Current Guidelines Research Articles

Low-Volume Metastases in Cervical Cancer: Does Size Matter?

The implementation of sentinel lymph node (SLN) biopsy is changing the scenario in the surgical treatment of early-stage cervical cancer, and the oncologic safety of replacing bilateral pelvic lymphadenectomy with SLN biopsy is currently under investigation. Part of the undisputed value of SLN biopsy is its diagnostic accuracy in detecting low-volume metastases (LVM) via pathologic ultrastaging. In early-stage cervical cancer, the reported incidence of LVM ranges from 4 to 20%. The prognostic impact and the role of adjuvant treatment in patients with LVM is still unclear. Some non-prespecified analyses in prospective studies showed no impact on the oncologic outcomes compared to node-negative disease. However, the heterogeneity of the studies, the differences in the disease stage and the use of adjuvant treatment, and the concomitant pelvic lymphadenectomy (PLND) make reaching any conclusions on this topic hard. Current guidelines suggest considering micrometastases (MIC) as a node-positive disease, while considering isolated tumor cells (ITC) as a node-negative disease with a low level of evidence. This review aims to highlight the unanswered questions about the definition, identification, and prognostic and therapeutic roles of LVM and to underline the present and future challenges we are facing. We hope that this review will guide further research, giving robust evidence on LVM and their impacts on clinical practice.

Relationship of Mild to Moderate Impairment of Left Ventricular Ejection Fraction With Fatal Ventricular Arrhythmic Events in Cardiac Sarcoidosis.

Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis and a severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we determined the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE). We retrospectively analyzed 401 patients with cardiac sarcoidosis without sustained ventricular arrhythmia at diagnosis. The primary end point was an FVAE, defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cutoff points for LVEF were used:a sex-specific lower threshold of normal range of LVEF (52% for men and 54% for women) and an LVEF of 35%, which is used in the current guidelines. During a median follow-up of 3.2 years, 58 FVAEs were observed, and the 5- and 10-year estimated incidences of FVAEs were 16.8% and 23.0%, respectively. All patients were classified into 3 groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (hazard ratio [HR], 3.24 [95% CI, 1.49-7.04]) and the mild to moderate impairment of LVEF group (HR, 2.16 [95% CI, 1.04-4.46]) were associated with a higher incidence of FVAEs than the maintained LVEF group after adjustment for covariates. Patients with cardiac sarcoidosis are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with cardiac sarcoidosis, mild to moderate impairment of LVEF is associated with FVAEs.

Inpatient thrombophilia workup; does hematology consult prevent unnecessary testing?

Hypercoagulable disorders are best described as a group of acquired and hereditary conditions that increase the risk for the development of thrombi within veins or arteries. In the setting of an unprovoked venous thromboembolism, common practice in the inpatient setting has been further investigation via a thrombophilia workup to establish an underlying cause. Current Hematology-Oncology guidelines argue against inpatient workup as the results rarely influence inpatient management. Following American Society of Hematology guidelines (Middledorp), the current study found that only 15% (11/72) of patients met appropriate criteria for thrombophilia testing. There was no relationship between appropriate thrombophilia testing and diagnosis of thrombophilia or initiation of anticoagulation. There was a relationship between appropriate thrombophilia testing and Hematology-Oncology consultation. This demonstrates the need for expert consultation if thrombophilia testing is being considered. The current study provides more evidence that a strong recommendation against inpatient testing should be made as testing does not aid in diagnosis or change management and is an overutilization of healthcare resources.

Predictive utility of remnant cholesterol in atherosclerotic cardiovascular disease.

Remnant cholesterol (RC) is the cholesterol carried in lipoproteins derived from the catabolism of chylomicrons and very low-density lipoproteins. Evidence supporting the causal relationship of RC with atherosclerotic cardiovascular disease (ASVD) is accumulating rapidly. The number of impactful contributions to this field are increasing and provide a pathophysiological insight into the current residual cardiovascular risk beyond low-density cholesterol (LDL)-cholesterol (LDL-C). They also raise the question of whether RC should be used in prediction models and become the target of new therapeutic interventions. The intent of this review is to highlight the recent advances on the role of RC in atherogenesis and the validation of RC as a predictor of ASVD. Numerous prospective and retrospective cohorts helped validate a significant causal relationship of RC with various forms of ASVD, independent of LDL-C. A recent large Mendelian randomization study reinforced the existence of this relationship and showed that the risk of atherosclerotic events was driven nearly entirely by a direct effect of RC. Both available and accumulating evidence suggest that a lifelong reduction in RC could translate into a substantial reduction in ASVD risk. The data support a revision of current guidelines to incorporate RC as an independent risk factor for ASVD. We propose that early screening of RC should be implemented and that RC lowering should become the target of future drug developments.

Prevalence of malocclusions requiring treatment according to the KIG classification : Amultipart cross-sectional study over a20-year period in the district of Viersen/North Rhine.

In Germany, the reimbursement of orthodontic treatment costs within the framework of the statutory health insurance (GKV) was restricted on 01January2002 by the introduction of the orthodontic indication groups (KIG). The aim of this study was to evaluate the prevalence of findings requiring treatment in aspecialist practice over a20-year period. The results were then compared with data from existing older studies. The distribution of treatment-eligible KIG (KIG classifications grades 3-5) among patients with statutory health insurance in an orthodontic practice in North Rhine was determined over a20-year period (2002-2021) after the introduction of the KIG system. This period was additionally scrutinized in four 5‑year periods according to the operating cycles of the practice. Findings were classified into the highest of 19 possible KIG treatment needs levels. Multiple classifications were not made. Orthodontic treatment was indicated in a total of4537 (2393 female, 2144 male) patients according to current statutory health insurance guidelines. The KIG classification "D" (increased overjet) was the most frequent within the observed 20years with 24.3%. Among 11 KIG classifications, 86.1% of the 6 most frequent and 13.9% of the 5 rarest findings were observed constantly over all periods. Of 19 possible indications, "D4" was the most frequent with 19.6%. Of 4537 patients, 20.7% had KIG grade3, 63.6% KIG grade4 and 15.7% KIG grade5. The prevalence of sagittal deviations "D" and "M" was 35.0%, transverse "B" and "K" 17.9% and vertical "O" and "T" 3.7%. Tooth position anomalies "E" and "P" had ashare of 24.6%. The present study confirms existing findings as well as the nationwide data of the National Association of Statutory Health Insurance Dentists (KZBV) from 2020: The sagittal deviations "D" (increased overjet) and "M" (negative overjet) represented the most frequent findings with KIG D4 as the most common classification. The prevalence and age distribution of KIG grades 3-5 requiring treatment corresponded to nationwide comparative data.

Fertilizer Management Strategies of Glycine max L. (Soybean) in Northcentral and North-Western North Dakota

Soybean (Glycine max L.) is a new cash crop grown in north central and northwestern North Dakota (ND). Soils and climate in these new soybean areas differ from current fertilizer guidelines. A three-year study to evaluate soybean fertility best management practices was initiated in the spring of 2016 and concluded in 2018. Each year had two sites and twelve treatments. One site was acidic (pH < 6.2) and the other was alkaline (pH > 7.2). Both site treatments were: untreated check, inoculated with rhizobia (Bradyrhizobium japonicum L.), broadcast urea (55 kg ha−1), broadcast MAP (110 kg ha−1), In-furrow 10-34-0 (28 L ha−1), in-furrow 6-24-6 (28 L ha−1), foliar 3-18-18 (28 L ha−1) at V5 and R2, and foliar 3-18-18 (28 L ha−1) with sulfate (1.1 kg ha−1) at V5 and R2. The acidic site had two treatments of sugar beet (Beta vulgaris L.) waste lime (4411 kg ha−1 and 8821 kg ha−1). The alkaline site received treatments of iron ortho-ortho-EDDHA (7.1 L ha−1), and naked ortho-ortho-EDDHA (7.1 L ha−1). An in-furrow treatment of cobalt (2.9 kg cobalt-sulfate ha−1) was added in 2018. Fertilizer treatments did not impact soybean yield, protein content and oil content at the 0.05 significance level.

Evaluation of a Protocol Change Promoting Lactated Ringers Over Normal Saline in the Treatment of Diabetic Ketoacidosis.

Current guidelines recommend normal saline (NS) for fluid resuscitation in the management of patients presenting with diabetic ketoacidosis (DKA). However, previous prospective studies have demonstrated improvement in patient-specific outcomes, including time to DKA resolution, when balanced crystalloid fluids are used. We conducted a single institution, retrospective cohort study of adult patients admitted with DKA before and after a protocol change within our institution, which shifted the default resuscitative and maintenance fluid in our DKA management protocol from NS to lactated Ringer's solution (LR). The primary outcome was time from DKA clinical presentation until DKA resolution. The secondary outcome was time to discontinuation of DKA protocol insulin drip. Of 246 patients meeting inclusion criteria, 119 were in the NS group (preprotocol change, where NS was the default resuscitative fluid) and 127 to the LR group (postprotocol change, where LR was the default resuscitative fluid). Time to DKA resolution was significantly decreased in the LR group (mean = 17.1 hours; standard deviation [SD] = 11.0) relative to the NS group (mean = 20.6 hours; SD = 12.2; P = .02). Duration of DKA protocol insulin drip was shorter in the LR group (mean = 16.0 hours; SD = 8.7) compared with the NS group (mean = 21.4 hours; SD = 12.5; P < .001). In this retrospective cohort study, protocolized DKA intravenous fluid management with LR resulted in shorter time to resolution of DKA and reduced duration of DKA protocol insulin drip.

Sports drinks do not increase acute kidney injury risk in males during industrial work in the heat when euhydration is maintained, a randomized crossover trial.

Industrial workers regularly perform physical labor under high heat stress, which may place them at risk for dehydration and acute kidney injury. Current guidelines recommend that workers should consume sports drinks to maintain euhydration during work shifts. However, the impact of fructose sweetened sports drinks on acute kidney injury risk is unknown. The purpose of this study was to investigate the effects of sports drink consumption on markers of acute kidney injury following simulated industrial work in the heat. Twenty males completed two matched 2 h simulated industrial work trial visits in a warm and humid environment (30°C and 55% relative humidity). During and following the bout of simulated work, participants consumed either a commercially available sports drink or a noncaloric placebo. Urine and blood samples, collected pre-, post-, and 16 h post-work were assayed for markers of hydration (plasma/urine osmolality, and urine specific gravity) and acute kidney injury (KIM-1 and NGAL). There were no differences in physiological or perceptual responses to the bout of work (interaction p>0.05 for all indices), and markers of hydration were similar between trials (interaction p>0.05 for all indices). KIM-1 (Placebo: Δ Ln 1.18±1.64; Sports drink: Δ Ln 1.49±1.10 pg/mL; groupwide d=0.89, p<0.001) and NGAL (Placebo: Δ Ln 0.44±1.11; Sports drink: Δ Ln 0.67±1.22 pg/mL; groupwide d=0.39, p=0.03) were elevated pre- to post-work, but there were no differences between trials (interaction p>0.05). These data provide no evidence that consumption of fructose sweetened sports drinks increases the risk of acute kidney injury during physical work in the heat.

Management of acute colonic pseudo-obstruction: opportunities to improve care?

Acute colonic pseudo-obstruction (ACPO) is a functional bowel obstruction characterised by colonic dilatation in the absence of mechanical obstruction on imaging. Complications include bowel ischaemia, perforation and death. The aim of this study was to explore outcomes for patients treated for ACPO and to assess adherence to current ACPO treatment guidelines. This is a retrospective service evaluation and included patients with a diagnosis of ACPO between 1 March 2018 and 31 March 2023. Process measures were identified following discussion with the clinical team from published guidance. Patients were identified using clinical coding and radiological text reports. Cases were eligible for inclusion if they had radiologically confirmed ACPO. Data were collected following review of patient notes into Microsoft Excel. Descriptive analysis was performed with no formal statistical assessment. A total of 45 patients were identified, of whom 13 were admitted under general surgery. All patients received admission bloods (n=45). Nearly all patients had computed tomography imaging (43/45, 96%). Only 3/45 (6.7%) of the patients received optimal conservative management (intravenous infusion, nil by mouth, flatus tube, treatment of reversible causes). In all, 11/45 (24%) required further treatment, of whom 7 received this within 72 h. The leading (11/45) complication following diagnosis of ACPO was hospital-acquired pneumonia. Mortality was seen in 9/45. ACPO is often managed remotely by general surgeons. This may impact on the quality of conservative management, and timeliness of endoscopic or pharmacological intervention. Further work is needed to optimise management.

Feasibility of alcohol interventions in cardiology: a qualitative study of clinician perspectives in Sweden.

This study aimed to identify barriers and facilitators to implementing alcohol screening and brief interventions (SBI) in cardiology services. This was a qualitative study. Individual, semi-structured interviews were conducted with 24 clinical cardiology staff (doctors, nurses, and assistant nurses) of varying experience levels and from various clinical settings (high-dependency unit, ward, and outpatient clinic), in three regions of Sweden. Reflexive thematic analysis was used, with deductive coding applying the Capability, Opportunity, Motivation (COM-B) theoretical framework. A total of 41 barriers and facilitators were identified, including 12 related to capability, 9 to opportunity, and 20 to motivation. Four themes were developed: (i) uncharted territory, where clinicians expressed a need to address alcohol use but lacked knowledge and a roadmap for implementing SBI; (ii) cardiology as a cardiovascular specialty, where tasks were prioritized according to established roles; (iii) alcohol stigma, where alcohol was reported to be a sensitive topic that staff avoid discussing with patients; and (iv) window of opportunity, where staff expressed potential for implementing SBI in routine cardiology care. Findings suggest that opportunities exist for early identification and follow-up of hazardous alcohol use within routine cardiology care. Several barriers, including low knowledge, stigma, a lack of ownership, and a greater focus on other risk factors, must be addressed prior to the implementation of SBI in cardiology. To meet current clinical guidelines, there is a need to increase awareness and to improve pathways to addiction care. In addition, there may be a need for clinicians dedicated to alcohol interventions within cardiology services. OSF (osf.io/hx3ts).

Liver transplantation in viral and autoimmune liver diseases

Despite substantial progress in the management of viral and autoimmune liver diseases, these entities remain relevant indications for liver transplantation. To provide an overview of the current knowledge regarding the management of viral and autoimmune liver diseases before and after liver transplantation. Selective literature search, including current guidelines and abstracts of key scientific meetings. Viral and autoimmune liver disease can be effectively treated in most cases, which has resulted in an overall decline in liver transplantations for this indication group. However, hepatitisD infection and primary sclerosing cholangitis remain difficult-to-treat liver diseases in some patients and may progress to end-stage liver disease despite best possible management. Viral or autoimmune hepatitis can lead to fulminant liver failure requiring emergency liver transplantation. In patients who are transplanted due to viral or autoimmune liver disease, specific measures to prevent recurrence of these diseases after transplantation are mandatory. In view of effective treatment modalities for chronic hepatitisB andC, even liver grafts from donors infected with these viruses can be considered for liver transplantation under certain circumstances.

Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.

Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research.

Genebe.net: Implementation and validation of an automatic ACMG variant pathogenicity criteria assignment.

We present GeneBe, an online platform streamlining the automated application of American College of Medical Genetics and Genomics (ACMG), Association for Molecular Pathology (AMP), and the College of American Pathologists (CAP) criteria for assessment of pathogenicity of genetic variants. GeneBe utilizes automated algorithms that evaluate 17 criteria from 28, closely aligning with current guidelines and leveraging data from diverse sources, including ClinVar. The user-friendly web interface enables manual refinement of assignments for specific criteria based on site-collected data. Our algorithm demonstrates a high correlation (r = 0.90) of assigned pathogenicity scores compared to expert assessments from the ClinGen Evidence Repository and substantial concordance with ClinVar verdict assignments (κ = 0.69). Comparative analysis with other published tools reveals that GeneBe performs similarly to VarSome while being superior over TAPES and InterVar. In contrast to some other tools, GeneBe's web implementation is tracker-free and third-party request-free, safeguarding user privacy. Additionally, GeneBe offers an Application Programming Interface (API) for enhanced flexibility and integration into existing workflows and is provided free of charge for research purposes. GeneBe is available at https://genebe.net.

Medication-related osteonecrosis of the jaw: evolving research for multimodality medical management.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating side effect of antiresorptive and antiangiogenic agents that can lead to progressive bone destruction in the maxillofacial region. Dental surgery, including tooth extractions, commonly trigger the onset of MRONJ. While guidelines suggest avoiding extraction when possible, complete avoidance is not always feasible, as necrosis can develop from dental and periodontal disease without dental procedures. The goal of this article is to provide an update review of current preventive and therapeutic approaches for MRONJ. A comprehensive electronic search was conducted on PubMed/MEDLINE, Embase, and Scopus databases. All English articles encompassing randomized controlled trials, systematic reviews, observational studies, and case studies were reviewed. The current medical treatments and adjuvant therapies for managing MRONJ patients were critically assessed and summarized. Pentoxifylline and alpha tocopherol (PENT-E), teriparatide, photobiomodulation (PBM), photodynamic therapy (PDT), and the use of growth factors have shown to enhance healing in MRONJ patients. Implementing these methods alone or in conjunction with surgical treatment has been linked to reduced discomfort and improved wound healing and increased new bone formation. While several adjuvant treatment modalities exhibit promising results in facilitating the healing process, current clinical practice guidelines predominantly recommend antibiotic therapy as a non-surgical approach, primarily addressing secondary infections in necrotic areas. However, this mainly addresses the potential infectious complication of MRONJ. Medical approaches including PENT-E, teriparatide, PBM, and PDT can result in successful management and should be considered prior to taking a surgical approach. Combined medical management for both preventing and managing MRONJ holds potential for achieving optimal clinical outcomes and avoiding surgical intervention, requiring further validation through larger studies and controlled trials.

The Impact of Bariatric Surgery on Postoperative Complications and Outcomes following Primary Total Hip Arthroplasty

AbstractThe prevalence of obesity is significantly increasing in the U.S. population and is associated with both increased incidence of total hip arthroplasty (THA) and potentially worsened postoperative outcomes. Current guidelines strongly encourage exercise-based weight loss in morbidly obese THA candidates to decrease patient risk profiles, but data on the impact of receiving bariatric surgery (BS) for weight loss prior to THA are limited and controversial. The purpose of this study was to clarify the impact of BS on postoperative complications and outcomes following THA. Using Current Procedural Terminology, International Classification of Diseases (ICD)-9, and ICD-10 codes, patients undergoing primary THA from 2010 to 2018 were retrospectively collected from PearlDiver's Mariner dataset. Patients were divided into three cohorts who underwent primary THA: nonmorbidly obese patients, morbidly obese patients, and morbidly obese patients who underwent THA within 2 years of BS. Patients were subsequently matched based on age, Charlson Comorbidity Index, gender, and tobacco use. The primary outcome of this study was the frequency of 90-day and 2-year postoperative complications following primary THA. Compared with morbidly obese non-BS patients, morbidly obese patients who underwent BS prior to receiving a primary THA were less likely to have blood transfusion (4.24 vs. 7.44%, p &lt; 0.05), cellulitis (2.92 vs. 6.11%, p &lt; 0.05), myocardial infarction (2.39 vs. 4.91%, p &lt; 0.05), and deep venous thrombosis (1.06 vs. 3.05%, p &lt; 0.05) at 90-day follow-up. The remaining 90-day postoperative outcomes were not found to be statistically different between cohorts. There were no significant differences in 2-year surgical complications between the morbidly obese non-BS cohort and morbidly obese BS cohort. In this study, we found that morbidly obese patients who underwent BS prior to THA had fewer 90-day medical complications and no significant differences in 2-year surgical complications compared with those who did not undergo BS prior to THA.

Racial disparities of gastric cancer in the USA: an overview of epidemiology, global screening guidelines, and targeted screening in a heterogeneous population.

Gastric cancer is the fifth most common cancer diagnosis and fourth leading cause of cancer-related death globally. The incidence of gastric cancer in the USA shows significant racial and ethnic disparities with gastric cancer incidence in Korean Americans being over five times higher than in non-Hispanic whites. Since gastric cancer is not common in the USA, there are no current screening guidelines. In countries with higher incidences of gastric cancer, screening guidelines have been implemented for early detection and intervention and this has been associated with a reduction in mortality. Immigrants from high incidence countries develop gastric cancer at lower rates once outside of their country of origin, but continue to be at higher risk for developing gastric cancer. This risk does seem to decrease with subsequent generations. With increasing availability of endoscopy, initiating gastric cancer screening guidelines for high-risk groups can have the potential to improve survival by diagnosing and treating gastric cancer at an earlier stage. This article aims to provide context to gastric cancer epidemiology globally, review risk factors for developing gastric cancer, highlight racial and ethnic disparities in gastric cancer burden in the USA, examine current guidelines that exist in high incidence countries, and suggest future studies examining the efficacy of additional screening in high-risk populations to reduce gastric cancer mortality and disparate burden on ethnic minorities in the USA.

Brief Review: Exploring Avicenna's Recommendations for Preventing Age-Related Sarcopenia and Improving Motor Control: Insights from Persian Medicine

Background: Sarcopenia, the age-related loss of muscle mass and function, is a significant concern in geriatric medicine. Avicenna, a prominent figure in Persian medicine, emphasized healthy living and provided detailed instructions for the elderly. Objectives: This review aims to evaluate the potential effectiveness of Avicenna's recommendations in preserving and improving motor control in the elderly population. Methods: A systematic search was conducted in electronic databases using relevant keywords to identify studies discussing Avicenna's recommendations for individuals over 65 years old. Avicenna suggested maintaining instinctive heat and essential body moisture through a balanced diet, including fresh fruits, vegetables, lean proteins, and whole grains. He also emphasized the importance of physical activity, moderate massage, and herbal remedies. Results: Comparing Avicenna's recommendations with current research on age-related sarcopenia reveals significant overlap. Studies support Avicenna's emphasis on milk and meat consumption for muscle health. Avicenna's recommendations for physical activity align with current exercise guidelines for older adults. Conclusions: Incorporating Avicenna's recommendations into geriatric medicine may lead to improved outcomes for elderly individuals at risk of sarcopenia and motor control issues. Further research is warranted to explore the mechanisms underlying Avicenna's recommendations and their impact on sarcopenia prevention and management, as well as motor control improvement.

Abstract A109: Novel germline genetic variants in pseudogenes associated with overall survival in advanced stage ovarian cancer treated with carboplatin, paclitaxel, and bevacizumab: Results from the ROSiA trial

Abstract A109: Novel germline genetic variants in pseudogenes associated with overall survival in advanced stage ovarian cancer treated with carboplatin, paclitaxel, and bevacizumab: Results from the ROSiA trial

FOLFIRINOX or Gemcitabine Plus Nab-paclitaxel as First Line Treatment in Pancreatic Cancer: A Real-World Comparison.

Advanced pancreatic cancer has a poor prognosis and a 5-year survival rate <5%; thus, treatment of patients with advanced unresectable or metastatic disease is challenging. Current guidelines recommend either gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX (FOL) as first-line treatment. Data on both efficacy and toxicity of FOL versus GnP in metastatic cancer are limited. This study aimed to compare the two chemotherapy regimens in terms of efficacy and toxicity in a real-world setting. This retrospective propensity score matching study reviewed the medical records of 123 consecutive patients with advanced or metastatic pancreatic cancer who received either GnP or FOL between March 2013 and January 2019 in Guglielmo da Saliceto Hospital, Piacenza. Fifty patients (40.65%) received FOL, administered in an attenuated dose, and seventy-three patients (59.35%) received GnP. After a propensity matching score, 100 patients were retrospectively evaluated. In the final matched cohort, there was no difference in neoadjuvant therapy, radiotherapy, and surgery performed before the first-line therapy between the two groups. Progression-free survival and overall survival were comparable between the two groups and no difference was found in the percentage of toxicity. There was no difference in outcomes between patients who received FOL and those who received GnP. Unexpectedly, no greater FOL-related toxicity was found, probably due to the dose reduction.

Patterns of initial distant metastases in 151 patients undergoing surveillance for treated Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is associated with high rates of recurrence and distant metastatic progression. Current guidelines for surveillance imaging are not evidence based. Better characterization of the pattern of distant metastatic spread will better inform surveillance and facilitate earlier detection of metastases. This retrospective study aimed to assess potential relationships between primary tumour site and site of initial distant metastasis, time to distant metastasis, overall survival (OS) and MCC-specific death (MSD). Patients with local or regional (Stage I-III) disease who were treated with curative intent and progressed to Stage IV were included in this study (n = 151). Fisher's exact test was used to assess differences in patterns of initial distant metastases based on primary tumour site. Time to initial distant metastasis was calculated from date of MCC diagnosis. OS and MSD were calculated from date of initial distant metastasis to date of death from any or MCC-related causes, respectively. Of 151 patients included in analysis, 89 (58.9%) had a single initial distant metastatic site, and 62 (41.1%) had multiple sites. Patients with upper limb primary tumours were significantly less likely to develop distant lymph node or liver metastases (p = 0.02 and 0.04, respectively). Median time to distant metastasis was 11 months (IQR 6.7-17.9 months). Median OS was 15.3 months, and was shorter for patients with liver (7.0 months, p = 0.0004) or bone metastases (8.9 months, p < 0.0001). Using skin/soft tissue metastasis as a reference group, patients with multiple metastatic sites had significantly higher hazards of MSD (HR = 3.46 univariate, 3.77 multivariate analysis). Time to distant metastasis, OS and MSD did not differ by viral status. Sites of initial distant metastasis are related to primary tumour sites and survival outcomes. Because patients often have multiple initial metastases, full-body cross-sectional rather than region-specific imaging may facilitate earlier detection of metastatic disease.