Extent of Resection and Long-Term Outcomes for Appendiceal Adenocarcinoma: a SEER Database Analysis of Mucinous and non-Mucinous Histologies.

BACKGROUND: Mucinous appendiceal adenocarcinomas (MAA) and non-mucinous appendiceal adenocarcinomas (NMAA) demonstrate differences in rates and patterns of recurrence, which may inform the appropriate extent of surgical resection (i.e., appendectomy versus colectomy). The impact of extent of resection on disease-specific survival (DSS) for each histologic subtype was assessed. PATIENTS AND METHODS: Patients with resected, non-metastatic MAA and NMAA were identified in the Surveillance, Epidemiology, and End Results database (2000-2020). Multivariable models were created to examine predictors of colectomy for each histologic subtype. DSS was calculated using Kaplan-Meier estimates and examined using Cox proportional hazards modeling. RESULTS: Among 4674 patients (MAA: n = 1990, 42.6%; NMAA: n = 2684, 57.4%), the majority (67.8%) underwent colectomy. Among colectomy patients, the rate of nodal positivity increased with higher T-stage (MAA: T1: 4.6%, T2: 4.0%, T3: 17.1%, T4: 21.6%, p < 0.001; NMAA: T1: 6.8%, T2: 11.4%, T3: 25.6%, T4: 43.8%, p < 0.001) and higher tumor grade (MAA: well differentiated: 7.7%, moderately differentiated: 19.2%, and poorly differentiated: 31.3%; NMAA: well differentiated: 9.0%, moderately differentiated: 20.5%, and 44.4%; p < 0.001). Nodal positivity was more frequently observed in NMAA (27.6% versus 16.4%, p < 0.001). Utilization of colectomy was associated with improved DSS for NMAA patients with T2 (log rank p = 0.095) and T3 (log rank p = 0.018) tumors as well as moderately differentiated histology (log rank p = 0.006). Utilization of colectomy was not associated with improved DSS for MAA patients, which was confirmed in a multivariable model for T-stage, grade, and use of adjuvant chemotherapy [hazard ratio (HR) 1.00, 95% confidence interval (CI) 0.81-1.22]. CONCLUSIONS: Colectomy was associated with improved DSS for patients with NMAA but not MAA. Colectomy for MAA may not be required.

Operative trends for pancreatic and hepatic malignancies during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic disrupted routine health care, including many elective and non-cancer operations in the United States. Most hepato-pancreato-biliary malignancy patients require outpatient imaging, tissue sampling, and staging, and many undergo neoadjuvant therapy before operative intervention. The aims of this study were to evaluate the effect of the COVID-19 pandemic on hepato-pancreato-biliary oncologic operations and to determine whether trends in neoadjuvant therapy were altered by the pandemic. METHODS: Adult patients in the United States undergoing oncologic operations for pancreatic, primary and secondary hepatic malignancies, with or without neoadjuvant therapy, were extracted from the Vizient Clinical Data Base. Control chart analysis was used to plot trends over time and to determine whether changes were statistically significant. Wilcoxon rank-sum tests also compared monthly operative volume from pre-pandemic (12 month) and pandemic (28 months) periods. RESULTS: A total of 36,553 patients were identified over 40 months. Mean monthly pancreatic oncologic operations were unaffected by the pandemic (P = .257). Operations for pancreatic oncologic operations with prior neoadjuvant therapy increased throughout the pandemic (P = .002). Oncologic operations for primary and secondary hepatic malignancies were significantly reduced for 4 and 2 months, respectively, at the beginning of the pandemic but returned to their pre-pandemic baseline within 4 months (P = .169 and P = .598). CONCLUSION: Pancreatic operation volumes for cancer did not change, but pancreatic operations after neoadjuvant therapy continued to increase during the pandemic. Operations for hepatic malignancy were transiently disrupted but quickly normalized. These observations suggest that surgery for hepato-pancreato-biliary malignancies was prioritized during the pandemic.

Racial disparities in rates of invasiveness of resected intraductal papillary mucinous neoplasms in the United States.

BACKGROUND: Racial and ethnic disparities have been observed in the multidisciplinary management of pancreatic ductal adenocarcinoma. Intraductal papillary mucinous neoplasm is the most common identifiable precursor to pancreatic ductal adenocarcinoma, where early surgical intervention before the development of an invasive intraductal papillary mucinous neoplasm improves survival. The association of race/ethnicity with the risk of identifying invasive intraductal papillary mucinous neoplasms during resection has not been previously defined. METHODS: The American College of Surgeons National Quality Improvement Program targeted pancreatectomy database (2014-2021) was queried for patients with race/ethnicity data who underwent resection of an intraductal papillary mucinous neoplasm. Backward Wald logistic regression modeling (P ≤ 0.05 for entry; P > .10 for removal) was used to identify independent predictors of invasion. RESULTS: A total of 4,505 cases of resected intraductal papillary mucinous neoplasms were identified, with 923 (20.5%) demonstrating invasive intraductal papillary mucinous neoplasms. The cohort of individuals other than non-Hispanic Whites were significantly more likely to have invasive intraductal papillary mucinous neoplasms (White, 19.9%; Black, 24.2%; Asian, 23.7%; Hispanic, 22.6%; P = .026). Such disparity could not be explained by greater comorbidity, as non-White patients were significantly younger (age <65 years: 41.7% vs 33.2%, P < .001) and had better physical status (American Society of Anesthesiologists score ≤2: 28.8% vs 25.2%, P = .053). After controlling for clinicodemographic variables, being an individual of race/ethnicity other than White was independently associated with higher odds of invasive intraductal papillary mucinous neoplasms (odds ratio, 1.280; 95% confidence interval, 1.046-1.566; P = .017). No differences in postoperative morbidity were observed. CONCLUSION: In a national cohort of patients with resected intraductal papillary mucinous neoplasms, individuals who identified as being of race/ethnicity other than White were significantly more likely to have invasive intraductal papillary mucinous neoplasms during surgical resection.

Recurrence-free survival dynamics following adjuvant chemotherapy for resected colorectal cancer: A systematic review of randomized controlled trials.

BACKGROUND: Several cytotoxic chemotherapies have demonstrated efficacy in improving recurrence-free survival (RFS) following resection of Stage II-IV colorectal cancer (CRC). However, the temporal dynamics of response to such adjuvant therapy have not been systematically quantified. METHODS: The Cochrane Central Register of Trials, Medline (PubMed) and Web of Science were queried from database inception to February 23, 2023 for Phase III randomized controlled trials (RCTs) where there was a significant difference in RFS between adjuvant chemotherapy and surgery only arms. Summary data were extracted from published Kaplan-Meier curves using DigitizeIT. Absolute differences in RFS event rates were compared at matched intervals using multiple paired t-tests. RESULTS: The initial search yielded 1469 manuscripts. After screening, 18 RCTs were eligible (14 Stage II/III; 4 Stage IV), inclusive of 16,682 patients. In the absence of adjuvant chemotherapy, the greatest rate of recurrence was observed in the first year (mean RFS event rate; 0-0.5 years: 0.22 ± 0.21; 0.5-1 years: 0.20 ± 0.09). Adjuvant chemotherapy was associated with significant decreases in the RFS event rates for the intervals 0-0.5 years (0.09 ± 0.09 vs. 0.22 ± 0.21, p < 0.001) and 0.5-1 years (0.14 ± 0.11 vs. 0.20 ± 0.09, p = 0.001) after randomization, but not at later intervals (1-5 years). In Stage IV trials, RFS event rates significantly differed for the interval 0-0.5 years (p = 0.012), corresponding with adjuvant treatment durations of 6 months. In Stage II/III trials, which included therapies of 6-24 months duration, there were marked differences in the RFS event rates between surgery and chemotherapy arms for the intervals 0-0.5 years (p < 0.001) and 0.5-1 years (p < 0.001) with smaller differences in the RFS event rates for the intervals 1-2 years (p = 0.012) and 2-3 years (p = 0.010). CONCLUSIONS: In a systematic review of positive RCTs comparing adjuvant chemotherapy to surgery alone for Stage II-IV CRC, observed RFS improvements were driven by early divergences that occurred primarily during active cytotoxic chemotherapy. Late recurrence dynamics were not influenced by adjuvant therapy use. Such observations may have implications for the use of chemotherapy for micrometastatic clones detectable by cell-free DNA-based methodologies.

Respondent Driven Sampling Method of Recruitment for a Case Control Study of Gastric Cancer Risk.

OBJECTIVE: Gastric cancer (GC) disproportionately affects ethnic minorities in the US including Asians and Pacific Islanders. Research with minority groups who are at high risk are needed to provide more effective treatment. Successful recruitment of minorities to research must overcome obstacles of language, access, fear and mistrust. Respondent Driven Sampling (RDS) is a sampling strategy designed to recruit underrepresented minority populations using social networks. However, there are no reports of RDS being used for a case-control study. METHODS: Our pilot study examined the feasibility of using RDS as a recruitment strategy to enroll a large number of participants to develop a GC screener. Our preliminary work showed that 750 cases and 5,250 controls would be needed to fully develop this tool. GC cases, who also served as the seeds, were asked to refer 2 more people to participate as controls in our study. Our pilot goal was to recruit 8 GC cases (as seeds) and 112 controls using three waves of referrals and recruitment. RESULTS: Twenty-seven GC cases were contacted of which 10 refused, 4 expressed interested to participate in the survey but were unwilling to recruit controls. Thirteen cases were recruited but only 5 Complete the survey. Of these 5, 3 cases did not pass on referral coupons and only 2 of the participants gave coupons to 3 potential controls. CONCLUSION: Our study revealed the limitations of using RDS with cancer patients to support recruitment. GC patients' constrained social networks, inadequate incentives or other factors may have contributed to the lack of success with using RDS in this setting.

COVID-19 Effect on Surgery for Gastrointestinal Malignancies: Have Operative Volumes Recovered?

BACKGROUND: COVID-19 disrupted elective operations, cancer screening, and routine medical care while simultaneously overwhelming hospital staff and supplies. Operations for gastrointestinal (GI) malignancies rely on endoscopic screening, staging, and neoadjuvant therapy (NAT), each of which was disrupted by the pandemic. The aim was to evaluate the effect of the COVID-19 pandemic on the US national rates of gastrointestinal oncologic operations. METHODS: The Vizient Clinical Data Base® was queried for oncologic operations for esophageal, gastric, and colorectal malignancies with and without NAT from March 2019 to March 2022. Control chart analysis examined operative volume over time while Wilcoxon rank sum tests were used to compare mean monthly volume before and during the pandemic. RESULTS: A total of 95,912 patients were identified over 36 months; 5.8% esophageal, 6.3% gastric, 77.5% colonic, and 10.4% rectal operations. Esophageal operative volume decreased for 9 months during the pandemic and was significantly lower during than before the pandemic (p=0.002). Gastric operations decreased for 10 months early in the pandemic, but rebounded so that after 2 years volumes were unchanged (p=0.49). Colonic operations experienced a sharp decrease for 4 months at the beginning of the pandemic, but volumes quickly increased and overall were unchanged (p=0.29). Rectal operations decreased for 13 months and were significantly lower during than before the pandemic (p=0.018). Oncologic operations for patients receiving NAT varied. CONCLUSION: COVID-19 significantly disrupted the volume of gastrointestinal oncologic operations in the USA. Esophageal and rectal oncologic operations experienced prolonged and significant reductions while gastric and colonic oncologic operations transiently decreased but rebounded during the pandemic.

A qualitative analysis of patients' experiences with an emergency department diagnosis of gastrointestinal cancer.

OBJECTIVES: Optimally, cancer is diagnosed through periodic screening or detection of early symptoms in primary care settings. However, an estimated 23%-52% of gastrointestinal (GI) cancers are diagnosed in the emergency department (ED). Cancer diagnosed in the ED has been associated with worse clinical and patient-reported outcomes even after adjustment for cancer stage. We sought to explore patients' accounts of patient and health care system factors related to their diagnosis in the ED and their lived experience of receiving a diagnosis in this setting. METHODS: Patients with an ED visit during or within 30 days of their GI cancer diagnosis at an urban academic hospital serving a largely disadvantaged population were recruited. Interviews were coded in NVivo 12 and analyzed using a thematic analysis approach. RESULTS: Patient-reported factors associated with their experiences included denial and avoidance of symptoms, mistrust of the health system, and lack of cancer screening knowledge. Health care system factors included misdiagnosis and delayed access to specialty care or tests. Experiences receiving a cancer diagnosis in the ED were overwhelmingly negative. CONCLUSIONS: This study highlights the unmet needs in identifying and diagnosing patients who ultimately present to the ED for evaluation and eventual diagnosis of cancer. Our results shed light on several modifiable factors, including the need for increased public awareness of the asymptomatic nature of cancer and the importance of cancer screening. Additionally, health care systems modifications beyond the ED are needed to improve access to timely care when symptoms arise.

Interpretation of Tumor Response Grade following Preoperative Therapy for Gastric Cancer: An Overview.

Gastric cancer is among the top five causes of cancer-related death worldwide. Preoperative chemotherapy has been established as an option in patients with locally advanced gastric cancer. However, chemotherapy yields variable results, owing to the cellular and molecular heterogeneity of this disease. Identifying patients who did or did not respond to preoperative therapy can allow clinicians to alter treatment modalities and provide important information related to prognostication. A pathologic response to preoperative therapies, called the Tumor Response Grade (TRG), has been evaluated to quantify treatment response. Multiple systems for TRG have been established. However, the literature has demonstrated inconsistent results for TRG systems and prognosis, possibly due to variability in interpretation of tumor response between systems and interobserver variability. Radiographic responses to preoperative therapies using RECIST 1.1 criteria and endoscopically assessed tumor response have demonstrated association with survival; however, their use in gastric cancer remains challenging given the inability to accurately and consistently identify and measure the tumor, especially in the setting of neoadjuvant therapy, where treatment-related changes can obscure the gastric wall layers. While the response to preoperative therapies with positron emission tomography (PET) has shown promising results in esophageal and esophagogastric junction (EGJ) malignancies, its role in gastric cancer is still under investigation. This review is focused on summarizing the available literature related to evaluating TRG in gastric cancer, as well as providing a brief overview of the use of radiographic and endoscopic methods to assess response to preoperative therapies. Lastly, we outline future directions regarding the use of a universal TRG system to guide care and assist with prognosis.

Combination of Immunotherapy and Radiation Therapy in Gastrointestinal Cancers: An Appraisal of the Current Literature and Ongoing Research.

Oncological outcomes are improving in gastrointestinal cancer with advancements in systemic therapies, and there is notable potential in combining immunotherapy and radiation therapy (RT) to allow for further improvements. Various preclinical and early phase II studies have shown promising synergy with immunotherapy and RT in gastrointestinal cancer. A few recent phase III studies have shown improved survival with the addition of immunotherapy to standard treatment for gastrointestinal cancer. The timing, duration, sequencing, and integration with other anti-cancer treatments are still areas of ongoing research. We have reviewed the published and ongoing studies of the combinations of immunotherapy and RT in gastrointestinal cancers.

Potentially Avoidable Admissions and Prolonged Hospitalization in Patients with Suspected Colon Cancer.

BACKGROUND: Suspicion of cancer in the Emergency Department (ED) may lead to potentially avoidable and prolonged admissions. We aimed to examine the reasons for potentially avoidable and prolonged hospitalizations after admissions from the ED for new colon cancer diagnoses (ED-dx). METHODS: A retrospective, single-institution analysis was conducted of patients with ED-dx between 2017 and 2018. Defined criteria were used to identify potentially avoidable admissions. Patients without avoidable admissions were examined for ideal length of stay (iLOS), using separate defined criteria. Prolonged length of stay (pLOS) was defined as actual length of stay (aLOS) being greater than 1 day longer than iLOS. RESULTS: Of 97 patients with ED-dx, 12% had potentially avoidable admissions, most often (58%) for cancer workup. Very little difference in demographic, tumor characteristics, or symptoms were found, except patients with potentially avoidable admissions were more functional (Eastern Cooperative Oncology Group [ECOG] score 0-1: 83% vs. 46%; p = 0.049) and had longer symptom duration prior to ED presentation {24 days (interquartile range [IQR] 7-75) vs. 7 days (IQR 2-21)}. Among the 60 patients who had necessary admissions but did not require urgent intervention, 78% had pLOS, most often for non-urgent surgery (60%) and further oncologic workup. The median difference between iLOS and aLOS was 12 days (IQR 8-16) for pLOS. CONCLUSIONS: Potentially avoidable admissions following Ed-dx were uncommon but were mostly for oncologic workup. Once admitted, the majority of patients had pLOS, most often for definitive surgery and further oncologic workup. This suggests a lack of systems to safely transition to outpatient cancer management.

Controlling Gastric Cancer in a World of Heterogeneous Risk.

Gastric cancer (GC) is a leading cause of global mortality but also a cancer whose footprint is highly unequal. This review aims to define global disease epidemiology, critically appraise strategies of prevention and disease attenuation, and assess how these strategies could be applied to improve outcomes from GC in a world of variable risk and disease burden. Strategies of primary prevention focus on improving the detection and eradication of the main environmental risk factor, Helicobacter pylori. In certain countries of high incidence, endoscopic or radiographic screening of the asymptomatic general population has been adopted as a means of secondary prevention. By contrast, identification and targeted surveillance of individuals with precancerous lesions (such as intestinal metaplasia) is being increasingly embraced in nations of low incidence. This review also highlights existing knowledge gaps in GC prevention as well as the role of emerging technologies for early detection and risk stratification.

The order of surgery and chemotherapy matters: Multimodality therapy and stage-specific differences in survival in gastric cancer.

BACKGROUND AND OBJECTIVES: Multimodality treatment improves survival for gastric cancer (GC). However, the effect of treatment sequence by stage remains unclear. We aim to compare outcomes between patients receiving neoadjuvant(neoadj) and adjuvant chemotherapy (adj). METHODS: Nonmetastatic GC patients with clinical stage ≥ T2N0 who underwent both resection and neoadj or adj were identified using the National Cancer Database (2005-2014). Multivariable Cox regression analyses were performed on propensity score-matched (PSM) cohorts stratified by stage to compare overall survival (OS). RESULTS: We identified 11 984 patients; 55% stage I (SI), 76% stage II (SII) and 57% stage III (SIII) received neoadj. Unadjusted analysis showed worse survival among SI neoadj patients (hazard ratio [HR] 1.195, confidence interval [CI] 1.04-1.38) and improved survival for SII (HR 0.93 CI 0.87-0.998) and SIII (HR 0.75, CI 0.68-0.84). After PSM, SI patients with neoadj had worse OS with increased risk of death compared to Adj (HR 1.186, CI 1.004-1.402). SII patients had no difference in OS (HR 0.98, CI 0.91-1.07) and SIII patients had improved OS (HR 0.78, CI 0.69-0.90). CONCLUSIONS: In patients who received surgery and chemotherapy, the benefit of neoadj was limited to SIII with worse survival for SI. A clinical trial to examine the optimal sequence of chemotherapy is warranted.

Association Between Socioeconomic and Insurance Status and Delayed Diagnosis of Gastrointestinal Cancers.

INTRODUCTION: Association between socioeconomic status (SES) and stage at diagnosis in gastrointestinal (GI) cancers is poorly described. Relationship between low SES and stage at diagnosis as well as the mediating role of insurance status (IS) was examined. METHODS: The Surveillance, Epidemiology, and End Results database was queried for esophageal, gastric, liver, biliary, pancreatic, colon, and rectal cancers diagnosed in 2012-2016. Relationship between census-tract SES index quintiles and late diagnosis (distant disease at diagnosis) was examined. Uni and multivariable logistic regressions were performed. Mediation analyses were conducted to determine the degree to which IS (private/Medicare versus Medicaid/uninsured) mediates the relationship between SES and late diagnosis of cancer. RESULTS: Analysis included 236,713 adult patients from 18 Surveillance, Epidemiology, and End Results areas. In univariable analysis, lowest SES quintile was significantly associated with late diagnosis for all cancers except gastric and biliary cancers. In multivariable analysis controlling for age, gender, marital status and race, this association remained significant for liver (odds ratio (OR) 1.41 [95% confidence interval (CI) 1.25-1.58]), pancreatic (OR 1.13 [95% CI 1.06-1.21]), and rectal (OR 1.31 [95% CI 1.20-1.42]) cancers. Further controlling for IS showed the largest effect size reduction for rectal cancer (OR 1.18 [95% CI 1.09-1.29]), with IS mediating 36.5% (P < 0.0001) of SES effect. CONCLUSIONS: Low SES is an independent risk factor for late diagnosis in liver, pancreas, and rectal cancers. Insurance is not a critical mediator of difference by SES for most GI cancers, with the exception of rectal cancer. Further research is needed to understand factors beyond IS that can account for SES differences in late diagnosis for GI cancers. Insurance related differences for rectal cancer deserves further attention.

Serum Pepsinogen as a Biomarker for Gastric Cancer in the United States: A Nested Case-Control Study Using the PLCO Cancer Screening Trial Data.

BACKGROUND: Gastric cancer lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, a gastric cancer precursor, and may be useful to detect persons at increased risk of gastric cancer. METHODS: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted in the United States between 1993 and 2001. ELISA-based pepsinogen tests were conducted on prediagnostic serum samples of 105 PLCO participants who developed gastric cancer and 209 age, sex, and race-matched controls. Pepsinogen positive (PG+) was defined as pepsinogen I ≤ 70 µg/L and pepsinogen I/II ratio ≤3.0. Results of conditional logistic regression models, and sensitivity and specificity, of PG+ for gastric cancer are reported. RESULTS: Gastric cancer cases were more likely to be PG+ (31.4% vs. 5.5%, P < 0.001) at baseline than controls. Compared to PG-, PG+ was associated with an 8.5-fold increased risk for gastric cancer [95% confidence interval (CI) = 3.8-19.4]. This risk remained significant after adjusting for Helicobacter pylori, family history of gastric cancer, education, smoking, and BMI (aOR, 10.6; 95% CI, 4.3-26.2). In subgroup analysis, PG+ individuals were 11-fold more like to develop non-cardia gastric cancer (OR, 11.1; 95% CI, 4.3-28.8); conversely, they were not significantly more likely to develop cardia gastric cancer (OR, 2.0; 95% CI = 0.3-14.2). PG+ status yielded low sensitivity but high specificity for both noncardia (44.3%; 93.6%) and cardia gastric cancer (5.7%; 97.2%). CONCLUSIONS: Prediagnostic serum pepsinogen levels from a large, prospective cohort study were associated with risk of gastric cancer, particularly noncardia gastric cancer. IMPACT: PG status may identify individuals at higher risk of noncardia gastric cancer for targeted screening or interventions. See related commentary by Zhou and Huang, p. 1257.

Evaluation of Survival and Postoperative Radiation Among Patients with Advanced Medullary Thyroid Carcinoma: An Analysis of the National Cancer Database.

BACKGROUND: This study compared survival between patients who had medullary thyroid cancer (MTC) treated with surgery alone and patients who underwent surgery and radiation (SRT). METHODS: Patients from the National Cancer Database (NCDB) with a diagnosis of stage 3 or 4 MTC, lymph node disease, and no distant metastases between 2008 and 2016 were studied. Kaplan-Meier analyses and log-rank statistics were used to estimate and compare overall survival between patients treated with surgery alone and those treated with SRT. Mutlivariable Cox proportional hazards models and propensity-matching were used to adjust for confounding and selection bias. RESULTS: Among 1370 patients, 1112 (81%) received surgery alone, and 258 (19%) received SRT. The hazard ratio for mortality in the SRT group was 1.784 (95% confidence interval [CI] 1.313-2.43) after multivariable adjustment for confounding variables. Furthermore, SRT remained associated with a higher mortality rate (p < 0.008) after propensity-matching in an effort to adjust for selection bias. CONCLUSIONS: This analysis of NCDB patients showed that SRT is associated with a significantly higher mortality rate among patients treated for stage 3 or 4 IV MTC with positive lymph node disease. Although this observation can be attributed to unmeasured confounders or selection bias, the cause for the profound survival differences deserves prospective evaluation, especially as adjuvant therapies for this disease continue to evolve.