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 re-bundles fibril when stalled [1]. 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.
AimsThe 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.MethodsTumour 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.ResultsThe 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).ConclusionStrict 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.
Background: In the 8th Edition of the American Joint Committee on Cancer Staging System (yAJCC) for breast cancer after neoadjuvant chemotherapy (NAC), tumor size is based on the largest focus of residual tumor, excluding treatment-related fibrosis. The goal of this study was to assess the impact of strict adherence to yAJCC criteria on residual breast tumor size and discrepancies between yAJCC stage and Residual Cancer Burden (RCB) class. Design: Breast cancer resections after NAC from 2016-2020 were identified in the Anatomic Pathology laboratory information system. Stage IV, pT4b, pT4d, pCR, neoadjuvant endocrine therapy alone and no response to NAC were exclusion criteria. Tumor size, ypT category and focality were reassessed using current yAJCC criteria and compared to the original reports. A median of 29 slides per case were reviewed (range, 9-113). Results: A total of 189 cases met inclusion criteria, including 58 (31%) TNBCs, 50 (26%) HER2+ and 81 (43%) hormone receptor-positive/HER2-negative (HR+/HER2-). The reassessed tumor size and ypT category differed from the original report in 113 (60%) and 107 (57%) cases, respectively. In all of these cases the tumor size or ypT category was smaller/lower on review. The 107 cases with lower ypT categories included 41% of TNBCs, 62% of HER2+ and 64% of HR+/HER2- (p=0.02) In the original report, 36 (19%) cases were classified as multifocal versus 131 (69%) after review (p=0.00001). yAJCC staging based on the reassessed ypT categories differed from the original report in 38 (20%) cases (all down-staged). There were 77/189 (41%) cases with yAJCC/RCB Class discrepancies in the original reports versus 95/189 (50%) after slide review (p=0.08). The yAJCC/RCB discrepant cases in the original reports included 47% of TNBCs, 38% of HER2+ and 38% of HR+/HER2- versus 47% of TNBCs, 48% of HER2+ and 54% of HR+/HER2- after review (p=0.62). The higher proportion of discrepancies among HR+/HER2- after review did not reach statistical significance (p=0.06). Conclusions: Strict adherence to 8th Ed. yAJCC criteria for measurement of the residual breast tumor after NAC resulted in smaller tumor size, lower ypT category, lower yAJCC stage and more tumors classified as multifocal. Changes in ypT category occurred more often among HER2+ and HR+/HER2- than TNBC. There was no significant change in the frequency of yAJCC/RCB discrepancies. Citation Format: Dawn Harter, Siobhan M O'Connor, Johann D Hertel, Benjamin C Calhoun. Breast tumor measurement after neoadjuvant chemotherapy using the 8th edition of the American Joint Committee on cancer staging system: Impact on estimates of tumor size and discrepancies with residual cancer burden class [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-02-10.
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.
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