Search

Importance: Serial circulating tumor DNA (ctDNA) has emerged as a routine surveillance strategy for patients with resected colorectal cancer, but how serial ctDNA monitoring is associated with potential curative outcomes has not been formally assessed., Objective: To examine whether there is a benefit of adding serial ctDNA assays to standard-of-care imaging surveillance for potential curative outcomes in patients with resected colorectal cancer., Design, Setting, and Participants: In this single-center (City of Hope Comprehensive Cancer Center, Duarte, California), retrospective, case cohort study, patients with stage II to IV colorectal cancer underwent curative resection and were monitored with serial ctDNA assay and National Cancer Center Network (NCCN)-guided imaging surveillance from September 20, 2019, to April 3, 2024. The median duration of follow-up was 26 months (range, 2-54 months)., Interventions: Serial ctDNA assays were performed every 3 months for 2 years and every 6 months for the 3 following years in conjunction with NCCN-guided radiographic surveillance., Main Outcomes and Measures: The primary outcome was the proportion of patients with clinical benefit from ctDNA testing, defined as the proportion of patients with a newly positive ctDNA assay and negative scheduled imaging (most recent or concurrent) that subsequently led to early imaging confirmation of recurrence, followed by curative-intent intervention with no evidence of recurrence at the time of data cutoff. Recurrence was categorized by ctDNA recurrence, radiographic recurrence, or concurrent ctDNA and imaging recurrence. Salvage resections and associated durable remissions were described within each of the 3 categories. Descriptive statistics were used to characterize the patient population., Results: In total, 184 patients (median age, 59 years [range, 32-88 years]; 97 female [52.7%]) were included in this study, and 129 (70.1%) had stage II to III disease. Forty-five patients (24.5%) had ctDNA or imaging-confirmed recurrence. Of these 45 patients, 14 had radiographic recurrence with negative ctDNA, and 11 had concurrent ctDNA and imaging recurrence. Twenty of 45 patients had ctDNA positivity with negative imaging at first ctDNA positivity; 6 had reflex imaging that was positive for recurrence, and 14 continued with serial imaging and ctDNA monitoring. Ten of 14 patients had subsequent recurrent disease, 3 patients had a spontaneous clearance of ctDNA, and 1 patient remained imaging negative 7 months after positive ctDNA, after which she was lost to follow-up. Altogether, 11 of 20 patients with ctDNA recurrence without initial concurrent imaging recurrence had subsequent metastasectomy, and only 3 were disease-free at the cutoff date in April 2024, representing 1.6% of the surveilled population., Conclusions and Relevance: In this cohort study of patients with stage II to IV colorectal cancer who underwent curative-intent resection, the addition of serial tumor-informed ctDNA assay to the standard NCCN-recommended surveillance had limited clinical benefits. Additional prospective research is needed to clarify the value of ctDNA testing in the surveillance setting.

Background and Objectives: Surgical site infections (SSIs) after cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) are a major cause of potentially avoidable morbidity. We explored the association of negative pressure wound therapy (NPWT) with SSI in patients undergoing CRS/HIPEC., Methods: Retrospective analysis of consecutive patients undergoing CRS/HIPEC for non-gynecologic cancers. Exposure was the receipt of NPWT versus traditional skin closure. Primary outcome was SSI within 90 days of surgery. We performed multivariable logistic regression (before and after entropy balancing) to evaluate the association of exposure with outcomes., Results: A total of 251 patients were included, of which 43 (17%) received NPWT and 26 (10.4%) developed SSIs. Baseline demographics and clinicopathologic characteristics were similar between the two groups with some exceptions: Patients who received NPWT had a higher Peritoneal Carcinomatosis Index (median 19 vs. 11, p = 0.002) and operative time (10 vs. 8.2 h, p = 0.003) but were less likely to undergo HIPEC (84% vs. 95%, p < 0.05). After entropy balancing, on multivariable logistic regression, NPWT was not associated with 90-day SSI (odds ratio = 0.90; 95% confidence interval = 0.21-3.80; p = 0.89)., Conclusion: NPWT was not associated with a reduction in SSIs. These findings prompt a reevaluation of the routine use of NPWT in CRS/HIPEC., (© 2024 Wiley Periodicals LLC.)

Background: For open minor hepatectomy, morbidity and recovery are dominated by the incision. The robotic approach may transform this "incision dominant procedure" into a safe outpatient procedure., Study Design: We audited outpatient (less than 2 midnights) robotic hepatectomy at 6 hepatobiliary centers in 2 nations to test the hypothesis that the robotic approach can be a safe and effective short-stay procedure. Establishing early recovery after surgery programs were active at all sites, and home digital monitoring was available at 1 of the institutions., Results: A total of 307 outpatient (26 same-day and 281 next-day discharge) robotic hepatectomies were identified (2013 to 2023). Most were minor hepatectomies (194 single segments, 90 bi-segmentectomies, 14 three segments, and 8 four segments). Thirty-nine (13%) were for benign histology, whereas 268 were for cancer (33 hepatocellular carcinoma, 27 biliary, and 208 metastatic disease). Patient characteristics were a median age of 60 years (18 to 93 years), 55% male, and a median BMI of 26 kg/m 2 (14 to 63 kg/m 2 ). Thirty (10%) patients had cirrhosis. One hundred eighty-seven (61%) had previous abdominal operation. Median operative time was 163 minutes (30 to 433 minutes), with a median blood loss of 50 mL (10 to 900 mL). There were no deaths and 6 complications (2%): 2 wound infections, 1 failure to thrive, and 3 perihepatic abscesses. Readmission was required in 5 (1.6%) patients. Of the 268 malignancy cases, 25 (9%) were R1 resections. Of the 128 with superior segment resections (segments 7, 8, 4A, 2, and 1), there were 12 positive margins (9%) and 2 readmissions for abscess., Conclusions: Outpatient robotic hepatectomy in well-selected cases is safe (0 mortality, 2% complication, and 1.6% readmission), including resection in the superior or posterior portions of the liver that is challenging with nonarticulating laparoscopic instruments., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Talimogene laherparepvec (TVEC) is a genetically modified oncolytic herpes simplex virus (HSV-1) that is used for the intralesional treatment of advanced or metastatic melanoma. Given that TVEC produces the granulocyte-macrophage colony-stimulating factor (GM-CSF), recent reports have suggested that radiation treatment (RT) given in conjunction with TVEC may provide synergistic immune activation at the site, and possibly systemically. However, studies on combining RT with TVEC remain limited. We conducted a retrospective review of melanoma patients from a single cancer center who received TVEC and RT in the same region of the body and compared them to patients who received TVEC with RT at another site (other than the site of TVEC injection). Between January 2015 and September 2022, we identified twenty patients who were treated with TVEC and RT; fourteen patients received TVEC and RT in the same region, and six had treatments in separate regions. Regions were determined at the time of analysis and were based on anatomic sites (such as arm, leg, torso, etc.). Kaplan-Meier analysis of progression-free survival (PFS), analyses of time to distant metastasis (DM), overall survival (OS), and locoregional control (LRC), and the corresponding log-rank test were performed. With a median follow-up of 10.5 months [mos] (range 1.0-58.7 mos), we found an improvement in PFS with TVEC and RT in the same region compared to different regions, which were 6.4 mos (95% CI, 2.4-NR mos) and 2.8 mos (95% CI, 0.7-4.4 mos), respectively; p = 0.005. There was also a significant improvement in DM when TVEC and RT were used in the same region compared to different regions: 13.8 mos (95% CI, 4.6-NR mos) and 2.8 mos (95% CI, 0.7-4.4 mos), respectively ( p = 0.001). However, we found no difference in overall survival (OS) between patients who had TVEC and RT in the same region (19.0 mos, 95% confidence interval [CI], 4.1-not reached [NR] mos) and those who received treatments in different regions (18.5 mos, 95% CI, 1.0-NR mos); p = 0.366. There was no statistically significant improvement in locoregional control (LRC) in patients who had TVEC and RT in the same region was 26.0 mos (95% CI, 6.4-26.0 mos) compared to patients who received TVEC and RT in different regions (4.4 mos) (95% CI, 0.7-NR mos) ( p = 0.115). No grade 3 or higher toxicities were documented in either group. Overall, there were improvements in PFS and DM when TVEC and RT were delivered to the same region of the body compared to when they were used in different regions. However, we did not find a significant difference in locoregional recurrence or OS. Future studies are needed to assess the sequence and timing of combining RT and TVEC to potentially enhance the immune response both locally and distantly.

Background and Objectives: Following gastric and esophageal cancer surgery, patients often experience significant, prolonged eating-related symptoms. One promising approach to help patients improve their eating-related quality of life (QOL) is through self-management coaching to aid in diet modification. We performed a randomized pilot study of a nutritionist-led telehealth intervention for the self-management of eating after gastroesophageal cancer surgery., Methods: Patients who were within 30 days of resuming oral intake after undergoing surgery for gastric and/or esophageal cancer were consented and then randomized to the intervention or usual care. The intervention was performed by a nutritionist trained in self-management coaching and delivered in four telehealth sessions over 4 months. The following outcomes were measured at baseline and at 6 months after baseline: QOL (EORTC QLQC30), weight, body mass index, and sarcopenia., Results: Fifty-three patients were enrolled. 22/27 usual care and 21/26 intervention patients completed the study for a retention rate of 81%. Differences between the intervention and control groups were not statistically significant, but the intervention group had indications of greater improvements in overall QOL as measured by EORTC QLQC30 Summary Score (8.7 vs. 2.3, p = 0.17) as well as greater improvements in 4/5 functional domains (p > 0.3). The intervention group also had slightly more weight gain (6 kg vs. 3 kg, p = 0.3) and less sarcopenia (3/16 vs. 9/18, p = 0.07)., Conclusions: This pilot study demonstrated the feasibility and acceptability of a telehealth intervention for self-management of eating symptoms after gastroesophageal cancer surgery. There were trends toward improved overall QOL in the intervention group. A larger study is needed to validate the results., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: While liver cancer stem cells (CSCs) play a crucial role in hepatocellular carcinoma (HCC) initiation, progression, recurrence, and treatment resistance, the mechanism underlying liver CSC self-renewal remains elusive. We aim to characterize the role of Methyltransferase 16 (METTL16), a recently identified RNA N 6 -methyladenosine (m 6 A) methyltransferase, in HCC development/maintenance, CSC stemness, as well as normal hepatogenesis., Methods: Liver-specific Mettl16 conditional KO (cKO) mice were generated to assess its role in HCC pathogenesis and normal hepatogenesis. Hydrodynamic tail-vein injection (HDTVi)-induced de novo hepatocarcinogenesis and xenograft models were utilized to determine the role of METTL16 in HCC initiation and progression. A limiting dilution assay was utilized to evaluate CSC frequency. Functionally essential targets were revealed via integrative analysis of multi-omics data, including RNA-seq, RNA immunoprecipitation (RIP)-seq, and ribosome profiling., Results: METTL16 is highly expressed in liver CSCs and its depletion dramatically decreased CSC frequency in vitro and in vivo. Mettl16 KO significantly attenuated HCC initiation and progression, yet only slightly influenced normal hepatogenesis. Mechanistic studies, including high-throughput sequencing, unveiled METTL16 as a key regulator of ribosomal RNA (rRNA) maturation and mRNA translation and identified eukaryotic translation initiation factor 3 subunit a (eIF3a) transcript as a bona-fide target of METTL16 in HCC. In addition, the functionally essential regions of METTL16 were revealed by CRISPR gene tiling scan, which will pave the way for the development of potential inhibitor(s)., Conclusions: Our findings highlight the crucial oncogenic role of METTL16 in promoting HCC pathogenesis and enhancing liver CSC self-renewal through augmenting mRNA translation efficiency., (© 2024. The Author(s).)

Biliary tract cancers are a rare diagnosis with a rising incidence. Up to 20% of patients have peritoneal metastases, resulting in symptoms of ascites, abdominal pain and potential bowel obstruction. A standard of care systemic treatment comprises gemcitabine, cisplatin and durvalumab (gem/cis/durva). However, the clinical benefit among patients with peritoneal metastases remains unknown. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivers chemotherapy directly to the peritoneal space, which could potentially improve efficacy with minimal systemic toxicity. We describe the design of a Phase I study investigating PIPAC with nab-paclitaxel plus systemic gem/cis/durva among biliary tract cancer patients with peritoneal metastases who have not received prior systemic treatment. The primary end point is safety of PIPAC with nab-paclitaxel in combination with systemic gem/cis/durva. Clinical Trial Registration: NCT05285358 (ClinicalTrials.gov).

Background: Esophagojejunostomy after minimally invasive total gastrectomy (MITG) for gastric cancer (GC) is technically challenging. Failure of the esophagojejunal anastomosis can lead to significant morbidity, leading to short- and long-term quality of life (QoL) impairment or mortality. The optimal reconstruction method following MITG remains controversial. We evaluated outcomes of minimally invasive esophagojejunostomy after laparoscopic or robotic total gastrectomies., Methods: We retrospectively reviewed MITG patients between 2015 and 2020 at two high-volume centers in China and the United States. Eligible patients were divided into groups by different reconstruction methods. We compared clinicopathologic characteristics, postoperative outcomes, including complication rates, overall survival rate (OS), disease-free survival rate (DFS), and patient-reported QoL., Results: GC patients (n = 105) were divided into intracorporeal esophagojejunostomy (IEJ, n = 60) and extracorporeal esophagojejunostomy (EEJ, n = 45) groups. EEJ had higher incidence of wound infection (8.3% vs 13.3%, P = 0.044) and pneumonia (21.7% vs 40.0%, P = 0.042) than IEJ. The linear stapler (LS) group was inferior to the circular stapler (CS) group in reflux [50.0 (11.1-77.8) vs 44.4 (0.0-66.7), P = 0.041] and diarrhea [33.3 (0.0-66.7) vs 0.0 (0.0-66.7), P = 0.045] while LS was better than CS for dysphagia [22.2 (0.0-33.3) vs 11.1 (0.0-33.3), P = 0.049] and eating restrictions [33.3 (16.7-58.3) vs 41.7 (16.7-66.7), P = 0.029] at 1 year. OS and DFS did not differ significantly between LS and CS., Conclusions: IEJ anastomosis generated better results than EEJ. LS was associated with a better patient eating experience, but more diarrhea and reflux compared with CS. Clinical and patient-reported outcomes show the superiority of IEJ with the LS reconstruction method in MITG for GC., (© 2023. The Author(s).)

Background: T4 colon cancers have been underrepresented in randomized trials comparing minimally invasive colectomy (MC) versus open colectomy (OC). Retrospective studies suggest improved survival with MC versus OC, but have not addressed the impact of tumor extent., Methods: Using the National Cancer Database (NCDB), we analyzed patients undergoing colectomy for T4 colon adenocarcinoma from 2010 to 2014. Propensity score matching was performed between MC and OC patients. Tumor extent was defined by zones based on adjacent organ involvement., Results: Of the 19 178 eligible patients, 6564 (34%) underwent MC. After matching, MC was associated with improved overall survival (hazard ratios: 0.71, 95% confidence interval: 0.67-0.76; median OS 59 vs. 42 months, p < 0.001). Compared to MC patients, those undergoing OC had: a higher margin positive rate (p = 0.009); lower median nodes examined (p < 0.001); a lower rate of adjuvant chemotherapy (p < 0.001); and a longer median time to chemotherapy (p < 0.001). Stratified survival analyses demonstrated that MC was associated with improved overall survival compared to OC in all zones except zone 3 and 4., Conclusions: Compared to OC, MC for T4 colon cancer is associated with improved oncologic outcomes when performed for zone 0-2 tumors. For, zone 3 and 4 tumors MC and OC have similar oncologic outcomes and patients should be cautiously selected., (© 2022 Wiley Periodicals LLC.)

N 6 -methyladenosine (m 6 A) is the most prevalent post-transcriptional RNA modification regulating cancer self-renewal. However, despite its functional importance and prognostic implication in tumorigenesis, the relevance of FTO, an m 6 A eraser, in pancreatic cancer (PC) remains elusive. Here, we establish the oncogenic role played by FTO overexpression in PC. FTO is upregulated in PC cells compared to normal human pancreatic ductal epithelial (HPDE) cells. Both RNAi depletion and CS1-mediated pharmacological inhibition of FTO caused a diminution of PC cell proliferation via cell cycle arrest in the G1 phase and p21cip1 and p27kip1 induction. While HPDE cells remain insensitive to CS1 treatment, FTO overexpression confers enhancements in growth, motility, and EMT transition, thereby inculcating tumorigenic properties in HPDE cells. Notably, shRNA-mediated FTO depletion in PC cells impairs their mobility and invasiveness, leading to EMT reversal. Mechanistically, this was associated with impaired tumorsphere formation and reduced expression of CSCs markers. Furthermore, FTO depletion in PC cells weakened their tumor-forming capabilities in nude mice; those tumors had increased apoptosis, decreased proliferation markers, and MET conversion. Collectively, our study demonstrates the functional importance of FTO in PC and the maintenance of CSCs via EMT regulation. Thus, FTO may represent an attractive therapeutic target for PC.

This review aims to summarize the recent advances in radiation oncology for pancreatic cancer. A systematic search of the MEDLINE/PubMed database and Clinicaltrials.gov was performed, focusing on studies published within the last 10 years. Our search queried "locally advanced pancreatic cancer [AND] stereotactic body radiation therapy (SBRT) [OR] hypofractionation [OR] magnetic resonance guidance radiation therapy (MRgRT) [OR] proton" and "borderline resectable pancreatic cancer [AND] neoadjuvant radiation" and was limited only to prospective and retrospective studies and metanalyses. For locally advanced pancreatic cancers (LAPC), retrospective evidence supports the notion of radiation dose escalation to improve overall survival (OS). Novel methods for increasing the dose to high risk areas while avoiding dose to organs at risk (OARs) include SBRT or ablative hypofractionation using a simultaneous integrated boost (SIB) technique, MRgRT, or charged particle therapy. The use of molecularly targeted agents with radiation to improve radiosensitization has also shown promise in several prospective studies. For resectable and borderline resectable pancreatic cancers (RPC and BRPC), several randomized trials are currently underway to study whether current neoadjuvant regimens using radiation may be improved with the use of the multi-drug regimen FOLFIRINOX or immune checkpoint inhibitors.

Recently, poly(ADP-ribosyl)ation polymerase inhibitors (PARPis), which induce synthetic lethality of tumor cells with DNA damage repair defects, have emerged as a promising therapy for ovarian, breast, and pancreatic cancer. Although the PARPi Olaparib is limited to treating cancer patients with DNA repair deficiencies, the PARPi Niraparib is FDA approved to treat ovarian cancer patients regardless of their status in DNA repair pathways. Despite differences in the affinity to PARP enzymes, the rationale behind the clinical use of Niraparib in patients without DNA repair deficiencies is still lacking. Moreover, only Olaparib has been approved for pancreatic ductal adenocarcinoma (PDAC) patients with BRCA mutations, accounting for only 5-7% of total PDACs. It remains unclear whether Niraparib could be beneficial to PDACs without BRCA mutations. We found that Niraparib inhibits ovarian and PDAC tumor cell growth, regardless of BRCA mutational status, more effectively than Olaparib. Unlike Olaparib, which is known to activate STAT3, Niraparib inhibits STAT3 activity in ovarian and PDAC cancer cell lines and patient tumors. Moreover, Niraparib regulates the expression of several STAT3 downstream genes involved in apoptosis. Overexpression of a constitutively activated STAT3 mutant rescues Niraparib-induced cancer cell apoptosis. Our results suggest that Niraparib inhibits pSTAT3 by interfering with SRC tyrosine kinase. Collectively, our studies provide a mechanism underlying Niraparib's ability to induce tumor cell apoptosis without BRCA mutations, suggesting the potential use of Niraparib for treating PDAC patients regardless of BRCA status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Kohut, Li, Martincuks, Austria, Zhang, Santiago, Borrero, Phan, Melstrom, Rodriguez-Rodriguez and Yu.)

Background: There has been an alarming increase in the number of young adults (YA) diagnosed with cancer. The emotional, psychosocial, and financial distress experienced by newly diagnosed YA undergoing cancer surgery remains largely unknown., Methods: A validated biopsychosocial distress screening tool (SupportScreen) was administered to patients diagnosed with cancer before surgery between 2009 and 2017 in a National Cancer Institute Comprehensive Cancer Center. Patients were stratified into YA less than or equal to 45 years and older adults (OA) above 45 years. Descriptive statistics and logistic regression were used to analyze distress outcomes., Results: In total, 4297 patients were identified, with YA comprising 13.3% (n=573) of the cohort. YA reported higher emotional distress, including increased anxiety (33.8% vs 27.4%, P =0.002), greater fear of procedures (26.7% vs 22%, P =0.018), and difficulty managing emotions (26% vs 20.7%, P =0.006). YA struggled more frequently to manage work/school (29.5% vs 19.3%, P <0.001), finding resources (17.8% vs 11.8%, P <0.001), changes in physical appearance (22.2% vs 13.4%, P <0.001), fatigue (36% vs 27.3%, P <0.001), and ability to have children (18.4% vs 3%, P <0.001). Financial toxicity was significantly higher in the YA group (40.5% vs 28%, P <0.001). While income level was strongly protective against emotional distress and financial toxicity in OAs, it was less protective against the risk of financial toxicity in YA. Younger age was an independent predictor of financial toxicity in a model adjusted to income (odds ratio=1.52, P =0.020)., Conclusions: YA in the prime of their personal and professional years of productivity require special attention when undergoing surgical evaluation for cancer. Resource allocation and counseling interventions should be integrated as part of their routine care to expedite their return to optimal physical and holistic health and mitigate psychosocial distress and financial toxicity., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Despite the use of first-line therapies like fluoropyrimidine and platinum-based cytotoxic chemotherapy, gastric cancer (GC) continues to carry a poor prognosis. Recent subgroup analyses of first-line phase III trials have demonstrated that patients with microsatellite instability-high (MSI-H) metastatic GC derive significant improvement in survival rates when immune checkpoint inhibitors (ICIs) are combined with chemotherapy compared with chemotherapy alone. However, it remains to be seen whether the success of ICIs in the metastatic setting can be translated into earlier stages of GC with resectable disease. We report 6 cases of locally advanced, nonmetastatic MSI-H GC that all demonstrated favorable response following treatment with pembrolizumab in addition to neoadjuvant chemotherapy. With the exception of immune-related colitis in one patient, pembrolizumab was well-tolerated. To our knowledge, this is the first reported US case series of patients treated with an ICI in combination with neoadjuvant chemotherapy for advanced, nonmetastatic, resectable or unresectable MSI-H GC.

Background: The coronavirus disease 2019 (COVID-19) pandemic created shortages of operating room (OR) supplies, forcing healthcare systems to make concessions regarding "standard" OR attire. At our institution, we were required to reduce shoe covers, reuse face masks, and allow washable head coverings. We determined if these changes affected surgical site infection (SSI) rates., Study Design: A single institutional study was performed to compare the SSI rates reported to the National Healthcare Safety Network in the 2 years preceding COVID-19 (PRE, January 1, 2018, to December 31, 2020) with the first 12 months after the pandemic (POST, April 1, 2020, to March 31, 2021). We confirmed our findings using propensity score matching and multivariate analysis., Results: Elimination of traditional shoe covers, disposable head covers, and single-use face masks was associated with a decreased SSI rate from 5.1% PRE to 2.6% POST (p < 0.001). Furthermore, this was despite a 14% increase in surgical volume and an increase in the number of contaminated/dirty cases (2.2% PRE vs 7.4% POST, p < 0.001). Use of disposable face masks decreased by 4.3-fold during this period from 3.5 million/y PRE to 0.8 million/y POST. Of note, inpatient hand hygiene throughout the hospital increased from 71% PRE to 85% POST (p < 0.001)., Conclusions: This analysis has practical applications as we emerge from the pandemic and make decisions regarding OR attire. These data suggest that disposable head covers and shoe covers and frequent changes of face masks are unnecessary, and discontinuation of these practices will have significant cost and environmental implications. These data also reinforce the importance of good hand hygiene for infection prevention., Competing Interests: Support: Dr Stewart’s institute receives funding from the Institute of Cannabis Research, University of Colorado, and Dr Stewart serves on the Scientific Program Committee of the Society of Surgical Oncology and the Conflict of Interest Committee of the American Hepato-Pancreatico-Biliary Association., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

CD8+ tumor-infiltrating lymphocytes (TILs) are associated with improved survival in triple-negative breast cancer (TNBC) yet have no association with survival in estrogen receptor-positive (ER+) BC. The basis for these contrasting findings remains elusive. We identified subsets of BC tumors infiltrated by CD8+ T cells with characteristic features of exhausted T cells (TEX). Tumors with abundant CD8+ TEX exhibited a distinct tumor microenvironment marked by amplified interferon-γ signaling-related pathways and higher programmed death ligand 1 expression. Paradoxically, higher levels of tumor-infiltrating CD8+ TEX associated with decreased overall survival of patients with ER+ BC but not patients with TNBC. Moreover, high tumor expression of a CD8+ TEX signature identified dramatically reduced survival in premenopausal, but not postmenopausal, patients with ER+ BC. Finally, we demonstrated the value of a tumor TEX signature score in identifying high-risk premenopausal ER+ BC patients among those with intermediate Oncotype DX Breast Recurrence Scores. Our data highlight the complex relationship between CD8+ TILs, interferon-γ signaling, and ER status in BC patient survival. This work identifies tumor-infiltrating CD8+ TEX as a key feature of reduced survival outcomes in premenopausal patients with early-stage ER+ BC.

Objective: To evaluate patient satisfaction scores as a function of physician and patient race and sex., Background: Patient satisfaction is increasingly used as a surrogate for physician performance. How patient and surgeon race and ethnicity affect perceptions of surgeon communication and care is not widely explored., Methods: Press Ganey patient satisfaction surveys collected from January 2019 to September 2020 were studied. Multivariate logistic regressions were used to identify factors associated with favorable surgeon performance as a function of patient and surgeon demographics., Results: A total of 4732 unique outpatient satisfaction survey responses were analyzed. The majority of patients were White (60.5%), followed by Asian (8.6%), Black (4.2%), and Hispanic (4.3%). URM accounted for 8.9% of the 79 surgeons evaluated, and 34% were female. Black, Hispanic, and Asian patients were more likely to report unfavorable experiences than their White counterparts (P < 0.01). Spanish-speaking patients were most likely to perceive that surgeon show less respect for patient concerns (13.9% vs 9.3%, P = 0.004) and inadequate time spent explaining health concerns (12.6% vs 9.2%, P < 0.001). Female surgeons were more likely to achieve the highest overall ratings for effective communication, whereas Asian surgeons received lower scores. Asian surgeons were more likely than non-Asian surgeons to receive lower scores in explanation (37.3% vs 44.1%, P = 0.003). After adjusting for confounding factors, Asian surgeons had 26% lower odds of receiving favorable scores for overall communication (odds ratio: 0.736, 95% confidence interval: 0.619-0.877, P = 0.001)., Conclusions: Both patient and surgeon race and sex drive negative perceptions of patient-physician communication. As URM report more negative experiences, further studies should focus on effects of surgeon cultural awareness on underrepresented patient satisfaction., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Attributable to the high likelihood of developing distant metastatic disease, resection of poorly differentiated gastroenteropancreatic neuroendocrine neoplasms is generally contraindicated. Some patients with no distant metastatic disease will nonetheless undergo surgical resection and their outcomes are not known. We aimed to determine whether surgery confers survival advantage over systemic therapy alone for patients with non-metastatic poorly differentiated gastroenteropancreatic neuroendocrine neoplasms., Methods: We performed a retrospective cohort study (2000-2012) of adults in the California Cancer Registry who had poorly differentiated gastroenteropancreatic neuroendocrine neoplasms (World Health Organization Grade 3) and no clinical evidence of distant metastasis (M0). Patients who underwent surgery were compared with those managed non-operatively. The adjusted Cox proportional hazards model was used to assess the risk of death., Results: Among 2,245 patients (45% female, 21% pancreatic, 79% gastrointestinal), 1,549 (69%) were treated with surgery, and 696 (31%) received either systemic therapy or palliative measures alone. Median survival was 31 months after surgery versus 9 months after non-operative therapy (log-rank test, P < .001). Rates of 5-year overall survival were 39% after surgery versus 10% in the non-operative group. Adjusting for age, sex, comorbidities, receipt of chemotherapy, and tumor size and location, patients treated with surgery had a 58% lower likelihood of death compared with non-operative therapy (hazard ratio: 0.42, 95% confidence interval: 0.36-0.50, P < .001). Restricting our results to those patients who were found to have no distant metastasis intraoperatively (ie, pathologically M0), 5-year survival after surgery reached 44%., Conclusion: While poorly differentiated gastroenteropancreatic neuroendocrine neoplasms carries a poor prognosis, for patients with no evidence of metastatic disease, resection appears to confer significant improvement in long-term survival. Although caution and an individualized approach in treating poorly differentiated gastroenteropancreatic neuroendocrine neoplasms is advised, future guidelines might reflect this survival advantage., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The advantages of robotic liver surgery are strongest for minor resections, where incision size drives recovery time, but cost remains a concern. We hypothesized that patients who underwent robotic minor liver resections would have superior peri-operative outcomes resulting in decreased cost., Methods: We queried the medical record and cost data for patients who underwent open or robotic minor (1-2 segment) liver resection from 1/2016-8/2019. Financial data were normalized to Medicare reimbursements., Results: There were 87 patients who underwent minor liver resections (robotic n = 46, open n = 41). Specimen size (173 ± 203 vs 257 ± 481 cm 3 ), surgical duration (233 ± 87 vs 227 ± 83 min), estimated blood loss (187 ± 236 vs 194 ± 165 mL), and margin status (89% vs 93% R0) were similar for robotic and open resections respectively, yet complications (3/46, 7% vs 10/41, 24%, p = 0.02) and length of stay (2.2 ± 2.2 vs 6.2 ± 2.9, p < 0.001) were significantly lower for patients who underwent robotic resection. These factors contributed to minor robotic liver resections costing $534 less than open resections ($3597 ± 1823 vs $4131 ± 1532, p = 0.03)., Conclusion: Patients undergoing robotic minor hepatectomy had superior peri-operative outcomes resulting in lower total cost of care when compared to open minor hepatectomy. Financial considerations should not adversely influence selection of a robotic approach for minor hepatectomy., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Functional impairments (measured by activities of daily living [ADLs]) and health-related quality of life (HRQOL) may complicate outcomes in older adults diagnosed with cancer. In this retrospective cohort analysis, we characterized ADLs and HRQOL in adults older than 65 y with upper gastrointestinal (UGI) cancers and evaluated for an association to cancer-specific survival., Materials and Methods: Patients with UGI cancers aged 65 y or older were selected from the Surveillance, Epidemiology and End Results and the Medicare Health Outcomes Survey-linked database. Demographics, comorbidities, stage, ADLs, and HRQOL were summarized by patients managed with and without surgery. Because of the wide variety of cancers, we subdivided patients into cohorts of esophagogastric [EG; n = 88] or hepatobiliary/pancreatic [n = 68]. Cancer-specific survival curves were modeled for changes in ADL and HRQOL scores after diagnosis. Risk factors for cancer-specific survival were assessed with hazard ratios (HRs) and adjusted for demographics, stage, comorbidities, and disease cohorts., Results: HRQOL scores declined after diagnosis, with a sharper decline in nonsurgery patients. On multivariate analysis, inability to perform specific ADLs was associated with worse survival in multiple cohorts: hepatobiliary/pancreatic nonsurgery patients unable to eat (HR 3.3 95% confidence interval (CI) 1.7-6.5); all patients with EG unable to use the toilet (HR 3.3 95% CI 1.5-7.9); EG nonsurgery cohort unable to dress or use the toilet (dress HR 14.1 95% CI 4.0-49.0; toilet HR 4.7 95% CI 1.8-12.3)., Conclusions: Older survivors with UGI cancers report declines in HRQOL, especially those not undergoing surgery. The ability to perform ADLs may be linked to survival in this population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In locally advanced basal cell carcinoma (BCC) patients who are not surgical candidates and where radiation therapy (RT) alone would offer lower control rates, the combination of vismodegib and RT delivered concurrently may potentially improve outcomes compared to single modality treatment. The current study presents a case of very advanced, multifocal BCC who received concurrent vismodegib and RT. The patient initially came in with four large primary areas of disease including the left preauriculum, right shoulder, chest wall and right lateral ankle. All sites achieved a clinical complete response, with a pathologic complete response at the right shoulder. The ankle lesion did not require RT and continues to have a clinical complete response. The findings from our case report support several other cases with similar efficacy when vismodegib and RT are combined., (Copyright: © Amini et al.)

Background: The rise in the incidence of gastric cancer (GC) and colorectal cancer (CRC) in young adults (YA) remains unexplained. We aim to identify differences in these malignancies between YA and older patients., Patients and Methods: We retrospectively analyzed the California Cancer Registry for all GC and CRC cases from 2000 to 2012. Pearson's Chi square analysis and stepwise regression model with backward elimination were used to analyze differences in demographic, clinical, and histopathologic features, and log-rank test to compare survival between young (≤ 40 years) and older adults (41-90 years) with GC or CRC, separately., Results: We analyzed 19,368 cases of GC and 117,415 cases of CRC. YA accounted for 4.6% of GC (n = 883) and 2.8% of CRC (n = 3273) patients. Compared with older patients, YA were more likely to be Hispanic (P < 0.0001) and have poorly differentiated (P < 0.0001), higher histologic grade (P < 0.0001), and signet ring features (P < 0.0001). Synchronous peritoneal metastases were more common in YA patients (32.1% vs. 14.1% GC, 8.8% vs. 5.4% CRC, P < 0.0001). The 5-year overall survival (OS) of YA with CRC or GC was longer than that of older patients with the same stage of malignancy; except YA with stage I GC, who demonstrated poor OS and disease-specific survival (DSS) (65.1% and 67.9%, respectively) which were significantly worse than those of adults aged 41-49 years (70.7% and 76.2%, respectively) and 50-64 years (69.1% and 78.1%, respectively)., Conclusions: YA with GC or CRC have distinctly worse clinical and histopathologic features compared with older patients and are disproportionately of Hispanic ethnicity. These results contribute to improving understanding of younger versus older GI cancer patients.

Background: Electrolyte abnormalities are commonly found after major abdominal surgery for malignancy. We hypothesized that the severity of hypophosphatemia developed in pancreatectomy patients would be associated with the incidence of complications postoperatively., Methods: A retrospective analysis of an institutional database was conducted for all pancreatic resections (2009-2017). Patient charts were reviewed for demographics, clinicopathologic factors, and perioperative outcomes., Results: In a cohort of 283 pancreatectomy patients, 107 (37.8%) and 134 (47.3%) developed mild (2.0-2.5 mg/dL) and moderate/severe hypophosphatemia (<2.0 mg/dL), respectively. Nadir serum phosphate levels were shown to occur on postoperative day (POD) 2 for patients without complications and POD3 for patients who had at least 1 complication. Patients who developed severe hypophosphatemia were significantly more likely to suffer fistula-related complications ( P = .0401)., Conclusions: Assessing the severity and timing of postpancreatectomy hypophosphatemia presents an opportunity for early detection of impending fistula-related complications.

Epigenetic mRNA modification is an evolving field. N 6 -methyladenosine (m 6 A) is the most frequent internal transcriptional modification in eukaryotic messenger RNAs (mRNAs). This review will discuss the functions of the m 6 A mRNA machinery, including its "writers" that are components of the methyltransferase complex, its "readers" and its "erasers" (specifically FTO and ALKBH5) in cancer. The writers deposit the m 6 A and include METTL3, METTL14, WTAP, VIRMA, and RBM15. M 6 A methylation is removed by the m6A demethylases (FTO and ALKBH5). Lastly, the most diverse members are the readers that can contribute to mRNA splicing, stability, translation, and nuclear export. Many of these functions continue to be elucidated. The dysregulation of this machinery in various malignancies and the associated impact on tumorigenesis and drug response will be discussed herein with a focus on solid tumors. It is clear that, by contributing to either mRNA stability or translation, there are downstream targets that are impacted, contributing to cancer progression and the self-renewal ability of cancer stem cells.

Background: Despite evidence that liver resection improves survival in patients with colorectal cancer liver metastases (CRCLM) and may be potentially curative, there are no population-level data examining utilization and predictors of liver resection in the United States., Methods: This is a population-based cross-sectional study. We abstracted data on patients with synchronous CRCLM using California Cancer Registry from 2000 to 2012 and linked the records to the Office of Statewide Health Planning Inpatient Database. Quantum Geographic Information System (QGIS) was used to map liver resection rates to California counties. Patient- and hospital-level predictors were determined using mixed-effects logistic regression., Results: Of the 24 828 patients diagnosed with stage-IV colorectal cancer, 16 382 (70%) had synchronous CRCLM. Overall liver resection rate for synchronous CRCLM was 10% (county resection rates ranging from 0% to 33%) with no improvement over time. There was no correlation between county incidence of synchronous CRCLM and rate of resection (R 2  = .0005). On multivariable analysis, sociodemographic and treatment-initiating-facility characteristics were independently associated with receipt of liver resection after controlling for patient disease- and comorbidity-related factors. For instance, odds of liver resection decreased in patients with black race (OR 0.75 vs white) and Medicaid insurance (OR 0.62 vs private/PPO); but increased with initial treatment at NCI hospital (OR 1.69 vs Non-NCI hospital), or a high volume (10 + cases/year) (OR 1.40 vs low volume) liver surgery hospital., Conclusion: In this population-based study, only 10% of patients with liver metastases underwent liver resection. Furthermore, the study identifies wide variations and significant population-level disparities in the utilization of liver resection for CRCLM in California., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)