Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.     

Retrospective review of the preoperative biliary and gastrointestinal evaluation for gastric bypass surgery

BACKGROUND: The purpose of this study was to analyze the frequency and results of preoperative biliary and gastrointestinal (GI) evaluation of patients undergoing Roux-en-Y gastric bypass (RYGB). METHODS: Retrospective review of the preoperative evaluation of 144 consecutive RYGB patients. RESULTS: Cholecystectomy had already been performed in 43 (30%) patients; 22% of those patients with an intact gallbladder had cholelithiasis. Ten patients (7%) had an upper GI x-ray (UGI), and 94 patients (65%) had an esophagogastroduodenoscopy (EGD). Abnormalities were found in 40% of the UGIs and 84% of the EGDs. A total of 96 patients (67%) were tested for Helicobacter pylori; 11% were positive. Twenty-one patients (15%) underwent preoperative colonoscopy; 48% were abnormal, but most of the abnormalities were not clinically significant. Three patients had barium enema x-ray, which was normal in all cases. CONCLUSIONS: The preoperative biliary and GI evaluation of bariatric surgery patients should include a routine ultrasound of the gallbladder. Routine preoperative EGD will detect a significant number of abnormalities that should be treated, but should rarely alter the bariatric surgical procedure or result in denial of bariatric surgery. Many abnormalities will be asymptomatic. Patients should be routinely screened for H. pylori and, if positive, treated before bariatric surgery. Lower GI evaluation should be performed selectively based on the patient's symptoms, physical findings, and guidelines for colorectal cancer and polyp screening.     

Oropharyngeal decontamination in intensive care patients: less is not more

Ventilator-associated pneumonia (VAP) is a common cause of morbidity, antibiotic use, increased length of stay and, possibly, increased mortality in ICU patients. Colonization of the oropharyngeal cavity with potentially pathogenic micro-organisms is instrumental in the pathogenesis of VAP, and selective oropharyngeal decontamination (SOD) with antibiotics (AB-SOD) or antiseptics, such as chlorhexidine gluconate (CHX-SOD), has been associated with reduced incidences of VAP. In a recent issue of Critical Care Scannapieco and colleagues investigated differences in oropharyngeal colonization between mechanically ventilated patients receiving oropharyngeal decontamination with 0.12% CHX-SOD either once or twice daily compared to placebo. CHX-SOD was associated with a reduction in Staphylococcus aureus colonization, but the study was underpowered to demonstrate a reduction in VAP incidence. We urgently need well-designed and adequately powered studies to evaluate the potential benefits of CHX-SOD on patient outcome in ICUs.     

Preserving female fertility following cancer treatment: Current options and future possibilities

Children and women of reproductive age are increasingly surviving cancer diagnoses, and therefore long‐term quality‐of‐life issues are of greater importance at the time of diagnosis. Cancer therapies including radiation and chemotherapy can be detrimental to fertility, and therefore many patients are motivated to preserve fertility prior to cancer treatment. The only highly successful method in preserving fertility to date is embryo cryopreservation, which may not be appropriate for some patients due to age, delay in treatment, cancer type and stage, as well as availability of an acceptable sperm donor. Alternative methods including oocyte cryopreservation and ovarian tissue banking may also preserve fertility while providing additional flexibility to patients. In vitro ovarian follicle maturation following tissue banking is one potential approach that would not require a delay in cancer therapy for ovarian stimulation, would not require an immediate sperm donor, and does not carry the risk of reintroducing malignant cells following tissue transplantation. In vitro follicle culture systems have resulted in successful live births in the mouse. However, many challenges must be addressed in translating the system to the human. This review summarizes current approaches to fertility preservation and discusses recent developments and future challenges in developing a human in vitro follicle culture system. Pediatr Blood Cancer 2009;53:289–295. © 2009 Wiley‐Liss, Inc.     

Human papillomavirus and epithelial ovarian neoplasia

In contrast to the strong association between human papillomavirus (HPV) and squamous cell carcinoma of the lower female genital tract, no viral DNA had been found in epithelial ovarian carcinoma. Recently, however, R. H. Kaufman, J. Bornstein, A. N. Gordon, E. Adam, A. L. Kaplan, and K. Adler-Storthy [Gynecol. Oncol. 27, 340-349 (1987)] reported the detection of HPV-6 DNA by in situ hybridization in 10 of 12 patients with advanced epithelial ovarian carcinoma. To further investigate the possible association between HPV and epithelial ovarian neoplasia, tumor from 12 patients with epithelial ovarian adenocarcinoma, 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian adenomas was examined for HPV DNA by the Southern hybridization technique. All the tissues were tested under low stringency for HPV-6 and under high stringency for HPV-6, HPV-16, HPV-18, HPV-31, and HPV-35. In addition, all tissues were tested by polymerase chain reaction for the presence of HPV-6 and HPV-11. Of the 12 patients with adenocarcinoma, 5 were poorly differentiated, 4 serous, 1 endometrioid, 1 mucinous, and 1 mixed. The neoplasms were of grades 2-4 with a predominance of stages III and IV (83%). Of the 3 patients with tumors of low malignant potential, all were serous and stage I. Of the 3 patients with adenomas, 1 was mucinous, 1 serous, and 1 Brenner. We were unable to detect HPV-related sequences in any of the specimens. On the basis of these findings, there appears to be no association between HPV and epithelial ovarian neoplasia.     

Multifocal disease in the upper genital canal

Multifocal disease, both benign and malignant, is seen commonly in the lower genital canal. Conversely, malignancies developing concomitantly in the uterus and ovary are frequently diagnosed as metastatic disease. In this series of 54 cases, the overall five-year survival was 72%, and 90% when the lesions were limited to the uterus and ovary, demonstrating that these lesions are multifocal and not metastatic. Furthermore, the frequency with which endometriosis is found in association with these malignancies dictates that the adjunctive therapy should probably be progesterone in most instances.     

The vestibule

The vestibule, or introitus, is a unique area in the lower genital canal. Of major importance is the understanding of the embryology of the area if the lesions are to be interpreted adequately. It is a "collision zone" formed at the junction of different germ layers. The newly recognized syndrome of severe dyspareunia caused by inflammation of the minor vestibular glands affects many women. At present, ablative therapy is all that can be offered to these patients. While excisional surgery is highly successful, medical therapy awaits the elucidation of the true cause of this disorder. Vestibular mucous cysts and vestibular papillae are common benign conditions which must be recognized as such, lest inappropriate therapy be recommended.     

Adenomas in minor vestibular glands

Sixty-four patients were treated by minor vestibular adnexectomy for persistent dyspareunia and vulvar pain and burning between 1982 and 1984. The incidental finding of vestibular gland adenomas was found in 12 cases. These masses were 1 to 2 cm in size and composed of mucous secreting glands characteristic of the vestibular glands. These lesions were benign and were associated with previous surgical manipulation and chronic inflammatory reaction of the vestibular tissues. Previous recognition of vestibular adenomas in the literature is rare.     

Melanoma of the larynx

Primary laryngeal melanomas (LM) are rare. In a review of all mucosal melanomas of the head and neck (MMHN) at Memorial Hospital from 1949 to 1983 we identified only three such cases. Review of the literature shows that LM usually involve the supraglottic larynx of elderly males. Although survival is as poor as for other MMHN, local recurrence is less frequent, even when primary therapy consists of more conservative surgical procedures than total laryngectomy.