Relationship between Aldehyde Dehydrogenase, PD-L1 and Tumor-Infiltrating Lymphocytes with Pathologic Response and Survival in Breast Cancer.

Aldehyde dehydrogenase 1A1 (ALDH1A1) is a cancer stem cell (CSC) marker related to clinical outcomes in breast cancer (BC). The aim of this study was to analyze the relationship between ALDH1A1, programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2-positive (HER2+) BC tumors, and its association with clinicopathological characteristics and outcomes. A retrospective, historical cohort study of patients diagnosed with early or locally advanced BC treated with neoadjuvant chemotherapy was conducted. ALDH1A1, PD-L1 expression and TILs were assessed using immunohistochemistry. A total of 75 patients were analyzed (42.7% TN, 57.3% HER2+ tumors). ALDH1A1+ was related to HTILs (p = 0.005) and PD-L1+ tumors (p = 0.004). ALDH1A1+ tumors presented higher CD3+ (p = 0.008), CD4+ (p = 0.005), CD8+ (p = 0.003) and CD20+ (p = 0.006) TILs. ALDH1A1+ (p = 0.018), PD-L1+ (p = 0.004) and HTILs (p < 0.001) were related to smaller tumors. ALDH1A1+ was related to pathologic complete response (pCR) (p = 0.048). At the end of the follow-up (54.4 [38.3−87.6] months), 47 patients (62.7%) remained disease-free, and 20 (26.7%) had died. HTILs were related to improved disease-free survival (p = 0.027). ALDH1A1+ was related to PD-L1+ and HITLs, that might be related to higher pCR rates with neoadjuvant therapy.

Adequacy of early-stage breast cancer systemic adjuvant treatment to Saint Gallen-2013 statement: the MCC-Spain study.

The St Gallen Conference endorsed in 2013 a series of recommendations on early breast cancer treatment. The main purpose of this article is to ascertain the clinical factors associated with St Gallen-2013 recommendations accomplishment. A cohort of 1152 breast cancer cases diagnosed with pathological stage < 3 in Spain between 2008 and 2013 was begun and then followed-up until 2017/2018. Data on patient and tumour characteristics were obtained from medical records, as well as their first line treatment. First line treatments were classified in three categories, according on whether they included the main St Gallen-2013 recommendations, more than those recommended or less than those recommended. Multinomial logistic regression models were carried out to identify factors associated with this classification and Weibull regression models were used to find out the relationship between this classification and survival. About half of the patients were treated according to St Gallen recommendations; 21% were treated over what was recommended and 33% received less treatment than recommended. Factors associated with treatment over the recommendations were stage II (relative risk ratio [RRR] = 4.2, 2.9-5.9), cancer positive to either progesterone (RRR = 8.1, 4.4-14.9) or oestrogen receptors (RRR = 5.7, 3.0-11.0). Instead, factors associated with lower probability of treatment over the recommendations were age (RRR = 0.7 each 10 years, 0.6-0.8), poor differentiation (RRR = 0.09, 0.04-0.19), HER2 positive (RRR = 0.46, 0.26-0.81) and triple negative cancer (RRR = 0.03, 0.01-0.11). Patients treated less than what was recommended in St Gallen had cancers in stage 0 (RRR = 21.6, 7.2-64.5), poorly differentiated (RRR = 1.9, 1.2-2.9), HER2 positive (RRR = 3.4, 2.4-4.9) and luminal B-like subtype (RRR = 3.6, 2.6-5.1). Women over 65 years old had a higher probability of being treated less than what was recommended if they had luminal B-like, HER2 or triple negative cancer. Treatment over St Gallen was associated with younger women and less severe cancers, while treatment under St Gallen was associated with older women, more severe cancers and cancers expressing HER2 receptors.

Recommendations for somatic and germline genetic testing of single pheochromocytoma and paraganglioma based on findings from a series of 329 patients.

BACKGROUND: Nowadays, 65-80% of pheochromocytoma and paraganglioma (PPGL) cases are explained by germline or somatic mutations in one of 22 genes. Several genetic testing algorithms have been proposed, but they usually exclude sporadic-PPGLs (S-PPGLs) and none include somatic testing. We aimed to genetically characterise S-PPGL cases and propose an evidence-based algorithm for genetic testing, prioritising DNA source. METHODS: The study included 329 probands fitting three criteria: single PPGL, no syndromic and no PPGL family history. Germline DNA was tested for point mutations in RET and for both point mutation and gross deletions in VHL, the SDH genes, TMEM127, MAX and FH. 99 tumours from patients negative for germline screening were available and tested for RET, VHL, HRAS, EPAS1, MAX and SDHB. RESULTS: Germline mutations were found in 46 (14.0%) patients, being more prevalent in paragangliomas (PGLs) (28.7%) than in pheochromocytomas (PCCs) (4.5%) (p=6.62×10(-10)). Somatic mutations were found in 43% of those tested, being more prevalent in PCCs (48.5%) than in PGLs (32.3%) (p=0.13). A quarter of S-PPGLs had a somatic mutation, regardless of age at presentation. Head and neck PGLs (HN-PGLs) and thoracic-PGLs (T-PGLs) more commonly had germline mutations (p=2.0×10(-4) and p=0.027, respectively). Five of the 29 metastatic cases harboured a somatic mutation, one in HRAS. CONCLUSIONS: We recommend prioritising testing for germline mutations in patients with HN-PGLs and T-PGLs, and for somatic mutations in those with PCC. Biochemical secretion and SDHB-immunohistochemistry should guide genetic screening in abdominal-PGLs. Paediatric and metastatic cases should not be excluded from somatic screening.

[Laparoscopy-assisted aortobifemoral bypass through the transperitoneal retrorenal approach]. / By-pass aortobifemoral con asistencia laparoscópica por vía transperitoneal retrorrenal.

The aim of laparoscopic vascular surgery in the aortoiliac segment is to replicate the excellent outcomes of open aortic surgery while providing the advantages of minimally invasive surgery. We report the case of a 49-year old man with disabling hip claudication and rest pain in his left lower extremity. On examination the patient had reduced right femoral pulse and absent pulses in his left lower extremity. Angiography revealed occlusive disease in the left aortoiliac segment and right common iliac artery stenoses. Laparoscopic aortobifemoral bypass was planned. The surgical technique included 70 degrees -right lateral decubitus position and retrorenal retrocolic dissection from the left common iliac artery to the left renal vein. Minilaparotomy consisted of aortic clamping, arteriotomy, and end-to-side aorto-prosthetic anastomosis with Dacron graft. Time to extubation was 5 hours; peristalsis was recovered 72 hours after surgery. The patient was discharged from hospital after cardiologic assessment 9 days after surgery.

By-pass aortobifemoral con asistencia laparoscópica por vía transperitoneal retrorrenal / Laparoscopy-assisted aortobifemoral bypass through the transperitoneal retrorenal approach

El objetivo de la cirugía vascular laparoscópica en el sector aortoilíaco es reproducir los excelentes resultados de la cirugía clásica minimizando la agresión quirúrgica. Presentamos el caso clínico de un varón de 49 años con claudicación invalidante en las caderas y dolor de reposo en el miembro inferior izquierdo (MII). A la exploración, el pulso femoral derecho era débil y había ausencia de pulsos en el MII. La aortoarteriografía demostró una oclusión ilíaca izquierda y un eje ilíaco derecho filiforme. Se consideró la opción quirúrgica de bypass aortobifemoral laparoscópico. La intervención quirúrgica se llevó a cabo con el paciente en decúbito lateral derecho de 70°; se realizó una disección aórtica retrocólica retrorrenal, desde origen de la arteria ilíaca primitiva izquierda hasta vena renal izquierda; la minilaparotomía consistió en pinzamiento aórtico, aortotomía y anastomosis aortoprotésica en terminolateral con dacron. Se extubó al paciente a las 5 h, que presentó peristalsis a las 72 h. Se le dio el alta ambulatoria tras revisión cardiología programada, al noveno día de la intervención (AU)

The aim of laparoscopic vascular surgery in the aortoiliac segment is to replicate the excellent outcomes of open aortic surgery while providing the advantages of minimally invasive surgery. We report the case of a 49-year old man with disabling hip claudication and rest pain in his left lower extremity. On examination the patient had reduced right femoral pulse and absent pulses in his left lower extremity. Angiography revealed occlusive disease in the left aortoiliac segment and right common iliac artery stenoses. Laparoscopic aortobifemoral bypass was planned. The surgical technique included 70°-right lateral decubitus position and retrorenal retrocolic dissection from the left common iliac artery to the left renal vein. Minilaparotomy consisted of aortic clamping, arteriotomy, and end-to-side aorto-prosthetic anastomosis with Dacron graft. Time to extubation was 5 hours; peristalsis was recovered 72 hours after surgery. The patient was discharged from hospital after cardiologic assessment 9 days after surgery (AU)