RESUMEN

Trichoblastomas are rare dermal neoplasms usually found on the scalp and face. Histology shows a proliferation of small basaloid cells arranged in cords or fields surrounded by cellular stroma. Trichoblastomas are usually not aggressive, but trichoblastic carcinomas arising from preexisting trichoblastomas have been described and have been linked to basal cell carcinoma. We found a tumor with features of trichoblastoma with presence of Merkel cells, but with a deeply infiltrative growth pattern into the fat and muscle tissue, without significant architectural or cellular atypia. Tumors with similar growth patterns were previously described as deeply invasive trichoblastic neoplasms. It appears to be a new entity that has been described before but has not been fully characterized: low-grade trichoblastic carcinoma. This malignancy seems to show only locally aggressive growth. Radical excision was accomplished with Mohs micrographic surgery.

RESUMEN

BACKGROUND: In the recent years two innovative approaches have become available for minimally invasive en bloc resections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. METHODS: Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. DISCUSSION: This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for the en bloc resection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. TRIAL REGISTRATION: Netherlands Trial Register, NL7083 , 06 July 2018.

Asunto(s)

Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Neoplasias del Recto , Cirugía Endoscópica Transanal , Resección Endoscópica de la Mucosa/efectos adversos , Europa (Continente) , Humanos , Estudios Multicéntricos como Asunto , Recurrencia Local de Neoplasia , Países Bajos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Recto/cirugía , Cirugía Endoscópica Transanal/efectos adversos , Resultado del Tratamiento

RESUMEN

A 31-year-old woman was seen at our clinic with itching papules of the back after hijama treatments. Hijama treatments consist of superficially cutting the skin followed by cupping and are applied for a diversity of complaints, including pain. Our patient initially presented with sensitive and burning sensations at the cutting sites, but recently, the cutting sites started to itch as well. At physical examination, we saw perfectly aligned papules with a sign of Wickham's striae on her back where the skin had been cut. Further examination revealed comparable, solitary papules on the inside of her wrist, flank and chest. A skin biopsy confirmed the diagnosis lichen planus. The patient was prescribed betamethasone cream and we advised against further hijama treatments.

Asunto(s)

Ventosaterapia/efectos adversos , Liquen Plano/etiología , Prurito/etiología , Administración Tópica , Adulto , Beclometasona/administración & dosificación , Biopsia , Fármacos Dermatológicos/administración & dosificación , Femenino , Humanos , Liquen Plano/tratamiento farmacológico , Liquen Plano/patología , Pomadas , Parestesia/etiología , Piel/patología , Enfermedades Cutáneas Papuloescamosas/tratamiento farmacológico , Enfermedades Cutáneas Papuloescamosas/etiología

RESUMEN

INTRODUCTION: The current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin-stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise κ scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC. METHODS: Nineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3). RESULTS: For the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, κ scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64. CONCLUSIONS: Diagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided.

Asunto(s)

Biomarcadores de Tumor/metabolismo , Carcinoma Neuroendocrino/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Diagnóstico Diferencial , Neoplasias Pulmonares/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Adenocarcinoma/clasificación , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Carcinoma Neuroendocrino/clasificación , Carcinoma Neuroendocrino/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/clasificación , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Células Escamosas/clasificación , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Humanos , Técnicas para Inmunoenzimas , Agencias Internacionales , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/metabolismo , Estadificación de Neoplasias , Pronóstico , Reproducibilidad de los Resultados , Carcinoma Pulmonar de Células Pequeñas/clasificación , Carcinoma Pulmonar de Células Pequeñas/metabolismo

RESUMEN

Peritoneal dissemination is diagnosed in 10-25 % of colorectal cancer patients. Selected patients are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. For these patients, earlier diagnosis, optimised selection criteria and a personalised approach are warranted. Biomarkers could play a crucial role here. However, little is known about possible candidates. Considering tumour cell adhesion as a key step in peritoneal dissemination, we aim to provide an overview of the functional importance of adhesion molecules in peritoneal dissemination and discuss the prognostic, diagnostic and therapeutic options of these candidate biomarkers. A systematic literature search was conducted according to the PRISMA guidelines. In 132 in vitro, ex vivo and in vivo studies published between 1995 and 2013, we identified twelve possibly relevant adhesion molecules in various cancers that disseminate peritoneally. The most studied molecules in tumour cell adhesion are integrin α2ß1, CD44 s and MUC16. Furthermore, L1CAM, EpCAM, MUC1, sLe(x) and Le(x), chemokine receptors, Betaig-H3 and uPAR might be of clinical importance. ICAM1 was found to be less relevant in tumour cell adhesion in the context of peritoneal metastases. Based on currently available data, sLe(a) and MUC16 are the most promising prognostic biomarkers for colorectal peritoneal metastases that may help improve patient selection. Different adhesion molecules appear expressed in haematogenous and transcoelomic spread, indicating two different attachment processes. However, our extensive assessment of available literature reveals that knowledge on metastasis-specific genes and their possible candidates is far from complete.

Asunto(s)

Biomarcadores de Tumor/genética , Moléculas de Adhesión Celular/genética , Neoplasias Colorrectales/patología , Neoplasias Peritoneales/genética , Antígeno Ca-125/genética , Adhesión Celular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Humanos , Proteínas de la Membrana/genética , Metástasis de la Neoplasia , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/cirugía , Peritoneo/patología , Pronóstico

RESUMEN

CONTEXT: Surgical and pathologic handling of lung physically affects lung tissue. This leads to artifacts that alter the morphologic appearance of pulmonary parenchyma. OBJECTIVE: To describe and illustrate mechanisms of ex vivo artifacts that may lead to diagnostic pitfalls. DESIGN: In this study 4 mechanisms of ex vivo artifacts and corresponding diagnostic pitfalls are described and illustrated. RESULTS: The 4 patterns of artifacts are: (1) surgical collapse, due to the removal of air and blood from pulmonary resections; (2) ex vivo contraction of bronchial and bronchiolar smooth muscle; (3) clamping edema of open lung biopsies; and (4) spreading of tissue fragments and individual cells through a knife surface. Morphologic pitfalls include diagnostic patterns of adenocarcinoma, asthma, constrictive bronchiolitis, and lymphedema. CONCLUSION: Four patterns of pulmonary ex vivo artifacts are important to recognize in order to avoid morphologic misinterpretations.

Asunto(s)

Errores Diagnósticos/prevención & control , Enfermedades Pulmonares/patología , Pulmón/patología , Mucosa Respiratoria/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Artefactos , Asma/diagnóstico , Asma/metabolismo , Asma/patología , Asma/cirugía , Biomarcadores/metabolismo , Biopsia/efectos adversos , Bronquiolos/metabolismo , Bronquiolos/patología , Bronquiolos/cirugía , Bronquiolitis Obliterante/diagnóstico , Bronquiolitis Obliterante/metabolismo , Bronquiolitis Obliterante/patología , Bronquiolitis Obliterante/cirugía , Diagnóstico Diferencial , Errores Diagnósticos/clasificación , Humanos , Pulmón/irrigación sanguínea , Pulmón/metabolismo , Pulmón/cirugía , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/metabolismo , Enfermedades Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Linfedema/diagnóstico , Linfedema/metabolismo , Linfedema/patología , Linfedema/cirugía , Contracción Muscular , Músculo Liso/metabolismo , Músculo Liso/patología , Músculo Liso/cirugía , Siembra Neoplásica , Mucosa Respiratoria/irrigación sanguínea , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/cirugía , Manejo de Especímenes/efectos adversos

RESUMEN

OBJECTIVE: To improve patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by evaluating various preoperatively assessable clinicopathological parameters as markers for survival after CRS and HIPEC. SUMMARY BACKGROUND DATA: Peritoneal metastases (PMs) originating from colorectal cancer are treated with CRS and HIPEC. Despite increasing survival, high morbidity and mortality warrant selection of patients with optimal benefit from this treatment. Many studies report a number of variables to be associated with survival after CRS and HIPEC, but no definitive analysis has been made to validate various markers. METHODS: In concordance with PRISMA guidelines, we performed a literature search encompassing 4110 articles to select 50 articles that reported the influence of 1 or more clinicopathological variables on overall survival after CRS and HIPEC. In absence of RCTs, 25 cohort studies could be used to perform a meta-analysis on 10 prognostic variables. RESULTS: We determined that concurrent liver metastasis, lymph node metastasis, Eastern Cooperative Oncology Group score, tumor differentiation, and signet ring cell histology are all negative prognostic variables on overall survival after CRS and HIPEC. Conversely, sex and location of primary could not be validated as prognostic markers. More research is required to make definitive conclusions about neoadjuvant chemotherapy, onset of PMs, and mucinous histology. CONCLUSIONS: Current clinical practice, which selects patients based on extraperitoneal metastasis, lymph node stage, performance status, and tumor histology, is validated by our pooled analysis. Our data merit further research into neoadjuvant chemotherapy in the setting of CRS and HIPEC for PMs.

Asunto(s)

Quimioterapia del Cáncer por Perfusión Regional , Neoplasias Colorrectales/patología , Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida , Selección de Paciente , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Humanos , Análisis de Supervivencia

RESUMEN

BACKGROUND: Prognosis of patients with colorectal cancer liver metastasis (CRCLM) is estimated based on clinicopathological models. Stratifying patients based on tumor biology may have additional value. METHODS: Tissue micro-arrays (TMAs), containing resected CRCLM and corresponding primary tumors from a multi-institutional cohort of 507 patients, were immunohistochemically stained for 18 candidate biomarkers. Cross-validated hazard rate ratios (HRRs) for overall survival (OS) and the proportion of HRRs with opposite effect (P(HRR < 1) or P(HRR > 1)) were calculated. A classifier was constructed by classification and regression tree (CART) analysis and its prognostic value determined by permutation analysis. Correlations between protein expression in primary tumor-CRCLM pairs were calculated. RESULTS: Based on their putative prognostic value, EGFR (P(HRR < 1) = .02), AURKA (P(HRR < 1) = .02), VEGFA (P(HRR < 1) = .02), PTGS2 (P(HRR < 1) = .01), SLC2A1 (P(HRR > 1) < 01), HIF1α (P(HRR > 1) = .06), KCNQ1 (P(HRR > 1) = .09), CEA (P (HRR > 1) = .05) and MMP9 (P(HRR < 1) = .07) were included in the CART analysis (n = 201). The resulting classifier was based on AURKA, PTGS2 and MMP9 expression and was associated with OS (HRR 2.79, p < .001), also after multivariate analysis (HRR 3.57, p < .001). The prognostic value of the biomarker-based classifier was superior to the clinicopathological model (p = .001). Prognostic value was highest for colon cancer patients (HRR 5.71, p < .001) and patients not treated with systemic therapy (HRR 3.48, p < .01). Classification based on protein expression in primary tumors could be based on AURKA expression only (HRR 2.59, p = .04). CONCLUSION: A classifier was generated for patients with CRCLM with improved prognostic value compared to the standard clinicopathological prognostic parameters, which may aid selection of patients who may benefit from adjuvant systemic therapy.

Asunto(s)

Aurora Quinasa A/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , Ciclooxigenasa 2/metabolismo , Neoplasias Hepáticas/secundario , Metaloproteinasa 9 de la Matriz/metabolismo , Estudios de Casos y Controles , Neoplasias Colorrectales/clasificación , Neoplasias Colorrectales/metabolismo , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Hígado/metabolismo , Neoplasias Hepáticas/clasificación , Neoplasias Hepáticas/metabolismo , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia

RESUMEN

OBJECTIVE: To investigate the individual and combined prognostic value of HIF1α, SLC2A1, and vascular endothelial growth factor A (VEGFA) in a multi-institutional cohort of patients with resected colorectal cancer liver metastasis (CRCLM). BACKGROUND: In the majority of patients with CRCLM, resection seems not to be curative, despite its curative intent. Overexpression of hypoxia-inducible factor 1α (HIF1α), glucose transporter 1 (SLC2A1; also known as GLUT1), and VEGFA has been associated with tumor progression and poor prognosis of patients with colorectal cancer (CRC). METHODS: Tissue microarrays were generated using CRCLM and patient-matched primary CRC from patients who underwent CRCLM resection between 1990 and 2010. Prognostic value of HIF1α, SLC2A1, and VEGFA was determined by immunohistochemistry. A 500-fold cross-validated hazard rate ratio (HRRav) for overall survival was calculated. RESULTS: HIF1α, SLC2A1, and VEGFA expression could be evaluated in 328, 350, and 335 patients, respectively. High SLC2A1 expression was associated with good prognosis (HRRav, 0.67; P (HRR >1)  < 0.01) and high VEGFA expression to poor prognosis (HRRav, 1.84; P (HRR < 1)  = 0.02), also after multivariate analysis including established clinicopathological prognostic variables (HRRav, 0.67; P (HRR > 1)  < 0.01 and HRRav, 1.50; P (HRR < 1)  = 0.02, respectively). SLC2A1 showed prognostic value particularly in patients treated with systemic therapy (P < 0.01), whereas the prognostic value of VEGFA expression was mainly observed in patients not treated with systemic therapy (P < 0.01). Prognosis was especially poor in patients with both low SLC2A1 and high VEGFA expression (P < 0.01). HIF1α expression was not associated with survival. CONCLUSIONS: SLC2A1 and VEGFA expression are prognostic molecular biomarkers for patients with CRCLM with added value to established clinicopathological variables.

Asunto(s)

Transportador de Glucosa de Tipo 1/análisis , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Factor A de Crecimiento Endotelial Vascular/análisis , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Transportador de Glucosa de Tipo 1/biosíntesis , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Neoplasias Hepáticas/química , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular/biosíntesis

RESUMEN

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the survival in selected colorectal cancer patients with peritoneal metastases. In these patients, the risk of a low anastomosis is sometimes diminished through the creation of a colostomy. Currently, the morbidity and mortality associated with the reversal of the colostomy in this population is unknown. METHODS: Our study involved two prospectively collected databases including all patients who underwent CRS-HIPEC. We identified all consecutive patients who had a colostomy and requested a reversal. The associations between four clinical and ten treatment-related factors with the outcome of the reversal procedure were determined by univariate analysis. RESULTS: 21 of 336 patients (6.3 %) with a stoma with a mean age of 50.8 (standard deviation 10.2) years underwent a reversal procedure. One patient was classified as American Society of Anesthesiologists (ASA) grade III, 6 as ASA grade II, and the remaining as ASA grade I. Median time elapsed between HIPEC and reversal was 394 days (range 133-1194 days). No life-threatening complications or mortality were observed after reversal. The reversal-related morbidity was 67 %. Infectious complications were observed in 7 patients (33 %). Infectious complications after HIPEC were negatively correlated with the ultimate restoration of bowel continuity (P = 0.05). Bowel continuity was successfully restored in 71 % of the patients. CONCLUSIONS: Although the restoration of bowel continuity after CRS-HIPEC was successful in most patients, a relatively high complication rate was observed. Patients with infectious complications after HIPEC have a diminished chance of successful restoration of bowel continuity.

Asunto(s)

Quimioterapia del Cáncer por Perfusión Regional/efectos adversos , Colostomía/efectos adversos , Hipertermia Inducida/efectos adversos , Neoplasias/terapia , Neoplasias Peritoneales/terapia , Adulto , Anciano , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias/patología , Neoplasias Peritoneales/secundario , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Prospectivos

RESUMEN

BACKGROUND: Natural orifice transluminal endoscopic surgery peritoneoscopy may be able to replace laparoscopic peritoneoscopy (LAP) for staging of GI malignancies if it is proven to be equally accurate and safe. OBJECTIVE: To compare transgastric peritoneoscopy (TGP) and transcolonic peritoneoscopy (TCP) to LAP, pairwise, in a randomized, blinded (to location and number of beads) human cadaver model with simulated peritoneal metastases. DESIGN: Metastases were simulated by 2.5-mm, color-coded beads, which were placed into the peritoneal cavity via an open approach. In previous porcine experiments, LAP resulted in a yield of 95%. By using a noninferiority design with a margin of equivalence of 15%, we needed a sample size of 34 beads for 80% power. Randomization was performed for number and location of beads. Eighteen experiments were performed on 6 fresh-frozen human cadavers. SETTING: Experimental surgical laboratory. INTERVENTION: LAP, TGP, and TCP were performed in randomized order by one of two surgeons/endoscopists blinded for location and number of beads. MAIN OUTCOME MEASUREMENTS: Number of beads detected and touched. RESULTS: LAP found and touched 33 beads (yield 97%), TGP 26 beads (76%; difference in yield vs LAP was -20.5 [95% CI, -26.3 to -9.27]), and TCP 29 beads (85%; difference in yield vs LAP was -11.8 [95% CI, -14.6 to 4.98]). Beads that were missed were mostly located at the inferior liver surface: TGP missed 6 of 9 of these beads (67%), TCP 4 of 9 (44%). LIMITATIONS: Cadaver model. CONCLUSION: In this prospective, blinded, comparative trial in a human cadaver model, TCP was comparable to LAP in detecting simulated metastases. TGP was inferior to LAP. Future development should focus on improved visualization of the inferior surface of the liver.

Asunto(s)

Laparoscopía/métodos , Cirugía Endoscópica por Orificios Naturales , Neoplasias Peritoneales/diagnóstico , Neoplasias Peritoneales/secundario , Cadáver , Femenino , Humanos , Masculino , Modelos Biológicos , Distribución Aleatoria , Reproducibilidad de los Resultados , Método Simple Ciego