Aims: To establish the relation between the amount of breast core needle biopsy (CNB) material examined and agreement between preoperative and postoperative histopathology parameters in invasive breast cancer. Methods: The CNB and surgical specimen histopathology reports of 113 patients with invasive breast carcinoma were reviewed and the total amount of CNB material examined for each case was determined. Agreement was calculated for tumour type, grade, mitoses, nuclear pleomorphism, and tubule formation. Associations between the amount of CNB material and histopathology agreement before and after surgery were explored using binary logistic regression. Results: Tumour type and grade agreed in 65.4% and 61.6% of cases, respectively. The components used to calculate grade-nuclear pleomorphism (57.4%), mitoses (59.4%), and tubule formation (55.6%)-agreed slightly less frequently. The proportion of cases with preoperative and postoperative assessments that agreed did not depend on the number of cores collected or the total amount of material examined. Conclusion: Neither tumour type and grade, nor the individual components used to calculate grade agreed consistently between the CNB and surgical specimen. The number of cores collected and the total amount of material reviewed by the pathologist does not influence the likelihood of agreement between preoperative and postoperative histopathology reports.

A patient is reported with small cell lung cancer treated with combination chemotherapy (cyclophosphamide, vincristine and etoposide [VP‐16‐213] who developed transient liver function abnormalities secondary to vincristine therapy. Serum transaminase (SGOT and SGPT) levels rose by 2 to 6 times, lactic dehydrogenase (LDH) 1.5 to 2 times, and alkaline phosphatase and gamma‐glutamyl transpeptidase (GGTP) 1.5 to 2 times normal. Enzyme abnormalities were observed by the 6th day following drug administration and returned to normal between 16 and 48 days, except for the GGTP elevations which persisted longer. Vincristine has been suspected to cause liver damage and to enhance radiation‐induced hepatic injury. The authors report this case of moderate transient transaminitis confirmed by rechallenge with vincristine.

Introduction Factor XI deficiency (FXI) is an autosomally inherited injury-related bleeding disorder. Although relatively rare worldwide, it is common amongst Ashkenazi and Iraqi Jewish ancestry with a heterozygosity rate as high as 8 to 9%. FXI deficiency does not provoke spontaneous bleeding; however, it predisposes to a potential risk of life-threatening bleeding at childbirth or surgery. Unfortunately, data regarding obstetrical and perioperative management of this condition is scarce, with less than 500 cases reviewed in the last 20 years. Therefore, this study aimed to expand this database and identify factors associated with increased bleeding risk. Methods We performed a retrospective chart review of patients (pts) with FXI deficiency who underwent childbirth or other surgical procedures between August 2011 to April 2021 within the Mount Sinai Health System in New York City. Data on age, sex, ethnicity, genotype, family or personal history of bleeding, type of anesthesia, estimated blood loss, peri-procedural bleeding complication, and type and timing of blood product or hemostatic agent administered in the peri-operative period were collected. Prior history of bleeding was defined as 1 or more of the following: easy bruisability, epistaxis, heavy menstrual bleeding, bleeding related to dental, surgical or obstetrical procedure. The paired t-test was used to compare the initial and subsequent FXI levels measured during pregnancy. We performed logistic regression to test the association between historical, laboratory, and procedural variables with the bleeding endpoint (defined as acute postpartum or postoperative hemorrhage or any bleeding warranting non-prophylactic administration of packed red blood cells, fresh frozen plasma [FFP], or tranexamic acid). Receiver operative characteristic (ROC) curve was plotted for FXI levels to identify the cutoff for optimal sensitivity and specificity. Analyses were performed using SPSS software. Results We identified 198 pts who underwent 252 procedures in total- including 143 vaginal deliveries, 64 C-sections and 45 other surgical procedures. Mean age was 36 years with 94% females, and ~70% were Ashkenazi Jews. c.403G>T p.E135X (42%) and c.901T>C p.F301L (44.8%) were the most common genotypes identified. 38 out of 252 procedures resulted in bleeding complications. In multivariable logistic regression, both prior history of bleeding (odds ratio (OR) 8.97, p=0.02) and lower FXI levels ( OR 1.03 per U/dL increase, p=0.05) were independently associated with the bleeding endpoint. Family history of bleeding, ethnicity, genotype, pre-procedural PTT and platelet levels were not associated with bleeding risk. There were no cases of epidural or spinal hematomas associated with neuraxial anesthesia in our cohort. Mean FXI level for pts receiving neuraxial anesthesia was 50 U/dl (3-118 U/dl). Five pts who had a negative bleeding history despite surgical challenges received neuraxial anesthesia at FXI level <10 U/dl without any complications (only 1/5 received prophylactic FFP). Mean FXI level for pts receiving prophylactic FFP was 25.6 U/dl (range 1-71 U/dl). 8 out of 21 (38%) pts suffered a bleeding complication despite prophylactic FFP use. ROC analyzing FXI levels as a risk factor for the bleeding endpoint resulted in an AUC of 0.605 with specificity of 96%, 94%, 91%, 83%, 49% and sensitivity of 11%, 12%, 19%, 35%, 65% respectively for cut-off values of 10, 20, 30, 40 and 50 U/dl. Of note, there was no significant variation in FXI levels during pregnancy [mean first measurement was 49.7 U/dl vs final measurement of 48.3 U/dl, p=0.3]. Conclusions Personal history of bleeding is the strongest predictor of perioperative or obstetrical bleeding in pts with FXI deficiency. Higher FXI levels correlate with a slightly lower but statistically significant odds of surgical bleeding. Although a FXI level cut-off of 40 U/dl may predict bleeding risk with reasonable specificity (83%), it lacks sensitivity and must be interpreted in the context of personal bleeding history. FXI levels remain stable during pregnancy and repeat measurements may not be necessary. Neuraxial anesthesia appears to be safe to use in this cohort. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Factor XI (FXI) deficiency is an autosomally inherited milder bleeding disorder which may predispose to a potential risk of life-threatening bleeding during childbirth or surgery. Unfortunately, data regarding obstetric and perioperative management of this condition are scarce, with limited cases reviewed in the last decade. Therefore, the present study aimed to expand this database and identify factors associated with increased bleeding risk. We performed a retrospective chart review of patients with FXI deficiency who underwent childbirth or other surgical procedures between August 2011 to April 2021 within a single academic health system and identified 198 patients who underwent 252 procedures, including 143 vaginal deliveries, 63 cesarean (C-sections) and 46 other surgical procedures. Thirty three of 252 procedures resulted in bleeding complications. On multivariable logistic regression analysis, personal history of bleeding was the strongest predictor of perioperative or obstetrical bleeding (OR = 5.92, p=0.001). Higher FXI levels correlated with lower odds of bleeding (OR 0.72 with every 10 U/dl increase in FXI level, p=0.05). On ROC analysis, FXI level of >40 U/dl predicted lower bleeding risk with reasonable specificity (75%) but lacked sensitivity (47%). Family history of bleeding, ethnicity, genotype, pre- procedural PTT and platelet levels were not associated with bleeding risk. There were no cases of epidural or spinal hematomas associated with neuraxial anesthesia. FXI levels remain stable during pregnancy and repeat measurements may not be necessary.