Frozen Section Timeout: Pilot Study to Reconcile Margins Using 3D Resected Specimen and Defect Scans.

OBJECTIVE: Opportunities exist to improve intraoperative communication and documentation of resection margin details. We instituted a "frozen section timeout" that centers around visualization of the paired resection specimen and surgical defect-facilitating effective, bidirectional exchange of information. METHODS: We designed an interactive form for use during the "frozen section timeout" including annotated 3D virtual models of the resected specimen and surgical defect, plus a "line-item" table for primary and supplemental margin results. The "timeout" was conducted over a Zoom call between the operating room and frozen section laboratory. The form was simultaneously projected and discussed while all members of the surgical care team stopped activities. Nurses, co-surgeons, and all other members of the surgical team were encouraged to take part in this process. RESULTS: Twenty-six frozen section timeouts were conducted during head and neck surgeries in the Department of Otolaryngology at Mount Sinai West Hospital. These timeouts were facilitated by the lead surgeon, and all other activities were halted to ensure that critical information was shared, documented, and agreed upon. During the timeout, the annotated specimen and defect scans were displayed, clearly demonstrating the at-risk margins and the corresponding location and breadth of supplemental margins harvested. CONCLUSION: Incorporating a frozen section timeout can improve intraoperative communication, increase transparency, and potentially eliminate uncertainty regarding margin status and tumor clearance. Visualization of at-risk margins and the corresponding location and breadth of supplemental margins promises an unprecedented level of documentation and understanding. This novel technique can establish a new and improved standard of care. LEVEL OF EVIDENCE: NA Laryngoscope, 134:725-731, 2024.

iPad Annotation of 3D Surgical Models Using Procreate®: Novel Documentation of Supplemental Margins.

We present a novel, efficient approach to demonstrating supplemental margins during oncologic resection. Surgeons and pathologists annotated 10 virtual models of surgical defects and resection specimens in 3D using an iPad-based application, Procreate®. Incorporating this method into the surgical workflow can improve interdepartmental communication and provide visual documentation of surgical steps taken to address at-risk margins. Laryngoscope, 2023.

WPOI-5: Accurately Identified at Intraoperative Consultation and Predictive of Occult Cervical Metastases.

BACKGROUND: Frozen section analysis of oral cancer specimens is ideal for assessing margin distances and depth of invasion (DOI); the latter impacts intraoperative decisions regarding elective neck dissection (END). Here, we show that intraoperative determination of worst pattern of invasion (WPOI), specifically WPOI-5, has a high level of accuracy. This relates to our demonstration herein that WPOI-5 predicts occult cervical metastases (OCM) for pT1 oral squamous carcinoma (OSC). METHODS: The presence of OCM was correlated with WPOI in 228 patients with primary T1/T2/cN0 OSC undergoing resection and END. Concordance between intraoperative and final pathology WPOI determination was assessed on 51 cases of OSC. RESULTS: WPOI-5 predicts OCM in pT1 patients, compared with WPOI-4/WPOI-3 (p < 0.0001). Most pT1 WPOI-5 tumors had DOI of 4-5 mm (24/59 or 40.7%). Only two pT1 WPOI-5 tumors had DOI < 4 mm (3.0 and 3.5 mm). If END were performed in this pT1 cohort for all WPOI-5 OSC patients regardless of DOI, OR all OSC patients with DOI ≥ 4 mm regardless of WPOI, then no OCM would be missed (p = 0.017, 100% sensitivity, 29% specificity, 77% positive predictive value, 23% negative predictive value). With respect to intraoperative WPOI-5 determination, the accuracy, sensitivity, and specificity was 92.16, 73.33, and 100.0%, respectively. CONCLUSIONS: DOI ≥ 4 mm is the dominant predictor of OCM. For the rare WPOI-5 OSC with DOI < 4 mm, it is reasonable to suggest that surgeons perform END. WPOI-5 may be accurately determined intraoperatively. As microscopic instruction is needed to accurately assess WPOI-5, a teaching link is included in this manuscript.

Variability in the identification of lymphovascular space invasion for early stage cervical cancer.

OBJECTIVE: To evaluate the inter- and intra-rater variability of lymphovascular space invasion (LVSI) in early stage cervical cancer. METHODS: We identified invasive cervical cancer tissue samples from radical hysterectomies in our institutional pathology database. The cases were stained with Hematoxylin & Eosin (H&E) and immunostains (CD-31 and D2-40). They were evaluated for the presence of LVSI by 6 pathologists on 3 separate occasions: with H&E staining only, then with H&E and immunostained specimens, and finally using a shared written criterion for diagnosis of LVSI. With 80 cases, a two-sided 95% confidence interval for the Kappa of 0.7 with a precision of 0.1 on each side was estimated. RESULTS: Stage distribution was: IA 10%, IB 85%, and IIA 5%. The majority of cases were squamous cell carcinoma (55%), followed by adenocarcinoma (39%) and adenosquamous or other histology (6%). The mean inter-rater Kappa was 0.41 (95% CI: 0.37-0.45) for H&E. Usage of immunohistochemistry made a statistically significant improvement in the mean Kappa, but it still remained low: 0.52 (p = 0.02). Adding evaluation criteria for LVSI did not significantly increase the mean Kappa: 0.49 (p = 0.16). The mean intra-rater variability of H&E staining alone compared with H&E staining plus immunostaining was 0.53 (range: 0.43-0.64). The mean Kappa comparing H&E staining and H&E staining with criteria was 0.50 (range: 0.40-0.59). CONCLUSIONS: We noted high inter- and intra-rater variability in the diagnosis of LVSI underscoring the challenges of LVSI diagnosis. Considering the significance assigned to LVSI and its implication for treatment, comprehensive guidelines with regards to determination of LVSI status are of paramount importance.

Impact of pathological response after neoadjuvant chemotherapy on adjuvant therapy decisions and patient outcomes in gastrointestinal cancers.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is frequently used in gastrointestinal cancers (GIC), and pathological, radiological, and tumor marker responses are assessed during and after NAC. AIM: To evaluate the relationship between pathologic, radiologic, tumor marker responses and recurrence-free survival (RFS), overall survival (OS), adjuvant chemotherapy (AC) decisions, and the impact of changing to a different AC regimen after poor response to NAC. METHODS AND RESULTS: Medical records of GIC patients treated with NAC at Mount Sinai between 1/2012 and 12/2018 were reviewed. One hundred fifty-six patients (58.3% male, mean age 63 years) were identified. Primary tumor sites were: 43 (27.7%) pancreas, 62 (39.7%) gastroesophageal, and 51 (32.7%) colorectal. After NAC, 31 (19.9%) patients had favorable pathologic response (FPR; defined as College of American Pathologists [CAP] score 0-1). Of 107 patients with radiological data, 59 (55.1%) had an objective response, and of 113 patients with tumor marker data, 61 (54.0%) had a ≥50% reduction post NAC. FPR, but not radiographic or serological responses, was associated with improved RFS (HR 0.28; 95% CI 0.11-0.72) and OS (HR 0.13; 95% CI 0.2-0.94). Changing to a different AC regimen from initial NAC, among all patients and specifically among those with unfavorable pathological response (UPR; defined as CAP score 2-3) after NAC, was not associated with improved RFS or OS. CONCLUSIONS: GIC patients with FPR after NAC experienced significant improvements in RFS and OS. Patients with UPR did not benefit from changing AC. Prospective studies to better understand the role of pathological response in AC decisions and outcomes in GIC patients are needed.

Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma.

Identification of the microsatellite instability (MSI) phenotype in endometrial carcinoma is important given that such tumors are the most common noncolorectal tumors to occur in hereditary nonpolyposis colorectal cancer syndrome, and may bear prognostic relevance. The objective of this study was to assess the utility of immunohistochemistry (IHC), a simple and fast technique, in detecting MSI in endometrial carcinoma. The study subjects consisted of 90 endometrial carcinoma patients with equal representation of MSI-high (MSI-H) and non-MSI-H tumors. MSI was tested using the standard polymerase chain reaction-based method and the 5 NCI-recommended markers. Overall, IHC with MLH1 and MSH2 antibodies detected 69% of MSI-H tumors with a specificity of 100%. Adding PMS2 and MSH6 to the antibody panel increased the sensitivity to 91% but decreased the specificity to 83%. The most common IHC abnormality in MSI tumors was concurrent loss of MLH1/PMS2. Assessment of staining was straightforward in most cases but not in all. Staining inadequacies existed. Five stains (4 MLH1 and 1 MSH6) were not interpretable because of the lack of any internal positive control. Two percent to 10% of the cases (depending on the antibody assessed) had only focal weak staining; the highest frequency (10%) occurred with MLH1 antibody. PMS2 staining detected 7 MLH1-staining present MSI-H cases, thus partly accounting for the increased sensitivity with the 4-antibody panel. MSH6 staining identified 9 cases with loss of MSH6 alone, 6 of 9 were non-MSI-H, thus partly accounting for the decreased specificity with the 4-antibody panel. In conclusion, our results suggest that IHC is useful in detecting MSI in endometrial carcinoma. Although IHC has a lower sensitivity with more apparent staining inadequacies in detecting MSI in endometrial carcinoma than it does in colorectal carcinoma, its use in endometrial carcinoma may be an important adjunct when screening for hereditary cases. In the future, as prognostic and therapeutic implications of MSI phenotype become better defined, it may be reasonable to perform IHC for mismatch repair proteins in large numbers of endometrial carcinomas.

Renal Papillary Necrosis Caused by Protein C Deficiency Leading to Recurrent Hydronephrosis.

A patient with history of a solitary functioning kidney and protein C deficiency (PCD) presented with recurrent severe hydronephrosis causing acute kidney injury upon chronic kidney disease. Work-up with endoscopic evaluation revealed renal papillary necrosis (RPN) and sloughed renal papillae to be the true cause of the recurrent obstruction. Pathologic evaluation of the sloughed tissue confirmed the diagnosis of RPN. This is the first case reported in the literature illustrating the unique presentation of RPN in the setting of PCD.

Gene Amplifications in Well-Differentiated Pancreatic Neuroendocrine Tumors Inactivate the p53 Pathway.

Neuroendocrine tumors (NETs) comprise a group of rare tumors derived from the diffuse neuroendocrine system or islet endocrine cells of the pancreas. The molecular mechanisms underlying NETs are largely unknown. The tumor suppressor p53 plays a critical role in maintaining genomic stability and tumor prevention. The p53 pathway is tightly regulated by a number of proteins, among which MDM2, MDM4, and WIP1 are key negative regulators of p53 protein levels or activity. Aberrant activation of these negative regulators can attenuate the p53 function that serves as an important mechanism of tumorigenesis. In this study, several genetic alterations in pancreatic NETs were studied. These tumors exhibit various chromosomal aberrations throughout the whole genome as examined by array-based comparative genomic hybridization. Although p53 mutations are rare in NETs (<3%), this study presents evidence that the p53 pathway is altered in pancreatic NETs through aberrant activation of its negative regulators. A high percentage of pancreatic NETs contain extra gene copies of MDM2 (22%), MDM4 (30%), and WIP1 (51%), which are correlated with expression of corresponding mRNAs and proteins. In addition, there is a higher frequency (23% v. 15% in the control population) of the G/G genotype of MDM2 SNP309, a functional single-nucleotide polymorphism in the MDM2 gene that attenuates the function of the p53 protein. Overall, approximately 70% of pancreatic NETs have one or more of these genetic changes. These findings suggest that the negative regulation of p53 function could be an important mechanism for the initiation and/or progression of pancreatic NETs, and reactivation of p53 could be a potential therapeutic strategy for patients with this disease.

Variants in hormone biosynthesis genes and risk of endometrial cancer.

We investigated the risk associated with variants in three genes involved in estrogen biosynthesis, CYP11A1, CYP17A1, and CYP19A1, in the population-based case-control study of Estrogen, Diet, Genetics, and Endometrial Cancer. This study was conducted in New Jersey in 2001-2006 with 417 cases and 402 controls. For CYP11A1, there was no association between the number of [TTTTA]( n ) repeats (D15S520) and risk. For CYP17A1, risk was somewhat lower among women with the C/C genotype at T-34C (rs743572) (adjusted OR = 0.65, 95% CI 0.41-1.02). For CYP19A1, risk was lower among women homozygous for the 3-bp deletion (rs11575899) in exon 4 (adjusted OR = 0.44, 95% CI 0.26-0.76), while the number of [TTTA]( n ) repeats was not significantly related to risk: the adjusted OR for n = 7/7 repeats versus n > 7/>7 repeats was 0.81 (95% CI 0.54-1.23). In stratified analyses, results for CYP19A1 were stronger among women with higher (> or =27.4) body mass index: for the homozygous deletion, OR = 0.30 (95% CI 0.15-0.62); for the n = 7/7 genotype, OR = 0.49 (95% CI 0.26-0.93). The interaction between the n = 7/7 genotype and BMI was statistically significant (p = 0.01). The insertion/deletion variant in CYP19A1 appears to be related to risk of endometrial cancer; risk associated with variants in this gene may vary according to BMI.

En bloc resection of diaphragm with lung for recurrent ovarian cancer: a case report.

INTRODUCTION: Multiple series have demonstrated the feasibility of full-thickness diaphragm resection for ovarian cancer metastatic to the diaphragm. However, direct extension of tumor into the lung is sometimes encountered, and successful resection of this type of implant has not been previously described in the gynecologic oncology literature. CASE REPORT: We present the first case of en bloc full-thickness diaphragm resection including a portion of lung tissue using the EndoGIA stapler with primary diaphragmatic closure. DISCUSSION: En bloc full-thickness diaphragm resection including a portion of lung tissue using the EndoGIA stapler is a safe, feasible, and effective method to optimize cytoreduction with disease-free margins in the context of invasive diaphragmatic ovarian cancer metastasis.