Non-mucinous Adenocarcinoma Research Articles

Predictive Value of Preoperative Fibrinogen and Albumin Score (FA Score) for Prognosis and Chemotherapeutic Efficacy in Resected Colorectal Cancer: A Retrospective Cohort Study.

Background: Limited research elucidated the role of preoperative fibrinogen and albumin (FA) score in colorectal cancer (CRC). We aimed to clarify the predictive value of FA score for prognosis and chemotherapeutic efficacy in CRC patients who underwent curative resection. Materials and Methods: Patients' clinicopathological parameters of 735 cases of resected CRC were recruited retrospectively. Optimal cut-off values of the preoperative plasma fibrinogen (F) and albumin (A) were confirmed by receiver operating characteristic (ROC) curves. Patients were categorized into three groups based on the FA score, and were further divided into a chemotherapy group and a non-chemotherapy group. Correlations between FA score and clinicopathological features, as well as overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) were assessed with Kaplan-Meier (KM) survival method, univariate and multivariate Cox proportional hazard models, and subgroup analyses. Results: The Kaplan-Meier survival curves revealed that higher FA score could predict poorer OS and CSS (P<0.001). Multivariate analyses revealed that FA score was an independent prognostic factor for OS (P=0.037). In addition, subgroup analyses based on the histological feature and primary tumor location showed that elevated FA score was significantly associated with worse OS, CSS and DFS (all, P<0.05) in patients with non-mucinous colorectal adenocarcinoma and rectal cancer (RECC). Subgroup analyses based on the TNM stage showed that elevated FA score was significantly associated with worse OS, CSS (all, P<0.05) in patients with TNM stage II tumors. Furthermore, chemotherapy could benefit the OS and CSS in TNM stage III CRC patients with FA score 1 and 2 (all, P<0.05). Conclusion: The preoperative FA score is an independent prognostic factor for CRC patients who underwent curative resection and may help predict the responses to chemotherapy in clinical practice. FA score may serve as a complementary to the TNM staging system to identify high-risk patients.

IMMUNOHISTOCHEMICAL EXPRESSION OF THYMIDYLATE SYNTHASE IN DIFFERENT GRADES OF COLORECTAL CARCINOMA

Objective: To Evaluate the Immunohistochemical Expression of Thymidylate Synthase in different grades and histological types of Colorectal Carcinoma.&#x0D; Study Design: Cross sectional, Descriptive study&#x0D; Place and duration of study: This study was conducted from June 2019 to November 2020 in the Department of Pathology at Postgraduate Medical Institute Lahore / Lahore General Hospital. &#x0D; Methodology: Forty resected gut specimens diagnosed on light microscopy as Colorectal adenocarcinoma were included on the basis of non-probability, consecutive sampling technique. Cases were reviewed and histological typing and grading was done separately by two competent Histopathologists. Immunohistochemical staining for Thymidylate Synthase was performed. Results of Thymidylate Synthase immunostaining were interpreted by the two observers based on the cytoplasmic staining of tumor cells. Thymidylate Synthase expression was quantified through a visual grading system depending upon the staining intensity and percentage of stained cells. &#x0D; Results: Out of 40 cases of adenocarcinoma, majority of the patients (45%) belong to the age range of 51-60 years. There were 31(77.5%) male patients while 9(22.5%) were females. 28 (22%) cases were classified as low grade while 12 (11%) cases were reported as high-grade carcinomas. Amongst these Thymidylate Synthase expression was seen in 78.6% of low-grade carcinoma and 91.6% of high-grade carcinomas. Regarding histological subtyping, 23(57.5 %) cases were identified as non-mucinous adenocarcinomas, (9)22.5% as mucinous adenocarcinoma and (8) 20% as signet ring adenocarcinoma. Thymidylate Synthase expression was found to be similar i.e., 78% in non- mucinous as well as mucinous carcinomas however, 100% positivity was noticed in signet ring carcinomas. The overall positivity for Thymidylate Synthase was found to be 82.5%. &#x0D; Conclusion: Colorectal carcinoma was prevalent among males of 51-60 years of age. 82.5% cases of colorectal carcinoma expressed Thymidylate synthase receptors and its expression was found to be higher in high grade tumors.&#x0D;

Endobronchial spread of adenocarcinoma is a distinct pattern of invasion and associated with inferior clinical outcomes in lung adenocarcinoma.

The spread of lung adenocarcinoma cells into the bronchi and bronchioles is not well documented. We termed this histological finding "endobronchial spreading of adenocarcinoma" (EBSA) and investigated its prevalence and clinical significance. We reviewed 320 resected specimens from patients diagnosed with invasive adenocarcinoma, and EBSA was observed in 144 patients (45%). EBSA was significantly associated with advanced pathological stage, higher histological grade, larger tumour invasion, lymphovascular infiltration, and spread through air spaces. Patients with EBSA had significantly shorter relapse-free survival (RFS) and cancer-specific survival (CSS) in univariate analysis (P < 0.001). In a subgroup analysis of patient with small-sized (invasion size ≤30 mm) adenocarcinoma in the localized stage, EBSA was an independent inferior prognostic indicator in multivariate analysis. In a subgroup analysis of patients with small-sized Grade 1 nonmucinous adenocarcinoma (n = 61), EBSA was observed in 11 patients, and the presence of EBSA was associated with significantly shorter RFS and CSS (P = 0.026 and P = 0.001, respectively). Our results demonstrated that EBSA is a significant risk factor for disease recurrence and cancer-related deaths. EBSA can be regarded as a distinctive pattern of invasion and its recognition can be beneficial in the diagnosis of lung adenocarcinoma.

Whole-lesion iodine map histogram analysis versus single-slice spectral CT parameters for determining novel International Association for the Study of Lung Cancer grade of invasive non-mucinous pulmonary adenocarcinomas

PurposeThe purpose of this study was to evaluate and compare the performances of whole-lesion iodine map histogram analysis to those of single-slice spectral computed tomography (CT) parameters in discriminating between low-to-moderate grade invasive non-mucinous pulmonary adenocarcinoma (INMA) and high-grade INMA according to the novel International Association for the Study of Lung Cancer grading system of INMA. Materials and methodsSixty-one patients with INMA (34 with low-to-moderate grade [i.e., grade I and grade II] and 27 with high grade [i.e., grade III]) were evaluated with spectral CT. There were 28 men and 33 women, with a mean age of 56.4 ± 10.5 (standard deviation) years (range: 29–78 years). The whole-lesion iodine map histogram parameters (mean, standard deviation, variance, skewness, kurtosis, entropy, and 1st, 10th, 25th, 50th, 75th, 90th, and 99th percentile) were measured for each INMA. In other sessions, by placing regions of interest at representative levels of the tumor and normalizing them, spectral CT parameters (iodine concentration and normalized iodine concentration) were obtained. Discriminating capabilities of spectral CT and histogram parameters were assessed and compared using area under the ROC curve (AUC) and logistic regression models. ResultsThe 1st, 10th, and 25th percentiles of the iodine map histogram analysis, and iodine concentration and normalized iodine concentration of single-slice spectral CT parameters were significantly different between high-grade and low-to-moderate grade INMAs (P < 0.001 to P = 0.002). The 1st percentile of histogram parameters (AUC, 0.84; 95% confidence interval [CI]: 0.73–0.92) and iodine concentration (AUC, 0.78; 95% CI: 0.66–0.88) from single-slice spectral CT parameters had the best performance for discriminating between high-grade and low-to-moderate grade INMAs. At ROC curve analysis no significant differences in AUC were found between histogram parameters (AUC = 0.86; 95% CI: 0.74–0.93) and spectral CT parameters (AUC = 0.81; 95% CI: 0.74–0.93) (P = 0.60). ConclusionBoth whole-lesion iodine map histogram analysis and single-slice spectral CT parameters help discriminate between low-to-moderate grade and high-grade INMAs according to the novel International Association for the Study of Lung Cancer grading system, with no differences in diagnostic performances.

Appendiceal Mucinous Incidental Neoplasm a Rare Case Report and Literature Review

Mucinous appendiceal tumors consist of mucinous adenocarcinoma, low-grade appendiceal mucinous neoplasm, and high-grade appendiceal mucinous neoplasm. The incidence of non-mucinous adenocarcinomas is reduced. The most recent edition of the World Health Organization classification and recent consensus guidelines will enable the consistent application of agreed nomenclature. Not only is precise diagnosis essential for effective patient management, but it also facilitates the comparison of results across centers and tumor registries. The most prevalent benign adenoma in the appendix is serrated. It is imperative to differentiate these conditions from low-grade appendiceal mucinous neoplasms, as the latter can also resemble harmless ailments. Adenocarcinomas of the goblet cells are a rare subtype of appendiceal neoplasm. While appendiceal neoplasms are uncommon, they are not entirely so, and even the most seasoned pathologists may find them difficult to diagnose. In addition, appendiceal neoplasia classification and terminology have been subjects of contention for decades. Nonmucinous appendiceal neoplasms are less prevalent than mucinous tumors, and their association with other appendiceal neoplasm subtypes remains uncertain. A literature review of appendiceal mucinous neoplasms identified during laparoscopic appendicectomies is presented here.

Role of colectomy in the management of appendiceal tumors: a retrospective cohort study

BackgroundAppendiceal tumors represent a range of histologies that vary in behavior. Recommendations for treatment with appendectomy versus right hemicolectomy (RHC) for different tumor types are evolving and sometimes conflicting. This study sought to characterize variation in the United States around surgical treatment of major appendiceal tumor types over time and describe differences in outcomes based on procedure.MethodsPatients diagnosed with appendiceal goblet cell adenocarcinoma (GCA), mucinous adenocarcinoma, neuroendocrine neoplasm (NEN), or non-mucinous adenocarcinoma from 2004–2017 were identified in the National Cancer Database. Trends in RHC over time and predictors of RHC were identified. Surgical outcomes for each histologic type and stage were compared.ResultsOf 18,216 patients, 11% had GCAs, 34% mucinous adenocarcinoma, 31% NENs, and 24% non-mucinous adenocarcinoma. Rate of RHC for NEN decreased from 68% in 2004 to 40% in 2017 (p = 0.008) but remained constant around 60–75% for other tumor types. Higher stage was associated with increased odds of RHC for all tumor types. RHC was associated with higher rate of unplanned readmission (5% vs. 3%, p < 0.001) and longer postoperative hospital stay (median 5 days vs. 3 days, p < 0.001). On risk-adjusted analysis, RHC was significantly associated with increased survival versus appendectomy for stage 2 disease of all tumor types (HRs 0.43 to 0.63) and for stage 1 non-mucinous adenocarcinoma (HR = 0.56).ConclusionsMost patients with appendiceal tumors undergo RHC, which is associated with increased readmission, longer length of stay, and improved survival for stage 2 disease of all types. RHC should be offered selectively for appendiceal tumors.

Prognostic implications of CT-defined ground glass opacity in clinical stage I–IIA grade 3 invasive non-mucinous pulmonary adenocarcinoma

To investigate the prognostic impact of computed tomography (CT)-defined ground glass opacity (GGO) in patients with clinical stage I-IIA grade 3 invasive non-mucinous pulmonary adenocarcinoma (INPA). The present study retrospectively enrolled 187 patients diagnosed with stage I-IIA grade 3 INPA. Their clinicopathological, radiological, and genetic information was evaluated systematically, and a 5-year follow-up was conducted to monitor disease recurrence and mortality. Patients were stratified based on the presence of a GGO component, and the Cox proportional hazard model was employed to assess the influence of clinicopathological factors and genetic variables on tumour outcomes. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Significant differences were observed in both OS and RFS based on the presence of a GGO component. The group with GGO exhibited superior OS (p=0.002) and RFS (p=0.029). Multivariate analysis revealed that the presence of a GGO component (hazard ratio [HR]=0.412, 95% confidence interval [CI]: 0.177-0.959, p=0.040), clinical T2 stage (HR=2.473, 95% CI: 1.498-4.083, p<0.001), pathological N2 stage (HR=3.049, 95% CI: 1.800-5.167, p<0.001), and mixed high-grade patterns (HR=2.392, 95% CI: 1.418-4.036, p=0.001) were predictors of RFS. The presence of a GGO component is strongly associated with a favourable prognosis in grade 3 INPA.

Incidence rate and histology of appendiceal neoplasms in complicated versus uncomplicated appendicitis: A meta-analysis and systematic review

IntroductionStudies evaluating the rate and histology of appendiceal neoplasms between complicated and uncomplicated appendicitis include a small number of patients. Therefore, we sought a meta-analysis and systematic review comparing the rates and types of appendiceal neoplasm between complicated and uncomplicated appendicitis.MethodsWe included articles published from the time of inception of the datasets to September 30, 2022. The electronic databases included English publications in Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, and Scopus.ResultsA total of 4962 patients with appendicitis enrolled in 4 comparative studies were included. The mean age was 43.55 years (16- 94), and half were male (51%). Based on intra-operative findings, 1394 (38%) had complicated appendicitis, and 3558 (62%) had uncomplicated appendicitis. The overall incidence rate of neoplasm was 1.98%. No significant difference was found in the incidence rate of appendiceal neoplasm between complicated (3.29%) and uncomplicated (1.49%) appendicitis (OR 0.44, 95% CI 0.16- 1.23; p < 0.087; I2 = 54.9%). The most common appendiceal neoplasms were Neuroendocrine Tumors (NET) (49.21%), Nonmucinous Adenocarcinoma (24.24%), Mixed Adeno-Neuroendocrine Tumor (MANEC) (11.40%), Mucinous Adenocarcinoma (4.44%). There was a significant difference between complicated and uncomplicated appendicitis in rates of adenocarcinoma (50% vs. 13%), NET (31% vs. 74%), MANEC (19% vs. 13%) (P < 0.001).ConclusionWhile there was no significant difference in the overall neoplasm rate between complicated and uncomplicated appendicitis, the NET rate was significantly higher in uncomplicated appendicitis. In comparison, the Adenocarcinoma rate was considerably higher in Complicated appendicitis. These findings emphasize the importance of evaluating risk factors for neoplasm when considering appendectomy in patients with appendicitis.

Stable Therapeutic Transgenic FIX Levels for More Than 10 Years in Subjects with Severe Hemophilia B Who Received scAAV2/8-LP1-Hfixco Adeno-Associated Virus Gene Therapy

Background: Previously, we reported data from a first-in-human, dose-escalation, Phase 1 gene therapy trial demonstrating a dose-dependent increase in transgenic factor IX (FIX) expression in 10 adults with severe hemophilia B (FIX activity ≤1%). This was achieved following a single intravenous infusion of a self-complementary adeno-associated virus (scAAV) vector containing the wild-type FIX gene (codon-optimized), under the control of a synthetic liver-specific promoter and pseudotyped AAV8 capsid (scAAV2/8-LP1-hFIXco; ClinicalTrials.gov:NCT00979238). We now report durable efficacy and long-term safety over at least 10 years of follow-up in these participants. Methods: FIX activity, annualized bleeding rate (ABR), use of FIX concentrates, safety (specifically transaminitis and oncogenesis), and FIX expression kinetics were evaluated in the 10 participants following a bolus infusion of scAAV2/8-LP1-hFIXco at a dose of 2x10 11vg/kg (N=2), 6x10 11vg/kg (N=2), or 2x10 12vg/kg (N=6), between 2010 and 2012. Results: As of December 31, 2022, the median follow-up was 10.7 years (range 4-12 years). A total of 11 treatment-related adverse events occurred in 10 participants, including transient elevation of liver transaminases within 3 months of vector infusion in 4 of 6 patients treated with the high vector dose, without any recurrence. Two new serious adverse events were reported: (1) non-mucinous lung adenocarcinoma in situ, identified incidentally following a bullectomy for spontaneous pneumothorax 5 years after gene therapy in a 48-year-old participant considered not related to gene therapy following molecular studies, and (2) adenocarcinoma of the prostate in a 72-year-old participant 12 years after gene therapy. Tissue evaluation of the latter case is ongoing. No FIX inhibitors, thrombosis, persistent transaminitis or deaths were observed. Transgenic FIX expression has remained stable, with mean (±SD) FIX activity (one-stage) for the three dose cohorts of 1.7±0.9, 2.3±0.9 and 4.9±2.2 IU/dL, respectively (Figure 1). The mean and median ABR over the 10-year period following gene therapy of all 10 participants were 1.95 and 1.6 compared to 16.5 and 14, respectively, before gene therapy. This represents an 8.5-fold reduction in bleeding events (Wilcoxon signed rank test p=0.002). In the 6 high-dose participants, the ABR was 21-fold lower (mean=1.16, median 1, paired t-test, p&amp;lt;0.008). Mean and median FIX concentrate usage before gene therapy in the 10 participants were 2869 and 2526 IU/kg dropping to 945 and 274 IU/kg, respectively, over a 10-year period after gene therapy (p=0.0003). All participants developed a persistent, high-titer polyclonal anti-AAV8 capsid-specific antibody response after administration of scAAV2/8-LP1-hFIXco. Conclusion: Expression of transgenic FIX has remained stable over a period of 10 years following systemic administration of scAAV2/8-LP1-hFIXco resulting in sustained clinical benefit, with substantial reduction in ABR and FIX concentrate use.

Clinical Significance of the Proposed Pathologic Criteria for Invasion by the International Association for the Study of Lung Cancer in Resected Nonmucinous Lung Adenocarcinoma

IntroductionAccurate diagnostic criteria for tumor invasion are essential for precise pathologic tumor (pT) staging. Recently, the International Association for the Study of Lung Cancer (IASLC) Pathology Committee suggested a new set of criteria for assessing tumor invasion, but the clinical usefulness of the proposed criteria has not been evaluated. MethodsThe study included 1295 patients with resected part-solid lung adenocarcinoma from January 2017 to December 2019 at the Samsung Medical Center, Seoul, Korea. The revised pT stage was determined by the extent of the newly measured invasive component using the IASLC criteria. The primary outcome was to compare the performance of the revised pT stage with the original pT stage in predicting recurrence-free survival and proof of invasion status (i.e., recurrence or lymph node metastasis). The secondary outcome was the correlation with radiologic surrogates of tumor invasiveness (consolidation-to-tumor ratio and maximum standardized uptake value) and pathologic risk factors. ResultsThe re-evaluation resulted in a 22% downstaging and 2.5% upstaging of pT, which improved the correlation with radiologic (consolidation-to-tumor ratio and maximum standardized uptake value) and pathologic risk factors. The revised pT staging allowed for more accurate discrimination of recurrence-free survival than the original pT staging (c-index = 0.794 versus 0.717). Moreover, the revised pT staging significantly improved the prediction of recurrence or lymph node metastasis (area under the curve = 0.818 versus 0.741, p < 0.001). ConclusionsTo our knowledge, this is the first study evaluating the clinical significance of the IASLC-proposed criteria for invasion. The proposed IASLC criteria offered better alignment with clinicopathologic risk factors and improved prognostication. Further studies are warranted to assess the impact of the IASLC criteria on treatment decisions and patient outcomes.

Micropapillary Pattern in Invasive Mucinous Adenocarcinoma of the Lung: Comparison With Invasive Non-Mucinous Adenocarcinoma.

Background. The presence of a micropapillary pattern is associated with poor outcomes in lung adenocarcinoma. This study aimed to assess the clinicopathological features of micropapillary pattern in mucinous adenocarcinoma of the lung. Methods. The patients were stratified into three groups: the invasive mucinous adenocarcinoma group (60 patients), the mixed invasive mucinous adenocarcinoma group (33 patients), and the invasive non-mucinous adenocarcinoma group (237 patients). The presence of micropapillary pattern and its clinicopathological features were analyzed and compared between the three groups. Results. Compared to mixed invasive mucinous adenocarcinoma, invasive mucinous adenocarcinoma had lower frequencies of micropapillary pattern (28.3% vs 87.9%, respectively; P < .001) and lymph node metastasis (00.0% vs 15.1%, respectively; P = .005). The frequency of tumor spread through air space (STAS) in invasive mucinous adenocarcinoma (23.3%) was higher than that in invasive non-mucinous adenocarcinoma (6.3%; P < .001), while lower than that in mixed invasive mucinous adenocarcinoma (60.6%; P < .001). When the three groups were all accompanied by micropapillary pattern, there was no obvious difference in STAS between invasive mucinous adenocarcinoma with micropapillary pattern and mixed mucinous adenocarcinoma with micropapillary pattern (P > .05). No filigree pattern occurred in invasive mucinous adenocarcinoma with micropapillary pattern. Conclusions. The micropapillary pattern is frequently observed in invasive mucinous adenocarcinoma and has a better prognosis compared to mixed invasive mucinous adenocarcinoma and invasive non-mucinous adenocarcinoma. However, the malignancy of the micropapillary pattern in mixed mucinous adenocarcinoma was similar to that in invasive non-mucinous adenocarcinoma, even with the presence of mucus. These findings suggest that the development mechanisms of the micropapillary pattern in invasive mucinous adenocarcinoma and mixed mucinous adenocarcinoma may differ.

OA20.04 Clinical Significance of IASLC Proposed Pathologic Criteria for Invasion in Resected Non-mucinous Lung Adenocarcinoma

OA20.04 Clinical Significance of IASLC Proposed Pathologic Criteria for Invasion in Resected Non-mucinous Lung Adenocarcinoma

EP05.01-15 Prognosis in Terms of Invasive Non-mucinous Adenocarcinoma Grading System

EP05.01-15 Prognosis in Terms of Invasive Non-mucinous Adenocarcinoma Grading System

Pulmonary invasive mucinous adenocarcinoma.

Invasive mucinous adenocarcinoma (IMA) is a relatively rare subtype of lung adenocarcinoma, composed of goblet and/or columnar tumour cells containing abundant intracytoplasmic mucin vacuoles. While a majority of IMAs are driven by KRAS mutations, recent studies have identified distinct genomic alterations, such as NRG1 and ERBB2 fusions. IMAs also more frequently present as a pneumonic-like pattern with multifocal and multilobar involvement, and comparative genomic profiling predominantly shows a clonal relationship, suggesting intrapulmonary metastases rather than synchronous primary tumours. Accordingly, these unique features require different therapeutic approaches when compared to nonmucinous adenocarcinomas in general. In this article, we review recent updates on the histopathological, clinical, and molecular features of IMAs, and also highlight some unresolved issues for future studies.

Survival Benefit of Primary Tumor Resection Combined With Chemotherapy in Patients With Unresectable Colorectal Mucinous Adenocarcinoma With Liver Metastasis.

To evaluate the survival benefit of combining primary tumor resection (PTR) and chemotherapy in patients with unresectable colorectal mucinous adenocarcinoma with liver metastasis (UCR-MAC-LM). We obtained data from the surveillance, epidemiology, and end results database for patients with UCR-MAC-LM from 2010 to 2017. Clinicopathological characteristics were analyzed using the χ2 test. Propensity score matching was performed to balance baseline characteristics. Kaplan-Meier analysis and log-rank tests were used to estimate and compare survival outcomes. Univariate and multivariate Cox regression analyses were conducted to identify the prognostic factors. A total of 10,178 patients with unresectable colorectal adenocarcinoma with liver metastasis were included, of whom 6.01% (n=612) had UCR-MAC-LM. The UCR-MAC-LM group had a higher proportion of female patients, a greater number of elderly patients, an increased incidence of right colon localization, larger tumor size, and higher T and N staging than the unresectable colorectal non-mucinous adenocarcinoma with liver metastasis group (P<0.05). Multivariate analysis identified several independent prognostic factors (P<0.05). Patients with unresectable colorectal adenocarcinoma with liver metastasis who underwent PTR+C had superior survival rates compared with those who received PTR/C alone or no treatment (cancer-specific survival, P<0.05; overall survival, P<0.05). Subgroup analysis revealed that 17 of 22 groups of patients with UCR-MAC-LM who received PTR+C had significantly prolonged long-term survival compared with those who received PTR/C alone. This surveillance, epidemiology, and end results-based study indicates that PTR+C may offer a survival advantage for a specific subgroup of patients with UCR-MAC-LM compared with PTR/C alone. Nonetheless, additional clinical trials are necessary to validate these findings.

Distinct Recurrence Pattern and Survival Outcomes of Invasive Mucinous Adenocarcinoma of the Lung: The Potential Role of Local Therapy in Intrapulmonary Spread.

Invasive mucinous adenocarcinoma (IMA) is distinct from non-mucinous adenocarcinoma, but studies on recurrent IMA are scarce. Thus, this study aimed to evaluate the recurrence patterns of IMA and the role of pulmonary local therapy (LT) in resectable pulmonary recurrence of IMA. The study reviewed 403 patients with surgically resected IMA between 1998 and 2018. The recurrence patterns were categorized as solitary pulmonary recurrence (SPR), multiple pulmonary recurrence (MPR), and extra-pulmonary recurrence (EPR). The clinicopathologic characteristics, overall survival (OS), and post-recurrence survival (PRS) were analyzed according to the recurrence pattern and LT administration. Recurrences were found in 91 (22.6%) patients, including 18 patients with SPR, 37 patients with MPR, and 36 patients with EPR. Compared with the MPR and EPR groups, the SPR group had a longer disease-free interval (32.5 vs. 9.6 vs. 10.1 months, respectively; p < 0.01) and a better OS (5-year OS: 88.5%, 41.5%, and 22.9%, respectively; p < 0.01). In case of resectable pulmonary recurrence, pulmonary LT was administered to 15 patients with SPR and 3 patients with MPR. These patients showed a better 5-year PRS than the other patients with pulmonary recurrence (86.3% vs. 30.4%; p < 0.01). Notably, long-term survival was observed for one patient with MPR undergoing LT and two patients with SPR undergoing a second LT for a second pulmonary recurrence. In this series, the patients with recurrent IMA showed different prognoses according to the recurrence pattern. The patients with pulmonary recurrence of IMA undergoing LT showed a favorable prognosis, suggesting the potential role of LT for resectable pulmonary recurrence of IMA.

A pretreatment prediction model of grade 3 tumors classed by the IASLC grading system in lung adenocarcinoma

PurposeThe new grading system for invasive nonmucinous lung adenocarcinoma (LUAD) in the 2021 World Health Organization Classification of Thoracic Tumors was based on a combination of histologically predominant subtypes and high-grade components. In this study, a model for the pretreatment prediction of grade 3 tumors was established according to new grading standards.MethodsWe retrospectively collected 399 cases of clinical stage I (cStage-I) LUAD surgically treated in Tianjin Chest Hospital from 2015 to 2018 as the training cohort. Besides, the validation cohort consists of 216 patients who were collected from 2019 to 2020. These patients were also diagnosed with clinical cStage-I LUAD and underwent surgical treatment at Tianjin Chest Hospital. Univariable and multivariable logistic regression analyses were used to select independent risk factors for grade 3 adenocarcinomas in the training cohort. The nomogram prediction model of grade 3 tumors was established by R software.ResultsIn the training cohort, there were 155 grade 3 tumors (38.85%), the recurrence-free survival of which in the lobectomy subgroup was better than that in the sublobectomy subgroup (P = 0.034). After univariable and multivariable analysis, four predictors including consolidation-to-tumor ratio, CEA level, lobulation, and smoking history were incorporated into the model. A nomogram was established and internally validated by bootstrapping. The Hosmer–Lemeshow test result was χ2 = 7.052 (P = 0.531). The C-index and area under the receiver operating characteristic curve were 0.708 (95% CI: 0.6563–0.7586) for the training cohort and 0.713 (95% CI: 0.6426–0.7839) for the external validation cohort.ConclusionsThe nomogram prediction model of grade 3 LUAD was well fitted and can be used to assist in surgical or adjuvant treatment decision-making.

Que faut-il connaître de la classification anatomopathologique des cancers pulmonaires ?: What do we need to know about the new histomolecular classification of lung cancers?

The latest WHO classification of thoracic tumors published in 2021 has integrated morphology, immunohistochemistry and molecular techniques, with greater emphasis on genetic testing than the 2015 WHO classification. Its major features include a section devoted entirely to the classification of small samples, their management and the immunohistochemical and molecular analyses to be performed. It provides guidelines concerning the histological subtyping of invasive non-mucinous adenocarcinomas and their grading, as well as their staging according to the new 8th edition pTNM classification, recognises the Spread Through Air Spaces (or STAS) as a poor prognostic factor. This new classification proposes a new terminology for pulmonary neuroendocrine neoplasms more in line with that of extrathoracic neuroendocrine tumors, and describes new entities such as bronchiolar adenoma, papillary muconodular ciliated tumor and SMARCA4-deficient tumors. Lastly for each tumor at the end of each chapter, essential and desirable criteria for its diagnosis are provided, as well as access to demonstrative virtual slides.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Clinical characteristics of patients with KRAS mutation detected by liquid biopsy.

KRAS mutation positive lung cancer is known to be clinically characterized by older age, males, and smokers. It is reported to be more common in mucinous adenocarcinoma, but all reports are based on analysis of tissue samples. Recently, blood samples have become available for analysis, suggesting a low detection rate of circulating tumor DNA in histological types, especially mucinous adenocarcinoma. In this study, we investigated the clinical characteristics of KRAS mutation-positive cases in the analysis of blood specimens, as these remain unclear. The clinical background of patients with KRAS mutation among those who underwent next-generation sequencing (NGS) analysis using blood samples was evaluated. NGS analysis was performed on 214 blood samples. KRAS mutations were detected in blood samples in 33 cases (15.4%), of which 31 cases (14.5%) had a histological pathology diagnosis. Mucinous adenocarcinoma accounted for 28.6% of cases with positive blood and tissue specimens, 10.0% of cases with positive blood specimens only, and 57.1% of cases with positive tissue specimens only. Mucinous adenocarcinoma tended to be less common in cases with positive blood specimens. In KRAS-positive patients with lung metastasis only, only one nonmucinous adenocarcinoma had a positive blood sample, and the others all had mucinous adenocarcinomas with positive tissue samples only. The results showed that the detection rate of KRAS-positive lung cancers detected by blood and tissue samples differs, and that the detection rate of blood samples may be poor, especially in the case of mucinous adenocarcinoma with lung metastases only.

Analysis of Clinicopathological Features on Spread Through Air Spaces of Lung Adenocarcinoma

The biological and molecular characteristics of spread through air spaces (STAS), a newly recognized invasive mode of lung cancer, remain controversial. The aim of this study was to investigate the clinicopathological features and molecular characteristics of STAS in patients with pulmonary adenocarcinoma. A total of 694 resected invasive non-mucinous lung adenocarcinomas diagnosed by clinicopathology from July 2019 to March 2021 in the First Affiliated Hospital of Guangzhou Medical University were collected, and the relationship between STAS and clinicopathological factors was analyzed. The state of protein expression of anaplastic lymphoma kinase (ALK) was detected by immunohistochemical method. Epidermal growth factor receptor (EGFR) was detected by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). ROS proto-oncogene 1-receptor (ROS1) was detected by reverse transcription-PCR (RT-PCR). A total of 344 STAS positive cases and 350 STAS negative cases were collected. By univariate analysis, STAS positivity was statistically associated with tumor maximum diameter (P<0.001), pleural invasion (P<0.001), lymphovascular invasion (P<0.001), nerve invasion (P=0.013), lymph node metastasis (P<0.001), clinical stage (P<0.001) and histological type (P<0.001). There was a statistical correlation between STAS and ALK protein expression (P=0.001). Multivariate analysis showed that STAS positive was correlated with pleural invasion (P=0.001), vascular invasion (P<0.001), lymph node metastasis (P=0.005)and ALK protein expression (P=0.032). STAS is associated with highly aggressive biological behavior of lung adenocarcinoma, suggesting a poor prognosis.