:1 for tumour size (+/-5 mm), histology, depth of invasion (+/-2 mm), and presence of capillary lymphatic space invasion (CLS). Descriptive statistics were calculated for all variables of interest. The association between cases and controls and lymph node metastases was carried out using a conditional logistic regression analysis. 81 women in the SLN cohort were matched with 1 control, 72 cases with 2 controls, and 65 cases with 3 controls. Among cases, 14 (17%) had pelvic lymph nodes metastases vs. 15 (7%) in the controls (p=0.0059, odds ratio= 2.8, 95% CI=1.3-5.9). Among the 14 cases of SLN metastases, 11 were detected by frozen section and 3 were detected on final paraffin sectioning. All were detected by H and E stains. The size of the SLN metastases ranged from less than 1 mm to 8 mm. Sentinel lymph node biopsy in early cervical cancer is a more sensitive procedure in detecting pelvic lymph node metastases compared to complete lymphadenectomy.
    Gynecologic Oncology 10/2009; 116(1):28-32. DOI:10.1016/j.ygyno.2009.10.049 · 3.69 Impact Factor
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    ABSTRACT: Radical trachelectomy is a fertility preserving alternative for early cervical cancer patients. This audit assesses the role of isthmic-vaginal smear in postoperative follow-up. A total of 94 patients were identified generating 913 smears. The final surgical margin was at the lower uterine segment in 37 cases (39.4%) and significantly correlated with the presence of lower uterine segment endometrial cells (LUSEC) in smears (P = 0.035). The most common abnormal diagnoses in the presence of LUSEC were ASC-US and AGUS seen in 14.2% and 11.9% of positive smears, respectively. The most common follow-up pattern was initial positive smears, which converted to negative (45.7% of patients), showing that reactive changes are another potential overcall pitfall. The only 2 central recurrences were successfully diagnosed by smears. This study summarizes our experience, emphasizing the role of isthmic-vaginal smears for early detection of central recurrence and highlighting the role of LUSEC and reactive changes as potential overcall pitfalls.
    Diagnostic Cytopathology 09/2009; 37(9):641-6. DOI:10.1002/dc.21059 · 1.52 Impact Factor
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    ABSTRACT: To compare the practices, adjuvant treatment, and outcomes of patients with preoperatively assessed grade 1 endometrioid endometrial cancer between two academic gynecologic oncology centers that use different treatment strategies. A retrospective analysis was performed at Duke University Medical Center (Duke) and the Toronto Sunnybrook Regional Cancer Center (Sunnybrook) between 1991 and 2007. Patients at Duke generally underwent surgical staging unless intraoperative assessment identified a negligible risk of nodal disease. Patients at Sunnybrook generally did not undergo surgical staging. A total of 494 patients (272 from Duke and 222 from Sunnybrook were identified with preoperative, central-review-confirming, grade 1, endometrioid, endometrial cancer. Groups were similar in grade, final histology, type of hysterectomy, and length of hospital stay. Patients from Sunnybrook were older (aged 62 years compared with 59 years, P=.001) and were more likely to have capillary lymphatic space involvement (18.2% compared with 8.3%, P=.003) and cervical involvement (12.2% compared with 3.7%, P<.001). Approximately 2% of cases were upgraded to high grade on final specimen. Lymphadenectomy was performed on 49.4% of patients at Duke compared with 11.7% of patients at Sunnybrook. Overall 3-year survival was 96% at Duke and 96% at Sunnybrook (P=.217). Three-year recurrence-free survival was 96% at Duke and 95% at Sunnybrook (P=.327). Despite differences in practice and slight differences in patient populations, the recurrence-free and overall survival of women with preoperative centrally reviewed grade 1 endometrial cancer is excellent and without statistically significant difference between the two centers. III
    Obstetrics and Gynecology 07/2009; 114(1):7-15. DOI:10.1097/AOG.0b013e3181aa97fc · 4.37 Impact Factor
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    ABSTRACT: To examine the impact of the polypoid morphology of uterine carcinosarcoma on clinical outcome, as well as its relationship to well-established prognostic factors. In a retrospective study of fifty eight patients with uterine carcinosarcoma treated with hysterectomy, we correlated the polypoid status of tumors with stage, lymphatic vascular invasion, myometrial invasion, size, carcinoma to sarcoma ratio, type of carcinomatous and sarcomatous components, disease free survival and overall survival. By multivariate analysis, the polypoid status had no impact on disease free survival (p=0.8958), but approached significance as a positive predictor for overall survival (p=0.0569); patients in the polypoid group lived on average 14.9 months longer than those with non-polypoid tumors. Polypoid neoplasms had a smaller average size and grew to a smaller maximum size than the non-polypoid tumors. While non-polypoid tumors were either carcinoma or sarcoma predominant, polypoid tumors were mostly sarcoma predominant (p=0.0348). Polypoid carcinosarcomas also demonstrated an appreciably lesser extent of myometrial invasion (p=0.0019), a markedly lower rate of lymphatic vascular invasion (p=0.0002), and tended to present as early stage tumors (p=0.0265). Carcinomatous component in polypoid tumors tended to have pure or nearly pure (>or=90%) endometrioid histology (p=0.1608). There was no relationship between polypoid status and type of sarcomatous component (p=0.5299). Polypoid carcinosarcomas differ from their non-polypoid counterparts in key histological parameters such as the carcinoma to sarcoma ratio, myometrial and lymphatic vascular invasion, stage and type of carcinomatous component. Patients with polypoid tumors may have a better survival outcome than those with non-polypoid tumors.
    Gynecologic Oncology 07/2009; 115(1):32-6. DOI:10.1016/j.ygyno.2009.06.018 · 3.69 Impact Factor
  • Mahmoud A Khalifa, Andy Smith
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    ABSTRACT: Metastasis to regional lymph nodes detected in cancer surgery specimens is a significant prognosticator and is also critical for subsequent planning of therapeutic options. Consequently, the status of regional lymph nodes has become a mandatory element of the synotic reporting on cancer resection specimens. Although pathologic reporting of lymph node metastasis is conceptually straightforward, several subtle processing and reporting issues deserve discussion. This review addresses pathology specific issues with particular emphasis on non-breast, non-cutaneous cancers.
    Journal of Surgical Oncology 03/2009; 99(4):260-4. DOI:10.1002/jso.21198 · 2.84 Impact Factor
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    ABSTRACT: To summarize our experience in the frozen section (FS) assessment of the trachelectomy surgical margin. All surgeries from 1994 to 2007 were performed by one surgeon. The FS examination was consistently carried out by a group of gynecologic pathologists according to the protocol described in details in this article. Cases were retrieved from the pathology files and the slides were reviewed by two pathologists. 132 patients were identified with complete pathology records. They ranged from 17 to 46 years old (median 31). Surgeries were performed for clinical Stages 1A (n=39) and 1B (n=93) tumors (63 adenocarcinoma, 59 squamous cell carcinoma, 7 adenosquamous and 3 others). In 78 cases, no residual tumor was seen in the trachelectomy specimens as it was resected by the preceding LEEP or cone. The margin was reported as negative in 123, suspicious in 3 and positive in 6 cases. It was revised in 16 cases (6 positive, 2 suspicious and 8 negative but <5 mm). Final margin assessment agreed with the FS diagnosis in 130 (98.5%) and showed interpretational overcall in 2 cases (1.5%); only one of which resulted in a revised margin. No false negative intraoperative assessment was found. We describe our FS protocol and summarize our data. This protocol is reliable since none of the patients was under-treated.
    Gynecologic Oncology 02/2009; 113(1):42-6. DOI:10.1016/j.ygyno.2008.12.025 · 3.69 Impact Factor

Publication Stats

630 Citations
118.88 Total Impact Points


  • 2004–2013
    • University of Toronto
      • • Department of Laboratory Medicine and Pathobiology
      • • Department of Obstetrics and Gynaecology
      Toronto, Ontario, Canada
  • 2000–2013
    • Sunnybrook Health Sciences Centre
      • • Division of Anatomic Pathology
      • • Division of Medical Oncology and Hematology
      Toronto, Ontario, Canada
  • 2009
    • Alexandria University
      Al Iskandarīyah, Alexandria, Egypt
  • 2007
    • Credit Valley Hospital
      Mississauga, Ontario, Canada