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Luiz P Kowalski

Publications and source records attributed to Luiz P Kowalski.

At least 19 recordsLinked to original sources

Neck dissection: then and now.

The significance of metastatic disease in the lymph nodes of the neck as a critical independent prognostic factor in head and neck cancer has long been appreciated. Although 19th century surgeons attempted to remove involved cervical lymph nodes at the time of resection of the primary cancer, a systematic approach to en bloc removal of cervical lymph node disease, described in detail by Jawdyński in 1888 and popularized and illustrated by Crile in the early 20th century, provided consistent and more effective treatment, and forms the basis of our current techniques. During the first half of the 20th century, developments included preservation of the accessory nerve in selected cases, elective neck dissection performed in association with resection of various primary tumors, bilateral neck dissection and limited neck dissection. The greatest impetus to the status of radical neck dissection came from Martin, whose technique consisted of resection of all lymph nodes from level I-V together with the accessory nerve, internal jugular vein, sternocleidomastoid muscle and various other structures in a single block of resected tissue. Martin's technical precepts were followed until the latter part of the 20th century when modifications in technique began to find general acceptance. The first description of an effective technique of modified radical neck dissection was published in Spanish by Suárez, in 1963. This technique, which preserves important structures, such as the internal jugular vein, sternocleidomastoid muscle and accessory nerve, was refined and popularized by various authors who published their results in the English language literature during the period from 1964 through 1990 and beyond. Modified or "functional" neck dissection avoids much of the morbidity of radical neck dissection while achieving equivalent degrees of control of regional disease in properly selected cases. By the late 20th century, the concept of selective neck dissection, consisting of resection of only the nodal groups at greatest risk for metastasis from a given primary site, was studied and developed. These limited dissections are now widely employed for elective, and in properly selected cases, therapeutic treatment and staging of the neck, and have been proposed for limited cervical recurrences after various chemoradiation protocols. Prospective studies have demonstrated similar rates of neck recurrence and survival after elective selective neck dissection compared to elective modified radical neck dissection. Other modifications and factors applied to treatment of cervical lymph node disease include the use of adjuvant and neo-adjuvant radiation and chemotherapy, a revised system for classification of neck dissections, the identification of various adverse prognostic factors such as extracapsular spread and extranodal soft tissue deposits, application of sentinel lymph node biopsy to staging of the neck, the use of immunohistochemical and molecular techniques for identification of lymph node metastases not detectable by light microscopy, and the possibility of endoscopic neck dissection. The authors conclude that neck dissection, as evolved over the past century, is a fundamental tool in management of patients with head and neck cancer, but is still a work in progress.

Head and Neck Neoplasms↗

Class distinction between follicular adenomas and follicular carcinomas of the thyroid gland on the basis of their signature expression.

BACKGROUND: Nodules of the thyroid gland are observed frequently in patients who undergo ultrasound studies. The majority of these nodules are benign, corresponding to goiters or adenomas, and only a small fraction corresponds to carcinomas. Among thyroid tumors, the diagnosis of follicular adenocarcinomas by preoperative fine-needle aspiration biopsy is a major challenge, because it requires inspection of the entire capsule to differentiate it from adenoma. Consequently, large numbers of patients undergo unnecessary thyroidectomy. METHODS: Using data from gene expression analysis, the authors applied Fisher linear discriminant analysis and searched for expression signatures of individual samples of adenomas and follicular carcinomas that could be used as molecular classifiers for the precise classification of malignant and nonmalignant lesions. RESULTS: Fourteen trios of genes were described that fulfilled the criteria for the correct classification of 100% of samples. The robustness of these trios was verified by using leave-1-out cross-validation and bootstrap analyses. The results demonstrated that, by combining trios, better classifiers could be generated that correctly classified >92% of samples. CONCLUSIONS: The strategy of classifiers based on individual signatures was a useful strategy for distinguishing between samples with very similar expression profiles.

Adenocarcinoma, Follicular↗

Craniofacial resection for malignant melanoma of the skull base: report of an international collaborative study.

OBJECTIVE: To report postoperative mortality, complications, and outcomes in a subset of patients with the histologic diagnosis of malignant melanoma extracted from an existing database of a large cohort of patients accumulated from multiple institutions. DESIGN: Retrospective outcome analysis. SETTING: Seventeen international tertiary referral centers performing craniofacial surgery for malignant skull base tumors. PATIENTS: A total of 53 patients were identified from a database of 1307 patients who had craniofacial resection for malignant tumors at 17 institutions. The median age was 63 years. Of the 53 patients, 25 (47%) had had prior single modality or combined treatment, which included surgery in 22 (42%), radiation in 11 (21%), and chemotherapy in 2 (4%). The margins of resection were close or microscopically positive in 7 (13%). Adjuvant radiotherapy was given in 22 (42%), chemotherapy in 3 (6%), and vaccine or interferon therapy in 2 (4%). Complications were classified into overall, local, central nervous system, systemic, and orbital. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were determined using the Kaplan-Meier method. Predictors of outcome were identified by multivariate analysis. RESULTS: Postoperative mortality occurred in 3 patients (6%) and postoperative complications were reported in 14 patients (26%). Local wound complications occurred in 6 patients (11%), central nervous system in 7 (13%), systemic in 3 (6%), and orbital in 1 (2%). With a median follow-up of 10 months (range, 1-159 months), the 3-year OS, DSS, and RFS rates were 28.2%, 29.7%, and 25.5%, respectively. The extent of orbital involvement and adjuvant postoperative radiation therapy (PORT) were independent predictors of DSS and OS on multivariate analysis, whereas only PORT was an independent predictor of RFS. Patients treated with PORT had significantly better 3-year OS (39% vs 18%; relative risk, 2.9; P = .007), DSS (41% vs 19%; relative risk, 3.0; P = .007), and RFS (39% vs 15%; relative risk, 4.2; P = .001). CONCLUSIONS: Craniofacial resection in patients with malignant melanoma of the skull base has mortality (6%) and complication rates (26%) comparable to other malignant tumors of the skull base. However, malignant melanoma is associated with a much poorer OS, DSS, and RFS. Adjuvant PORT correlated with improved 3-year OS, DSS, and RFS on multivariate analysis. These factors must be taken into account when considering craniofacial resection in a patient with malignant melanoma invading the skull base.

Adolescent↗

Planned neck dissection following chemoradiotherapy for advanced head and neck cancer: is it necessary for all?

In the absence of large-scale randomized trials evaluating dissection versus observation of the involved neck after neoadjuvant chemoradiotherapy, there is a need to collect data that will either support or ultimately refute a role for planned posttreatment neck dissection. A significant percentage of patients with extensive (N2 or N3) neck disease who demonstrate a complete response to chemoradiation therapy may harbor residual occult metastases, and identification of this subset of patients remains a clinical challenge. Because surgical salvage rates are greatly diminished when occult nodal disease becomes clinically manifest, planned posttreatment neck dissection is advocated but may not be necessary in all patients. The role of positron emission tomography chemoradiotherapy (PET-CT) in this scenario remains unproven but holds promise in being able to identify which patients may be harboring residual disease in the neck after chemoradiotherapy. The implementation of as yet unidentified molecular tumor markers in combination with PET-CT may ultimately prove to be effective in identifying patients who will best benefit from posttherapy neck dissection. Correlation of imaging results and pathologic node status will be important in determining the accuracy and, therefore, the value of this imaging modality for predicting the presence or absence of residual disease.

Carcinoma, Squamous Cell↗

Epithelial lacrimal gland tumors: a clinicopathological study of 18 cases.

OBJECTIVE: The aim of this study was to report the clinicopathological features of 18 epithelial tumors of the lacrimal gland treated in a single institution. STUDY DESIGN AND SETTING: Clinical data and treatment were recorded and histological features reviewed. RESULTS: Twelve tumors (66.7%) were adenoid cystic carcinoma (ACC), 5 (27.8%) pleomorphic adenoma (PA), and 1 (5.5%) carcinoma ex pleomorphic adenoma. All patients with ACC presented with advanced clinical stage, and most were treated by wide surgical resection followed by adjuvant radiotherapy. No recurrence was observed in 4 cases of ACC; however, 7 patients died from persistence of disease or by local and/or distant recurrence. All PA patients were successfully treated by surgical resection. CONCLUSIONS: Epithelial lacrimal gland tumors are mainly PA and ACC, and malignancies are more common than benign tumors. Although ACC presented typically with advanced clinical stage, 33% of the patients survived without tumor recurrence or metastasis.

Adenoma, Pleomorphic↗

Elective and therapeutic selective neck dissection.

Selective neck dissection is a modification of the more comprehensive modified radical or radical neck dissection that is designed to remove only those nodal levels considered to be at risk for harboring nodal metastases. The role of selective neck dissection continues to evolve: while initially designed as a staging and diagnostic procedure for patients without clinical evidence of nodal disease, a growing body of literature suggests that selective neck dissection has a therapeutic role in patients with clinical and histologic evidence of nodal metastases. The rationale behind selective neck dissection, its application in the clinically negative but histologically node-positive neck and the extended application of selective neck dissection in patients with clinical evidence of nodal disease are discussed.

Carcinoma, Squamous Cell↗

Expression profile of malignant and non-malignant diseases of the thyroid gland reveals altered expression of a common set of genes in goiter and papillary carcinomas.

Using cDNA microarrays with 3800 cDNA fragments, we determined the expression profile of normal thyroid tissue, goiter, adenoma and papillary carcinoma (10 samples from each class). After background correction and statistical analysis, we identified a set of 160 genes as being differentially expressed in all pair-wise comparisons. Here we demonstrate that, at least on the basis of these differentially expressed genes, a positive correlation between goiter and papillary carcinomas could be observed. We identified a common set of genes whose expression is diminished in both goiter and papillary carcinomas as compared to normal thyroid tissue. Moreover, no genes with inverse correlation in samples from goiter and papillary carcinomas could be detected. Using Real-Time PCR and/or tissue microarrays, we confirmed the altered expression of some of the identified genes. Of notice, we demonstrate that the reduced mRNA levels of p27(kip1) observed in papillary carcinomas as compared to either goiter or normal thyroid tissues (P<0.001) is accompanied by an altered protein distribution within the cell. In papillary carcinomas, P27(KIP1) is preferentially cytoplasmic as opposed to goiter or normal thyroid tissue, where P27(KIP1) is preferentially located in the nucleus. The exploitation of the data presented here could contribute to the understanding of the molecular events related to thyroid diseases and gives support to the notion that common molecular events might be related to the frequent observation of areas of papillary carcinomas in the gland of patients with goiter.

Carcinoma, Papillary↗

Craniofacial resection for malignant paranasal sinus tumors: Report of an International Collaborative Study.

BACKGROUND: Malignant tumors of the superior sinonasal vault are rare, and, because of this and the varied histologic findings, most outcomes data reflect the experience of small patient cohorts. This International Collaborative study examines a large cohort of patients accumulated from multiple institutions experienced in craniofacial surgery, with the aim of reporting benchmark figures for outcomes and identifying patient-related and tumor-related predictors of prognosis after craniofacial resection (CFR). METHODS: Three hundred thirty-four patients from 17 institutions were analyzed for outcome. Patients with esthesioneuroblastoma were excluded and are being reported separately. The median age was 57 years (range, 3-98 years). One hundred eighty-eight patients (56.3%) had had prior single-modality or combined treatment, which included surgery in 120 (36%), radiation in 79 (23.7%), and chemotherapy in 56 (16.8%). The most common histologic findings were adenocarcinoma in 107 (32%) and squamous cell carcinoma in 101 (30.2%). The margins of resection were close or microscopically positive in 95 (30%). Adjuvant radiotherapy was given in 161 (48.2%) and chemotherapy in 16 (4.8%). Statistical analyses for outcomes were performed in relation to patient characteristics, tumor characteristics, including histologic findings and extent of disease, surgical resection margins, prior radiation, and prior chemotherapy to determine predictive factors. RESULTS: Postoperative mortality occurred in 15 patients (4.5%). Postoperative complications occurred in 110 patients (32.9%). The 5-year overall, disease-specific, and recurrence-free survival rates were 48.3%, 53.3%, and 45.8%, respectively. The status of surgical margins, histologic findings of the primary tumor, and intracranial extent were independent predictors of overall, disease-specific, and recurrence-free survival on multivariate analysis. CONCLUSIONS: CFR for malignant paranasal sinus tumors is a safe surgical treatment with an overall mortality of 4.5% and complication rate of 33%. The status of surgical margins, histologic findings of the primary tumor, and intracranial extent are independent predictors of outcome.

Adenocarcinoma↗

Complications of craniofacial resection for malignant tumors of the skull base: report of an International Collaborative Study.

BACKGROUND: Advances in imaging, surgical technique, and perioperative care have made craniofacial resection (CFR) an effective and safe option for treating malignant tumors involving the skull base. The procedure does, however, have complications. Because of the relative rarity of these tumors, most existing data on postoperative complications come from individual reports of relatively small series of patients. This international collaborative report examines a large cohort of patients accumulated from multiple institutions with the aim of identifying patient-related and tumor-related predictors of postoperative morbidity and mortality and set a benchmark for future studies. METHODS: One thousand one hundred ninety-three patients from 17 institutions were analyzed for postoperative mortality and complications. Postoperative complications were classified into systemic, wound, central nervous system (CNS), and orbit. Statistical analyses were carried out in relation to patient characteristics, extent of disease, prior radiation treatment, and type of reconstruction to determine factors that predicted mortality or complications. RESULTS: Postoperative mortality occurred in 56 patients (4.7%). The presence of medical comorbidity was the only independent predictor of mortality. Postoperative complications occurred in 433 patients (36.3%). Wound complications occurred in 237 (19.8%), CNS-related complications in 193 (16.2%), orbital complications in 20 (1.7%), and systemic complications in 57 (4.8%) patients. Medical comorbidity, prior radiation therapy, and the extent of intracranial tumour involvement were independent predictors of postoperative complications. CONCLUSIONS: CFR is a safe surgical treatment for malignant tumors of the skull base, with an overall mortality of 4.7% and complication rate of 36.3%. The impact of medical comorbidity and intracranial tumor extent should be carefully considered when planning therapy for patients whose tumors are amenable to CFR.

Adolescent↗

Expression of PCNA, p53, Bax, and Bcl-X in oral poorly differentiated and basaloid squamous cell carcinoma: relationships with prognosis.

BACKGROUND: The aim of this study was to compare the clinical features and proliferating cell nuclear antigen (PCNA), p53, Bcl-X, and Bax expression in primary oral basaloid squamous cell carcinoma (BSCC) and poorly differentiated squamous cell carcinoma (PDSCC) matched by stage and site and to assess the possible prognostic significance of these variables. METHODS: Seventeen cases of oral BSCC were compared with 27 PDSCCs matched by stage and tumor site. In addition, PCNA, p53, Bax, and Bcl-X expression in both carcinomas were evaluated in relation to their clinicopathologic features and prognostic values using the Kaplan-Meier method and Cox regression models. RESULTS: No statistically significant differences were found between the groups (BSCC and PDSCC) in regard to clinical features and immunohistochemical reactivity for antibodies PCNA, p53, and Bcl-X. In comparison with PDSCC, the BSCC group exhibited a higher Bax score (p = .031). The 5-year and 10-year overall survival, cancer-specific survival, and disease-free survival rates demonstrated no significant differences between the BSCC and PDSCC groups, and the PCNA, p53, Bax, and Bcl-X also showed no prognostic value. CONCLUSIONS: These results suggest that the clinical and biologic course of BSCC is similar to PDSCC in the oral cavity when clinical stage and site are matched.

Adult↗

DNA methylation in the CTCF-binding site I and the expression pattern of the H19 gene: does positive expression predict poor prognosis in early stage head and neck carcinomas?

Loss of allele-specific expression by the imprinted genes IGF2 and H19 has been correlated with a differentially methylated region (DMR) upstream to the H19 gene. The H19-DMR contains seven potential CCCTC-binding factor (CTCF) binding sites. CTCF is a chromatin insulator and a multifunctional transcription factor whose binding to the H19-DMR is suppressed by DNA methylation. Our study included a group of 41 head and neck squamous cell carcinoma (HNSCC) samples. The imprinting status of the H19 gene was analyzed in 11 out of 35 positive cases for H19 gene expression, and only 1 of them showed loss of imprinting. We detected a significant correlation (P = 0.041, Fisher's exact test) between H19 expression and tumor recurrence. Among H19 positive cases, six were T2, in which five developed recurrence and/or metastasis. Inversely, in the group of tumors that showed no H19 gene expression, 5 out of 24 were T2 and only 1 presented regional recurrence. These data support the hypothesis that H19 expression could be used as a prognostic marker to indicate recurrence in early stage tumors. We also examined the methylation of the CTCF binding site 1 in a subgroup of these samples. The H19 gene silencing and loss of imprinting were not correlated with the methylation pattern of the CTCF binding site 1. However, the significant correlation between H19 expression and tumor recurrence suggest that this transcript could be a marker for the progression of HNSCC.

Adult↗

Treatment results on advanced neck metastasis (N3) from head and neck squamous carcinoma.

OBJECTIVE: To analyze the long-term results of patients with N3 neck metastasis from squamous carcinoma of the head and neck. STUDY DESIGN: This study is based on the analysis of a retrospective cohort of 224 previously untreated patients with squamous cell carcinoma of the head and neck and lymph node metastasis sized greater than 6 cm (N3) who were evaluated from 1981 to 1996. RESULTS: Fifty-four patients (24.1%) underwent neck dissection, 137 underwent radiotherapy alone (61.2%), and 33 received only supportive care (14.7%). Control of the neck metastasis was achieved in 46 cases among the treated ones (24.1%), varying from 51.9% for the patients who underwent surgery to 13.1% for radiotherapy alone ( P < 0.001). Exclusive distant metastasis occurred in 37.0% of the cases who had control of the neck disease. The 3-year overall survival rates were 17.9% for patients who underwent surgery and 7.0% for radiotherapy alone ( P = 0.003). The multivariate analysis showed as independent predictive factors the treatment approach ( P < 0.001) and tumor site ( P = 0.016). CONCLUSIONS: This study confirms the poor prognosis of patients with N3 neck disease, mainly when treated by radiotherapy alone. A radical neck dissection associated with adjuvant radiotherapy is indicated whenever feasible. Because of the high rate of distant metastasis, protocols including adjuvant chemotherapy should be investigated.

Adult↗

Overexpression of Fos-related antigen-1 in head and neck squamous cell carcinoma.

The activating protein-1 (AP-1) family of transcription factors has been implicated in the control of proliferation and differentiation of keratinocytes, but its role in malignant transformation is not clear. The aim of this study is to assess the pattern of mRNA expression of jun-fos AP-1 family members in 45 samples of head and neck squamous cell carcinomas (HNSCC) and matched adjacent mucosa by means of Northern blot analysis. Transcripts of all family members were identified, except for JunB that was detected only by means of reverse transcription polymerase chain reaction. Neither c-Fos nor JunD or FosB mRNA differed between tumours and normal tissues. We observed a strong Fos-related antigen-1 (Fra-1) and Fra-2 expression, but only Fra-1 mRNA densitometric values were higher in tumour, compared to normal adjacent mucosa (t-test, P = 0.006). A direct relationship between the positive expression of Fra-1 mRNA, above tumour median, was associated with the presence of compromised lymph nodes (Fischer exact test, P = 0.006). In addition, Fra-1 protein staining was assessed in a collection of 180 tumours and 29 histologically normal samples adjacent to tumours in a tissue array. Weak reactivity, restricted to the basal cell layer, was detected in 79% of tumour adjacent normal tissues, opposed to the intense reactivity of cancer tissues. In the subgroup of oral cancers, we have observed a shift in Fra-1 immunoreactivity, as long as the number of patients in each category, cytoplasmic or nuclear/cytoplasmic staining, was analysed (Fischer exact test, P = 0.0005). Thus, Fra-1 gene induction and accumulation of Fra-1 protein may contribute to the neoplastic phenotype in HNSCC.

Adult↗

Cancer of the oral cavity: a comparison between institutions in a developing and a developed nation.

BACKGROUND: The literature suggests that the natural history of squamous cell carcinoma of the oral cavity may vary and the prognosis is different in patients from developing and developed nations. The objective of this study was to compare the clinical presentation, management, and outcome of patients with oral cancer treated at tertiary care cancer institutions in a developing nation (Brazil- Centro de Tratamento e Pesquisa Hospital do Cancer A. C. Camargo [HCACC]) with those from a developed nation (United States- Memorial Sloan-Kettering Cancer Center [MSKCC]). METHODS: Between January 1990 and December 1994, 602 patients underwent initial treatment in the study institutions. RESULTS: Overall, patients from HCACC had a higher predominance of men (78.8% vs 54.6%; p <.001) and a higher prevalence of tobacco (88.1% vs 77.8%; p =.002) and alcohol consumption (80.9% vs 69.8%; p =.004). More patients at HCACC had advanced disease (stage III/IV; 73.4% vs 37.4%; p<.001). Even though the overall outcome was poorer in patients from HCACC (p <.001), after controlling for stage, there was not a statistically significant difference in disease-free or overall survival between the two institutions. Only at cancer-specific survival for early-stage disease (stage I/II) patients showed a difference (p =.05). Moreover, clinical stage (RR, 3.7; 95% CI, 2.6-5.5) and definitive treatment (RR, 3.3; 95% CI, 2.4-4.6) were the only factors that remained as significant predictors of outcome on multivariate analysis. Finally, the rate of subsequent second primary cancers was higher in patients from HCACC (p =.03). CONCLUSIONS: Statistically significant differences were found in clinical presentation, tumor characteristics, and outcome in OC patients between the two institutions from a developing and developed nation. Overall outcome was poorer in HACC patients. However, after controlling for site, stage, and treatment, the outcome of these patients was similar, with the exception of a higher rate of occurrence of second primary cancers in patients from HACC. Given that the use of standard protocols of treatment offer similar outcomes, the establishment of education programs and screening measures for early diagnosis might be the best chance to improve overall outcome in OC patients in developing nations.

Alcohol Drinking↗

Clinical significance of c-myc and p53 expression in head and neck squamous cell carcinomas.

c-myc and p53 genes were frequently deregulated in head and neck squamous cell carcinoma (HNSCC). To determine if the concomitant expression of the two oncogenes might have prognostic value, the survival and free disease time of 140 consecutive HNSCC patients followed up for a median time of 29.9 months was analyzed in the light of p53 and c-myc expression assessed by immunohistochemistry. Positive c-myc and p53 staining was detected respectively in 35.7 and 50.7% of the tumors. Double positivity emerged in 16.4% of the cases. Overall-survival of patients was not associated with the immunoreactivity of p53 or c-myc considered separately or grouped in subsets. Considering only the advanced stages, the concomitant expression of both oncogenes in tumors was associated with worse disease-free survival (P = 0.004) suggesting a role for p53 and c-myc genes in progression of this HNSCC subset. Clinical parameters (presence of lymph nodes, histologic grade and tumor width) remained important indicators of overall survival (OS).

Adult↗