Surgical treatment of microinvasive cervical cancer: analysis of pathologic features with implications on radicality.

OBJECTIVES: To evaluate pathologic features with implications on surgical radicality in women treated with radical hysterectomy and pelvic lymphadenectomy for cervical cancer stage IA1 with lymph vascular space invasion (LVSI) and stage IA2 by correlating findings in conization and hysterectomy specimens. METHODS: Women with cervical cancer stage IA1 with LVSI and stage IA2 diagnosed by loop electrosurgical excisional procedure or cold knife conization were treated with radical hysterectomy and pelvic lymphadenectomy from January 1999 to December 2011 in 2 institutions. RESULTS: Fifty patients were enrolled: 40 with stage IA2 and 10 with stage IA1 with LVSI. Median age was 43 (30-67) years. All patients underwent cervical conization for diagnosis (45 loop electrosurgical excisional procedure, 5 cold knife). Lymph vascular space invasion was detected in 15 patients (30%). Two patients had positive pelvic nodes. No parametrial involvement was detected in the entire cohort. Positive margins were present in 35 patients, and residual disease was detected in 22 patients (44%). Positive margins predicted residual disease at radical hysterectomy (P = 0.02). Medium follow-up time was 51 months. One patient developed a pelvic recurrence, and there were no disease-related deaths. CONCLUSIONS: Patients with positive margins in cone biopsy specimens have an increased risk of residual disease at radical hysterectomy and require careful evaluation before conservative surgery. Pelvic lymph node evaluation is essential because lymph node metastasis may occur even in early stages. The lack of parametrial invasion in this study reinforces the knowledge that the select group of patients with microinvasive cervical carcinoma stages IA1 LVSI and stage IA2 have a very low risk of parametrial infiltration. Less radical surgery can be carefully considered for these patients.

[The surgeon and the metastatic disease]. / Le chirurgien et la maladie métastatique.

For a long time, metastatic disease was a prohibited zone for surgeons locked into their roles in controlling primary non-disseminated tumours. However, this has changed at the end of the 20th century with the apparition of effective chemotherapies and targeted therapies. Since then, surgeons have been able to treat hepatic, pulmonary, peritoneal and brain metastases. The more chemotherapy progresses and controls disease, the more surgeons can operate on residual disease. With this final surgery acting on the defined perimeter of systemic treatment efficacy, it appears to offer gains in progression-free survival. Gains in overall survival have not yet been demonstrated. Further, new technologies should enable surgeons to reduce the lower limits of their fields of action, increasing their therapeutic perimeters. Metastatic disease constitutes a unique model of therapeutic synergy that can be accredited to multidisciplinary strategy.

[Changes of metastatic potential of residual hepatocellular carcinoma in nude mice after in vivo chemotherapy and the corresponding mechanisms].

OBJECTIVE: To explore the changes of metastatic potential of residual hepatocellular carcinoma (HCC) after in vivo chemotherapy and its mechanism. METHODS: Nude mouse models of orthotopic HCC in the nude mouse livers was established using human hepatocellular carcinoma cell line MHCC97L cells. Oxaliplatin (10 mg/kg, once per week) was administered intraperitoneally (i.p.) to mice in the trial group. Mice in the control group received 0.2 ml of 0.9% sodium chloride on the same days. On day 7 after the third injection, all mice were sacrificed and tumor fragments of equal volume (2 mm×2 mm×2 mm) from each mouse of the oxaliplatin-treated and untreated groups were reinoculated into the livers of each new recipient mouse correspondingly. The growth, metastasis and molecular phenotype of the reinoculated tumors in both groups were determined. RESULTS: In the new recipient mice, compared with untreated tumors, oxaliplatin pre-treated tumors grew significantly slower [(2624.59 ± 491.60) mm(3) vs. (3849.72 ± 827.09) mm(3), P < 0.001], but gave more spontaneous metastasis to the lung (10/12 vs. 3/12, P = 0.012). A decreased expression of E-cadherin and increased expression of N-cadherin, vimentin and transcription factor Snail were detected in the oxaliplatin pre-treated tumors by immunohistochemistry, which provided the evidence of epithelial mesenchymal transition (EMT) in these tumors. CONCLUSION: Residual hepatocellular carcinomas after in vivo chemotherapy grow slower but gain enhanced metastatic potential to the lung, associated with epithelial mesenchymal transition.

Bioluminescence as gold standard for validation of optical imaging modalities in peritoneal carcinomatosis animal models.

BACKGROUND: The outcome of cytoreductive surgery in patients with peritoneal carcinomatosis is influenced by incomplete resection as a result of inadequate detection of a tumor, i.e. residual disease. The future perspective of complete resection, made possible by application of intraoperative near-infrared fluorescence imaging (NIRF), led to the development and validation of a bioluminescent colorectal peritoneal carcinomatosis xenograft rat model to act as the gold standard for the evaluation of new optical imaging modalities. METHODS: Twenty nude rats were inoculated intraperitoneally with 2 × 10(6) luciferase-labeled human colorectal tumor cells (HT-29-luc-D6). The peritoneal carcinomatosis index (PCI) was estimated using visual observation (PCI-VO) and VO combined with bioluminescence imaging (PCI-BLI). Subsequently, the BL images were presented, and residual tumor tissue was localized by PCI-BLI scoring and compared with the PCI-VO. RESULTS: BLI revealed additional tumor tissue, confirmed by HE staining, compared to VO alone in 7 out of 8 rats (p < 0.02). CONCLUSION: The developed model turned out to be suitable. The use of BLI for tumor detection was more sensitive compared to VO alone. In this model, BLI significantly detected residual disease, and therefore, BLI can be denominated as the gold standard for the evaluation of optical imaging modalities like NIRF.

Residual hepatocellular carcinoma after oxaliplatin treatment has increased metastatic potential in a nude mouse model and is attenuated by Songyou Yin.

BACKGROUND: The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC. METHODS: Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells. RESULTS: MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelial-mesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively). CONCLUSIONS: The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC.

Histological detection of minimal metastatic disease in inguinal non-sentinel lymph nodes in penile cancer.

UNLABELLED: The aim of this study was to detect lymphatic spread by serial step-section technique in non-sentinel lymph nodes (NSLNs), which were earlier assessed as negative by histological examination. PATIENTS AND METHODS: Inguinal dissection specimens of 13 men with penile cancer were investigated. The LNs were sectioned at multiple levels (150 mum-intervals) and then H&E- and immuno-stained for cytokeratin (Lu-5). RESULTS: 196 LNs of 13 men were examined. In 2 out of 13 patients (15%) previously ranked as pN0, minimal lymph node involvement was detected by serial step sections and both immunohistochemistry and H&E staining. Both patients have had an uneventful follow-up of currently 62 and 16 months. CONCLUSION: Conventional histological examination of NSLNs fails to detect lymphatic spread in penile cancer. Step-section technique at 3 section levels, rather than immunohistochemistry, helps to safely detect minimal metastatic disease. The prognostic relevance is still unclear and has to be investigated in larger cohort studies.

Metastatic renal cell carcinoma mimicking pituitary adenoma: case report.

A 54-year-old man, with a past history of renal cell carcinoma, presented with bitemporal visual field defect, hyponatremia, and diabetes insipidus. Endocrinological examination revealed panhypopituitarism. Computed tomography and magnetic resonance imaging showed an intrasellar mass with suprasellar extension. The initial radiological impression was pituitary adenoma. The tumor was decompressed via the transsphenoidal route. Histological examination revealed metastatic renal cell carcinoma. The clinical characteristics of metastatic pituitary carcinoma appear to be panhypopituitarism, and neuroimaging findings of strong enhancement of the tumor and bony destruction without marked sellar enlargement.

Solitary brain metastasis from renal cell carcinoma 15 years after nephrectomy: case report.

A 77-year-old man presented with a metastatic brain tumor 15 years after nephrectomy for a renal cell carcinoma. Neurological examination showed recent memory disturbance and slight right hemiparesis. Magnetic resonance imaging revealed a round well-demarcated mass extending from the left thalamus to the left trigone of the lateral ventricle. Preoperative angiography showed tumor staining. Surgery was performed by opening the inferior temporal sulcus. Only biopsy could be performed because of extensive bleeding from the tumor. Histological examination identified metastatic renal cell carcinoma. Gamma knife surgery was performed which resulted in resolution of his hemiparesis. Metastatic renal cell carcinoma should be considered even if nephrectomy was performed 10 or more years before presentation.

Carcinoma residual de mama / Residual breast carcinoma

Antecedentes: Siguiendo la amplia resección local de los cánceres de mama, 1 de cada 4 pacientes tiene enfermedad residual en la retumorrectomía o en la pieza de mastectomía. Objetivos: Determinar si el carcinoma residual de mama se correlaciona con mayor recidiva local o distinta supervivencia global. Lugar de aplicación: División de Cirugía General y práctica privada. Diseño: Estudio retrospectivo y descriptivo. Población: 139 pacientes consecutivos con mastectomía o tratamiento conservador luego de una biopsia diferida del tumor. Método: Revisión de las historias clínicas. Luego de la resección de carcinomas de mama palpables o no palpables en los que existen bordes comprometidos en la pieza de resección o sospecha mamográfica de carcinoma residual, se estudia el especímen de la retumorrectomía o la pieza de mastectomía. Los pacientes fueron seguidos una media de 63 meses y fueron documentadas las recidivas locales y la supervivencia. Resultados: El estudio retrospectivo de los 139 pacientes tratados con cirugía conservadora o mastectomía identificó 53 (38,1 por ciento) de carcinomas residuales, 42,5 por ciento para los carcinomas invasores (43/101) y 26,3 por ciento para los no invasores (10/38). De los 52 pacientes con tratamiento conservador, 15 (28,8 por ciento) tenían carcinoma residual. No hubo diferencia estadísticamente significativa ni para las recidivas locales (p = 0,56) o supervivencia entre los pacientes con o sin carcinoma residual. No fue demostrada ninguna relación de acuerdo a la edad los pacientes, el componente intraductal extensivo o el compromiso axilar. Conclusiones: El hallazgo de carcinoma residual de mama luego de amplia biopsia diferida no afecta la recidiva local o la supervivencia en pacientes con tratamiento conservador o mastectomía. Para minimizar el riesgo del carcinoma residual, se debe considerar la amplia excisión de las lesiones o la mastectomía en el manejo del carcinoma multifocal y de los no palpables radiológicamente multicéntricos

Carcinoma residual de mama / Residual breast carcinoma

Antecedentes: Siguiendo la amplia resección local de los cánceres de mama, 1 de cada 4 pacientes tiene enfermedad residual en la retumorrectomía o en la pieza de mastectomía. Objetivos: Determinar si el carcinoma residual de mama se correlaciona con mayor recidiva local o distinta supervivencia global. Lugar de aplicación: División de Cirugía General y práctica privada. Diseño: Estudio retrospectivo y descriptivo. Población: 139 pacientes consecutivos con mastectomía o tratamiento conservador luego de una biopsia diferida del tumor. Método: Revisión de las historias clínicas. Luego de la resección de carcinomas de mama palpables o no palpables en los que existen bordes comprometidos en la pieza de resección o sospecha mamográfica de carcinoma residual, se estudia el especímen de la retumorrectomía o la pieza de mastectomía. Los pacientes fueron seguidos una media de 63 meses y fueron documentadas las recidivas locales y la supervivencia. Resultados: El estudio retrospectivo de los 139 pacientes tratados con cirugía conservadora o mastectomía identificó 53 (38,1 por ciento) de carcinomas residuales, 42,5 por ciento para los carcinomas invasores (43/101) y 26,3 por ciento para los no invasores (10/38). De los 52 pacientes con tratamiento conservador, 15 (28,8 por ciento) tenían carcinoma residual. No hubo diferencia estadísticamente significativa ni para las recidivas locales (p = 0,56) o supervivencia entre los pacientes con o sin carcinoma residual. No fue demostrada ninguna relación de acuerdo a la edad los pacientes, el componente intraductal extensivo o el compromiso axilar. Conclusiones: El hallazgo de carcinoma residual de mama luego de amplia biopsia diferida no afecta la recidiva local o la supervivencia en pacientes con tratamiento conservador o mastectomía. Para minimizar el riesgo del carcinoma residual, se debe considerar la amplia excisión de las lesiones o la mastectomía en el manejo del carcinoma multifocal y de los no palpables radiológicamente multicéntricos (AU)