An edge-simplicity bias in the visual input to young infants.

The development of sparse edge coding in the mammalian visual cortex depends on early visual experience. In humans, there are multiple indicators that the statistics of early visual experiences has unique properties that may support these developments. However, there are no direct measures of the edge statistics of infant daily-life experience. Using head-mounted cameras to capture egocentric images of young infants and adults in the home, we found infant images to have distinct edge statistics relative to adults. For infants, scenes with sparse edge patterns-few edges and few orientations-dominate. The findings implicate biased early input at the scale of daily life that is likely specific to the early months after birth and provide insights into the quality, amount, and timing of the visual experiences during the foundational developmental period for human vision.

Prognostic factors in clinicopathology of oesophagogastric adenocarcinoma: a single-centre longitudinal study of 347 cases over a 20-year period.

Oesophagogastric adenocarcinoma (EGA) includes oesophageal (EA), gastro-oesophageal junctional (GEJA), and gastric (GA) adenocarcinomas. The prognostic values of clinicopathological factors in these tumours remain obscure, especially for GEJA that has been inconsistently classified and staged. We studied the prognosis of EGA patients among the three geographic groups in 347 consecutive patients with a median age of 70 years (range 47-94). All patients were male, and 97.1% were white. Based on tumour epicentre location, EGAs were sub-grouped into EA (over 2 cm above the GEJ; n=3, 18.1%), GEJA (within 2 cm above and 3 cm below the GEJ; n=231, 66.6%), and GA (over 3 cm below the GEJ; n=53, 15.3%). We found that the median overall survival (OS) was the longest in EA (62.9 months), compared to GEJA (33.4), and GA (38.1) (p<0.001). Significant risk factors for OS included tumour location (p=0.018), size (p<0.001), differentiation (p<0.001), adenocarcinoma subtype (p<0.001), and TNM stage (p<0.001). Independent risk factors for OS comprised low-grade papillary adenocarcinoma [odds ratio (OR) 0.449, 95% confidence interval (CI) 0.214-0.944, p<0.05), mixed adenocarcinoma (OR 1.531, 95% CI 1.056-2.218, p<0.05), adenosquamous carcinoma (OR 2.206, 95% CI 1.087-4.475, p<0.05), N stage (OR 1.505, 95% CI 1.043-2.171, p<0.05), and M stage (OR 10.036, 95% CI 2.519-39.993, p=0.001)]. EGA was further divided into low-risk (common well-moderately differentiated tubular and low-grade papillary adenocarcinomas) and high-risk (uncommon adenocarcinoma subtypes, adenosquamous carcinoma) subgroups. In this grouping, the median OS was significantly longer in the low-risk (83 months) than in the high-risk (10 months) subgroups (p<0.001). In conclusion, the prognosis of EGA patients was significantly better in EA than in GEJA or GA and could be stratified into low and high-risk subgroups with significantly different outcomes.

Esophageal adenocarcinoma heterogeneity in clinicopathology and prognosis: A single center longitudinal study of 146 cases over a 20-year period.

Recent genomic studies suggest that esophageal adenocarcinoma (EAC) is not homogeneous and can be divided into true (tEAC) and probable (pEAC) groups. We compared clinicopathologic and prognostic features between the two groups of EAC. Based on endoscopic, radiologic, surgical, and pathologic reports, tumors with epicenters beyond 2 cm of the gastroesophageal junction (GEJ) were assigned to the tEAC group (N = 63), while epicenters within 2 cm of, but not crossing the GEJ, were allocated to the pEAC group (N = 83). All 146 consecutive patients were male (age: median 70 years, range: 51-88) and White-predominant (98.6 %). There was no significant difference in gastroesophageal reflux disease, obesity, comorbidity, and the prevalence of Barrett's esophagus, and cases diagnosed during endoscopic surveillance. However, compared to the pEAC group, the tEAC group had significantly more cases with hiatal hernia (P = 0.003); their tumors were significantly smaller in size (P = 0.007), more frequently with tubular/papillary adenocarcinoma (P = 0.001), had fewer cases with poorly cohesive carcinoma (P = 0.018), and demonstrated better prognosis in stage I disease (P = 0.012); 5-year overall survival (34.9 months) was significantly longer (versus 16.8 months in pEACs) (P = 0.043). Compared to the patients without resection, the patients treated with endoscopic or surgical resection showed significantly better outcomes, irrespective of stages. We concluded that EACs were heterogeneous with two distinct tEAC and pEAC groups in clinicopathology and prognosis; resection remained the better option for improved outcomes. CONDENSED ABSTRACT: Esophageal adenocarcinoma can be divided into true or probable groups with distinct clinicopathology and better prognosis in the former than in the latter. we showed that resection remained the better option for improved outcomes.

Systemic Therapy for Melanoma: ASCO Guideline Update.

PURPOSE: To provide guidance to clinicians regarding the use of systemic therapy for melanoma. METHODS: American Society of Clinical Oncology convened an Expert Panel and conducted an updated systematic review of the literature. RESULTS: The updated review identified 21 additional randomized trials. UPDATED RECOMMENDATIONS: Neoadjuvant pembrolizumab was newly recommended for patients with resectable stage IIIB to IV cutaneous melanoma. For patients with resected cutaneous melanoma, adjuvant nivolumab or pembrolizumab was newly recommended for stage IIB-C disease and adjuvant nivolumab plus ipilimumab was added as a potential option for stage IV disease. For patients with unresectable or metastatic cutaneous melanoma, nivolumab plus relatlimab was added as a potential option regardless of BRAF mutation status and nivolumab plus ipilimumab followed by nivolumab was preferred over BRAF/MEK inhibitor therapy. Talimogene laherparepvec is no longer recommended as an option for patients with BRAF wild-type disease who have progressed on anti-PD-1 therapy. Ipilimumab- and ipilimumab-containing regimens are no longer recommended for patients with BRAF-mutated disease after progression on other therapies.This full update incorporates the new recommendations for uveal melanoma published in the 2022 Rapid Recommendation Update.Additional information is available at www.asco.org/melanoma-guidelines.

Systemic therapy for melanoma: ASCO guideline update

To provide guidance to clinicians regarding the use of systemic therapy for melanoma. American Society of Clinical Oncology convened an Expert Panel and conducted an updated systematic review of the literature. The updated review identified 21 additional randomized trials. Neoadjuvant pembrolizumab was newly recommended for patients with resectable stage IIIB to IV cutaneous melanoma. For patients with resected cutaneous melanoma, adjuvant nivolumab or pembrolizumab was newly recommended for stage IIB-C disease and adjuvant nivolumab plus ipilimumab was added as a potential option for stage IV disease. For patients with unresectable or metastatic cutaneous melanoma, nivolumab plus relatlimab was added as a potential option regardless of BRAF mutation status and nivolumab plus ipilimumab followed by nivolumab was preferred over BRAF/MEK inhibitor therapy. Talimogene laherparepvec is no longer recommended as an option for patients with BRAF wild-type disease who have progressed on anti­PD-1 therapy. Ipilimumab- and ipilimumab-containing regimens are no longer recommended for patients with BRAF-mutated disease after progression on other therapies. This full update incorporates the new recommendations for uveal melanoma published in the 2022 Rapid Recommendation Update. Additional information is available at www.asco.org/melanoma-guidelines

Socioeconomic Disparities in Pancreas Cancer Resection and Survival in the Veterans Health Administration.

BACKGROUND: Disparities based on socioeconomic factors such as race, ethnicity, marital status, and insurance status are associated with pancreatic cancer resection, but these disparities are usually not observed for survival after resection. It is unknown if there are disparities when patients undergo their treatment in a non-fee-for-service, equal-access healthcare system such as the Veterans Health Administration (VHA). METHODS: Patients having T1-T3 M0 pancreatic adenocarcinoma diagnosed between 2006 and 2017 were identified from the VHA Corporate Data Warehouse. Socioeconomic, demographic, and tumor variables associated with resection and survival were assessed. RESULTS: In total, 2580 patients with early-stage pancreatic cancer were identified. The resection rate was 36.5%. Surgical resection was independently associated with younger age [odds ratio (OR) 0.94, p < 0.001], White race (OR 1.35, p = 0.028), married status (OR 1.85, p = 0.001), and employment status (retired vs. unemployed, OR 1.41, p = 0.008). There were no independent associations with Hispanic ethnicity, geographic region, or Social Deprivation Index. Resection was associated with significantly improved survival (median 21 vs. 8 months, p = 0.001). Among resected patients, survival was independently associated with younger age (HR 1.019, p = 0.002), geographic region (South vs. Pacific West, HR 0.721, p = 0.005), and employment (employed vs. unemployed, HR 0.752, p = 0.029). Race, Hispanic ethnicity, marital status, and Social Deprivation Index were not independently associated with survival after resection. CONCLUSIONS: Race, marital status, and employment status are independently associated with resection of pancreatic cancer in the VHA, whereas geographic region and employment status are independently associated with survival after resection. Further studies are warranted to determine the basis for these inequities.

Associations of gender, race, and ethnicity with disparities in short-term adverse outcomes after pancreatic resection for cancer.

BACKGROUND: Several studies have identified disparities in pancreatic cancer treatment associated with gender, race, and ethnicity. There are limited data examining disparities in short-term adverse outcomes after pancreatic resection for cancer. The aim of this study is to evaluate associations of gender, race, and ethnicity with morbidity and mortality after pancreatic resection for malignancy. METHODS: The American College of Surgeons National Surgical Quality Improvement database was retrospectively reviewed. The χ2 test and Student's t-test were used for univariable analysis and hierarchical logistic regression for multivariable analysis. RESULTS: Morbidity and major morbidity after pancreaticoduodenectomy are associated with male gender, Asian race, and Hispanic ethnicity, whereas 30-day mortality is associated with the male gender. Morbidity and major morbidity after distal pancreatectomy are associated with the male gender. Morbidity after pancreaticoduodenectomy is independently associated with male gender, Asian race, and Hispanic ethnicity; major morbidity is independently associated with male gender and Asian race, and mortality is independently associated with Hispanic ethnicity. CONCLUSIONS: Gender, race, and ethnicity are independently associated with morbidity after pancreaticoduodenectomy for cancer; gender and race are independently associated with major morbidity; and ethnicity is independently associated with mortality. Further studies are warranted to determine the basis of these associations.

CCL20 induces colorectal cancer neoplastic epithelial cell proliferation, migration, and further CCL20 production through autocrine HGF-c-Met and MSP-MSPR signaling pathways.

CCL20-CCR6 interactions promote colorectal cancer through direct effects on neoplastic epithelial cells and through modulating the tumor microenvironment. The mechanism of these effects on neoplastic epithelial cells is poorly understood. This study demonstrates that CCL20 induces secretion of hepatocyte growth factor (HGF) and phosphorylation of HGF's cognate receptor c-Met in HT29 and HCT116 colorectal cancer cell lines both in concentration- and time-dependent manners. Similar to CCL20, HGF induces migration, autofeedback CCL20 secretion, and ERK1/2 phosphorylation in the colon cancer cells. CCL20-dependent ERK1/2 phosphorylation is blocked by HGF inhibition, and CCL20-dependent migration and CCL20 secretion are blocked by inhibition of HGF or ERK. Interestingly, unlike CCL20, HGF does not induce proliferation of colon cancer cells, and CCL20-dependent cell proliferation is not blocked by direct HGF inhibition. CCL20-dependent proliferation, however, is blocked by the multi-tyrosine kinase inhibitor crizotinib. Exploring this effect, it was found that CCL20 also induces production of MSP and phosphorylation of MSP's receptor MSPR by the colorectal cancer cells. CCL20-dependent cell proliferation is inhibited by directly blocking MSP-MSPR interactions. Thus, CCL20-mediated migration and CCL20 secretion are regulated through a pathway involving HGF, c-Met, and ERK, while CCL20-mediated proliferation is instead regulated through MSP and its receptor MSPR.

Clinical Implications of Colorectal Cancer Stem Cells in the Age of Single-Cell Omics and Targeted Therapies.

The cancer stem cell (CSC) concept emerged from the recognition of inherent tumor heterogeneity and suggests that within a given tumor, in analogy to normal tissues, there exists a cellular hierarchy composed of a minority of more primitive cells with enhanced longevity (ie, CSCs) that give rise to shorter-lived, more differentiated cells (ie, cancer bulk populations), which on their own are not capable of tumor perpetuation. CSCs can be responsible for cancer therapeutic resistance to conventional, targeted, and immunotherapeutic treatment modalities, and for cancer progression through CSC-intrinsic molecular mechanisms. The existence of CSCs in colorectal cancer (CRC) was first established through demonstration of enhanced clonogenicity and tumor-forming capacity of this cell subset in human-to-mouse tumor xenotransplantation experiments and subsequently confirmed through lineage-tracing studies in mice. Surface markers for CRC CSC identification and their prospective isolation are now established. Therefore, the application of single-cell omics technologies to CSC characterization, including whole-genome sequencing, RNA sequencing, and epigenetic analyses, opens unprecedented opportunities to discover novel targetable molecular pathways and hence to develop novel strategies for CRC eradication. We review recent advances in this field and discuss the potential implications of next-generation CSC analyses for currently approved and experimental targeted CRC therapies.

The improvement in post-operative mortality following pancreaticoduodenectomy between 2006 and 2016 is associated with an improvement in the ability to rescue patients after major morbidity, not in the rate of major morbidity.

BACKGROUND: The postoperative mortality rate of pancreaticoduodenectomy is decreasing over time. It is unknown whether this is related to reduction in incidence of major morbidity or failure to rescue. We aimed to make this determination. METHODS: ACS-NSQIP was retrospectively reviewed from 2006 to 2016. Comparisons were assessed with Spearman's rank-order correlation test, chi-square test with linear-by-linear association, and multivariable hierarchical logistic regression. RESULTS: Mortality decreased significantly from 2.9% to 1.5% (p < 0.001). This decrease was independent of preoperative variables on multivariable analysis (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.55-5.21, p < 0.001). In contrast, no change in incidence of major morbidity was seen on univariable (26.8% to 25.9%, p = 1.00) or multivariable analysis (OR 1.22, 95% CI 1.03-1.45, p = 0.060). Failure to rescue was observed to decrease on univariable (9.8% to 4.1%, p < 0.001) and multivariable analysis (OR 3.65, 95% CI 2.07-6.76, p < 0.001). CONCLUSION: There has been a sizeable reduction in the mortality rate after pancreaticoduodenectomy from 2006 to 2016. This predominantly results from a reduction in failure to rescue rate rather than a decrease in incidence of major morbidity.

Unraveling the identity of gastric cardiac cancer.

The classification of gastric cardiac carcinoma (GCC) is controversial. It is currently grouped with esophageal adenocarcinoma (EAC) as an adenocarcinoma of the gastroesophageal junction (GEJ). Recently, diagnostic criteria for adenocarcinoma in the GEJ were established and GCC was separated from EAC. We viewed published evidence to clarify the GCC entity for better patient management. GCC arises in the cardiac mucosa located from 3 cm below and 2 cm above the GEJ line. Compared with EAC, GCC is more like gastric cancer and affects a higher proportion of female patients, younger patients, those with a lower propensity for reflux disease, a wider histopathologic spectrum, and more complex genomic profiles. Although GCC pathogenesis mechanisms remain unknown, the two-etiology proposal is appealing: in high-risk regions, the Correa pathway with Helicobacter pylori infection, chronic inflammation, low acid and intestinal metaplasia, dysplasia and carcinoma may apply, while in low-risk regions the sequence from reflux toxin-induced mucosal injury and high acid, to intestinal metaplasia, dysplasia and carcinoma may occur. In early GCC a minimal risk of nodal metastasis argues for a role of endoscopic therapy, whereas in advanced GCC, gastric cancer staging rules and treatment strategy appear to be more appropriate than the esophageal cancer staging scheme and therapy for better prognosis stratification and treatment. In this brief review we share recent insights into the epidemiology, histopathology and genetics of GCC and hope that this will stimulate further investigations in order to improve the clinical management of patients with GCC.

Systemic Therapy for Melanoma: ASCO Guideline.

PURPOSE: To provide guidance to clinicians regarding the use of systemic therapy for melanoma. METHODS: ASCO convened an Expert Panel and conducted a systematic review of the literature. RESULTS: A systematic review, one meta-analysis, and 34 additional randomized trials were identified. The published studies included a wide range of systemic therapies in cutaneous and noncutaneous melanoma. RECOMMENDATIONS: In the adjuvant setting, nivolumab or pembrolizumab should be offered to patients with resected stage IIIA/B/C/D BRAF wild-type cutaneous melanoma, while either of those two agents or the combination of dabrafenib and trametinib should be offered in BRAF-mutant disease. No recommendation could be made for or against the use of neoadjuvant therapy in cutaneous melanoma. In the unresectable/metastatic setting, ipilimumab plus nivolumab, nivolumab alone, or pembrolizumab alone should be offered to patients with BRAF wild-type cutaneous melanoma, while those three regimens or combination BRAF/MEK inhibitor therapy with dabrafenib/trametinib, encorafenib/binimetinib, or vemurafenib/cobimetinib should be offered in BRAF-mutant disease. Patients with mucosal melanoma may be offered the same therapies recommended for cutaneous melanoma. No recommendation could be made for or against specific therapy for uveal melanoma. Additional information is available at www.asco.org/melanoma-guidelines.

Discharge destination following rectal cancer resection: an analysis of preoperative and intraoperative factors.

PURPOSE: Rectal cancer resections can be associated with long and complicated postoperative recoveries. Many patients undergoing these operations are discharged to rehabilitation or skilled nursing facilities. The purpose of this study was to identify preoperative and intraoperative factors associated with increased risk for non-home discharge after rectal cancer resection. METHODS: Rectal cancer resections were identified in the National Surgical Quality Improvement Program Targeted Proctectomy Dataset (years 2016 through 2017) by ICD code. Patients with unknown discharge destination or who experienced in-hospital mortality were excluded. Univariate and multivariate logistic regression analyses were performed to identify preoperative and intraoperative variables associated with non-home discharge destination. Multiple imputation was used to account for missing values. RESULTS: Among the 3637 patients comprising the study sample, 292 (8.0%) patients were discharged to rehabilitation, skilled care, or acute care facilities. Preoperative factors associated with non-home discharge on multivariate analysis included older age, non-independent functional status, insulin-dependent diabetes, and hypoalbuminemia (all p < 0.05). Having received neoadjuvant chemotherapy was associated with home discharge (OR 0.625, 95% CI 0.427-0.914, p = 0.015). Intraoperative factors associated with non-home discharge on multivariate analysis were concurrent cystectomy (p = 0.004) and myocutaneous flap reconstruction (p < 0.001). Patients discharged to non-home facilities had longer initial lengths of stay (14.1 versus 7.0 days, p < 0.001) and higher reoperation rates (12.7 versus 5.0%, p < 0.001), but similar readmission rates (14.7 versus 15.0%, p = 1.0). CONCLUSION: Several preoperative and intraoperative factors are associated with increased risk for non-home discharge after rectal cancer resection. These data can aid in perioperative planning and discharge optimization.

Twenty-Three-Hour-Stay Colectomy Without Increased Readmissions: An Analysis of 1905 Cases from the National Surgical Quality Improvement Program.

BACKGROUND: Isolated case series from highly specialized centers suggest the feasibility of a 23-h hospital stay after colectomy. We sought to determine preoperative variables associated with discharge within 23 h after colectomy to identify patients best suited for a short-stay model. METHODS: The American College of Surgeons NSQIP Colectomy-Targeted database was used to identify patients who underwent elective colectomy from 2012 to 2017. All cases with missing length of stay or inpatient death were excluded. Patients with a postoperative hospital stay ≤1 day were identified. Univariate and multivariate analyses were conducted to identify factors associated with early discharge. RESULTS: A total of 1905 patients were discharged within 23 h after surgery (1.6%). These patients were noted to be younger (59 versus 61 years, p < 0.001) and less likely to have insulin-dependent diabetes (3.0 versus 4.4%, p < 0.001), preoperative dyspnea (2.2 versus 6.0%, p < 0.001), COPD (3.0 versus 4.2%, p = 0.011), and hypertension (40.7 versus 46.9%, p < 0.001) than patients who stayed longer. Shorter operative time (OR 0.986, 95% CI 0.985-0.987, p < 0.001), minimally invasive techniques (OR 2.969, 95% CI 2.686-3.282, p < 0.001), lack of ostomy (OR 0.614, 95% CI 0.478-0.788, p < 0.001), and lack of ureteral stenting (OR 0.641, 95% CI 0.500-0.821, p < 0.001) were associated with early discharge in multivariable analysis. There was no increased incidence of readmission in patients discharged within 23 h. CONCLUSIONS: Twenty-three-hour-stay colectomy is feasible on a national level and does not result in an increased incidence of readmission. Patients undergoing elective procedures without significant medical comorbidities may be eligible for early discharge. Preoperative factors may be used to select patients best suited for this short-stay model.

Prediction of Discharge Destination Following Major Hepatectomy.

BACKGROUND: Anatomic hepatectomies can be associated with complicated post-operative recoveries, often with discharge to post-acute care facilities. This study identifies preoperative and intraoperative factors associated with increased risk for non-home discharge destination after major hepatectomy. METHODS: Patients undergoing major hepatectomy were identified in the NSQIP Targeted Hepatectomy Dataset (2014-2016). Multivariable logistic regression was performed. Patients from 2014 to 2015 were used for training cohort with nomogram generation and 2016 for validation cohort. RESULTS: Overall, 226 of 3750 patients (6.0%) were discharged to rehab, skilled care, or acute care facilities. Preoperative factors associated with non-home discharge on multivariable analysis were outside patient transfers, older age, presence of ascites, ASA physical status 3 or higher, and low preoperative hematocrit (all p < 0.05). Intraoperative factors significantly predictive were concurrent lysis of adhesions, Pringle maneuver, and biliary reconstruction (all p < 0.05). Predictors from testing cohort were validated in validation cohort. Nomograms based on preoperative variables alone and both preoperative and intraoperative variables were generated. CONCLUSION: We identify several preoperative and intraoperative factors that are associated with increased risk for non-home discharge after major hepatectomy. Preoperative anemia represents a potentially modifiable risk factor. Nomograms for preoperative planning as well as immediately following surgery were generated.

Fast-Track Pancreaticoduodenectomy: Factors Associated with Early Discharge.

BACKGROUND: Pancreaticoduodenectomy is a complex surgery frequently associated with prolonged hospitalizations. However, there are a subset of patients discharged within 5 days from surgery; the preoperative and intraoperative characteristics of this subset are unknown. METHODS: The NSQIP Targeted Pancreatectomy Dataset was used from 2014 to 2016. Patients who died within 30 days were excluded. A total of 10,741 patients undergoing pancreaticoduodenectomy were identified. Univariable and multivariable logistic regression analyses were performed for preoperative and intraoperative ACS-NSQIP variables to identify predictors of early discharge. Early discharge was defined as discharge 3-5 days after surgery. RESULTS: A total of 1105 patients (10.3%) were discharged within 5 days following pancreaticoduodenectomy. On multivariable analysis, preoperative factors associated with early discharge included younger age (OR 0.988, p < 0.001), non-obesity (OR 0.737, p = 0.001), those receiving neoadjuvant chemotherapy (OR 1.424, p < 0.001), and lack of COPD (OR 0.489, p = 0.005) or hypertension (OR 0.805, p = 0.007). Intraoperative factors associated with early discharge on multivariable analysis were shorter operation duration (OR 0.999, p = 0.002), minimally invasive surgery (OR 3.537, p < 0.001), and hard pancreatic texture (OR 1.480, p < 0.001). Intraoperative factors associated with non-early discharge were epidural placement (OR 0.485, p < 0.001), drain placement (OR 0.308, p < 0.001), and jejunostomy tube placement (OR 0.278, p < 0.001). Patients discharged within 5 days had a 14.7% readmission rate compared to 17.0% for later discharges (p = 0.047). CONCLUSIONS: Multiple preoperative and intraoperative factors, including some that are potentially modifiable, were significantly associated with early discharge after pancreaticoduodenectomy. Patients with these characteristics may benefit from enhanced recovery after surgery programs and expedited disposition planning postoperatively.