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Background While neoadjuvant chemoradiotherapy (CRT) is considered the standard of care for patients with locally advanced esophageal or gastroesophageal junction (GEJ) cancer, the optimal radiation dosing remains undefined. We aimed to assess the perioperative and long-term outcomes comparing patients treated with low-dose (LD-RT) versus high-dose (HD-RT) radiation therapy. Methods Our institutional database was queried for patients with cT2-T4 or node-positive esophageal or GEJ cancer, who underwent surgery with neoadjuvant chemoradiation from 2010 through 2019. LD-RT and HD-RT regimens were defined as receiving total radiation dose ≤45 Gy and ≥50 Gy, respectively. Kaplan-Meier analysis, Cox proportional hazard modeling, and logistical regression were utilized for statistical analysis. Results A total of 287 patients were identified: 77 (27%) received LD-RT; 210 (73%) received HD-RT. Median follow-up from diagnosis to death or last contact was 37.1 months for the study cohort. Older age at diagnosis (odds ratio [OR] 1.03/year, p = 0.02) and year of diagnosis (OR 0.77/year, p < 0.001) were independently associated with receipt of HD-RT relative to LD-RT. Compared with HD-RT, LD-RT was associated with improved 5 year overall survival (OS; 55.1 vs. 44.1%, p = 0.03). On multivariate hazard modeling, receipt of HD-RT was independently associated with worse OS (hazard ratio [HR] 1.79, 95% 1.19–2.68, p = 0.005), disease-free survival (HR 1.78, 95% CI 1.09–2.88, p = 0.02), and recurrence-free survival (HR 1.68, 95% CI 1.11–2.55, p = 0.01) compared with those treated with LD-RT. Conclusions Despite less frequent utilization than HD-RT strategies, LD-RT is associated with improved survival in those treated with neoadjuvant CRT for esophageal or GEJ cancer.

Superior mesenteric artery (SMA) syndrome is an uncommon phenomenon caused by the compression of the third portion of the duodenum between the aorta and the SMA. Here, we present a previously healthy 15-year-old male who presented with early satiety and 20 kg weight loss. Computed tomography (CT) demonstrated a massive retroperitoneal liposarcoma displacing the entire small intestine into the right upper quadrant. Following resection of the large mass, the patient was intolerant of oral intake despite evidence of bowel function. Abdominal CT revealed a narrowing of the duodenum at the location of the SMA. A nasojejunal feeding tube was placed past this area, and enteral nutrition was initiated before slowly resuming oral intake. Post-operative SMA syndrome is an uncommon complication but should be considered in patients intolerant of oral intake following resection of large abdominal tumors associated with extensive retroperitoneal fat loss, even in the absence of concomitant major visceral resection.

The use of restricted versus expanded panel genetic testing in breast cancer is controversial, with some institutions offering predominantly abbreviated gene panel testing. Our community program has offered larger panel testing for several years. We sought to evaluate the outcomes of large panel genetic testing and understand their impact on patient care. A retrospective review of our multi-institutional tumor registry was performed from 2015 to 2018 for patients undergoing surgery for breast cancer. Referral to genetic counseling and outcomes of panel testing were examined. 2237 patients met study criteria. Median age was 63 years (range 22–99). Eight hundred and thirty-eight patients (37.4%) were referred for genetic counseling. Of these patients, 509 (60.7%) had negative results, 108 (12.8%) had deleterious mutations (37 not included in abbreviated panels), and 221 (26.3%) had variants of undetermined significance (VUS). Bilateral mastectomy rates for patients with deleterious mutations were 53.7%, versus 31% for negative and 32.6% for VUS. Large panel testing finds a significant number of actionable mutations. The increased identification of VUS did not result in higher mastectomy rates. •About 12-14 % of patients with breast cancer referred for genetic testing will have an actionable mutation identified.•A variant of unknown significance (VUS) is not associated with an increased rate of unnecessary bilateral mastectomies.•Expanded panel genetic testing should be considered for patients diagnosed with breast cancer meeting testing criteria.

Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-β (Aβ) plaque pathology in transgenic 6799 mice (Tg6799 mice) when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in Tg6799 mice when left untreated until after a more advanced stage of the disease's development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant Aβ plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment to Tg6799 mice, withheld until after a mid-level progression of AD-like pathology, reduced Aβ levels/plaques and depressive-like behavior. Moreover, this treatment paradigm dramatically improved working memory as compared to control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed.

After neoadjuvant chemotherapy (NAC) for clinically node-positive breast cancer (NPBC), targeted axillary dissection (TAD) reduces the false negative rate (FNR) of axillary node sampling. Axillary lymph node dissection (ALND) is indicated if the clipped node cannot be identified. Prior studies have indicated that a sentinel lymph node harvest (SLNH) of ≥3 also leads to low FNR. We investigated the performance of SLNH thresholds at inferring the status of the axilla during TAD. Retrospective review of the Legacy Health System Tumor Registry was performed. We identified NPBC patients between 2011 and 2016 managed with NAC and TAD. In 29 patients, the FNR of the SLNB component of TAD was 11% with SLNH of ≥3; with SLNH of ≤2 nodes the FNR was 20%. In patients with NPBC receiving NAC, adequate SLNH is associated with acceptably low FNR. The decision to pursue ALND for clip identification should be made on a case-by-case basis. •Adjuvant localization techniques for the clipped node in targeted axillary dissection are increasing in use, but can fail due to technical or device-specific errors.•In patients undergoing TAD, a harvest of 3 or greater sentinel lymph nodes can accurately predict the disease status of the axilla with a low false negative rate.•With adequate lymph node harvest, the oncologic benefit of axillary lymph node dissection for clip identification should be considered on a case by case basis.

Neoadjuvant chemotherapy (NAC) is increasingly used in the treatment of breast cancer. The time interval from last dose of cytotoxic chemotherapy to surgery (TTS) can vary widely. We aimed to evaluate the effect of TTS on postoperative complications. A retrospective review for women treated with NAC at our institution between January 2011 through December 2016 was performed. Charts were reviewed for postoperative wound complications, and multivariate analysis was performed. 455 patients were identified. Median TTS was 30 days (range 11–228). On multivariate analysis, TTS of less than 28 days was associated with 70% higher odds of any wound complication (p < 0.05). Increasing age had the strongest association with the presence of any wound complication (p < 0.0001). The majority of complications were treated in the outpatient setting (n = 80, 83%). Following NAC for breast cancer, TTS less than 28 days is a risk factor for postoperative wound complications; however, the majority of complications are minor and treated in the outpatient setting. Additional data are needed to determine optimal TTS for oncologic outcomes. •Significant practice variability exists for time to surgery after neoadjuvant chemotherapy for breast cancer.•Time to surgery less than 28 days increases odds of any wound complication by 70%.•Increasing age is the dominant risk factor for postoperative wound complications after neoadjuvant chemotherapy.

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a rare cancer. Patients in rural areas may face reduced access to advanced treatments often only available at referral centers. We evaluated the association of referral center treatment with treatment patterns, outcomes, and geography in patients with ICC.MethodsWe queried the Oregon State Cancer Registry for ICC between 1997 and 2016, collecting clinicopathologic, demographic, and oncologic data. Patients were classified by treatment at a referral center or non-referral center. ‘Crowfly’ distance to the nearest referral center (DRC) was calculated. Outcomes were evaluated using Kaplan–Meier, Cox proportional hazards modeling, and logistic regression.ResultsOver 20 years, 740 patients with ICC had a median age of 66 years. Slightly more than half (n = 424, 57%) were non-referral center treated and 316 (43%) were referral center treated. Referral center treatment increased over time (odds ratio [OR] 1.03/year, p < 0.05). Referral center-treated patients had improved overall survival in all patients (median 9 vs. 4 months, p < 0.001), in the non-metastatic group (median 13 vs. 6 months, p < 0.001), and in patients not receiving liver resection (median 6 vs. 3 months, p < 0.05). On multivariable analysis, referral center-treated patients more often underwent chemotherapy, resection, or radiation (all p < 0.05). Increasing DRC (OR 0.98/20 km, p < 0.05) was independently associated with non-referral center treatment.ConclusionPatients with ICC who are evaluated at a referral center are more likely to receive treatments associated with better oncologic outcomes, including patients who are not managed with hepatic resection. Increasing the DRC is associated with treatment at a non-referral center; interventions to facilitate referral, such as telemedicine, may lead to improved outcomes for patients with ICC in rural states.

Cancer remains a significant cause of mortality in developed countries, due in part to difficulties in early detection, understanding disease biology, and assessing treatment response. If effectively harnessed, circulating biomarkers promise to fulfill these needs through non-invasive “liquid” biopsy. While tumors disseminate genetic material and cellular debris into circulation, identifying clinically relevant information from these analytes has proven difficult. In contrast, cell-based circulating biomarkers have multiple advantages, including a source for tumor DNA and protein, and as a cellular reflection of the evolving tumor. While circulating tumor cells (CTCs) have dominated the circulating cell biomarker field, their clinical utility beyond that of prognostication has remained elusive, due to their rarity. Recently, two novel populations of circulating tumor-immune hybrid cells in cancer have been characterized: cancer-associated macrophage-like cells (CAMLs) and circulating hybrid cells (CHCs). CAMLs are macrophage-like cells containing phagocytosed tumor material, while CHCs can result from cell fusion between cancer and immune cells and play a role in the metastatic cascade. Both are detected in higher numbers than CTCs in peripheral blood and demonstrate utility in prognostication and assessing treatment response. Additionally, both cell populations are heterogeneous in their genetic, transcriptomic, and proteomic signatures, and thus have the potential to inform on heterogeneity within tumors. Herein, we review the advances in this exciting field.

The impact of neoadjuvant chemotherapy (NAC) on overall and recurrence-free survival (OS, RFS) in resectable intrahepatic cholangiocarcinoma (ICC) is poorly characterized. We sought to investigate the association of NAC with oncologic outcomes in ICC. We identified n = 52 patients with ICC undergoing hepatectomy from 2004 to 2017. Oncologic outcomes were analyzed using Kaplan-Meier and multivariate Cox proportional hazard modeling. The median patient age was 64-years. NAC was administered in ten (19%) patients, most commonly with gemcitabine-cisplatin (n = 8, 80%). Median RFS and OS were 15 months. and 49 months, respectively. Controlling for stage and margins, NAC was independently associated with improved OS (HR 0.16, P = 0.01) but not RFS (HR 0.54, P = 0.27). NAC was not associated with major post-operative complications (P = 0.25) or R1 margins (P = 0.58). NAC in ICC may hold oncologic benefits beyond downstaging borderline resectable disease, such as identifying patients with favorable biology who are more likely to benefit from resection. •Neoadjuvant chemotherapy in intrahepatic cholangiocarcinoma is associated with improved overall survival.•Neoadjuvant chemotherapy is not associated with major post-operative complications or negative margins.•Non-progression during neoadjuvant chemotherapy may signify more indolent disease biology that is more likely to benefit from resection.