The segmentation of the vertebral artery: An ambiguous anatomical concept

The course of the vertebral artery from its subclavian artery origin up to its termination at the vertebrobasilar junction is divided into four segments (V1–V4). This segmentation, based on schemes that have evolved since the late nineteenth century, should be a consistent and reproducible anatomical concept. However, the current literature offers conflicting definitions of that scheme, not infrequently within a single article or monograph. The principal inconsistency found in modern publications concerns the termination of the V2 segment, which is either set at the C2 or C1 transverse foramen depending on the scheme considered. Consequently, the portion of the vertebral artery extending between C2 and C1—a frequent site of pathological involvement—either belongs to the V2 or V3 segment. This discrepancy can affect the validity of studies evaluating the diagnosis and management of vertebral artery disorders. A V3 segment extending from the transverse foramen of C2 to the posterior atlanto-occipital membrane and subdivided into vertical, horizontal, and oblique subsegments—a pattern suggested by Barbieri in 1867 and adopted in some modern publications—would provide a simple, precise, and reliable solution without significantly altering the widely accepted division of the vertebral artery into four segments (V1–V4).

Deciphering Tumor Niches: Lessons From Solid and Hematological Malignancies

Knowledge about the hematopoietic niche has evolved considerably in recent years, in particular through in vitro analyzes, mouse models and the use of xenografts. Its complexity in the human bone marrow, in particular in a context of hematological malignancy, is more difficult to decipher by these strategies and could benefit from the knowledge acquired on the niches of solid tumors. Indeed, some common features can be suspected, since the bone marrow is a frequent site of solid tumor metastases. Recent research on solid tumors has provided very interesting information on the interactions between tumoral cells and their microenvironment, composed notably of mesenchymal, endothelial and immune cells. This review thus focuses on recent discoveries on tumor niches that could help in understanding hematopoietic niches, with special attention to 4 particular points: i) the heterogeneity of carcinoma/cancer-associated fibroblasts (CAFs) and mesenchymal stem/stromal cells (MSCs), ii) niche cytokines and chemokines, iii) the energy/oxidative metabolism and communication, especially mitochondrial transfer, and iv) the vascular niche through angiogenesis and endothelial plasticity. This review highlights actors and/or pathways of the microenvironment broadly involved in cancer processes. This opens avenues for innovative therapeutic opportunities targeting not only cancer stem cells but also their regulatory tumor niche(s), in order to improve current antitumor therapies.

Prostatic urethra recurrence after transurethral resection of bladder tumor (TURBT) for non-muscle-invasive bladder cancer (NMIBC)

Urinary bladder cancer is frequently multifocal and has a high incidence of recurrence. Although the prostatic urethra is a frequent site of tumor relapse in patients with non-muscle-invasive bladder cancer treated with TURBT, such tumors are often underappreciated. Here we present two cases having urethral recurrence after TURBT.

RISK FACTORS FOR HUMERAL HEAD OSTEONECROSIS IN PATIENTS WITH PROXIMAL HUMERAL FRACTURES TREATED OPERATIVELY

Proximal humerus presents the second most frequent site of posttraumatic osteonecrosis. This complication is usually related to poor functional outcomes. The aim of this study is to identify and analyze the risk factors for posttraumatic humeral head osteonecrosis in surgically treated patients. Ninety-one patients with 92 acute proximal humeral fractures were operated on for a period of 39 months. Operative methods include open reduction and internal fixation and closed reduction and percutaneous fixation. Fractures were classified according to Neer, AO and LEGO classifications. The mean age of patients was 60.9 years. From 91 operated patients for follow-up were available 82. The mean follow-up period was 15 months. Patient data was collected prospectively. Functional results are present using age and gender adjusted Constant score. In 41 patients, the result is excellent, in 28-good, in 11-fair and in 3 poor. Bone union was evident in all cases. No deep wound infections, nerve injuries, vascular injuries and implant failure were observed. Osteonecrosis was seen in 5 (6.1%) patients. Patients with posttraumatic osteonecrosis had significant lower Constant results. Analyzing the pre- and intraoperative factors in patients with osteonecrosis, we find that the most significant factors for this complication are increasing fracture severity and а combination of short medial metaphyseal extension and disrupted medial hinge.

Engineering of human mini-bones for the standardized modeling of healthy hematopoiesis, leukemia and solid tumor metastasis

The bone marrow microenvironment provides indispensable factors to sustain blood production throughout life. It is also a hotspot for the progression of hematologic disorders and the most frequent site of solid tumor metastasis. Pre-clinical research relies on xenograft mouse models, precluding the human-specific functional interactions of stem cells with their bone marrow microenvironment. Human mesenchymal cells can be exploited for the in vivo engineering of humanized ossicles (hOss). Those mini-bones provide a human niche conferring engraftment of human healthy and malignant blood samples, yet suffering from major reproducibility issue. Here, we report the standardized generation of hOss by developmental priming of a custom-designed human mesenchymal cell line. We demonstrate superior engraftment of cord blood hematopoietic cells and primary acute myeloid leukemia samples, but also validate our hOss as metastatic site for breast cancer cells. Finally, we report the first engraftment of neuroblastoma patient-derived xenograft cells in a humanized model, recapitulating clinically reported osteolytic lesions. Collectively, our hOss constitute a powerful standardized and malleable platform to model normal hematopoiesis, leukemia and solid tumor metastasis.

Squamous Cell Metastasis of Cancer from Cervix to Breast: A Case Report

Squamous cell metastasis from cervical cancer to breast is an extremely rare entity, approximately 29 cases have been documented worldwide since 1947 and it is the second documented case in Ecuador, the incidence is very low, it represents only 1,2 of all malignant neoplasms of the breast, which limits the expertise in the diagnosis and treatment of this metastasis, with the outermost quadrant of the breasts being the most frequent site of presentation. We present the clinical case of a 46-year-old married woman with a history of stage IVB squamous cell cancer of the cervix, who received chemotherapy, a Paclitaxel/Carboplatin regimen for 6 cycles. There was no good response and we had radiotherapy and brachytherapy treatment. The second line of chemotherapy with monodroga Gemcitab is proposed, the scheme is completed for 8 cycles. There is no favorable response, so a second-line chemotherapy treatment with Ifosfomide is proposed. The same metastases are present in the breast as after imaging and pathology examinations, it is concluded that the patient presents cervical Ca squamous cell metastases (cancer) from the cervix, 6 months after the diagnosis of the deceased patient. Metastasis to the breast from a neoplasm of other organs is very rare, the incidence of which is very low and the prognosis is gloomy. Keywords: metastasis, squamous cells, cancer of the cervix. RESUMEN La metástasis de células escamosas de cáncer de cérvix a mama es una entidad extremadamente rara, se ha documentado a nivel mundial aproximadamente 29 casos desde 1947 y es el segundo caso documentado en el Ecuador, la incidencia es muy baja, representa tan solo el 1,2 de todas las neoplasias malignas de la mama, lo que limita la experticia en el diagnóstico y tratamiento de esta metástasis, siendo el sitio más frecuente de presentación el cuadrante superior externo de las mamas. Se presenta el caso clínico de una paciente de 46 años, casada, con antecedentes de cáncer de cérvix de células escamosas en estadio IVB por lo que recibió tratamiento de quimioterapia, esquema Paclitaxel/Carboplatino por 6 ciclos. No hubo buena respuesta y recibió tratamiento de radioterapia y braquiterapia. Se propone segunda línea de quimioterapia con monodroga Gemcitab, se completa el esquema por 8 ciclos. No existió respuesta favorable por lo que se propone tratamiento de segunda línea de quimioterapia con Ifosfomida. Presenta metástasis en mama la misma que posterior a exámenes de imagen y patología se concluye que la paciente presenta metástasis de células escamosas de Ca (cáncer) de Cérvix a mama, 6 meses posterior al diagnóstico la paciente fallece. La metástasis en la mama de una neoplasia de otros órganos es muy raro cuya incidencia es muy baja y de pronóstico sombrío. Palabras claves: metástasis, células escamosas, cáncer de cérvix.

On the question of primary malignant neoplasms of ductus hepatici

Among the neoplasms of large extrahepatic bile ducts, cancers occupy the first place in terms of frequency and importance, and the common bile duct, especially its beginning the place where it flows into the duodenum (papilla Vateri), is the most frequent site of cancer localization.

A humanized orthotopic tumor microenvironment alters the bone metastatic tropism of prostate cancer cells

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men, and bone is the most frequent site of metastasis. The tumor microenvironment (TME) impacts tumor growth and metastasis, yet the role of the TME in PCa metastasis to bone is not fully understood. We used a tissue-engineered xenograft approach in NOD-scid IL2Rγnull (NSG) mice to incorporate two levels of humanization; the primary tumor and TME, and the secondary metastatic bone organ. Bioluminescent imaging, histology, and immunohistochemistry were used to study metastasis of human PC-3 and LNCaP PCa cells from the prostate to tissue-engineered bone. Here we show pre-seeding scaffolds with human osteoblasts increases the human cellular and extracellular matrix content of bone constructs, compared to unseeded scaffolds. The humanized prostate TME showed a trend to decrease metastasis of PC-3 PCa cells to the tissue-engineered bone, but did not affect the metastatic potential of PCa cells to the endogenous murine bones or organs. On the other hand, the humanized TME enhanced LNCaP tumor growth and metastasis to humanized and murine bone. Together this demonstrates the importance of the TME in PCa bone tropism, although further investigations are needed to delineate specific roles of the TME components in this context.

Salvage local treatment for localized radio-recurrent prostate cancer: a narrative review and future perspectives

Although dose escalation protocols have improved biochemical control in prostate cancer radiotherapy, 10–45% of patients will experience disease recurrence. The prostate and seminal vesicles are the most frequent site of the first relapse. Traditionally, these patients have been managed with hormonal therapy, which is not curative. Recent improvements in diagnostic tests (e.g., multiparametric magnetic resonance and molecular imaging, including PET/CT scan with choline or Ga-PSMA) and new treatment techniques (e.g., stereotactic body radiation therapy or other minimally invasive alternatives like high-intensity focus ultrasound, cryoablation or high-dose-rate brachytherapy) offer new therapeutic strategies with the potential to cure some patients with limited adverse effects. In this narrative review, the authors present the most recent evidence to help identify the most suitable candidates for salvage treatment.

Age-related Cellular and Microstructural Changes in the Rotator Cuff Enthesis

Rotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age-related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age-related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased non-mineralized zone. Proliferation, migration, and colony forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.