Utility of intraoperative pathology consultations of whipple resection specimens and their impact on final margin status.

The resection margin status is a significant surgical prognostic factor for the long-term outcomes of patients undergoing pancreaticoduodenectomy (Whipple procedure). As a result, surgeons frequently rely on intraoperative consults (IOCs) involving frozen sections to evaluate margin clearance during these resections. Nevertheless, the impact of this practice on final margin status and long-term outcomes remains a topic of debate. This study aimed to assess the impact of IOCs on the clearance rate of resection margins following Whipple procedure and distal pancreatectomy. A retrospective database review of all patients who underwent Whipple procedure or distal pancreatectomy at our institution between 2018 and 2020 was performed to evaluate the utility of IOCs by gastrointestinal surgeons and its correlation with final postoperative surgical margin status. A significant variation in the frequency of IOC requests for margins among surgeons was noted. However, the use of frozen section analysis for intraoperative margin assessment was not significantly associated with the clearance rate of final post-operative margins. More frequent use of IOC did not result in higher final margin clearance rate, an important prognostic factor following Whipple procedure.

ABCC2 brush-border expression predicts outcome in papillary renal cell carcinoma: a multi-institutional study of 254 cases.

AIMS: Papillary renal cell carcinoma (PRCC) histologic subtyping is no longer recommended in the 2022 WHO classification. Currently, WHO/ISUP nucleolar grade is the only accepted prognostic histologic parameter for PRCC. ABCC2, a renal drug transporter, has been shown to significantly predict outcomes in PRCC. In this study we evaluated the prognostic significance of ABCC2 IHC staining patterns in a large, multi-institutional PRCC cohort and assessed the association of these patterns with ABCC2 mRNA expression. METHODS AND RESULTS: We assessed 254 PRCCs for ABCC2 IHC reactivity patterns that were stratified into negative, cytoplasmic, brush-border <50%, and brush-border ≥50%. RNA in situ hybridization (ISH) was used to determine the transcript level of each group. Survival analysis was performed with SPSS and GraphPad software. RNA-ISH showed that the ABCC2 group with any brush-border staining was associated with a significant increase in the transcript level, when compared to the negative/cytoplasmic group (P = 0.034). Both ABCC2 groups with brush-border <50% (P = 0.024) and brush-border ≥50% (P < 0.001) were also associated with worse disease-free survival (DFS) in univariate analysis. Multivariate analysis showed that only ABCC2 IHC brush-border (<50% and ≥50%) reactivity groups (P = 0.037 and P = 0.003, respectively), and high-stage disease (P < 0.001) had a DFS of prognostic significance. In addition, ABCC2 brush-border showed significantly worse DFS in pT1a (P = 0.014), pT1 (P = 0.013), ≤4 cm tumour (P = 0.041) and high stage (P = 0.014) groups, while a similar analysis with high WHO/ISUP grade in these groups was not significant. CONCLUSION: ABCC2 IHC brush-border expression in PRCC correlates with significantly higher gene expression and also independently predicts survival outcomes.

Post-traumatic Fungal Keratitis and Endophthalmitis Caused by Coniochaeta Hoffmannii with Late Recurrence following Therapeutic Full-thickness Penetrating Keratoplasty.

BACKGROUND: To report a rare case of fungal keratitis and endophthalmitis due to Coniochaeta hoffmannii. METHODS: Case report. RESULTS: A 71-year-old immunocompetent male sustained a corneal laceration, traumatic cataract, and retinal detachment due to penetrating injury from a nail pulled from a wooden deck. The patient's postoperative course was complicated by infectious keratitis. Fungal cultures, DNA sequencing and analysis of the internal transcribed spacer sequence confirmed Coniochaeta hoffmannii. Topical and oral voriconazole treatments were initiated; however, due to impending perforation, a therapeutic corneal transplant was required. One year later, the patient developed a new corneal infiltrate at the graft-host junction: Corneal scrapings were culture positive for Coniochaeta hoffmannii. This was treated with topical and intrastromal voriconazole along with oral itraconazole 200 mg once daily for 8 months. CONCLUSIONS: Coniochaeta hoffmannii may cause recalcitrant keratitis and endophthalmitis, which required longstanding antifungal treatment.

Porcine liver injury model to assess tantalum-containing bioactive glass powders for hemostasis.

This study evaluates compositions of tantalum-containing mesoporous bioactive glass (Ta-MBG) powders using a porcine fatal liver injury model. The powders based on (80-x)SiO2-15CaO-5P2O5-xTa2O5 compositions with x = 0 (0Ta/Ta-free), 1 (1Ta), and 5 (5Ta) mol% were made using a sol-gel process. A class IV hemorrhage condition was simulated on the animals; hemodynamic data and biochemical analysis confirmed the life-threatening condition. Ta-MBGs were able to stop the bleeding within 10 min of their application while the bleeds in the absence of any intervention or in the presence of a commercial agent, AristaTM (Bard Davol Inc., Rhode Island, USA) continued for up to 45 min. Scanning electron microscopy (SEM) imaging of the blood clots showed that the presence of Ta-MBGs did not affect clot morphology. Rather, the connections seen between fibrin fibers of the blood clot and Ta-MBG powders point towards the powders' surfaces embracing fibrin. Histopathological analysis of the liver tissue showed 5Ta as the only composition reducing parenchymal hemorrhage and necrosis extent of the tissue after their application. Additionally, 5Ta was also able to form an adherent clot in worst-case scenario bleeding where no adherent clot was seen before the powder was applied. In vivo results from the present study agree with in vitro results of the previous study that 5Ta was the best Ta-MBG composition for hemostatic purposes. Graphical abstract.

Tissue stress from laparoscopic grasper use and bowel injury in humans: establishing intraoperative force boundaries.

OBJECTIVES: We aim to determine what threshold of compressive stress small bowel and colon tissues display evidence of significant tissue trauma during laparoscopic surgery. DESIGN: This study included 10 small bowel and 10 colon samples from patients undergoing routine gastrointestinal surgery. Each sample was compressed with pressures ranging from 100 kPa to 600 kPa. Two pathologists who were blinded to all study conditions, performed a histological analysis of the tissues. Experimentation: November 2018-February 2019. Analysis: March 2019-May 2020. SETTING: An inner-city trauma and ambulatory hospital with a 40-bed inpatient general surgery unit with a diverse patient population. PARTICIPANTS: Patients were eligible if their surgery procured healthy tissue margins for experimentation (a convenience sample). 26 patient samples were procured; 6 samples were unusable. 10 colon and 10 small bowel samples were tested for a total of 120 experimental cases. No patients withdrew their consent. INTERVENTIONS: A novel device was created to induce compressive "grasps" to simulate those of a laparoscopic grasper. Experimentation was performed ex-vivo, in-vitro. Grasp conditions of 0-600 kPa for a duration of 10 s were used. RESULTS: Small bowel (10), M:F was 7:3, average age was 54.3 years. Colon (10), M:F was 1:1, average age was 65.2 years. All 20 patients experienced a significant difference (p<0.05) in serosal thickness post-compression at both 500 and 600 kPa for both tissue types. A logistic regression analysis with a sensitivity of 100% and a specificity of 84.6% on a test set of data predicts a safety threshold of 329-330 kPa. CONCLUSIONS: A threshold was discovered that corresponded to both significant serosal thickness change and a positive histological trauma score rating. This "force limit" could be used in novel sensorized laparoscopic tools to avoid intraoperative tissue injury.

A case of primary pulmonary Schizophyllum commune empyema treated with video-assisted thoracoscopic decortication.

Schizophyllum commune (S. commune) is an environmental basidiomycete bracket fungus that can rarely cause invasive fungal disease. Its diagnosis is challenging and often missed. We present a rare case of a 56-year-old diabetic gentleman with a 6-months history of progressive productive cough, small volume hemoptysis and non-resolving fungal empyema treated with video-assisted thoracoscopic decortication. Pulmonary infection of S. Commune is extremely rare and can manifest as complex fungal empyema. Close cooperation between respirologists, thoracic surgeons and microbiologists is critical in the diagnosis and treatment of such cases.

Defining the Relationship Between Compressive Stress and Tissue Trauma During Laparoscopic Surgery Using Human Large Intestine.

Excessive magnitudes of compressive stress exerted on gastrointestinal tissues can lead to pathological scar tissue or adhesion formation, bleeding, inflammation or even death from bowel perforation and sepsis. It is currently unknown however, at exactly what magnitude of compressive stress that these pathologies occur. A novel simple compressive device was engineered to provide an objective means of producing discrete compressive stresses on human tissues. Samples of human large intestine (colon) were removed from consenting patients as a part of their standard surgical procedure. These samples were compressed with a range of loads normally produced by standard laparoscopic graspers in representative abdominal surgeries. After compression, specimens were processed for histological analysis and assessed. The two independent pathologists who were blinded to stress magnitudes were both able to quantify increasing tissue damage that corresponded to increasing amounts of compressive force. A threshold between 350-450 kPa was discovered that corresponded to both significant serosal thickness change and a positive histological trauma score rating. Whether the tissue injury quantified is pathologic is subject for future in-vivo longitudinal investigation but certainly based on literature, can be the basis of pathological adhesion formation or an area for hemorrhage and scar formation.

Evaluating TNM stage prognostic ability in a population-based cohort of gastric adenocarcinoma patients in a low-incidence country.

OBJECTIVES: TNM stage is the preeminent cancer staging system and a fundamental determinant of disease prognosis. Our goal was to evaluate the predictive power of TNM stage for gastric adenocarcinoma (GAC), in a low-incidence country. METHODS: A province-wide chart review of GAC patients diagnosed from April 1, 2005 to March 31, 2008 was conducted in Ontario and linked to routinely collected vital status data with a follow-up on March 31, 2012. TNM staging was classified using the sixth and seventh Union International for Cancer Control/American Joint Committee on Cancer editions. Kaplan-Meier and log-rank tests compared stage-stratified survival estimates. Discrimination was evaluated using Harrell's C statistic. RESULTS: The cohort included 2366 patients. One- and 5-year survival was 43% and 17%. Using the sixth edition, 9% of patients had stage I disease, 5.4% stage II, 7.3% stage III, and 64% stage IV; 15% were not staged. Using the seventh edition, 9% were stage I, 7.7% stage II, 16% stage III, and 54% stage IV; 14% were not staged. Stage-stratified 5-year survival ranged from 68% to 7% with the sixth edition and from 70% to 4% with the seventh edition. Harrell's C statistic was 0.64 (0.63-0.65) for the broad sixth edition staging categories and 0.68 (0.67-0.69) for the broad seventh edition. Discriminative power was similar for the refined stage categories and across multiple subgroup analyses; it was best in non-metastatic patients. CONCLUSION: Existing staging systems for GAC used in North America predict individualized prognosis poorly. The creation of a more complex prediction tool is necessary to provide accurate and precise prognostication information to oncologists, patients, and their families.

Pedunculated polyp of the ileum protruding from a large diverticulum.

INTRODUCTION: A 52-year-old woman presented with iron deficiency anaemia and postprandial right lower quadrant pain. Abdominal examination was unremarkable and laboratory results showed mild anaemia (haemoglobin 11.3 g/dL). Upper and lower endoscopies did not reveal any source of bleeding. Video capsule endoscopy was performed which showed a large polypoid lesion in the mid-ileum (figure 1). Abdominal contrast enhanced CT demonstrated a heterogeneously enhancing pedunculated polyp measuring approximately 6 cm (figure 2). Retrograde double-balloon enteroscopy was performed which revealed a large pedunculated polyp with hyperplastic-like mucosa protruding from a large diverticulum located approximately 70 cm proximal to the ileocaecal valve (figure 3A). The stalk appeared to arise from the base of the diverticulum (figure 3B). A technetium-99m pertechnetate scintigraphy revealed no ectopic gastric mucosa.Figure 1Video capsule endoscopy shows a large polypoid lesion.Figure 2CT shows a heterogeneously enhancing pedunculated polyp (arrow).Figure 3Retrograde double-balloon enteroscopy images. (A) Large pedunculated polyp protruding from a large diverticulum. (B) The stalk appears to arise from the base of the diverticulum. QUESTION: What is the diagnosis?

The role of extended preoperative steroids in hearing preservation cochlear implantation.

INTRODUCTION: Steroids have been shown to reduce the hearing threshold shifts associated with cochlear implantation. Previous studies have examined only the administration of steroids just prior to surgery. The aim of this study is to examine the role of extended preoperative systemic steroids in hearing preservation cochlear implantation. METHODS: An animal model of cochlear implantation was used. 24 Hartley strain guinea pigs with a mean weight of 768 g and normal hearing were randomised into a control group, a second group receiving a single dose of systemic dexamethasone one day prior to surgery, and a third group receiving a daily dose of systemic dexamethasone for 5 days prior to surgery. A specially designed cochlear implant electrode by Med-EL (Innsbruck) was inserted through a dorsolateral approach to an insertion depth of 5 mm and left in-situ. Auditory brain stem responses at 8 kHz, 16 kHz and 32 kHz were measured preoperatively, and 1 week, 1 month and 2 months postoperatively. Cochlear histopathology was examined at the conclusion of the study. RESULTS: At 1-week post operative, both groups receiving dexamethasone prior to implantation had smaller threshold shifts across all frequencies and which was significant at 32 kHz (p < 0.05). There were no differences among the three groups in the area of electrode related fibrosis. Spiral ganglion neuron (SGN) density was significantly higher in the group receiving steroids for 5 days, but only in the basal cochlear turn. DISCUSSION: This is study demonstrates the benefits of extended preoperative systemic steroids on hearing outcomes and SGN density in an animal model of cochlear implantation surgery.

Consensus Recommendations for the Diagnosis and Management of Pancreatic Neuroendocrine Tumors: Guidelines from a Canadian National Expert Group.

Pancreatic neuroendocrine tumors (pNETs) are rare heterogeneous tumors that have been steadily increasing in both incidence and prevalence during the past few decades. Pancreatic NETs are categorized as functional (F) or nonfunctional (NF) based on their ability to secrete hormones that elicit clinically relevant symptoms. Specialized diagnostic tests are required for diagnosis. Treatment options are diverse and include surgical resection, intraarterial hepatic therapy, and peptide receptor radionuclide therapy (PRRT). Systemic therapy options include targeted agents as well as chemotherapy when indicated. Diagnosis and management should occur through a collaborative team of health care practitioners well-experienced in managing pNETs. Recent advances in pNET treatment options have led to the development of the Canadian consensus document described in this report. The discussion includes the epidemiology, classification, pathology, clinical presentation and prognosis, imaging and laboratory testing, medical and surgical management, and recommended treatment algorithms for pancreatic neuroendocrine cancers.

Analysis of addenda in anatomic pathology as a quality monitoring initiative.

CONTEXT: Along with the integration of immunohistochemical markers and molecular techniques into routine practice, addenda in surgical pathology reporting have not only increased in frequency but also evolved to include prognostic and therapeutic information. Because of the lack of uniform practice with respect to issuing addenda, information that can significantly change the diagnosis, prognosis, or treatment plan may be issued as an addendum as opposed to an amendment. OBJECTIVE: To audit addenda and identify instances of amendments masquerading as addenda. DESIGN: All addenda during a 36-month period were reviewed. Each addendum report was classified by accession class, issuing pathologist, subspecialty category, indication for addendum, whether the addendum constituted a change in diagnostic meaning, whether a change in prognosis occurred, and if a change in treatment plan was necessary. RESULTS: All cytology and autopsy addenda were deemed appropriate. Thirty-three of 5028 (6.5 of 1000) surgical pathology addenda were deemed to have changes: Among the 33 faux addenda, 30 (91%) contained supplemental diagnostic information that would alter patient management and 31 (94%) contained additional information that would change the prognosis from that entailed by the original diagnosis. CONCLUSIONS: Our study demonstrates that not infrequently, surgical pathology addenda contain information that significantly alters the report and thus merit an amendment. Quality monitoring initiatives that evaluate pathologist and departmental performance should assess both addenda and amendments.

A pathologist's survey on the reporting of sessile serrated adenomas/polyps.

AIM: The purpose of this survey was to ascertain reporting habits of pathologists towards sessile serrated adenomas/polyps (SSA/P). METHODS: A questionnaire designed to highlight diagnostic criteria, approach and clinical implications of SSA/P was circulated electronically to 45 pathologists in the UK and North America. RESULTS: Forty-three of 45 pathologists agreed to participate. The vast majority (88%) had a special interest in gastrointestinal (GI) pathology, had great exposure to GI polyps in general with 40% diagnosing SSA/P at least once a week if not more, abnormal architecture was thought by all participants to be histologically diagnostic, and 11% would make the diagnosis if a single diagnostic histological feature was present in one crypt only, while a further 19% would diagnose SSA/P in one crypt if more than one diagnostic feature was present. The vast majority agreed that deeper sections were useful and 88% did not feel proliferation markers were useful. More than one-third did not know whether, or did not feel that, their clinicians were aware of the implications of SSA/P. CONCLUSIONS: 98% of pathologists surveyed are aware that SSA/P is a precursor lesion to colorectal cancer, the majority agree on diagnostic criteria, and a significant number feel that there needs to be greater communication and awareness among pathologists and gastroenterologists about SSA/P.

Ki-67 is a reliable pathological grading marker for neuroendocrine tumors.

In neuroendocrine tumors (NETs), proliferation markers, especially Ki-67, have become increasingly important. This study was designed to examine the reproducibility of Ki-67 for use in the current classification of NETs. A retrospectively assembled integrated database with prospectively collected data of patients undergoing multidisciplinary management for NETs from 2000 to 2009 was analyzed. Original pathology was reviewed to reassess Ki-67 values. Ki-67 was then categorized to grades G1 (≤2 %), G2 (3-20 %), or G3 (>20 %) according to the European Neuroendocrine Tumor Society (ENETS) guidelines and the 2010 World Health Organization (WHO) classification. Original Ki-67 values were compared to reviewed values. All statistical analyses were carried out using SAS 9.1.3. A total of 184 patients were included of which 48 % were male. The most common primary NET site was the small bowel, in 27 %. On pathology review, there was 94 % agreement for G1, with 4 % of cases upgraded at review to G2 and 2 % of cases upgraded to G3. For G2, there was 94 % agreement, with 6 % of cases downgraded to G1 and 0 % upgraded. For G3, there was 90 % agreement, with 10 % of cases downgraded to G2 and none to G1 (kappa = 0.89). Ki-67 is a proliferative marker for NETs that is highly reproducible when used to grade tumors according to ENETS and WHO categories. The high inter-institutional reliability in the determination of tumor grade as assessed by Ki-67 makes it a reliable tool in the assessment of patients with NETs.

Management of Metastatic Solid Pseudopapillary Cancer of the Pancreas: A Case Report.

Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms predominantly found in females. The tumors are often histologically benign and patient outcomes are correspondingly favorable. This report presents the case of a 21-year-old woman who presented with metachronous metastatic SPT, and details the diagnosis and management of this patient. The patient underwent a distal pancreatectomy for resection of the primary neoplasm with negative margins. A surveillance ultrasound performed at 43 months post-operatively revealed new hepatic lesions; these lesions were surgically resected and pathologically demonstrated to be metastatic SPT of the pancreas. This case report demonstrates the potential for latent metastasis of resected SPT, imaging characteristics of metastatic disease, the need for surveillance of patients following resection of SPT of the pancreas and a review of relevant literature on SPT.

Hybrid intravascular ultrasound and optical coherence tomography catheter for imaging of coronary atherosclerosis.

OBJECTIVE: To demonstrate the feasibility of imaging human coronary atherosclerosis using a novel hybrid intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging catheter. BACKGROUND: IVUS and OCT have synergistic advantages and recent studies involving both modalities suggest the use of a hybrid imaging catheter may offer improved guidance of coronary interventions and plaque characterization. METHODS: A 1.3 m custom hybrid IVUS-OCT imaging probe was built within a 4F catheter using a 42 MHz ultrasound transducer and an OCT imaging fiber. Coplanar images were simultaneously acquired ex vivo by both modalities in 31 arterial segments from 11 cadaveric human coronaries. IVUS and OCT images were acquired at 250 µm intervals, of which 13 of the arterial segments were selected as representative of a diverse set of pathological findings. The selected segments were then imaged with either digital X-ray or micro-CT, processed for histological analysis and compared with the corresponding IVUS and OCT images. RESULTS: Images of human coronary atherosclerosis using the hybrid IVUS-OCT catheter demonstrated a range of vascular pathologies that were confirmed on histology. The anticipated synergistic advantages of each modality were qualitatively apparent, including the deeper tissue penetration of IVUS and the superior contrast, resolution and near-field image quality of OCT. CONCLUSIONS: Preliminary ex vivo images using a hybrid IVUS-OCT catheter demonstrated feasibility in using the device for intracoronary imaging of atherosclerosis. Future studies will include in vivo imaging and larger samples sizes to enable quantitative comparisons of tissue characterization and feature identification using hybrid imaging catheters versus standalone IVUS and OCT imaging techniques. © 2012 Wiley Periodicals, Inc.