Incidence and management of leukopenia/neutropenia in 233 kidney transplant patients following single dose alemtuzumab induction.

BACKGROUND: The purpose of this study was to determine the incidence and management strategies for post-transplant leukopenia/neutropenia in kidney recipients receiving alemtuzumab induction during the first year following transplantation. METHODS: We prospectively identified 233 adult patients who underwent kidney transplantation with alemtuzumab induction at a single institution. The incidence and severity of leukopenia (white blood cell count [WBC] ≤2500/mm(3)) and neutropenia (absolute neutrophil count [ANC] ≤500/mm(3)) were evaluated at 1, 3, 6, and 12 months post-transplantation. We determined any association with cytomegalovirus (CMV) infection, graft rejection, and infections requiring hospitalization. We also reviewed interventions performed, including medication adjustments, treatment with granulocyte stimulating factor, and hospitalization. RESULTS: The combined incidence of either leukopenia or neutropenia was 47.5% (n = 114/233) with an average WBC nadir of 1700 ± 50/mm(3) at 131.0 ± 8.5 days and an average ANC nadir of 1500 ± 100/mm(3) at 130.4 ± 9.6 days. No significant difference in graft rejection, CMV infection, or infections requiring hospitalization was found in the leukopenia/neutropenia group vs the normal WBC group (P = .3). The most common intervention performed for leukopenia/neutropenia group was prophylactic medication adjustment. Six patients (5.2%) required a change in >1 medication. The majority of these patients also required granulocyte stimulating factor (61.5%; 32/52), with an average of 2.5 doses given. A total of 25 patients (21.9%) required hospitalization due to leukopenia/neutropenia with an average length of stay of 6 days. CONCLUSIONS: Kidney transplant patients receiving alemtuzumab induction required significant interventions due to leukopenia/neutropenia in the first year post-transplantation. These results suggest the need for additional studies aimed at defining the optimum management strategies of leukopenia/neutropenia in this population.

Cytomegalovirus disease in African-American kidney transplant patients.

BACKGROUND: Cytomegalovirus (CMV) disease is a serious infection after kidney transplantation. The risk factors and the impact of CMV disease in African-American (AA) kidney transplant patients have not been well characterized. METHODS: We performed a retrospective analysis on 448 AA patients transplanted between 1996 and 2005. A 3-month universal chemoprophylaxis with ganciclovir or valganciclovir was administered to CMV donor-positive/recipient-negative (D+/R-) patients and to those treated with anti-thymocyte globulin for rejection, but not routinely to those with other D/R serostatus. RESULTS: A total of 31 AA patients (7%) developed clinical CMV disease. Compared with other D/R serostatus groups, the D+/R- group had the highest 3-year cumulative incidence of CMV disease (16.9% vs. 6.3% in D+/R+, 4.9% in D-/R+, and 2.4% in D-/R-). The D+/R- group also had the worst 3-year death-censored allograft survival (75% vs. 92% in D+/R+, 94% in D-/R+, and 96% in D-/R-, log-rank P = 0.01). Multivariate analysis found that D+/R- serostatus (odds ratio [OR] 5.4, 95% confidence interval [CI] 0.6-48.2, P = 0.003) and donor age > 60 years (OR 9.1, 95% CI 1.3-65, P = 0.03) were independent risk factors for CMV disease. CONCLUSION: The D+/R- group has the highest incidence of CMV disease and the worst 3-year renal allograft survival despite 3-month universal prophylaxis. Prolonged chemoprophylaxis may be needed to prevent the late development of CMV disease and to improve allograft survival in the high-risk group of AA kidney transplant recipients.

Long-term outcome of single pediatric donor kidney transplants between African-American and non-African-American adults.

BACKGROUND: African-American (AA) ethnicity has been considered a risk factor for graft loss after kidney transplant. The long-term graft survival of single pediatric donor kidney transplants in AA adults has not been reported. METHODS: We retrospectively compared the outcome of 43 AA and 32 non-African-American (NAA) adults transplanted with single pediatric kidneys from donors aged 10 years or less in our center. A combination of tacrolimus, mycophenolic acid and steroid was utilized as the maintenance therapy. RESULTS: Similar immunosuppressive dose and targeted level were achieved between the AA and the NAA groups. Median body weight (BW) of donors was 20 kg (8 - 36) in the AA group and 19 kg (8.5 - 35) in NAA group. There was no statistically significant difference in the incidence of rejection between the AA and NAA groups (26 vs. 16%, p = 0.45). The surgical complications, delayed graft function, and development of proteinuria and focal and segmental glomerulosclerosis (FSGS) were similar in both groups. The patient and graft survivals in the AA group were slightly higher compared to the NAA group. The death-censored analysis demonstrated no difference in graft survival between the AA and NAA groups (p = 0.90): 86 vs. 82% at 1 year, 70 vs. 71% at 3 years, and 62 vs. 64% at 5 years. CONCLUSIONS: Single pediatric donor kidney transplant in AA adults can be achieved with acceptable complications and equivalent long-term outcomes as in NAA adults in the era of potent immunosuppressive regimen.

Effect of ischemia-reperfusion on the incidence of acute cellular rejection and timing of histologic hepatitis C virus recurrence after liver transplantation.

BACKGROUND: Because of a critical shortage of deceased donor (DD) livers, more extended criteria allografts are being utilized; these allografts are at increased risk for ischemia-reperfusion injury (IRI). We assessed whether, in a large cohort of patients transplanted for hepatitis C virus (HCV) either via a DD or live donor (LD), there was a relationship between the degree of IRI and the frequency and timing of acute cellular rejection (ACR) and histologic HCV recurrence. METHODS: During an 8-year study, patients were separated into four groups based on peak alanine aminotransferase (ALT) levels and three groups based on severity of IRI on postreperfusion liver biopsy. RESULTS: The mean follow-up time of 433 DD and 44 LD recipients was 1212 days. We noted a strong correlation in DD between peak ALT and the histologic degree of IRI (P = .01). There was no difference in the incidence or grade of ACR among the four groups. There was no correlation between the severity of IRI and the incidence or time to histologic recurrence of HCV. CONCLUSIONS: The magnitude of peak ALT correlated with the severity of IRI on postreperfusion liver biopsy. Among this large HCV cohort, there was no correlation between the severity of IRI and the incidence or timing of histologic HCV recurrence or incidence of ACR.

A comparison of long-term survivals of simultaneous pancreas-kidney transplant between African American and Caucasian recipients with basiliximab induction therapy.

African Americans (AA) have traditionally been thought to have higher immunologic risk than Caucasians (CA) for rejection and allograft loss. The impact of ethnicity on the outcome of simultaneous pancreas-kidney (SPK) transplant with basiliximab induction has not been reported. In this study, we retrospectively analyze the long-term results of 36 AA and 55 CA recipients of primary SPK. The actual patient survival rates of AA and CA groups were 91.7% vs. 90.1% at 1 year, 93.3% vs. 88.1% at 3 years, and 94.4% vs. 83.3% at 5 years. The actual kidney survival of AA and CA were 91.7% vs. 89.1% at 1 year, 90% vs. 81% at 3 years, and 83.3% vs. 75% at 5 years. The actual pancreas survival of AA and CA were 88.9% vs. 85.5% at 1 year, 83.3% vs. 78.6% at 3 years and 72.2% vs. 70.8% at 5 years. Death-censored analyses also found no difference in pancreas and kidney graft survival rates over 5 years. Higher rejection rate, but the same low CMV infection, and comparable quality of graft function were noted in AA group. AA may not have worse long-term outcomes than CA recipients of SPK with basiliximab induction and tacrolimus (TAC), mycophenolate acid (MFA) and steroid maintenance immunotherapy.

Primary pelvic non-Hodgkin's lymphoma.

OBJECTIVE: To describe five cases of primary pelvic non-Hodgkin's lymphoma, a rare gynecologic malignancy. METHODS: The charts of five women with primary pelvic non-Hodgkin's lymphoma were reviewed. Histologic classification was based on the Working Formulation, and staging was based on the Ann Arbor system. Disease status was monitored with physical examination and imaging studies. RESULTS: During a 10-month period, five women were diagnosed with primary pelvic non-Hodgkin's lymphoma, including one parasacral, one uterine, one vaginal, and two ovarian tumors. Presentations included abdominal and pelvic pain, abdominal and pelvic mass, and abnormal vaginal bleeding. Treatment included combination chemotherapy, with or without radiation. Four patients were alive and disease free 20--33 months after therapy. CONCLUSION: Primary pelvic non-Hodgkin's lymphoma may present like other more common gynecologic cancers. It should be considered in the differential diagnosis of gynecologic malignancy.

Adenocarcinoma of the endometrium after endometrial ablation.

BACKGROUND: Endometrial ablation is a relatively new technique for treating abnormal uterine bleeding not associated with malignancy. Long-term outcome data after endometrial ablation are limited, and incidence of endometrial adenocarcinoma after ablation is unknown. CASE: A 55-year-old black woman who had endometrial ablation for abnormal uterine bleeding after excluding uterine cancer presented 5 years later with similar symptoms and a histologic diagnosis of well-differentiated adenocarcinoma of the uterus. She refused surgery and had radiation treatment for probable stage I endometrial adenocarcinoma. CONCLUSION: It is unlikely in this high-risk patient that the endometrial ablation masked an undetected malignancy or delayed the diagnosis. Given the interval, the adenocarcinoma might have occurred de novo.

Avoidance of female genital tract complications in relation to pelvic surgery for cancer.

As pelvic surgeons, it is essential that the colorectal surgeon and gynecologist have knowledge of and mutual respect for the areas of expertise that each specialty offers. The surgeon will encounter situations in which knowledge of the gynecologic anatomy is essential if injury is to be avoided during colorectal procedures. Gynecologic oncologists are trained not only to resect gynecologic cancers, but to also manage any complications that may result from cancer therapy or progressive disease. In many communities in which a gynecologic oncologist is not available, the surgical oncologist or colorectal surgeon will be consulted to assist in the management of gynecologic cancers. These surgeons must have the technical prerequisites and detailed knowledge about the mechanisms of spread, patterns of distant and local recurrences, the probability for cure, and the treatment methods to achieve management in the various cancers. We will discuss problems and complications of the female genital tract encountered by the colorectal surgeon during pelvic surgery for both bowel and gynecologic cancers, with an emphasis on prevention. Additionally, issues such as prophylactic oophorectomy and hysterectomy, management of gastrointestinal (GI) tract involvement in gynecologic cancer patients, the approach to peritoneal carcinomatosis, and situations where both the gynecologic and colorectal teams are required will be presented.

Factors leading to delay in diagnosis of invasive cervical cancer.

Objective: Screening for cervical cancer has been one of the major successes in American health care. The reasons for screening failure have not been well described. We have encountered 24 patients in the past year on our gynecologic oncology service who have presented with grossly visible stage IB or higher cervical cancers. A questionnaire was developed to determine why these patients presented with invasive cervical cancer, a theoretically preventable disease.Methods: All patients seen at our hospital center with grossly visible cervical cancer were offered entry into this prospective study, approved by the IRB. After informed consent was obtained, a questionnaire was administered to the patients by a physician. The questions involved sexual and gynecologic history, symptom review, social history, and personal concerns involving gynecologic exams. Twenty-four patients were approached for the study and 20 were enrolled. Four patients were unable to participate secondary to medical or social conditions that did not allow them to complete the questionnaire.Results: Of the 20 patients enrolled in this study, 14 of 20 (70%) presented with bleeding irregularities. Upon further questioning, 19 of 20 (95%) reported a history of abnormal bleeding. Only 3 of 20 (15%) patients reported a history of an abnormal Papanicolaou smear, and 7 of 20 (35%) reported not having had a Papanicolaou in the past 5 years. Two patients had never had a Papanicolaou smear. Seventeen of 20 (85%) of all patients in the study had medical insurance at the time of diagnosis, and only 2 patients reported lack of insurance as the reason they had not been seen by a gynecologist in the past 2 years. The majority of the study patients, 17 of 20 (85%) had contact with medical personnel in the 2 years prior to diagnosis. Sixteen of the 20 patients had been seen by a physician, 5 of 20 had surgery or other invasive procedures, and 6 of 20 had been seen in an emergency department. Only 5 of 20 patients knew that a Papanicolaou smear is a screening test for cervical cancer. Five of the 20 thought it to be a test for infections, and 10 of 20 did not know the purpose of a Papanicolaou smear. The main reason women gave for not having had a Papanicolaou smear in the past 2 years was that they felt healthy and had no symptoms (12/20).Conclusion: The majority of patients in our study (17/20) reported contact with a physician within 2 years of diagnosis of their invasive cervical cancer. It appears that failure to screen and lack of understanding regarding Papanicolaou smear screening, rather than lack of access to medical care, is a major cause for delay in diagnosis of cervical cancer.

Papillary serous carcinoma of the peritoneal surface: matched-case comparison with papillary serous ovarian carcinoma.

Between 1984 and 1991, 199 patients underwent laparotomy for epithelial "ovarian" malignancy. In 29 cases (15%) normal-sized ovaries (< 4 cm in diameter) with minimal invasion by papillary serous carcinoma were found. This entity in the setting of peritoneal carcinomatosis has been previously described and is reported here as papillary serous cancer of the peritoneal surface (PSPS). The clinical, surgical, and pathologic features of PSPS are compared with a group of age-, grade-, and stage-matched cases with papillary serous ovarian carcinomas (PSOC). PSPS was also characterized by ascites (mean = 3036 cc), malignant washings (91%), and omental involvement with bulky infiltration and/or multiple tumor nodules (96%). Mean cytoreduction in the PSPS group was 65.5% compared to 79% in the PSOC group (P = 0.049). Patients received combination chemotherapy with platinum-based regimens. In general, there was a poor response to treatment with a disease-free interval of 3.4 and median survival time of 19 months in PSPS compared to 11.7 and 31 months in the PSOC patients. Patients with PSPS have more limited cytoreduction, shorter disease-free interval, and shorter overall survival time. Such differences prompt re-evaluation of treatment modalities for PSPS and recognition that this is a condition distinct from PSOC.

Adjuvant chemotherapy and radiation in patients with poor prognostic stage Ib/IIa cervical cancer.

After radical hysterectomy and pelvic lymphadenectomy, 35 women with multiple negative prognostic factors (nodal metastases, stromal invasion > 65%, parametrial extension, positive surgical margins, lymphovascular involvement, lesion size > 4 cm, and adenosquamous or poorly differentiated cancers) were offered adjuvant therapy. Thirteen patients (37.1%) received radiation alone and 22 (62.9%) were treated with a platinum-based regimen of chemotherapy and radiotherapy. In the group receiving radiation, 2 (14.3%) had recurrences. In the 22 women treated with both modalities, there have been no recurrences with a mean follow-up time of 37.1 months. The results in the combined modality group were encouraging given the fact that these women had on average 3.5 poor prognostic features compared to the radiotherapy group where there was an average of 2.2 high-risk factors.

Surgical transposition of the ovary: radiologic appearance.

Therapeutic irradiation of the pelvis of a young female patient will result in loss of ovarian function. In a surgical technique termed ovarian transposition, the ovary is repositioned to the iliac fossa or paracolic gutter outside the radiation field. The computed tomographic (CT) scans and sonograms of five patients with cervical carcinoma who underwent this procedure were reviewed. The normal transposed ovary was of soft-tissue attenuation, often with one or more small cysts. Large cysts developed in the ovaries of three patients. One cyst was functional, another was due to a mesothelial inclusion cyst, and the third was most probably related to the transposition itself. Since the transposed ovary is difficult to palpate, CT or sonography can be used to demonstrate and follow up a cystic mass. Recognition of the appearance and location of the transposed ovary is important to avoid misinterpretation of a solid or cystic mass in patients who are at risk for tumor recurrence.

Evaluation and management of the pelvic mass: a review of 540 cases.

The management of 540 patients with the diagnoses of "pelvic mass/uterine leiomyomata" was reviewed with respect to preoperative evaluation, surgical procedures, and final pathologic diagnosis. Approximately 6170 patients were admitted to the Gynecology Service at St. Luke's-Roosevelt Hospital Center from July 1984 to June 1985. During this period, 36 of 432 diagnostic laparoscopies (8.3%) and 503 of 1666 laparotomies (30.2%) were performed to evaluate or treat these women. The final diagnoses in the 249 patients admitted with the impression of leiomyomata were: leiomyomata, 235 (94.4%); benign adnexal masses, seven (2.8%); cancers, four (1.6%); and miscellaneous, three (1.2%). Of the 291 patients evaluated for pelvic mass, the findings were: benign ovarian or tubal cysts, 98 (33.7%); leiomyomata, 42 (14.4%); cancers, 40 (13.7%); benign cystic teratomas, 38 (13.1%); endometriosis, 28 (9.6%); miscellaneous, 23 (7.9%); and pelvic inflammatory disease, 22 (7.6%). Correlation between the patient's age, preoperative impression, and final diagnosis is presented with particular attention to the 44 patients (8.1%) in whom malignancy was found. All the possibilities that such masses may represent must be considered preoperatively, and the patient be informed of her risk of malignancy.

Diagnostic conization of the cervix: review of 460 consecutive cases.

During a five-year period, 460 patients underwent cervical conization on the Gynecology Service at Memorial Hospital. The pertinent medical history of the 393 patients was reviewed as it related to the diagnosis of cervical intraepithelial neoplasia. All patients had repeat Papanicolaou smears and 94.4% had complete colposcopic examination using standard colposcopic procedures, endocervical curettage, and directed biopsies. For the purpose of this review, patients were separated into seven groups according to the primary and most significant indication for conization. The indications for the procedure and the histopathologic findings are discussed for each category. The usefulness of conization in the authors' institution varied according to the indication for which it was carried out. In this series of 393 patients, 18 patients (4.7%) initially diagnosed to have only intraepithelial disease, were found to have invasive carcinoma.