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We present a case of the syndrome of inappropriate antidiuretic hormone (SIADH) secondary to cisplatin therapy in a patient with advanced-stage large cell neuroendocrine carcinoma of the cervix. This occurred after the first cycle of cisplatin and then again after the second cycle. Carboplatin was substituted for cisplatin, and there were no further episodes of SIADH.

The distinction between uterine serous and endometrioid carcinomas can usually be achieved by morphologic examination alone. However, there are occasional 'morphologically ambiguous endometrial carcinomas' that show overlapping serous and endometrioid features and defy histologic classification. The primary aim of this study was to assess the clinical significance of p53 overexpression using immunohistochemistry in such tumors. Related aims included (1) assessing interobserver diagnostic concordance for histologic subclassification of these tumors using a panel of pathologists with and without gynecologic pathology expertise and (2) elucidating the histologic features that correlate with p53 status. Thirty-five such cases were identified during the study period. p53 overexpression was seen in 17 of 35 cases. Tumors with p53 overexpression were associated with a significantly inferior progression-free survival and disease-specific survival compared with those that lacked p53 overexpression (3-year progression-free survival and disease-specific survival were 94 and 100% in patients with no p53 overexpression, and 52 and 54% in patients with p53 overexpression; P=0.02 and 0.003, respectively). The consensus diagnosis rendered by gynecologic pathologists was predictive of disease-specific survival (P=0.002), but not progression-free survival (P=0.11). Although the interobserver diagnostic concordance (kappa=0.70) was substantial for gynecologic pathologists, and highly associated with p53 status (77% of 'favor serous' cases showed p53 overexpression, whereas only 25% of 'favor endometrioid' cases showed p53 overexpression; P=0.005), the concordance between the consensus diagnosis of the two specialized pathologists versus each of three non-specialized pathologists was poor (kappa=0.13-0.25). The histologic feature that correlated most with p53 overexpression was the presence of diffuse high nuclear grade. p53 immunohistochemistry assays in morphologically ambiguous endometrial carcinomas are roughly as clinically informative as gynecologic pathology consultation and can be helpful for prognostic assessment and therapeutic decision making in difficult endometrial carcinomas.

Objective: To describe the incidence of isolated paraaortic nodal metastasis in surgically staged endometrial cancer patients with negative pelvic lymph nodes., Methods: Using a prospectively maintained database we identified all cases of endometrial cancer that had both pelvic and aortic nodal dissection and determined the rate of isolated paraaortic nodal metastasis in the setting of negative pelvic nodes. For this report a satisfactory pelvic node dissection meant the identification of 8 or more pelvic nodes on final pathology., Results: 1942 endometrial cancer patients were surgically treated at our institution from 1/93 to 1/08. 847 had both pelvic and paraaortic nodes removed during surgery and identified by pathology. 734 had negative pelvic nodes with at least one paraaortic node identified. Only 12 (1.6%) had positive paraaortic nodes with negative pelvic nodes. Seven (1%) of 640 cases with 8 or more negative pelvic nodes had positive paraaortic nodes. Final grade for these cases included: G1 (2), G2 (2), G3 (1), papillary serous (1), and undifferentiated (1). Of the 570 cases with a final diagnosis of grade 1 endometrial cancer, 187 had both pelvic and aortic node dissection during the same operation, and 2/187 (1%) had a positive paraaortic node with negative pelvic nodes., Conclusions: Isolated paraaortic nodal metastasis in the setting of negative pelvic nodes occurs in approximately 1% of surgically staged endometrial cancer cases. This low rate seems consistent for low- and high-grade lesions. Future studies looking at the incidence of isolated paraaortic nodal metastasis in the setting of negative sentinel pelvic nodes are warranted.

Objectives: To determine whether HA-CMC was associated with the development of postoperative intra-abdominal collections in patients undergoing laparotomy for ovarian, fallopian tube, or primary peritoneal malignancies., Methods: We retrospectively identified all laparotomies performed for these malignancies from March 1, 2005 to December 31, 2007. The use of HA-CMC was identified. Laparotomies for malignant bowel obstruction or repair of fistulae were excluded. Intra-abdominal collections, non-infected and infected, were defined as localized intraperitoneal fluid accumulations in the absence of re-accumulating ascites. All other complications were also captured. Appropriate statistical tests were applied using SPSS 15.0., Results: We identified 219 laparotomies with HA-CMC and 204 without HA-CMC. Upper abdominal resections were performed in 65/219 (30%) HA-CMC cases compared to 39/204 (19%) cases without HA-CMC (P=0.01). The rates of large bowel and/or rectal resections were similar in both cohorts. Intra-abdominal collections were seen in 18/219 (8.2%) HA-CMC cases compared to 5/204 (2.5%) cases without HA-CMC (P=0.009). HA-CMC was independently associated with the diagnosis of a postoperative intra-abdominal collection (P=0.01). All but 2 collections developed in patients undergoing debulking procedures., Conclusions: HA-CMC appears to be associated with a higher rate of postoperative intra-abdominal collections. This seems to be greatest in patients who are undergoing a debulking procedure.

Objective: To obtain prospective outcomes data on patients (pts) undergoing palliative operative or endoscopic procedures for malignant bowel obstruction due to recurrent ovarian cancer., Methods: An institutional study was conducted from July 2002 to July 2003 to prospectively identify pts who underwent an operative or endoscopic procedure to palliate the symptoms of advanced cancer. This report focuses on pts with malignant bowel obstruction due to recurrent ovarian cancer. Procedures performed with an upper or lower gastrointestinal (GI) endoscope were considered "endoscopic." All other cases were classified as "operative." Following the procedure, the presence or absence of symptoms was determined and followed over time. All pts were followed until death., Results: Palliative interventions were performed on 74 gynecologic oncology pts during the study period, of which 26 (35%) were for malignant GI obstruction due to recurrent ovarian cancer. The site of obstruction was small bowel in 14 (54%) cases and large bowel in 12 (46%) cases. Palliative procedures were operative in 14 (54%) pts and endoscopic in the other 12 (46%). Overall, symptomatic improvement or resolution within 30 days was achieved in 23 (88%) of 26 patients, with 1 (4%) postprocedure mortality. At 60 days, 10 (71%) of 14 pts who underwent operative procedures and 6 (50%) of 12 pts who had endoscopic procedures had symptom control. Median survival from the time of the palliative procedure was 191 days (range, 33-902) for those undergoing an operative procedure and 78 days (range, 18-284) for those undergoing an endoscopic procedure., Conclusion: Patients with malignant bowel obstructions due to recurrent ovarian cancer have a high likelihood of experiencing relief of symptoms with palliative procedures. Although recurrence of symptoms is common, durable palliation and extended survival are possible, especially in those patients selected for operative intervention.

Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a high risk for endometrial cancer (EC) and frequently present with a gynecologic cancer as their first or sentinel malignancy. Identification of these patients is important given their personal and family risk for synchronous and metachronous tumors. The revised Bethesda Guidelines provide screening criteria for HNPCC in colorectal cancers. However, there are currently no such screening recommendations for women with endometrial carcinoma. We applied some of the colorectal cancer screening criteria, including age and tumor morphology, to endometrial endometrioid carcinoma. The purpose of this study was to describe patient and tumor characteristics and to assess the ability of these criteria to enhance detection of mismatch repair (MMR) deficiency, and hence HNPCC in EC. Immunohistochemistry (IHC) for DNA mismatch repair (IHC-MMR) proteins was performed in a defined subset of patients with EC. This included women younger than 50 years of age and women >or=50 years whose tumors showed morphologic features suggestive of MMR deficiency (TM-MMR). The extent of IHC-MMR in the older patient group was compared with that in a comparison group of EC >or=50 years that was previously analyzed for microsatellite instability status. Seventy-one patients met the selection criteria for IHC testing; 32 (45%) showed abnormal results. The rate of IHC abnormality in the younger group was approximately 30% with a nearly equal distribution of MLH1/PMS2 and MSH2/MSH6 abnormalities. In the older age group, TM-MMR triggered IHC analysis in 31 of 34 cases. Of these, 18 cases showed loss of IHC-MMR (58% of cases), 7 with loss of MSH2/MSH6. In contrast, the rate of microsatellite instability in the comparison group was only 21%. The IHC abnormal group showed more frequent tumor infiltrating lymphocytes, dedifferentiated EC, more tumors centered in the lower uterine segment, and more frequent synchronous clear cell carcinomas of the ovary than tumors with a normal immunophenotype. Although many of the patients with loss of IHC-MMR showed personal and/or family history (13 of 32) of HNPCC-associated tumors, most did not. Tumor morphology (TM-MMR) along with IHC-MMR enhances the detection of EC patients at risk of HNPCC.

Objective: To compare the accuracy of D&C vs office endometrial biopsy in predicting final post-hysterectomy FIGO grade in patients diagnosed with a preoperative FIGO grade 1 endometrial adenocarcinoma., Methods: We reviewed 1423 consecutive cases of endometrial cancer treated at our institution between 1/1/93 and 5/31/06 and identified cases with an unequivocal preoperative endometrial biopsy demonstrating FIGO grade 1 endometrial adenocarcinoma. All cases were pathologically confirmed and underwent surgical therapy at our institution. FIGO grade and histology diagnosed in the hysterectomy specimen were noted. The findings in the hysterectomy specimen were then compared between those patients who had a preoperative D&C vs an office endometrial sampling. Chi-square and Fisher-exact test were used as appropriate., Results: We identified 490 cases with a preoperative FIGO grade 1 endometrial adenocarcinoma. In 482 cases, FIGO grade was determined to be greater in 71 (14.7%) cases; in the final hysterectomy specimen, 66 (13.7%) were found to be grade 2 and 5 (1%) were found to be grades 2-3/3. Serous or clear cell histology was diagnosed in 6 (1.2%) additional cases. D&C was performed in 187 (38.6%) cases and office endometrial sampling in 298 (61.4%); in 5 cases the method used was not discernible. The final post-hysterectomy FIGO grade was higher in 16/187 (8.7%) cases diagnosed by D&C compared to 52/298 (17.4%) diagnosed by office endometrial sampling (P=0.007)., Conclusions: Preoperative FIGO grade 1 diagnosis correlates with final grade diagnosis in 85% of cases. While D&C more accurately reflects final FIGO grade, a higher grade will be found in 8.7% of the cases at the time of hysterectomy.

Surgery is the cornerstone of treatment for patients with advanced ovarian cancer. The majority of patients with advanced ovarian cancer who experience a clinical remission after initial surgery will develop a recurrence. The optimal management for patients with recurrent ovarian cancer remains to be defined. Chemotherapy is frequently used with varying response rates. Repeat surgical cytoreduction appears to offer a survival benefit for select patients with recurrent ovarian cancer and should be considered. Surgery also plays a role in the palliation of certain patients. Continued investigations, especially randomized trials, are needed to further define the optimal treatment modalities for these patients.

Objectives: To analyze progression-free (PFS) and overall survival (OS) in patients with small cell neuroendocrine carcinoma of the cervix (SCNEC), and to determine whether platinum-based combination chemotherapy is beneficial for this population., Methods: We performed a retrospective analysis of all patients with SCNEC who were treated at our institution between 1/1990 and 2/2007. Patients were excluded if pathologic diagnosis was not confirmed at our institution. Standard statistical methods were utilized., Results: Seventeen patients met inclusion criteria. The estimated 3-year PFS and OS rates for the entire group were 22% and 30%, respectively. Median time to progression was 9.1 months. Extent of disease was the only significant prognostic factor. Median OS for patients with early stage disease (IA1-IB2) was 31.2 months and 6.4 months for patients with advanced stage disease (IIB-IV, P=0.034). In the early-stage disease group, the 3-year distant recurrence-free survival rate was 83% for patients who received chemotherapy and 0% for patients who did not receive chemotherapy as part of their initial treatment (P=0.025). The estimated 3-year OS rate was 83% for patients who received and 20% for patients who did not receive chemotherapy as part of their initial treatment (P=0.36)., Conclusion: Given the rarity of SCNEC this retrospective analysis is limited by a small number of patients. However, the natural history of this rare disease is akin to small cell lung cancer and the prognosis is poor due to the tumor's propensity for distant spread. The treatment should conform to the treatment of small cell lung cancer.

Objective: To evaluate the ability of a preoperative diagnosis of FIGO grade 1 endometrial adenocarcinoma and intraoperative depth of myoinvasion (DOI) to predict low-risk (LR) and high-risk (HR) final uterine pathology., Methods: We reviewed 1423 consecutive cases of endometrial cancer treated at our institution between 1/1/93 and 5/31/06 to identify cases with a preoperative endometrial biopsy demonstrating FIGO grade 1 endometrial adenocarcinoma. All cases were pathologically reviewed at our institution and underwent surgical therapy at our institution. We excluded equivocal preoperative biopsies as well as those with serous or clear cell histology. Final uterine pathologic findings were grouped into low- and high-risk. Chi-square and Fisher-exact tests were used as appropriate., Results: We identified 490 cases with a median age of 60 years (range 29-90 years). In 482 cases in which final pathologic grade was assessable, FIGO grade was greater in 71 (14.7%) cases; (66 [13.7%] were grade 2, and 5 [1%] were grades 2-3/3). Serous or clear cell histology was diagnosed in 6 (1.2%) additional cases. HR final uterine pathology was seen in 86 (18.5%) cases. Frozen section assessment of DOI, when performed, was associated with HR pathology (p<0.001). HR pathology was present in 3 (3.6%) of 84 cases with either no tumor or myoinvasion identified on frozen section. Lymph node metastasis was identified in 9 (4.4%) of 205 patients that underwent nodal evaluation., Conclusions: Preoperative FIGO grade 1 diagnosis correlates with final post-hysterectomy grade in 85% of cases. The rate of HR uterine pathology based on preoperative grade 1 alone is 18.5%. Frozen section may help further stratify for the risk of final HR uterine pathology but is not entirely accurate. The rate of HR uterine pathology is 4% if no cancer or myoinvasion is identified on frozen section and 18% if myoinvasion up to 50% is identified.

Background: The objective of this study was to compare the human immunodeficiency virus (HIV) viral load (VL) and CD4 counts in patients infected with HIV with and without cervical cancer. The authors hypothesized that HIV-positive women with cervical cancer would have a greater risk of immune suppression., Methods: A case-control study was conducted that included all HIV-positive patients who were seen at the authors' institution from January 1, 1995 to April 20, 2006 with invasive cervical cancer (cases) and without invasive cervical cancer (controls). Patients were included only if they had a CD4 count recorded<6 months before or<3 months after their diagnosis of invasive cervical cancer (cases) or at their last gynecologic examination (controls). Controls were matched to cases on a 4:1 ratio according to current smoking history. Patients were considered immunocompetent if they had both a CD4 count>200 cells/microL and a VL<10,000 copies/mL., Results: In total, 15 cases and 60 controls were identified. The median CD4 count for cases was 208 cells/microL (range, 18-1102 cells/microL) compared with 445 cells/microL (range, 20-1201 cells/microL) for controls (P=.03). The median VL was 16,918 copies/mL (range, 50-214,915 copies/mL) for cases compared with 1430 copies/mL (range, 50-571,000 copies/mL) for controls (P=.15). Only 1 of 14 cases (7%) was immunocompetent compared with 35 of 55 controls (64%; odds ratio, 0.04; 95% confidence interval, 0-0.37; P<.001). This significance was maintained after adjusting for other factors (P=.002)., Conclusions: Women with HIV who were diagnosed with invasive cervical cancer appeared to have a much greater degree of immunosuppression than women with HIV without invasive cervical cancer., (Copyright (c) 2008 American Cancer Society.)

Surgery plays an integral part in the primary management of early-stage and advanced-stage epithelial ovarian cancer. Surgical staging is essential for disease grossly confined to the ovaries or pelvis. Comprehensive surgical staging often results in upstaging of patients who were presumed to be at an early stage. Accurate staging has an impact on prognosis and treatment strategies. Optimal surgical cytoreduction leads to improved outcomes in patients with advanced disease; before initiation of chemotherapy, it offers the most favorable outcome and should be offered to all patients. Intraperitoneal catheters for postoperative chemotherapy instillation may be offered and placed at the time of cytoreduction. Neoadjuvant chemotherapy and interval cytoreduction are a possibility for patients who are not amenable to an optimal cytoreduction based on preoperative findings or in those who are at extremely high risk for surgery.

Gynecologic malignancies are most often diagnosed in postmenopausal women, but these malignancies also arise in premenopausal women, in whom issues of fertility can be a major concern. An increasing number of women are delaying childbearing. This has led to a significant increase in the number of women diagnosed with a gynecologic malignancy before desired completion of childbearing. Many of the standard treatments for these malignancies result in permanent sterility; however, there are now options for select young women who desire to preserve fertility. Patients should be told that data on fertility-sparing procedures are limited and that many of these options are of an experimental, nonstandard nature. The care of these patients is challenging and complex and requires a multidisciplinary approach, which should include gynecologic oncologists, reproductive endocrinologists, and perinatologists.

Objectives: The literature on the role of cytoreductive surgery beyond the secondary cytoreductive setting is limited. In this study, we reviewed the outcomes of patients with recurrent epithelial ovarian carcinoma who underwent tertiary cytoreduction., Methods: We performed a retrospective chart review of all patients with recurrent epithelial ovarian carcinoma who underwent tertiary cytoreduction at our institution from 1/1/90 to 12/31/02. Disease-specific survival (DSS) was calculated from the time of tertiary cytoreduction to last follow-up. Univariate and multivariate analyses were used to analyze outcomes and to identify potential prognostic factors., Results: A total of 26 patients were identified. The median follow-up after tertiary cytoreduction was 22.3 months (range, 0-71.7 months), with an overall median DSS of 33.4 months (95%CI, 20.4-46.4). On univariate analysis, treatment-free interval (TFI) before tertiary cytoreduction and residual disease after the procedure, as well as time to first recurrence, were found to be significant prognostic factors. Median DSS was 15 months for a TFI < or =12 months compared with 60.4 months for a TFI > 12 months (P = 0.002). The median DSS for patients with residual disease < or =0.5 cm was 36.3 months compared with 10.6 months for patients with residual disease >0.5 cm (P <0.0001). On multivariate analysis, TFI and residual disease after tertiary cytoreduction retained prognostic significance (P < 0.05 for both)., Conclusion: Further cytoreductive surgery may offer a survival benefit in patients who experience a recurrence after secondary cytoreduction. This benefit appears to be greatest in patients with a longer TFI (>12 months) and in whom an optimal (< or = 0.5 cm) cytoreduction can be achieved.

The reported experience with early-stage (FIGO stage I/II) ovarian carcinoma (OC) is limited given that the majority of women with OC are diagnosed at an advanced stage. There has not been an extensive review of these tumors, and since the pathologic criteria differentiating invasive and borderline tumors have evolved over time, the issue of whether a proportion of these tumors should be reclassified has not been addressed. We identified patients with stage I/II invasive OC who underwent primary surgical management at Memorial Sloan-Kettering Cancer Center from 1980 to 2000. Patients known to have a BRCA mutation or a family history of breast/ovarian cancer were excluded. Hematoxylin and eosin slide review, blinded to clinical outcomes, using current diagnostic criteria for ovarian carcinomas and borderline ovarian tumors, was performed. Progression-free survival (PFS) and disease-specific survival (DSS) were estimated and compared. Hematoxylin and eosin slides were reviewed for 140 of the 145 patients identified. The diagnosis was changed to borderline (low malignant potential) in 41 cases (29.3%). Twenty-nine (70.7%) of 41 changes in diagnosis involved endometrioid and mucinous tumors. This was attributable to the application of recently revised criteria for distinguishing borderline tumors from carcinomas. None of the originally diagnosed clear cell carcinomas was reclassified as borderline. The distribution of histologic subtypes among the 94 carcinomas included 26 serous (27.7%), 25 clear cell (26.6%), 22 endometrioid (23.4%), 10 mixed (10.6%), 6 mucinous (6.4%), 2 malignant Brenner (2.1%), and 3 adenocarcinomas, not otherwise specified (3.2%). Adjuvant therapy was given to 84 (89.4%) of the 94 patients with carcinomas. The 5-year PFS and DSS were significantly greater for the group of cases that was reclassified as borderline (4.5% vs. 26.2% progressed [P = 0.006]; 4.5% vs. 25.6% died [P = 0.003]). The 5-year PFS and DSS were significantly worse for carcinomas with a TP53 mutation (22.6% vs. 41.2% progressed [P = 0.04]; 21.7% vs. 24.7% died [P = 0.04]). There were no statistically significant differences in outcome between stages I versus II, tumor grades, clear cell histology versus other, and stage IC preoperative versus intraoperative rupture. We concluded that a large number of cases originally diagnosed as early-stage sporadic OC were borderline tumors. Clear cell histology does not confer a worse prognosis compared with other histologies. The presence of a TP53 mutation was an adverse prognostic indicator.

Objective: The objective was to determine the response rate to platinum retreatment of "platinum-resistant" ovarian cancer after intervening nonplatinum therapy., Methods: We retrospectively identified 30 patients with platinum-resistant ovarian cancer who received nonplatinum chemotherapy for recurrent epithelial ovarian cancer prior to additional platinum therapy. All patients were treated between July 1, 1997, and June 30, 2001. Platinum resistance was defined as less than a partial response to platinum therapy or progression within 6 months of the last platinum therapy., Results: Overall, 7 of 30 patients experienced an objective response to platinum therapy (partial response, 23%; complete response, 0%) based on CT scan (2/21) and/or CA-125 (5/9) criteria. The median time to progression for the group was 17 weeks (range, 4-59 weeks). Several predictive factors were identified. The interval since the last platinum treatment did not appear to be predictive in this group. Only 1 of 16 patients who did not have an objective response to the most recent platinum-based therapy responded to platinum rechallenge. Similarly, no patient who received more than three intervening nonplatinum treatments responded to additional platinum therapy (0/10)., Conclusions: Our small retrospective series suggest that the platinum-resistant category is heterogenous and includes patients who may respond to retreatment with platinum-based agents. This group includes the patients with prior platinum responses and early progression. However, patients without an objective response to the last prior platinum therapy or more than three intervening treatments are unlikely to respond to subsequent platinum therapy.

There are limited treatment options for patients with recurrent cervical carcinoma. Because of low response rates and a negligible impact on long-term survival, the use of chemotherapy in patients with unresectable recurrent disease should be considered palliative. Generally, radiation therapy in previously irradiated patients is considered palliative. For patients who develop recurrent disease after definitive surgery who have not received prior radiation therapy, salvage radiation therapy is the treatment of choice. Similarly, patients who have received definitive primary radiation therapy are candidates for surgical resection of their recurrence. However, there are specific criteria for surgical resection. Radical hysterectomy may be an option for the very rare patient with a small (<2 cm) centrally located recurrence in the cervix or vaginal fornices. However, for most patients, pelvic exenteration remains the only therapeutic option that offers the possibility of long-term survival. Patients who are candidates for exenteration are those with central local recurrences that have not extended to the pelvic sidewalls. The introduction of high-dose-rate intraoperative radiation therapy (HDR-IORT) combined with radical surgical resection has widened the scope of patients who may be offered surgery. Patients who in the past may not have been surgical candidates may benefit from radical surgical resection combined with HDR-IORT. All patients who are surgically fit and have undergone previous radiation therapy should be considered for surgical resection for centrally located recurrences. Patients whose recurrences extend close to the pelvic sidewalls should be referred to centers where HDR-IORT is available.