Race and clinical outcome in patients with carcinoma of the uterine cervix treated with radiation therapy

Epidemiologic and in vitro data have shown that the association of house-dust mite (HDM) allergy and snail allergy in the same patients was due to cross-reactivity between HDM and snail allergenic components. However, the cross-reacting allergen(s) have not yet been identified. In vitro reactivity of seven patients' sera to the various extracts and hemolymph of four different Helix snail species was analyzed by IgE detection and immunodots and Western blots. Cross-reactivity between snails and Dermatophagoides pteronyssinus was assessed by immunodot and ELISA inhibition in two patients. Heterologous inhibition of the snail immunodot and ELISA was observed in one serum. Western blotting showed a specific binding on all four snail species extracts; molecular weights of snail allergens ranged from < 21 to 200 kDa. Marked individual differences were observed in the seven sera under study; most sera demonstrated IgE recognition of multiple bands, illustrating that no single allergen is responsible for cross-reactivity between snail and mite. These results confirm that cross-reactivity exists between snails of the Helix genus and HDM. This cross-reactivity, involving more than a single allergen, may be of clinical significance in atopic patients allergic to D. pteronyssinus. The identity of the cross-reacting allergens remains to be determined. Potential candidates include the thermostable minor allergens of D. pteronyssinus, tropomyosin and hemocyanin.     

Intraarterial chemotherapy combined with radiation therapy for advanced cancer of the uterine cervix

The results of intraarterial chemotherapy (IACT) combined with definitive radiation therapy for 23 advanced and bulky carcinomas of uterine cervix are reported. IA-CT with cisplatin 50 mg and doxorubicin 30 mg was administered by one shot method in bilateral internal iliac arteries. The protocol consisted of one to three treatment session every 3 weeks. Nine of eleven patients with clinical stage III achieved a complete local response (82%), and the 3- and 5-year survival in these cases were 72% and 72%, respectively. These results were superior to the response (58%), 3- and 5-year survivals (68%, 58%) obtained in 19 patients treated mainly with radiation therapy alone. The side effect of grade 2 and 3 for the intestine, such as ileus and hemorrhagic colitis, was noted in 3 patients (15%). In addition, 3 of 8 patients with radical surgery and postoperative radiation therapy after IA-CT developed insufficient fracture of pelvic bone. These complications accompanied by IA-CT combined with radiation therapy and/or surgery increased slightly, compared with that by the previous therapy without IA-CT, but were not critical. The results suggest that IA-CT following radiation therapy is effective to improve the prognosis of patients with Stage III cervical cancer.     

Carcinoembryonic antigen in patients treated with radiation therapy for invasive squamous cell carcinoma of the uterine cervix

Plasma carcinoembryonic antigen (CEA) levels in 75 patients with invasive cervical cancer were measured during and after radiation therapy. Initial CEA levels were elevated in 65% of the patients, the incidence varying with stage of disease. Of the 32 patients followed during therapy, CEA levels rose in 26 (81%). CEA values after therapy in the same 32 patients showed three patterns: (1) decline to normal, associated with a disease-free state; (2) decline but not to normal, associated with heavy cigarette smoking or persistent disease; and (3) decline to normal, followed by a rise to abnormal, associated with tumor recurrence. Elevation of CEA levels preceded recognition of recurrent cervical cancer by as much as 4 months in five of seven patients.     

Outcome of obstructive uropathy after pelvic irradiation in patients with carcinoma of the uterine cervix

A prospective, randomized study was performed to assess the effectiveness of postoperative closed suction drainage. One hundred and twelve consecutive procedures involving autologous iliac-crest bone graft were performed, from December 29, 1992, to July 1, 1993, following a traumatic injury of the spine in 108 patients. Sixty of the sites from which the bone graft had been obtained were drained with a single large Hemovac device. The drains were maintained for two to five days postoperatively. The remaining fifty-two incisions were closed without a drainage device. All patients were evaluated clinically for problems with wound-healing. The incisions were considered to be healed when they had been asymptomatic for one year. Of eleven patients who had problems with wound-healing, six had been managed with a drain and five had not. The findings of this study do not support the routine use of drainage at the donor sites of iliac-crest bone grafts.     

Prognostic value of bcl-2 expression in patients with operable carcinoma of the uterine cervix

The nucleus retroambiguus (NRA) is a group of premotor neurons at the transition between brainstem and spinal cord. It projects to certain motoneuronal cell groups, among which is a distinct set of motoneurons in the lumbar enlargement innervating muscles including iliopsoas, adductor longus, and hamstrings. To find out whether these NRA-motoneuronal projections are monosynaptic, injections of wheat germ-agglutinin horseradish peroxidase (WGA-HRP) into the NRA were combined with injections of cholera toxin subunit b (CTb) into the hamstring muscles. Electron microscopical examination revealed that the NRA terminal profiles make monosynaptic contacts with dendrites of motoneurons innervating these muscles. The NRA terminal profiles formed asymmetrical synapses, and contained spherical and a few dense core vesicles. These findings provide evidence of monosynaptic NRA-hindlimb motoneuronal projections which are likely to be excitatory.     

Neuroendocrine differentiated carcinoma of the uterine cervix

Cervical neuroendocrine carcinomas (CNC) are rare tumors. The term includes the cervical carcinoid, the small cell (oat-cell) carcinoma and the primitive neuroectodermal tumor (PNET). Between 1979 and 1993 eight CNC out of 788 cervical carcinomas were identified by conventional light microscopy and immunohistochemistry. Three tumors were small cell carcinomas with positive staining for NSE (6/8 tumors) and chromogranin A (2/8). In one case a PNET was diagnosed by identifying rosette like structures and negative immunohistochemistry for neuroendocrine markers. Two patients (including PNET) died of disease 3.1 (1.3 to 4.8) years after diagnosis. The others showed no evidence of disease after a mean follow up to 4.4 years. Three of them got pelvic radiation postoperatively. Four tumors showed foci of squamous cell carcinoma [3] and adenocarcinoma [2]. There is no evidence, that these foci influence the prognosis on CNC. Therefore, it is important to recognize the neuroendocrine component, as this type of carcinoma requires special therapeutic considerations. The authors favour the metaplastic origin of CNC from a multipotent (endocervical) stem cell.     

The management and natural history of severe dysplasia and carcinoma in situ of the uterine cervix

From 1951 to 1972, a total of 631 cases of invasive carcinoma of the cervix were diagnosed in Frederiksberg, Copenhagen, Denmark. Treatment was either by surgery or radiotherapy, a combination of both being rarely used. The crude five-year survival rates were 99 per cent in stage Ia, 79 per cent in stage Ib, 67 per cent in stage IIa, 45 per cent in stage IIb, 23 per cent in stage III, 5 per cent in stage IV and 63 per cent for all stages. The relative survival rates were respectively 100 per cent, 81 per cent, 73 per cent, 48 per cent, 26 per cent, 5 per cent and 66 per cent. Radical hysterectomy were found more effective than radiotherapy in stage Ib carcinoma of the cervix. This difference was not explained by age but other factors possibly playing a role are considered. The combination of surgery and radiotherapy is discussed and only seems indicated for patients with stage Ib carcinoma and lymph node metastases.     

Stage I carcinoma of the uterine cervix in patients under 40 years of age

A retrospective analysis was made 94 patients, 39 years of age or younger, who were treated for Stage I carcinoma of the uterine cervix from 1942 through 1972 at the Los Angeles Tumor Institute and the Southern California Cancer Center. Comparisons were made between the frequency of Stage I and other stages of carcinoma of the uterine cervix, as well as the frequency of Stage I carcinoma in young and older individuals. Survival rates for the younger group were compared to those for the same stage of disease for all ages of patients. There is discussion of the treatment modalities used in light of recommendations for future plans of therapy for these young patients. Tumor recurrences are discussed, with special reference to 43 patients who survived over 10 years. Eight of these patients were found to show new or recurrent tumors after this period of time. The importance of careful, long-term follow-up and early secondary treatment for recurrent lesions is emphasized, since subsequent radical surgery may salvage a number of these individuals.     

Angiogenesis in squamous cell carcinoma in situ and microinvasive carcinoma of the uterine cervix

OBJECTIVE: To evaluate angiogenesis in squamous cell carcinoma in situ (CIS) and microinvasive squamous cell carcinoma of the uterine cervix and to investigate the relations among angiogenesis, stromal inflammation, and depth of invasion. METHODS: Three groups of women were studied: 22 controls who had undergone hysterectomy for benign conditions; 18 with squamous cell CIS of the cervix who underwent cone biopsy, hysterectomy, or both; and 14 with microinvasive squamous cell carcinoma who underwent conization of the cervix and subsequent surgical management according to depth of invasion. All specimens were stained immunohistochemically for factor VIII-related antigen. Areas below the basement membrane with the highest angiogenic density were selected. The degree of stromal inflammatory reaction was assessed. Statistical analyses included Kruskal-Wallis, analyses of variance and covariance, Scheffe and Bonferroni-Dunn post hoc procedures, and Pearson correlation analysis. P < .05 was considered statistically significant. RESULTS: Microvessel counts per high-power field (x 400) of microinvasive squamous cell carcinoma of the cervix differed significantly from those of controls and squamous cell CIS (median 34.5 per high-power field, range 9-76 versus median 17, range 7-47, and median 19, range 8-39, respectively; P < .005). Microvessel counts per high-power field in squamous cell CIS did not differ significantly from those of controls (P = .91). Among patients with microinvasive squamous cell carcinoma of the cervix, no significant correlation was found between microvessel counts per high-power field and the depth of invasion (r = 0.19, P = .51). Stromal inflammatory reaction (graded 0-3) differed significantly among controls, squamous cell CIS, and microinvasive carcinoma (mean 0.40, 0.83, and 1.64, respectively; P < .005). CONCLUSIONS: Microinvasive squamous cell carcinoma of the uterine cervix is angiogenic, but depth of invasion is not associated with increased angiogenicity. Squamous cell CIS is not angiogenic.     

Organ preservation in locally advanced carcinoma of the uterine cervix

The purpose of this study was to demonstrate the potential usefulness of the combination of gadolinium and dysprosium to enhance the different between normal and necrotic liver tissue. Small regions of acute necrosis were induced by injecting 200-300 microliters of 95% alcohol into the liver of 26 rats. MRI was performed 24 hours after necrosis induction, before and immediately after injection of one or both contrast agents. Using a mixed T1/T2-weighted sequence, the signal intensity of (SI) of the normal liver was reduced by 70%, whereas the necrotic regions had more than a 50% increase in SI after double contrast. The region that was enhanced corresponded largely with the region of necrosis as observed postmortem. The lesion size, when identified, was largely underestimated using either of the agents along, albeit using the common pulse sequences. The double contrast effect of simultaneous administration of gadolinium and dysprosium allows accurate delineation of liver necrosis.     

Squamous cell carcinoma markers in neoplasms of the uterine cervix

In an extremely well-controlled study, Cohen et al. (1998) add to prior knowledge of stress-illness relationships by showing that self-reports of stress occurrence and duration of 1 month or more, rather than estimates of stressor severity, predict susceptibility to experimentally induced colds (i.e., viral replication and cold symptoms). Although ruling out obvious behavioral and personality factors as causes of the association of stressors to colds, they were unable to identify mediational immune factors, a deficit attributable to the difficulty of assessing the multi-layered, dynamic physiological processes within the bidirectional connections of the nervous (stress) and immune systems. The findings provide an interesting complement to data, showing that people use stressor duration in evaluating the illness implications of somatic symptoms (Cameron et al., 1995), and suggest caution with regard to overestimating the prevalence of stress-induced colds in natural settings.     

Prognostic factors in patients with carcinoma of the uterine cervix treated with external beam irradiation and IR-192 high-dose-rate brachytherapy

The spectral properties of the protochlorophyllide forms in the epicotyls of dark-grown pea seedlings have been studied in a temperature range, from 10 to 293 K with conventional fluorescence emission and excitation spectroscopy as well as by fluorescence line narrowing (FLN) at cryogenic temperatures. The conventional fluorescence techniques at lower temperatures revealed separate bands at 628, 634-636, 644 and 655 nm. At room temperature (293 K) the 628 and 634-636 nm emission bands strongly overlapped and the band shape was almost independent of the excitation wavelength. Under FLN conditions, vibronically resolved fluorescence spectra could be measured for the 628 and 634-636 nm bands. The high resolution of this technique excluded the excitonic nature of respective excited states and made it possible to determine the pure electronic (0,0) range of the spectra of the two components. Thus it was concluded that the 628 and 634-636 nm (0,0) emission bands originate from two monomeric forms of protochlorophyllide and the spectral difference is interpreted as a consequence of environmental effects of the surrounding matrix. On the basis of earlier results and the data presented here, a model is discussed in which the 636 nm form is considered as an enzyme-bound protochlorophyllide and the 628 nm form as a protochlorophyllide pool from which the substrate is replaced when the epicotyl is illuminated with continuous light.     

Small-cell neuroendocrine carcinoma of the uterine cervix associated with micro-invasive squamous cell carcinoma and adenocarcinoma in situ

A case of small-cell neuroendocrine carcinoma of the uterine cervix associated with squamous cell carcinoma and adenocarcinoma in situ is reported. The tumor consisted mainly of uniform small cells with a population of intermediate cells that resembled carcinoid tumor cells. Foci of micro-invasive squamous cell carcinoma and adenocarcinoma in situ were recognized separately, adjacent to the main tumor. Both Grimelius stain and immunostaining of serotonin were positive for small-cell and intermediate-cell carcinoma. Neurosecretory granules were demonstrated by electron microscopy. Microacini with positive mucin staining and microvilli-like structures suggested glandular or exocrine differentiation of the tumor. Three distinctive types of differentiation, neuroendocrine, exocrine and squamous characteristics, were expressed in the tumor.     

Late rectal sequelae following definitive radiation therapy for carcinoma of the uterine cervix: a dosimetric analysis

OBJECTIVE: The structure of the collagen scar during healing of a myocardial infarction is a determinant of the function of the remodeled tissue. We hypothesize that the passive deformations of both scar and normal tissue are related to the underlying collagen uncoiling as the tissue stretches, and that the unloaded tortuosity of the collagen may be a determinant of tissue stiffness at low ventricular pressure. Hence collagen uncoiling and tissue strain were measured during passive loading in normal tissue, and in healing infarct tissue. METHODS: Left ventricles of rats were infarcted by ligation of the left anterior descending artery for 2 weeks. Surface strains were measured during passive inflation in the scar region in one set of excised hearts, and other arrested hearts were fixed at different ventricular pressures, after which collagen tortuosity was measured in the infarcted and normal tissue. RESULTS: Passive loading strains were smaller in the scar in both the fiber and cross-fiber directions. Tortuosity decreased with load in normal and infarcted tissue, with fibrils tending to straighten more in the scar tissue at higher pressures (1.056 +/- 0.009 vs. 1.024 +/- 0.009 at P = 20 mmHg) with similar tortuosities at zero pressure (1.110 +/- 0.012 vs. 1.098 +/- 0.019). The decrease in tortuosity with strain was greater for the infarcted tissue. CONCLUSIONS: The greater stiffness of infarcted tissue at low pressure is not due to 'straightened' collagen fibers, and there may be a different three-dimensional structure of infarct vs. normal coiled collagen fibers which can affect the material properties of these tissues.     

Cystoscopic staging of carcinoma uterine cervix, revisited

Of the 378 cases of stage 3 carcinoma uterine cervix, only 10 showed vesical invasion, while 19 of 24 cases of stage 4 disease had vesical invasion. Results of this procedure did not alter the management of the disease in any of these cases. From the whole series it was concluded that cysto-urethroscopy is an unnecessary, cost ineffective, invasive procedure which has no role in either diagnosis or in planning the definitive treatment of carcinoma uterine cervix.     

The long-term course of carcinoma in situ of the uterine cervix

The malignant potential of carcinoma in situ (CIS) of the uterine cervix has been the subject of great controversy. Despite refinements and additions to knowledge in this area, few reports on the long-term course of the disease have appeared in the past decade. Recent developments in diagnostic and therapeutic techniques coupled with changes in the patient population with this disease have prompted renewed interest in conservative management. Results of long-term observation of a group of patients followed initially without ablative therapy are reported. The data indicate that CIS of the uterine cervix is not the inevitably progressive disease that it has been considered to be. Unequivocal invasive cancer develops in only a small percentage of cases and can be controlled, if not cured, by current therapeutic modalities. The intraepithelial lesion, however, tends to persist despite conization, and eventually requires ablative therapy in most cases. Conservative procedures should be regarded as temporizing, at least until their long-term benefits can be recorded.     

Uterosacral space involvement in locally advanced carcinoma of the uterine cervix

PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino) propanamide, methanesulfonate] is a structurally novel anticonvulsant having Na+ channel-blocking and glutamate release-inhibiting properties, as well as being a MAOB inhibitor. Its anticonvulsant activity was evaluated in the maximal electroshock (MES) test and in chemically induced seizures (bicuculline, BIC; picrotoxin, PIC; 3-mercaptopropionic acid, 3-MPA; pentylenetetrazole, PTZ; strychnine, STRYC). Behavioral toxicity was evaluated in the rotorod test with measurements of spontaneous locomotor activity and passive avoidance responding. The anti-MES activity of PNU-151774E in both mice and rats, respectively, produced ED50 values of 4.1 mg/kg and 6.9 mg/kg after i.p. administration or 8.0 mg/kg and 11.8 mg/kg after p.o. administration. Oral anti-MES activity in rats peaked between 1 and 2 h after administration and was evident up to 4 h. This activity was related to brain levels of unchanged drug which peaked at 37 mM within 1 h. Oral ED50 values (mg/kg) effective in blocking tonic extension seizures by chemical convulsants in mice were: BIC (26.9), PIC (60.6), 3-MPA (21.5), STRYC (104.1) and PTZ (26.8). This potency was associated with high therapeutic indices relative to: MES (78.2), BIC (23.3), PIC (10.3), 3-MPA (29.1) and STRYC (6.0). No evidence of tolerance to anti-MES activity after repeated dosing was observed. PNU-151774E did not show anti-absence seizure activity as assessed by i.v. infusion of PTZ. PNU-151774E impaired spontaneous activity in rats only at the oral rotorod ED50 dose of 700 mg/kg p.o. PNU-151774E did not impair passive avoidance responding at doses up to 40 times the oral MES ED50 dose in rats. These results indicate that PNU-151774E is an anticonvulsant effective in various seizure models with a wide therapeutic window, and with a low potential to induce tolerance and locomotor or cognitive side effects.     

Identification and biosynthesis of fibrinogen in human uterine cervix carcinoma cells

Fibrinogen has been detected in ME-180 human uterine cervix carcinoma cells, and synthesis of fibrinogen by ME-180 cells has been measured using [35S] L-methionine incorporation. Expression of mRNA for the B beta-chain of the fibrinogen in ME-180 cells has been identified by PCR-assisted mRNA amplification. The A alpha-, B beta-, and gamma-chains of fibrinogen synthesized by ME-180 cells were chemically and immunologically identical to those of plasma fibrinogen. These findings suggest that fibrinogen is present and synthesized in ME-180 human uterine cervix carcinoma cells, and that fibrinogen plays a role in these malignant tumor cells.     

Technically accurate intracavitary insertions improve pelvic control and survival among patients with locally advanced carcinoma of the uterine cervix

The purpose of this study was to document whether the technical qualities of a brachytherapy application impacts on the outcome of patients with locally advanced cervix cancer treated by definitive irradiation. A previous report from the patterns of care study demonstrated the importance of brachytherapy in the treatment of locally advanced cervix cancer. Locally advanced disease was defined as FIGO stages Ib (if tumor diameter was < or = 4 cm), IIb (if disease was bilateral or involved the lateral aspect of either parametrium), and III. Localization films from 128 patients with locally advanced squamous cell carcinoma of the cervix were reviewed by a radiation physicist and a radiation oncologist with expertise in gynecologic radiotherapy. All patients received external beam irradiation followed by one brachytherapy application (median point A dose = 8040 cGy; range, 4083-10,020 cGy). Brachytherapy parameters assessed were (a) the distance between the right colpostat source and the distal tandem source, (b) the distance between the left colpostat source and the distal tandem source, and (c) the symmetry of colpostat placement. Implants were scored as "ideal" (n = 8) when all three parameters were deemed satisfactory, "unacceptable" (n = 17) when none of the parameters was deemed satisfactory, and "adequate" (n = 41) in all other cases. Significantly improved 5-year local control was seen when comparing ideal and adequate placements to unacceptable placements (68% vs 34%, P = 0.02). A strong trend toward improved 5-year survival was also noted among the group with ideal and adequate implants as opposed to unacceptable implants (60% vs 40%). Multivariate analysis showed that the technical adequacy of the brachytherapy implant was the most important prognostic discriminant of local control. In conclusion, these analyses demonstrate the direct influence of competent technical implant performance on tumor control and even survival. While only a small fraction of implants for cervical cancer are performed poorly in the United States, there is a need for continued emphasis of the principles for proper implant technique.