Pathological measurement and staging of residual breast cancer after neoadjuvant chemotherapy.

AIMS: The 8th Edition of the American Joint Committee on Cancer Staging System (yAJCC) excludes treatment-related fibrosis from the measurement of residual tumour after neoadjuvant chemotherapy (NAC) for breast cancer. The impact of the 8th Ed. yAJCC on post-NAC pathologic staging was examined in 188 breast cancer specimens from 183 patients with measurable residual tumour. METHODS: Tumour size, ypT, and ypN categories were reassessed with the current yACC criteria and compared to the original pathology reports. Histological patterns of response in the breast were categorised as concentric or scattered. RESULTS: The reassessed breast tumour size or ypT category differed from the original report in 101 (53.7%) cases. Changes in the ypT and/or ypN category resulted in downstaging of 45/185 (24.3%). A smaller reassessed tumour size or lower ypT category occurred more often in hormone receptor-positive/HER2-negative (HR+/HER2-) (68.3%) and HER2-positive (HER2+) tumours (74.0%) than triple-negative breast cancer (TNBC) (37.5%) (P < 0.001). A scattered pattern of response was more frequent in HR+/HER2- (54.9%) and HER2+ (66.0%) tumours than TNBC (35.7%) (P = 0.006). Changes in size, ypT, or multifocality based on the 8th Ed. yAJCC criteria were more frequent in tumours with a scattered pattern of response (P < 0.001). CONCLUSION: Strict adherence to yAJCC criteria for measurement of the residual breast tumour after NAC resulted in smaller tumour size, lower ypT category, lower yAJCC stage, and more frequent classification of residual tumour as multifocal. Downstaging based on 8th Ed. yAJCC criteria was associated with tumour subtype and histological pattern of response.

Recurrent Hemarthrosis following Resections of Benign Bone Tumors: A Case Report of Two Pediatric Cases.

Introduction/Cases. Two pediatric patients presenting with benign bone tumors of the distal femur at the level of the suprapatellar fat pad developed late onset recurrent knee hemarthrosis following surgical treatment of the lesions. A sinus tract from the intramedullary bone to the knee capsule was discovered in both patients during surgical exploration. Resection of the sinus tract and full closure of the knee capsule resulted in no further recurrence. Conclusion. Postoperative knee effusions in patients following resection near the distal femur could represent hemarthrosis that require additional workup and treatment. Resection of the sinus tract successfully treats the hemarthrosis.

Ca2+ -induced orientation of tandem collagen binding domains from clostridial collagenase ColG permits two opposing functions of collagen fibril formation and retardation.

To penetrate host tissues, histotoxic clostridia secrete virulence factors including enzymes to hydrolyze extracellular matrix. Clostridium histolyticum, recently renamed as Hathewaya histolytica, produces two classes of collagenase (ColG and ColH). The high-speed AFM study showed that ColG collagenase moves unidirectionally to plane collagen fibril and rebundles fibril when stalled . The structural explanation of the roles for the tandem collagen-binding segment (CBDs) is illuminated by its calcium-bound crystal structure at 1.9 Å resolution (Rwork = 15.0%; Rfree = 19.6%). Activation may involve calcium-dependent domain rearrangement supported by both small-angle X-ray scattering and size exclusion chromatography. At pCa ≥ 5 (pCa = -log[Ca2+ ]), the tandem CBD adopts an extended conformation that may facilitate secretion from the bacterium. At pCa ≤ 4, the compact structure seen in the crystal structure is adopted. This arrangement positions the two binding surfaces ~ 55 Å apart, and possibly ushers ColG along tropocollagen molecules that allow for unidirectional movement. A sequential binding mode where tighter binding CBD2 binds first could aid in processivity as well. Switch from processive collagenolysis to fibril rearrangement could be concentration dependent. Collagen fibril formation is retarded at 1 : 1 molar ratio of tandem CBD to collagen. Tandem CBD may help isolate a tropocollagen molecule from a fibril at this ratio. At 0.1 : 1 to 0.5 : 1 molar ratios fibril self-assembly was accelerated. Gain of function as a result of gene duplication of CBD for the M9B enzymes is speculated. The binding and activation modes described here will aid in drug delivery design. ACCESSION CODES: The full atomic coordinates of the tandem CBD and its corresponding structure factor amplitudes have been deposited in the Protein Data Bank (PDB accession code 5IKU). Small-angle X-ray scattering data and corresponding ab initio models have been submitted to the Small Angle Scattering Biological Data Bank (SASBDB). Accession codes CL2, collagenase module 2, CN2, CP2 are assigned to envelopes for tandem CBD at -log[Ca2+ ] (pCa) 3, 4, 5, and 6, respectively. Accession code DC64 was assigned to the complex of polycystic kidney disease-CBD1-CBD2 with mini-collagen.