BRCA1 alterations with additional defects in DNA damage response genes may confer chemoresistance to BRCA-like breast cancers treated with neoadjuvant chemotherapy.

The BRCA-like phenotype is a feature that some sporadic breast cancers share with those occurring in BRCA1 or BRCA2 mutation carriers. As tumors with the phenotype have defects in the DNA damage response pathway, which may increase sensitivity to drugs such as DNA cross-linking agents and PARP inhibitors, a method to identify this phenotype is important. The prediction of chemoresistance, which frequently develops in these tumors, is also crucial for improving therapy. We examined genomic aberrations and BRCA1 promoter methylation in tumors of 73 breast cancer (20 HR-/HER2- and 53 HR+/HER2-) patients, who received neoadjuvant chemotherapy with anthracycline, cyclophosphamide, and taxane, using SNP array CGH and quantitative PCR. The methylation and/or loss or uniparental disomy (UPD) of BRCA1 (BRCA1 alterations) and the loss or UPD of BRCA2 (BRCA2 alterations) were detected in 27 (37%) and 21 (29%), respectively, of the 73 tumors. Tumors with BRCA1 or BRCA2 alterations were associated with a higher number of genomic aberrations (P < 0.001 and P < 0.001) and higher percentage of TP53 alterations (P < 0.001 and P < 0.001) than those without. Overall survival (OS) rates were similar between patients with or without BRCA1 or BRCA2 alterations. However, when 27 patients with BRCA1-altered tumors were classified into those with or without the loss or UPD of PALB2, PAGR1, RAD51B, FANCM, MLL4, or ERCC1/2 in tumors, patients with additional defects in DNA damage response genes had worse OS (P = 0.037, 0.045, 0.038, 0.044, 0.041, or 0.019) than those without. These defects may confer chemoresistance and predict poor outcomes in patients with BRCA1-altered breast cancer.

[Efficacy and tolerability of controlled-release oxycodone against nab-paclitaxel-induced musculoskeletal pain in breast cancer patients].

Paclitaxel therapy often causes musculoskeletal pain, and some clinical studies have indicated that this pain is due to nerve injury, rather than muscle or joint lesion. We report four clinical cases in which controlled-release oxycodone improved pain intensity in breast cancer patients with severe musculoskeletal pain caused by nab-paclitaxel therapy. In each case, oxycodone was well-tolerated and the symptoms of peripheral neuropathy were quite mild, indicating that oxycodone exhibited a preventive or therapeutic effect on peripheral neuropathy. Therefore, oxycodone may have favorable efficacy and tolerability against cancer therapy-related pain with a neuropathic element in breast cancer patients.

Comparative anatomical study of the kidney position in amniotes using the origin of the renal artery as a landmark.

The anatomical relationship between the kidney position and its arterial supply was investigated in 21 mammals, 1 bird, and 3 reptiles (n = 1 for each species) and in 43 human cadavers. The following observations were made. (1) Although the right kidney was located caudal to the left kidney in 29 out of 43 human cadavers (67.4%), the origin of the right renal artery from the aorta was located cranial to the origin of the left renal artery in 36 human cadavers (83.7%). Therefore, the relative positions of the kidneys do not correspond with the relative origins of the renal arteries in humans. (2) Among the mammals that were examined, the position of the kidney and the branching level of the renal artery on the right side were usually cranial to those on the left side. (3) In the bird and most reptiles that were examined, kidneys were typically located in the pelvic region and were supplied by segmental arterial branches. These results suggest that the right kidney and its arterial supply are generally located cranial to the left kidney in phylogeny of mammals. While the presence of a human accessory renal artery in 9 out of 86 sides (10.5%) and a cranial origin of the left renal artery relative to the right renal artery in 7 out of 43 cadavers (16.3%), shows some variation in the arterial supply to the kidneys, the origin of the renal arteries can generally be used as phylogenetic landmarks indicating the relative positions of the kidneys. Hence, from an ontological perspective, the human right kidney may be initially situated cranial to the left kidney during the early stages of development. Thereafter, the human right kidney may shift downwards secondary.

A case of an accessory palmaris longus muscle and a duplicate palmaris longus muscle with special reference to their nerve supply--morphologic significance of a common innervation trunk.

During a dissection of the forearm and hand, a duplicate palmaris longus muscle with an accessory palmaris longus muscle was observed on the right side of a 73-year-old Japanese male cadaver. Duplications of the palmaris longus muscle have been reported by many authors. Humphry (1872) suggested the presence of radial, intermediate, and ulnar sectors in the superficial layers of the forearm flexor muscular angulus, based on a comparison of fore- and hind limbs and comparative anatomical theory. The palmaris longus muscle usually differentiates from the intermediate sector but differentiation from the other two sectors may also be possible. Some authors have asserted that a common innervation trunk is critical for determining an ontogenetic relation between the muscles (Fuchino, 1960; Honma, 1980; Yamada, 1986). We examined the nerve supply in addition to scrutinize these anomalous palmaris longus muscles. In our case, the ramification of the innervating nerves was specific. The branches to the second palmaris longus muscle and the flexor carpi radialis arose as a common trunk from the median nerve. The branches to the first palmaris longus muscle and the accessory palmaris longus muscle originated as another common trunk from the median nerve. From these observations, we speculated that the second palmaris longus muscle has differentiated from the flexor carpi radialis, while the accessory palmaris longus muscle has differentiated from the first palmaris longus muscle, based on Humphry's suggestion.