Resected Adenocarcinoma Research Articles

The potential role of serial circulating tumor DNA (ctDNA) testing after upfront surgery to guide adjuvant chemotherapy for early stage pancreatic cancer: The AGITG DYNAMIC-Pancreas trial.

107 Background: Recurrence rates following upfront resection of pancreatic adenocarcinoma are high, with some benefit from adjuvant chemotherapy (AC). A biomarker that improves risk stratification and/or provides real time indication of AC benefit could improve routine clinical management and accelerate trial progress. Previous studies in pancreas cancer suggest that patients with detectable ctDNA post surgery are at an elevated risk of recurrence. Detectable ctDNA at the completion of AC may also be associated with an elevated recurrence risk. Methods: Patients with early stage pancreatic adenocarcinoma were enrolled following upfront resection at 26 Australian centres. Patients were ECOG 0-1 and fit for AC. A tumour-informed ctDNA assay was used to identify somatic mutations for tracking in circulating cell-free DNA. ctDNA+ patients received 6 months of AC (FOLFIRINOX or gemcitabine/capecitabine selected at the clinician's discretion), while ctDNA- patients could de-escalate to 3 months at the clinician’s discretion. ctDNA was assessed again at the end of AC. The primary study endpoint was the feasibility of ctDNA-guided therapy. Secondary endpoints included the association of ctDNA with clinicopathologic risk factors and survival outcomes. Results: A total of 102 patients were enrolled from March 2019 to Nov 2023. Median age was 68 years (range 41 – 86), with 50% male and 95% ECOG 0-1. Tumours were located in the head of pancreas in 72%. Histology revealed T1 (18%), T2 (50%), and T3 (32%) tumors, with nodal involvement in 71%, and an R0 resection in 77%. Post-operative Ca19-9 was elevated in 29%. Forty patients (40%) were ctDNA+ve post resection, 54 (53%) were ctDNA-ve, and no result was obtained in 4 (4%) due to the absence of tumor mutation, and as a result, they were considered ineligible. The presence or absence of ctDNA was not associated with known clinicopathologic risk factors. Median time to ctDNA collection was 5 weeks (range 3 – 9) and to commencing AC was 6 weeks (range 4-12). Of 54 ctDNA-ve patients, 24 (44%) were de-escalated to receive a planned 3 months of AC. With a median follow-up of 36 months (range 2-56) the median recurrence free survival (RFS) in ctDNA+ve patients was 13 months compared to 22 months for ctDNA-ve patients (HR 0.52, p = 0.003). Conclusions: A tumor informed ctDNA approach to AC selection is feasible for patients undergoing upfront resection of pancreatic adenocarcinoma, with the first blood draw to be scheduled at week 5, allowing time for ctDNA analysis to determine AC selection. A high proportion of patients had detectable ctDNA, which appears independent of known prognostic markers. ctDNA detection was associated with earlier recurrence. Analyses of the impact of changes in ctDNA over time on survival are ongoing. Clinical trial information: ACTN12618000335291.

Social factors in the receipt of treatment for locally advanced esophageal cancer.

e16093 Background: Treatment for locally advanced esophageal cancer consists of chemoradiation (chemoRT) followed by esophagectomy. Studies have suggested Black patients were less likely to undergo surgery for esophageal cancer with inferior survival rates, attributing this to differences in access to surgery. These studies have not always accounted for differences in the natural history of adenocarcinoma and squamous cell carcinoma, which have strong racial correlations and different rates of surgical resection. The current study examined outcomes and patterns of care for patients with locally advanced esophageal cancer, both adenocarcinoma and squamous cell carcinoma, in relation to their sociodemographic characteristics. Methods: Patients with clinical stage T2-4, N0-2, and M0 adenocarcinoma or squamous cell carcinoma of the mid or distal esophagus diagnosed between 2010-2021 were included from 11 hospitals across our healthcare system. Treatment decision-points included receipt of chemoRT, unresectable disease after chemoRT defined by metastatic disease or upper mediastinal lymphadenopathy, and receipt of surgery stratified by histology. Age, race, sex, insurance status, socioeconomic status measured by social deprivation index (SDI), and outcome data were collected. Chi-squared test was used for categorical variables and Kruskal-Wallis for continuous variables. Results: 513 patients were included, of whom 472 patients underwent chemoRT (366 adenocarcinoma, 106 squamous cell). Female patients (n =97) were less likely to undergo chemoRT (84% vs. 94%, p = 0.003). Patients without insurance were less likely to undergo chemoRT (86% vs 93%, p = 0.023). After completing chemoRT, 419 patients (82%) were resectable. Surgery was performed in 262/330 patients (79%) with adenocarcinoma and 38/89 patients (43%) with squamous cell carcinoma, reflecting the differences in natural history by histology. Among 330 patients with resectable adenocarcinoma, higher SDI was associated with a lower rate of surgery, while there was no difference in the receipt of surgery based on sex, race or insurance status. There were no detectable social factors associated with receipt of surgery for squamous cell carcinoma. Conclusions: Within our healthcare system, female and Medicaid/uninsured patients are less likely to undergo chemoRT for locally advanced esophageal cancer. Further studies are needed to evaluate whether sex-specific bias plays a role in the receipt of chemoRT. Among patients with resectable locally advanced esophageal adenocarcinoma treated with chemoRT, those with high SDI are less likely to undergo surgery. Further studies are needed to assess which component factors of socioeconomic status most impact the receipt of surgery so they can be targeted. The previous findings that race impacts treatment of locally advanced esophageal cancer are not seen in our healthcare system when accounting for histology.

Circulating tumor DNA for recurrence monitoring following resection for pancreas adenocarcinoma.

e16365 Background: Detecting early recurrence among patients with resected pancreatic cancer may facilitate earlier treatment and better outcomes for patients with resected pancreatic ductal adenocarcinoma (PDAC). Circulating tumor DNA (ctDNA) has shown promise as a tumor-specific biomarker for PDAC but has not yet entered routine clinical use. This study aims to conduct analytical and clinical validation of Signatera ctDNA profiling to predict recurrence in patients with PDAC. Methods: A retrospective IRB-approved protocol evaluating the use of Signatera ctDNA testing among patients who underwent resection at Northwell Health during 2019-2023. The utility of ctDNA status to predict PDAC recurrence during follow-up was assessed using cox regression. Results: There were 91 ctDNA tests among 24 patients. With a median follow-up of 15 months, recurrence was observed in 38% (9/24) of patients and 8 patients died. Among patients with recurrence, most of them had positive ctDNA before showing signs of recurrence on the imaging (6/9, 66.7%) with mean lead time of 116 days, while 2 of them had positive ctDNA after recurrence and one patient never had positive ctDNA. At the time of recurrence, eight patients had elevated CA19-9, while two patients with normal CA19-9 had positive ctDNA. The median recurrence-free survival (RFS) was 23 months (95% CI, 11-not reached). Patients with detectable preoperative ctDNA had significantly decreased median RFS (14 months; 7 of 10 (70%) recurred) when compared with patients negative for ctDNA [not reached; 2/14 (14.3%) recurred; P= 0.005). In multivariable Cox model after adjusting for potential risk factors, detection of ctDNA was associated with RFS. (table). Conclusions: Signatera ctDNA profiling identified relapse earlier than imaging for most patients. These results suggest the potential for a prospective trial evaluating early treatment interventions in this deadly disease to improve survival rates. [Table: see text]

494TiP Efficacy and safety of cadonilimab and COX-2 inhibitor combined with oxaliplatin and capecitabine (XELOX) in perioperative treatment for locally advanced resectable gastric adenocarcinoma: A prospective, single-center, randomized, phase II trial

494TiP Efficacy and safety of cadonilimab and COX-2 inhibitor combined with oxaliplatin and capecitabine (XELOX) in perioperative treatment for locally advanced resectable gastric adenocarcinoma: A prospective, single-center, randomized, phase II trial

Neoadjuvant dual checkpoint inhibition followed by immune-chemoradiation in patients with resectable gastric adenocarcinoma.

4067 Background: Localized gastric cancer is a potentially curable condition and long-term outcomes depend on YP staging. Currently, preferred adjunctive therapy depends on geographic location. Preliminary data from NCT01928394 have shown promising clinical activity of immunotherapy (IO) agents nivolumab (nivo) +/- ipilimumab (ipi) in the metastatic setting. We conducted a single-arm study using IO + chemotherapy followed by immune-chemoradiation prior to surgery, followed by adjuvant IO, in patients with localized gastric adenocarcinoma. Our primary objective was to determine safety and toxicity with this approach. Secondary objectives included efficacy by YP staging and R0 resection rate. Methods: Patients with localized gastric adenocarcinoma were enrolled into NCT03776487 (n=30). Participants received the following: (1) biweekly chemotherapy with 4 doses of 5-Fluorouracil (5-FU)/Oxaliplatin, (2) nivo 240mg q2weeks (x3) and ipi 1mg/kg q6weeks (x1), (3) immune-chemoradiation (biweekly nivo + 5FU Mon-Fri concurrently with a total of 45 Gy given in 25 fractions), and (4) surgical resection. Those with residual disease received adjuvant nivolumab monthly for 6 doses. Correlative studies are planned. To assess preliminary efficacy, the clinical and pathologic complete response rates (pCR) were estimated along with the corresponding exact 95% confidence interval. Adverse events and toxicities were summarized using descriptive statistics. Results: Median follow-up was 27.4 months at the time of data cutoff. Of 30 enrolled, 23 patients completed surgery and seven did not due to progression of disease(n=5) and worsening co-morbidities(n=2). The side effect profile was similar to prior IO studies, with no grade 5 events observed. Three patients (10%) experienced grade 4 events (acute kidney injury, myocarditis, and neutropenia). The most frequent grade 3 toxicity was nausea and vomiting (10%). From the 23 participants that underwent resection, 22 had pathologic data at the time of analysis, with 9 achieving ypT0ypN0 (40.9%, 95% CI: 20.7%, 63.7%). There was an 86% R0 resection rate. Conclusions: Our results are encouraging and support further development of this strategy for localized gastric adenocarcinomas. The regimen is safe and potentially generalizable. Clinical trial information: NCT03776487 .

440P Maximal tumor area as an independent prognostic factor: Enhancing prognostic assessment in resectable gastric adenocarcinoma

440P Maximal tumor area as an independent prognostic factor: Enhancing prognostic assessment in resectable gastric adenocarcinoma

Close margin of adverse histologic factors with a negative primary tumor margin is not associated with increased locoregional recurrence in colon cancer

PurposeLocoregional recurrence after resection of colon cancer is increased when primary tumor margin is positive (<1 ​mm). Data is limited regarding the risk of locoregional recurrence with close margin (<1 ​mm) of histologic factors, such as intravascular tumor, intranodal tumor, tumor deposits, or extranodal extension. We hypothesized that close margin of these factors doesn't affect locoregional recurrence. MethodsA retrospective review of all colon cancer surgical resections for adenocarcinoma from 2007 to 2020 was performed. Inclusion criteria were specimens with a negative primary tumor margin but a close margin of adverse histologic factors, defined as intravascular tumor, intranodal tumor, tumor deposits, or extranodal extension within 1 ​mm of a mesenteric or circumferential margin. ResultsAmong 4435 pathology reports reviewed, 45 (1 ​%) of cases met inclusion criteria. Average follow-up was 38 months. The adverse histologic factor was identified as intranodal tumor in 24 (53 ​%) cases, intravascular tumor in 8 (17.8 ​%), tumor deposits in 5 (11.1 ​%), and more than one pathologic feature in 6 (13.3 ​%). There were 9 (20 ​%) recurrences; 6 (13 ​%) had distant recurrences only, 2 (4 ​%) patients had locoregional recurrences only, and 1 (2 ​%) patient had both locoregional and distant recurrence. The adverse histologic factor in these three patients was intravascular in two and both intravascular and intranodal in one. ConclusionBased on our results, we do not have evidence that the presence of intravascular tumor, intranodal tumor, tumor deposits, or extranodal extension within 1 ​mm of a mesenteric or circumferential margin is associated with increased risk of locoregional recurrence.

An Analysis on the Effect of Income Changes in the Resection of Early-Stage Pancreatic Adenocarcinoma.

The impact of socioeconomic inequalities on cancer care and outcomes has been well recognized and the underlying causes are likely multifactorial. Income is regarded as a cornerstone of socioeconomic status and has been assumed to correlate with access to care. We therefore sought to investigate whether income and changes in income would affect the rate of patients undergoing surgical resection for early-stage pancreatic cancer. Inflation-adjusted income data were obtained from the United States Census Bureau from 2010 to 2019. The cancer data were obtained from the SEER database. Counties present in both data sets were included in the analysis. Patients with stage I or II pancreatic cancer who underwent formal resection were deemed to have undergone appropriate surgical management. Patients were grouped into an early (2010-2014) and late (2015-2019) time period. The final analysis included 23968 patients from 173 counties across 11 states. The resection rate was 45.1% for the entire study and rose from 42.8% to 47.4% from the early to late time periods (P < .001). The median change in income between the two time periods was an increase by $2387. The rate of resection was not dependent on income class or income change in our study population. Our surgical care of pancreatic cancer is improving with more patients undergoing resection. In addition, there are now fewer disparities between patients of lower-income and higher-income groups with respect to receiving surgical intervention. This implies that our access to care has improved over the past decade. This is an encouraging finding with regards to reducing health care disparities.

Colorectal cancer harboring EGFR kinase domain duplication response to EGFR tyrosine kinase inhibitors.

Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare, recurrent oncogenic variant that constitutively activates EGFR in non-small-cell lung cancer. Herein, we report the case of a 70-year-old man with resectable colorectal adenocarcinoma who underwent surgery followed by adjuvant therapy. He relapsed with multiple liver metastases and received standard chemotherapy until his disease became refractory. Comprehensive genomic profiling of his postoperative colorectal cancer tissue revealed EGFR-KDD. He was treated with an EGFR tyrosine kinase inhibitor (TKI), afatinib and achieved a partial response (- 55%) after 8 weeks; however, he developed massive malignant ascites after 13 weeks. Osimertinib, another EGFR-TKI, controlled his tumors for 9 months. Patient-derived cancer organoids from his malignant ascites confirmed sensitivity to EGFR-TKIs. The findings suggest that EGFR-TKIs can be a potential treatment option for this molecular subgroup.

Impact of perioperative prognostic nutritional index changes on the survival of patients with stage II/III colorectal cancer.

To assess the impact of perioperative prognostic nutritional index (PNI) changes on prognosis and recurrence after colorectal cancer surgery. A total of 475 patients who underwent curative resection for primary colorectal adenocarcinoma and were diagnosed with pathological stage (pStage) II/III were retrospectively reviewed. The patients were divided into two groups: the high group (preoperative PNI ≤ postoperative PNI, n = 290) and the low group (preoperative PNI > postoperative PNI, n = 185). The low group exhibited significantly higher recurrence and mortality rates (all p < 0.001). Kaplan-Meier analysis showed worse overall and recurrence-free survival in the low group (all p < 0.001). Perioperative PNI changes predicted prognosis and recurrence independent of preoperative nutritional conditions. Subgroup analyses showed better overall survival and recurrence-free survival in the high group across various parameters, such as patient background, surgical outcomes, adjuvant chemotherapy, and pathological characteristics. Multivariate analysis revealed that the low group based on perioperative PNI changes (hazard ratio [HR]: 5.809, 95% confidence interval [CI]: 3.451-9.779, p < 0.001), pathological T stage (HR: 1.962, 95% CI: 1.184-3.253, p = 0.009), and pathological N stage (HR: 3.434, 95% CI: 1.964-6.004, p < 0.001) were identified as independent predictors of worse overall survival. Patients with pStage II/III colorectal cancer who demonstrate a lower postoperative PNI levels compared to preoperative had poorer overall survival and recurrence-free survival. Perioperative PNI changes can serve as useful biomarkers for predicting survival and recurrence.

Early outcomes of MR-guided SBRT for patients with recurrent pancreatic adenocarcinoma

BackgroundLocal treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9–13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC.MethodsPatients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40–50 Gy in 4–5 fractions with target and OAR delineation per institutional standards. Endpoints included local control per RECIST v1.1, distant failure, overall survival (OS), and acute and chronic toxicities per Common Terminology Criteria for Adverse Events, v5.ResultsFifteen patients with LR-PAC were identified with median follow-up of 10.6 mos (2.8–26.5 mos) from MRgSBRT. There were 8 females and 7 males, with a median age of 69 years (50–83). One patient underwent neoadjuvant radiation for 50.4 Gy in 28 fractions followed by resection, and one underwent adjuvant radiation for 45 Gy in 25 fractions prior to recurrence. MRgSBRT was delivered a median of 18.8 mos (3.5–52.8 mos) following resection. OS following recurrence at 6 and 12 mos were 87% and 51%, respectively, with a median survival time of 14.1 mos (3.2–27.4 mos). Three patients experienced local failure at 5.9, 7.8, and 16.6 months from MgSBRT with local control of 92.3% and 83.9% at 6 and 12 months. 10 patients experienced distant failure at a median of 2.9 mos (0.3–6.7 mos). Grade 1–2 acute GI toxicity was noted in 47% of patients, and chronic GI toxicity in 31% of patients. No grade > 3 toxicities were noted.ConclusionsThis is the first report on toxicity and outcomes of MRgSBRT for LR-PAC in the literature. MRgSBRT is a safe, feasible treatment modality with the potential for improved local control in this vulnerable population. Future research is necessary to better identify which patients yield the most benefit from MRgSBRT, which should continue to be used with systemic therapy as tolerated.Trial Registration: Jefferson IRB#20976, approved 2/17/21.

Tumor inflammatory microenvironment contribution to survival in resected upstaged adenocarcinomas

IntroductionTumor Inflammatory microenvironment (TIME) encompasses several immune pathways modulating cancer development and escape that are not entirely uncoded. The results achieved with immunotherapy elicited the scientific debate on TIME also in non-small cell lung cancer (NSCLC). We aimed to investigate whether TIME (in terms of PD-L1 expression and/or Tumor Infiltrating Lymphocytes - TILs) played a separate role in terms of survival (OS) in resected upstaged lung adenocarcinomas (ADCs), excluding other perioperative variables as confounders. Materials and methodsThis retrospective study included 50 patients with a clinically resectable lung ADC, undergoing surgery (lobectomy or segmentectomy) at the Thoracic Unit of Padova University Hospital between 2016 and 2022 and receiving an unexpected pathological upstaging (IIB or higher). ResultsDespite microscopical variables increasing from IIB to IIIB, survival was not significantly related to them. OS was better in TIME-active patients (defined as the presence of positive PD-L1 and/or TILs>10 %) than double negatives (PD-L1-/TILs-) (p = 0.01). In IIB or higher ADCs, TIME-active patients showed an improved survival compared to double negatives, merging the current TIME theories. ConclusionTIME seems to be associated with survival independently from other microscopical parameter, even in case of resected upstaged adenocarcinomas.

Sublobar Resection for Subsolid Lung Adenocarcinomas: How Much Margin Is Enough?

Sublobar Resection for Subsolid Lung Adenocarcinomas: How Much Margin Is Enough?

Comparison of the different versions of NCCN guidelines for predicting margin-negative resection of pancreatic cancer in patients undergoing upfront surgery.

The purpose of this study was to compare the different versions of the National Comprehensive Cancer Network (NCCN) guidelines for defining resectability of pancreatic ductal adenocarcinoma (PDAC) in predicting margin-negative (R0) resection, and to assess inter-reader agreement. This retrospective study included 283 patients (mean age, 65.1 years ± 9.4 [SD]; 155 men) who underwent upfront pancreatectomy for PDAC between 2017 and 2019. Two radiologists independently determined the resectability on preoperative CT according to the 2017, 2019, and 2020 NCCN guidelines. The sensitivity and specificity for R0 resection were analyzed using a multivariable logistic regression analysis with generalized estimating equations. Inter-reader agreement was assessed using kappa statistics. R0 resection was accomplished in 239 patients (84.5%). The sensitivity and specificity averaged across two readers were, respectively, 76.6% and 29.5% for the 2020 guidelines, 74.1% and 32.9% for the 2019 guidelines, and 72.6% and 34.1% for the 2017 guidelines. Compared with the 2020 guidelines, both 2019 and 2017 guidelines showed significantly lower sensitivity for R0 resection (p ≤ .009). Specificity was significantly higher with the 2017 guidelines (p = .043) than with the 2020 guidelines. Inter-reader agreements for determining the resectability of PDCA were strong (k ≥ 0.83) with all guidelines, being highest with the 2020 guidelines (k = 0.91). The 2020 NCCN guidelines showed significantly higher sensitivity for prediction of R0 resection than the 2017 and 2019 guidelines.

Correlation between relative dose intensity of adjuvant S-1 chemotherapy and psoas muscle mass volume and survival after resection of pancreatic ductal adenocarcinoma: A retrospective study.

This study aimed to investigate the prognostic relationship between relative dose intensity (RDI) of adjuvant S-1 chemotherapy and psoas muscle mass volume (PMV) in patients with resected pancreatic ductal adenocarcinoma. We enrolled 105 patients with histologically confirmed pancreatic ductal adenocarcinoma who had undergone pancreatectomy. Adjuvant S-1 chemotherapy was administered to 72 (68.6%) of the 105 patients and not to the remaining 33 patients. Patients who received adjuvant S-1 chemotherapy were stratified into high- and low-RDI groups by the cutoff value for RDI. Five-year overall survival (OS) and relapse-free survival (RFS) rates were significantly higher in the high- than in the low-RDI group. Similarly, both the 5-year OS and RFS rates were significantly greater among patients in the high-PMV group than among patients in the low-PMV group. The RDI was an independent prognostic factor in our study patients. Furthermore, patients who received adjuvant S-1 chemotherapy were stratified into 3 groups: those with both high RDI and high-PMV, Group A; those with either high RDI or high PMV (but not both), Group B; and those with both low RDI and low-PMV, group C. There were statistically significant differences in 5-year OS and RFS between 3 patient groups (5-year overall survival: P = .023, 5-year relapse-free survival: P = .001). The area under the curve for the combination of RDI and PMV (0.674) was greater than that for RDI alone (0.645). A sufficient dosage of adjuvant S-1 chemotherapy is important in improving survival of patients with resected pancreatic ductal adenocarcinoma. A combination of RDI and PMV may predict the prognosis of patients with resected pancreatic ductal adenocarcinoma more effective than RDI alone.

Overall Volume of Upper Gastrointestinal Surgery Positively Impacts Gastric Cancer Outcomes at Centers with Low Gastrectomy Volume.

The relationship between hospital volume and surgical mortality is well documented. However, complete centralization of surgical care is not always feasible. The present study investigates how overall volume of upper gastrointestinal surgery at hospitals influences patient outcomes following resection for gastric adenocarcinoma. National Cancer Database (2010-2019) patients with pathologic stage 1-3 gastric adenocarcinoma who underwent gastrectomy were identified. Three cohorts were created: low-volume hospitals (LVH) for both gastrectomy and overall upper gastrointestinal operations, mixed-volume hospital (MVH) for low-volume gastrectomy but high-volume overall upper gastrointestinal operations, and high-volume gastrectomy hospitals (HVH). Chi-squared tests were used to analyze sociodemographic factors and surgical outcomes and Kaplan-Meier method for survival analysis. In total, 26,398 patients were identified (LVH: 20,099; MVH: 539; HVH: 5,760). The 5-year survival was equivalent between MVH and HVH for all stages of disease (MVH: 56.0%, HVH 55.6%; p = 0.9866) and when stratified into early (MVH: 69.9%, HVH: 65.4%; p = 0.1998) and late stages (MVH: 24.7%, HVH: 32.0%; p = 0.1480), while LVH had worse survival. After matching patients, postoperative outcomes were worse for LVH, but there was no difference between MVH and HVH in terms of adequate lymphadenectomy, margin status, readmission rates, and 90-day mortality rates. Despite lower gastrectomy volume for cancer, postoperative gastrectomy outcomes at centers that perform a high number of upper gastrointestinal cancer surgeries were similar to hospitals with high gastrectomy volume. These hospitals offer a blueprint for providing equivalent outcomes to high volume centers while enhancing availability of quality cancer care.

The Value of Clinical Characteristics and Hematological Parameters for Prognostic Assessment of Pancreatic Cancer Patients Undergoing Radical Resection

To explore the relationship between baseline clinical characteristics and hematological parameters of patients undergoing radical resection for pancreatic ductal adenocarcinoma (PDAC) and their prognosis, and to provide references for stratifying the patients' clinical risks. We retrospectively collected clinical data from 445 patients who underwent radical surgical treatment for PDAC at West China Hospital, Sichuan University between January 2010 and February 2019. Then, we conducted retrospective clinical analysis with the collected data. Data on patients' basic clinical characteristics, routine blood test results, and tumor indicators were collected to explore their effects on the postoperative overall survival (OS) of PDAC patients. Cox proportional hazards regression was used to identify factors affecting OS. Statistical analysis was performed using the SPSS 23.0 software package. The postoperative median overall survival (mOS) was 17.0 months (95% CI: 15.0-19.0). The 1, 2, 3, 4, and 5-year survival rates of the patients included in the study were 60.6%, 33.4%, 19.1%, 12.7%, and 9.6%, respectively. The multivariate Cox proportional hazards model analysis demonstrated that a number of factors independently affect postoperative survival in PDAC patients. These factors include tumor location (hazards ratio [HR]=1.574, 95% CI: 1.233-2.011), degree of tumor cell differentiation (HR=0.687, 95% CI: 0.542-0.870), presence of neural invasion (HR=0.686, 95% CI: 0.538-0.876), TNM staging (HR=1.572, 95% CI: 1.252-1.974), postoperative adjuvant therapy (HR=1.799, 95% CI: 1.390-2.328), preoperative drinking history (HR=0.744, 95% CI: 0.588-0.943), and high serum CA199 levels prior to the surgery (HR=0.742, 95% CI: 0.563-0.977). In PDAC patients, having tumors located in the head of the pancreas, moderate and high degrees of differentiated, being free from local neurovascular invasion, being in TNM stage Ⅰ, undergoing postoperative adjuvant therapy, no history of alcohol consumption prior to the surgery, and preoperative serum CA199 being less than or equal to 37 U/mL are significantly associated with a better prognosis.

Low rectal resection for low rectal endometriosis and rectal adenocarcinoma: Are we discussing the same risks?

To evaluate the rate and risk factors for anastomosis leakage in patients undergoing colorectal resection with low anastomosis for rectal endometriosis and rectal adenocarcinoma. A retrospective cohort study evaluating prospectively collected data was conducted. Patients undergoing colorectal resection for rectal endometriosis and rectal adenocarcinoma with low anastomosis (<7 cm from the anal verge [AV]) from September 2018 to January 2023 were included in the analysis. The main outcome was the rate of anastomosis leakage. A multivariate logistic regression was conducted to evaluate risk factors for anastomosis leakage in both groups. A total of 159 patients underwent colorectal resection with low anastomosis due to rectal endometriosis (n = 99) and rectal adenocarcinoma (n = 60). Patients with endometriosis were significantly younger than those with adenocarcinoma (35.7 ± 5.1 vs 63.7 ± 12.6; P = 0.001). The leakage rate was similar between the endometriosis (n = 12, 12.1%) and adenocarcinoma (n = 9, 15.0%) patients (P = 0.621). The anastomosis height less than 5 cm from the AV (adjusted odds ratio [aOR] 12.12, 95% confidence interval [CI] 2.24-23.54) was significantly associated with the anastomosis leakage. Protective stoma was associated with the decrease of the leakage risk (aOR 0.12, 95% CI 0.01-0.72). The type of disease (rectal endometriosis or adenocarcinoma) was not associated with the anastomosis leakage (aOR 2.87, 95% CI 0.34-21.23). Despite the different pathogenesis, the risk of anastomotic leakage was found to be similar between patients with low rectal endometriosis and those with rectal adenocarcinoma. These results must be considered by the gynecologist and colorectal surgeon to deliver proper information before rectal surgery for endometriosis.

Stroma AReactive Invasion Front Areas (SARIFA) predict poor survival in adenocarcinomas of the stomach and gastrooesophageal junction: a validation study

Recently, the presence of “Stroma AReactive Invasion Front Areas” (SARIFA) has been described as a promising adverse prognostic factor in gastric cancer. However, the validity of this approach still needs to be tested. The aim of this study was to independently assess the utility of the proposed method in a well-characterised cohort of primary resected adenocarcinomas of stomach and gastrooesophageal junction (n = 392). SARIFA status was analysed on routine slides of resection specimens. Cases were divided into SARIFA-positive and negative groups and analysed in relation to clinicopathological and survival data. SARIFA positivity was found in 15.1% (n = 59) cases and was significantly associated with Lauren phenotype (p < 0.001), pT (p = 0.001), pN (p = 0.018), UICC stage (p = 0.031), tumour budding (p = 0.002), overall survival (p < 0.001) and cancer-specific survival (p < 0.001). SARIFA-positive tumours had a worse prognosis in the multivariate setting (HR = 1.847, 95% CI: 1.300–2.624, p = 0.001). SARIFA status is an independent prognostic factor in gastric cancer, in particular in locally advanced tumours.

Density of tumor-infiltrating NK and Treg cells is associated with 5 years progression-free and overall survival in resected lung adenocarcinoma

Surgical resection of pulmonary adenocarcinoma is considered to be curative but progression-free survival (PFS) has remained highly variable. Antitumor immune response may be important, however, the prognostic significance of tumor-infiltrating natural killer (NK) and regulatory T (Treg) lymphocytes is uncertain. Resected pulmonary adenocarcinoma tissues (n = 115) were studied by immunohistochemical detection of NKp46 and FoxP3 positivity to identify NK and Treg cells, respectively. Association of cell densities with clinicopathological features and progression-free survival (PFS) as well as overall survival (OS) were analyzed with a follow-up time of 60 months. Both types of immune cells were accumulated predominantly in tumor stroma. NK cell density showed association with female gender, non-smoking and KRAS wild-type status. According to Kaplan-Meier analysis, PFS and OS proved to be longer in patients with high NK or Treg cell densities (p = 0.0293 and p = 0.0375 for PFS, p = 0.0310 and p = 0.0448 for OS, respectively). Evaluating the prognostic effect of the combination of NK and Treg cell density values revealed that PFS and OS were significantly longer in NKhigh/Treghigh cases compared to the other groups combined (p = 0.0223 and p = 0.0325, respectively). Multivariate Cox regression analysis indicated that high NK cell density was independent predictor of longer PFS while high NK and high Treg cell densities both proved significant predictors of longer OS. The NKhigh/Treghigh combination also proved to be an independent prognostic factor for both PFS and OS. In conclusion, NK and Treg cells can be components of the innate and adaptive immune response at action against progression of pulmonary adenocarcinoma.