Christopher J. Jolles

Dietary vitamins A, C, and E and selenium as risk factors for cervical cancer.

The relation between cervical cancer and dietary intake of vitamins A, C, and E, beta-carotene, and selenium was examined in a population-based case-control study in Utah. Cervical cancer cases (n = 266) and population-based controls (n = 408) were interviewed between 1984 and 1987. Protective effects were observed for vitamins A, C, and E and beta-carotene but were attenuated by age, level of education, and lifetime cigarette use. Associated risk (comparing highest with lowest quartiles of intake) went from 0.53 (crude) to 0.71 (adjusted) for vitamin A; from 0.55 (crude) to 0.82 (adjusted) for beta-carotene; from 0.45 (crude) to 0.55 (adjusted) for vitamin C; from 0.58 (crude) to 0.60 (adjusted) for vitamin E; and from 0.95 (crude) to 0.70 (adjusted) for selenium. Adjustment for number of sex partners and church attendance, factors significantly related to cervical cancer risk, only slightly attenuated these adjusted risk estimates.

Systemic immunosuppression induced by photodynamic therapy (PDT) is adoptively transferred by macrophages.

Abstract— Some derivatives of hematoporphyrins are strongly retained by tumor tissue as compared to normal tissue, and exposure of these photosensitizers to radiation in the visible spectrum can cause serious biological damage. These properties have been exploited in the development of a new treatment for cancer termed photodynamic therapy (PDT). However, recent studies have also demonstrated that PDT can also induce a state of systemic immunosuppression. The purpose of this study was to determine whether PDT‐induced suppression of contact hypersensitivity (CHS) responses was an active phenomenon that could be adoptively transferred by viable splenocytes from PDT‐treated mice. Although induction of adoptively transferable suppressor cells in PDT‐treated mice required exposure to antigen, the suppressor cells were found to be antigen nonspecific in their function. Furthermore, splenocytes from PDT‐treated mice were capable of generating levels of allospecific cytotoxic T lymphocyte (CTL) activity which were comparable to those generated by normal control mice, but the ability of irradiated spleen cells from PDT‐treated mice to stimulate a mixed lymphocyte response (MLR) was dramatically impaired. Finally, chromatographic separation of T cells, B cells and macrophages showed that the cell type which mediates adoptively transferable suppression of CHS responsiveness is in the macrophage lineage.

Systemic immunosuppression induced by peritoneal photodynamic therapy

Although photodynamic therapy is being used increasingly for the diagnosis and treatment of human cancer, its effect on immune responses has received little attention. This aspect was examined in a murine model. Mice given peritoneal photodynamic therapy had markedly decreased contact hypersensitivity responsiveness, not observed with cutaneous photodynamic therapy. The immunosuppression was systemic, because contact hypersensitivity was depressed at distal, unirradiated sites. Photodynamic therapy induced adoptively transferable cells that inhibited contact hypersensitivity responses in naive mice. The immunosuppression was reversible, but persisted for 3 weeks after photodynamic therapy. An acute-phase response characterized by leukocytosis and elevated serum amyloid P levels was observed in mice given photodynamic therapy but not in mice treated with either laser or dye alone. These data suggest a link between the acute-phase response and immunosuppression. Thus, although photodynamic therapy shows promise in cancer treatment, the induction of decreased systemic immunoresponsiveness is an important observation with potentially detrimental consequences.

Photodynamic therapy of human ovarian epithelial carcinoma, OVCAR-3, heterotransplanted in the nude mouse

OBJECTIVE Our objective was to develop an animal model for the study of photodynamic therapy in the treatment of human ovarian epithelial carcinoma. STUDY DESIGN The human ovarian carcinoma OVCAR-3 was heterotransplanted into nude, athymic mice and treated with photodynamic therapy consisting of the hematoporphyrin derivative Photofrin II 10 ng/kg and argon-pumped dye laser light at 630 nm (200 J/cm2). Growth of tumors on one side of seven mice (treated tumors, n = 7) was compared with contralateral tumors (control tumors, n = 8) not exposed to laser. Hematoporphyrin derivative uptake was determined in tumor and other tissues. RESULTS Photodynamically treated tumors were completely ablated, and all remained absent. Hematoporphyrin derivative uptake was nonselective for tumor compared with other tissues. CONCLUSION This model provides reproducible parameters for the study of photodynamic therapy in the treatment of gynecologic malignancies and demonstrates the need for methods to increase selective uptake of hematoporphyrin derivatives.

Myonecrosis following deep pelvic hyperthermia

A case report is presented in which severe myonecrosis of the inferior anterior abdominal wall followed treatment of a recurrent pelvic tumour with an annular phased array (AA) deep heating device. This unusual complication has not been observed at this institution in 107 patients previously treated with deep pelvic or abdominal hyperthermia, who had undergone a total of 368 hyperthermia sessions. The injury was confirmed radiographically and histopathologically, and was associated with serum enzymatic elevations characteristic of muscular injury. The implications for clinical trials employing the AA or similar devices are discussed.

Comparative efficacy of oral flurbiprofen, intramuscular morphine sulfate, and placebo in the treatment of gynecologic postoperative pain.

This single-dose, double-blind, randomized, placebo-controlled study compared the efficacy of 50 mg of oral flurbiprofen (Ansaid, Upjohn), 10 mg of intramuscular morphine sulfate, and placebo in 92 patients with moderate to severe postoperative gynecologic pain. According to pain intensity, pain relief, and pain intensity difference scores, the morphine-treated patients experienced significantly more pain reduction than the other patients by the first hour after treatment. The flurbiprofen group obtained the same level of significant pain relief as the morphine group by two hours after dosing, but relief persisted longer than in the morphine-treated patients. Evaluation of other efficacy variables revealed similar levels of significant pain reduction in both the flurbiprofen and morphine groups compared with the placebo group. Flurbiprofen was well tolerated and led to fewer side effects than either morphine or placebo.

Pseudomyxoma peritonei associated with secondary infertility

In summary, we report a case of secondary infertility attributed to pseudomyxoma peritonei caused by ruptured appendiceal mucocele. Resection of the tumor and visible mucinous ascites resulted in spontaneous conception. We hypothesize secondary infertility was caused by significant peritoneal inflammation and inhibition of sperm-oocyte interaction from the ascites.

Adjuvant radiation in early stage, unfavorable histology endometrial carcinoma is associated with improved local control and survival

OBJECTIVE Unfavorable histology endometrial carcinomas confer worse prognosis. We determined the association of adjuvant radiation on local recurrence and survival for unfavorable, early stage endometrial cancer. METHODS We retrospectively identified 125 patients who had a hysterectomy for early stage (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3 endometrioid), endometrial carcinoma treated between 1992 and 2011. Patients were restaged according to current FIGO 2009 guidelines. Primary endpoint was local control and secondary endpoints were distant recurrence and overall survival. RESULTS The median age of the cohort was 67 years old with a mean follow up 152 months. Adjuvant radiation was delivered in 60 patients (48%). There were a total of 24 recurrences; 5 had local-regional recurrences, 4 local and distant recurrence, 12 distant only recurrences, and 3 had unspecified recurrences. The 5-year local-regional control was 97.8% in patients who received radiation and 80.1% in patients who did not receive radiation (p=0.018). The 5-year overall survival rate was 68.1% if patients did not receive radiation and 84.9% if they did receive radiation (p=0.0062). On univariate analysis, only radiation (HR 0.12, 95% CI: 0.03 to 0.49, p-value=0.018) was associated with a significant increase in local relapse free survival. CONCLUSIONS Adjuvant radiation therapy was significantly associated with an improvement in local-regional control and overall survival in patients with unfavorable histology, early stage endometrial cancer.

Advanced ovarian dysgerminoma with cure of tumor persistent in meninges

Isolated meningeal recurrence of ovarian cancer is uncommon. It is generally assumed that such cases are not accompanied by prolonged survival. We report the cure of a patient with advanced ovarian dysgerminoma who developed febrile carcinomatous meningitis 2 weeks after receiving her fifth course of combination chemotherapy (5 months after initiation of chemotherapy). No parenchymal brain disease was identified. The persistence of disease in the leptomeninges is related to the ability of the blood-brain barrier to exclude chemotherapeutic agents. The patient responded to craniospinal radiation and remains free of disease 2 years after completion of treatment.