Causes of death in patients operated for colorectal cancer.

BACKGROUND: Colorectal cancer remains the third leading cause of cancer-related mortality in the United States. This study evaluates the causes of death in patients operated on for colorectal cancer and their determinants. METHODS: An Instructional Review Board-approved database containing patients who underwent surgical resection for colorectal cancer from 2004 to 2018 (last followed up in December 2020) in a tertiary care institution. Data on the underlying cause of death was extracted from the Registry of Vital Records and Statistics in Massachusetts. RESULTS: A total of 576 deaths were recorded in the database, of which 290 (50.35%) patients died of colorectal cancer. Deaths from colorectal cancer gradually decreased over time, whereas deaths from other cancers increased, and deaths from cardiovascular diseases remained stable. Patients who died from colorectal cancer were younger, died earlier in the disease course, had fewer comorbidities, higher rates of stage IV disease, rectal cancer, neoadjuvant therapy, extramural vascular invasion, perineural invasion, R0 resection, and preserved mismatch repair protein status. On multivariate analysis, age (adjusted odds ratio for 10-year increase = 0.79, 95% confidence interval 0.65-0.95), American Society of Anesthesiologists score (adjusted odds ratio = 0.64, confidence interval 0.42-0.98), stage IV disease (adjusted odds ratio = 3.02, confidence interval 1.59-5.9), neoadjuvant therapy (adjusted odds ratio = 7.91, confidence interval 2.64-28.13), extramural vascular invasion (adjusted odds ratio = 2.3, confidence interval 1.36-3.91) & time from diagnosis to death (adjusted odds ratio = 0.76, confidence interval 0.68-0.83) predicted death due to colorectal cancer versus other causes, whereas tumor location, perineural invasion, R0 resection, and mismatch repair protein status did not. CONCLUSION: There is a declining trend of deaths from colorectal cancer, presumably reflecting advances in colorectal cancer management strategies and better screening over time. However, younger patients disproportionately contribute to death due to colorectal cancer and need aggressive screening and management strategies.

Metformin Does not Affect Outcomes in Patients With Locally Advanced Rectal Cancer Treated With Neoadjuvant Therapy and Resection.

INTRODUCTION: There is emerging evidence that metformin may have a protective effect in patients with cancer. However, its current evidence in locally advanced rectal cancer (LARC) is inconclusive. We aim to assess the effect of metformin on long-term outcomes in patients with LARC who received neoadjuvant therapy and surgical resection. METHODS: A retrospective review of 324 patients with nonmetastatic LARC who received neoadjuvant therapy and major surgical resection from 2004 to 2018. There were 27 patients who received metformin before surgery and 297 patients who did not receive metformin. RESULTS: Metformin users were associated with a significantly higher age, BMI, ASA score, and 30-day readmissions (P < .05). There was no difference in overall survival (OS, P = .18) or disease-free survival (DFS, P = .33) between the two groups. On Cox regression, metformin intake did not predict OS (HR 0.85, 95% CI 0.4-1.77) when controlled for age (HR 1.04, 1.02-1.06), sex (HR 1.13, 0.69-1.85), BMI (HR 0.97, 0.92-1.02), ASA score (HR: 1.7, 1.06-2.73), TNT (HR 0.31, 0.1-0.92), pathological Stage III disease (HR 2.55, 1.51-4.32), extramural vascular invasion (EMVI) (HR 3.06, 1.7-5.5), and adjuvant therapy (HR 0.1, 0.04-0.27 for <25 months OS and HR 0.3, 0.15-0.59 for ≥25 months). Disease-free survival showed a similar trend with no significant effect of metformin (HR 0.77, 0.39-1.52) when controlled for age, sex, BMI, ASA, TNT, Stage III disease, EMVI, and adjuvant therapy. CONCLUSION: Metformin does not affect long-term survival in LARC treated with neoadjuvant therapy followed by surgical resection. Studies with larger sample sizes are needed to validate the findings further.

Fact or fiction? Does the position of the end-to-end (EEA) stapler spike matter for colorectal anastomoses using a double-stapled technique?

AIM: Surgeons often have strong opinions about how to perform colorectal anastomoses with little data to support variations in technique. The aim of this study was to determine if location of the end-to-end (EEA) stapler spike relative to the rectal transection line is associated with anastomotic integrity. METHOD: This study was a retrospective analysis of a quality collaborative database at a quaternary centre and regional hospitals. Patients with any left-sided colon resection with double-stapled anastomosis were included (December 2019 to August 2022). Our primary endpoint was a composite outcome including positive air insufflation test, incomplete anastomotic donut, or thin/eccentric donut. Our secondary endpoint was clinical leak. RESULTS: Overall, 633 patients were included and stratified by location of the stapler spike relative to the rectal transection line. Of note, 86 patients had an end-colon to anterior rectum ("reverse Baker") anastomosis with no crossing staple lines. The rates of the composite endpoint based on position of the stapler spike were 12.4% (anterior), 8.1% (through), 12.8% (posterior), 5.1% (corner), and 2.3% for the "reverse Baker" (p = 0.03). The overall rate of clinical leak was 3.8% and there were no differences between methods. In a multivariate analysis, the "reverse Baker" anastomosis was associated with decreased odds of poor anastomotic integrity when compared to anastomoses with crossing staple lines (OR 0.20, 95% CI: 0.05-0.87, p = 0.03). CONCLUSIONS: For anastomoses with crossing staple lines, the position of the stapler spike relative to the rectal staple line is not associated with differences in anastomotic integrity. In contrast, anastomoses with no crossing staple lines resulted in significantly lower rates of poor anastomotic integrity, but no difference in clinical leaks.

Incidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

INTRODUCTION: Whether neoadjuvant chemoradiation for locally advanced rectal cancer (LARC) induces secondary cancers is controversial. This retrospective cohort study describes the incidence of secondary cancers in LARC patients. METHODS: We compared 364 LARC patients who received conventional (50.4 Gy) or short course neoadjuvant radiation (25 Gy x 5 fractions) followed by resection to 142 patients with surgically resected rectal cancer who did not receive radiation at a single institution from 2004 to 2018. Secondary cancer was defined as any nonmetastatic noncolorectal malignancy diagnosed via biopsy or definitive imaging criteria at least 6 mo after completion of neoadjuvant therapy or after resection in the comparison group. RESULTS: Among the neoadjuvant radiation group (364 patients, 40% female, age 61 ± 13 y), 32 patients developed 34 (9.3%) secondary cancers. Three cases involved a pelvic organ. Among the comparison group (142 patients, 39% female, age 64 ± 15 y), 15 patients (10.6%) developed a secondary cancer. Five cases involved pelvic organs. Secondary cancer incidence did not differ between groups. Latency period to secondary cancer diagnosis was 6.7 ± 4.3 y. Patients who received radiation underwent longer median follow-up (6.8 versus 4.5 y, P < 0.01) and were significantly less likely to develop a pelvic organ cancer (odds ratio 0.18; 95% confidence interval, 0.04-0.83; P = 0.02). No genetic mutations or cancer syndromes were identified among patients with secondary cancers. CONCLUSIONS: Neoadjuvant chemoradiation is not associated with increased secondary cancer risk in LARC patients and may have a local protective effect on pelvic organs, especially prostate. Ongoing follow-up is critical to continue risk assessment.

Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection.

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

Colitis-Associated Colorectal Cancer Survival is Comparable to Sporadic Cases after Surgery: a Matched-Pair Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) confers an increased lifetime risk of colorectal cancer (CRC). The pathogenesis of colitis-associated CRC is considered distinct from sporadic CRC, but existing is mixed on long-term oncologic outcomes. This study aims to compare clinicopathological characteristics and survival between colitis-associated and sporadic CRC. METHODS: Data was retrospectively extracted and analyzed from a single institutional database of patients with surgically resected CRC between 2004 and 2015. Patients with IBD were identified as having colitis-associated CRC. The remainder were classified as sporadic CRC. Propensity score matching was performed. Univariate and survival analyses were carried out to estimate the differences between the two groups. RESULTS: Of 2275 patients included in this analysis, 65 carried a diagnosis of IBD (2.9%, 33 Crohn's disease, 29 ulcerative colitis, 3 indeterminate colitis). Average age at CRC diagnosis was 62 years for colitis-associated CRC and 65 for sporadic CRC. The final propensity score matched cohort consisted of 65 colitis-associated and 130 sporadic CRC cases. Patients with colitis-associated CRC were more likely to undergo total proctocolectomy (p < 0.01) and had higher incidence of locoregional recurrence (p = 0.026) compared to sporadic CRC patients. There were no significant differences in time to recurrence, tumor grade, extramural vascular invasion, perineural invasion, or rate of R0 resections. Overall survival and disease-free survival did not differ between groups. On multiple Cox regression, IBD diagnosis was not a significant predictor of survival. CONCLUSIONS: Patients with colitis-associated CRC who undergo surgical resection have comparable overall and disease-free survival to patients with sporadic CRC.

Development of a peripheral blood transcriptomic gene signature to predict bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common lung disease of extreme prematurity, yet mechanisms that associate with or identify neonates with increased susceptibility for BPD are largely unknown. Combining artificial intelligence with gene expression data is a novel approach that may assist in better understanding mechanisms underpinning chronic lung disease and in stratifying patients at greater risk for BPD. The objective of this study is to develop an early peripheral blood transcriptomic signature that can predict preterm neonates at risk for developing BPD. Secondary analysis of whole blood microarray data from 97 very low birth weight neonates on day of life 5 was performed. BPD was defined as positive pressure ventilation or oxygen requirement at 28 days of age. Participants were randomly assigned to a training (70%) and testing cohort (30%). Four gene-centric machine learning models were built, and their discriminatory abilities were compared with gestational age or birth weight. This study adheres to the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) statement. Neonates with BPD (n = 62 subjects) exhibited a lower median gestational age (26.0 wk vs. 30.0 wk, P < 0.01) and birth weight (800 g vs. 1,280 g, P < 0.01) compared with non-BPD neonates. From an initial pool (33,252 genes/patient), 4,523 genes exhibited a false discovery rate (FDR) <1%. The area under the receiver operating characteristic curve (AUC) for predicting BPD utilizing gestational age or birth weight was 87.8% and 87.2%, respectively. The machine learning models, using a combination of five genes, revealed AUCs ranging between 85.8% and 96.1%. Pathways integral to T cell development and differentiation were associated with BPD. A derived five-gene whole blood signature can accurately predict BPD in the first week of life.

Association of age with treatment at high-volume hospitals and distance traveled for care, in patients with rectal cancer who seek curative resection.

BACKGROUND: The association between volume and outcomes has led to recommendations that patients undergo surgery at high-volume centers. We aimed to determine if older patients with rectal cancer are undergoing operations at high-volume centers. METHODS: We identified patients ≥50 years old who underwent rectal cancer resection using the NCDB (2004-2015). Tertiles were used to categorize facility volume and distance traveled. RESULTS: Higher facility volume was associated with improved outcomes. Patients >75 years old were less likely than patients 50-59 years old to be treated at high-volume centers. Traveling >16.8 miles was associated with treatment at high-volume facilities, however patients >75 years old were less likely to travel >16.8 miles. CONCLUSIONS: Higher facility volume is associated with improved outcomes after rectal cancer resection. However, older patients are less likely to be treated at high-volume facilities. Older patients travel shorter distances for care, suggesting that care integration across networks must be optimized.

Minimally Invasive and Robotic Surgery for Ulcerative Colitis.

Significant advancements have been made over the last 30 years in the use of minimally invasive techniques for curative and restorative operations in patients with ulcerative colitis (UC). Numerous studies have demonstrated the safety and feasibility of laparoscopic and robotic approaches to subtotal colectomy (including in the urgent setting), total proctocolectomy, completion proctectomy, and pelvic pouch creation. Data show equivalent or improved short-term postoperative outcomes with minimally invasive techniques compared to open surgery, and equivalent or improved long-term bowel function, sexual function, and fertility. Overall, while minimally invasive techniques are safe and feasible for properly selected UC patients, surgeons must remember to abide by the principles of high-quality proctectomy and pouch creation and convert to open if necessary.

Immunologic resilience and COVID-19 survival advantage.

BACKGROUND: The risk of severe coronavirus disease 2019 (COVID-19) varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR). OBJECTIVE: We sought to examine whether deficits in IR that antedate or are induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection independently predict COVID-19 mortality. METHODS: IR levels were quantified with 2 novel metrics: immune health grades (IHG-I [best] to IHG-IV) to gauge CD8+ and CD4+ T-cell count equilibrium, and blood gene expression signatures. IR metrics were examined in a prospective COVID-19 cohort (n = 522); primary outcome was 30-day mortality. Associations of IR metrics with outcomes in non-COVID-19 cohorts (n = 13,461) provided the framework for linking pre-COVID-19 IR status to IR during COVID-19, as well as to COVID-19 outcomes. RESULTS: IHG-I, tracking high-grade equilibrium between CD8+ and CD4+ T-cell counts, was the most common grade (73%) among healthy adults, particularly in females. SARS-CoV-2 infection was associated with underrepresentation of IHG-I (21%) versus overrepresentation (77%) of IHG-II or IHG-IV, especially in males versus females (P < .01). Presentation with IHG-I was associated with 88% lower mortality, after controlling for age and sex; reduced risk of hospitalization and respiratory failure; lower plasma IL-6 levels; rapid clearance of nasopharyngeal SARS-CoV-2 burden; and gene expression signatures correlating with survival that signify immunocompetence and controlled inflammation. In non-COVID-19 cohorts, IR-preserving metrics were associated with resistance to progressive influenza or HIV infection, as well as lower 9-year mortality in the Framingham Heart Study, especially in females. CONCLUSIONS: Preservation of immunocompetence with controlled inflammation during antigenic challenges is a hallmark of IR and associates with longevity and AIDS resistance. Independent of age, a male-biased proclivity to degrade IR before and/or during SARS-CoV-2 infection predisposes to severe COVID-19.

Early antimicrobial prophylaxis in autologous stem cell transplant recipients: Conventional versus an absolute neutrophil count-driven approach.

BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of developing life-threatening infections. There is discordance in published recommendations for timing of pre- and post-transplant antimicrobial prophylaxis in this patient population, and these recommendations are unsubstantiated by any published comparative analyses. METHODS: An observational, pre- and post-intervention study of consecutive autologous HSCT recipients was conducted over a 2-year period. In the pre-intervention cohort, antimicrobial prophylaxis was initiated on the day prior to transplant. In the post-intervention cohort, antimicrobials were initiated once absolute neutrophil count (ANC) reached ≤500 cells/mm3 . The primary outcome assessed was frequency of febrile occurrences. Secondary outcomes included total days of prophylaxis, positive blood cultures, all-cause mortality, Clostridioides difficile infection rates, and length of stay. RESULTS: A total of 208 patients were included in the final analysis, with 105 and 103 patients in the pre- and post-intervention cohorts, respectively. The majority of patients included were male. Lower rates of fever occurrences were observed in the post-intervention cohort (83% pre- vs. 69% post-intervention; p = 0.019). A significant reduction in the mean antibacterial days per patient was identified (9.7 vs. 4.6 days; p < 0.001). Other than lower rates of febrile neutropenia in the post-intervention cohort, no differences were identified in secondary outcomes. In multivariable analyses, ANC-driven prophylaxis was independently associated with decreased febrile events. CONCLUSIONS: Delaying prophylaxis until severe neutropenia was not associated with increased febrile events or other secondary clinical outcomes evaluated. This approach is associated with a significant reduction in antimicrobial exposure.

A Facile High-Throughput Model of Surface-Independent Staphylococcus aureus Biofilms by Spontaneous Aggregation.

Many microbes in their natural habitats are found in biofilm ecosystems attached to surfaces and not as free-floating (planktonic) organisms. Furthermore, it is estimated that nearly 80% of human infections are associated with biofilms. Biofilms are traditionally defined as three-dimensional, structured microbial communities that are attached to a surface and encased in a matrix of exopolymeric material. While this view of biofilm largely arises from in vitro studies under static or flow conditions, in vivo observations have indicated that this view of biofilms is essentially true only for foreign-body infections on catheters or implants where biofilms are attached to the biomaterial. In mucosal infections such as chronic wounds or cystic fibrosis or joint infections, biofilms can be found unattached to a surface and as three-dimensional aggregates. In this work, we describe a high-throughput model of aggregate biofilms of methicillin-resistant Staphylococcus aureus (MRSA) using 96-well plate hanging-drop technology. We show that MRSA forms surface-independent biofilms, distinct from surface-attached biofilms, that are rich in exopolymeric proteins, polysaccharides, and extracellular DNA (eDNA), express biofilm-related genes, and exhibit heightened antibiotic resistance. We also show that the surface-independent biofilms of clinical isolates of MRSA from cystic fibrosis and central catheter-related infections demonstrate morphological differences. Overall, our results show that biofilms can form by spontaneous aggregation without attachment to a surface, and this new in vitro system can model surface-independent biofilms that may more closely mimic the corresponding physiological niche during infection.IMPORTANCE The canonical model of biofilm formation begins with the attachment and growth of microbial cells on a surface. While these in vitro models reasonably mimic biofilms formed on foreign bodies such as catheters and implants, this is not the case for biofilms formed in cystic fibrosis and chronic wound infections, which appear to present as aggregates not attached to a surface. The hanging-drop model of biofilms of methicillin-resistant Staphylococcus aureus (MRSA), the major causative organism of skin and soft tissue infections, shows that these biofilms display morphological and antibiotic response patterns that are distinct from those of their surface-attached counterparts, and biofilm growth is consistent with their in vivo location. The simplicity and throughput of this model enable adoption to investigate other single or polymicrobial biofilms in a physiologically relevant setting.

Recurrence of Clostridium Difficile and Cytomegalovirus Infections in Patients with Ulcerative Colitis Who Undergo Ileal Pouch-Anal Anastomosis.

BACKGROUND: Patients with ulcerative colitis (UC) are at increased risk for infections such as Clostridium difficile and cytomegalovirus (CMV) colitis due to chronic immunosuppression. These patients often undergo multiple surgeries putting them at risk for recurrence of the infection. However, rates of recurrence in this setting and outcomes are not well understood. AIM: The aim of this study is to determine rates of recurrence of C difficile and CMV infection in patients undergoing multistage UC surgeries and effects of antibiotic prophylaxis on outcomes. METHODS: All patients with UC who underwent IPAA between 2001 and 2017 (at two tertiary referral centers were identified. History of C. difficile or CMV colitis prior to any surgery and recurrence after IPAA was noted RESULTS: A total of 633 patients with UC who underwent IPAA were identified, of whom 8.1% patients had C. difficile and 2.7% had CMV infections. 9.8% of C. difficile and 5.9% of CMV patients recurred after IPAA. Rates of abdominal sepsis (14.7% vs. 12.7%), 90-day mortality (0% vs. 0.4%), pouchitis (36.8% vs. 45.0%), or return to stoma (7.4% vs. 5.4%) were similar between patients who did or did not have infections. In patients with C. difficile infection prior to first surgery, none of the patients who received prophylaxis had recurrent infection. CONCLUSIONS: Rates of C. difficile and CMV infections remain high in patients undergoing surgery for UC, with substantial minority developing recurrent infection during subsequent surgical procedures. Antibiotic prophylaxis in patients with a history of C difficile may reduce the rate of recurrent infection.

Revision of Pancreatic Neck Margins Based on Intraoperative Frozen Section Analysis Is Associated With Improved Survival in Patients Undergoing Pancreatectomy for Ductal Adenocarcinoma.

OBJECTIVE: To test the hypothesis that complete, tumor-free resection at the pancreatic neck, achieved either en-bloc or non-en-bloc (ie, revision based on intraoperative frozen section [FS] analysis), is associated with improved survival as compared with incomplete resection (IR) in pancreatic ductal adenocarcinoma. SUMMARY BACKGROUND DATA: Given the likely systemic nature of pancreatic ductal adenocarcinoma, the oncologic benefit of achieving a histologically complete local resection, particularly through revision of a positive intraoperative FS at the pancreatic neck, remains controversial. METHODS: Clinicopathologic and treatment data were reviewed for 986 consecutive patients with ductal adenocarcinoma at the head, neck, or uncinate process of the pancreas who underwent open pancreatectomy as well as intraoperative FS analysis between 1998 and 2012 at Massachusetts General Hospital and between 1998 and 2013 at the University of Verona. Overall survival (OS) and perioperative morbidity and mortality were compared across 3 groups: complete resection achieved en-bloc (CR-EB), complete resection achieved non-en-bloc (CR-NEB), and IR. RESULTS: The CR-EB cohort comprised 749 (76%) patients, CR-NEB 159 patients (16%), and IR 78 patients (8%). Other than a higher incidence of vascular resection among CR-NEB and IR patients, no demographic, pathologic (eg, tumor grade, lymph node positivity, superior mesenteric artery involvement), or treatment factors (eg, neoadjuvant and adjuvant therapy use) differed between the groups. Median OS was significantly higher in patients with CR-EB (28 mo, P = 0.01) and CR-NEB resections (24 mo, P = 0.02) as compared with patients with IR resections (19 mo). After adjusting for clinicopathologic and treatment characteristics, CR-EB and CR-NEB margin status were found to be independent predictors of improved OS (relative to IR, CR-EB hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.49-0.86; CR-NEB HR 0.69, 95% CI 0.50-0.96). There were no intergroup differences in perioperative morbidity and mortality, including rates of pancreatic fistula. CONCLUSIONS: For patients with ductal adenocarcinoma at the head, neck, or uncinate process of the pancreas undergoing pancreatectomy, complete tumor extirpation via either en-bloc or non-en-bloc complete resection based on FS analysis is associated with improved OS, without an associated increased perioperative morbidity or mortality.

Henle fibre layer haemorrhage: clinical features and pathogenesis.

BACKGROUND: To describe the clinical presentation and characteristic imaging features of deep retinal haemorrhages primarily located in the Henle fibre layer (HFL) of the macula. The spectrum of aetiologies and a comprehensive theory of pathogenesis are presented. METHODS: This is a retrospective, multicentre case series evaluating eyes with retinal haemorrhage in HFL. Clinical features, underlying aetiology, systemic and ocular risk factors, visual acuity, and multimodal imaging including fundus photography and cross-sectional and en face optical coherence tomography (OCT) are presented. RESULTS: Retinal haemorrhages localised to HFL in 33 eyes from 23 patients were secondary to acute blunt trauma to the head (n=2), eye (n=1) and trunk (n=1), ruptured intracranial aneurysm (Terson's syndrome, n=3), general anaesthesia (n=1), epidural anaesthesia (n=1), hypertension with anaemia (n=1), decompression retinopathy (n=1), postvitrectomy with intraocular gas (n=1), retinal vein occlusion (n=7), myopic degeneration (n=2), macular telangiectasia type 2 (n=1), and polypoidal choroidal vasculopathy (n=1). Defining clinical features included deep retinal haemorrhage with feathery margin and petaloid pattern radiating from the fovea. OCT demonstrated characteristic hyper-reflectivity from the haemorrhage delineated by obliquely oriented fibres in the Henle layer. Spontaneous resolution of HFL haemorrhage occurred after 3 months in 15 patients with follow-up. CONCLUSION: The characteristic petaloid-shaped, deep intraretinal haemorrhage with a feathery margin localised to HFL is associated with various disorders. The terminology 'Henle fiber layer hemorrhage (HH)' is proposed to describe the clinical and OCT findings, which may result from abnormal retinal venous pressure from systemic or local retinovascular disorders affecting the deep capillary plexus or from choroidal vascular abnormalities.

Evaluation of Pathologic Response on Overall Survival After Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Single-institution studies have shown improved outcomes among patients with a pathologic complete response (pCR) following neoadjuvant therapy. We sought to evaluate the impact of pCR and near-complete response (nCR) on overall survival (OS) using a large national database. METHODS: The National Cancer Database was queried for patients given a diagnosis of pancreatic cancer from 2004 to 2014. A pCR was defined as no tumor identified in the pancreas after surgical resection. An nCR was defined as a primary tumor less than 1 cm without lymph node metastases. The primary outcome was OS. RESULTS: A total of 5364 patients underwent neoadjuvant chemotherapy and/or radiation followed by pancreatectomy. Forty-one patients (0.8%) had a pCR, 54 (1%) had an nCR, and the remaining 5266 (98.2%) had an otherwise incomplete response. Patients with pCR had a median OS of 43 months compared with 24 months for nCR and 23 months for incomplete response (P < 0.0001). Only pCR was associated with improved OS on adjusted Cox regression. CONCLUSIONS: For patients given a diagnosis of pancreatic cancer who underwent neoadjuvant treatment and surgical resection, achieving a pCR was associated with improved OS compared with those with residual tumor. An association between nCR and improved survival was not observed.

Association of Time Between Radiation and Salvage APR and Margin Status in Patients With Anal Cancer Treated With Concurrent Chemoradiation.

There is a controversy regarding the optimal time to assess anal squamous cell carcinoma (SCC) response to chemoradiation and when salvage abdominoperineal resection (APR) should be offered. A retrospective cohort study was performed on patients with stage I-III anal SCC treated with chemoradiation in the National Cancer Database (2004-2015). The time between radiation and APR was recorded. Logistic regression and Cox proportional hazard analysis were used to determine predictors of resection margin status and overall survival. The cohort included 23 050 patients, of whom 545 (2.4%) underwent salvage APR. The median (IQR) time between radiation and resection was 3.8 (2.4-5.5) months. The rate of positive margins was 19.0%. Positive margins were more common in male, non-white patients with larger tumors, pathologic upstaging of T stage, and ≥3 months between chemoradiation and resection (all P < .05). Observing for ≥3 months between chemoradiation and APR remained associated with positive margins, even after adjusting for pretreatment tumor size (odds ratio = 2.56, 95% CI 1.46-4.47). Our data, based on the largest published cohort of anal SCC patients treated with chemoradiation and subsequent APR, suggest that patients at high risk of local treatment failure, particularly non-white men with large tumors, may benefit from early interim restaging and earlier consideration of salvage surgery.

Socioeconomic determinants of the surgical treatment of colorectal liver metastases.

OBJECTIVE: We hypothesized that differences in resection rates of colorectal liver metastases exist based on socioeconomic status (SES) inequalities. METHODS: The NCDB was utilized to study patients of different median household income diagnosed with colon adenocarcinoma from 2010 to 2015. RESULTS: A total of 21,258 patients met inclusion criteria, of whom 3,587 (16.9%) underwent metastasectomy. Patients of the highest income quartile were more likely to undergo metastasectomy compared to the lowest quartile (OR 1.20, CI 1.07-1.37, p = 0.003). Overall, patients in the highest income quartile had a median OS of 17.1 months compared with 13.0 months for the lowest quartile (HR 0.85, CI 0.81-0.90, p < 0.001). While metastasectomy was associated with improved OS across all groups, the disparity by income quartile widened (29.2 vs. 22.0 months, respectively; HR 0.51, CI 0.49-0.54, p < 0.001). CONCLUSION: Higher income patients were more likely to undergo metastasectomy compared with lower income patients and were associated with longer OS.