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Given the exponentially aging population and rising life expectancy in the United States, surgeons are facing a challenging frail population who may require surgery but may not qualify based on their general fitness. There is an urgent need for greater awareness of the importance of frailty measurement and the implementation of universal assessment of frail patients into clinical practice. Pairing risk stratification with stringent protocols for prehabilitation and minimally invasive surgery and appropriate enhanced recovery protocols could optimize and condition frail patients before, during, and immediately after surgery to mitigate postoperative complications and consequences on patient function and quality of life. In this paper, highlights from the 2022 Society for Surgery of the Alimentary Tract State-of-the-Art Session on frailty in surgery are presented. This work aims to improve the understanding of the impact of frailty on patients and the methods used to augment the outcomes for frail patients during their surgical experience., (Copyright © 2023 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Little is known about the epidemiology of Merkel cell carcinoma (MCC) and mucosal melanoma (MM). Using the United States (US) National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program data, we compared MCC and MM with cutaneous malignant melanoma (CMM) with respect to incidence rates and prognostic factors to better understand disease etiologies. We describe the proportional incidences of the three cancers along with their survival rates based on 20 years of national data. The incidence rates in 2000-2019 were 203.7 per 1,000,000 people for CMM, 5.9 per 1,000,000 people for MCC and 0.1 per 1,000,000 people for MM. The rates of these cancers increased over time, with the rate of MM tripling between 2000-2009 and 2010-2019. The incidences of these cancers increased with age and rates were highest among non-Hispanic Whites. Fewer MCCs and MMS were diagnosed at the local stage compared with CMM. The cases in the 22 SEER registries in California were not proportional to the 2020 population census but instead were higher than expected for CMM and MCC and lower than expected for MM. Conversely, MM rates were higher than expected in Texas and New York. These analyses highlight similarities in the incidence rates of CMM and MCC-and differences between them and MM rates-by state. Understanding more about MCC and MM is important because of their higher potential for late diagnosis and metastasis, which lead to poor survival.

Introduction: Preoperative eGFR has been found to be a reliable predictor of post-operative outcomes in patients with normal creatinine levels who undergo surgery. The aim of our study was to evaluate the impact of preoperative eGFR levels on short-term post-operative outcomes in patients undergoing pancreatectomy., Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) pancreatectomy file (2014-2017) was queried for all adult patients (age ≥ 18) who underwent pancreatic resection. Patients were stratified into two groups based on their preoperative eGFR (eGFR < 60 mL/min/1.73m 2 and eGFR ≥ 60 mL/min/1.73m 2 ). Outcome measures included post-operative pancreatic fistula, discharge disposition, hospital length of stay, 30-day readmission rate, and 30-day morbidity and mortality. Multivariate logistic regression analysis was performed., Results: A total of 21,148 were included in the study of which 12% (n = 2256) had preoperative eGFR < 60 mL/min/1.73m 2 . Patients in the eGFR < 60 group had prolonged length of stay, were less likely to be discharged home, had higher minor and major complication rates, and higher rates of mortality. On logistic regression analysis, lower preoperative eGFR (< 60 mL/min/1.73m 2 ) was associated with higher odds of prolonged length of stay [aOR: 1.294 (1.166-1.436)], adverse discharge disposition [aOR: 1.860 (1.644-2.103)], minor [aOR: 1.460 (1.321-1.613)] and major complications [aOR: 1.214 (1.086-1.358)], bleeding requiring transfusion [aOR: 1.861 (1.656-2.091)], and mortality [aOR: 2.064 (1.523-2.797)]., Conclusion: Preoperative decreased renal function measured by eGFR is associated with adverse outcomes in patients undergoing pancreatic resection. The results of this study may be valuable in improving preoperative risk stratification and post-operative expectations., (© 2021. The Society for Surgery of the Alimentary Tract.)

Background: The aim of this study is to assess the impact of frailty on short-term outcomes after hepatectomy for colorectal liver metastasis (CRLM)., Methods: Patients were identified using the National Surgical Quality Improvement Program (NSQIP). Patients were divided into 3 categories using the 5-item Modified Frailty Index (mFI)., Results: There were 5230 patients included. 52%, 35%, and 13% had mFI scores of 0, 1, and ≥ 2 respectively. Patients with a ≥ 2 mFI score were more likely to experience minor complication (OR 1.34, 95% CI 1.06-1.69), major complication (OR 1.56, 95% CI 1.15-2.12), readmission (OR 1.55, 95% CI 1.12-2.14), unfavorable discharge (OR 2.48, 95% CI 1.62-3.80), 30-day mortality (OR 3.02, 95% CI 1.02-8.95), prolonged length of stay (OR 1.47, 95% CI 1.18-1.83), and bile leak (OR 1.51, 95% CI 1.02-2.24)., Conclusion: Frailty is associated with increased post-operative complications. The 5-item mFI can guide risk stratification, optimization, and counseling., (© 2021. The Society for Surgery of the Alimentary Tract.)

Cancer screening is an important way to reduce the burden of cancer. The COVID-19 pandemic created delays in screening with the potential to increase cancer disparities in the United States (U.S.). Data from the 2014-2020 Behavioral Risk Factor Surveillance System (BRFSS) survey were analyzed to estimate the percentages of adults who reported cancer screening in the last 12 months consistent with the U.S. Preventive Services Task Force (USPSTF) recommendation for cervical (ages 21-65), breast (ages 50-74), and colorectal cancer (ages 50-75) prior to the pandemic. Cancer screening percentages for 2020 (April-December excluding January-March) were compared to screening percentages for 2014-2019 to begin to look at the impact of the COVID-19 pandemic. Screening percentages for 2020 were decreased from those for 2014-2019 including several underserved racial groups. Decreases in mammography and colonoscopy or sigmoidoscopy were higher among American Indian/Alaskan Natives, Hispanics, and multiracial participants, but decreases in pap test were also highest among Hispanics, Whites, Asians, and African-Americans/Blacks. Decreases in mammograms among women ages 40-49 were also seen. As the 2020 comparison is conservative, the 2021 decreases in cancer screening are expected to be much greater and are likely to increase cancer disparities substantially.

Background: R0 resection for pancreatic cancer is considered standard of care, but is not always achieved. This study looks at R1/R2 resection outcomes compared with chemotherapy alone. Our hypothesis is that patients with margin-positive disease have better outcomes than those receiving chemotherapy alone., Study Design: Stage II pancreatic cancer patients who underwent R1/R2 surgery with/without neoadjuvant chemotherapy, from the National Cancer Database (NCDB) 2010 to 2017 were identified and compared with similar staged patients who received chemotherapy alone. The surgical group was then analyzed by subset based on receipt of chemotherapy: upfront surgery (+/- adjuvant therapy) and neoadjuvant therapy followed by surgery (+/- adjuvant therapy)., Results: There were 11,699 Stage II pancreatic cancer patients included, 9,521 (81.4%) of whom were treated with chemotherapy alone, 15.7% (n = 1,836) had upfront surgery, and 2.9% (n = 342) had neoadjuvant therapy with surgery. R1/R2 neoadjuvant patients had the best overall survival at a mean of 19.75 months (95% CI 17.91, 22.28) compared with the upfront surgery group (17.77 months, 95% CI 15.64, 19.55) and the chemotherapy alone group (10.12 months, 95% CI 8.97, 11.50) (hazard ratio [HR] 0.46 upfront surgery and 0.32 neoadjuvant group, respectively, p < 0.0001). Even with R2 resection, survival was better in surgical patients compared with patients who underwent chemotherapy only (15.76 mo vs 10.22 mo, p = 0.06). Patients with R1/R2 resections had improved survival if they received neoadjuvant/adjuvant chemotherapy, though the survival rates were significantly lower than those with standard R0 resections (n = 16,129)., Conclusions: R1 resection has benefit over chemotherapy alone in pancreatic cancer. Pancreatic cancer patients who are left with microscopic R1 disease have better survival than without surgery, particularly in the setting of neoadjuvant therapy., (Copyright © 2021. Published by Elsevier Inc.)

Background: Negotiation is an essential professional skill. Surgeons negotiating new roles must consider: 1) career level (e.g., new graduate, mid-career or leadership), 2) practice environment (e.g., academic, private practice), 3) organization (e.g., academic, university-affiliated, specialized center), and 4) work-life needs (e.g., geography, joint recruitment)., Methods: A review of the literature related to surgical job negotiation was conducted. Expert opinion was also sought., Results: Current data and experience suggest that negotiation must be tailored to practice type, surgeon experience/skill set and should always occur with the advice of legal counsel. Understanding principled negotiation and engaging in preparation and practice will also improve negotiation skills., Conclusions: Our findings shed light on common blind spots among surgeons negotiating new professional roles and provide guidance on optimizing job negotiation skills., Competing Interests: Declaration of competing interest The authors have no conflict of interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Gastrointestinal cancers are increasingly being treated with NAT before surgical resection. Currently, quality metrics are linked to the number of LNs resected to determine subsequent treatment and prognosis. We hypothesize that NAT decreases LN metastasis, downstages patients, and decreases overall lymph node yields (LNY) compared to initial surgical resection. With increasing use of NAT, this brings into question the validity of quality metrics., Methods: Gastric (stage II/III), pancreatic (stage I/II/III), and rectal cancers (stage II/III) (2010-2015) treated with surgery with/without NAT were identified in National Cancer Database. We evaluated total LNY and LN metastasis with/without NAT and clinical and pathological stage to evaluate rates of downstaging., Results: A total of 7934 gastric, 15,908 pancreatic, and 21,354 rectal cancer patients were included of which 61.1%, 21.2%, and 85.7% received NAT, respectively. NAT patients were more likely to be downstaged (39.9% vs 11.1% gastric P< 0.001, 30.6% vs 3.2% pancreatic P< 0.001, 52.0% vs 16.3% rectal P< 0.001), have lower LNYs (18.8 vs 19.1 gastric P = 0.239, 18.4 vs 17.5 pancreatic P< 0.001, 15.7 vs 20.0 rectal P< 0.001) and have N0 pathologic disease (43.6% vs 26.7% gastric P< 0.001, 51.1% vs 30.9% pancreatic P< 0.001, 65.9% vs 49.4% rectal P< 0.001) when compared to initial surgical resection., Conclusion: NAT for gastrointestinal cancers results in overall lower LN yields, lower LN metastases, and significant downstaging of tumors. As all patients undergoing NAT receive multimodality therapy, LN yield recommendations may not be true quality metric changing., Competing Interests: The authors declare no conflict of interests., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: After implementing a formal resident well-being and resiliency program in our surgery residency, we performed in-depth qualitative interviews to understand residents' perceptions of: (1) the impact and benefits, (2) the essential elements for success, and (3) the desired changes to the well-being program., Design: The well-being program is structured to address mental, physical, and social aspects of resident well-being through monthly experiential sessions. All General Surgery residents participated in the program; content is delivered during residents' protected educational time. For this study, we conducted individual semistructured interviews: residents were asked for their feedback to understand the value, benefits, and drawbacks of program., Setting: Accreditation Council for Graduate Medical Education-accredited General Surgery residency program PARTICIPANTS: We used purposeful selection to maximize diversity in recruiting residents who had participated in program for at least 1 year. Recruitment continued until themes were saturated. Eleven residents were interviewed including 2 from each residency year., Results: Residents reported benefits in 3 thematic spheres: (1) Culture/Community, (2) Communication/Emotional Intelligence, and (3) Work-Life Integration Skills. Key structural elements of success for a well-being program included a committed leader, a receptive department culture, occurrence during protected time, and interactive sessions that taught applicable life skills. In discussing opportunities for improvement, residents desired more faculty-level involvement. Some residents were skeptical of the benefit of time spent learning nontechnical skills; some wanted more emphasis placed on accountability to patients and work., Conclusions: Our qualitative assessment of a novel resident well-being program demonstrates reported benefits that reflect the intent of the program. Residents most benefited from sessions that were interactive, introduced readily applicable skills for their day-to-day lives, and included reinforcement of principles through experiential learning. Engagement of the department leadership is essential to the success of the program, as is ongoing feedback and modification to ensure that program is tailored to the needs of residents., (Copyright © 2019 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Pancreatic cancer is the third leading cause of cancer related deaths in the US. Although lymph node (LN) metastasis is a prognostic indicator, the extent of LN resection is still debated. Our goal was to use the distribution of the ratio of positive to negative LNs to derive a more adequate number of necessary examined LNs based on the target LN threshold (TLNT)., Study Design: Using the National Cancer Database, we performed a retrospective study of surgically resected pancreatic adenocarcinoma (2010 to 2015). We evaluated the number of positive LNs and total LNs examined and the log of the ratio of positive LNs to negative LNs (LODDS). The distribution of LODDS was examined to determine a target LNs examined threshold sufficient to detect N1 disease. Using the LODDS distribution of N1 cases, target LNs examined threshold were calculated to encompass 90 of the N1 group distribution., Results: Of the total 24,038 resected patients included in this study, 26% underwent operation only, 18% received neoadjuvant therapy, and 56% underwent adjuvant therapy. In all, 8,144 (34%) patients had N0 disease and 15,894 (66%) had N1 disease. To capture 90% to 95% of the N1 group, the minimum number of LNs examined would be 18 (LODDS -2.74) to 24 (LODDS -3.04), respectively., Conclusions: Although previous studies have suggested 11 to 17 LNs required for adequate LN sampling in pancreatic cancer, our findings suggest that to capture 90% of cases with N1 disease, 18 LNs is more appropriate., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Although the overall rate of colorectal cancer (CRC) has remained stable, studies have shown an increase in the rate of CRC in young patients (<50) nationwide. We hypothesize that the rectal cancer (RC) rate in young people has increased in rural Appalachia. The goal is to provide insight into the future of RC epidemiology in underserved populations. This Institutional Review Board-approved retrospective study evaluated RC patients diagnosed in 2003 to 2016, and compared the ratio of early-onset RC to the state and national ratios using West Virginia State Cancer Registry, North American Association of Central Cancer Registries (NAACCR) and Surveillance, Epidemiology, and End Results Program Database. Demographics include age, gender, ethnicity, and county. We also evaluated cancer stage, family history, and comorbidities, including body mass index, smoking, and alcohol history. The rate of early-onset RC in our area is 1.5 times higher than the national rates. In our population, 100 per cent of patients were white with an equal gender distribution. Young patients with RC were noted to be more overweight than national rates. Young RC patients are more likely to have a first- or second-degree relative with cancer diagnosis. Smoking was strongly associated with young RC. Compared with national statistics, a higher proportion of young patients had Stage 1 or 2 disease which correlated with better survival. The rate of early-onset RC in the Tristate Appalachian area in West Virginia is higher than the national rate with risk factors including white ethnicity, obesity, diabetes mellitus, smoking, family history, and history of pelvic surgeries. It warrants further investigation and discussion of current CRC screening guidelines that begin at age 50.

Objectives: Non-small-cell lung cancer (NSCLC) patient survival depends on a number of factors, including early diagnosis and initiation of treatment. Standard treatment options for patients with NSCLC include surgery, radiation therapy, and chemotherapy. The objective of this study was to evaluate the impact that the initiation of timely treatment has on patient survival among a cohort of privately insured patients with NSCLC in South Carolina., Methods: Data for the study were retrospectively obtained from the South Carolina Central Cancer Registry and the state health plan Blue Cross and Blue Shield claims. Patients were diagnosed as having NSCLC between January 1, 2005 and December 31, 2010, were aged 18 years or older, and were covered under the state health plan for at least 1 year before diagnosis. The final study sample included 746 patients. Kaplan-Meier curves and Cox proportional hazard modeling were conducted to examine factors associated with survival, stratified by stage at diagnosis., Results: The majority in the study cohort (80%) received timely (≤6 weeks) rather than untimely (>6 weeks) care (20%). The mean survival time for patients receiving timely treatment by stage was 36.9, 27.1, and 12.4 months for localized, regional, and distant metastasis, respectively. The mean survival time for patients receiving untimely care by stage was 39.4, 33.8, and 25.2 months for localized, regional, and distant metastasis, respectively. Among patients with NSCLC in the distant metastasis stage, those receiving timely treatment experienced significantly decreased survival (hazard ratio 2.2) in comparison to those receiving untimely care., Conclusions: Initiation of treatment within 6 weeks is not associated with greater survival time across all stages of cancer (localized, regional, and distant metastasis). Additional research is needed to examine the impact of other treatment quality metrics on the survival of patients with NSCLC, different time thresholds for treatment initiation that may be more meaningful to survival among patients with NSCLC, and timely care among patients with NSCLC in other geographic areas and populations.

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Background: The treatment for a contralateral breast cancer (CBC) presents a growing dilemma given the expanding number of long-term survivors. We hypothesize that there will be specific surgical treatment trends with demographic differences between the treatment groups., Methods: The Surveillance, Epidemiology, and End Results (SEER) cancer database was queried to identify CBC patients from 1998 to 2010. Relevant data were compared among the surgical treatment groups of lumpectomy, mastectomy, and mastectomy/reconstruction., Results: Of 1,534 patients, 31% underwent lumpectomy and 69% underwent mastectomy [201 (21%) mastectomy/reconstruction; 748 (69%) mastectomy alone]. Older patients (age >80 years) were more likely to undergo lumpectomy; those with larger tumors (T4) or node-positive disease more often underwent mastectomy. Overall survival was significantly higher in the mastectomy/reconstruction group (P = .05)., Conclusions: Younger age, larger tumor size, and positive nodal disease were independently associated with mastectomy. As the number of long-term breast cancer survivors increases, factors contributing to CBC treatments must be studied to maximize survival potential., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Major gastric resection alters digestive function and may lead to profound weight loss. The objective of our study was to evaluate trends in body weight loss after curative gastrectomy for malignancy. A review of patients who underwent gastrectomy from 1999 to 2012 at two institutions was conducted. Patient demographics and treatment were assessed. Student's t test and analysis of variance were used to compare groups. Of 168 patients, two patients (1.2%) were Stage 0, 73 (43.5%) Stage I, 46 (27.4%) Stage II, 45 (26.8%) Stage III, and two (1.2%) stage unknown. Fifty-eight patients (34.5%) underwent total gastrectomy with Roux-en-Y esophagojejunostomy and 110 patients (65.5%) underwent subtotal gastrectomy. The average per cent decreases in body mass index (BMI) postgastrectomy at one month, six months, 12 months, and 24 months were 7.6, 11.7, 11.5, and 11.1 per cent, respectively (P = 0.003). The decreases in BMI were the same for all time periods whether patients had subtotal or total gastrectomy. Weight loss after gastric cancer resection is an important measure of quality of life. By understanding patterns of weight change after gastrectomy, we can better counsel and prepare our patients for the long-term effects of gastric cancer surgery.

Objectives: Although the National Lung Screening Trial (NLST) lauds the efficacy of low-dose computed tomography (LDCT) at reducing lung cancer mortality, it has not been widely used for population-based screening. By examining the availability of U.S. LDCT screening centers, and underlying rates of lung cancer incidence, mortality, and smoking prevalence, the need for additional centers may be determined., Materials and Methods: Locations of 203 LDCT screening centers from the Lung Cancer Alliance Screening Centers of Excellence database, a list of active NLST and International Early Lung and Cardiac Action Program (I-ELCAP) screening centers, and an independently conducted survey of Society of Thoracic Radiology members were geocoded and mapped. County-level rates of lung cancer incidence, mortality, and smoking prevalence were also mapped and overlaid with the locations of the 203 LDCT screening centers., Results and Conclusions: Results showed the majority of LDCT screening centers were located in the counties with the highest quartiles of lung cancer incidence and mortality in the Northeast and East North Central states, but several high-risk states had no or few identified screening centers including Oklahoma, Nevada, Mississippi, and Arkansas. As guidelines are implemented and reimbursement for LDCT screening follows, equitable access to LDCT screening centers will become increasingly important, particularly in regions with high rates of lung cancer incidence and smoking prevalence., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Long-term survival rates after treatment for breast cancer are directly influenced by early deaths resulting from disease. For longer-term breast cancer survivors, survival rates appear deceptively low. We hypothesize that the actual survival curve for long-term survivors approaches the overall survival of the general population. The Surveillance, Epidemiology, and End Results database (1988 to 2002) was used to identify patients with nonmetastatic breast cancer who underwent definitive surgical treatment. The survival of the general population was constructed by using national life tables with an age-matched population. Comparisons of survivals were made for 3-, 5-, and 7-year breast cancer survivor cohorts. Of 237,180 patients, 92.4 per cent survived three years, 82.1 per cent five years, and 58.1 per cent seven years. Stage I patients have equivalent or better survivals compared with the age-matched general population in all three cohorts. Stage II patients reached equivalent conditional survival between eight and nine years after diagnosis regardless of cohort. Stage III patients required achieving nine to 10 years after diagnosis to achieve equivalent survival probability, except in 7-year survivors, in whom 10 to 11 years was required. In all stages, once equivalence was reached, survival exceeded the general population over the remaining years. Initial cancer stage influences overall survival for many years after diagnosis. Patients with Stage I cancer return to the general population risk as early as three years after diagnosis, whereas higher stages can require up to nine years to achieve parity with a more generalized population. These findings should be factored into general health screening issues for long-term breast cancer survivors.

Aim: To evaluate the timing of chemotherapy in gastric cancer by comparing survival outcomes in treatment groups., Methods: Patients with surgically resected gastric adenocarcinoma from 1988 to 2006 were identified from the Los Angeles County Cancer Surveillance Program. To evaluate the population most likely to receive and/or benefit from adjunct chemotherapy, inclusion criteria consisted of Stage II or III gastric cancer patients > 18 years of age who underwent curative-intent surgical resection. Patients were categorized into three groups according to the receipt of chemotherapy: (1) no chemotherapy; (2) preoperative chemotherapy; or (3) postoperative chemotherapy. Clinical and pathologic characteristics were compared across the different treatment arms., Results: Of 1518 patients with surgically resected gastric cancer, 327 (21.5%) received perioperative chemotherapy. The majority of these 327 patients were male (68%) with a mean age of 61.5 years; and they were significantly younger than non-chemotherapy patients (mean age, 70.7; P < 0.001). Most patients had tumors frequently located in the distal stomach (34.5%). Preoperative chemotherapy was administered to 11.3% of patients (n = 37) and postoperative therapy to 88.7% of patients (n = 290). An overall survival benefit according to timing of chemotherapy was not observed on univariate or multivariate analysis. Similar results were observed with stage-specific survival analyses (5-year overall survival: Stage II, 25% vs 30%, respectively; Stage III, 14% vs 11%, respectively). Therefore, our results do not identify a survival advantage for specific timing of chemotherapy in locally advanced gastric cancer., Conclusion: This study supports the implementation of a randomized trial comparing the timing of perioperative therapy in patients with locally advanced gastric cancer.

Chemokine receptors mediate cancer progression and metastasis. We have previously examined chemokine receptor CCR9 expression in pancreatic cancer. Here, our objective was to evaluate pancreatic stellate cells (PSCs) as a source of CCL25, the CCR9 ligand, and as an activator of CCL25-CCR9 signaling in pancreatic cancer cells. CCL25 and CCR9 expression levels in human pancreatic cancer tissues and normal human pancreas were assessed by immunohistochemsitry. In vitro secretion of CCL25 in PSCs and PANC-1 cells was verified by enzyme-linked immunosorbent assay. Pancreatic cancer cell invasion was measured using a modified Boyden chamber assay with CCL25, PSC secreted proteins, and PANC-1 secreted proteins as the chemoattractant. There was immunostaining for CCR9 expression in human pancreatic tumor tissues, but not in normal pancreatic tissue. CCL25 expression was absent in the normal pancreatic tissue sample, but was observed in cancer cells and in the stromal cells surrounding the tumor. In vitro, both PANC-1 cells and PSCs secreted CCL25. In an invasion assay, exposure to CCL25, PSC- and PANC-1-conditioned media significantly increased the invasiveness of PANC-1 cells. Inclusion of a CCR9-neutralizing antibody in the invasion assay blocked the increase in invading cells elicited by the chemoattractants. Our studies show that pancreatic cancer invasiveness is enhanced by autocrine and paracrine stimulation of CCR9. PSCs in the tumor microenvironment appear to contribute to paracrine activation of CCR9. Investigations into CCR9 as a potential therapeutic target in pancreatic cancer must consider cancer cell autocrine signaling and also paracrine signaling from interactions in the tumor microenvironment.

Background: Sentinel lymph node biopsy (SLNB) has become the preferred method for axillary nodal staging. The authors examined SLNB utilization in urban versus rural settings as this procedure was adopted and hypothesized that SLNB rates among urban populations increased faster, while the technology shift and acceptance of SLNB were slower at rural centers., Methods: The Surveillance, Epidemiology and End Results database was used to identify patients with invasive node-negative ductal or lobular breast cancer diagnosed from 1998 to 2008. Exclusion criteria were distant metastatic disease, T4 tumors, or incomplete data. Residential setting was divided into groups on the basis of population density., Results: The overall rate of SLNB increased with time (from 10% in 1998 to 73% in 2008). The adoption of SLNB was slower in rural settings than among urban populations (P < .001). By 2003, only urban areas were using SLNB in >50% of cases. Overall, there was a 2-year lag between the increases in SLNB utilization rates in these groups. There was a significant difference in SLNB rates according to tumor size., Conclusion: The overall rate of SLNB remained near 50% and was lower in rural locations in 2004. By 2008, the SLNB rate for T1 and T2 tumors had increased to >50% in all population categories. SLNB utilization was lower in all population categories as tumor size increased. There was an overall 2-year lag in the adoption of SLNB in less populated areas. Although this may represent a more conservative approach, the difference may be attributable to a shortage of experienced surgeons, lack of training, or lack of technological support at smaller institutions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) is a leading worldwide health concern that is responsible for thousands of deaths each year. The primary source of mortality for patients with CRC is the development and subsequent progression of metastatic disease. The most common site for distant metastatic disease is the liver. Although patients with metastatic disease to the liver have several effective treatment options, the only one for cure remains surgical resection of the liver metastases. Historically, most patients with liver metastases have had unresectable disease, and only a small percentage of patients have undergone complete curative resection. However, improved systemic therapies have led to an evolution in strategies to treat metastatic CRC to the liver. Under most conditions the management of these patients remains complex; and as chemotherapy options and new targeted therapies continue to improve outcomes, it is clear that a multidisciplinary approach must be the foundation on which advanced surgical and medical techniques are employed. Here, in this review, we highlight the role of targeted therapies in the surgical management of patients with metastatic CRC to the liver.

Recent reports have indicated that KRAS and TP53 mutations predict response to therapy in colorectal cancer. However, little is known about the relationship between these two common genetic alterations. Micro-RNAs (miRNAs), a class of noncoding RNA implicated in cellular processes, have been increasingly linked to KRAS and TP53. We hypothesized that lethal-7a (let-7a) miRNA regulates KRAS through TP53. To investigate the relationship between KRAS, TP53, and let-7a, we used HCT116 KRAS(mut) human colorectal cancer cells with four different genotypic modifications in TP53 (TP53(-/-), TP53(+/-), TP53(mut/+), and TP53(mut/-) ). Using these cells we observed that K-Ras activity was higher in cells with mutant or knocked out TP53 alleles, suggesting that wild-type TP53 may suppress K-Ras activity. Let-7a was present in HCT116 KRAS(mut) cells, though there was no correlation between let-7a level and TP53 genotype status. To explore how let-7a may regulate K-Ras in the different TP53 genotype cells we used let-7a inhibitor and demonstrated increased K-Ras activity across all TP53, thus corroborating prior reports that let-7a regulates K-Ras. To assess potential clinical implications of this regulatory network, we examined the influence of TP53 genotype and let-7a inhibition on colon cancer cell survival following chemoradiation therapy (CRT). We observed that cells with complete loss of wild-type TP53 alleles ((-/-) or (-/mut)) were resistant to CRT following treatment with 5-fluorouracil and radiation. Further increase in K-Ras activity with let-7a inhibition did not impact survival in these cells. In contrast, cells with single or double wild-type TP53 alleles were moderately responsive to CRT and exhibited resistance when let-7a was inhibited. In summary, our results show a complex regulatory system involving TP53, KRAS, and let-7a. Our results may provide clues to understand and target these interactions in colorectal cancer.

Aim: To examine surgical and medical outcomes for patients with cholangiocarcinoma using a population-based cancer registry., Methods: Using the California Cancer Registry's Cancer Surveillance Program, patients with intrahepatic cholangiocarcinoma treated in Los Angeles County from 1988 to 2006 were identified and evaluated for clinical and pathologic factors and therapies received (surgery, radiation, and chemotherapy). The surgical cohort was further categorized into three treatment groups: patients who received adjuvant chemotherapy, adjuvant chemoradiation, or underwent surgery alone (no chemotherapy or radiation administered). Survival was assessed by Kaplan-Meier method; and Cox proportional hazard modeling was used in multivariate analysis., Results: Of 825 patients, 60.2% received no treatment. Of the remaining 328 patients, 18.5% chemotherapy only, 7.4% chemoradiation, and 13.8% underwent surgery. More male patients underwent surgical resection (P = 0.004). Surgical patients were younger than the patients receiving chemotherapy or chemoradiation (P < 0.001). Of the surgical cohort (n = 114), 60.5% underwent surgery alone while 39.5% underwent surgery plus adjuvant therapy (chemotherapy, n = 20; chemoradiation, n = 21) (P < 0.001). Median survival for all patients in the study was 6.6 mo. Median survival was highest for patients who underwent surgery (23 mo), whereas both chemotherapy (9 mo) and chemoradiation (8 mo) alone were each less effective (P < 0.001). By multivariate analysis, extent of disease, receipt of surgery, and administration of chemotherapy (with/without surgery) were independent predictors of overall survival., Conclusion: This study demonstrates that surgery is a critical treatment modality. Multimodality treatment has yet to be standardized, but play a role in optimal therapy for cholangiocarcinoma.

Gastrointestinal stromal tumors (GISTs) in adolescence are far less common than adult GISTs and have varied GIST genotypes that present diagnostic and therapeutic challenges. Here, we discuss a 21-year-old male with diagnosis of unresectable, imatinib-resistant GIST. At initial evaluation, a neoadjuvant treatment approach was recommended. As such, the patient received imatinib over the course of one year. Unfortunately, the GIST increased in size, and a subsequent attempt at surgical resection was aborted fearing infiltration of major vascular structures. The patient was then referred to our institution, at which time imatinib therapy was discontinued. Surgical intervention was again considered and the patient underwent successful resection of massive intra-abdominal GIST with total gastrectomy and Roux-en-Y esophagojejunostomy. Since pediatric GISTs are typically resistant to imatinib, we performed genotype analysis of the operative specimen that revealed KIT mutations associated with imatinib sensitivity and resistance. Given the sequencing data and operative findings, the patient was started postoperatively on sunitinib. This case illustrates the importance of understanding both adult and pediatric GISTs when implementing appropriate treatment regimens. Since the genotype of GISTs dictates phenotypic behavior, mutational analysis is an important component of care especially for adolescents whose disease may mirror the pediatric or adult population.

Despite the wide acceptance of laparoscopic surgical techniques, its use for gastric cancer has been limited. Laparoscopic total gastrectomy poses many technical challenges when compared with open gastrectomy. Our objective was to evaluate our institutional experience and surgical technique for total gastrectomy. Through a review of patients undergoing total gastrectomy (1999 to 2011), 50 patients were identified. During the first decade, 25 per cent of total gastrectomies were performed laparoscopically compared with 77 per cent since 2009. Compared with open cases, laparoscopic cases yielded a significantly higher number of examined lymph nodes (29 vs 19), lower estimated blood loss (200 vs 450 mL), and shorter length of stay (8 vs 14 days). Median operative time, average tumor size, and number of positive lymph nodes were not different. Morbidity rates were much lower in the laparoscopic series; and 30-day mortality rates were similar in both groups. Laparoscopic total gastrectomy and D2 lymphadenectomy are comparable in safety and have improved efficacy than our open total gastrectomy experience. After initiation of a laparoscopic total gastrectomy program in 2009, the majority of cases in our institution are now performed by laparoscopic techniques.

The RAS gene family is among the most studied and best characterized of the known cancer-related genes. Of the three human ras isoforms, KRAS is the most frequently altered gene, with mutations occurring in 17%-25% of all cancers. In particular, approximately 30%-40% of colon cancers harbor a KRAS mutation. KRAS mutations in colon cancers have been associated with poorer survival and increased tumor aggressiveness. Additionally, KRAS mutations in colorectal cancer lead to resistance to select treatment strategies. In this review we examine the history of KRAS, its prognostic value in patients with colorectal cancer, and evidence supporting its predictive value in determining appropriate therapies for patients with colorectal cancer.

The application of orthotopic liver transplantation (OLT) for patients with hepatocellular cancer (HCC) necessitates highly selective criteria to maximize survival and to optimize allocation of a scarce resource. The objective of this study was to compare the outcomes of OLT for HCC in patients transplanted under Milan and UCSF criteria. The United Network of Organ Sharing (UNOS) database was queried for patients who had undergone OLT for HCC from 2002 to 2007, and 1,972 patients (Milan criteria, n = 1, 913; UCSF criteria, n = 59) were identified. Patients were stratified by pretransplant criteria (Milan versus UCSF), and clinical and pathologic factors and overall survival were compared. There were no differences in age, gender, diabetes mellitus, body mass index, and hepatitis B, or C status between the two groups. Overall survival was similar between the Milan and UCSF cohorts (1-, 2-, 3-, and 4-year survival rates: 88%, 81%, 76%, and 72% versus 91%, 80%, 68% and 51%, respectively, P = 0.21). Although the number of patients within UCSF criteria was small, our results nevertheless suggest that patients with HCC may have equivalent survival when transplanted under Milan and UCSF criteria. Long-term followup may better determine whether UCSF criteria should be widely adopted.

Background: Cancer risk assessment is an important decision-making tool for women considering irreversible risk-reducing surgery. Our objective was to determine the prevalence of BRCA testing among women undergoing bilateral prophylactic mastectomy (BPM) and to review the characteristics of women who choose BPM within a metropolitan setting., Methods: We retrospectively reviewed records of women who underwent BPM in the absence of cancer within 2 health care systems that included 5 metropolitan hospitals. Women with invasive carcinoma or ductal carcinoma in situ (DCIS) were excluded; neither lobular carcinoma in situ (LCIS) nor atypical hyperplasia (AH) were exclusion criteria. We collected demographic information and preoperative screening and risk assessment, BRCA testing, reconstruction, and associated cancer risk-reducing surgery data. We compared women who underwent BRCA testing to those not tested., Results: From January 2002 to July 2009, a total of 71 BPMs were performed. Only 25 women (35.2%) had preoperative BRCA testing; 88% had a BRCA mutation. Compared with tested women, BRCA nontested women were significantly older (39.1 vs. 49.2 years, P < 0.001), had significantly more preoperative biopsies and mammograms and had fewer previous or simultaneous cancer risk-reducing surgery (oophorectomy). Among BRCA nontested women, common indications for BPM were family history of breast cancer (n = 21, 45.6%) or LCIS or AH (n = 16, 34.8%); 9 nontested women (19.6%) chose BPM based on exclusively on cancer-risk anxiety or personal preference., Conclusion: Most women who underwent BPM did not receive preoperative genetic testing. Further studies are needed to corroborate our findings in other geographic regions and practice settings.

Purpose: Severe primary graft dysfunction (PGD) is the major early problem following lung transplantation. Aprotinin, a serine protease inhibitor, has many anti-inflammatory properties that might reduce or prevent lung injury. Our hypothesis was that the incidence of PGD could be reduced by a combination of donor lung perfusion and systemic administration of aprotinin to recipients., Methods and Materials: The study was randomized and placebo controlled. Donor lungs were perfused during procurement with 4 L Perfadex containing aprotinin (280 mg load + 70 mg/hL) or placebo. Aprotinin or placebo was also administered peri-operatively to the recipients. The study was powered to detect a 10% improvement in the primary endpoint of developing ISHLT grade III PGD anytime within 48 hr following the transplant procedure., Results: There were 48 patients randomized. Diagnosis and the use of bypass were different between groups. The study was stopped prematurely at the planned interim analysis point because of published concerns about renal toxicity of aprotinin. There was no difference in the occurrence of the primary endpoint between groups of patients. The median change from the baseline creatinine level at 24, 48, 72 hr; 7 and 30 d following the transplant was not associated with the administration of aprotinin., Conclusions: There was no statistically significant difference in the incidence of the primary endpoint between groups in the study. Excess renal failure related to aprotinin administration in a patient population at high risk for the event was not observed., (© 2010 John Wiley & Sons A/S.)

Introduction: Patients with unilateral breast cancer have an increased risk of developing contralateral breast cancer. A recent population-based study demonstrated that the proportion of patients with unilateral breast cancer in the United States who underwent contralateral prophylactic mastectomy (CPM) has increased by 150% in recent years. The current study evaluated patients who underwent breast cancer surgery in a metropolitan-based hospital system to determine factors associated with CPM., Methods: We reviewed the records of all patients who underwent surgical treatment for breast cancer in 2006 and 2007 in a single health care system, which included six different hospitals. Exclusion criteria included preoperative diagnosis of bilateral disease, stage IV disease, and a history of previous breast cancer. We recorded patient, treatment, tumor, and surgeon characteristics. Multivariate logistic regression models were used to predict CPM use., Results: Of 571 eligible patients, 276 (48.3%) underwent breast-conserving surgery (BCS), 130 (22.8%) underwent unilateral mastectomy, and 165 (28.9%) underwent mastectomy and a CPM. Among mastectomy patients, 55.9% underwent CPM. Young age (<40 vs. >55 years), large tumor size (>5 vs. <2 cm), positive family history, lobular histology, multicentric disease, and surgeon gender (female) were independent predictors of increased CPM rates. Body mass index, tumor grade, estrogen receptor status, and preoperative breast magnetic resonance imaging were not associated with increased CPM rates., Conclusions: Our study is the first to evaluate specific surgeon characteristics associated with CPM use. Prospective studies are needed to examine factors affecting patient decision-making to develop resources that may assist patients in this process.

Introduction: ERBB2 is overexpressed in 15-25% of upper gastrointestinal adenocarcinomas. We use a stable lentiviral shRNA model to demonstrate that ERBB2 suppression in upper gastrointestinal adenocarcinomas with documented ERBB2 amplification effectively decreases ERBB2 protein levels and decreases cell viability. Further, we evaluate tumor growth of cells treated with the ERBB2 shRNA., Methods: Three upper gastrointestinal adenocarcinoma cells lines with varying ERBB2 levels were treated with one of three separate lentiviral green fluorescent protein (GFP)-labeled ERBB2 shRNA vectors or a nonsilencing control shRNA vector for 6 h. Protein levels on day 6 and cell viability was evaluated on days 3-10. A xenograft in vivo experiment was performed using OE19 cells pretransduced with ERBB2 shRNA to evaluate tumor growth., Results: ERBB2 protein levels decreased by 80%. ERBB2 knockdown significantly decreased cell viability in cell lines with high ERBB2 levels. In vivo tumor growth was suppressed in ERBB2-shRNA-treated groups., Conclusion: ERBB2 suppression based on a stable lentiviral shRNA transfection system effectively decreases cell viability in cell lines with amplification of ERBB2 as compared to cell lines without overexpression. ERBB2 knockdown significantly decreases tumor growth in vivo. ERBB2-directed therapy may be of benefit in the subset of patients with gastrointestinal adenocarcinomas exhibiting overamplification of ERBB2.

Background: Although the incidence of adenocarcinoma of the esophageal and gastroesophageal junction has increased at an alarming rate in the past 30 years, little improvement has been made in treatment strategies. Previous studies have demonstrated that many upper gastrointestinal (GI) adenocarcinomas exhibit ERBB2 amplification. In cancers proven to have similar amplification, such as breast, ERBB2-targeted therapies have dramatically improved overall survival and disease-free rates of survival. This study uses siRNA to knockdown ERBB2 in GI adenocarcinoma cell lines to evaluate cell viability, apoptosis, and changes in cell cycle., Methods: A cell line with a baseline amount of ERBB2 (Seg-1) and 2 upper GI adenocarcinoma cell lines with known amplification of ERBB2 (esophageal [OE19] and gastric [MKN45]) were treated with 120 pmol of 1 of 2 independent ERBB2 siRNAs or control siRNA for 6 hours., Results: We demonstrate that knockdown of ERBB2 in esophageal and gastric cancer cell lines with known ERBB2 amplification effectively decreases ERBB2 protein levels and decreases cell viability mainly via apoptotic pathways., Conclusion: ERBB-directed therapy may be of benefit in the subset of patients with GI adenocarcinomas exhibiting amplification of ERBB2.