Smoking history is associated with reduced efficacy of neoadjuvant therapy in pancreatic adenocarcinoma.

BACKGROUND: Differential responses to neoadjuvant therapy (NAT) exist in pancreatic ductal adenocarcinoma (PDAC); however, contributing factors are poorly understood. Tobacco smoke is a common risk factor for PDAC, with nicotine-induced chemoresistance observed in other cancers. This study aimed to explore the potential association between tobacco use and NAT efficacy in PDAC. METHODS: A single-center, retrospective analysis was conducted that included all consecutive patients with PDAC who underwent surgical resection after NAT with a documented smoking history (N = 208). NAT response was measured as percentage fibrosis in the surgical specimen. Multivariable models controlled for covariates and survival were modeled using the Kaplan-Meier method. RESULTS: Postoperatively, major responses to NAT (>95% fibrosis) were less frequently observed in smokers than in nonsmokers (13.7% vs 30.4%, respectively; P = .021). Pathologic complete responses were similarly less frequent in smokers than in nonsmokers (2.1% vs 9.9%, respectively; P = .023). On multivariate analysis controlling for covariates, smoking history remained independently associated with lower odds of major fibrosis (odds ratio [OR], 0.25; 95% CI, 0.10-0.59; P = .002) and pathologic complete response (OR, 0.21; 95% CI, 0.03-0.84; P = .05). The median overall survival was significantly longer in nonsmokers than in smokers (39.1 vs 26.6 months, respectively; P = .05). CONCLUSION: Tobacco use was associated with diminished pathologic responses to NAT. Future research to understand the biology underlying this observation is warranted and may inform differential NAT approaches or counseling among these populations.

Type of neoadjuvant treatment strategy is associated with differential pathologic responses in pancreatic ductal adenocarcinoma.

BACKGROUND: Tumor fibrosis after neoadjuvant treatment (NAT) for pancreatic ductal adenocarcinoma (PDAC) correlates with treatment response. Herein we assessed how different NAT strategies influence pathologic responses and survival. METHODS: Patients with surgically resected PDAC who received NAT (1991-2020) were included. Descriptive statistics compared outcomes amongst fibrosis groups (none, minor <50 â€‹%, partial 51%-94 â€‹%, major ≥95 â€‹%) and NAT (chemotherapy alone, chemoradiation, or chemotherapy â€‹+ â€‹chemoradiation (total neoadjuvant therapy, TNT)). RESULTS: Patients with major fibrosis most often received TNT (65.8 â€‹%, p â€‹< â€‹0.001). Major fibrosis was associated with the greatest rate of downstaging (77.8 â€‹%, p â€‹< â€‹0.001), highest R0 margin rate (100 â€‹%, p â€‹< â€‹0.01), and lowest mean positive lymph node ratio (0.80, p â€‹< â€‹0.01). Amongst complete responders, 11/14 (78.6 â€‹%) received TNT. Median overall (66.3 months, p â€‹= â€‹0.003) and disease-free (54.7months, p â€‹= â€‹0.05) survival were highest with major fibrosis. CONCLUSIONS: Major fibrosis and complete pathologic responses after NAT are most frequent with a TNT strategy and are associated with improved outcomes.

Discrepancies in survival after conversion to open in minimally invasive pancreatoduodenectomy.

BACKGROUND: The extent by which conversion to open (CTO) during minimally invasive procedures for pancreatic cancer impact survival outcomes is not fully understood. METHODS: The 2010-2017 National Cancer Database identified 12,424 non-metastatic patients who underwent pancreatoduodenectomy for ductal adenocarcinoma. Patients were stratified into three cohorts: open (OPD), completed MIPD (cMIPD), and CTO. Subgroups were dichotomized by hospital MIPD volume. RESULTS: Across the study period, 80.6% of patients underwent OPD, 19.4% MIPD, and 24% were CTO. Median overall survival was worse after CTO (21.8 months) than for OPD (23.6 months) or cMIPD (25.2 months) (p < 0.001). Although this effect persisted for <10 MIPD/year, CTO did comparably to OPD at hospitals performing ≥10MIPD/year (CTO = 26.8 months, OPD = 27.9 months; p = 0.128). Ninety-day mortality after CTO was worse at ≤ 10 MIPD/year hospitals (9.3% vs. 2.6%). CONCLUSIONS: Short and long-term survival is impacted by CTO after MIPD, especially at lower surgical volumes, stressing careful adoption while ascending the learning curve.

Total Neoadjuvant Treatment for Pancreatic Ductal Adenocarcinoma Is Associated With Limited Lymph Node Yield but Improved Ratio.

INTRODUCTION: The lymph node yield (LNY) and lymph node ratio (LNR) of nodal metastases following pancreatoduodenectomy (PD) have been reported as prognostic parameters in patients with pancreatic ductal adenocarcinoma (PDAC). However, they have not been compared in the setting of various neoadjuvant therapy modalities. METHODS: A single institutional retrospective study identified 134 patients diagnosed with resectable, BLR- and LA-PDAC who underwent PD at Fox Chase Cancer Center between 2010 and 2019. Patients were categorized based on first-line treatment as follows: surgery first (SF), total neoadjuvant therapy (TNT), and single modality neoadjuvant therapy (SMNT). The histopathological reports of the surgical specimens were examined to obtain LNY and determine the counts of lymph nodes with metastases. Subsequently, LNR was calculated as the number of positive lymph nodes divided by the number of lymph nodes examined. RESULTS: Overall, 49, 38, 27, 12, and 8 patients underwent SF approach, SMNT, incomplete TNT, induction TNT, and consolidation TNT, respectively. There was no difference in R0 resection and vascular resection between the groups (P = 0.096 and 0.794, respectively). The median counts of LNY were 22, 15, 21, 11.5, and 10, respectively (P < 0.001). The average LNR was 0.16, 0.07, 0.03, 0.02, and 0.02, respectively (P < 0.001). There were statistically significant differences in overall survival in the TNT groups (log-rank test P = 0.030). CONCLUSIONS: PDAC patients who undergo the TNT modality exhibit lower LNY and improved LNR compared with the SF approach and SMNT neoadjuvant therapy groups. This is likely explained by the increased treatment response and lymph node obliteration associated with the TNT approach. Our results question the minimal requirement of 11-18 harvested lymph nodes for PD following TNT.

Total neoadjuvant therapy is associated with improved overall survival and pathologic response in pancreatic adenocarcinoma.

BACKGROUND: Few studies have evaluated outcomes of total neoadjuvant therapy (TNT) compared with single modality neoadjuvant therapy (SMNT) or surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC). METHODS: A single-institution retrospective review of PDAC patients who underwent pancreatectomy was conducted (1993-2019). Overall survival (OS) estimates from diagnosis and from surgery were determined using Kaplan-Meier methods; Cox proportional hazards models adjusted for covariates. RESULTS: Surgery was performed upfront (SF) in 168 (46.9%), while 111 (31.0%) had chemotherapy or chemoradiation before resection (SMNT), and 79 (22.1%) underwent TNT (chemotherapy and chemoradiation). Resection margins were more frequently R0 in the TNT group (86.1%) compared with SMNT (64.0%) and SF (72%) (p < 0.001). Complete pathologic response was more common in the TNT group (10.1%) compared with SMNT (3.6%) or SF (0.6%) (p = 0.001), resulting in prolonged survival (median OS = 100.2 months). TNT patients demonstrated longer median OS from surgery (33.6 months) compared with SF (19.1 months) and SMNT (17.4 months) (p = 0.010), which persisted after controlling for covariates. CONCLUSIONS: TNT is associated with more frequent complete pathologic response, a higher rate of margin negative resection, and prolonged OS as compared with SF or SMNT. Additional studies to identify subgroups that derive the greatest benefit are warranted.

Tumor mutational burden and somatic mutation status to predict disease recurrence in advanced melanoma.

Tumor mutational burden (TMB) has recently been identified as a biomarker of response to immune checkpoint inhibitors in many cancers, including melanoma. Co-assessment of TMB with inflammatory markers and genetic mutations may better predict disease outcomes. The goal of this study was to evaluate the potential for TMB and somatic mutations in combination to predict the recurrence of disease in advanced melanoma. A retrospective review of 85 patients with stage III or IV melanoma whose tumors were analyzed by next-generation sequencing was conducted. Fisher's exact test was used to assess differences in TMB category by somatic mutation status as well as recurrence locations. Kaplan-Meier estimates and Cox-proportional regression model were used for survival analyses. The most frequently detected mutations were TERT (32.9%), CDKN2A (28.2%), KMT2 (25.9%), BRAF V600E (24.7%), and NRAS (24.7%). Patients with TMB-L + BRAFWT status were more likely to have a recurrence [hazard ratio (HR), 3.43; confidence interval (CI), 1.29-9.15; P = 0.01] compared to TMB-H + BRAF WT. Patients with TMB-L + NRASmut were more likely to have a recurrence (HR, 5.29; 95% CI, 1.44-19.45; P = 0.01) compared to TMB-H + NRAS WT. TMB-L tumors were associated with local (P = 0.029) and in-transit (P = 0.004) recurrences. Analysis of TMB alone may be insufficient in understanding the relationship between melanoma's molecular profile and the body's immune system. Classification into BRAFmut, NRASmut, and tumor mutational load groups may aid in identifying patients who are more likely to have disease recurrence in advanced melanoma.

Total neoadjuvant therapy for pancreatic adenocarcinoma increases probability for a complete pathologic response.

BACKGROUND: Multiple neoadjuvant therapy protocols have been proposed in the treatment of pancreatic adenocarcinoma, including chemotherapy (CT), chemoradiation (CRT), and total neoadjuvant therapy (TNT), defined as a CT plus CRT. A pathologic complete response (pCR) can be achieved in a minority of cases. We hypothesize that TNT is more likely to confer pCR than other neoadjuvant therapies, which may improve overall survival (OS). METHODS: A retrospective review of the National Cancer Database (NCDB) from 2006 to 2016 was performed, identifying patients who underwent any neoadjuvant therapy followed by definitive pancreatic resection for locally advanced or borderline resectable pancreatic adenocarcinoma. A pathologic complete response was defined as down-staging from any clinical stage to pathologic stage 0. RESULTS: A total of 5402 patients who received neoadjuvant therapy followed by resection were identified. 177 patients (3.3%) achieved a pCR. Of the patients who achieved a pCR, 57 received CT, 41 CRT and 79 received TNT. On multivariate analysis, TNT was more likely to confer a pCR than CRT (OR 1.67, CI 1.13-2.46, p = 0.0103) or CT (OR 2.61, CI 1.83-3.71, p < 0.0001). Patients who achieved pCR had a significantly higher OS, with median survival of 64.9 months, compared to 21.6 months in patients who did not achieve pCR (p < 0.0001). CONCLUSION: TNT may be more likely to achieve a pCR than CT or CRT. Patients who achieve a pCR have a significant OS benefit as compared to those who have residual disease. TNT should be considered for patients requiring neoadjuvant therapy, as it may increase the likelihood of achieving a pCR, thus potentially improving OS.

Combined Inhibition of AKT and KIT Restores Expression of Programmed Cell Death 4 (PDCD4) in Gastrointestinal Stromal Tumor.

The majority of gastrointestinal stromal tumor (GIST) patients develop resistance to the first-line KIT inhibitor, imatinib mesylate (IM), through acquisition of secondary mutations in KIT or bypass signaling pathway activation. In addition to KIT, AKT is a relevant target for inhibition, since the PI3K/AKT pathway is crucial for IM-resistant GIST survival. We evaluated the activity of a novel pan-AKT inhibitor, MK-4440 (formerly ARQ 751), as monotherapy and in combination with IM in GIST cell lines and preclinical models with varying IM sensitivities. Dual inhibition of KIT and AKT demonstrated synergistic effects in IM-sensitive and -resistant GIST cell lines. Proteomic analyses revealed upregulation of the tumor suppressor, PDCD4, in combination treated cells. Enhanced PDCD4 expression correlated to increased cell death. In vivo studies revealed superior efficacy of MK-4440/IM combination in an IM-sensitive preclinical model of GIST compared with either single agent. The combination demonstrated limited efficacy in two IM-resistant models, including a GIST patient-derived xenograft model possessing an exon 9 KIT mutation. These studies provide strong rationale for further use of AKT inhibition in combination with IM in primary GIST; however, alternative agents will need to be tested in combination with AKT inhibition in the resistant setting.

Partial Gastrectomy is Associated with Improved Overall Survival in Signet-Ring Cell Gastric Cancer.

BACKGROUND: Signet-ring cell gastric cancer (SRGC) is a histological variant of gastric adenocarcinoma (GAC) with a worse prognosis compared to non-signet-ring cell gastric cancer (NSRGC). To our knowledge, the overall survival (OS) among patients with SRGC undergoing total/near-total (TG) versus partial gastrectomy (PG) has never been reported from a large-scale Western database. METHODS: We performed a retrospective analysis of patients with both SRGC and NSRGC using The National Cancer Database. RESULTS: In total, 17,086 patients were included. Patients who underwent TG versus PG were 25.5% (n = 770) versus 74.5% (n = 2246) for SRGC, and 20.9% (n = 2943) versus 79.1% (n = 11,127) for NSRGC, respectively. Patients who had SRGC were more likely to undergo TG (25.5% versus 20.9% P< 0.0001). Patients with distal gastric tumors were less likely to undergo TG (16.5% versus 25.4% P < 0.0001). Patients undergoing PG for the SRGC histological variant had better OS (HR = 0.68, CI=0.61-0.76; P < 0.0001) versus those who underwent TG. Similarly, NSRGC patients undergoing PG also had improved OS, but to a lesser extent (HR = 0.91, CI = 0.85-0.96; P= 0.002). Overall, PG for GAC was associated with improved OS compared to TG, although the OS benefit is more profound in the SRGC histological variant (P < 0.0001). CONCLUSIONS: Our results show that TG is not associated with improved OS in patients who undergo gastrectomy for GAC, even when adjusted for tumor location. The survival differences are more pronounced in the SRGC histology variant. The worst survival is observed in patients with SRGC who undergo TG after adjusting for different covariates.

Pancreatic cancer in the era of COVID-19 pandemic: Which one is the lesser of two evils?

Pancreatic adenocarcinoma remains one of the deadliest malignancies affecting the older population. We are experiencing a paradigm shift in the treatment of pancreatic cancer in the era of coronavirus disease 2019 (COVID-19) pandemic. Utilizing neoadjuvant treatment and further conducting a safe surgery while protecting patients in a controlled environment can improve oncological outcomes. On the other hand, an optimal oncologic procedure performed in a hazardous setting could shorten patient survival if recovery is complicated by COVID-19 infection. We believe that oncological treatment protocols must adapt to this new health threat, and pancreatic cancer is not unique in this regard. Although survival may not be as optimistic as most other malignancies, as caregivers and researchers, we are committed to innovating and reshaping the treatment algorithms to minimize morbidity and maximize survival as caregivers and researchers.

Treatment at an Academic Cancer Center Confers Better Survival by Stage for Signet-Ring Cell and Non-signet-Ring Cell Gastric Cancer.

BACKGROUND: The literature lacks large-scale population studies comparing survival outcomes between signet-ring cell gastric carcinoma (SRGC) and non-SRGC (NSRGC) when treatment is delivered at academic versus community cancer centers. METHODS: The National Cancer Database (NCDB) from 2004 to 2016 was queried to examine the association between treatment facility category and overall survival of patients who underwent gastrectomy for resectable gastric adenocarcinoma (GAC). RESULTS: The study investigated 22,871 patients. Upstaging of resectable GAC to pathologic stage 4 was more evident at community centers (3.5%) than at academic centers (2.8%) for the NSRGC variant (p = 0.211), whereas it was comparable between the two facility categories for the SRGC variant (5.9% vs 6%, respectively). Patients with pathologic stage 1 or 3 NSRGC who underwent gastrectomy at academic programs had better overall survival (OS) (hazard ratio [HR], 0.68; p < 0.0001) than those who underwent gastrectomy at community centers (HR, 0.79; p < 0.0065). Similarly, patients with stage 2 SRGC had better OS when treated at academic versus community centers (HR, 0.54; p = 0.0019). No statistically significant improvement in OS was observed between patients with stage 2 NSRGC (HR, 0.84; p = 0.083) and those with stage 3 SRGC (HR, 0.78; p = 0.054) who were treated at academic centers. No survival benefit was demonstrated for stage 1 SRGC when academic and community centers were compared (p = 0.56). CONCLUSIONS: This is the first study based on a large-scale database in the Western population that addressed the overall survival-by-stage of two distinct GAC histologic variants. Treatment at academic centers was associated with significant improvements in OS.

Predicting positive peritoneal cytology in pancreatic cancer.

INTRODUCTION: Positive cytology from peritoneal washings obtained prior to potential resection of pancreatic cancer is associated with grim prognosis, equivalent to M1 disease. We examine our experience with pancreatic cancer patients who underwent pre-resection lavage in an attempt to predict who would have malignant cells on peritoneal cytology. METHODS: We conducted a retrospective review of patients undergoing pancreatectomy for pancreatic adenocarcinoma at a tertiary care institution from 1995 to 2019 and had pre-resection lavage performed. Demographic and clinicopathologic data were collected. Logistic regression models were used to identify predictors of positive cytology. RESULTS: Three hundred ninety-nine patients underwent pancreatic resection and had lavage performed. Forty-three (10.8%) had positive peritoneal cytology. Those with positive cytology had higher median Ca19-9 value than those with negative cytology at diagnosis (368.5 vs 200 U/mL, p = 0.007) and after neoadjuvant therapy (100.3 vs 43 U/mL, p = 0.013). After controlling for preoperative therapy received, an initial Ca19-9 greater than 1220 U/mL (OR 2.72, 95% CI 1.07-6.89, p = 0.035), locally advanced disease (OR 4.86, 95% CI 1.31-18.09, p = 0.018), and BMI ≥ 25 kg/m2 (OR 2.67, 95% CI 1.04-6.97, p = 0.042) were associated with positive cytology in multivariate logistic regression model. The associated ROC curve had an AUC of 0.7507, suggesting adequate discrimination of those with positive peritoneal cytology. CONCLUSION: Diagnostic laparoscopy remains an important adjunct to the workup, diagnosis, and staging of pancreatic adenocarcinoma. Patients with locally advanced disease, significantly elevated serum Ca19-9 at diagnosis, and BMI ≥ 25 kg/m2 may be at higher risk for positive peritoneal cytology, regardless of whether neoadjuvant therapy is administered.

Feasibility of Fitness Tracker Usage to Assess Activity Level and Toxicities in Patients With Colorectal Cancer.

PURPOSE: Performance status (PS) is a subjective assessment of patients' overall health. Quantification of physical activity using a wearable tracker (Fitbit Charge [FC]) may provide an objective measure of patient's overall PS and treatment tolerance. MATERIALS AND METHODS: Patients with colorectal cancer were prospectively enrolled into two cohorts (medical and surgical) and asked to wear FC for 4 days at baseline (start of new chemotherapy [± 4 weeks] or prior to curative resection) and follow-up (4 weeks [± 2 weeks] after initial assessment in medical and postoperative discharge in surgical cohort). Primary end point was feasibility, defined as 75% of patients wearing FC for at least 12 hours/d, 3 of 4 assigned days. Mean steps per day (SPD) were correlated with toxicities of interest (postoperative complication or ≥ grade 3 toxicity). A cutoff of 5,000 SPD was selected to compare outcomes. RESULTS: Eighty patients were accrued over 3 years with 55% males and a median age of 59.5 years. Feasibility end point was met with 68 patients (85%) wearing FC more than predefined duration and majority (91%) finding its use acceptable. The mean SPD count for patients with PS 0 was 6,313, and for those with PS 1, it was 2,925 (122 and 54 active minutes, respectively) (P = .0003). Occurrence of toxicity of interest was lower among patients with SPD > 5,000 (7 of 33, 21%) compared with those with SPD < 5,000 (14 of 43, 32%), although not significant (P = .31). CONCLUSION: Assessment of physical activity with FC is feasible in patients with colorectal cancer and well-accepted. SPD may serve as an adjunct to PS assessment and a possible tool to help predict toxicities, regardless of type of therapy. Future studies incorporating FC can standardize patient assessment and help identify vulnerable population.

Clinical and Histological Basis of Adenosquamous Carcinoma of the Pancreas: A 30-year Experience.

BACKGROUND: Adenosquamous carcinoma (ASC) of the pancreas is a rare form of malignancy with a poor prognosis. We herein report our case series with review of the contemporary literature. METHODS: With institutional review board approval, we identified 23 patients with pancreatic ASC. RESULTS: ASC was more common in women (61%), with a median age of 73 y at presentation. The tumor was in the head of the pancreas in 65% of cases. Six cases (26%) had resectable disease, three (13%) were borderline resectable, and eight (34.7%) were locally advanced or metastatic. First-line treatment included pancreatic resection in eight cases (34.8%), concurrent neoadjuvant chemoradiation in three (13%), and neoadjuvant chemotherapy in two (8.7%). Most resected tumors had pathological T3 stage (80%). Pathological nodal disease was demonstrated in 60%, and margins were positive in three cases. Complete pathological response was not observed, although fibrosis presented in only one case (10%). Eventually, twenty patients developed metastatic disease. Overall survival is 11.5 [95% confidence interval 6, 14.5] months. CONCLUSIONS: ASC demonstrates a more aggressive malignant phenotype and carries a worse prognosis. Oncological resection is the mainstay of treatment. Neoadjuvant chemoradiation is an emerging approach in the management of ASC that has been extrapolated from the adenocarcinoma neoadjuvant trials.

Retroperitoneal Sarcomas: Does Laterality Matter?

BACKGROUND: Sarcomas are malignant tumors of connective tissue that can vary widely in etiology. Parameters such as grade, extent of resection, and tumor integrity have been shown to affect prognosis. Our principal aim was to examine associations between the laterality of retroperitoneal sarcomas and tumor characteristics, treatment, and patient outcomes. MATERIALS AND METHODS: We performed a retrospective study of patients treated at our tertiary referral center with a diagnosis of primary retroperitoneal sarcoma who underwent tumor resection. Categorical variables were compared using the chi-square test, whereas continuous variables were compared using one-way analysis of variance. Cox regression was used to estimate the risk of death. RESULTS: Data from 106 patients were analyzed. A greater proportion of bilateral or midline tumors were leiomyosarcomas (P = 0.02), whereas right-sided tumors were more likely to be liposarcoma (P = 0.02). There was no significant relationship between laterality and tumor grade or stage. Two-thirds of patients had at least one contiguous organ resected (n = 68, 65.4%). Patients with nephrectomy during sarcoma resection were more likely to have right-sided disease (P = 0.02). Splenectomy and pancreatectomy were associated with left-sided disease (P < 0.01; P < 0.01), and pancreaticoduodenectomies with bilateral or midline disease (P < 0.001). Adjusting for age, sex, race, grade, stage, histology, and treatment, there was no increased risk of death or recurrence based on laterality. CONCLUSIONS: Although laterality did not seem to have a measurable relationship with patient outcomes or survival, there was a significant association between laterality, tumor histology, and resection of contiguous organs. These preliminary findings warrant further investigation.

Soft tissue sarcoma of the extremity: Characterizing symptom duration and outcomes.

BACKGROUND: We sought to investigate how the interval between symptom onset and diagnosis of soft tissue sarcoma (STS) of the extremity was associated with survival. METHODS: Patients treated for extremity STS years 2006-2015 were stratified by symptom duration: at least two, six or twelve months between symptom onset and diagnosis. Chi-square tests compared patient and tumor-related characteristics based on symptom duration. Survival analysis included Cox regression and Kaplan-Meier estimates. RESULTS: Of 113 patients included, mean age was 56.7 years, 52.2% were male, and 75.2% were white. Median tumor size was 75 mm, 48.7% were grade 3, and 38.1% were stage I. With symptom duration of either at least 6 or 12 months, a greater proportion of patients who experienced the specified symptom duration had lower grade tumors (p < 0.01 and p = 0.01, respectively) and lower stage disease (p < 0.01 and p = 0.02, respectively) than those who did not. Among all patients, survival estimates were similar between those who experienced a symptom duration of 2 (p = 0.12), 6 (p = 0.18) or 12 (p = 0.61) months and those who did not. CONCLUSION: Patients with extremity STS who tolerated a longer symptom duration had less advanced disease. Reasons for prolonged symptom duration and methods to address these factors warrant further investigation.

Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria.

BACKGROUND & AIMS: In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US. METHODS: We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% white) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999, through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined. RESULTS: The mean size of gastric adenocarcinomas was 23.0 ± 16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI, 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively. CONCLUSIONS: The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases.

Granular cell tumor experience at a comprehensive cancer center.

BACKGROUND: Granular cell tumors (GCTs) are rare lesions occurring almost anywhere in the body. Multiple case reports have been published. However, there are very few large-scale studies regarding GCT. The aim of this study was to define characteristics, treatment patterns and outcomes of patients with GCT. METHODS: An institutional review board-approved retrospective chart review was performed. Descriptive statistics, chi-square analyses, and Kaplan-Meier survival estimates were produced. RESULTS: Fifty patients were treated for GCT at our institution between 1992 and 2015. The median age was 47 y; 62% of patients were female and 64% were whites. Median tumor size was 0.8 cm. Four percent of patients had malignant tumors, 10.0% had atypical tumors, and 86.0% had benign tumors. The most frequent location of tumors was the gastrointestinal tract (n = 30; 60%), followed by skin/subcutaneous tissues (n = 19; 38%), then respiratory tract (n = 1; 2%). Most patients underwent surgical excision or endoscopic removal of their tumors without prior biopsy. Three patients (6%) had multifocal tumors; they were more likely to experience recurrence than patients with unifocal tumors (33.3% versus 10.6%, respectively; P = 0.05). Six patients (12.0%) experienced recurrence, with a median time to recurrence of 13.5 mo. Overall cancer-specific 5-y survival was 98.0%. Overall recurrence-free 5-y survival was 86.4%. Patients with atypical tumors had a lower recurrence-free 5-y survival rate than those with benign tumors (75.0% versus 89.7%, respectively; P = 0.04). CONCLUSIONS: Patients with GCT fair well, particularly when tumors are benign. Patients with multifocal tumors are more likely to experience recurrence and should be closely monitored.

Randomized Clinical Trials in Pancreatic Cancer.

The management of pancreatic cancer has grown rapidly in the last decade. The Gastrointestinal Tumor Study Group trial in 1985 supported postoperative chemoradiation, and a more recent study recommended 6 months of adjuvant gemcitabine and capecitabine or monotherapy with gemcitabine or fluorouracil plus folinic acid, in the absence of neoadjuvant therapy. Clinicians are now studying the role of targeted therapy in pancreatic cancer and neoadjuvant chemotherapy in resectable, borderline resectable, and locally advanced pancreatic cancer. This article critically evaluates the evolution of pancreatic cancer management, focussing on level 1a, prospective randomized control trials from 2007 to 2017.