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Background:  Patients with primary hyperhidrosis present with sweating in two or more sites in nearly 85% of cases. In this study, we examined whether the number of hyperhidrosis sites is related to the surgery outcomes., Methods:  One hundred ninety-three hyperhidrosis patients who underwent bilateral videothoracoscopic sympathectomy after failure or dissatisfaction with clinical treatment were distributed into three groups based on the number of hyperhidrosis sites (one site, two sites, and three or more sites of hyperhidrosis). The primary endpoints in the study were as follows: quality of life prior to surgery, improvement of quality of life after surgery, clinical improvement of sweating, presence or absence of compensatory hyperhidrosis, and general satisfaction after 1 month of surgery., Results:  Patients with two or more hyperhidrosis sites had worse quality of life before surgery than patients with a single hyperhidrosis site. There was an improvement in the quality of life in more than 95% of the patients, clinical improvement in more than 95% of patients, severe compensatory hyperhidrosis in less than 10%, and low general satisfaction after 1 month of surgery in only 2.60% of the patients, with no differences among the three groups., Conclusions:  Patients with more than one preoperative hyperhidrosis site present worse quality of life prior to surgery than those with a single hyperhidrosis site, but the number of hyperhidrosis sites before surgery does not affect surgery outcomes., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The transcriptional repressor DREAM is involved in thyroid-specific gene expression, thyroid enlargement and nodular development, but its clinical utility is still uncertain. In this study we aimed to investigate whether DREAM mRNA levels differ in different thyroid tumors and how this possible difference would allow the use of DREAM gene expression as molecular marker for diagnostic and/or prognosis purpose., Materials and Methods: We quantified DREAM gene mRNA levels and investigated its mutational status, relating its expression and genetic changes to diagnostic and prognostic features of 200 thyroid tumors, being 101 malignant [99 papillary thyroid carcinomas (PTC) and 2 anaplastic thyroid carcinomas] and 99 benign thyroid lesions [49 goiter and 50 follicular adenomas (FA)]., Results: Levels of mRNA of DREAM gene were higher in benign (0.7909 ± 0.6274 AU) than in malignant (0.3373 ± 0.6274 AU) thyroid lesions (p < 0.0001). DREAM gene expression was able to identify malignancy with 66.7% sensitivity, 85.4% specificity, 84.2% positive predictive value (PPV), 68.7% negative predictive value (NPV), and 75.3% accuracy. DREAM mRNA levels were also useful distinguishing the follicular lesions FA and FVPTC with 70.2% sensitivity, 73.5% specificity, 78.5% PPV, 64.1% NPV, and 71.6% accuracy. However, DREAM gene expression was neither associated with clinical features of tumor aggressiveness, nor with recurrence or survival. Six different genetic changes in non-coding regions of DREAM gene were also found, not related to DREAM gene expression or tumor features., Conclusion: We suggest that DREAM gene expression may help diagnose thyroid nodules, identifying malignancy and characterizing follicular-patterned thyroid lesions; however, it is not useful as a prognostic marker.

Objectives: Report the long-term outcomes of the AMS 800 artificial sphincer (AS) for the treatment post-prostatectomy incontinence (PPI) in a single center in Brazil., Materials and Methods: Clinical data from patients who underwent the procedure were retrieved from the medical records of individuals with more than 1 year of follow-up from May 2001 to January 2016. Continence status (number of pads that was used), complications (erosion or extrusion, urethral atrophy, and infection), malfunctions, and need for secondary implantation were evaluated. The relationship between complications and prior or subsequent radiation therapy (RT) was also examined., Results: From May 2001 to January 2016, 121 consecutive patients underwent AS implantation for PPI at an oncological referral center in Brazil. At the last visit, the AS remained implanted in 106 patients (87.6%), who reported adequate continence status (maximum of 1 pad/day). Eight-two subjects (67.8%) claimed not to be using pads on a regular basis at the final visit (completely dry). Revision occurred in 24 patients (19.8%).Radiation therapy (RT) for prostate cancer following radical prostatectomy was used in 47 patients before or after AS placement. Twelve patients with a history of RT had urethral erosion compared with 3 men without RT (p=0.004)., Conclusion: Considering our outcomes, we conclude that AS implantation yields satisfactory results for the treatment of PPI and should remain the standard procedure for these patients. Radiation therapy is a risk factor for complication., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Objective:: To describe the clinical features, imaging findings and pathological aspects of breast cancer diagnosed in women under the age of 40 years., Method:: A retrospective, descriptive study was performed through analysis of medical records between November 2008 and August 2012. One hundred and twenty (120) patients were included, of whom 112 underwent mammography, 113 underwent ultrasonography, and 105 underwent magnetic resonance imaging (MRI). The histopathological data was obtained in most cases from post-surgical analysis, which was available for 113 patients., Results:: The mean age at diagnosis of primary breast cancer was 34 years. Only 11 patients (9.0%) had a family history of breast or ovarian cancer in first-degree relative. Ninety-two (92) patients sought medical attention after showing breast symptoms, and the presence of a palpable nodule was the main complaint. One hundred and twenty-two (122) primary tumors were diagnosed, of which 112 were invasive (95%). The most common histological type was invasive ductal carcinoma (73.8%). Luminal B was the predominant molecular subtype (42.6%). Ultrasonography was positive in 94.5% of the cases and the most common finding were nodules (94.8%). At mammography, the malignancy was observed in 92.8% and the presence of suggestive calcifications was the dominant feature. The MRI was positive in 98% of patients, and mass lesions were the most common., Conclusion:: Most cases of breast cancer diagnosed in patients under the age of 40 years, in our population, had symptoms at diagnosis and tumor with more aggressive biological behavior. Despite the ultrasound has been the most widely used method, we found improved characterization of breast lesions when also used mammography and MRI.

Endometrial and cervical cancers are the most prevalent gynecologic neoplasms. While endometrial cancer occurs in older women, cervical cancer is more prevalente in young subjects. The most common clinical manifestation in these two gynecological cancers is vaginal bleeding. In the first case, diagnosis is made based on histological and imaging evaluation of the endometrium, while cervical cancers are diagnosed clinically, according to the International Federation of Gynecology and Obstetrics (FIGO). The authors present a case of synchronous gynecological cancer of the endometrium and cervix diagnosed during staging on MRI and confirmed by histological analysis of the surgical specimen.

Background: The aim of this study was to analyze the outcomes of oncologic patients with associated aneurysm of the abdominal aorta (AAA), treated at a specialized cancer (Ca) hospital more than a 10-year period., Methods: This was a retrospective study, and the data were obtained from our institution's prospective database. Between September 2003 and 2013, a total of 36 consecutive patients with AAA in association with Ca underwent surgical repair. Of these, 9 patients were excluded because the Ca treatment was performed at another service. Most of the patients were male (22) and the most frequent form of neoplasia was prostate Ca. Surgery for AAA repair was performed after the Ca treatment in 19 cases, before Ca treatment in 7 cases and concomitantly in 1 case. The intraoperative characteristics, treatment technique used, complications, patients' clinical evolution, and survival outcomes were analyzed., Results: Endovascular aneurysm repair (EVAR) was used in 19 cases (70.4%) and conventional open repair (OR) in 8 cases (29.6%). Surgical treatment was uneventful in 19 cases, however, when present, postoperative complications occurred more frequently with EVAR (36.84% vs. 12.5%). There were no cases of death related to the aneurysm surgery. Most of the patients in both groups were alive at the end of the study. The probability of survival in our study was 65.8% at 3 years and 53% at 5 years, with no statistically significant difference between the EVAR and OR groups. The main cause of death was progression of the neoplastic disease., Conclusions: Patients who present Ca in association with AAA benefit from surgical treatment of both conditions, simultaneously or not. In these cases, it is important for the treatment to be individualized, and the disease of greater severity should be treated first. The endovascular and conventional open techniques were shown to be equivalent., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Penile carcinomas (PeCa) are relatively rare, but devastating neoplasms, more frequent among people of underprivileged socioeconomic status. There is mounting evidence that immune cells may trigger various mechanisms that enhance tumor growth and metastasis, but no data on the peritumoral inflammation is available for PeCa. The objectives of the present study are to evaluate the immunohistomorphology of tumoral inflammation in PeCa, and to correlate it with clinicopathological parameters, which could contribute to the prognostic evaluation. One hundred and twenty-two patients with the diagnosis of usual-type squamous cell penile carcinoma were included. Paraffin-embedded tissue was submitted to immunohistochemical evaluation of p16 protein, CD3, CD4, CD8, CD20, CD68, CD138, granzyme B, and Fox-P3. The Fisher's exact test was employed for comparison between histological variables and parameters, and the Kaplan-Meier method for the analysis of survival. Improved 5-year overall survival was significantly associated to age ≤60 years, stage I + II, tumor size T1 + T2, lymph node status N0, and absent perineural invasion. In a multivariate analysis age ≥60 years, presence of lymph node metastasis, urethral invasion, and high histologic grade retained a significantly more unfavorable outcome. Improved 5-year failure free survival was associated to stage of the disease I + II, lymph node status N0, absence of perineural, vascular, and urethral invasion, and Fox-P3 expression. In a multivariate analysis, presence of lymph node metastasis, perineural and vascular invasion, and of Fox-P3-positive lymphocytes together with low inflammatory infiltrate retained a significantly more unfavorable outcome. These results support the prognostic value of determining the levels of Fox-P3-positive lymphocytes by immunohistochemistry in PeCa, as this parameter adds value to the traditional clinicopathological features.

Background: Topoisomerase 2 alpha (TOP2A), HER-2/neu, and survivin are genes that lie on chromosome 17 and correlate with the prognosis and prediction of target-driven therapy against tumors. In a previous study, we showed that TOP2A transcripts levels were significantly higher in soft tissue sarcomas (STS) than in benign tumors and desmoid-type fibromatoses (FM). Because these genes have been insufficiently examined in STS, we aimed to identify alterations in TOP2A and HER-2 expression by fluorescent in situ hybridization and immunohistochemistry, as well as that of survivin, and correlate them with clinicopathologic findings to assess their prognostic value., Methods: Eighteen FM and 244 STS were included. Fluorescent in situ hybridization and immunohistochemistry were performed on a tissue microarray., Results: TOP2A and survivin were more highly expressed in sarcomas than in FM. TOP2A was an independent predictor of an unfavorable prognosis; it was combined with formerly established prognostic factors (primarily histologic grade and tumor size at diagnosis) to create a prognostic index that evaluated overall survival. Gene amplification/polysomy (13%) did not correlate with protein overexpression. Survivin and HER-2 expression were not associated with patient outcomes., Conclusions: These findings might become valuable in the management of patients with STS and possibly in the prospective evaluation of responses to new target-driven therapies.

Unlabelled: Radiation therapy and radiochemotherapy protocols can cause swallowing difficulties., Aim: To evaluate swallowing in patients undergoing radiation therapy and radiochemotherapy protocol only for the treatment of laryngeal tumors., Methods: A prospective study of 20 patients, with a mean age of 62 years, at the end of oncological therapy. Six patients (30%) underwent radiation therapy, and 14 patients (70%) underwent combined therapy. The mean time between treatment and an evaluation of swallowing was 8.5 months. Videofluoroscopy was done to assess the preparatory, oral and pharyngeal phases of swallowing., Results: All patients had only an oral diet. Normal swallowing was present in only 25% of patients. The swallowing videofluoroscopic examination identified the following changes: bolus formation (85%), bolus ejection (60%), oral cavity stasis (55%), changes in the onset of the pharyngeal phase (100%), decreased laryngeal elevation (65%), and hypopharyngeal stasis (80%). Laryngeal penetration was observed in 25% of the cases; 40% presented tracheal aspiration. The grade of penetration/aspiration was mild in 60% of cases. Aspiration was silent in 35% of patients. Although 75% of patients had dysphagia, only 25% complained of swallowing difficulties., Conclusion: Patients with laryngeal cancer that underwent radiation therapy/combined treatment can present changes in all swallowing phases, or may be asymptomatic.

Background: Alternative splicing (AS) is a central mechanism in the generation of genomic complexity and is a major contributor to transcriptome and proteome diversity. Alterations of the splicing process can lead to deregulation of crucial cellular processes and have been associated with a large spectrum of human diseases. Cancer-associated transcripts are potential molecular markers and may contribute to the development of more accurate diagnostic and prognostic methods and also serve as therapeutic targets. Alternative splicing-enriched cDNA libraries have been used to explore the variability generated by alternative splicing. In this study, by combining the use of trapping heteroduplexes and RNA amplification, we developed a powerful approach that enables transcriptome-wide exploration of the AS repertoire for identifying AS variants associated with breast tumor cells modulated by ERBB2 (HER-2/neu) oncogene expression., Results: The human breast cell line (C5.2) and a pool of 5 ERBB2 over-expressing breast tumor samples were used independently for the construction of two AS-enriched libraries. In total, 2,048 partial cDNA sequences were obtained, revealing 214 alternative splicing sequence-enriched tags (ASSETs). A subset with 79 multiple exon ASSETs was compared to public databases and reported 138 different AS events. A high success rate of RT-PCR validation (94.5%) was obtained, and 2 novel AS events were identified. The influence of ERBB2-mediated expression on AS regulation was evaluated by capillary electrophoresis and probe-ligation approaches in two mammary cell lines (Hb4a and C5.2) expressing different levels of ERBB2. The relative expression balance between AS variants from 3 genes was differentially modulated by ERBB2 in this model system., Conclusions: In this study, we presented a method for exploring AS from any RNA source in a transcriptome-wide format, which can be directly easily adapted to next generation sequencers. We identified AS transcripts that were differently modulated by ERBB2-mediated expression and that can be tested as molecular markers for breast cancer. Such a methodology will be useful for completely deciphering the cancer cell transcriptome diversity resulting from AS and for finding more precise molecular markers.

Sellar and parasellar masses blocking inhibitory hypothalamic dopaminergic tonus can produce hyperprolactinemia. One of these conditions, seldom reported, is internal carotid artery aneurysm causing pituitary stalk compression and hyperprolactinemia, the majority of which is related to small increases in serum prolactin levels. The aim of this study is to report the case of a patient with an internal carotid aneurysm and severe hiperprolactinemia. A 72 years old female patient, on oncology follow-up for clinically controlled cervical carcinoma, was evaluated due to worsening chronic headaches. During the investigation, computed tomography and magnetic resonance imaging (MRI) showed a sellar mass associated with high prolactin level (1.403 microg/L) that initially was considered a macroprolactinoma, and treated with bromocriptine. However, subsequent pituitary MRI suggested an internal carotid aneurysm, which was confirmed by an angioresonance imaging of cerebral vessels. On low bromocriptine dose (1.25 mg/day), there was a prompt normalization of prolactin levels with a great increase (> 600 microg/L) after withdrawal, which was confirmed several times, suggesting HPD. We report a patient with internal carotid artery aneurysm with severe hyperprolactinemia never reported before in patients with HPD, and the need for a differential diagnosis with macroprolactinomas even considering high prolactin levels.

Penile squamous cell carcinoma (SCC) is a rare malignancy with highest incidence in underdeveloped and developing countries. Oncogenic human papilloma virus (HPV) DNA, mainly types 16 and 18, are found in ∼ 100% of patients with uterine cervix carcinoma. The incidence of this virus in SCC and its variations range from 30.5 to 80%. Despite controversies, contrary to the cervical carcinoma, in the carcinogenesis and disease progression of SCC, HPV-dependent and HPV-independent tumors need to be considered. Lymphadenectomies continue to be the gold standard treatment of lymph node metastases. Undesirable accuracy on staging system methods and high rates of lymphadenectomy complications are the principal objections to these surgical procedures; therefore, the main issue in patients with SCC is to know who should or should not undergo lymphadenectomy. The search for primary tumor anatomopathological and biomarker risk factors for lymph node metastases, such as has occurred in other tumors, may be an important tool to select lymphadenectomies candidates better. Histological subtypes, tumor grade, growth pattern, tumor thickness, lymphatic embolization by neoplasic cells and depth of infiltration have been reported as important prognostic factors for lymph node metastases. In our series, lymphatic vascular permeation, palpable lymph node after primary tumor control (cN stage), pattern of invasion, p53 and PCNA immunoreactivity are independent lymph node metastases risk factors in the multivariate model. It is strongly recommended that patients be concentrated in specialized centers or cancer hospitals and multi-centric prospective studies carried out on tumor markers in this rare disease, in order to stage better lymph node disease and avoid unnecessary surgeries with high morbidity rates.

Background: Postoperative complications are relevant outcomes in patients with head and neck tumor who have undergone surgery. Few trials have assessed predictive factors in older patients. We assessed the predictive effect of preoperative clinical factors on postoperative complications., Methods: We conducted a cohort study with 242 patients older than 70 years with head and neck cancer who underwent surgery. Logistic regression identified predictive factors for postoperative complications. Significant variables were used to build a predictive index., Results: Comorbidities were present in 87.6% of patients, and 56.6% had some type of complication (44.6% local and 28.5% systemic). Male sex, bilateral neck dissection, presence of 2 or more comorbidities, reconstruction, and clinical stage IV were associated with postoperative complications. The predictive index showed a receiver operating characteristics curve (ROC) area of 0.69., Conclusion: It is possible to predict postoperative complications in older patients with head and neck tumors who underwent oncologic surgery using clinical preoperative variables.

Background: The aim of this study was to evaluate risk factors of neck recurrence in patients with pN+ necks submitted to a modified or a classic radical neck dissection and the safety of preserving the internal jugular vein in the treatment of a subgroup of these patients., Methods: The medical records of 311 untreated patients with squamous cell carcinoma of the oral cavity (106 cases), oropharynx (95 cases), larynx (49 cases), and hypopharynx (61 cases) were reviewed. Their clinical stages (CS) were CS II in 1%, CS III in 19.9%, CS IVA in 76.2%, and CS IVB in 19.6% of the cases. All patients were pN+., Results: Ipsilateral neck recurrence occurred in 18 cases (5.8%), 14 cases (4.5%) where the internal jugular vein was resected, and 4 cases (1.3%) where the internal jugular vein was preserved. Neck recurrence did not have significant correlation with tumor site (P = .852), T stage (P = .369), N stage (P = .963), adjuvant radiotherapy (P = .701), number of positive lymph nodes (P = .886), jugular vein preservation (P = .240), and extracapsular spread (P = .670). There was significant correlation between neck recurrence and the lymph node size (.040)., Conclusions: Modified radical neck dissection with internal jugular vein preservation can be performed in selected patients with lymph node metastases, with no significant increase in the risk of neck recurrence.

Purpose: The aim of this study is to evaluate risk factors of neck recurrence in patients with pN1-N2 neck stage, submitted to a modified radical neck dissection with preservation of the internal jugular vein., Materials and Methods: We reviewed the medical records of 72 patients with squamous cell carcinoma of the oral cavity (43 cases) and oropharynx (29 cases). The clinical stage of the neck was N1 in 23 cases and N2a-c in 49., Results: Neck recurrences occurred in 6 cases at the side in which the internal jugular vein was preserved. Neck recurrence did not have significant correlation with tumor site (P = .391), T stage (P = .999), N stage (P = .203), adjuvant radiotherapy (P = .999), number of positive lymph nodes (P = .180), lymph nodes size (P = .429), and extracapsular spread (P = .400)., Conclusions: Modified radical neck dissection with internal jugular vein preservation can be performed in selected patients with lymph node metastases, with no significant increase on the risk of neck recurrence.

Objectives: To find clinical factors related to administration of substandard treatment in older patients with head and neck cancer., Study Design: Historic cohort., Methods: Patients of 70 years of age of older with diagnosis of resectable head and neck cancer were included. Treatment offered to patients was classified as standard or substandard by experienced surgeons. Relation of age, clinical stage, comorbidities, performance status, and treatment with substandard treatment was explored. The effect of substandard treatment on survival was assessed., Results: Three hundred twelve patients were included. Substandard treatment was offered to 19.9% of patients. Associated factors related to selection of substandard treatment were higher age, oro/hypopharynx tumor site, severe comorbidity, advanced clinical stage, and low Karnofsky Index. Patients submitted to substandard treatment had lower overall and cancer-specific survival (45.9% vs. 19.9% and 63.0% vs. 33.1%, respectively)., Conclusion: Selection of substandard treatment decreases overall and cancer-specific survival. Selecting substandard treatment for reasons such as chronologic age, tumor site, or moderate or mild comorbidities worsen patient prognosis.

Background: The number of aged patients with head and neck cancer is increasing. Comorbidities are common in this population. It is necessary to evaluate the effect of comorbidities as measured with the ACE-27 index on recurrence and survival of elderly patients with head and neck cancer, adjusting by other prognostic factors as age, clinical stage and functional status index., Patients: Three hundred and ten patients greater than 70 years of age with head and neck cancer in a referral cancer center were studied. Comorbidity measured with the ACE-27 index was the main independent variable. The outcomes were recurrence and survival., Results: Comorbidities were present in 75% of patients. Five-year disease-free survival, overall survival and cancer-specific survival were 63.1, 42.8 and 55.8%, respectively. Advanced clinical stage and Karnofsky index < or =70 were associated with recurrence. Age >80 years, male gender, Karnofsky index < or =80, advanced clinical stage, and ACE value > or =2 were independently associated with overall survival. The ACE-27 value was not associated with cancer-specific survival. The Karnofsky performance index was associated with overall survival and mortality and acted as a confounding factor on multivariable analysis on overall and cancer-specific survival., Conclusions: Comorbidity measured with ACE-27 was a prognostic factor for overall survival in patients older than 70 years with head and neck cancer. The Karnofsky performance index could be included in multivariable analysis of survival for older patients with head and neck cancer.

Unlabelled: The impact of clinical, pathologic, and surgical variables on the postoperative morbidity, mortality, and survival of patients undergoing extended resections of colon carcinoma were evaluated., Methods: The medical records of 95 patients who underwent extended resections for colon carcinoma between 1953 and 1996 were reviewed. In all cases, in addition to colectomy, 1 or more organs and/or structures were resected en bloc due to a macroscopically based suspicion of tumor invasion. The clinical, pathologic, and surgical parameters were analyzed. Overall survival rates were analyzed according to the method of Kaplan and Meier. Multivariate analysis was performed using the Cox proportional hazards model., Results: Eighty-six patients were treated by curative surgeries and the remaining by palliative resections. Invasion of the organs and/or adjacent structures and regional lymph nodes was found microscopically in 48 and 31 patients, respectively. The median follow-up without postoperative mortality was 47.7 months. The 5-year overall survival rates was 52.6%. The 5-year overall survival rates for patients undergoing curative and palliative surgeries was 58.3% and 0%, respectively. The mean survival time in the palliative surgery group was 3.1 months. Multivariate analysis showed that Karnofsky performance status was strongly related to the risk of postoperative complications (P = .01), and postoperative deaths were associated with the type of surgery and Karnofsky performance status at the time of admission (P = .001)., Conclusions: Some patients with locally advanced colon adenocarcinomas undergoing extended resections have a 5-year overall survival rates of 58.3%. Patients could benefit from palliative-intent procedures, but these measures should cautiously be indicated and avoided in patients with low Karnofsky performance status due to high rates of postoperative mortality and poor survival.

Estrogen (ER) and progesterone (PR) receptors in the normal uterine cervix, cervical intraepithelial neoplasia and invasive carcinoma were studied in consecutive samples from Hospital do Cáncer, São Paulo, between 1996 and 1997. Tissue was collected by removing a fragment of the tumoral area using a 5-mm diameter biopsy punch, followed by removal of a macroscopically normal area as close as possible from the tumor. Histopathological confirmation was obtained for all specimens analyzed. A total of 24 normal tissues, 17 cases of cervical intraepithelial neoplasia and 7 of invasive carcinomas were studied. The ER/PR ratio was determined by immunohistochemistry using monoclonal antibodies specific for each receptor. Adjacent tissue slides were submitted to generic PCR for human papillomavirus (HPV) DNA detection followed by typing by dot blot hybridization. About half (45.8%) of the tumors were HPV DNA positive while 29.1% of the patients were also HPV positive in their respective normal tissue. ER was negative in the tumoral epithelium of 11 HPV-positive patients (P=0.04). There was a trend in the ER distribution in normal tissue that was opposite to that from lesions, but it was not statistically significant (P=0.069). No difference in ER distribution in stromal tissues was observed between HPV-positive and HPV-negative tissues. PR staining was negative in the epithelium of all cases studied. The results obtained from this small number of cases cannot be considered to be conclusive but do suggest that factors related to viral infection affect the expression of these ER/PR cervix receptors.

Purpose: Gold standard treatment for invasive penile carcinoma remains amputation and lymphadenectomy. This procedure has high morbidity and new prognostic factors on the incidence of metastasis would help select candidates to lymphadenectomy. Mutations in the p53 gene common in several neoplasms can be related to the prognosis. We studied 82 patients with penile carcinoma staged according to the 1978 TNM system who underwent amputation and bilateral lymphadenectomy to evaluate the prognostic value of immunohistochemical p53 staining in the primary tumor., Materials and Methods: Immunoreactivity of p53 was studied with other clinicopathological variables, including patient age, stage, histological grade, tumor thickness, lymphatic and venous embolization, corpora cavernosa, corpus spongiosum and urethral infiltration, and human papillomavirus (HPV) status. We also determined its association with lymph node metastasis, the survival rate and the risk of death. In addition, we studied the association of p53 and HPV DNA with prognosis. All slides were reviewed by 1 pathologist. HPV DNA was detected by polymerase chain reaction using GP5/6+ generic primers. p53 expression was measured by immunohistochemical testing with monoclonal Clone DO-7 mouse anti-human p53 protein antibody (Dako A/S, Glostrup, Denmark). The Cox regression hazards method was used for multifactorial analysis., Results: Nuclear accumulation of p53 was detected in 34 of 82 samples (41.5%). Clinical lymph node N stage (p = 0.045), lymphatic (p <0.001) and venous (p = 0.04) embolization by neoplastic cells, p53 positivity (p = 0.012) and p53 grade (p = 0.004) were significantly associated with lymph node metastasis. Followup was 0.1 to 453 months (mean 88.7). Multivariate analysis revealed that only lymphatic embolization (relative risk 9.4, 95% confidence interval [CI] 2.8 to 31.6) and p53 positivity (relative risk 4.8, 95% CI 1.6 to 14.9) were independent factors for lymph node metastasis. Patients with negative p53 had significantly better 5 and 10-year overall survival than those in whom tumors stained positive for p53 (64.5% and 54.6% versus 30.2% and 26.4%, respectively, p = 0.009). When tumors were p53 positive and HPV DNA positive, overall survival was worse. Multivariate analysis revealed that only age (relative risk 2.9, 95% CI 1.6 to 5.1) and lymph node metastasis (relative risk 3.2, 95% CI 1.8 to 5.8) were independent risk factors for death., Conclusions: Immunoreactivity of p53 is an independent factor for lymph node metastasis. The association of positive p53 with positive HPV DNA was related to a worse prognosis.

Background: The aim of this study was to search for mutations in the human mutS homolog 2 (hMSH2) and human mutL homolog 1 (hMLH1) genes in 25 unrelated Brazilian kindreds with suspected hereditary nonpolyposis colorectal cancer (HNPCC)., Methods: The families were grouped according to the following clinical criteria: Amsterdam I or II; familial colorectal cancer (CRC); an early age of onset of CRC in the proband only; or with at least one or two relatives who had HNPCC-related cancers; CRC in the proband only. All patients were studied with direct sequencing., Results: Ten mutations were detected (10 of 25 [40%]); of nine different mutations, seven were novel. The hMLH1 gene had a higher mutation detection rate than hMSH2 (8 of 25 [32%] vs. 2 of 25 [8%]). Only 3 of these 10 families fulfilled the Amsterdam criteria. Two different polymorphisms were detected in the hMLH1 gene and four in the hMSH2 gene., Conclusions: The hMLH1 gene had a higher mutation detection rate than hMSH2. The physician who deals with CRC must take into consideration the heredity issue with patients who present with an early age of onset or a familial history of CRC- or HNPCC-related cancers, including gastric cancer, even if they do not fulfill the former Amsterdam criteria.

Objective: To evaluate survival in patients with metastatic iliac nodal involvement from carcinoma of the penis., Patients and Methods: Thirteen patients with metastases to the iliac nodes were selected from 68 with squamous cell carcinoma of the penis who had undergone amputation and bilateral ilio-inguinal lymphadenectomy. The 1978 Tumour-Nodes-Metastasis system was used for staging. Deep and superficial lymph nodes were removed during the inguinal procedure. Lymph nodes below the common iliac artery (external and obturator) were removed and histologically evaluated for the presence of metastases., Results: The mean (median, range) follow-up was 55.5 (8. 8, 0.3-235) months, at the end of which five patients were free of cancer, seven had died from cancer or treatment-related complications and one was lost to follow-up. Four of the five survivors had metastases to only one iliac lymph node., Conclusion: Ilio-inguinal lymphadenectomy may have a significant role in increasing the survival of patients with metastases to only one iliac lymph node.

Objectives: The present study evaluates the cost-effectiveness of two follow-up routines: a strict follow-up with frequent visits, imaging, and laboratory examinations was compared to a follow-up with infrequent visits that were scheduled mainly on the basis of the patient's symptoms., Methods: A retrospective evaluation was undertaken of 130 patients who underwent a complete resection of non-small cell lung cancer (NSCLC). All patients had complete follow-up for at least 2 years after their operation. The patients were separated into two groups: strict (n = 67), with a routine follow-up policy; and symptom (n = 63), seen on a symptom-oriented basis. The costs of the follow-up routines and the yield of each schedule were compared between the two groups., Results: There were no significant differences in the disease-free interval until the first detection of recurrence. In most patients, metastatic diseases were diagnosed on the basis of symptoms, rather than by routine tests. The patients who had recurrent cancer diagnosed after surgery had a dismal survival rate irrespective of the follow-up schedule. The majority of patients with recurrence died of malignancy within a 2-year period. The costs of strict vs symptom follow-up were significantly different, because of the greater number of routine imaging procedures performed in patients having strict follow-up. On the other hand, when we analyzed only the frequency of hospitalization and the cost per day of hospital treatment for medical problems other than cancer recurrence, the patients in the strict group had a less expensive follow-up than the patients in the symptom group., Conclusions: The present study showed that a more cost-effective routine follow-up scheme should be advised for patients with completely resected NSCLC, without affecting overall outcome. Routine imaging follow-up is of questionable value, and it may be indicated only in academic settings.

Background: An ipsilateral neck dissection is mandatory during initial treatment stages II-IV oral carcinomas. However, no consensus exists whether or not to perform an elective contralateral neck dissection., Methods: Five hundred thirteen consecutive cases of squamous cell carcinoma (269 tongue, 135 floor of the mouth, 44 inferior gingiva, 65 retromolar trigone) were reviewed. Tumor stages were: 69 T1, 227 T2, 217 T3-T4, 263 N0, 250 N1-N3. A total of 563 neck dissections were performed in 448 patients. Univariate and multivariate analysis of risk factors were performed using logistic regression., Results: Two hundred twenty-three patients (49.8%) had positive nodes in the specimen (182 ipsilateral, 36 bilateral, 5 contralateral). Contralateral neck recurrences occurred in 38 cases (33 not submitted to a contralateral neck dissection initially). Multivariate logistic regression analysis demonstrated that clinical stage (p = .0001), tumor crossing midline (p = .0011), and floor of the mouth involvement (p = .0236) were the most important predictors of contralateral metastasis., Conclusion: The contralateral side of the neck is a common and potentially preventable site of recurrence in tumors of the oral cavity. The multivariate model obtained discriminates patients with low and high risk (more than 20%) of contralateral metastasis. The application of this mathematical model can be useful for the indication of contralateral neck dissections, because not all tumors crossing midline are associated to a high risk (stages I and II tumors not involving the floor of the mouth) and not all tumors not crossing midline are at low risk (stages III and IV tumors involving the floor of the mouth).

The decision regarding treatment of supraglottic carcinoma remains controversial, despite recent advances in radiotherapy and surgical procedures. The need to evaluate the prognostic importance of demographic, clinical, pathologic, and treatment-related variables prompted this study. The patient population was of 164 consecutive cases of supraglottic carcinoma. Clinical charts were reviewed and cases were restaged according to the 1987 version of the UICC-AJC classification based on the initial clinical description: 18 T1, 30 T2, 58 T3, 58 T4, 61 NO, 24 N1, and 79 N2a-N3. Management policy for these patients varied during the study, reflecting different opinions of the responsible physicians and technical advances. Seventy-seven patients (47%) underwent surgery, patients who underwent surgery and radiotherapy, respectively, remained alive with no evidence of disease. The 5-year actuarial survival rates were 58.5% for patients initially treated by surgery, and 16.3% for patients in the radiotherapy group. Although several demographic, clinical, and pathologic variables were studied, only initial treatment (p <.0001), N stage (p = .0003), and T stage (p = .0017) were deemed to have independent prognostic value by multivariate regression techniques based on Cox's proportional hazards model. This study has shown that survival of supraglottic carcinoma patients depends on the treatment modality, T stage, and N stage. Our results are disappointing with regard to radiotherapy as a treatment for supraglottic carcinoma in patients with tumors at clinical stages III and IV.

Purpose: The present study evaluates the results of surgical treatment of lung metastases, as well as attempts to identify subgroups of patients who would benefit the most from the operation., Case and Methods: This is a prospective analysis of patients with history of neoplasia, submitted to resection of pulmonary nodules, with the diagnosis or suspicion of metastases. The 182 patients were operated upon through a lateral thoracotomy., Results: The patients submitted to pulmonary resection for suspected metastases showed no malignant tissue in 34 patients (18.6%), and in six patients (3.2%) were diagnosed a second lung primary tumor. Overall survival of the patients was 28% at 56 months, and disease-free survival was 9%. Multivariate analysis showed that disease free interval (p = 0.002), complete resection (p = 0.039), and number of malignant nodules resected (p = 0.016) significantly affected overall survival. Disease-free survival was affected only by complete resection (p = 0.0001) and number of malignant nodules resected (p = 0.004)., Conclusion: Resection of pulmonary metastasis improve survival in a selected group of patients. More studies are necessary to define the value of other therapies in the results of survival in resected pulmonary metastasis.

A total of 302 patients with stage Ib and IIa cervical carcinoma were submitted to radical hysterectomy and lymphadenectomy during the period from 1980 to 1994. The morbidity rate was 37.5% and the mortality rate 0.6%. The most common intraoperative complications were injuries to the great pelvic vessels and the most frequent postoperative complications involved the urinary tract. The leading causes of morbidity were urinary infection (20.8%), bladder dysfunction (9.2%) and ureteral fistulas (2.9%). Although the rate of complications was high, morbidity has been decreasing over the last five years. Thus, radical hysterectomy continues to be one of the methods for the treatment of early cervical carcinoma that presents an acceptable 5-year survival rate.

Unlabelled: The theory of field cancerization in tumors of the head and neck reflects the complex oncogenesis that occurs in this region. The mechanisms that control cell proliferation at the molecular level in epidermoid carcinomas (ECs) of the upper aerodigestive tract are still unclear. Mutations in p53 are the genetic alterations most often detected in ECs of the head and neck and seem to contribute actively to the carcinogenic process triggered by p53 as a tumor-suppressor gene and to its association with tobacco. The objective of the present study was to investigate the expression of p53 protein in epidermoid head and neck carcinomas by immunohistochemistry and its immunohistochemical correlation with other prognostic factors. The study was conducted on 63 consecutive ECs cases not submitted to previous treatment. Specimens of the tumor and of the normal adjacent mucosa were collected during surgery and submitted to immunohistochemical reaction for the determination of the expression of anti-protein p53 antibody (M7001 DAKO A/S, Denmark). Anatomo-clinical and demographic data were not significantly correlated with the presence of lymph node metastases or p53 expression in the tumor or in the adjacent normal mucosa. Tumor localization in the larynx was significantly correlated with p53 expression. Histological grading as grades I, II, III and IV was correlated with significant p53 expression (p = 0.025)., Conclusions: 1) in the studied material obtained from 63 cases of head and neck ECs, we detected a 48 percent rate of immunohistochemically detectable p53 overexpression; 2) we did not detect a relationship between demographic patient data and p53 expression in the tumor or in the normal adjacent mucosa; 3) p53 overexpression was significantly more frequent in ECs material from the larynx: and 4) The presence of 12 cases with p53 overexpression in the normal adjacent mucosa and with a p53-negative tumor is in agreement with the theory of field cancerization. Follow-up of this patient series for a longer period of time will permit a better analysis of these values.

Background: In 1988, Catalona proposed a modified bilateral inguinal lymphadenectomy for staging of lymph node metastasis from penile carcinoma. All three patients with penile carcinoma submitted to this procedure and without histologically confirmed metastases were free of disease within a mean follow-up time of 14.6 months., Methods: In a prospective study, the authors evaluated thirteen patients staged by the TNM system and submitted to modified bilateral inguinal lymphadenectomy., Results: None of the patients had histologic metastases in the medial quadrant lymph nodes. Two of these patients developed regional lymph node metastases within 13.2 months (mean follow-up time)., Conclusions: Catalona's procedure was not reliable. We therefore recommend standard inguinal lymphadenectomy as the minimal treatment for patients with infiltrating carcinoma of the penis.

Background: The presence of neck metastasis reduces the probability of regional control and survival. The purpose of this study is to identify risk factors for contralateral neck metastasis in a series of 218 patients with pyriform sinus carcinoma., Patients and Methods: Tumor stages were: 31 T1-T2, 187 T3-T4, 40 N0, 174 N1-N3, and 4 NX. A total of 182 patients (83%) had metastatic lymph nodes (23 in the contralateral neck)., Results: Thirty-five patients presented neck recurrences (27 in contralateral undissected neck). Logistic regression identified T and N stages, epilarynx and posterior pharyngeal wall involvement, hemilarynx fixation, and ipsilateral level 1 metastasis as important predictors of contralateral metastasis. Five-year survival rates were 41% (pN0), 23% (contralateral pN0), and 31% (contralateral positive nodes)., Conclusions: The contralateral side of the neck was the most common site of recurrence. A lateral neck dissection is advisable for the contralateral side of the neck for high-risk patients.

The results are presented of disease-free interval and overall survival in 53 elderly patients with colon or rectum adenocarcinoma treated with curative surgery. The average age was 75.3 years (median = 75.0); 21 patients were male and 32 were female. Tumor location was as follows: rectum 18 (34%), sigmoid 17 (32.1%), right colon 14 (26.4%), and transverse colon 4 (7.5%) All patients were surgically treated following the classical patterns for tumor resection. After pathological examination, which included the histological grade differentiation, the disease stage was reevaluated following the pTNM system. Overall and disease-free survival at 5 years, for all patients, independent of histological grade differentiation and disease stage, were 75.3% and 55.5%, respectively. Overall survival at 5 years for patients with grades I and II histological differentiation was 74.1% and 85.0%, respectively. None of the grade III patients (2 cases) survived more than 1 year. The 5 years disease-free survival for patients with histological grade differentiation I and II was 56.8% and 60%, respectively. There was no statistically significant difference in overall survival for patients with stages SI, SII, and SIII, but the disease-free survival at 5 years by stages was found to be significant with rates of 100%, 67.6%, and 22.6%. Postoperative mortality was 4 (7.5%). The postoperative mortality and survival rates obtained in this group of patients encourage us not to consider age as a limiting factor for curative surgical treatment.

From 4132 patients treated with radiation therapy due to gynecological malignancy from 1974 to 1988, 527 (12.75%) developed some grade of actinic rectitis with clinical manifestation. The authors analyzed the efficacy of colostomy in the management of 10 women with actinic rectitis grades I and II (Sherman classification) submitted to clinical treatment without response. Pelvic radiation therapy, clinical findings, proctoscopy and rectal biopsy were the basis for the diagnosis and staging of the actinic rectitis. All colostomies were made in the transverse colon and the median follow up from colostomy to last review was 53 months. Eight patients had complete remission of clinical findings after colostomy, but one had recurrence of symptoms 2 years later. One patient had incomplete remission but with clinical improvement and one patient had tumor recurrence. From 8 patients with complete clinical remission, 2 had the colostomies closed, but in 1 was restored 3 months later due to rectum-vaginal fistula.

Ninety-two patients with IIB osteosarcoma of the extremities were treated with intraarterial (IA) cisplatinum (CDDP) followed by surgery [amputation (61.6%) or resection with endoprosthesis (38.4%)]. Postoperative chemotherapy alternating adriamycin and CDDP was used. The total three-year survival was 62.1%, and the disease-free survival was 41.1%. The pathologic evaluation of the degree of tumor necrosis in response to the IA CDDP showed that in 53.2%, the necrosis was over 90%. The multivariate analysis of prognostic factors has shown that the highest survival was among females with tumors smaller than 15 cm. Patients with lesions equal to or larger than 15 cm were three times as likely to die of the disease. A second, more aggressive study is now underway, in which high dose methotrexate (HDMTX) is preoperatively combined with adriamycin and CDDP. Following operation, ifosfamide is added to the cases with a smaller degree of tumor necrosis, while the other group of patients will continue with HDMTX, in addition to CDDP and adriamycin (these last two drugs are used in both arms). Until now, complete remission has been achieved in 82% and 86%, respectively, with a follow-up examination varying from four to 26 months (average, 14 months). This is of extreme importance, because the majority of the authors' patients have tumors at initial evaluation larger than 10 cm in diameter.

Eighty-five women with vulvar squamous cell carcinoma were subjected to radical vulvectomy with bilateral inguinal and femoral node dissection or to radical vulvectomy with bilateral inguinofemoral and deep pelvic node dissection. The association between lymph node status (metastatic or not) and several parameters was analyzed: tumor location, size and clinical stage; tumor thickness, histologic grade and mitotic index; blood vessel, lymphatic and perineural infiltration; and lymphocytic and plasma cell infiltrates. There were no metastases to the pelvic lymph nodes without previous inguinal lymph node involvement. Unilateral vulvar carcinomas did not have contralateral metastatic nodes when there was no ipsilateral nodal involvement. Lymphatic vessel infiltration showed a statistically significant correlation with inguinal node metastases (P less than .05). No correlation was found between lymph node metastasis and tumor size, clitoral invasion, tumor thickness, histologic grade, blood vessel and perineural infiltration, lymphocytic and plasma cell infiltrates, and mitotic index.

Despite the tremendous progress that pediatric oncology has achieved in the treatment of Wilms' tumor over the last several decades, survival rates in our institution before 1970 did not exceed 8%. In order to correct the problem standardized therapy was instituted in 1970 through a multimodal oncological team. Results using the new approach were reviewed in 1979 (50 patients) and showed an overall 34% 2-year survival rate. Although encouraging, these results were still far below the ones reported in the literature. This prompted us to use a vigorous professional and lay educational program in the city. Treatment methods were replaced by those advocated by the Second National Wilms' Tumor Study. A second evaluation period initiated in 1979 and extended through 1984 (35 patients) yielded an overall 83% survival rate. A retrospective study of the two periods by univariate and multivariate survival analysis revealed that, although much of the improvement in survival could be attributed to a shift in stage distribution towards earlier disease, the admission period itself had an important additional explanatory effect with respect to survival. This was probably due to the improvement in treatment protocols used in the latter period. Age was a prognostic variable only for patients admitted during the 1979-1984 period.

Ninety-four soft-tissue sarcomas of head and neck occurring among 10,700 malignancies, seen during the period 1953-1980 in the head-and-neck surgical department, were studied with reference to age, sex, ethnic origin, site, histological type and survival. The objective was to review our own experience with sarcomas in these sites seen in the Department of Pathology, A.C. Camargo Hospital. The predominant site was the head. Fibrosarcoma was the most frequent type in adults and rhabdomyosarcoma, located exclusively in the head, was the most frequent in children.