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.     

A case of small cell carcinoma of the uterine cervix presenting Cushing''s syndrome

GABAA agonists do not respond to the same degree to allosteric modulators of the GABAA receptor complex such as benzodiazepines. We report there the effects of two steroids (alfaxalone and pregnenolone sulfate) on the inhibition induced by two GABAA agonists, 3-amino propane sulphonic acid (3-APS) and muscimol, on the extracellular evoked potentials obtained in CA1 of mice hippocampi. Alfaxalone (1 microM) potentiates the effects of both agonists, although incubation times longer than 15 minutes are required to potentiate the inhibitory effect of muscimol. Lower doses of pregnenolone sulfate at shorter incubation periods are able to inhibit the effects produced by single doses of 3-APS as compared to muscimol (15 microM during 5 min vs 30 microM during 5 min). Our results confirm the possibility that there might be differences in the interaction between GABAA agonists and modulatory steroids.     

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.     

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.     

Mucosal de novo cancer of the rectum following radiation therapy for uterine cancer

A 54-year-old woman who underwent a hysterectomy and radiation therapy for carcinoma of the uterine cervix developed mucosal de novo cancer of the rectum 12 years later. The rectal lesion was elevated, measuring 0.8 x 0.7 x 0.3 cm, and its surface was relatively smooth. Microscopically, this tumor consisted of a well-differentiated tubular adenocarcinoma which had invaded the depth of the mucosa. Late radiation injuries were observed around the tumor. We diagnosed this lesion as a radiation-induced mucosal de novo adenocarcinoma of the rectum on the basis of the criteria of Black and Ackerman (Clin Radiol 16:278, 1965). This case underscores the need for careful long-term follow-up studies of the large intestines of patients who underwent therapeutic irradiation for uterine cancer.     

Papillary squamous cell carcinoma of the uterine cervix: diagnostic pitfalls

BACKGROUND: In 1989, a Boeing 737-400 aircraft crashed at Kegworth, near Nottingham, England. The survivors suffered a large number of pelvic and lower limb injuries, and approximately one-third of the passengers died. Subsequent research has suggested that the "brace-for-impact" position that passengers are advised to adopt prior to a crash landing might be modified in order to reduce the incidence of such injuries. The aim of this research was to evaluate biomechanically such a modified crash brace position. HYPOTHESIS: A modified brace position would help to prevent injuries to some passengers in the event of an impact aircraft accident. METHODS: Impact testing on forward-facing seats was performed at the Royal Air Force Institute of Aviation Medicine, Farnborough, England. Aircraft seats, mounted on a sled, were propelled down a track to impact at -16 Gx. A test dummy was used as the experimental model. Four dummy positions were investigated: a) upper torso braced forward and lower legs inclined slightly rearward of the vertical; b) upper torso braced forward and lower legs inclined forward; c) upper torso upright and lower legs inclined slightly rearward of the vertical; and d) upper torso upright and lower legs inclined forward. The impact pulses used were based on Federal Aviation Administration guidelines. Transducers located in the head, spine, and lower limbs of the dummy recorded the forces to which each body segment was exposed during the impact. These forces were compared for each brace position. RESULTS: Impact testing revealed that the risk of a head injury as defined by the head injury criterion was greater in the upright position than in the braced forward position. The risk of injury to the lower limbs was dependent in part on the flailing behavior of the limbs. Flailing did not occur when the dummy was placed in a braced, legs-back position. CONCLUSIONS: A modified brace position would involve passengers sitting with the upper torso inclined forward so that the passenger's head rested against the structure in front, if possible. The legs would be positioned with the feet resting on the floor in a position slightly behind the knee. The position differs from those previously recommended in that the feet are positioned behind the knee. This study suggests that such a position would reduce the potential for head and lower limb injury in some passengers, given that only a single seat type and single size of occupant have been evaluated. Standardization to such a position would improve passenger understanding and compliance. Such a recommendation should not obscure the fact that an occupant seated in a forward-facing aircraft seat, restrained only by a lap belt, is exposed to considerable forces during an impact accident. Such forces are capable of producing injuries in the femur, pelvis, and lumbar spine.     

Small cell carcinoma of the uterine cervix: a clinicopathological review

Small cell carcinoma of the cervix is rare, with an aggressive natural history. We report on a series of 11 patients treated at the Christie Hospital, Manchester and examine their treatment and survival. Eleven patients with small cell carcinoma of the cervix were identified retrospectively from patient case notes. Treatment was individualised and included a variety of combinations of surgery radiotherapy and chemotherapy. Four patients were disease-free between 21 and 108 months (crude disease-free survival 36%). They presented with earlier disease and were older than the average for the group. They were all initially treated with radical radiotherapy. 7 patients died between 7 and 25 months. Despite combination chemotherapy, survival with advanced disease was poor. Published studies are small and fail to provide definitive answers on the best management of small cell carcinoma of the cervix. Drawing on the experience of small cell carcinoma of the lung however, combination therapy with radiotherapy, chemotherapy and possibly surgery requires careful assessment by an oncologist.     

Microinvasive carcinoma of the uterine cervix: A long-term followup study of eighty cases

One hundred and eleven patients with microinvasive carcinoma of the uterine cervix were studied over a 21-year period. Thirty-five cases of carcinoma in situ with questionable stromal invasion were excluded. Cases with pathologic examination of less than a cervical cone or the entire cervix were not accepted. The sole pathologic criterion for inclusion was unequivocal invasion to a depth of no more than 5.0 mm. Ninety-one patients were followed for 5 years or until death, and 80 patients for 10 years or until death. One patient was lost to follow-up at 5.5 years. The two deaths officially attributed to cervix cancer prior to 10 years were signed out by nonphysician assistant coroners. Available clinical evidence indicates that at least one of these patients, and probably both, did not die of cervix cancer. From these data, simple hysterectomy would seem to be the maximal treatment indicated. Since the prognosis of microinvasive carcinoma is similar to that of carcinoma in situ, it is suggested that such cases not be included when considering the end results of Stage I cervix cancer.     

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.     

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.     

Adenocarcinoma of the uterine cervix associated with pregnancy: a retrospective 10-year investigative study

Plasma proteins, especially albumin, account for much of the normal anion gap. The relationship between globulins and the anion gap has not received much attention except for reports of a narrowing of the gap associated with certain monoclonal immunoglobulin G gammopathies. The author presents a patient with polyclonal gammopathy, the magnitude of which correlated strongly and positively with the anion gap, along with data from 400 patients attending a renal hypertension clinic, which show a significant positive correlation between the anion gap and total globulins. These results indicate that both albumin and globulin concentrations should be taken into account when attempting to explain abnormalities or changes in the magnitude of the gap.     

Establishment of a new cell line, OKT1, from small cell carcinoma secreting ectopic ACTH of the uterine cervix

We have earlier shown that enterocyte mitochondria contain a phospholipase D (PLD) activity which can be stimulated by oxygen free radicals, divalent cations and polyamines. The functional significance of this enzyme in mitochondria is not known but it can be investigated using selective inhibitors. In the present study, mitochondrial PLD was activated by exposure to oxidants (X+XO or menadione), calcium or polyamines and the effect of antimalarial drugs, chloroquine, amodiaquin and primaquine on PLD activity was studied. Chloroquine and amodiaquine inhibited Ca2+ stimulated PLD activity in dose dependent manner whereas these drugs had no significant effect on PLD activated by oxidants or polyamines. Increasing the calcium concentration relieved the PLD inhibition by these drugs. Primaquine did not have any effect on calcium stimulated PLD activity whereas it slightly activated the enzyme. These results indicate that chloroquine and amodiaquine may bind with calcium making it unavailable for PLD activation.     

Clear cell adenocarcinoma of the uterine cervix: a histological and histochemical study

A case of Mullerian clear cell adenocarcinoma of the uterine cervix occurring in a young women is presented. A detailed histological and histochemical study of this type of tumour is important so as to separate it from the clear cell tumour of mesoenphric origin. The association of Mullerian clear cell adenocarcinoma and other abnormalities of the vagina and cervix with the administration of maternal nonsteroidal oestrogens has been recently stressed in the literature. However, our patient is illustrative of the 30-50% of cases reported to date which have few if any of the associated abnormalities of the genital tract and have no known exposure to non-steroidal oestrogens.     

Outcome of patients with brain metastases after combined modality therapy in small cell lung cancer (SCLC): a retrospective study

The authors evaluated the role of whole brain radiotherapy (WBRT) on the outcome of brain metastasis and survival in 41 patients with small cell lung cancer (SCLC) treated in their department. In addition to chemotherapy, radiotherapy was given to the primary site in all responder patients. Six patients presented brain metastasis initially and 10 patients after the fourth course of chemotherapy. Brain metastases were symptomatic in 12 of 16 patients with a median time of 5 months (1-14) until symptoms developed. All patients but 2 with brain metastasis received WBRT (30 Gy in 10 fractions) in addition to chemotherapy. The median survival time of patients with brain metastasis was 8.3 months (3.5 to 16) compared to 12 months (4 to 34+) for patients without brain metastasis. In addition, the median survival time for patients with brain metastasis who responded to systemic chemotherapy was better than that of nonresponders. The authors found no improvement in survival in patients who received concomitant WBRT after chemotherapy compared to patients who received WBRT after completion of chemotherapy. In conclusion, the role of consolidating cranial irradiation in addition to chemotherapy in SCLC patients is unclear and warrants prospective randomized studies.     

Reirradiation therapy for brain metastases from small cell lung cancer

Several evidences support the hypothesis that central catecholamines may play a significant role in the production and/or maintenance of different alterations that characterize portal hypertension. The aim of the present work was to study the possible modifications in norepinephrine (NE) metabolism in several telencephalic and diencephalic areas rich in NE in experimental prehepatic portal hypertension. NE uptake was studied as an index of NE metabolism. The experiments were carried out in vitro in encephalic areas and nuclei, obtained according to the punch-out technique. Results indicated that portal hypertensive rats showed an enhancement of NE uptake in olfactory bulb (OB), preoptic area (PA), and supraoptic, periventricular, paraventricular, and arcuate nuclei (SON, PeVN, PaVN, and AN, respectively) compared to sham-operated rats. However, no modifications on NE uptake was observed in the median eminence (ME). Present results suggest that the changes observed in central NE uptake may be related to the development and/or maintenance of the portal hypertensive state.