The mRNA and protein levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence, and risk of death in cervical cancer patients.

INTRODUCTION: Patients with cervical cancer (CC) may experience local recurrence very often after treatment; when only clinical parameters are used, most cases are diagnosed in late stages, which decreases the chance of recovery. Molecular markers can improve the prediction of clinical outcome. Glycolysis is altered in 70% of CCs, so molecular markers of this pathway associated with the aggressiveness of CC can be identified. METHODS: The expression of 14 glycolytic genes was analyzed in 97 CC and 29 healthy cervical tissue (HCT) with microarray; only LDHA and PFKP were validated at the mRNA and protein levels in 36 of those CC samples and in 109 new CC samples, and 31 HCT samples by qRT-PCR, Western blotting, or immunohistochemistry. A replica analysis was performed on 295 CC from The Cancer Genome Atlas (TCGA) database. RESULTS: The protein expression of LDHA and PFKP was associated with poor overall survival [OS: LDHA HR = 4.0 (95% CI = 1.4-11.1); p = 8.0 × 10-3 ; PFKP HR = 3.3 (95% CI = 1.1-10.5); p = 4.0 × 10-2 ] and disease-free survival [DFS: LDHA HR = 4.5 (95% CI = 1.9-10.8); p = 1.0 × 10-3 ; PFKP HR = 3.2 (95% CI = 1.2-8.2); p = 1.8 × 10-2 ] independent of FIGO clinical stage, and the results for mRNA expression were similar. The risk of death was greater in patients with overexpression of both biomarkers than in patients with advanced FIGO stage [HR = 8.1 (95% CI = 2.6-26.1; p = 4.3 × 10-4 ) versus HR = 7 (95% CI 1.6-31.1, p = 1.0 × 10-2 )] and increased exponentially as the expression of LDHA and PFKP increased. CONCLUSIONS: LDHA and PFKP overexpression at the mRNA and protein levels was associated with poor OS and DFS and increased risk of death in CC patients regardless of FIGO stage. The measurement of these two markers could be very useful for evaluating clinical evolution and the risk of death from CC and could facilitate better treatment decision making.

Different Association of Human Papillomavirus 16 Variants with Early and Late Presentation of Cervical Cancer.

The median age of cervical cancer (CC) presentation coincides with the mean age of menopause presentation (49 years) in Mexico. Here, we investigated the association between different HPV16 variants and early (≤ 49 years) or delayed (≥ 50 years) CC presentation. We conducted a case-case study that included 462 CCs, 386 squamous cell carcinomas (SCC), 63 adenocarcinomas (ACC), and 13 additional cell types. Variants were identified by PCR and DNA sequencing. The risk conferred by each variant for developing CC earlier than 50 years was analyzed using a univariate logistic regression model considering old-aged patients (≥ 50 years) and non-HPV16 cases as the reference variables. Overall, the frequency of HPV16 was 50.9%, and the only identified variants were the European A1/2 (31.2%) and the Asian-American D2 (10.8%), and D3 (8.9%). D2 was mainly associated with ≤ 49-year-old patients (15.9%); A1/2 was uniformly distributed between the two age groups (~31%), whereas D3 increased with age to a frequency of 11.8% in the older group. Only the D2 variant conferred a 3.3-fold increase in the risk of developing CC before 50 years of age (OR = 3.3, 95% CI = 1.7-6.6, p < 0.001) in relation with non-HPV16 cases. Remarkably, this risk was higher for ACC (OR = 6.0, 95% CI = 1.1-33, p < 0.05) than for SCC (OR = 2.8, 95% CI = 1.3-5.9, p < 0.01). Interestingly, when analyzing only the HPV16-positive CC, D2 increases (OR = 2.5, 95% CI = 1.2-5, p < 0.05) and D3 decreases (OR = 0.45, 95% CI 0.2-0.9, p < 0.05) the risk to develop CC before 50 years old in relation with A1/2 variant. These results indicated that D2 variant is associated with early and D3 with delayed CC presentation, whereas A1/2 variant was uniformly distributed between the two age groups.

CDKN3 mRNA as a Biomarker for Survival and Therapeutic Target in Cervical Cancer.

The cyclin-dependent kinase inhibitor 3 (CDKN3) gene, involved in mitosis, is upregulated in cervical cancer (CC). We investigated CDKN3 mRNA as a survival biomarker and potential therapeutic target for CC. CDKN3 mRNA was measured in 134 CC and 25 controls by quantitative PCR. A 5-year survival study was conducted in 121 of these CC patients. Furthermore, CDKN3-specific siRNAs were used to investigate whether CDKN3 is involved in proliferation, migration, and invasion in CC-derived cell lines (SiHa, CaSki, HeLa). CDKN3 mRNA was on average 6.4-fold higher in tumors than in controls (p = 8 x 10-6, Mann-Whitney). A total of 68.2% of CC patients over expressing CDKN3 gene (fold change ≥ 17) died within two years of diagnosis, independent of the clinical stage and HPV type (Hazard Ratio = 5.0, 95% CI: 2.5-10, p = 3.3 x 10-6, Cox proportional-hazards regression). In contrast, only 19.2% of the patients with lower CDKN3 expression died in the same period. In vitro inactivation of CDKN3 decreased cell proliferation on average 67%, although it had no effect on cell migration and invasion. CDKN3 mRNA may be a good survival biomarker and potential therapeutic target in CC.

The distribution of high-risk human papillomaviruses is different in young and old patients with cervical cancer.

Despite numerous human papillomavirus (HPV) frequency studies in women with cervical cancer (CC), little is known of HPV frequency trends according to patient age. In this work, we compare the mean age and frequency distribution by age of CC patients positive for different HPVs. This study included 462 CC patients. HPVs were detected by PCR and typed using DNA sequencing. A total of 456 patients (98.7%) were positive for HPV: 418 (90.5%) had single and 38 (8.2%) had double HPV infections. HPV16 (46.5%), HPV18 (10.4%), HPV45 (6.7%), and HPV31 (4.1%) were the most frequent viral types in single-infected patients. The mean ages of single-infected patients with HPV16 (49.2±13.3), HPV18 (47.9±12.2), HPV45 (47.9±11.7), or HPV39 (42.6±8.9) were significantly lower than the mean ages of patients singly (53.9±12.7; p<0.001, t-test) or doubly (55.4±12.7; p<0.05, t-test) infected with the remaining HPVs. Three different trends were identified: one for HPV16, another for HPVs18/45/39, and a third for the rest of HPVs. The frequency trend of HPV16 shows two peaks. The first (63.2%) was found in the youngest women (≤35 years), followed by a decreasing trend until the age of 55-60 years (31.1%). The second peak arose at 61-65 years (52.5%), followed by a decreasing trend. The trend for HPVs18/45/39 declined from the youngest (19.3%) to the oldest (>70 years; 12.8%) women. In contrast, the trend for the remaining HPVs increased from the youngest (15.8%) to the oldest (46.2%) women. Unlike other life-style factors, low-risk sexual behavior was associated with late onset of CC independent of low-oncogenic HPV types (p<0.05, Wald chi-square statistic). The data indicate that most CCs in young women depend on the presence of high-oncogenic HPVs. In contrast, almost half of CCs in older patients had low-oncogenic HPVs, suggesting they could depend on the presence of other factors.

Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.

We investigated the role of tumor copy number (CN)-altered genome (CN-AG) in the carcinogenesis of cervical cancer (CC), especially its effect on gene expression, biological processes, and patient survival. Fifty-nine human papillomavirus 16 (HPV16)-positive CCs were investigated with microarrays-31 for mapping CN-AG and 55 for global gene expression, with 27 CCs in common. Five-year survival was investigated in 55 patients. Deletions and amplifications >2.5 Mb were defined as CN alterations. The %CN-AG varied from 0 to 32.2% (mean = 8.1±8.9). Tumors were classified as low (mean = 0.5±0.6, n = 11), medium (mean = 5.4±2.4, n = 10), or high (mean = 19.2±6.6, n = 10) CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated directly by gene dosage. In contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.2% of deregulated genes in whole tumors (r2 = 0.232, p = 0.006; analysis of variance), including genes located in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This suggests that the remaining genes are not deregulated directly by gene dosage, but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profile of APC/C-dependent proteasome proteolysis were associated with poor patient survival (p<0.05, log-rank test). Along with glycolysis, they were linearly associated with FIGO stage (r>0.38, p<0.01, Spearman test). Therefore, inhibition of APC/C-dependent proteasome proteolysis and glycolysis could be useful for CC treatment. However, whether they are indispensable for tumor growth remains to be demonstrated.

Heterogeneity of microRNAs expression in cervical cancer cells: over-expression of miR-196a.

In recent years, the study of microRNAs associated with neoplastic processes has increased. Patterns of microRNA expression in different cell lines and different kinds of tumors have been identified; however, little is known about the alterations in regulatory pathways and genes involved in aberrant set of microRNAs. The identification of these altered microRNAs in several cervical cancer cells and potentially deregulated pathways involved constitute the principal goals of the present study. In the present work, the expression profiles of cellular microRNAs in Cervical Cancer tissues and cell lines were explored using microRNA microarray, Affymetrix. The most over-expressed was miR-196a, which was evaluated by real time PCR, and HOXC8 protein as potential target by immunohistochemistry assay. One hundred and twenty three human microRNAs differentially expressed in the cell tumor, 64 (52%) over-expressed and 59 (48%) under-expressed were observed. Among the microRNAs over-expressed, we focused on miR-196a; at present this microRNA is poorly studied in CC. The expression of this microRNA was evaluated by qRT-PCR, and HOXC8 by immunohistochemistry assay. There is not a specific microRNA expression profile in the CC cells, neither a microRNA related to HPV presence. Furthermore, the miR-196a was over-expressed, while an absence of HOXC8 expression was observed. We suggest that miR-196a could be played as oncomiR in CC.

[Cervical cancer. Epidemiological profile in 1,217 patients. Seguro popular]. / Cancer cervicouterino. Perfil epidemiológico en 1,217 pacientes. Seguro popular.

BACKGROUND: Cervical cancer is the most common and most lethal gynecological cancer in Mexico. OBJECTIVE: To show epidemiological aspects of patients with cervical cancer treated at General Hospital of Mexico with Seguro Popular (free of cost health plan). MATERIAL AND METHOD: A retrospective, observational and descriptive study of files from patients with cervical cancer treated at General Hospital of Mexico, from January 2005 to December 2008. RESULTS: We attended 1,217 patients, 69% of them came from some state of the country; 725 (59%) only had basic studies and 181 (15%) didn't study; 692 (57%) had their first intercourse before 18 years old; 772 (63%) had more than three children and 629 (55%) never had made a cervical cytology; 1,090 (89%) had diagnosis of squamous cell carcinoma and 127 (11%) adenocarcinomas; 990 (81%) were invasive carcinomas and 227 (19%) in situ; 580 patients (51%) had FIGO stages 0 and I, and 555 (49%) stages II-IV. For stages 0, the median age was 35 years, for stage I, 42 years; 50 years for stage II, 54 for stage III and 51 for stage IV. CONCLUSIONS: This study showed that 69% of the patients came from some state of the country, a frequency of carcinomas in situ lesser than reported at other series in this country and 49% of advanced stages. Most patients had risk factors reported for this disease.

The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer: de-regulation of mitochondrial genes may be involved.

Although human papillomavirus (HPV) infection is the main causal factor for cervical cancer (CC), there are data suggesting that genetic factors could modulate the risk for CC. Sibling studies suggest that maternally inherited factors could be involved in CC. To assess whether mitochondrial DNA (mtDNA) polymorphisms are associated to CC, HPV infection and HPV types, a case-control study was performed in the Mexican population. Polymorphism of mtDNA D-loop was investigated in 187 CC patients and 270 healthy controls. HPV was detected and typed in cervical scrapes. The expression of 29 mitochondrial genes was analyzed in a subset of 45 tumor biopsies using the expression microarray ST1.0. The Amerindian haplogroup B2 increased the risk for CC (odds ratio (OR)=1.6; 95% confidence interval (CI): 1.05-2.58) and enhanced 36% (OR=208; 95% CI: 25.2-1735.5) the risk conferred by the HPV alone (OR=152.9; 95% CI: 65.4-357.5). In cases, the distribution of HPV types was similar in all haplogroups but one (D1), in which is remarkable the absence of HPV18, a very low frequency of HPV16 and high frequencies of HPV45, HPV31 and other HPV types. Two mtDNA genes (mitochondrial aspartic acid tRNA (MT-TD), mitochondrial lysine tRNA (MT-TK)) could be involved in the increased risk conferred by the haplogroup B2, as they were upregulated exclusively in B2 tumors (P<0.01, t-test). Although the association of mtDNA with CC and HPV infection is clear, other studies with higher sample size will be needed to elucidate the role of mtDNA in cervical carcinogenesis.

[Pelvic exenterations for cervical cancer (prognosis factors)]. / Exenteraciones pélvicas por cancer cervicouterino (factores pronósticos).

BACKGROUND: Pelvic exenteration offers the last chance of cure for some patients with cervical cancer recurrent after radiation therapy. OBJECTIVE: To analyze factors associated with recurrence and survival after pelvic exenterations, based on a 40 years institutional experience. MATERIAL AND METHOD: Retrospective, longitudinal and closed study from files of patients who survived to exenterative procedures at Oncology Department at the Hospital General de México, from January 1966 to December 2006, were screened in order to know risk factors predicting recurrence and survival in a follow up for at least three years. RESULTS: Prognostic factors in 161 patients eligible for this analysis were: diagnosis of recurrence prior 1 year 44/96 (45.8%) vs. 27/41 (65.8%) diagnosis after this time (p = 0.03), central recurrences 32/38 (84.2%) vs. 14/49 (28.5%) infiltration of lateral wall of the pelvis (0.0001), patients with 35 years old or less had a better prognosis when compared with the others: 23/33 (69%) vs. 60/128 (46%), (0.01); Infiltration of urinary bladder and or rectal wall 30/75 (40%) vs. 53/86 (61%) absence of these (0.006), tumor involving myometrium with or without adnexal metastases 6/25 (24%) vs. 77/136 (56%) absence of these reports (0.002), presence of three or more positive lymph nodes 5/16 (31%) vs. 56/90 (62%) absence of lymph nodes metastasis (0.02) and findings of hydronephrosis 2/15 (13.3%) vs. 13/19 (68.4%) of normal reports (0.01). CONCLUSIONS: Better evolution in this series was for patients who had central recurrences.

A great diversity of Amerindian mitochondrial DNA ancestry is present in the Mexican mestizo population.

There are limited data on mitochondrial DNA (mtDNA) variation in the Mexican mestizo population. To examine the genetic diversity and matrilineal ancestry, the full mtDNA hypervariable regions I and II were sequenced in 270 unrelated mestizos from different regions of Mexico. A total of 202 different haplotypes were identified and the haplotype diversity was 0.9945. Amerindian haplotypes predominated in the sample with a proportion of 93.3%, followed by European (6.0%) and African haplotypes (0.7%). The frequency of the Amerindian haplogroups A2, B2, C1 and D1 was 51.1, 17.8, 18.5 and 5.9%, respectively. The frequency of Amerindian haplogroups was higher in the central region than in Mexico City, whereas it was the contrary for European haplogroups. This difference was accounted principally by the high frequency of B2 haplotypes in the central region. The minimum spanning network, the mismatch distribution and Tajima's D neutrality test suggest a population expansion for each Amerindian haplogroup, which could be initiated more recently for haplogroups A2 and D1. The present knowledge combined with other nuclear genetic markers will be essential in future association studies to correct for genetic substructure in mestizo populations.

[Cervical cancer. Current view of its epidemiology and risk factors]. / Cáncer del cuello uterino. Panorama actual de su epidemiología y de sus factores de riesgo.

An epidemiologic analysis and a global evaluation of risk factors related to the etiopathogenesis of cervical cancer are reported here. Cervical cancer is the second cause of female malignancies worldwide and represents a health problem in some countries of Africa and Latin America like Haiti, Zimbabwe, Bolivia and Ecuador, with incidence rates from 44.2 to 93.9 per 100,000. Highest death rates are reported in Haiti, Nicaragua, Ecuador and Mexico (53.5 to 17.1 per 100,000, respectively). Although at this time in Mexico it has been reported a 55.4% of early tumors and a decrease of 20% in death rates, in this country cervical cancer is the main cause of death for women malignancies. Sexual activity and parity before 18 years old, human papilloma virus infection (HPV) and some nutritional deficiencies mainly related with antioxidants agents, are in these countries the most important risk factors. Mexican investigations have showed oncogenic HPV genotypes in 80% of aceto white lesions of the cervix, a 50% of HPV16 genome in cervical carcinomas and a variety of HPV16 infection, named HPV16AA-c. Women infected with these viruses, are younger and have more aggressive carcinomas.

Tumor de senos endodérmicos del ovario con patrón hepatoide predominante y metástasis a hígado / Tumor of endodemic ovarian sinus with prevailing hepatoid pattern and liver metastasis

Se presenta el caso de una mujer de 16 años de edad, con tumor de senos endodérmicos del ovario derecho, macroscópicamente sólido y con patrón histológico de crecimiento predominantemente de tipo hepatoide. Este tumor cursó con metástasis masivas a hígado y ascitis, lo que planteó el diagnóstico diferencial de tumor de senos endodérmicos de tipo hepatoide con metástasis a hígado o carcinoma hepatocelular con metástasis a ovario, o bien un carcinoma hepatoide del ovario. Se considera que éste es el primer caso en los archivos de la Unidad de Patología del Hospital General, en el que un tumor de senos endodérmicos presenta un patrón hepatoide tan extenso.

Cáncer del endometrio en el Hospital General de México (27 años de experiencia) / Endometrial cancer at Hospital General de Mexico (An experience of 27 years)

Objetivo. Informar la experiencia con cáncer del endometrio de una institución que atiende población abierta. Material y métodos. Análisis de 260 casos de cáncer del endometrio vistos en el Servicio de Oncología del hospital General de México, entre 1966 y 1993 inclusive, destacándose el estudio de factores de riesgo y los resultados del tratamiento, a partir de la clasificiación clínico-quirúrgica vigente, a la que se agregó dentro de la etapa IIIc, la invasión parametrial no contemplada en dicha clasificación. Resultados. Ciento veinte (46.1 por ciento) enfermas fueron obesas, 78 (30.0 por ciento) hipertensas y 65 (25.0 por ciento) diabéticas. Ciento treinta y una (50.3 por ciento) indicaron nuliparidad o baja paridad. Unicamente 116 (48.7 por ciento) de 238 se clasificaron en estadio I. Evolucionaron de 24 a 10 años (media de 30 meses) sin evidencia de enfermedad, 66 (52.3 por ciento) de 128 enfermas clasificadas de la siguiente manera: 39 de 51 en estadio I: 76.4 por ciento (18/20 Ia, 90.0 por ciento; 13/15 Ib, 86.6 por ciento y 8/16 Ic, 50.0 por ciento. P=0.003). Diecisiete de 23 en estadio II, 73.9 por ciento (5/6 IIa, 83.3 por ciento y 12/17 IIb, 70.5 por ciento); 10 de 37 en estadio III, 27.0 por ciento (5/14 IIIa, 35.7 por ciento; 2/6 IIIb, 33.3 por ciento y 3/17 IIIc, 17.6 por ciento) y 1/17 en estadio IV, 5.8 por ciento. Conclusiones. El alto porcentaje de lesiones avanzadas influyó negativamente en los resultados finales. Los factores pronósticos más adversos en tumores pélvicos fueron: La invasión profunda del miometrio en cánceres limitados al cuerpo uterino (etapa Ic) y la invasión parametrial en lesiones más avanzadas

Cáncer del endometrio clasificación clínico-quirúrgica y resultados del tratamiento (Análisis de 134 pacientes) / Endometrial cancer. Clinico-surgical calsification and therapy results. Analisis of 134 patients

Informar los factores pronósticos del cáncer endometrial en pacientes del Hospital General de México, tomando como base la clasificación clínico-quirúrgica vigente de la enfermedad. Etapificación de 134 expediente de pacientes con cáncer endometrial tratadas convencionalmente en el Hospital General de México, en los que se documentaron los factores pronósticos del padecimiento. En 127 casos se tomó como base, la Clasificación clínico-quirúrgica de la Federación Internacional de Ginecología y Obstetricia (FIGO). Evolucionaron de 24 meses a 10 años con una media de 30 meses, sin evidencia de enfermedad, 58 a 105 adenocarcinoam, (55.2 por ciento); 5 de 11 adenoacantomas, (45.4 por ciento) y 4 de 14 carcinomas adenoescamosos, (28.5 por ciento). Asimismo, 36 de 72 pacientes con edad igual o menor a 60 años, (50.0 por ciento) y 17 de 43 con edad igual o mayor a los 61 años, (39.5 por ciento). De acuerdo a la clasificación vigente de la FIGO, se obtuvo una evolución sin evidencia de enfermedad, en 66 de 127 enfermas tratadas, (51.9 por ciento). La cifra incluye 39 de 51 pacientes clasificadas en estadio I: 76.4 por ciento (188 de 21 Ia, 90 por ciento; 13 de 15 Ib, 86.6 por ciento y 8 de 16 Ic, 50.0 por ciento. P=0.003). Diez y siete de 23 en estadio II, 73.9 por ciento (5 de 6 IIa, 83.3 por ciento y 12 de 17 IIb, 70.5 por ciento); 10 de 37 en estadio III, 27.0 por ciento, (5 de 14 IIIa, 35.7 por ciento; 2 de 6 IIIb, 33.3 por ciento y 3 de 17 IIIc, 17.6 por ciento); y 1 de 17 en estadio IV, 5.8 por ciento. P=0.001. La clasificación de la FIGO para el carcinoma del endometrio, ha contribuido a predecir la evolución natural de la enfermedad. En esta serie, los factores pronósticos mas adversos en tumores limitados a la pelvis fueron, la invasión profunda del miometrio (estadio Ic) y la invasión parametrial

Carcinoma del endometrio. Causas de fracaso terapéutico en 69 pacientes / Carcinoma of the endometrium. Treatment failure in 69 patients

El objetivo del presente trabajo fue estudiar las causas de los fracasos terapéuticos en el cáncer endometrial, a partir de la Clasificación Clínico-quirúrgica del padecimiento, en pacientes de una Institución que atiende a población abierta. Se realizó un análisis con la Clasificación actual, de 69/212 casos tratados de forma convencional en el Hospital General de México entre 1966 y 1993, en los que se demostró fracaso de la terapéutica. Se incluyeron ingresos con enfermedad diseminada, muertes postratamiento, residuales tumorales. Los resultados fueron: Diez y seis pacientes (23.1 por ciento) ingresaron con diseminación tumoral; 5 (7.1 por ciento) fallecieron a causa del tratamiento. Diez de 13 con tumor parametrial (76.9 por ciento) y 1 de 5 en estadio IVa, terminó su tratamiento con residual terminal no rescatable. Treinta y cinco pacientes (50.7 por ciento) desarrollaron recurrencias tumorales, el 94.3 por ciento dentro de los 3 primeros años; 19 a nivel locorregional (54.2 por ciento) y 16 con actividad a distancia (45.7 por ciento). Diez de los 49 casos en estadio I (20.4 por ciento), evolucionaron con recurrencias tumorales no rescatables, de los que 8 (80.0 por ciento) fueron estadios Ic. Asimismo, 5/16 (31.3 por ciento) en estadio IIb; 17/27 (62.9 por ciento) en estadio III y 3/5 en estadio IVa. Dos de 14 enfermas manejadas con hormonoterapia (14.2 por ciento), mostraron respuestas objetivas en enfermedad avanzada o recurrente y de 0 a 6 con quimioterapia. Se concluye que los factores pronósticos más adversos en esta serie fueron: La presencia de invasión profunda del miometrio para el estadio I; la invasión parametrial para el estadio III y la diseminación a distancia en el IV

Complicaciones de la histerectomía radical en el manejo de cáncer cérvicouterino estadios Ib y IIa. Experiencia con 145 pacientes / Radical hysterectomy complications management of cervico.uterine cancer, Stages Ib and IIa. (Experience with 145 patients)

Se presenta el estado actual de las complicaciones de la histerectomía radical en el manejo del cáncer cérvicouterino invasor Ib y IIa, mediante el análisis de 145 casos operados en el Servicio de oncología del Hospital General de México, SSA entre enero de 1989 y marzo de 1994, haciendo especial énfasis en las complicaciones urinarias apreciadas cuando se conservaron las arterias vesicales superiores, (99 casos) y cuando estas fueron seccionadas, (46 casos). No hubo mortalidad. Se presentaron 20, (13.7 por ciento) complicaciones transoperatorias: 10, (6.8 por ciento lesiones del plexo hipogástrico; cinco (3.4 por ciento) secciones ureterales y dos (1.3 por iento) lesiones de venas iliacas. Treinta y nueve enfermas, (26.8 por ciento) desarrollaron complicaciones en los primeros 30 días: atonía vesical, 30 (20.6 por ciento); infección de herida, cinco (3.4 por ciento); fístula ureterovaginal, tres (2.0 por ciento); fístula vesicovaginal, tres (2.0 por ciento). Cinco pacientes, (3.4 por ciento) tuvieron complicaciones tardías: tres (2.0 por ciento) fístula ureterovaginal; una (0.6 por ciento oclusión intestinal y una (0.6 por ciento) linfocele. Con conservación de las arterias vesicales superiores, la duración de la cirugía fue en promedio una hora mayor, (4.15 h, vs. 3.15 h) se apreció en estas pacientes un mayor sangrado transoperatorio, (1,125 cc vs. 980 cc). Sin embargo, en estos casos hubo un menor número de complicaciones posopeatorias (29/99; 29.2 vs 19/46, 41.3 por ciento; p<0.05), con un menor número de fístulas ureterovaginales. (1/99, 1.0 por ciento vs. 5/46, 10.8 por ciento)

Exenteraciones pélvicas por ca. cervicouterino (factores pronósticos) / Pelvice exenterations for cervical cancer (prognosis factors)

Se muestra el análisis de los factores que influyeron en el prónostico de 104 pacientes sometidas a exenteraciones pélvicas por cáncer cérvico-uterino recurrente a radiación, en el Servicio de Oncología del Hospital General de México, S.S., que sobrevivieron a la cirugía y que tuvieron un mínimo de seguimiento de tres años. Influyeron significativamente en el pronóstico de esta serie, la edad menor o mayor a 35 años: 15/22 68.1 por ciento vs 36/82, 43.9 por ciento, P=0.03; el reporte previo a la cirugía de tumor localizado al cérvix y/o vagina: 17/22, 77.2 por ciento vs. el informe de tumor parametrial fijo: 11/39, 28.2 por ciento, P=0.008, el reporte de urografía normal, 9/13, 69.2 por ciento, vs, el de hidronefrosis o exclusión renal: 2/13, 15.3 por ciento, P=0.01; la presencia o ausencia de invasión vesical y/o rectal: 15.41, 36.5 por ciento vs. 36/63, 57.1 por ciento, P=0.03; la presencia o ausencia de invasión al miometrico con o sin metástasis a ovarios, 2/15, 13.0 por ciento vs. 49/89, 55.5 por ciento, P=0.03 y la ausencia de metástasis ganglionares, 40/68, 58.8 por ciento vs. la presencia de 3 o más ganglios metastásicos, 4/15, 26.6 por ciento, P=0.01. No tuvo influencia estadísticamente significativa para el pronóstico, el tipo de radioterapia administrada, el tipo de exenteración efectuada, ni el tiempo transucrrido entre la terminación de la radioterapia y la cirugía. (Un año o menos)

Tratamiento quirúrgico del cáncer cervicouterino recurrente a radiación / Surgery of recurrence posradiotherapy of cancer the uterine cervix

Presentamos nuestra experiencia con 331 pacientes con cáncer cervicouterino recurrente a radiación, exploradas quirúrgicamente en el Servicio de Oncología del Hospital General de México, SS, entre 1980 y 1989 inclusive. Ciento treinta y dos pacientes (39.8 por ciento) fueron candidatas a exenteraciones pélvicas y 10 (3.0 por ciento) a histerectomía radicales. En 189 (57.0 por ciento) se demostró un tumor irresecable, requiriendo 43 de estas enfermas (22.6 por ciento) algún tipo de cirugía derivativa. Se realizaron 68 exenteraciones anteriores, 62 totales y dos posteriores. Cincuenta de éstas (37.8 por ciento), desarrollaron complicaciones postoperatorias, las cuales estuvieron encabezadas por infecciones de la herida quirúrgica (22.7 por ciento), abscesos pélvicos (18.9 por ciento) y dehiscencia de las suturas ureterales (10.6 por ciento) e intestinales (7.5 por ciento). Once pacientes exenteradas evolucionaron hacia la muerte (8.3 por ciento). La mortalidad operatoria de las exenteraciones anteriores fue de 5.8 por ciento y del 9.6 por ciento para las totales. Evolucionaron 24 meses sin evidencia de enfermedad, 48 de 95 pacientes (50.5 por ciento) de las que se tuvo seguimiento. La cifra incluye 28 de 48 (58.3 por ciento) de las exenteraciones anteriores, 15 de 38 de las totales, (42.1 por ciento); cero de dos de las posteriores y cuatro de siete, (57.1 por ciento) de las histerectomías radicales. No hubo diferencias estadísticamente significativas en los resultados por etapa clínica aun cuando el antecedente de estadios Ib y IIa se acompañó de un mejor pronóstico (5/8, 62.5 por ciento). La presencia de metástasis ganglionares en los espécimenes quirúrgicos tuvo una influencia estadísticamente significativa en el pronóstico únicamente cuando se diagnosticaron tres o más ganglios metastásicos (3/15, 20.0 por ciento). En ausencia de metástasis ganglionares la evolución sin evidencia de enfermedad fue del 62.5 por ciento.

Cáncer de ovario: experiencia con 186 pacientes / Ovarian cancer: experience with 186 patients

Se muestra la experiencia del Servicio de Oncología del Hospital General de México, SS, con 186 pacientes atendidas de 1981 a 1990 por neoplasias epiteliales malignas del ovario, de las que 50, (26.9 por ciento) fueron clasificadas en etapa I;2, (10 por ciento) en etapa II; 113, (60.7 por ciento ) en etapa III y 21 (11.2 por ciento)en etapa IV. Se realiza un análisis de los aspectos epidemiológicos y clínicos relevantes y en cuanto a los resultados del tratamiento, se señala que en 137 pacientes, (73.6 por ciento) se obtuvo seguimiento y que este fue sin evidencia de enfermedad de 12 a 60 meses con una media de 18, en 32. (23.3 por ciento). La cifra incluye 22 de 26 pacientes clasificadas en etapa I, (84.6 por ciento); 1 de 2 en etapa II; 9 de 89, (10.1 por ciento) en etapa III y 0 de 20 en etapa IV. La evolución por esquema de tratamiento no mostró para la etapa I diferencias importantes (únicacmente cirugía, cirugía más radioterapia o cirugía más quimioterapia). Para el estadio III evolucionaron sin evidencia de cáncer, únicamente aquellas pacientes cuya cirugía dejó un tumor residual de 2 cm, o menos por unidad. Se incluyen 1 de 59 pacientes tratadas únicamente con cirugía, (1.6 por ciento); 3 de 15. (20 por ciento) de las manejadas con radioterapia postoperatoria a la totalidad del abdomen más sobredosis a la pelvis y 5 de 15, (33.3 por ciento) de las manejadas con 2 agentes de qio,opteraóa. (ciclofosfamida más cisplatino o ciclofosfamida más adriamicina). En 3 de 11 pacientes, (27.2 por ciento) en etapa III sometidas a cirugías de revisión sin evidencia de enfermedad postratamiento complementario, se demostró tumor residual macroscópico.