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Biomedical subjects

G Delgado

Publications and source records attributed to G Delgado.

At least 19 recordsLinked to original sources

Histopathologic predictors of the behavior of surgically treated stage IB squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study.

Disagreement persists about the superiority of Reagan and Ng's method over that of Broders' for the histologic grading of squamous carcinoma of the cervix. Uncertainty about the predictive value and reproducibility of any of the grading methods prompted a comparison of factors previously suggested as indicating the biologic behavior for cervical squamous carcinoma. One hundred ninety-five women, who were enrolled in a Gynecologic Oncology Group treatment protocol of Stage IB squamous carcinoma of the cervix and underwent radical hysterectomy with pelvic and paraaortic node sampling, formed the study population. The tumors were graded first by participating institutional pathologists, with submitted slides subjected to an independent review by two pathologists (R.J.Z. and S.W.). The histologic parameters examined included the presence and amount of keratinization, nuclear pleomorphism, mitotic rate, gestalt grading, pattern of invasion at the stromal interface, and inflammatory cell infiltrate. The depth of invasion and presence or absence of vascular invasion also were assessed. The probability of pelvic lymph node metastasis and the progression-free interval were determined for each parameter. Surprisingly, none of the grading methods was effective in predicting nodal spread or progression-free interval. However, an increasing depth of invasion strongly correlated with nodal spread and a diminished progression-free interval (P less than 0.0001). Vascular invasion was less effective in these predictions (0.05 less than P less than 0.10). Both measurements were reasonable reproducible. It was concluded that histologic grading of surgically treated cervical carcinoma is not useful but that the depth of invasion and vascular invasion are important predictors of behavior that should be reported routinely.

Carcinoma, Squamous Cell

Ovarian metastases in stage IB carcinoma of the cervix: a Gynecologic Oncology Group study.

Surgical and pathologic findings at laparotomy for radical hysterectomy in 990 patients with clinical stage IB carcinoma of the cervix were analyzed to determine the frequency of metastases to the ovary. Ovarian spread was identified in 4 of 770 (0.5%) patients with squamous carcinoma and 2 of 121 (1.7%) with adenocarcinoma. No patients with adenosquamous carcinoma (n = 82) or other histologic types (n = 17) had ovarian metastases. Although the frequency of metastases was greater among patients with adenocarcinoma, this was not statistically significant (p = 0.19, Fisher's exact test). All 6 patients with ovarian metastases had other evidence of extracervical disease. Three underwent radical hysterectomy and bilateral salpingo-oophorectomy. Of these, one patient received extended field radiotherapy and died of disease 18 months after diagnosis. Two patients, one treated with combination chemotherapy and one with no adjunctive therapy, are alive without evidence of disease at 59 and 62 months, respectively. Three patients underwent exploratory laparotomy with salpingo-oophorectomy and lymphadenectomy without hysterectomy. All three patients died of disease at 2, 3, and 30 months; the first and last patient received adjunctive radiotherapy. Not all patients underwent oophorectomy. Of 347 patients with at least unilateral ovarian preservation, no postoperative pelvic radiotherapy, and no gross extracervical disease or metastasis to the paraaortic nodes, pelvic recurrence developed in 16. There was no excess of pelvic recurrences in patients with adenocarcinoma (0/41) or adenosquamous carcinoma (1/29, 3.4%) when compared with those with squamous carcinoma (15/270, 5.6%). This suggests no excess of occult ovarian metastases in nonsquamous tumors of the cervix. There is no evidence in these data of an increased risk of ovarian preservation in patients with stage IB carcinoma of the cervix with no gross extracervical disease.

Adenocarcinoma

Radiotherapy of malignant subdiaphragmatic implants in advanced ovarian carcinoma: a new technique.

We report the development of a new technique using remote afterloading intraoperative radiation therapy to deliver a tumoricidal dose to diaphragmatic tumor implants. A multi-positional lucite applicator was designed based on anatomic studies of the diaphragmatic surface to accommodate a high dose rate iridium source in a series of needles placed 1.5 cm apart. The applicator curvature can vary from planar to full accommodation of the diaphragmatic surface with a constant source to surface distance of 0.5 cm. The applicator has been piloted in three patients with ovarian carcinoma with residual subdiaphragmatic disease found at second look laparotomy, to deliver a dose of 1,500 to 2,000 cGy at 0.5 cm. Tolerance of the diaphragm and hepatic surface has been excellent. There were no postoperative complications and no deterioration in liver function studies. The additional postoperative external beam irradiation directed with the aid of surgically placed clips and gated to respiratory movements permits achievement of a tumoricidal dose while limiting the treated volume and related toxicities.

Brachytherapy

Uterine serous carcinoma. A morphologically diverse neoplasm with unifying clinicopathologic features.

This study compares the clinicopathologic features of 13 pure uterine papillary serous carcinomas (UPSC) with 19 tumors consisting of UPSC admixed with other types of endometrial carcinoma and nine UPSC associated with endometrial polyps. The mean patient age, frequency of preoperative clinical understaging, postoperative pathologic stage, and survival of patients was similar for the three groups. Surprisingly, widespread metastasis, recurrence, and death occurred even in those cases where myometrial invasion amounted to less than 1 mm or where tumor was confined to an endometrial polyp. Poor prognosis appeared to be related to a propensity for vascular invasion and multifocal carcinogenesis. The latter was manifested by the presence of cytologically malignant cells closely resembling the invasive serous carcinoma in the surface endometrium adjacent to the tumor in 89% of cases and in multiple sites in the genital tract and abdomen. This lesion, designated "intraepithelial carcinoma," was present in the endocervix in nine (22%) of the 41 cases, in the fallopian tube in two cases (5%), on the surface of the ovary in four cases (10%), and on peritoneal surfaces or omentum in 10 cases (25%). In addition, we found that UPSC display considerable morphologic heterogeneity. Foci of clear-cell carcinoma were identified in 13 (32%) of the 41 tumors. In five (12%) neoplasms, the invasive component was composed primarily of glands; and in 22 (54%) tumors, thin as opposed to thick papillae predominated. Accordingly, UPSC may be broadly defined as a carcinoma that displays foci of well-differentiated papillae lined by cells that are markedly atypical cytologically. UPSC frequently contain areas of clear cells. Glands with papillary infoldings sometimes predominate in the invasive component. Because the behavior of endometrial neoplasms, in which at least 25% of the carcinoma exhibits a glandular or papillary architecture with serous differentiation, is similar, the term "uterine serous carcinoma" is an appropriate designation for these tumors, regardless of whether other patterns of differentiation are present or whether the tumor is associated with a polyp.

Adenocarcinoma

Lack of protective effect of thromboxane synthetase inhibitor (CGS-13080) on single dose radiated canine intestine.

The effect of a thromboxane A2 synthetase inhibitor (CGS-13080) on canine intestine was studied using a single dose of radiation, and radioactive microspheres were used to determine resultant blood flow. Thromboxane A2 causes vasospasm and platelet aggregation and may play a dominant role in radiation injury. However, there was no effect on the intestinal blood flow diminution occurring after radiation in this laboratory model using this thromboxane A2 synthetase inhibitor.

Animals

Identification of human papillomavirus type 16 in primary and recurrent cervical cancer following radiation therapy.

Formalin-fixed, paraffin-embedded tissue blocks from 13 women with cervical carcinoma that recurred following radiation therapy were evaluated for the presence of human papillomavirus (HPV) by in situ hybridization using ribonucleic acid 35S-labeled probes for HPV types 6, 11, 16, and 18. Ten of thirteen patients also had pretreatment biopsies from their primary tumors available for analysis. HPV 16 was detected in both primary and recurrent lesions in 4 women. In 1 case, HPV was detected in the primary tumor and not in the recurrence. HPV 16 was also present in three recurrent cancers from which primary lesions were not available for probing. Radiation therapy did not alter the hybridization signal strength or pattern, suggesting that the HPV genome copy number was not significantly affected. The persistence of HPV 16 in recurrent cervical carcinoma is consistent with the theory that HPV plays a role in maintaining the malignant state.

Adult

Manometric characterization of rectal dysfunction following radical hysterectomy.

Bladder dysfunction thought to be due to partial denervation has been described following radical hysterectomy. Some patients experience acute and chronic rectal dysfunction characterized by difficulty with defecation and loss of defecatory urge. To define this abnormality, anorectal pressure profiles were examined in 15 patients with Stage I carcinoma of the cervix before and after radical hysterectomy. Profiles were done using standard anorectal manometry with a water-infused system. In all patients preoperative manometric profiles were normal; postoperative studies were abnormal in all patients. Features seen include altered relaxation of the internal sphincter, increased distension needed to trigger relaxation, and decreased rectal sensation; external sphincters and resting internal sphincters were unchanged. Postoperatively, 12 patients reported problems with rectal function. A physiologic defect is definable in patients undergoing radical hysterectomy; this suggests disruption of the spinal reflex arcs controlling rectal emptying. These physiologic abnormalities correlate with the clinical symptomatology experienced by some patients. Continuing definition and evaluation of management options in this situation should be useful in developing effective therapy for rectal dysfunction following radical hysterectomy.

Defecation

Reverse hysterocolposigmoidectomy (RHCS) for resection of panpelvic tumors.

Lateral retroperitoneal approaches to abdominopelvic masses are commonly employed; the reverse hysterocolposigmoidectomy (RCHS) in addition utilizes transabdominal entry of the vaginal and rectovaginal spaces to provide medial access to the uterosacral and cardinal ligaments as well expose a tumor-free segment of the rectosigmoid for en bloc resection of panpelvic tumors. Thirty-one patients underwent reverse hysterocolpectomy for extensive, symptomatic pelvic malignancies. All patients had complete resection of pelvic tumor, and there were no perioperative deaths. Sigmoid resection was required in 25 patients with 22 primary reanastomosis and 3 end colostomies performed. In 6 patients, vaginal entry facilitated tumor resection while sparing the rectosigmoid. Average operative blood loss was 2677 cc. Early postoperative morbidity (1-30 days) occurred in 13 patients; febrile morbidity (6 patients) was the common complication. Late morbidity (1-6 months) was seen in 10 patients, including 1 fatal pulmonary embolism at 5 months. Subsequent therapy was tolerated well. Mean survival/follow-up is 15.7 months (range, 1 to 49 months). Seventeen patients are alive, seven patients without evidence of disease (average 13.4 months), and ten patients are alive with disease (average follow-up, 28.3 months). Thirteen patients are dead of disease or complication (average survival, 13.7 months). We conclude that RHCS facilitates resection of extensive pelvic tumors with acceptable morbidity.

Adult

Long-chain phenols from the bark of Amphypterygium adstringens.

The hexane extract of the stem bark of Amphypterygium adstringens at a dose of 100 mg/kg subcutaneously exhibited significant hypocholesterolemic effect on 24-h fasted rats, lowering the cholesterol levels by 31%, an effect similar to 15 mg/kg estrone given by the same route. Column chromatography of the active extract allowed the isolation of two mixtures of long chain phenols (Mixture I and Mixture II). According to GC/MS analysis, Mixture I contained five alkyl phenolic acids and Mixture II three alkyl phenolic aldehydes. Neither of the mixtures exhibited significant hypocholesterolemic activity at doses up to 15 mg/kg subcutaneously.

Animals

[Ureteroscopy. Experience and results].

Ureteroscopy is an Endo-urological procedure which has been practiced around the world in all teaching centers of Urology. It presents obvious advantages. Our experience has been satisfactory, not only due to the coordinated and joint work, but for the results obtained in behalf of our patients who went back to their regular activities shortly after. As all the new procedures, it has a learning curve which is given after the initial training has been acquired but its performance will give expertise, same as radiologic technology and the development of new instruments with smaller diameter and accessories which allow the easier access to ureter and lithotripsy.

Adolescent

Radical hysterectomy morbidity in relation to age.

The complications of radical hysterectomy in patients 65 years and older were compared with those in women younger than 65. There was no statistical difference in complication rates between the two groups, although the older women had a significantly higher incidence of preoperative medical problems. No surgical deaths occurred in either group. Our data indicate that selected older women can tolerate radical hysterectomy as well as younger ones.

Adult

Oral contraceptive use, human papillomavirus infection, and risk of early cytological abnormalities of the cervix.

Oral contraceptive (OC) use was examined as a risk factor for cytological abnormalities of the cervix among 1964 women receiving Papanicolaou smears at three hospitals in the Washington, D.C., area. A single pathologist classified cytological results from all women as normal (n = 1423), atypia (n = 314), low grade squamous intraepithelial lesion (SIL; n = 208), or high grade SIL (n = 19). Women in each of the three abnormal groups were compared to women with normal cytological diagnoses. A subset of 579 patients, including most of the women with low or high grade SIL and a matched group of controls, was tested for human papillomavirus (HPV) by type-specific Southern blot hybridization to examine the effects of OC use while taking into account the effects of HPV infection. OC use was found to be unrelated to risk of atypia or low grade SIL but was associated with an elevated risk of high grade SIL that increased with longer duration of use (relative risk = 4.6, 95% confidence interval = 1.1-18.1 for greater than or equal to 5 years of use). HPV infection was associated, as expected, with risk of low and high grade SIL but not with atypia. Taking the HPV results into consideration did not alter the OC findings. There was no evidence that OC use synergistically increased the risk of cervical neoplasia among HPV-infected women, although small numbers prevented a reliable evaluation for high grade SIL. OC use did appear to increase the detection of HPV types 16/18, but the etiological importance of this finding is unclear.

Adult

Neuroleptic malignant syndrome treated with subcutaneous lisuride infusion.

A schizophrenic patient developed a characteristic clinical picture of neuroleptic malignant syndrome (NMS) while admitted to the hospital during an exacerbation of his psychiatric symptoms. Oral treatment of the NMS with bromocriptine (7.5 mg/day) or levodopa/carbidopa (125/12.5 mg) provoked intense vomiting in spite of domperidone (60 mg/day), which led to their discontinuation. In view of the deterioration of the symptoms, treatment was begun with lisuride (1-2 mg/24 h) subcutaneously. An obvious improvement was shown in 24 h, but levodopa/carbidopa (125/12.5 mg t.d.s. orally) had to be added later to achieve complete resolution of the NMS. During the recovery phase, while being treated with subcutaneous lisuride infusion and levodopa (p.o.), the patient presented with confusion, agitation, and hallucination. Lisuride infusion was stopped and levodopa was continued until complete resolution of the NMS. This case indicates that parenteral administration of lisuride or other dopamine agents such as levodopa (i.v.) or apomorphine (s.c.) may be considered an effective and practical way of treating NMS, particularly when the patient's condition makes it difficult or impossible to use other dopaminergic drugs by the oral route.

Adult

The use of in situ hybridization to show human papillomavirus deoxyribonucleic acid in metastatic cancer cells within lymph nodes.

Southern blot hybridization has been used to identify human papillomavirus types in both primary tumors and lymph node metastases. However, this technique requires fresh-frozen tissue and is incapable of localizing deoxyribonucleic acid sequences to specific cell types in the tumor sample. In contrast, in situ hybridization precisely locates viral sequences within tumor cells while preserving cellular architecture. Further, in situ hybridization requires only small samples of formalin-fixed, paraffin-embedded tissues. Five lymph nodes (from four patients) containing metastatic cervical squamous tumor cells (identified with hematoxylin and eosinophil staining) were analyzed with in situ hybridization techniques with human papillomavirus type 16 deoxyribonucleic acid probes labeled with sulfur 35. The primary cervical cancer from all four patients had been shown to contain human papillomavirus type 16 sequences by Southern blot. Three specimens from two patients clearly showed the presence of human papillomavirus type 16 sequences within the nuclei of metastatic tumor cells, whereas two specimens were nondiagnostic most likely as a result of the small volume of cancer relative to the size of the lymph node. This information indicates that it is the tumor cells themselves that contain viral deoxyribonucleic acid and provides additional evidence linking human papillomavirus with cervical carcinogenesis.

Autoradiography

Rapid dysplastic transformation of human genital cells by human papillomavirus type 18.

This study delineates differences in biologic activity between human papillomavirus (HPV) types 16 and 18. Human cervical and foreskin epithelial cells were cultured and transfected with recombinant HPV-16 and -18 DNA, resulting in immortalized cell lines. Normal epithelial cells as well as HPV-16 and -18 immortalized cells of both early passages (less than 40 population doublings) and late passages (greater than 180 population doublings) were transplanted in athymic mice. Normal squamous cells formed well-stratified epithelium, while HPV immortalized cells developed either normal-appearing epithelium or typical dysplastic changes. Dysplastic changes were seen in none of the 13 grafts with early-passage HPV-16 cell lines, while 9 of 14 grafts with early-passage HPV-18 cell lines developed dysplasias (P less than 0.0004). These results support previous clinical observations suggesting that HPV-18 may be associated with a more aggressive and rapidly progressive form of cervical neoplasia.

Cell Transformation, Viral

Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.

There were 732 evaluable patients with primary, previously untreated, histologically confirmed stage I squamous carcinoma of the cervix with greater than or equal to 3-mm invasion. Of these, 645 had no gross disease beyond the cervix/uterus, had negative paraaortic lymph nodes, and had undergone a radical hysterectomy with pelvic lymphadenectomy. The 3-year disease-free interval (DFIs) for the 545 patients with negative pelvic nodes was 85.6%, and for the 100 with positive pelvic nodes, 74.4%. A large number of pelvic nodes involved with tumor was not correlated with a poorer prognosis; the DFIs were 72.1, 86.4, and 64.6% for one, two, and three or more positive pelvic nodes, respectively. DFI correlated strongly with depth of tumor invasion, both in absolute terms (mm) and infractional thirds. The DFI was 94.6% for less than or equal to 5 mm, 86.0% for 6-10 mm, 75.2% for 11-15 mm, 71.5% for 16-20 mm, and 59.5% greater than or equal to 21 mm. In fractional terms, the DFI was 94.1% for superficial third, 84.5% for middle third, and 73.6% for deep third invasion. With respect to clinical tumor size, the DFIs were 94.8, 88.1, and 67.6% for occult, less than or equal to 3 cm, and greater than 3 cm, respectively. The DFI was 77.0% for those with positive capillary-lymphatic spaces (CLS) and 88.9% for those with negative CLS. Tumor grade and parametrial status correlated with DFI. DFI was not significantly different for age, disease status of the surgical margins, tumor description (e.g., exophytic), quadrant involved with tumor, uterine extension, and keratinizing status of tumor cells. Clinical tumor size, CLS, and depth of tumor invasion were independent prognostic factors.

Carcinoma, Squamous Cell

Human cervical cells immortalized in vitro with oncogenic human papillomavirus DNA differentiate dysplastically in vivo.

Human papillomavirus (HPV) types 16 and 18 are associated with cervical dysplasia and carcinoma. In vitro integration of HPV-16 or HPV-18 DNA into cultured human cervical cells results in their immortalization. In this study, in vivo differentiation of human cervical cells immortalized with recombinant HPV-16 or HPV-18 DNA was studied by implanting confluent monolayers of HPV-16 and HPV-18 DNA immortalized cell lines under dorsal skin flaps of immunodeficient mice. Grafts of a human cervical cancer cell line (C4-1) and cultured normal cervical cells served as controls. Histologic analysis 2 to 3 weeks after grafting demonstrated dysplastic differentiation of the HPV-16 and HPV-18 cell lines as characterized by abnormal mitotic figures, nuclear pleomorphism, and loss of basal polarity. RNA in situ hybridization confirmed the presence of viral transcripts in the dysplastic grafts. G-banded chromosome analysis showed that both the HPV-16 and HPV-18 cell lines were aneuploid. Even after prolonged periods of implantation tumors did not form and invasion of underlying mouse stroma did not occur. Normal cervical cells differentiated normally and the C4-1 cell line formed tumors and demonstrated more pronounced nuclear abnormalities than the HPV immortalized grafts. Integration of HPV-16 and HPV-18 DNA into cervical cells leads to an indefinite growth capacity. These aneuploid cells differentiate abnormally in vivo, but do not form tumors or invade host tissue, consistent with a multistage theory of cervical carcinogenesis.

Animals

Hysterectomy with extended surgical staging and radiotherapy versus hysterectomy alone and radiotherapy in stage I endometrial cancer: a comparison of complication rates.

Extended surgical staging (ESS) has been added to total hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) in patients with clinical Stage I endometrial cancer in order to better define patterns of metastatic spread and the response to treatment. Adjuvant radiotherapy has a demonstrated efficacy in decreasing central recurrence in Stage I disease. The combined use of radical surgery and pelvic radiotherapy for cervical cancer patients results in an increased incidence of complications. This study compares major complication rates in Stage I endometrial cancer patients who underwent either TAHBSO with ESS or TAHBSO alone followed by adjuvant external beam radiotherapy (RT). Records of 52 patients with clinical stage I endometrial cancer were reviewed. Thirty-two patients underwent TAHBSO plus ESS and 20 patients had TAHBSO alone. All patients received postoperative, whole pelvis external radiotherapy. Four patients suffered complications potentially related to treatment which required rehospitalization, and all 4 were in the group which had undergone ESS. A comparison of complication rates between the ESS + RT group (4/37 or 10.8%) and TAHBSO + RT group (0/20) suggested a trend toward significance (P less than 0.10). Treatment protocols using extended surgical staging prior to adjuvant radiotherapy in Stage I endometrial cancer should examine complications potentially related to this combination, to further define treatment risks and benefits.

Adult