ABSTRACT
This study presents a new technique for robotic-assisted intracorporeal rectal transection and hand-sewn anastomosis for low anterior resection that overcomes some limitations of conventional techniques. By integrating the advantages of the robotic platform, ensuring standardized exposure during rectal transection, and emphasizing the importance of avoiding complications associated with staple crossings, this innovation has the potential to significantly improve outcomes and reduce costs for patients with lower rectal tumors.
Subject(s)
Laparoscopy , Rectal Neoplasms , Robotic Surgical Procedures , Humans , Laparoscopy/methods , Rectum/surgery , Rectum/pathology , Anastomosis, Surgical/methods , Rectal Neoplasms/surgery , Rectal Neoplasms/pathologyABSTRACT
BACKGROUND: Soft tissue sarcomas are rare malignant tumors with significant heterogeneity. The importance of classifying histological grades is fundamental to defining the treatment approach. OBJECTIVE: To evaluate magnetic resonance imaging (MRI) in predicting the histological grade of soft tissue sarcomas. METHODS: A retrospective observational study included patients over 18 years undergoing MRI and primary tumor surgery at AC Camargo Cancer Center from January 2015 to June 2022. Two radiologists evaluated MRI criteria (size, margin definition, heterogeneity of the T2 signal, high-intensity peritumoral signal on T2, and postperitumoral contrast), and a grading prediction score was calculated. χ2 and logistic regression analyses were conducted. RESULTS: Sixty-eight patients were included (38 men; median: 48 years). Moreover, 52 high-grade and 16 low-grade tumors were observed. The MRI criteria associated with histological grade were peritumoral high-intensity T2-weighted signals (p < 0.001) and peritumoral postcontrast enhancement (p = 0.006). Logistic regression confirmed their significance (odds ratio [OR]: 11.8 and 8.8, respectively). Each score point increment doubled the chance of high-grade tumors (OR: 2.0; p = 0.014). CONCLUSION: MRI effectively predicts histological grades of soft tissue sarcomas. Peritumoral high-intensity T2-weighted signals and peritumoral postcontrast enhancement are valuable indicators of high-grade tumors. This highlights MRI's importance in treatment decision-making for sarcoma patients.
ABSTRACT
BACKGROUND: The initial approach to the treatment of desmoid tumors has changed from surgical resection to watchful waiting. However, surgery is still sometimes considered for some patients, and it is likely that a few patients would benefit from tumor removal if the likelihood of local recurrence could be predicted. However, to our knowledge, there is no tool that can provide guidance on this for clinicians at the point of care. QUESTION/PURPOSE: We sought to explore whether a combined molecular and clinical prognostic model for relapse in patients with desmoid tumors treated with surgery would allow us to identify patients who might do well with surgical excision. METHODS: This was a retrospective, single-center study of 107 patients with desmoid tumors who were surgically treated between January 1980 and December 2015, with a median follow-up of 106 months (range 7 to 337 months). We correlated clinical variables (age, tumor size, and localization) and CTNNB1 gene mutations with recurrence-free survival. Recurrence-free survival was estimated using a Kaplan-Meier curve. Univariate and multivariable analyses of time to local recurrence were performed using Cox regression models. A final nomogram model was constructed according to the final fitted Cox model. The predictive performance of the model was evaluated using measures of calibration and discrimination: calibration plot and the Harrell C-statistic, also known as the concordance index, in which values near 0.5 represent a random prediction and values near 1 represent the best model predictions. RESULTS: The multivariable analysis showed that S45F mutations (hazard ratio 5.25 [95% confidence interval 2.27 to 12.15]; p < 0.001) and tumor in the extremities (HR 3.15 [95% CI 1.35 to 7.33]; p = 0.008) were associated with a higher risk of local recurrence. Based on these risk factors, we created a model; we observed that patients considered to be at high risk of local recurrence as defined by having one or two factors associated with recurrence (extremity tumors and S45F mutation) had an HR of 8.4 compared with patients who had no such factors (95% CI 2.84 to 24.6; p < 0.001). From these data and based on the multivariable Cox models, we also developed a nomogram to estimate the individual risk of relapse after surgical resection. The model had a concordance index of 0.75, or moderate discrimination. CONCLUSION: CTNNB1 S45F mutations combined with other clinical variables are a potential prognostic biomarker associated with the risk of relapse in patients with desmoid tumors. The developed nomogram is simple to use and, if validated, could be incorporated into clinical practice to identify patients at high risk of relapse among patients opting for surgical excision and thus help clinicians and patients in decision-making. A large multicenter study is necessary to validate our model and explore its applicability. LEVEL OF EVIDENCE: Level III, therapeutic study.
Subject(s)
Fibromatosis, Aggressive , Humans , Fibromatosis, Aggressive/genetics , Fibromatosis, Aggressive/surgery , Retrospective Studies , Neoplasm Recurrence, Local/surgery , Mutation , Prognosis , beta Catenin/geneticsABSTRACT
BACKGROUND: Cancer patients configure a risk group for complications or death by COVID-19. For many of them, postponing or replacing their surgical treatments is not recommended. During this pandemic, surgeons must discuss the risks and benefits of treatment, and patients should sign a specific comprehensive Informed consent (IC). OBJECTIVES: To report an IC and an algorithm developed for oncologic surgery during the COVID-19 outbreak. METHODS: We developed an IC and a process flowchart containing a preoperative symptoms questionnaire and a PCR SARS-CoV-2 test and described all perioperative steps of this program. RESULTS: Patients with negative questionnaires and tests go to surgery, those with positive ones must wait 21 days and undergo a second test before surgery is scheduled. The IC focused both on risks and benefits inherent each surgery and on the risks of perioperative SARS-CoV-2 infections or related complications. Also, the IC discusses the possibility of sudden replacement of medical staff member(s) due to the pandemic; the possibility of unexpected complications demanding emergency procedures that cannot be specifically discussed in advance is addressed. CONCLUSIONS: During the pandemic, specific tools must be developed to ensure safe experiences for surgical patients and prevent them from having misunderstandings concerning their care.
Subject(s)
COVID-19/epidemiology , Informed Consent , Neoplasms/surgery , SARS-CoV-2 , Algorithms , Humans , Surgical OncologyABSTRACT
PURPOSE: Incidence and mortality of prostate cancer (PCa) are still increasing in developing countries. Limited access to the health system or more aggressive disease are potential reasons for this. Ethnic and social differences in developed countries seem to make inappropriate to extrapolate data from other centers. We aim to report the epidemiological profile of a PSA-screened population from a cancer center in Brazil. MATERIALS AND METHODS: We retrospectively selected 9.692 men enrolled in a PCa prevention program, comprising total PSA level and digital rectal examination at the first appointment, associated with complementary tests when necessary. Men aged over 40 years-old were included after shared decision-making process. Prostate biopsy (TRUS) was performed when clinically suspected for PCa. After the diagnosis, patients underwent appropriate treatment. RESULTS: TRUS was performed in 5.5% of men and PCa incidence was 2.6%. Overall ratio between number of patients who needed to be screened in order to diagnose one cancer was 38.9 patients, with 2.1 biopsies performed to diagnose a cancer. Positive predictive value (PPV) of TRUS biopsy in this strategy was 47.2%, varying from 38.5% (<50 years-old) to 60% (>80 years-old). We evidenced 70 patients (27.9%) classified as low risk tumors, 74 (29.5%) as intermediate risk, and 107 (42.6%) as high-risk disease. CONCLUSIONS: PSA-screening remains controversial in literature. In front of a huge miscegenated people and considering the big proportion of high-risk PCa, even in young men diagnosed with the disease, it is imperative to inform patients and health providers about these data particularities in Brazil.
Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms , Adult , Aged , Aged, 80 and over , Biopsy , Brazil/epidemiology , Early Detection of Cancer , Humans , Male , Middle Aged , Predictive Value of Tests , Prostate-Specific Antigen/analysis , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/epidemiology , Public Health , Retrospective StudiesABSTRACT
The Brazilian Society of Surgical Oncology was established over 30 years ago. Despite that, surgical oncology was finally recognized as a Board-Certified medical specialty in 2017 and has strengthened its role in the standardization of surgical and multimodal approaches in our country. This article aims to describe the process and the main challenges of the specialists training who are qualified for job opportunities and who meet the expectations of the recently created competence matrix for surgical oncologists in Brazil. Thus, we hope to expose the challenges of teaching surgical oncology, describe its history and experiences in important country services, and outline the minimum requirements for creating a more humanistic surgical oncologist who is updated and fully committed with multidisciplinary treatment for cancer patients. We conclude that the main characteristic that the surgical oncologist must have is the ability to offer holistic treatments to the patient, based on the highest level of evidence, love, and compassion, to direct the treatment and understand all of the afflictions that arise with a cancer diagnosis. Moreover, the surgical oncologist in training and in the field must be continuously updating himself to offer the best options of treatment to patients.
Subject(s)
Curriculum , Education, Medical, Graduate/organization & administration , Surgical Oncology/education , Brazil , Certification , Clinical Competence/standards , Humans , Internship and Residency/organization & administration , Societies, Medical , Specialization , Specialty BoardsABSTRACT
INTRODUCTION: Soft tissue sarcomas (STSs) are rare tumors and constitute only 1% of all tumors in adults. Indeed, due to their rarity, most cases in Brazil are not treated according to primary international guidelines. METHODS: This consensus addresses the treatment of STSs in the extremities. It was made by workgroups from Brazilian Societies of Surgical Oncology, Orthopaedics, Clinical Oncology, Pathology, Radiology and Diagnostic Imaging, and Radiation Oncology. The workgroups based their arguments on the best level of evidence in the literature and recommendations were made according to diagnosis, staging, and treatment of STSs. A meeting was held with all the invited experts and the topics were presented individually with the definition of the degree of recommendation, based on the levels of evidence in the literature. RESULTS: Risk factors and epidemiology were described as well as the pathological aspects and imaging. All recommendations are described with the degree of recommendation and levels of evidence. CONCLUSION: Recommendations based on the best literature regional aspects were made to guide professionals who treat STS. Separate consensus on specific treatments for retroperitoneal, visceral, trunk, head and neck sarcomas, and gastrointestinal stromal tumor, are not contemplated into this consensus.
Subject(s)
Extremities/pathology , Sarcoma/therapy , Soft Tissue Neoplasms/therapy , Biopsy , Brazil , Chemotherapy, Adjuvant , Extremities/surgery , Humans , Lymph Nodes/pathology , Neoplasm Metastasis/diagnosis , Neoplasm Metastasis/therapy , Neoplasm Staging , Palliative Care , Postoperative Complications/therapy , Radiotherapy, Adjuvant , Risk Factors , Sarcoma/diagnostic imaging , Sarcoma/pathology , Soft Tissue Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/pathologySubject(s)
Anastomosis, Surgical , Rectum , Robotic Surgical Procedures , Female , Humans , Anastomosis, Surgical/methods , Anastomosis, Surgical/adverse effects , Colon/surgery , Constriction, Pathologic/surgery , Constriction, Pathologic/etiology , Postoperative Complications/surgery , Postoperative Complications/etiology , Rectum/surgery , Robotic Surgical Procedures/methods , Suture Techniques , Aged, 80 and overABSTRACT
Solitary bone metastasis from testicular tumor is rare. In literature, only few cases of isolated bone metastasis at first presentation have been reported, and none of them have been treated with extended surgery of the pelvic bone. Case Presentation: We report the case of a 33-year-old man with an iliac bone osteolytic metastasis as the first presentation of a non-seminomatous germ-cell testis tumor (NSGCT), treated with post-chemotherapy en bloc resection of residual tumor in the left iliac bone (Type I + II internal hemipelvectomy). After a 72-month follow-up, the patient has been asymptomatic, with no signs of local recurrence or metastasis and negative serum tumor markers. Conclusions: In selected cases, testicular NSGCT with iliac bone metastasis and normal or normalizing tumor markers can be treated, in association with chemotherapy, by extended surgery, including bone resection, to obtain gain in survival and maintain limb function.
Subject(s)
Bone Neoplasms/secondary , Hemipelvectomy , Neoplasms, Germ Cell and Embryonal/surgery , Testicular Neoplasms/surgery , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Bleomycin/therapeutic use , Bone Neoplasms/diagnosis , Bone Neoplasms/drug therapy , Cisplatin/therapeutic use , Etoposide/therapeutic use , Humans , Male , Neoplasm Metastasis , Neoplasm, Residual , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/pathology , Orchiectomy , Pelvic Bones/pathology , Testicular Neoplasms/drug therapy , Testicular Neoplasms/pathology , Treatment OutcomeABSTRACT
PURPOSE: Patients with cancer of the lower and middle rectum who are candidates for curative surgery often have negative opinions on definitive colostomy. The purpose of this study is to compare the quality of life (QoL) of patients who undergo standard treatment for rectal cancer with sphincter preservation or definitive colostomy. METHODS: A total of 125 patients with adenocarcinoma of the lower or middle rectum who underwent radical surgery with curative intent with a follow-up ≥ 1 year were recruited: 83 patients (group 1) were subjected to low anterior resection and low colorectal or coloanal anastomosis-thus preserving their sphincter-and 42 (group 2) were treated with abdominoperineal resection, followed by terminal definitive colostomy. QoL was assessed with the EORTC QLQ-C30 and QLQ-CR29 questionnaires. RESULTS: Health and global quality of life were similar between groups; however, patients who underwent definitive colostomy had higher scores on the emotional (p value = 0.016) and cognitive function scales (p value = 0.017). Patients with sphincter preservation presented with more symptoms that were related to stool frequency (p value < 0.001), intestinal constipation (p value = 0.005), fecal incontinence (p value = 0.001), buttock pain (p value = 0.023), and nausea and vomiting (p value = 0.036), whereas patients with permanent colostomy had higher scores for dysuria (p value = 0.033). CONCLUSION: Although global QoL scores did not differ between groups, patients who underwent definitive colostomy had significantly better functional and symptom scale scores, reflecting greater function with fewer symptoms.
Subject(s)
Colostomy , Quality of Life , Rectal Neoplasms/surgery , Adolescent , Adult , Aged , Anal Canal , Cross-Sectional Studies , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Liposarcoma of the gallbladder is an extremely rare sarcoma, with only five cases reported in the literature according to our knowledge. CASE PRESENTATION: A 71-year-old woman was referred to the Surgical Oncology Division of Napoleão Laureano Hospital (João Pessoa, PB, Brazil) due to a solid mass at the right side of the abdomen and fever, with no signs of jaundice. Abdominal ultrasonography and computed tomography (CT) evidenced an extensive gallbladder lobular formation adhered to the inferior border of the right hepatic lobe and cholelithiasis. The CT report suggested gallbladder liposarcoma. A cholecystectomy associated with resection of segments IV-B and V of the liver were performed. Intraoperative frozen sections were compatible with gallbladder sarcoma. Anatomopathological examination and immunohistochemistry confirmed dedifferentiated liposarcoma with foci of heterologous leiomyosarcomatous differentiation and undifferentiated fusocellular areas of high histological grade. CONCLUSION: This is the first case of dedifferentiated liposarcoma of the gallbladder to be reported.
Subject(s)
Cholecystectomy/methods , Gallbladder Neoplasms/surgery , Gallbladder/pathology , Liposarcoma/surgery , Aged , Brazil , Female , Gallbladder/diagnostic imaging , Gallbladder/surgery , Gallbladder Neoplasms/diagnosis , Gallbladder Neoplasms/pathology , Humans , Liposarcoma/diagnosis , Liposarcoma/pathology , Tomography, X-Ray Computed , UltrasonographyABSTRACT
BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-ß (ERß). The expression of ERß isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. METHODS: This study aimed to investigate the expression levels of the ERß1, ERß2, ERß4 and ERß5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. RESULTS: Decreased expression of ERß isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p < 0.001). In FAP patients, ERß1 and ERß5 isoforms showed significant down-expression in polyps (p < 0.001) compared with matched normal tissues. However, no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERß isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERß was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p < 0.05). In sporadic colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERß1 and ERß5 expression levels were associated with better disease-free survival (p = 0.002). CONCLUSION: These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.
Subject(s)
Adenomatous Polyposis Coli/genetics , Colorectal Neoplasms/genetics , Estrogen Receptor beta/genetics , Gene Expression Regulation, Neoplastic , Adenomatous Polyposis Coli/mortality , Adenomatous Polyposis Coli/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Databases, Genetic , Female , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Protein Isoforms , RNA Isoforms , Sequence Analysis, DNAABSTRACT
BACKGROUND: Genome-wide profiling of rare tumors is crucial for improvement of diagnosis, treatment, and, consequently, achieving better outcomes. Desmoplastic small round cell tumor (DSRCT) is a rare type of sarcoma arising from mesenchymal cells of abdominal peritoneum that usually develops in male adolescents and young adults. A specific translocation, t(11;22)(p13;q12), resulting in EWS and WT1 gene fusion is the only recurrent molecular hallmark and no other genetic factor has been associated to this aggressive tumor. Here, we present a comprehensive genomic profiling of one DSRCT affecting a 26-year-old male, who achieved an excellent outcome. METHODS: We investigated somatic and germline variants through whole-exome sequencing using a family based approach and, by array CGH, we explored the occurrence of genomic imbalances. Additionally, we performed mate-paired whole-genome sequencing for defining the specific breakpoint of the EWS-WT1 translocation, allowing us to develop a personalized tumor marker for monitoring the patient by liquid biopsy. RESULTS: We identified genetic variants leading to protein alterations including 12 somatic and 14 germline events (11 germline compound heterozygous mutations and 3 rare homozygous polymorphisms) affecting genes predominantly involved in mesenchymal cell differentiation pathways. Regarding copy number alterations (CNA) few events were detected, mainly restricted to gains in chromosomes 5 and 18 and losses at 11p, 13q, and 22q. The deletions at 11p and 22q indicated the presence of the classic translocation, t(11;22)(p13;q12). In addition, the mapping of the specific genomic breakpoint of the EWS-WT1 gene fusion allowed the design of a personalized biomarker for assessing circulating tumor DNA (ctDNA) in plasma during patient follow-up. This biomarker has been used in four post-treatment blood samples, 3 years after surgery, and no trace of EWS-WT1 gene fusion was detected, in accordance with imaging tests showing no evidence of disease and with the good general health status of the patient. CONCLUSIONS: Overall, our findings revealed genes with potential to be associated with risk assessment and tumorigenesis of this rare type of sarcoma. Additionally, we established a liquid biopsy approach for monitoring patient follow-up based on genomic information that can be similarly adopted for patients diagnosed with a rare tumor.
Subject(s)
Abdominal Neoplasms/diagnostic imaging , Desmoplastic Small Round Cell Tumor/diagnostic imaging , Abdominal Neoplasms/genetics , Abdominal Neoplasms/therapy , Adult , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Chromosomes, Human, Pair 11/genetics , DNA, Neoplasm/blood , DNA, Neoplasm/genetics , Desmoplastic Small Round Cell Tumor/genetics , Desmoplastic Small Round Cell Tumor/therapy , Humans , Male , Molecular Diagnostic Techniques , Polymorphism, Genetic , Translocation, GeneticABSTRACT
Glauco Baiocchi, M.D., Ph.D., Maria Dirlei Begnami, M.D., Ph.D., Michael Jenwei Chen, M.D., Elza Mieko Fukazawa, M.D., Ph.D., Levon Badiglian-Filho, M.D., Ph.D., Antonio Cassio Assis Pellizzon, M.D., Ph.D., Fernando Augusto Soares, M.D., Ph.D., and Ademar Lopes, M.D., Ph.D. OBJECTIVE: To evaluate HER-2 expression as a predictor of the response to radiotherapy and its value as a prognostic marker. STUDY DESIGN: A retrospective analysis was performed in a series of 34 individuals with advanced stage cervical cancer who underwent radiotherapy followed by radical hysterectomy. HER-2 expression was measured by immunohistochemistry in biopsies from all patients prior to radiotherapy and in 14 patients with residual tumors after radiotherapy. The presence of gene amplification was also examined. RESULTS: Eighteen (53%) patients had residual disease after radical hysterectomy. HER-2 was expressed in 26.5% of cases. Gene amplification by FISH was detected in 2.9% of cases. HER-2 expression was associated with a higher risk of residual disease after radiotherapy (p= 0.019). HER-2 expression did not correlate with the risk of recurrence or death. CONCLUSION: The prevalence of HER-2 expression is low in cervical cancer, and although HER-2 can predict the response to radiotherapy, it does not correlate with poor outcomes.
Subject(s)
Receptor, ErbB-2 , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/radiotherapy , Female , Humans , Immunohistochemistry , Receptor, ErbB-2/analysis , Receptor, ErbB-2/metabolism , Retrospective Studies , Uterine Cervical Neoplasms/chemistry , Uterine Cervical Neoplasms/surgeryABSTRACT
BACKGROUND: Although the standard of care after recurrence of epithelial ovarian cancer (EOC) is chemotherapy, increasing data suggest that combining cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising option for patients with recurrent EOC. Our aim was to determine the prognostic value of the addition of HIPEC to secondary cytoreductive surgery (SCR) in recurrent EOC. METHODS: We analyzed a series of 79 patients with platinum-sensitive recurrent EOC who were treated from May 2000 to January 2014. Fifty patients who underwent SCR were compared to 29 who had SCR in combination with HIPEC. RESULTS: The SCR group had a higher median age (58.4 years) compared to the SCR + HIPEC group (51.6 years) (p = 0.006). The median hospital stay length was longer for SCR + HIPEC versus SCR patients (11 and 8 days, respectively; p = 0.009). More subjects experienced National Cancer Institute grade III-IV morbidity in the SCR + HIPEC group (34.5 %) compared to the SCR group (10.6 %) (p = 0.015). Conversely, there were no deaths in the SCR + HIPEC group and 2 (4.0 %) deaths the SCR group. The median disease-free survival did not differ between SCR and SCR + HIPEC patients (18.6 and 15.8 months, respectively; p = 0.82); nor did median overall survival (59.3 and 58.3 months, respectively; p = 0.95). The presence of carcinomatosis was the only variable that remained linked to a higher risk of recurrence and death in the multivariate analysis. CONCLUSIONS: Our data suggest that the addition of HIPEC to cytoreduction in patients with recurrent platinum-sensitive EOC does not improve survival.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced/methods , Neoplasm Recurrence, Local/therapy , Ovarian Neoplasms/therapy , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Clear Cell/surgery , Adenocarcinoma, Clear Cell/therapy , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/surgery , Adenocarcinoma, Mucinous/therapy , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/surgery , Cystadenocarcinoma, Serous/therapy , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Endometrial Neoplasms/therapy , Female , Follow-Up Studies , Humans , Injections, Intraperitoneal , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Prognosis , Survival RateABSTRACT
This study aimed to establish and characterize primary cell cultures and xenografts derived from penile carcinoma (PeCa) in order to provide experimental models for cellular processes and efficacy of new treatments. A verrucous squamous cell carcinoma (VSCC) was macrodissected, dissociated, and cultivated in KSFM/DF12 medium. Cell cultures were evaluated at passage 5 (P5) using migration and invasion assays and were serially propagated, in vivo, in BALB/c nude mice until passage 3 (X1-X3). Immunophenotypic characterization of cultures and xenografts was performed. Genomic (CytoScan HD, Affymetrix) and transcriptomic profiles (HTA 2.0 platform, Affymetrix) for VSCC, cell cultures, and xenografts were assessed. P5 cells were able to migrate, invade the Matrigel, and produce tumors in immunodeficient mice, demonstrating their malignant potential. The xenografts unexpectedly presented a sarcomatoid-like carcinoma phenotype. Genomic analysis revealed a high similarity between the VSCC and tumor-derived xenograft, confirming its xenograft origin. Interestingly, a subpopulation of P5 cells presented stem cell-related markers (CD44(+)CD24(-) and ALDH1(high)) and sphere-forming capacity, suggesting their potential xenograft origin. Cell cultures and xenografts retained the genomic alterations present in the parental tumor. Compared to VSCC, differentially expressed transcripts detected in all experimental conditions were associated with cellular morphology, movement, and metabolism and organization pathways. Malignant cell cultures and xenografts derived from a verrucous penile carcinoma were established and fully characterized. Nevertheless, xenograft PeCa models must be used with caution, taking into consideration the selection of specific cell populations and anatomical sites for cell/tumor implantation.
Subject(s)
Carcinoma, Verrucous/pathology , Disease Models, Animal , Heterografts , Penile Neoplasms/pathology , Tumor Cells, Cultured , Aged , Animals , Carcinoma, Verrucous/genetics , Flow Cytometry , Humans , Immunohistochemistry , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Oligonucleotide Array Sequence Analysis , Penile Neoplasms/geneticsABSTRACT
PURPOSE: The SLC8A1 gene, which encodes the Na(+)/Ca(2+) exchanger, has a key role in calcium homeostasis. Our previous gene expression oligoarray data revealed SLC8A1 under expression in penile carcinoma. We investigated whether dysregulation of SLC8A1 expression is associated with apoptosis and cell proliferation in penile carcinoma via modulation of the calcium concentration. The underlying mechanisms of SLC8A1 under expression were also explored, focusing on copy number alteration and miRNA. MATERIALS AND METHODS: Transcript levels of the SLC8A1 gene and miR-223 were evaluated by quantitative polymerase chain reaction to compare penile carcinoma samples with normal glans tissue. SLC8A1 copy number was evaluated by microarray based comparative genomic hybridization. In normal and tumor samples we investigated caspase-3 and Ki-67 immunostaining as well as calcium distribution by laser ablation imaging inductively coupled plasma mass spectrometry. RESULTS: SLC8A1 under expression was detected in penile carcinoma samples (p = 0.001), confirming our previous data. It was not associated with gene copy number loss. In contrast, miR-223 over expression (p = 0.002) inversely correlated with its putative repressor SLC8A1 (r = -0.426, p = 0.015). SLC8A1 under expression was associated with decreased calcium distribution, high Ki-67 and low caspase-3 immunoexpression in penile carcinoma compared to normal tissue. CONCLUSIONS: Down-regulation of the SLC8A1 gene, most likely mediated by its regulator miR-223, can lead to decreased calcium in penile carcinoma and consequently to suppressed apoptosis and increased tumor cell proliferation. These data suggest that the miR-223-NCX1-calcium signaling axis may represent a potential therapeutic approach to penile carcinoma.
Subject(s)
Apoptosis/physiology , Calcium/metabolism , Carcinoma/genetics , Carcinoma/metabolism , Down-Regulation , Gene Expression Regulation, Neoplastic , Penile Neoplasms/genetics , Penile Neoplasms/metabolism , Sodium-Calcium Exchanger/genetics , Adult , Aged , Aged, 80 and over , Carcinoma/pathology , Cell Proliferation , Humans , Male , Middle Aged , Penile Neoplasms/pathology , Young AdultABSTRACT
OBJECTIVES: The aims of this study were to determine the sensitivity and negative predictive value (NPV) of sentinel lymph node (SLN) detection in cervical cancer using a combination technique, and to test the SLN algorithm that was proposed by the Memorial Sloan Kettering Cancer Center (MSKCC). METHODS: The study included 57 FIGO stage IA2-IIA patients who were treated at the Erasto Gaertner Hospital, Curitiba, from 2008 to 2010. The patients underwent SLN mapping by technetium lymphoscintigraphy and patent blue dye injection. Following SLN detection, standard radical hysterectomy, including parametrectomy and systematic bilateral pelvic lymphadenectomy, was performed. The SLNs were examined by immunohistochemistry (IHC) when the hematoxylin and eosin results were negative. RESULTS: The median age of patients was 42 years (range 24-71), the median SLN count was 2 (range 1-4), and the median total lymph node (LN) count was 19 (range 11-28). At least one SLN was detected in 48 (84.2 %) patients, while bilateral pelvic detection of SLNs was noted in 28 (58.3 %) cases-one case had bilateral pelvic SLNs and a para-aortic SLN, 19 (39.6 %) had unilateral pelvic LNs, and one (2.1 %) had an SLN in the para-aortic area. Metastatic LNs were found in 9 of 57 (15.8 %) patients. Eight of nine patients with LN metastasis had a positive SLN, yielding an overall sensitivity of 88.9 % and NPV of 97.5 %. Of the 75 sides that were mapped, the SLN detection method predicted LN involvement in 74 (98.6 %) hemi-pelvises. A total of ten hemi-pelvises had LN metastasis, nine of which involved the SLN, resulting in a sensitivity of 90 %, NPV of 98.5 %, and a false negative (FN) of 10 %. In two cases (4.2 %), the SLN was positive only after IHC. CONCLUSIONS: Our SLN procedure is a safe and accurate technique that increases metastatic nodal detection rates by 4.2 % after IHC. The SLN method performed better when analyzing each side; however, one FN occurred, even after applying the MSKCC algorithm.
Subject(s)
Adenocarcinoma/secondary , Algorithms , Carcinoma, Squamous Cell/secondary , Lymph Nodes/pathology , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/surgery , Adult , Aged , Carcinoma, Squamous Cell/surgery , Female , Follow-Up Studies , Humans , Hysterectomy , Longitudinal Studies , Lymph Nodes/surgery , Lymphatic Metastasis , Lymphoscintigraphy , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Prospective Studies , Sentinel Lymph Node Biopsy , Uterine Cervical Neoplasms/surgeryABSTRACT
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.