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Brain metastasis (BM) frequently occurs in patients with cutaneous melanoma, lung, and breast cancer; although, BM rarely arises from cancers of the gastrointestinal tract (GIT). The reported incidence of GIT cancer BM is less than 4%. In the last few years, effective systemic therapy has prolonged the survival of GIT patients and consequently, the incidence of developing BM is rising. Therefore, the epidemiology and biology of BM arising from GIT cancer requires a more comprehensive understanding. In spite of the development of new therapeutic agents for patients with metastatic GIT cancers, survival for patients with BM still remains poor, with a median survival after diagnosis of less than 4 months. Limited evidence suggests that early detection of isolated intra-cranial lesions will enable surgical resection plus systemic and/or radiation therapy, which may lead to an increase in overall survival. Novel diagnostic methods such as blood-based biomarker biopsies may play a crucial role in the early detection of BM. Circulating tumor cells and circulating cell-free nucleic acids are known to serve as blood biomarkers for early detection and treatment response monitoring of multiple cancers. Blood biopsy may improve early diagnosis and treatment monitoring of GIT cancers BM, thus prolonging patients’ survivals.

Background Although the incidence and mortality have decreased, gastric cancer (GC) is still a public health issue globally. An international study reported higher survival in Korea and Japan than other countries, including the United States. We examined the determinant factors of the high survival in Japan compared with the United States. Methods We analysed data on 78,648 cases from the nationwide GC registration project, the Japanese Gastric Cancer Association (JGCA), from 2004-2007 and compared them with 16,722 cases from the Surveillance, Epidemiology, and End Results Program (SEER), a United States population-based cancer registry data from 2004-2010. We estimated 5-year relative survival and applied a multivariate excess hazard model to compare the two countries, considering the effect of number of lymph nodes (LNs) examined. Results Five-year relative survival in Japan was 81.0%, compared with 45.0% in the United States. After controlling for confounding factors, we still observed significantly higher survival in Japan. Among N2 patients, a higher number of LNs examined showed better survival in both countries. Among N3 patients, the relationship between number of LNs examined and differences in survival between the two countries disappeared. Conclusion Although the wide differences in GC survival between Japan and United States can be largely explained by differences in the stage at diagnosis, the number of LNs examined may also help to explain the gaps between two countries, which is related to stage migration.

BACKGROUND: Recent studies have shown an association in non-metastatic colorectal cancer between patient survival and immunoprofiling (expression of CD3, CD4, CD8, CD45, and FOXP3 T cells at the invasive margin (IM) and the tumor center (TC)) regardless of stage. Patients with peritoneal carcinomatosis have a dismal prognosis, but survival can be significantly improved in selected patients who undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, current patient selection for CRS/HIPEC is suboptimal. The purpose of this study is to evaluate immune profiles of patients with peritoneal carcinomatosis and their correlation with overall survival (OS). METHODS: The study cohort included patients from a prospectively maintained database of adults with colorectal peritoneal carcinomatosis who underwent CRS/HIPEC. Immunohistochemistry (IHC) using antibodies to CD3, CD4, CD8, CD45RO, and FOXP3 T cells was performed. IHC image density was calculated using ImageJ software, and an immunoscore was determined. RESULTS: Eighty tumors were evaluated from 66 patients. These included 14 primary sites and 66 metastatic sites. R0/R1 resection was achieved in 44 (66.7%) patients. Known prognostic factors including resection status (HR 1.99, p = 0.004) and lymph node status (HR 3.49, p = 0.002) were associated with overall survival. On multivariate analysis, increased CD3/CD4 IM (HR 0.54, p = 0.03) ratio positively was associated with improved OS. DISCUSSION: This is the first study to assess the utility of subtypes of T cells as prognostic markers in patients with colorectal peritoneal carcinomatosis, which may play a role in patients with low-volume disease. Further studies into immune mechanisms may improve patient selection for cytoreductive surgery and HIPEC as well as provide novel pathways for effective immunotherapy.

Background For patients with pancreatic adenocarcinoma (PA), the optimal time interval between neoadjuvant chemoradiation (CR) to surgical resection has not been well established. Methods The National Cancer Database from 2006 to 2014 was queried for patients ≥18 y old diagnosed with PA who received neoadjuvant CR. Survival and short-term outcomes were compared between patients who had pancreaticoduodenectomy ≤12 wk and >12 wk after completion of CR. Results 1610 patients met selection criteria. Average radiation to surgery (RS) interval was 58.2 ± 39.5 d. 1419 patients had RS interval ≤12 wk (mean 47.4 d) and 191 had RS interval >12 wk (mean 138.8 d). Demographics, CA 19-9 levels, types of chemotherapy and radiation dosage were similar between the two groups. There were more patients with clinical stage III cancers in the >12 wk group than in the ≤12 wk group (33.5% versus 14%). Short-term outcomes were similar between the two groups. However, a long-term survival benefit was observed in the >12 wk group (median 25.8 versus 30.2 mo P = 0.049). An interval >12 wk was associated with significantly prolonged survival on multivariate analysis (HR: 0.80, 95% CI: 0.65-0.99; P = 0.042). Higher clinical stage and positive surgical margins were independently associated with worse survival. Conclusions Surgical resection beyond 12 wk after CR for PA did not worsen short-term outcomes. Waiting may contribute to better patient selection, especially those with locally advanced tumors. In the absence of progressive disease, patients need to be continuously evaluated for surgical resection after CR.

BACKGROUND: Adequate lymph node (LN) sampling is critical for accurate nodal staging in colon cancer (CC), particularly for T3N0 disease as current guidelines recommend considering adjuvant chemotherapy when less than 12 LNs are examined. The impact of sidedness on nodal staging accuracy in patients with T3N0 disease has not been previously studied. METHODS: Patients with pathologic T3 CC were identified from a prospective multicenter international trial of ultrastaging in CC. The probability of true nodal negativity (TNN) based on the number of LN examined was calculated for right and left CC. These results were then validated in a cohort of patients with similar inclusion criteria selected from the National Cancer Database (NCDB) between 2006 and 2014. RESULTS: Three hundred and seventy patients met the inclusion criteria in the trial cohort; 48% were LN-negative. Of 153,945 patients in the NCDB, 57% were LN-negative. The probability of TNN when 12 LNs were examined was 68% for right and 64% for left CC in the trial cohort and 77% and 72% in the NCDB. The number of LNs needed to achieve any given probability of TNN was significantly different between right and left CC in both the trial (P

Although resection historically played a prominent role in the treatment of metastatic melanoma, recent advances have altered the therapeutic landscape, and potentially the role of surgery. We examined surgical selection and metastasectomy outcomes before and after the onset of the effective drug therapy era. Patients with stage IV melanoma were identified and characterized by treatment era (either 1965–2007 or 2008–2015) and by systemic therapy agents. BRAF and/or MEK inhibitors, as well as checkpoint inhibitors, were included as modern agents. Selection factors for metastasectomy were examined by era. A matched-pair analysis of outcomes of surgical and non-surgical patients receiving modern systemic agents was performed. Among 2353 eligible patients, 1065 (45.2%) underwent surgical treatment. Factors associated with selection for metastasectomy in the early era included female sex, no prior stage III disease, single-organ involvement, and M1a (vs. M1c) disease (all p

Brain metastasis (BM) frequently occurs in patients with cutaneous melanoma, lung, and breast cancer; although, BM rarely arises from cancers of the gastrointestinal tract (GIT). The reported incidence of GIT cancer BM is less than 4%. In the last few years, effective systemic therapy has prolonged the survival of GIT patients and consequently, the incidence of developing BM is rising. Therefore, the epidemiology and biology of BM arising from GIT cancer requires a more comprehensive understanding. In spite of the development of new therapeutic agents for patients with metastatic GIT cancers, survival for patients with BM still remains poor, with a median survival after diagnosis of less than 4 months. Limited evidence suggests that early detection of isolated intra-cranial lesions will enable surgical resection plus systemic and/or radiation therapy, which may lead to an increase in overall survival. Novel diagnostic methods such as blood-based biomarker biopsies may play a crucial role in the early detection of BM. Circulating tumor cells and circulating cell-free nucleic acids are known to serve as blood biomarkers for early detection and treatment response monitoring of multiple cancers. Blood biopsy may improve early diagnosis and treatment monitoring of GIT cancers BM, thus prolonging patients' survivals.

Locally advanced rectal cancer represents a complex spectrum of disease pathology and requires an individualized, multidisciplinary approach to care. Locally advanced rectal cancer generally includes stage II and III disease. These tumors invade through the muscularis propria into pericolorectal tissues (T3), penetrate to the surface of visceral peritoneum (T4a), directly invade or adhere to other organs or structures (T4b), or are associated with evidence of locoregional nodal disease (N1-2). During the last 30 years, refined operative techniques and better neoadjuvant and adjuvant treatments have reduced the rates of local recurrence and prolonged disease-free survival. A thorough understanding of the evaluation, staging and therapeutic options is essential to developing individualized treatment algorithms.

Accurate preoperative clinical staging is essential to optimize the treatment of rectal cancer. Primary surgical resection is typically indicated for stage I disease, whereas neoadjuvant therapy is recommended for stages II and III. The objective of this study is to examine the accuracy of clinical staging using current imaging modalities in predicting pathologic stage and, thus, selecting appropriate treatment. Adult patients with nonmetastatic rectal cancer who underwent primary surgical resection were identified from the National Cancer Database between 2006 and 2014. Data on clinical and pathologic staging was obtained. Kappa index was used to determine the correlation between clinical and pathologic staging. A total of 13,175 patients were identified. The correlation between clinical and pathologic staging was 69 per cent for stage I (31% upstaged) (Kappa 0.54, P < 0.001). One-third of patients who were clinically staged as stage I, and were therefore treated with primary surgical resection, had pathologic stage II or III disease. Based on their clinical staging, those patients did not receive the neoadjuvant therapy recommended by present guidelines. Where accurate clinical staging is in doubt, oncologists should carefully examine the quality of staging modality and perhaps consider multimodal imaging using both endorectal ultrasound and MRI.

Colon cancer (CC) is the third most common cancer diagnosed in the United States and the incidence has been rising among young adults. We and others have shown a relationship between the immune infiltrate and prognosis, with improved disease-free survival (DFS) being associated with a higher expression of CD8+ T cells. We hypothesized that a microbial signature might be associated with intratumoral immune cells as well as DFS. We found that the relative abundance of one Operational Taxonomic Unit (OTU), OTU_104, was significantly associated with recurrence even after applying false discovery correction (HR 1.21, CI 1.08 to 1.36). The final multivariable model showed that DFS was influenced by three parameters: N-stage, CD8+ labeling, as well as this OTU_104 belonging to the order Clostridiales. Not only were CD8+ labeling and OTU_104 significant contributors in the final DFS model, but they were also inversely correlated to each other (p=0.022). Interestingly, CD8+ was also significantly associated with the microbiota composition in the tumor: CD8+ T cells was inversely correlated with alpha diversity (p=0.027) and significantly associated with the beta diversity. This study is the first to demonstrate an association among the intratumoral microbiome, CD8+ T cells, and recurrence in CC. An increased relative abundance of a specific OTU_104 was inversely associated with CD8+ T cells and directly associated with CC recurrence. The link between this microbe, CD8+ T cells, and DFS has not been previously shown.

The survival benefit of an extended versus standard lymphadenectomy for gastric cancer (GC) is often attributed to upstaging when more lymph nodes (LNs) are removed, i.e., stage migration. An extended lymphadenectomy is defined as 30 or more LNs examined, a surrogate for a D2 dissection. The aim of this study is to examine whether the survival benefit of extended lymphadenectomy persists when stage migration is not possible. The National Cancer Data Base was queried to identify patients with pathologic N3 (pN3, ≥7 positive LNs) gastric adenocarcinoma. Overall survival (OS) was compared by extent of lymphadenectomy (7–14, 15–29, and ≥30 LN) and stratified by Tstage. Of 2101 pN3 patients, 419 (19.9%) had 7 to 14 LNs examined, 1164 (55.4%) had 15 to 29 LNs examined, and 518 (24.7%) had ≥30 LNs examined. Unadjusted three-year OS in the entire cohort was 24.6, 27.3, 30.5 per cent for 7 to 14 LNs, 15 to 29 LNs, and ≥30 LNs, respectively (P = 0.003). On adjusted survival analysis by stage for patients with pT1-T2N3 disease, removing ≥30 LNs significantly improved OS compared with removing 7 to 14 LNs (hazard ratio [HR] 2.45, 95% confidence interval = 1.25–4.82, P = 0.009). Extended lymphadenectomy may confer a survival benefit in select patients with pT1N3 and pT2N3 GC, highlighting the importance of the number of LNs examined rather than stage migration on survival. For the majority of the N3 population, pT3-pT4, the extent of lymphadenectomy did not significantly improve the OS.

Studies on perioperative outcomes of octogenarians with gastric cancer are limited by small sample size. Our aim was to determine the outcomes of gastrectomy and the variation of treatments associated with advanced age (≥80 y).The National Surgical Quality Improvement Program database was queried from 2005 to 2011. Patients who underwent gastrectomy for malignancy were identified using International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes.Of 2591 cases, 487 patients were octogenarians (≥80) and 2104 were nonoctogenarians (80). Overall, 4.9% of patients had disseminated cancer. Octogenarians had higher 30-d mortality (7.2% versus 2.5%, P 0.01) and more major complications (31.4% versus 25.5%, P 0.01), though fewer octogenarians underwent total gastrectomy (24.0% versus 43.2%, P 0.01) and extended lymphadenectomy (10.1% versus 17.4%, P 0.01) than the nonoctogenarian cohort. On multivariate analysis, age ≥80 y was associated with major complications (OR, 1.3; 95% CI, 1.03-1.6; P = 0.03) and increased mortality (OR, 3.0; 95% CI, 1.9-4.9; P 0.01).Advanced age (≥80 y) was associated with worse outcomes in patients undergoing gastrectomy for malignancy. Therefore, careful staging is necessary to reduce unnecessary operations in this population. Furthermore, surgeons must place greater attention on optimizing the octogenarian population before surgery.

Expression of CD3+ T cells, CD8+ cytotoxic T cells, CD45RO+ memory T cells, and FOXP3+ regulatory T cells at the invasive margin (IM) and tumor center (TC) has correlated with survival in gastric adenocarcinoma (GA) patients from East Asia, independent of anatomic staging. The reason for improved survival in East Asians compared with Western patients is a subject of debate. This study examined the immune profiles of a cohort of Western patients with GA, and their association with overall survival (OS). Immunohistochemistry (IHC) using antibodies to CD3, CD4, CD8, CD45RO, and FOXP3 was performed on a randomly selected resected GA specimens from 88 Western patients. Cutoffs for high or low expression of each marker were determined with maximally selected rank statistics, and multivariable Cox proportional-hazards models constructed to evaluate the relationship between OS and expression of each marker at the IM and TC. Immune cell density was independent of anatomic staging. High expression of CD3, CD4, CD8, and CD45RO at the IM along with CD4 and FOXP3 at the TC were associated with improved OS. A combined marker of CD3, CD8, CD45RO, and FOXP3 associated with OS in East Asian GA was also validated. This is the first report in US patients to demonstrate that high expression of multiple subsets of T lymphocytes in GA is associated with better OS independent of clinical factors and anatomic stage. Further evaluation of immune-modulating mechanisms may explain survival differences between Western and Eastern patients and provide opportunity for novel treatments.

Accurate preoperative clinical staging is essential to optimize the treatment of rectal cancer. Primary surgical resection is typically indicated for stage I disease, whereas neoadjuvant therapy is recommended for stages II and III. The objective of this study is to examine the accuracy of clinical staging using current imaging modalities in predicting pathologic stage and, thus, selecting appropriate treatment. Adult patients with nonmetastatic rectal cancer who underwent primary surgical resection were identified from the National Cancer Database between 2006 and 2014. Data on clinical and pathologic staging was obtained. Kappa index was used to determine the correlation between clinical and pathologic staging. A total of 13,175 patients were identified. The correlation between clinical and pathologic staging was 69 per cent for stage I (31% upstaged) (Kappa 0.54

With reductions in public funding, alternate research funding is essential to surgical oncologists (SOs). We aimed to examine current trends in industry funding of SOs. Society of Surgical Oncology surgeons were identified and matched with board certification and years in practice. Departmental and hospital data were evaluated, and industry payments from 2013 to 2017 were matched with the Open Payment Data. Of the 1670 SOs identified, 922 (55%) had academic positions: 588 (64%) males and 334 (36%) females. Between 2013 and 2017, research payments totaling $46,596,706 were made to 162 SOs (17.5%): $40,774,716 (87%) for research related to drugs and clinical trials, compared with $5,194,199 (11%) for surgical devices (p = 0.018). Funding correlated with academic leadership and years in practice (p = 0.0001 and p = 0.0037). Massachusetts ($9,060,976), Texas ($7,656,228), and New York ($4,210,864) received the most funding, whereas Utah ($1,533,166/SO), Massachusetts ($1,294,425/SO), and Oregon ($1,241,702/SO) received the highest average payments per SO. The majority of funding was from Novartis ($16,045,608), Amgen ($6,810,832), and Merck ($3,758,299), for an oncolytic vaccine (talimogene laherparepvec, $5,939,007), a BRAF inhibitor (dabrafenib, $5,727,309), and a KIT inhibitor (imatinib, $4,323,586). Male SOs received funding more frequently than females (120/588 [20%] vs. 42/334 [12.6%]; p = 0.0027). Males also received more general payments (travel/lodging, food/beverage, consulting/speaker fees): $48,830 vs. $11,867 per male and female, respectively (p = 0.0001). The majority of industry research payments to SOs are related to novel pharmaceuticals, which highlights the expanding influence SOs play in systemic therapies. Industry payments are influenced by location, gender, and academic leadership.

Although uncommon in comparison to other gastrointestinal malignancies, the poor long-term outcomes associated with small intestine adenocarcinoma cause a large burden on healthcare today. Despite advances in other sites, the exact biologic behavior of duodenal, jejunal, and ileal adenocarcinoma remains poorly understood and is reflected by the lack of consensus on optimal treatment strategies. A thorough understanding of the risk factors, clinical presentation, and methods of diagnosis is paramount to establish an early diagnosis, which provides the best chance for long-term meaningful survival.

Stage II–III rectal cancer requires multidisciplinary cancer care, and adolescents and young adults (AYA, ages 15–39 years) often do not receive optimal cancer therapy. Overall, 3295 AYAs with clinical stage II–III rectal cancer were identified in the National Cancer Database. Factors associated with the receipt of adjuvant and surgical therapies, as well as overall survival (OS), were examined. The majority of patients were non-Hispanic White (72.0 %), male (57.5 %), and without comorbidities (93.8 %). A greater proportion of Black and Hispanic patients did not receive radiation (24.5 and 27.1 %, respectively, vs. 16.5 % for non-Hispanic White patients), surgery (22.4 % and 21.6 vs. 12.3 %), or chemotherapy (21.5 % and 24.1 vs. 14.7 %) compared with non-Hispanic White patients (all p

Various mechanisms, including somatic and visceral nociceptive stimulation, have been suggested as a cause for pain after laparoscopic cholecystectomy (LC). We therefore conducted a prospective randomized controlled trial (PRCT) to evaluate whether somatovisceral pain blockade reduces pain after LC. Analgesic efficacy of multimodal analgesia is superior to standard analgesia for patients undergoing elective LC for symptomatic cholelithiasis. Specifically, topical cystic plate and port-site injection with 0.25 % bupivacaine significantly reduces pain after LC. This study was designed as single-blinded PRCT. This study was conducted in an academic medical center. Between February and May 2010 we randomly assigned 63 patients with symptomatic cholelithiasis in a 1:1 ratio to non-opioid/opioid analgesic combinations (Control Group, n = 32) and non-opioid/opioid analgesic combinations plus topical 0.25 % bupivacaine onto the cystic plate and local 0.25 % bupivacaine port-site injection, post-LC (Study Group, n = 31). Primary endpoint was patient-reported pain 1, 4, 6, 12, 24 h and 1 week post-LC using the Visual Analog Scale (VAS 0–10). Study groups were comparable clinicopathologically. There were no adverse events. A statistically significant reduction in mean pain score was apparent in Study Group patients in comparison with Control Group (mean VAS 4.83 ± 2.33 vs. 6.80 ± 1.87; p

Pancreatic surgery outcomes are associated with surgeon and center experience. Anesthesiologists as potential value drivers for pancreatic surgery have not been explored. We sought to evaluate whether anesthesiologists impact perioperative costs for pancreatic surgery.Within an integrated health care system, 796 pancreatic surgeries (526 PDs and 270 DPs) were performed from January 2014 to June 2017. Mean direct operative and anesthesia costs driven by anesthesiologists (operating room (OR) time, anesthesia billing and anesthesia procedures) were determined for each case. The volumes of pancreatic cases per anesthesiologist were calculated, and those above the 75th percentile for volume (4 cases) were considered high-volume. A multivariable analysis of OR/anesthesia costs was performed.Mean OR and anesthesia costs for PD were $7064 for low-volume anesthesiologists (LVA), higher than $5968 for high-volume anesthesiologists (HVA) (p0.001). By multivariable analysis, HVA were associated with decreased costs of $2278 (p0.001). Teams of HVA and high-volume surgeons (HVS) were also associated with decreased mean costs of $1790 (p = 0.04).These data suggest that anesthesiologists experienced in the management of complex pancreatic operations such as PDs may contribute to improved efficiencies in care by reducing perioperative costs.

The survival benefit of an extended versus standard lymphadenectomy for gastric cancer (GC) is often attributed to upstaging when more lymph nodes (LNs) are removed, i.e., stage migration. An extended lymphadenectomy is defined as 30 or more LNs examined, a surrogate for a D2 dissection. The aim of this study is to examine whether the survival benefit of extended lymphadenectomy persists when stage migration is not possible. The National Cancer Data Base was queried to identify patients with pathologic N3 (pN3, ≥7 positive LNs) gastric adenocarcinoma. Overall survival (OS) was compared by extent of lymphadenectomy (7-14, 15-29, and ≥30 LN) and stratified by T stage. Of 2101 pN3 patients, 419 (19.9%) had 7 to 14 LNs examined, 1164 (55.4%) had 15 to 29 LNs examined, and 518 (24.7%) had ≥30 LNs examined. Unadjusted three-year OS in the entire cohort was 24.6, 27.3, 30.5 per cent for 7 to 14 LNs, 15 to 29 LNs, and ≥30 LNs, respectively (P = 0.003). On adjusted survival analysis by stage for patients with pT1-T2N3 disease, removing ≥30 LNs significantly improved OS compared with removing 7 to 14 LNs (hazard ratio [HR] 2.45, 95% confidence interval = 1.25-4.82, P = 0.009). Extended lymphadenectomy may confer a survival benefit in select patients with pT1N3 and pT2N3 GC, highlighting the importance of the number of LNs examined rather than stage migration on survival. For the majority of the N3 population, pT3-pT4, the extent of lymphadenectomy did not significantly improve the OS.

An initiative was established to improve value-based care for pancreatic surgery in a large nonprofit health system. Cost data were presented bimonthly to a hepatobiliary clinical performance group via videoconference.The direct costs were calculated for all patients undergoing distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) between January 2014 and July 2017. Median length of stay, 30-day and 90-day mortality rates, readmission rate, and costs were stratified by surgeon volume using 2 published criteria: "volume pledge" criteria (≥5 PDs/year) and Leapfrog criteria (≥11 PDs/year).There were 270 DPs and 526 PDs performed in 14 hospitals spanning 4 states. Median PD costs were lower for high-volume surgeons (≥5 PDs/year), $21,026 vs $24,706 (p = 0.005). High-volume surgeons had a shorter length of stay (9 days vs 11 days; p0.001) for PD and DP (6 days vs 7 days; p = 0.001). Increased costs for low-volume surgeons included operative/anesthesia costs ($7,321 vs $6,325; p = 0.03), room and board ($5,828 vs $4,580; p = 0.01), and intensive care costs ($4,464 vs $3,113; p = 0.04). Operating time was increased for high-volume surgeons for DP and PD (p0.001). There was no difference in 30-day or 90-day mortality rates or readmissions for DP or PD when stratified by volume pledge criteria. There was no difference in total costs for DP or PD when stratified by Leapfrog criteria.There was a significant cost reduction for PD but not DP when the threshold of 5 PDs was used as a definition of high volume. The sharing of detailed financial data with HPB surgeons on a regular basis provides an opportunity to evaluate practice patterns and thereby reduce direct costs.

Recent randomized trials suggest improved outcomes in patients with locally advanced colon cancer (LACC) treated with neoadjuvant chemotherapy (NAC). Optimal selection of patients for NAC depends on accurate clinical staging. The purpose of this study was to examine the degree of correlation between clinical and pathologic staging in patients with colon cancer (CC). Adult patients with non-metastatic CC who underwent surgery were identified from the National Cancer Data Base between 2006 and 2014. Data on clinical and pathologic staging was obtained. Kappa index was used to determine the correlation between clinical and pathologic staging. One hundred five thousand five hundred sixty-nine patients were identified. The overall correlation rate between clinical and pathologic staging for T stage was 80% (kappa 0.7) and 83% for N stage (kappa 0.6). The correlation rate was 54% for T1, 76% for T2, 95% for T3, and 94% for T4 (P

Purpose: To improve lymph node (LN) staging in patients with colon cancer (CC). The present study describes the selection of CC-specific miRNAs and assesses their utility as a micro metastases detection assay. Methods: 30 miRNAs have been selected from a microarray assay and 16 miRNAs from database mining for their specific upregulation in colon cancer tissues as compared to normal adjacent tissues. Differential expression was validated by RT-qPCR in a larger cohort of samples (n=20) and compared to normal lymphatic tissues (n=6) and normal peripheral blood lymphocytes (PBLs, n=14). The selected miRNA panel was then used for the screening of 84 lymph nodes (LN) obtained from colon cancer patients (n=20) Results: After validation, a panel of 8 miRNAs was found to be significantly upregulated in CC compared to normal adjacent tissues and to normal lymphatic tissues: miR-96, miR-183, miR-194, miR-200a, miR-200b, miR200c, miR-203 and miR-429. A total of 84 LNs were analysed: 12 LN metastases were detected by H&E, 18 by CK staining whereas 32 were detected by the CC-specific miRNA analysis. This represents an increase of 40% in the detection rate. Conclusion: This study demonstrated the ability of a CC-specific 8 miRNA panel in detecting micro metastases in CC patients.

Surgical resection of metastases to the adrenal gland can improve overall survival of patients with stage IV melanoma, but its relative value with respect to current nonsurgical therapies is unknown. We hypothesized that surgery remains an optimal first-line treatment approach for resectable adrenal metastases. A search of our institution's prospectively collected melanoma database identified stage IV patients treated for adrenal metastases between January 1, 2000, and August 11, 2014. The 91 study patients had a mean age of 60.3 years at diagnosis of adrenal metastasis and 24 had undergone adrenalectomy. Improved survival was associated with an unknown primary lesion, surgical resection, and nonsurgical therapies. Median overall survival from diagnosis of adrenal metastases was 29.2 months with adrenalectomy versus 9.4 months with nonoperative treatment. Adrenalectomy, either as complete metastasectomy or targeted to lesions resistant to systemic therapy, is associated with improved long-term survival in metastatic melanoma.

We recently reported, in a prospective randomized trial, that ultra-staging of patients with colon cancer is associated with significantly improved disease-free survival (DFS) compared with conventional staging. That trial did not control for lymph node (LN) number or adjuvant chemotherapy use.The current international prospective multicenter cooperative group trial (ClinicalTrials.gov identifier NCT00949312; "Ultra-staging in Early Colon Cancer") evaluates the 12-LN quality measure and nodal ultra-staging impact on DFS in patients not receiving adjuvant chemotherapy. Eligibility criteria included biopsy-proven colon adenocarcinoma; absence of metastatic disease;12 LNs staged pathologically; pan-cytokeratin immunohistochemistry (IHC) of hematoxylin and eosin (HE)-negative LNs; and no adjuvant chemotherapy.Of 445 patients screened, 203 patients were eligible. The majority of patients had intermediate grade (57.7%) and T3 tumors (64.9%). At a mean follow-up of 36.8 ± 22.1 months (range 0 to 97 months), 94.3% remain disease free. Recurrence was least likely in patients with ≥12 LNs, HE-negative LNs, and IHC-negative LNs (pN0i-): 2.6% vs 16.7% in the pN0i+ group (p0.0001).This is the first prospective report to demonstrate that patients with optimally staged node-negative colon cancer (≥12 LNs, pN0i-) are unlikely to benefit from adjuvant chemotherapy; 97% remain disease free after primary tumor resection. Both surgical and pathologic quality measures are imperative in planning clinical trials in nonmetastatic colon cancer.

Long-acting somatostatin analogues (S-LAR) improve recurrence-free survival in patients with metastatic neuroendocrine tumor (NET) from gastrointestinal (GI) primary, but their impact on overall survival when combined with aggressive cytoreductive surgery is unclear.We reviewed our institutional cancer database to identify patients who underwent cytoreductive surgery for metastatic NET from GI primary between December 1997 and June 2013. Additionally, a cohort selected from 3,384 metastatic neuroendocrine cases in the SEER-Medicare database (January 2003 to December 2009) was used to verify and expand on our results.Most of the 49 patients from our institution had primary lesions in the small intestine (22 of 49 [44.9%]) or pancreas (14 of 49 [28.6%]); 37 patients (75.5%) had metastatic disease at initial diagnosis. These patients underwent 1 (32 of 49 [65.3%]), 2 (11 of 49 [22.4%]), or at least 3 (6 of 49 [12.3%]) surgical procedures; 33 patients (67.3%) underwent resection plus ablation, 19 (38.7%) underwent major hepatectomy, and 34 (69.4%) received S-LAR (29.4% administered preoperatively). Median follow-up was 112 months. Rates of 1-, 5-, 10-, and 15-year disease-specific survival (DSS) were 94%, 78%, 64%, and 31%, respectively, in the 34 patients undergoing aggressive cytoreductive surgery plus S-LAR. Of the SEER-Medicare population, 1,741 patients met inclusion criteria. The DSS for the 104 patients treated with combination therapy was 68.3% at 5 years and 60.6% at 10 years, as compared with 54.7% and 51.8%, respectively, for the 202 patients receiving surgery alone, and 50.0% and 36.0%, respectively, for the 342 patients receiving S-LAR alone (p0.0001). The group receiving neither treatment (n = 1,093) had 5-year and 10-year DSS of 34.3% and 26.3%, respectively.Long-acting somatostatin analogues combined with aggressive cytoreductive surgery improves the long-term survival of select patients with metastatic NET from GI primary.

Gastric adenocarcinoma studies show improved survival for Asians but have not reported stage-specific overall survival (OS) or disease-specific survival (DSS) by race. The Surveillance, Epidemiology and End Results database was queried for cases of gastric adenocarcinoma between 1998 and 2008. We evaluated OS and DSS by race and stage. Number of assessed lymph nodes was compared among surgical patients. Of 49,058 patients with complete staging data, 35,300 were white, 7709 were Asian, and 6049 were black. Asians had significantly better OS for all stages ( P < 0.001) and significantly better DSS for Stages I ( P < 0.0001) and II ( P = 0.0006). As compared with blacks, whites had significantly better DSS for Stages I ( P < 0.0001), II ( P = 0.0055), III ( P = 0.0165), and IV ( P < 0.0001). Among the 28,133 (57%) surgical patients, average number of evaluated lymph nodes was highest for Asians ( P < 0.0001). Among surgical patients with 15 or more nodes evaluated, DSS was worse in blacks with Stage I disease ( P < 0.05). Blacks with gastric adenocarcinoma have a worse DSS, which disappears when surgical treatment includes adequate lymphadenectomy. Race-associated survival differences for gastric adenocarcinoma might simply reflect variations in surgical staging techniques and socioeconomic factors.

The tumor status of the regional lymph nodes is the most important prognostic indicator in colorectal cancer (CRC), as it is in other solid tumors. Sentinel lymph node biopsy (SLNB), which has profoundly impacted the treatment of melanoma and breast cancer, has been applied in CRC in an attempt to improve nodal staging accuracy. The challenge lies in identifying patients who have tumor-negative nodes but are at high risk of regional or distant failure and therefore may benefit from adjuvant chemotherapy. Because standard pathological analysis of lymph nodes may incorrectly stage colon cancer, multiple studies have investigated nodal ultrastaging based on identification and immunohistochemical and/or molecular assessment of the sentinel node. This review focuses on the technique of SNLB, its feasibility and validity, and the controversies that remain regarding the clinical significance of nodal ultrastaging in CRC.

The association between tumor mismatch repair status and obesity in colon cancer is not well understood. The authors of this study hypothesized that mismatch repair deficiency in colon cancer may be associated with a lower Body Mass Index (BMI) and improved patient outcome due to an enhanced tumor immune microenvironment. For this study, 70 patients were randomly selected from a prospective trial evaluating nodal ultrastaging for colon cancer. The mismatch repair status of tumors and immunomarker expression were correlated with clinicopathologic characteristics and evaluated for disease-free survival. Patients with mismatch repair-deficient tumors (n = 11) had a lower mean BMI than those with mismatch repair-proficient tumors (n = 59) (22.16 vs. 26.30 kg/m2, respectively; p = 0.029).The findings showed that CD3+ T cells were inversely associated with mismatch repair proficiency (p = 0.048). Mismatch repair-proficient tumors in nonobese patients (BMI

In 2016, the National Comprehensive Cancer Network included neoadjuvant chemotherapy as a treatment option for patients with clinical T4b colon cancer. However, there is little published data on the survival impact of neoadjuvant chemotherapy for locally advanced colon cancer. Adult patients with non-metastatic clinically staged T3 or T4 colon cancer who underwent surgical resection were identified from the National Cancer Data Base between 2006 and 2014. Treatment was categorized as neoadjuvant chemotherapy followed by surgery and surgery followed by adjuvant chemotherapy. Overall survival was compared between the two groups using propensity score matching. Of 27,575 patients that met inclusion criteria, 26,654 (97%) were treated with surgery followed by adjuvant chemotherapy and 921 (3%) received neoadjuvant chemotherapy followed by surgery. After propensity score matching, patients with T4b colon cancer treated with neoadjuvant chemotherapy had a 23% lower risk of death at 3 years compared to patients that had adjuvant chemotherapy (HR 0.77, 95% CI 0.60–0.98; p = 0.04). However, neoadjuvant chemotherapy did not demonstrate a similar significant benefit for patients with T3 and T4a disease. Patients with clinical T4b colon cancer treated with neoadjuvant chemotherapy may have an improved survival compared to those who receive adjuvant chemotherapy. Further prospective investigation is warranted.

Systemic therapy for metastatic melanoma has evolved rapidly during the last decade, and patient treatment has become more complex.To evaluate the survival benefit achieved through surgical resection of melanoma metastatic to the abdominal viscera in patients treated in the modern treatment environment.This retrospective review of the institutional melanoma database from the John Wayne Cancer Institute at Providence St Johns Health Center, a tertiary-level melanoma referral center, included 1623 patients with melanoma diagnosed as having potentially resectable abdominal metastases before (1969-2003) and after (2004-2014) advances in systemic therapy.Overall survival (OS).Of the 1623 patients identified in the database with abdominal melanoma metastases, 1097 were men (67.6%), and the mean (SD) age was 54.6 (14.6) years. Of the patients with metastatic melanoma, 1623 (320 [19.7%] in the 2004-2014 period) had abdominal metastases, including 336 (20.7%) with metastases in the gastrointestinal tract, 697 (42.9%) in the liver, 138 (8.5%) in the adrenal glands, 38 (2.3%) in the pancreas, 109 (6.7%) in the spleen, and 305 (18.8%) with multiple sites. Median OS was superior in surgical (n = 392; 18.0 months) vs nonsurgical (n = 1231; 7.0 months) patients (P .001). The most favorable 1-year and 2-year OS was seen after surgery for gastrointestinal tract (52% and 41%) and liver (51% and 38%) metastases, respectively. Multivariable analysis found increasing age (hazard ratio [HR], 1.01; 95% CI, 1.00-1.01; P = .02) and the presence of ulceration (HR, 1.21; 95% CI, 1.01-1.45; P = .04) were associated with a worse OS. Alternatively, treatment with metastasectomy (HR, 0.59; 95% CI, 0.46-0.74; P .001) and metastases involving the gastrointestinal tract (HR, 0.65; 95% CI, 0.48-0.87; P = .004) were associated with a better OS. The systemic treatment era did not significantly affect outcomes (HR, 0.82; 95% CI, 0.67-1.02; P = .15). Overall, patients with gastrointestinal tract metastases undergoing complete, curative resection derived the greatest benefit, with a median OS of 64 months.To our knowledge, this series is the largest single-institution experience with abdominal melanoma metastases, demonstrating that surgical resection remains an important treatment consideration even in the systemic treatment era.

Background There is no consensus on the relationship between patient sex and the location, stage, and oncologic outcome of colon cancer (CC). We hypothesized that there is a sex-specific difference in the biology and management of CC. Study Design Our cohort was drawn from a database of patients enrolled in international trials of nodal ultrastaging for nonmetastatic CC. These trials required strict adherence to surgical and pathologic quality measures. Postoperative follow-up included colonoscopy at 1 and 4 years and annual CT scans. Sex-specific differences in tumor biology, location, stage, and recurrence were evaluated by chi-square, Fischer's exact, and independent t -tests. Results The cohort included 435 males (median age 69 years) and 423 females (median age 70 years). Females had more right-sided (p = 0.03) and earlier T stage (p = 0.05) tumors, but there was no sex-based difference in pathologic grade, total lymph nodes retrieved, nodal positivity (p = 0.47) or lymphovascular invasion (p = 0.45). The overall 4-year disease-free survival (DFS) was comparable in females and males (77.9% and 77.5%, respectively). By multivariate analysis, only nodal positivity and cancer recurrence affected overall survival (OS) (p = 0.008). Neither sex nor primary tumor affected DFS or OS. Conclusions This is the first prospective study to demonstrate sex-specific differences in location and T stage of CC when surgical and pathologic management adhered to strict quality standards. The predominance of right-sided CC in females suggests that flexible sigmoidoscopy may be inadequate for screening and surveillance. Interestingly, earlier stage and right-sided location did not confer a DFS or OS advantage for women. Additional studies are needed to determine why females have a higher propensity for right-sided lesions and a potential difference in CC biology.

Unanswered questions remain in determining which high-risk node-negative colon cancer (CC) cohorts benefit from adjuvant therapy and how it may differ in an equal access population. Machine-learned Bayesian Belief Networks (ml-BBNs) accurately estimate outcomes in CC, providing clinicians with Clinical Decision Support System (CDSS) tools to facilitate treatment planning. We evaluated ml-BBNs ability to estimate survival and recurrence in CC. We performed a retrospective analysis of registry data of patients with CC to train–test–crossvalidate ml-BBNs using the Department of Defense Automated Central Tumor Registry (January 1993 to December 2004). Cases with events or follow-up that passed quality control were stratified into 1-, 2-, 3-, and 5-year survival cohorts. ml-BBNs were trained using machine-learning algorithms and k-fold crossvalidation and receiver operating characteristic curve analysis used for validation. BBNs were comprised of 5301 patients and areas under the curve ranged from 0.85 to 0.90. Positive predictive values for recurrence and mortality ranged from 78 to 84 per cent and negative predictive values from 74 to 90 per cent by survival cohort. In the 12-month model alone, 1,132,462,080 unique rule sets allow physicians to predict individual recurrence/mortality estimates. Patients with Stage II (N0M0) CC benefit from chemotherapy at different rates. At one year, all patients older than 73 years of age with T2–4 tumors and abnormal carcinoembryonic antigen levels benefited, whereas at five years, all had relative reduction in mortality with the largest benefit amongst elderly, highest T-stage patients. ml-BBN can readily predict which high-risk patients benefit from adjuvant therapy. CDSS tools yield individualized, clinically relevant estimates of outcomes to assist clinicians in treatment planning.

713 Background: It is debatable whether robotic colectomies is advantageous over laparoscopic colectomies for colon cancer (CC). We aim to evaluate oncologic and perioperative outcomes between robotic and laparoscopic colectomies in a national database. Methods: The National Cancer Database was queried from 2010-2014 for patients with resectable (stage I-III) CC. Lymph node (LN) retrieval, length of stay (LOS), perioperative outcomes and OS were analyzed based on type of surgery: right colectomy vs. left colectomy and robotic (ROBO) vs. laparoscopic (LAP). Results: 61,903 patients met inclusion criteria. There was no difference in inadequate LN retrieval (< 12 LN), or short-term mortality between ROBO and LAP groups. There was a significant decrease in conversion to an open operation and LOS for ROBO vs. LAP groups as well as increased 5 year OS (Table). ROBO colectomies increased four-fold over 5 years. About half were done at community hospitals (56%) and at low ROBO volume hospitals (47.2%). Inadequate LN retrieval in the ROBO group was greater at low volume centers (9.2%) compared to high volume centers (12.3%) (p < 0.0001) as well as at community hospitals (12.2%) compared to academic hospitals (8.5%) (p=0.0003). Conclusions: This population analysis showed that robotic colectomies was associated with equivalent short-term outcomes and LN retrieval as laparoscopic colectomies. However, half of robotic colectomies were done at community hospitals or low volume hospitals, where the rate of inadequate LN retrieval was higher than at academic hospitals or high volume centers. As robotic colectomies increases, it is important that technology is implemented judiciously so that oncologic outcomes are not compromised. [Table: see text]

166 Background: Prognosis remains poor for metastatic gastric cancer. Gastrectomy in the setting of stage IV disease is typically reserved for palliation of symptoms such as bleeding or obstruction. The potential survival benefit of resection on survival is controversial. The objective of this study is to determine using the National Cancer Database (NCDB) whether there was an increase in overall survival in patients diagnosed with metastatic cancer who underwent a gastrectomy in addition to chemotherapy. Methods: The NCDB was queried between 2004-2014 for patients with metastatic gastric cancer (adenocarcinoma, mucinous adenocarcinoma, or signet ring carcinoma) who received chemotherapy. Kaplan-Meier analysis and multivariate Cox proportional hazards regression analysis was done using SAS software. Results: A total of 20,599 patients met inclusion criteria. A minority of these patients (2,508; 12.2%) underwent gastric resection in addition to chemotherapy. The median overall survival for those who underwent gastrectomy was 14.1 months compared to 8.6 months for chemotherapy alone (p < 0.0001). Other factors influencing survival included age, race, Charlson-Deyo co-morbidity index, year of diagnosis, primary tumor site, grade, and metastasis to multiple organs. Following multivariate analysis, patients who underwent gastrectomy and chemotherapy had a 36% lower risk of death compared to patients that had received chemotherapy alone (HR 0.64, 95% CI 0.48–0.80, P < 0.0001). Conclusions: In this population analysis, the addition of gastrectomy to chemotherapy was associated with improved overall survival for patients with stage IV gastric cancer and should be considered for patients that are surgical candidates. Patients who underwent gastrectomy had a 36% decreased risk of death compared to those who had chemotherapy alone. However, only a small proportion of patients in the United States received multimodality treatment.

Although staging for colon cancer has become more complex over time, it is not clear that this complexity has improved prognostic assessment. Even with revisions in the 7th edition of the AJCC staging system, a clear rank order of prognosis from substage to substage has not been established. Improved staging models will need to be developed, and attempts at further identifying those high-risk patients within each stage may be clinically useful. Through improved quality measures with lymph node yield, advances in colon cancer staging accuracy have been made over the last decade. Determining how to incorporate ultrastaging and molecular techniques will be the challenge for future staging models.