Oncogenic Fatty Acid Metabolism Rewires Energy Supply Chain in Gastric Carcinogenesis.

BACKGROUND & AIMS: Gastric carcinogenesis develops within a sequential carcinogenic cascade from precancerous metaplasia to dysplasia and adenocarcinoma, and oncogenic gene activation can drive the process. Metabolic reprogramming is considered a key mechanism for cancer cell growth and proliferation. However, how metabolic changes contribute to the progression of metaplasia to dysplasia remains unclear. We have examined metabolic dynamics during gastric carcinogenesis using a novel mouse model that induces Kras activation in zymogen-secreting chief cells. METHODS: We generated a Gif-rtTA;TetO-Cre;KrasG12D (GCK) mouse model that continuously induces active Kras expression in chief cells after doxycycline treatment. Histologic examination and imaging mass spectrometry were performed in the GCK mouse stomachs at 2 to 14 weeks after doxycycline treatment. Mouse and human gastric organoids were used for metabolic enzyme inhibitor treatment. The GCK mice were treated with a stearoyl- coenzyme A desaturase (SCD) inhibitor to inhibit the fatty acid desaturation. Tissue microarrays were used to assess the SCD expression in human gastrointestinal cancers. RESULTS: The GCK mice developed metaplasia and high-grade dysplasia within 4 months. Metabolic reprogramming from glycolysis to fatty acid metabolism occurred during metaplasia progression to dysplasia. Altered fatty acid desaturation through SCD produces a novel eicosenoic acid, which fuels dysplastic cell hyperproliferation and survival. The SCD inhibitor killed both mouse and human dysplastic organoids and selectively targeted dysplastic cells in vivo. SCD was up-regulated during carcinogenesis in human gastrointestinal cancers. CONCLUSIONS: Active Kras expression only in gastric chief cells drives the full spectrum of gastric carcinogenesis. Also, oncogenic metabolic rewiring is an essential adaptation for high-energy demand in dysplastic cells.

Xenogeneic cross-circulation for physiological support and recovery of ex vivo human livers.

BACKGROUND AND AIMS: The scarcity of suitable donor livers highlights a continuing need for innovation to recover organs with reversible injuries in liver transplantation. APPROACH AND RESULTS: Explanted human donor livers (n = 5) declined for transplantation were supported using xenogeneic cross-circulation of whole blood between livers and xeno-support swine. Livers and swine were assessed over 24 hours of xeno-support. Livers maintained normal global appearance, uniform perfusion, and preservation of histologic and subcellular architecture. Oxygen consumption increased by 75% ( p = 0.16). Lactate clearance increased from -0.4 ± 15.5% to 31.4 ± 19.0% ( p = 0.02). Blinded histopathologic assessment demonstrated improved injury scores at 24 hours compared with 12 hours. Vascular integrity and vasoconstrictive function were preserved. Bile volume and cholangiocellular viability markers improved for all livers. Biliary structural integrity was maintained. CONCLUSIONS: Xenogeneic cross-circulation provided multisystem physiological regulation of ex vivo human livers that enabled functional rehabilitation, histopathologic recovery, and improvement of viability markers. We envision xenogeneic cross-circulation as a complementary technique to other organ-preservation technologies in the recovery of marginal donor livers or as a research tool in the development of advanced bioengineering and pharmacologic strategies for organ recovery and rehabilitation.

Single-Cell Transcriptomics Reveals a Conserved Metaplasia Program in Pancreatic Injury.

BACKGROUND & AIMS: Acinar to ductal metaplasia (ADM) occurs in the pancreas in response to tissue injury and is a potential precursor for adenocarcinoma. The goal of these studies was to define the populations arising from ADM, the associated transcriptional changes, and markers of disease progression. METHODS: Acinar cells were lineage-traced with enhanced yellow fluorescent protein (EYFP) to follow their fate post-injury. Transcripts of more than 13,000 EYFP+ cells were determined using single-cell RNA sequencing (scRNA-seq). Developmental trajectories were generated. Data were compared with gastric metaplasia, KrasG12D-induced neoplasia, and human pancreatitis. Results were confirmed by immunostaining and electron microscopy. KrasG12D was expressed in injury-induced ADM using several inducible Cre drivers. Surgical specimens of chronic pancreatitis from 15 patients were evaluated by immunostaining. RESULTS: scRNA-seq of ADM revealed emergence of a mucin/ductal population resembling gastric pyloric metaplasia. Lineage trajectories suggest that some pyloric metaplasia cells can generate tuft and enteroendocrine cells (EECs). Comparison with KrasG12D-induced ADM identifies populations associated with disease progression. Activation of KrasG12D expression in HNF1B+ or POU2F3+ ADM populations leads to neoplastic transformation and formation of MUC5AC+ gastric-pit-like cells. Human pancreatitis samples also harbor pyloric metaplasia with a similar transcriptional phenotype. CONCLUSIONS: Under conditions of chronic injury, acinar cells undergo a pyloric-type metaplasia to mucinous progenitor-like populations, which seed disparate tuft cell and EEC lineages. ADM-derived EEC subtypes are diverse. KrasG12D expression is sufficient to drive neoplasia when targeted to injury-induced ADM populations and offers an alternative origin for tumorigenesis. This program is conserved in human pancreatitis, providing insight into early events in pancreas diseases.

Peak density of immature nerve cells occurs with high-grade dysplasia in intraductal papillary mucinous neoplasms of the pancreas.

The development of neural structures within tumors is now considered vital for carcinogenesis. However, the time course of this development in human pre-invasive neoplasia has been incompletely described. Therefore, we performed a detailed analysis of nerves across the neoplastic spectrum in resected intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Histology and multiplexed immunochemistry demonstrated that nerve density increased from low-grade (LG) to high-grade dysplasia (HG) but did not further increase once invasive IPMN (INV IPMN) was present. Higher nerve density correlated with increasing expression of nerve growth factor (NGF) by the tumor cells. Intra-tumoral nerves were immature and lacked markers of sympathetic, parasympathetic, and sensory lineages. Here, we show for the first time the presence of neural precursor cells (NPCs) within the stroma of pancreatic tumors. The density of these doublecortin (DCX)-positive NPCs increased from LG to HG, but not from HG to INV IPMN. We conclude that peak neural density of tumors is reached in high-grade dysplasia (often termed carcinoma in situ) rather than after invasion. These findings suggest that nerve-tumor interactions are important in IPMN progression and may serve as the basis for future mechanistic studies and novel therapeutic modalities. © 2022 The Pathological Society of Great Britain and Ireland.

The use of natural language processing in detecting and predicting falls within the healthcare setting: a systematic review.

Falls are a common problem associated with significant morbidity, mortality, and economic costs. Current fall prevention policies in local healthcare settings are often guided by information provided by fall risk assessment tools, incident reporting, and coding data. This review was conducted with the aim of identifying studies which utilized natural language processing (NLP) for the automated detection and prediction of falls in the healthcare setting. The databases Ovid Medline, Ovid Embase, Ovid Emcare, PubMed, CINAHL, IEEE Xplore, and Ei Compendex were searched from 2012 until April 2023. Retrospective derivation, validation, and implementation studies wherein patients experienced falls within a healthcare setting were identified for inclusion. The initial search yielded 2611 publications for title and abstract screening. Full-text screening was conducted on 105 publications, resulting in 26 unique studies that underwent qualitative analyses. Studies applied NLP towards falls risk factor identification, known falls detection, future falls prediction, and falls severity stratification with reasonable success. The NLP pipeline was reviewed in detail between studies and models utilizing rule-based, machine learning (ML), deep learning (DL), and hybrid approaches were examined. With a growing literature surrounding falls prediction in both inpatient and outpatient environments, the absence of studies examining the impact of these models on patient and system outcomes highlights the need for further implementation studies. Through an exploration of the application of NLP techniques, it may be possible to develop models with higher performance in automated falls prediction and detection.

DEVIL, VAAD and vLSC constitute a spectrum of HPV-independent, p53-independent intra-epithelial neoplasia of the vulva.

AIMS: We aimed to characterise a large cohort of non-invasive, human papillomavirus (HPV) and p53-independent verruciform lesions, such as 'vulvar acanthosis with altered differentiation' (VAAD), 'differentiated exophytic vulvar intra-epithelial lesion' (DEVIL) and 'verruciform lichen simplex chronicus' (vLSC). METHODS AND RESULTS: From January 2008 to December 2020 we retrospectively identified 36 eligible patients with verruciform non-invasive lesions (n = 36) and collected clinical, histological and follow-up parameters. Verruciform non-invasive lesions occurred at a median age of 71 years, with a median follow-up of 33.5 months. Clinically, pruritus was only reported in patients with VAAD (n = 3, 21%). Lesion colour was significantly different across categories (P = 0.028). Apart from the histopathological criteria already known to distinguish these entities (hypogranulosis, epithelial pallor and low-magnification architecture), no other significant criteria were discovered and significant overlap was observed, particularly between VAAD and DEVIL. Patients with vLSC trended towards longer survival without recurrence compared to VAAD and DEVIL (P = 0.082), but showed comparable invasion-free survival interval (P = 0.782). Squamous cell carcinomas (SCC) associated with either VAAD, DEVIL or vLSC displayed similar clinical, histopathological and biological parameters. In non-invasive precursor lesions, stromal oedema was associated with invasion (P = 0.015) and remained so upon Cox regression analysis (P = 0.009). CONCLUSION: Our study of HPV and p53 independent non-invasive verruciform lesions of the vulva highlights significant clinical, histopathological and biological overlap between VAAD, DEVIL and vLSC, suggesting that these pre-invasive lesions should be viewed as a spectrum. We also show that stromal features such as oedema might play an import role in progression to invasion.

Age, operation time and surgical approach can be used to detect incidental gallbladder carcinoma in cholecystectomy specimens from low-incidence settings.

AIMS: Gallbladders resected for non-neoplastic diseases are systemically examined microscopically to rule out incidental dysplasia and carcinoma. The main aim of this study was to test whether a pre-grossing algorithm can detect incidental gallbladder carcinoma. The secondary aim was to test whether the algorithm can detect high-grade dysplasia. METHODS AND RESULTS: A retrospective study of clinical, pathological and radiological findings in cholecystectomy recipients was performed on a test set to develop a classification and regression tree algorithm. Cholecystectomy cases were included; exclusion criteria were age <18 years, missing pathology reports, preoperative suspicion of neoplastic disease, and cholecystectomy for non-gallbladder oncological disease. Five thousand nine hundred and eighty-two cholecystectomies from 2006 to 2018 were included in the study, with 18 cases of incidental gallbladder carcinoma and 11 cases of high-grade dysplasia. Three hundred and ninety controls were randomly selected for the testing set. Patient age, surgical approach, operation duration, dilatation of the biliary tract and gallbladder gross anomalies were statistically significant distinguishing factors in multivariate analysis (P < 0.00-0.026). Unsupervised testing with a conditional inference tree suggested that age, procedure type and operation duration can be used to identify incidental gallbladder carcinoma from controls, whereas high-grade dysplasia also requires grossing parameters to identify half of the cases (5/11). CONCLUSION: Readily available clinical parameters and postoperative data can be used to detect incidental gallbladder carcinoma. High-grade dysplasia mostly requires grossing and microscopic examination.

Gastric neuroendocrine tumours from long-term proton pump inhibitor users are indolent tumours with good prognosis.

AIMS: Proton pump inhibitors (PPIs) are among the most widely used medications in the United States. Most PPI users have persistent hypergastrinaemia during treatment. However, gastric neuroendocrine tumours diagnosed in long-term PPI users are rarely reported. Their clinicopathological features and prognosis are not characterised. It remains unclear whether or not they can be classified as Type III sporadic tumours. METHODS AND RESULTS: We retrospectively characterised 66 gastric neuroendocrine tumours from patients without atrophic gastritis and gastrinoma from two tertiary care medical centres, including 38 tumours in patients who had used PPIs for at least 1 year and 28 tumours from patients without long-term PPI use (control group, Type III tumours). Compared to controls, tumours from long-term PPI users tended to be in the pT1-2 category (98% versus 79%, P = 0.09) and less often invaded the serosa (3% versus 18%, P = 0.08) or lymphovascular spaces (11% versus 32%, P = 0.06). Using Kaplan-Meier analysis, long-term PPI users had significantly longer overall survival than controls (P = 0.035). While three control patients developed distant metastasis and seven died, long-term PPI users were without distant metastasis (P = 0.06) or death (P = 0.002) during follow-up. However, five long-term PPI users developed additional gastric neuroendocrine tumour(s), while none of the controls did (P = 0.07). CONCLUSIONS: Our results show that gastric neuroendocrine tumours of long-term PPI users are probably less aggressive compared to Type III sporadic tumours and have an indolent disease course. Our findings support the classification of gastric neuroendocrine tumours in long-term PPI users as a separate subtype.

Distinct Histologic, Immunohistochemical and Clinical Features Associated With Serous Endometrial Intraepithelial Carcinoma Involving Polyps.

The origin of serous endometrial intraepithelial carcinoma (SEIC) is debated, due to its premalignant and independently malignant nature. It often arises next to endometrial serous carcinoma (ESC), with a propensity for polypoid growth. We aimed to better characterize this discrepancy by analyzing the clinical, histologic, and immunohistochemical features of polypoid carcinoma associated with SEIC (P-SEIC), and compared them with usual endometrial serous carcinoma without SEIC (UESC). Consecutive patients with P-SEIC were recruited and compared with UESC controls from our institutional research center. Clinical, histologic, and immunohistochemical (IHC, ER, PR, P53, Napsin-A, WT1, P16) were analyzed. BRCA testing results and familial history were also extracted from clinical databases. Welch T test, Pearson χ, and Fisher exact test were performed in SPSS version 23. A total of 37 P-SEIC and 25 UESC were the basis of a case-control study. P-SEIC was associated with more bilateral ovarian involvement (P=0.026), yet showed lower rates of myometrial invasion (P=0.002). P-SEIC showed a statistically different IHC profile: p53+, p16+, ER+, PR+, and WT-1+, and high rates of Napsin-A, while UESC was p53+, p16+, WT-1-, Napsin-A-, with lower rates of ER and PR. We also identified 2 patients who received prophylactic salpingo-oophorectomy for BRCA mutations and who subsequently developed P-SEIC with its unique IHC pattern. Our results suggest different underlying expression profiles and possibly diverging molecular signatures between both P-SEIC and UESC. If confirmed in further molecular studies, it could lead to a distinct molecular subclass.

The impact of intraductal carcinoma of the prostate on the site and timing of recurrence and cancer-specific survival.

BACKGROUND: To investigate the effect of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens in the context of the site of recurrence, time to recurrence, and cancer-specific survival in two academic cohorts of locally, regionally, or distantly recurrent prostate cancer. METHODS: Our cohort included men enrolled into two academic tissue repositories from 1993 to 2011, who were treated with first-line RP who later experienced local recurrence, regional recurrence, or distant metastasis (together termed clinical recurrence, CR). RP material was reviewed to identify IDC-P and to update grading to current standards. The primary endpoint was the initial location of CR. Secondary endpoints included time to CR and cancer-specific survival. Pearson's chi-square, Welch's t-test, Mann-Whitney U test and Fisher's exact test were performed for univariate analyses. Multinomial logistic regression was used for multivariate analyses. Cancer-specific survival was analyzed with the generalized Wilcoxon test and Cox regression. RESULTS: Eighty-five patients with CR were included in the analysis. IDC-P was present in 78.5% of patients from Center 1 and 70.0% from Center 2 (P = 0.547). IDC-P was independently associated with distant metastasis at initial CR (multivariate odds ratio = 6.27, P = 0.015). IDC-P status did not affect time to recurrence; median survival without recurrence was at 53 months for IDC-P(+) and at 50 months for IDC-P(-) (P = 0.441). Distant metastases at the initial CR event had a 36% reduction of cancer-specific survival compared to local recurrences (P = 0.007). Additionally, prostatic-bed radiotherapy (adjuvant or salvage for biochemical recurrence before distant metastasis) was associated with a 25% reduction in cancer-specific mortality compared to no radiotherapy (P = 0.023). Similar reduction in cancer-specific mortality was observed in the subgroup of patients with distant metastasis and IDC-P when treated with radiotherapy (29%, P = 0.050). CONCLUSIONS: In our cohort, presence of IDC-P was an independent factor for distant metastasis at initial CR, but did not have a significant impact on time to CR. Furthermore, metastatic patients showed statistically reduced cancer-specific mortality when treated with radiotherapy. This reduction in cancer-specific mortality was also identified in patients with IDC-P. Future large scale validation studies should take into account the presence of IDC-P and confirm its impact on disease progression.

Mesoscopic characterization of prostate cancer using Raman spectroscopy: potential for diagnostics and therapeutics.

OBJECTIVE: To test if Raman spectroscopy (RS) is an appropriate tool for the diagnosis and possibly grading of prostate cancer (PCa). PATIENTS AND METHODS: Between 20 and 50 Raman spectra were acquired from 32 fresh and non-processed post-prostatectomy specimens using a macroscopic handheld RS probe. Each measured area was characterized and categorized according to histopathological criteria: tissue type (extraprostatic or prostatic); tissue malignancy (benign or malignant); cancer grade (Grade Groups [GGs] 1-5); and tissue glandular level. The data were analysed using machine-learning classification with neural network. RESULTS: The RS technique was able to distinguish prostate from extraprostatic tissue with a sensitivity of 82% and a specificity of 83% and benign from malignant tissue with a sensitivity of 87% and a specificity of 86%. In an exploratory fashion, RS differentiated benign from GG1 in 726/801 spectra (91%; sensitivity 80%, specificity 91%), from GG2 in 588/805 spectra (73%; sensitivity 76%, specificity 73%), from GG3 in 670/797 spectra (84%; sensitivity 86%, specificity 84%), from GG4 in 711/802 spectra (88%; sensitivity 77%, specificity 89%) and from GG5 in 729/818 spectra (89%; sensitivity 90%, specificity 89%). CONCLUSION: Current diagnostic approaches of PCa using needle biopsies have suboptimal cancer detection rates and a significant risk of infection. Standard non-targeted random sampling results in false-negative biopsies in 15-30% of patients, which affects clinical management. RS, a non-destructive tissue interrogation technique providing vibrational molecular information, resolved the highly complex architecture of the prostate and detect cancer with high accuracy using a fibre optic probe to interrogate radical prostatectomy (RP) specimens from 32 patients (947 spectra). This proof-of-principle paves the way for the development of in vivo tumour targeting spectroscopy tools for informed biopsy collection to address the clinical need for accurate PCa diagnosis and possibly to improve surgical resection during RP as a complement to histopathological analysis.

Wound dehiscence in a sample of 1 776 cystectomies: identification of predictors and implications for outcomes.

OBJECTIVE: To investigate the incidence and predictors of wound dehiscence in patients undergoing radical cystectomy (RC). PATIENTS AND METHODS: In all, 1 776 patient records with Current Procedural Terminology (CPT) codes for radical cystectomy (RC) were extracted from the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) between 2005 and 2012. Stratification was made based on the occurrence of postoperative wound dehiscence, defined as loss of integrity of fascial closure. Descriptive and logistic regression models were used to identify predictors of postoperative wound dehiscence. The implications of wound dehiscence on peri- and postoperative outcomes such as complications, mortality, prolonged length of stay (>11 days), and prolonged operative time (>411 min), were assessed. RESULTS: Of 1 776 patients analysed, 57 (3.2%) had a documented wound dehiscence. In multivariable analyses, chronic obstructive pulmonary disease (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.0-4.0; P = 0.03) and high body mass index (OR 2.3, 95% CI 1.3-4.4; P = 0.008) were significant predictors of wound dehiscence. While female gender had significantly lower proportions of wound dehiscence, multivariable analyses did not confirm this (OR 0.4, 95% CI 0.4-1.4; P = 0.75). CONCLUSIONS: Our study is the first to identify predictors of wound dehiscence after RC in a large, contemporary multi-institutional cohort. Identifying patients at risk of postoperative wound complications may guide the use of preventative measures at the time of surgery.

Racial disparities in operative outcomes after major cancer surgery in the United States.

BACKGROUND: Numerous studies have recorded racial disparities in access to care for major cancers. We investigate contemporary national disparities in the quality of perioperative surgical oncological care using a nationally representative sample of American patients and hypothesize that disparities in the quality of surgical oncological care also exists. METHODS: A retrospective, serial, and cross-sectional analysis of a nationally representative cohort of 3,024,927 patients, undergoing major surgical oncological procedures (colectomy, cystectomy, esophagectomy, gastrectomy, hysterectomy, pneumonectomy, pancreatectomy, and prostatectomy), between 1999 and 2009. RESULTS: After controlling for multiple factors (including socioeconomic status), Black patients undergoing major surgical oncological procedures were more likely to experience postoperative complications (OR: 1.24; p < 0.001), in-hospital mortality (OR: 1.24; p < 0.001), homologous blood transfusions (OR: 1.52; p < 0.001), and prolonged hospital stay (OR: 1.53; p < 0.001). Specifically, Black patients have higher rates of vascular (OR: 1.24; p < 0.001), wound (OR: 1.10; p = 0.004), gastrointestinal (OR: 1.38; p < 0.001), and infectious complications (OR: 1.29; p < 0.001). Disparities in operative outcomes were particularly remarkable for Black patients undergoing colectomy, prostatectomy, and hysterectomy. Importantly, substantial attenuation of racial disparities was noted for radical cystectomy, lung resection, and pancreatectomy relative to earlier reports. Finally, Hispanic patients experienced no disparities relative to White patients in terms of in-hospital mortality or overall postoperative complications for any of the eight procedures studied. CONCLUSIONS: Considerable racial disparities in operative outcomes exist in the United States for Black patients undergoing major surgical oncological procedures. These findings should direct future health policy efforts in the allocation of resources for the amelioration of persistent disparities in specific procedures.

The health care burden of skeletal related events in patients with renal cell carcinoma and bone metastasis.

PURPOSE: We examined temporal trends in skeletal related events and associated charges in patients with renal cell carcinoma metastatic to bone. We also identified patient and hospital characteristics associated with skeletal related events and related mortality. MATERIALS AND METHODS: Using the Nationwide Inpatient Sample we abstracted data on patients with renal cell carcinoma who were diagnosed with concomitant bone metastasis between 1998 and 2010. Patients who experienced a skeletal related event were identified and hospital charges were calculated. Multivariate regression models fitted with generalized estimating equations were used to examine predictors of skeletal related events and related in-hospital mortality. RESULTS: Between 1998 and 2010 a weighted estimate of 144,889 renal cell carcinoma hospital visits of patients with bone metastasis was identified in the Nationwide Inpatient Sample, of which 20.8% involved a skeletal related event. In these cases from 1998 to 2010 the inflation adjusted mean yearly costs associated with hospital admission increased by 207% in 2013 United States dollars (estimated annual percent change 8.94%, p<0.001). Conversely, the rates of skeletal related events and skeletal related event associated mortality decreased significantly (estimated annual percent change -1.11% and -2.9%, respectively, each p<0.001). CONCLUSIONS: The prevalence and in-hospital mortality of skeletal related event associated hospitalization for metastatic renal cell carcinoma is decreasing but such charges to health care in the United States are increasing at an alarming rate. These findings highlight the need for cost-effective treatment strategies to prevent or treat these morbid complications.

Radical cystectomy in the elderly: national trends and disparities in perioperative outcomes and quality of care.

INTRODUCTION: To examine national trends of radical cystectomy (RC) for urothelial carcinoma of urinary bladder in octogenarian patients and to assess the rates of adverse outcomes. MATERIALS AND METHODS: Within the Nationwide Inpatient Sample (NIS), we focused on RCs performed between 1998 and 2007. Age was stratified as <80 versus ≥80 years. Propensity-based matched analyses were used to account for treatment selection biases. Generalized linear regression analyses were fitted to predict adverse perioperative events according to age. RESULTS: Of 12,274 RC patients, 1,605 were ≥80 years (13.1%). The RC rates in octogenarians increased significantly from 9.9% in 1998 to 13.7% in 2007. Most elderly patients were treated at low-/intermediate-volume hospitals (81.7%) and nonacademic centers (60.6%). After propensity score matching, the inpatient mortality rate was higher in octogenarians (4.6 vs. 2.6%, p < 0.001). In multivariable analyses, octogenarians were at increased risk of blood transfusions (OR: 1.30) and postoperative complications (OR: 1.22). CONCLUSIONS: Most octogenarians undergoing RC are treated at low-/intermediate-volume hospitals and at nonacademic centers. The inpatient hospital mortality is about twice as high in these patients, and adverse perioperative outcomes are more frequent. Such patients may benefit from RC at high-volume and/or academic centers to maximally reduce adverse perioperative outcomes.

Is there any evidence of a "July effect" in patients undergoing major cancer surgery?

BACKGROUND: The "July effect" refers to the phenomenon of adverse impacts on patient care arising from the changeover in medical staff that takes place during this month at academic medical centres in North America. There has been some evidence supporting the presence of the July effect, including data from surgical specialties. Uniformity of care, regardless of time of year, is required for patients undergoing major cancer surgery. We therefore sought to perform a population-level assessment for the presence of a July effect in this field. METHODS: We used the Nationwide Inpatient Sample to abstract data on patients undergoing 1 of 8 major cancer surgeries at academic medical centres between Jan. 1, 1999, and Dec. 30, 2009. The primary outcomes examined were postoperative complications and in-hospital mortality. Univariate analyses and subsequently multivariate analyses, controlling for patient and hospital characteristics, were performed to identify whether the time of surgery was an independent predictor of outcome after major cancer surgery. RESULTS: On univariate analysis, the overall postoperative complication rate, as well as genitourinary and hematologic complications specifically, was higher in July than the rest of the year. However, on multivariate analysis, only hematologic complications were significantly higher in July, with no difference in overall postoperative complication rate or in-hospital mortality for all 8 surgeries considered separately or together. CONCLUSION: On the whole, the data confirm an absence of a July effect in patients undergoing major cancer surgery.

CONTEXTE: L'effet « juillet ¼ désigne les répercussions négatives que peut avoir sur les soins aux patients le roulement du personnel médical qui survient au cours de ce mois d'été dans les centres médicaux universitaires d'Amérique du Nord. Certaines preuves ont étayé l'existence de l'effet juillet, notamment des données provenant des spéciali tés chirurgicales. Peu importe le temps de l'année, l'uniformité des soins est indispensable pour les patients qui doivent subir des interventions chirurgicales majeures pour le cancer. Nous avons donc voulu effectuer une évaluation à l'échelle des populations au sujet de l'existence d'un effet juillet dans cette branche de la médecine. MÉTHODES: Nous avons utilisé la base de données Nationwide Inpatient Sample pour extraire les données relatives aux patients soumis à l'une de 8 interventions chirurgicales majeures pour le cancer dans des centres médicaux universitaires entre le 1er janvier 1999 et le 30 décembre 2009. Les principaux paramètres examinés ont été les complications postopératoires et la mortalité perhospitalière. Nous avons effectué des analyses univariées et, par la suite, des analyses multivariées en tenant compte des caractéristiques des patients et des hôpitaux afin de vérifier si la date à laquelle la chirurgie a eu lieu était un prédicteur indépendant des résultats après une chirurgie majeure pour le cancer. RÉSULTATS: L'analyse univariée a révélé que les taux de complications postopératoires globales et de complications des interventions urogénitales et hématologiques plus spécifiquement ont été plus élevés en juillet qu'à d'autres moments de l'année. Toutefois, à l'analyse multivariée, seules les complications des suites d'interventions pour un cancer hématologique ont été significativement plus élevées en juillet, sans différence au plan du taux de complications postopératoires globales ou du taux de mortalité perhospitalière pour les 8 interventions considérées séparément ou ensemble. CONCLUSION: Globalement, les données confirment l'absence d'un effet juillet chez les patients soumis à une intervention chirurgicale majeure pour un cancer.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, a two cases report.

INTRODUCTION AND IMPORTANCE: Fine needle aspiration is the standard method for the pathological evaluation of pancreatic masses. In the following context, rare variants of such masses might present a challenge. Our goal is to describe the clinical, cytological, and histological findings of two cases of undifferentiated carcinoma with osteoclast-like giant cells (UCOCGC) a rare variant of pancreatic ductal adenocarcinoma (PDAC). CASE PRESENTATION: Two cases were identified. Cytological findings exhibit similarities between the two cases. One patient received multiple chemotherapy regimens and a surgery and recurred within three years of diagnosis, while the other succumbed to cholangitis resulting from hepatic metastases a year after their initial surgery. DISCUSSION: UCOCGC is a rare variant of pancreatic cancer, characterized by a unique cytological aspect. Recognizing this variant is essential considering its distinct prognosis compared to usual pancreatic adenocarcinoma. CONCLUSION: We presented two cases of UCOCGC a rare pancreatic cancer variant, exposing diagnostic particularities and clinical evolution.

Impact of Transfer Learning Using Local Data on Performance of a Deep Learning Model for Screening Mammography.

Purpose To investigate the issues of generalizability and replication of deep learning models by assessing performance of a screening mammography deep learning system developed at New York University (NYU) on a local Australian dataset. Materials and Methods In this retrospective study, all individuals with biopsy or surgical pathology-proven lesions and age-matched controls were identified from a South Australian public mammography screening program (January 2010 to December 2016). The primary outcome was deep learning system performance-measured with area under the receiver operating characteristic curve (AUC)-in classifying invasive breast cancer or ductal carcinoma in situ (n = 425) versus no malignancy (n = 490) or benign lesions (n = 44). The NYU system, including models without (NYU1) and with (NYU2) heatmaps, was tested in its original form, after training from scratch (without transfer learning), and after retraining with transfer learning. Results The local test set comprised 959 individuals (mean age, 62.5 years ± 8.5 [SD]; all female). The original AUCs for the NYU1 and NYU2 models were 0.83 (95% CI: 0.82, 0.84) and 0.89 (95% CI: 0.88, 0.89), respectively. When NYU1 and NYU2 were applied in their original form to the local test set, the AUCs were 0.76 (95% CI: 0.73, 0.79) and 0.84 (95% CI: 0.82, 0.87), respectively. After local training without transfer learning, the AUCs were 0.66 (95% CI: 0.62, 0.69) and 0.86 (95% CI: 0.84, 0.88). After retraining with transfer learning, the AUCs were 0.82 (95% CI: 0.80, 0.85) and 0.86 (95% CI: 0.84, 0.88). Conclusion A deep learning system developed using a U.S. dataset showed reduced performance when applied "out of the box" to an Australian dataset. Local retraining with transfer learning using available model weights improved model performance. Keywords: Screening Mammography, Convolutional Neural Network (CNN), Deep Learning Algorithms, Breast Cancer Supplemental material is available for this article. © RSNA, 2024 See also commentary by Cadrin-Chênevert in this issue.