Postoperative irradiation in stage II thymomas: is it worth it?-shedding some light in the guidelines' gray zone.

Thymomas are rare, indolent tumors. Early stages (I-II) benefit from surgical treatment, while locally advanced diseases (stages III-IV) usually require a multidisciplinary approach. The role of postoperative radiotherapy (PORT) on anterior mediastinum for radically resected Masaoka-Koga stage II thymomas remains controversial. This study aims to determine the impact of PORT on the disease-free survival (DFS) of stage II thymomas. We retrospectively collected the clinical and oncologic data [age, sex, myasthenia gravis (MG) prevalence, Masaoka-Koga stage, World Health Organization (WHO) histologic subtype] of those patients who underwent radical exeresis in our Unit between January 2000 and December 2020. Kaplan-Meier estimates of DFS were then performed. Our study included 195 patients (M/F = 98/97). Almost all patients were affected by MG (90.7%) and most of them were operated by median sternotomy (93.3%). Thymoma stage was IIa in 87 cases (44.6%) and IIb in 108 cases (55.4%). The most represented histologic subtype was AB (27.7%), followed by B2 (24.6%), A (19%), B1 (14.9%) and B3 (13.8%). PORT was performed in 113 patients (58%, 39 stage IIa and 74 stage IIb). During the surveillance, 8 patients (4.1%) presented pleural recurrences and no local relapses. DFS was comparable in stage IIa and IIb patients, independently from PORT administration (p = .395 and p = .858, respectively). Moreover, PORT did not affect DFS considering the histologic subtypes (p = .304 for A and AB thymomas, p = .608 for B1, B2 and B3 thymomas). In our wide series, PORT administration didn't show any additional benefit on DFS. Therefore, based on our experience, patients with stage II thymoma who underwent radical surgery should not undergo any local adjuvant treatment.

Predictors of outcome following two-stage revision total knee arthroplasty.

PURPOSE: Two stage revision arthroplasty remains the gold standard for peri-prosthetic joint infections of the knee. However, the functional outcomes of revision surgeries and the factors governing them require further investigation. The purpose of this study was to (a) evaluate impact of early and late stage I surgery and interval between stage I and stage II; (b) understand the impact of infecting organism and resistance; (c) to estimate long term survivorship and causes of failure. METHODS: A retrospective review of 86 patients, who underwent two stage revision for prosthetic joint infections of the knee, was performed. Time between onset of symptoms to stage I (T1), and T1 to re-implantation (T2), along with microbiological studies, were analysed for their impact on functional outcomes, failure modalities and survivorship. RESULTS: In this study, the mean KSS-Knee improved from 64.0 ± 10.0 pre-operatively to 76.9 ± 10.4, and 77.2 ± 10.1 at the 5 and 10 year follow up respectively. The KSS-Function improved from 44.4 ± 8.8 pre-operatively to 72.2 ± 9.5 and 79.8 ± 8.1 at 5 and 10 year follow-up respectively. This study also found that T1 and T2 remained critical factors in determining functional outcome and longevity of the implant and a delay in these intervals was a significant predictor of failure. Gram negative, poly-microbial infections and organisms with methicillin and vancomycin resistance demonstrated lower survivorship (p-value, 0.001 at 5, 10 and 12 years). Re-infections occurred in 4 cases while 9 cases failed due to aseptic causes. CONCLUSION: Two-stage revision arthroplasty produced good functional outcomes when the infection was caused by single sensitive organism that did not exhibit high resistance to antibiotics. Stage I performed within 4 weeks and the subsequent re-implantation procedure undertaken within 6 weeks demonstrated better outcomes.

High expression of PAX8-AS1 correlates with poor prognosis and response to fluorouracil-based chemotherapy in stage II colon cancer.

Decisions regarding adjuvant therapy in patients with stage II colon cancer remains controversial and challenging. We aimed to determine novel biomarkers that help to predict relapse free survival (RFS) and identify a subset of patients with stage II colon cancer who could gain survival benefits from adjuvant chemotherapy. Public microarray datasets of stage II colon cancer samples were extracted from Gene Expression Omnibus database. Global gene expression changes were then analyzed between the paired early relapse and long-term survival group to identify the differentially expressed mRNAs and lncRNAs. Based on Lasso Cox regression modeling analysis, a total of 30 mRNAs and 2 lncRNAs were finally identified. With specific formula, stage II patients in training and validation sets were divided into low and risk groups with significantly different RFS. PAX8-AS1 is the novel lncRNA which showed the highest upregulation in early relapse group. Patients with high PAX8-AS1 expression level showed notably poorer RFS in both meta GEO cohort (P = 0.04, Figure 4B) and FUSCC cohort (P < 0.001, Figure 4C). Among the stage II patients with high PAX8-AS1 level, administration of fluorouracil-based adjuvant chemotherapy provided a substantial improvement in RFS (P = 0.002, Figure 3C). Further mechanistic study unveiled that PAX8-AS1 increases the response of CRC cells to chemotherapy in vitro and in vivo by maintaining the mRNA stability of PAX8. In conclusion, PAX8-AS1 as a novel and reliable biomarker for predicting prognosis and identification of patients with stage II disease who could gain survival benefit from fluorouracil-based adjuvant chemotherapy.

Molecular profiling of risk factors for relapse in Japanese patients with stage II colorectal cancer: a retrospective cohort study.

BACKGROUND: The association between the molecular profiles and prognosis of Stage II colorectal cancer remains unclear. This study aimed to examine the risk factors for relapse of Stage II colorectal cancer using molecular profiling. METHODS: We retrospectively enrolled patients with pStage II colorectal cancer who did not receive perioperative adjuvant therapy and whose surgically resected specimens were evaluated using gene expression and whole-exome analyses between January 2014 and December 2018. We evaluated the long-term outcomes and examined the risk factors for relapse-free survival. RESULTS: We evaluated 322 patients with pStage II colorectal cancer, including 126 (39.1%) with right colon cancer. Eighty-seven patients (27.0%) had pT4 tumor, 175 (54.3%) had positive venous invasion, 120 (37.3%) had positive lymphatic invasion, and 68 (21.1%) had perineural invasion. The presence of mutations in key genes for colorectal cancer development based on whole-exome analyses was as follows: APC, 245 (76.1%); TP53, 208 (64.6%); and KRAS, 134 (41.6%). According to the consensus molecular subtype classification based on gene expression, 76 patients (23.6%) had consensus molecular subtype 4 and a significantly lower relapse-free survival than the other patients (5-year relapse-free survival: 83.8% vs. 92.9%, p = 0.017). Perineural invasion (hazard ratio: 5.316, p < 0.001) and consensus molecular subtype 4 (hazard ratio: 2.399, p = 0.020) were identified as independent risk factors for relapse-free survival. CONCLUSIONS: Molecular profiling of Stage II colorectal cancer to assess the risk factors for relapse may contribute to the indication and drug selection for adjuvant chemotherapy.

Perioperative anesthetic management of patients with hypoplastic left heart syndrome undergoing the comprehensive stage II surgery-A review of 148 cases.

BACKGROUND: Patients with hypoplastic left heart syndrome undergo the comprehensive stage 2 procedure as the second stage in the hybrid approach toward Fontan circulation. The complexity of comprehensive stage 2 procedure is considered a potential limitation, and limited information is available on its anesthetic management. This study aims to address this gap. METHODS: A single-center retrospective cohort study analyzed 148 HLHS patients who underwent comprehensive stage 2 procedure, divided into Group A (stable condition, n = 116) and Group B (requiring preoperative intravenous inotropic therapy, n = 32). Demographic data, intraoperative hemodynamics, anesthetic management, and postoperative outcomes were collected. RESULTS: Etomidate (40%) was the most common induction agent, followed by esketamine (24%), midazolam (16%), and propofol (13%). Inhaled induction was rarely necessary (2%), occurring only in Group A patients. No statistical differences were found between groups for induction drug choice. Post-cardiopulmonary bypass management included moderate hypoventilation, inhaled nitric oxide (100%), and hemodynamic support with milrinone (97%) and norepinephrine (77%). Group B patients more frequently required additional levosimendan (20%) and epinephrine (18%). Extracorporeal membrane oxygenation was necessary in 8 patients (5%) with no between-group differences. Switching from fentanyl to remifentanil reduced postoperative ventilation time overall. However, Group B experienced significantly longer ventilation (6.3 vs. 3.5 h) and ICU stay (22 vs. 14 days). In-hospital mortality was 5% overall (Group A: 4%, Group B: 9%). Long-term survival analysis revealed a significant advantage for Group A. CONCLUSION: The use of short-acting opioids and adjusted ventilation modes enables optimal pulmonary blood flow and rapid transition to spontaneous breathing. Differentiated hemodynamic support with milrinone, norepinephrine, supplemented by levosimendan and epinephrine in high-risk patients, can mitigate the effects on the preoperatively volume-loaded right ventricle. However, differences in long-term survival probability were observed between groups. TRIAL REGISTRATION: Local ethics committee, Medical Faculty, Justus-Liebig-University-Giessen (Trial Code Number: 216/14).

Tumour Budding Is a Useful Predictor to Identify High-Risk Stage II Colon Cancer Patients After Curative Surgery.

Aim. Although it is now accepted in the literature that tumour budding (TB) is a useful survival indicator in colon cancer (CC), there are still uncertainties about daily use. Here we methodologically examined the role of TB on survival in CC. Methods. In our study, we examined colon cancer patients who had surgery up to 15 years before presentation. TB was calculated separately using different comprehensive methodological methods. Results. We first investigated an optimal evaluation method. Relationship with prognostic factors was better (Venous invasion [p = .001], advanced pT [p = .003], perineural invasion [p = .040], MSS [p = .016], advanced size [p = .001], tumour obstruction [p = .005], margin involvement [p = .043], and nodal involvement [p = .028]) in Method-1. Similarly, with the same method, the success of the cut-off value, the correlation of TB data (r = .724), and the repeatability of the method (Κappa = .53-.75) were quite good (ROC = .816 [.707-.925]). Then, survival analysis was performed using the best three methods, including this method. In univariate analysis using Method-1, survival analyses were worse in high TB patients (RFS: 81%, p < .001; OS: 84%, p < .001). Multivariate analyses using the same method confirmed that high TB for RFS and OS was an independent poor prognostic parameter for survival (p = .002, Hazard ratio [HR]: 1.42 [1.13-1.80]) and OS (p = .014, HR: 1.38 [1.07-1.79]). Conclusions. With our study, we showed that tumour budding calculated by the standard method is a very valuable prognostic parameter in stage II CC and can contribute to the detection of patients with poor prognosis in stage II CC.

Mechanism of action of montmorillonite powder on injury and repair factors in Stage II pressure ulcers in model mice.

BACKGROUND: This study aims to elucidate the therapeutic effects and underlying mechanisms of montmorillonite powder on wound healing in mice with Stage II pressure ulcers, thereby providing a robust foundation for its clinical application in the treatment of such ulcers. MATERIALS AND METHODS: Sixty 8-week-old specific pathogen-free male BALB/c mice were randomly allocated into three groups: a model group (where Stage II pressure ulcers were induced using the magnet pressure method and the wounds were dressed with gauze soaked in 0.9% sodium chloride solution), a treatment group (where, following the induction of Stage II pressure ulcer models, wounds were uniformly treated with montmorillonite powder), and a control group (where magnets were placed in the same location without exerting magnetic pressure). Skin histopathology was assessed via light microscopy. Wound healing progress over various intervals was quantified utilizing Image-Pro Plus software. Histopathological alterations in the wounds were examined through hematoxylin and eosin (H&E) staining. The expression of growth factor proteins within the wound tissue was analyzed using the streptavidin-peroxidase method. Furthermore, the levels of vascular endothelial growth factor (VEGF), collagen types I and III (COL-I, COL-III) proteins were quantified via Western blotting, serum concentrations of inflammatory mediators in mice were determined by enzyme-linked immunosorbent assay, and the levels of oxidative stress markers in wound tissues were measured using UV-visible spectrophotometry. RESULTS: The treatment group exhibited significantly reduced serum levels of interleukin-1ß, interleukin-6, and tumor necrosis factor-alpha, and elevated levels of interleukin-4 compared to the model group (p < 0.05). Additionally, the expression of transforming growth factor-beta1, basic fibroblast growth factor, epidermal growth factor, VEGF, COL-I, and COL-III proteins in wound tissues was significantly higher in the treatment group than in the model group (p < 0.05). Levels of superoxide dismutase and glutathione peroxidase in wound tissues were higher, and levels of malondialdehyde were lower in the treatment group compared to the model group (p < 0.05). CONCLUSION: Montmorillonite powder facilitates wound healing and augments the healing rate of Stage II pressure ulcers in model mice. Its mechanism of action is likely associated with mitigating wound inflammation, reducing oxidative stress damage, promoting angiogenesis, and enhancing the synthesis of growth factors and collagen.

Adjuvant Therapy for High-Risk Stage II Melanoma: Current Paradigms in Management and Future Directions.

Melanoma is the fifth most common cancer in the United States and accounts for the majority of all skin cancer-related deaths, making it the most lethal cutaneous malignancy. Systemic adjuvant therapy for stage IIB-IV melanoma is now approved for patients who have undergone surgical resection, given the appreciable risk of recurrence and mortality in this patient population. Despite the lower stage, high-risk stage II melanoma (stage IIB/IIC) can often exhibit an even more aggressive course when compared to stage IIIA/IIIB disease, thus justifying consideration of adjuvant therapy in these patients. In this review, we highlight the current standard of practice for the treatment of stage IIB/C melanoma, with a focus on adjuvant therapies supported by published landmark clinical trials, including anti-PD-1 therapy. Notably, adjuvant therapies approved thus far in this patient population have demonstrated an improvement in recurrence-free survival, while their impact on overall survival is pending. Finally, this review highlights currently ongoing trials and future directions for research and treatment possibilities for high-risk clinical stage II melanoma.

Effect of Nutrition on Drug-Induced Liver Injury: Insights from a High-Fat Diet Mouse Model.

Objectives: Literature suggests that a high-fat diet (HFD) potentially increases the risk of chemical/drug-induced toxicity after an acute overdose. Drug/chemical-induced hepatotoxicity has been well studied, and the mechanism that regulates this toxicity has been extensively examined using different experimental animal models. Our study focuses on drug-induced hepatotoxicity in HFD-fed female Balb/C mice. This study addresses the effect of nutrition on the magnitude of acetaminophen (APAP)-induced hepatotoxicity at different time intervals. Materials and Methods: Female Balb/C mice, after the weaning period separated into two different groups, normal diet (ND) and HFD receiving groups; after 15 weeks, they were dosed with a single dose (300 mg/kg per os (p.o.) of APAP. Blood samples were collected at different time intervals (0, 6 and 24 hours), and liver samples were collected at the end time point. Liver injury parameters [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)], antioxidant assay (sodium dismutase, glutathione, and catalase), and histopathology study were conducted. Pharmacokinetic (PK) analysis was done using the RP-HPLC system and Phoenix WinNonlin 8.3 software. Results: APAP-induced liver injury decreased AST and ALT in the HFD group compared with the ND group at 6 and 24 hours (p < 0.01 and p < 0.001), respectively. Antioxidant enzyme levels remained constant in the HFD group, whereas histopathology showed remarkable changes. The PK's of APAP in HFD indicate lower plasma concentrations of APAP (p < 0.05), with two-fold higher clearance and volume of distribution. Conclusion: HFD significantly reduced susceptibility to APAP-mediated liver injury in Balb/C mice compared with ND mice. Our study mimics the clinical scenario where the same dose of the drug is prescribed to the normal and obese population. Our results suggest the potential need for dose titration to assess an individual's nutritional state in a clinical scenario.

Immunohistochemical analysis of tumor budding in stage II colon cancer: exploring zero budding as a prognostic marker.

Tumor budding, a biomarker traditionally evaluated using hematoxylin and eosin (H&E) staining, has gained recognition as a prognostic biomarker for stage II colon cancer. Nevertheless, while H&E staining offers valuable insights, its limitations prompt the utilization of pan-cytokeratin immunohistochemistry (IHC). Consequently, this study seeks to evaluate the prognostic significance of tumor budding using IHC in a contemporary cohort of stage II colon cancer patients, aiming to deepen our understanding of this critical facet in cancer prognosis. We conducted a retrospective, population-based cohort study including 493 patients with stage II colon cancer and evaluated tumor budding using IHC, following the H&E-based guidelines proposed by the International Tumor Budding Consensus Conference Group. Correlation between H&E-based and IHC-based tumor budding was assessed using a four-tiered scoring system that included a zero budding (Bd0) category. Survival analyses explored the prognostic significance of tumor budding assessed by IHC and H&E. As expected, IHC-based tumor budding evaluation yielded significantly higher bud counts compared to H&E (p < 0.01). Interestingly, 21 patients were identified with no tumor budding using IHC. This was associated with significantly improved recurrence-free survival (HR = 5.19, p = 0.02) and overall survival (HR = 4.47, p = 0.04) in a multivariate analysis when compared to tumors with budding. The Bd0 category demonstrated a 100% predictive value for the absence of recurrence. In conclusion, IHC-based tumor budding evaluation in stage II colon cancer provides additional prognostic information. The absence of tumor budding is associated with a favorable prognosis and may serve as a potential marker for identifying patients with no risk of recurrence.

Survival Outcomes in Patients with Monobloc-Resected Stage IIC (pT4bN0) Colon Cancer: A Retrospective Observational Cohort Study.

BACKGROUND: Stage II colon cancer (CC) exhibits considerable prognostic heterogeneous. Our objective was to assess survival but also the prognosis impact of microsatellite instability (MSI) in patients with stage IIC (T4bN0M0) CC. PATIENTS AND METHODS: We conducted a retrospective observational study including all patients who had primary stage IIC CC resection between 2010 and 2020 in 2 expert centers. The primary endpoint was overall survival (OS) and disease-free survival (DFS) and time-to-relapse (TTR) were secondary endpoints. RESULTS: Sixty-six patients, median age of 74 years [30-95], were included, with 37.9% presenting MSI (n = 25). Organ invasion involved the last ileal loop (n = 17), another colonic segment (n = 15), omentum (n = 13), visceral peritoneum (n = 13), and the bladder (n = 4). Surgical quality criteria showed complete monobloc resection in all patients and 93.9% R0 resection. After a median follow-up of 5 years [3.5-6.6], the entire population showed a 5-year OS of 65.2% [53.0-80.3] and 5-year DFS of 53.5% [41.1-69.6], with 18.9% [6.8-29.4] experiencing relapses at 5 years. The MSI phenotype correlated with improved 5-year OS (75.5% [56.5-100] vs. 59.5% [44.9-79.0], HR 0.41 [0.17-0.99]; P = .04), but DFS and TTR did not differ. Adjuvant chemotherapy was administered to 34.9% of patients. Univariate analysis identified age > 65 years, MSI status, and the number of nodes as factors associated with OS. CONCLUSION: These data underline, in relation to a low rate of relapse, the lack of consensus regarding the appropriate indication for adjuvant chemotherapy in this high-risk stage II population.

Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201).

BACKGROUND: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. METHODS: In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. RESULTS: Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. CONCLUSION: The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).

Principles of risk assessment in colon cancer: immunity is key.

In clinical practice, the administration of adjuvant chemotherapy (ACT) following tumor surgical resection raises a critical dilemma for stage II colon cancer (CC) patients. The prognostic features used to identify high-risk CC patients rely on the pathological assessment of tumor cells. Currently, these factors are considered for stratifying patients who may benefit from ACT at early CC stages. However, the extent to which these factors predict clinical outcomes (i.e. recurrence, survival) remains highly controversial, also uncertainty persists regarding patients' response to treatment, necessitating further investigation. Therefore, an imperious need is to explore novel biomarkers that can reliably stratify patients at risk, to optimize adjuvant treatment decisions. Recently, we evaluated the prognostic and predictive value of Immunoscore (IS), an immune digital-pathology assay, in stage II CC patients. IS emerged as the sole significant parameter for predicting disease-free survival (DFS) in high-risk patients. Moreover, IS effectively stratified patients who would benefit most from ACT based on their risk of recurrence, thus predicting their outcomes. Notably, our findings revealed that digital IS outperformed the visual quantitative assessment of the immune response conducted by expert pathologists. The latest edition of the WHO classification for digestive tumor has introduced the evaluation of the immune response, as assessed by IS, as desirable and essential diagnostic criterion. This supports the revision of current cancer guidelines and strongly recommends the implementation of IS into clinical practice as a patient stratification tool, to guide CC treatment decisions. This approach may provide appropriate personalized therapeutic decisions that could critically impact early-stage CC patient care.

An invasion front gene expression signature for higher-risk patient selection in stage IIA MSS colon cancer.

Stage II colon cancer (CC) encompasses a heterogeneous group of patients with diverse survival experiences: 87% to 58% 5-year relative survival rates for stages IIA and IIC, respectively. While stage IIA patients are usually spared the adjuvant chemotherapy, some of them relapse and may benefit from it; thus, their timely identification is crucial. Current gene expression signatures did not specifically target this group nor did they find their place in clinical practice. Since processes at invasion front have also been linked to tumor progression, we hypothesize that aside from bulk tumor features, focusing on the invasion front may provide additional clues for this stratification. A retrospective matched case-control collection of 39 stage IIA microsatellite-stable (MSS) untreated CCs was analyzed to identify prognostic gene expression-based signatures. The endpoint was defined as relapse within 5 years vs. no relapse for at least 6 years. From the same tumors, three different classifiers (bulk tumor, invasion front, and constrained baseline on bulk tumor) were developed and their performance estimated. The baseline classifier, while the weakest, was validated in two independent data sets. The best performing signature was based on invasion front profiles [area under the receiver operating curve (AUC) = 0.931 (0.815-1.0)] and contained genes associated with KRAS pathway activation, apical junction complex, and heme metabolism. Its combination with bulk tumor classifier further improved the accuracy of the predictions.

Stage II endometrial cancer: The diagnostic power of hysteroscopic excisional biopsy and MRI in the pre-operative cervical stroma assessment.

INTRODUCTION/BACKGROUND: Stage II Endometrial cancer (EC) accounts only for 12% of cases. Recent evidences redraw the weight of radicality in this stage as it would seem to have no impact on survival outcomes claiming for radicality when free surgical margins are not ensured to be achieved by simple hysterectomy. Thus, an accurate pre-operative evaluation might be crucial. This study aims to estimate the diagnostic power of Hysteroscopic excisional biopsy (HEB) of cervical stroma alone and combined with Magnetic resonance imaging (MRI) to predict the stage and concealed parametrial invasion in patients with preoperative stage II EC. METHODOLOGY: From January 2019 to November 2023, all patients evaluated at the Department of Gynaecology Oncology of Humanitas, Istituto Clinico Catanese, Catania, Italy, with a diagnosis of EC and evidence of cervical stromal diffusion on preoperative MRI and/or office hysteroscopy evaluation, considered suitable for laparoscopic modified type B hysterectomy, were consecutively included in the study. These underwent endometrial and cervical hysteroscopy excisional biopsy (HEB) for histological evaluation before definitive surgery. The data obtained were compared with the definitive histological examination (reference standard). RESULTS: Sixteen patients met the including/excluding criteria and were considered into the study. Stage II endometrial cancer were confirmed in 3 cases (18.7%). We reported 2 (12,5%) parametrial involvement (IIIB), 4 (25%) cases of lymph nodes metastasis (IIIc), 7 (43,7%) cases of I stage. MRI had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy (95% CIs) of 71%, 44%, 50%, 66% and 56.2 % respectively. HEB showed sensitivity, specificity, PPV, NPV and accuracy (95 % CI) of 85 %, 89 %, 85 %, 88 % and 87 % respectively. Comparing HEB + MRI to HEB alone, no statistical differences were noted in all fields. Considering parametrial invasion, MRI had better sensitivity but there were no statistical differences to HEB in other fields, showing both a worthy NPV. CONCLUSION: HEB was accurate in all fields for cervical stroma assessment and had a fine NPV to exclude massive cervical involvement up to parametrial. Considering the new FIGO staging a preoperative molecular and histological evaluation of the cervical stroma may be useful. Operative hysteroscopy seems to be a feasible and accurate method for this purpose.

Unraveling the role of tumor sidedness in prognosis of stage II colon cancer.

Background: Stage II colon cancer has varying risks for metastasis, and treatment strategies depend on molecular and clinicopathological features. While tumor-sidedness is a well-accepted prognostic factor for stage III/IV colon cancer, its role in stage II is controversial. Understanding its effect in stage II is crucial for improving treatment strategies. Methods: We analyzed clinical and follow-up data of colon cancer from the Surveillance, Epidemiology, and End Results database (2004-2017). Patients were divided into a primary study cohort (2010-2017) and a validation cohort (2004-2009). The baseline characteristics between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) groups were compared. Moreover, the effect of tumor size on cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis. Results: The study involved 87,355 patients in the study cohort and 65,858 in the validation cohort. Of the study cohort, 52.3% were diagnosed with RCC. The median age was 64 years old, with 48.5% females and 76.8% of white people. In addition, stage II RCC showed better CSS compared with LCC (5-year CSS 88.0% vs 85.5%, P < 0.001), while stage III/IV RCC demonstrated poorer outcomes. Multivariate Cox regression analysis identified that the right-sidedness was a positive prognostic factor in stages I/II but negative in stages III (HR 1.10, P < 0.001) and IV (HR 1.26, P < 0.001). Chemotherapy rates decreased in RCC, particularly in stage II (RCC vs LCC: 16.2% vs 28.5%, P < 0.001). Subgroup analysis, stratified by T3/T4 stages and chemotherapy status, further highlighted better survival outcomes in RCC. Conclusions: RCC is associated with a significantly better prognosis in stage II. The importance of considering tumor-sidedness in clinical decision-making and the design of future clinical trials should be emphasized.

The prognostic value of tumor budding in a thoroughly characterized stage II colon cancer population in the context of a national screening program.

Tumor budding as a prognostic marker in colorectal cancer has not previously been investigated in a cohort of screened stage II colon cancer patients. We assessed the prognostic significance of tumor budding in a thoroughly characterized stage II colon cancer population comprising surgically resected patients in the Region of Southern Denmark from 2014 to 2016. Tumors were re-staged according to the 8th edition of UICC TNM Classification, undergoing detailed histopathological evaluation and tumor budding assessment following guidelines from the International Tumor Budding Consensus Conference. Prognostic evaluation utilized Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models for time to recurrence (TTR), recurrence-free survival (RFS), and overall survival (OS). Out of 497 patients, 20% were diagnosed through the national colorectal cancer screening program. High-grade tumor budding (Bd3) was found in 19% of tumors and was associated with glandular subtype, perineural invasion, mismatch repair proficient tumors, and tumor recurrence (p < 0.001, p < 0.001, p = 0.045, and p = 0.007 respectively). In multivariable Cox regression, high-grade budding was a significant prognostic factor for TTR compared to low-grade (Bd3 HR 2.617; p = 0.007). An association between tumor budding groups and RFS was observed, and the difference was significant in univariable analysis for high-grade compared to low-grade tumor budding (Bd3 HR 1.461; p = 0.041). No significant differences were observed between tumor budding groups and OS. High-grade tumor budding is a predictor of recurrence in a screened population of patients with stage II colon cancer and should be considered a high-risk factor in a shared decision-making process when stratifying patients to adjuvant chemotherapy.

Prognostic impact of limited resection vs. inadequate adjuvant therapy in patients with pathologic stage II or III non-small cell lung cancer: results from the Korean Association of Lung Cancer Registry.

BACKGROUND: For patients with stage II and III non-small cell lung cancer (NSCLC), various multi-modality treatments are required. However, depending on the individual conditions of patients, there will be a significant difference in prognosis. Therefore, this study investigated the clinical impact of inadequate treatment (limited surgery and inadequate adjuvant therapy) in patients with NSCLC stage II or III using data from the Korean Association of Lung Cancer Registry (KALC-R) between 2014 and 2016. METHODS: Of the 8,110 new lung cancer cases registered at the Korea Central Cancer Registry in 2014-2016, 721 patients with stage II or III NSCLC were selected and divided into three groups according to differences in cancer treatment methods. In group A, patients underwent standard surgery and completed adjuvant therapy. In group B, patients underwent standard surgery without completing adjuvant therapy. In group C, patients received adjuvant therapy after limited surgery. After performing propensity score matching (PSM) for selected patients, overall survival (OS) and disease-free survival (DFS) rates of the three groups of patients with stage II and III NSCLC patients were then compared. RESULTS: Of the 721 patients with NSCLC, 239, 437, and 45 belonged to groups A, B, and C, respectively. After 1:3 PS matching for groups B and C, the 5-year survival rate of patients with stage II or III NSCLC were 68.0% and 26.7% for groups B and C, respectively and the DFS rate was 59.1% and 16.2% for groups B and C, respectively. CONCLUSIONS: The therapeutic effect of the standard surgery was the best. Although patients received adjuvant therapy, limited resection resulted in a poorer prognosis in compromised patients compared with omitting adjuvant therapy followed by standard surgery. Thus, surgical treatment should be considered in patients who are unable to complete surgical and adjuvant therapy.

Risk stratification of stage II rectal mucinous adenocarcinoma to predict the benefit of adjuvant chemotherapy following neoadjuvant chemoradiation and surgery.

Background: The treatment strategy for stage II rectal mucinous adenocarcinoma (RMA) recommends neoadjuvant chemoradiotherapy (NCR) followed by total mesorectal excision (TME). However, the necessity of adjuvant chemotherapy (AC) remains controversial. Materials and methods: Chi-square test was used to assess the relationship between pathological classification, AC and clinicopathological characteristics. Kaplan-Meier (KM) curves and the log-rank test were utilized to analyze differences in overall survival (OS) and cancer-specific survival (CSS) among different groups. Cox regression identified prognostic factors. Nomogram was established utilizing the independent prognostic factors. X-tile divided patients into three risk subgroups. Results: Compared to RMA, rectal adenocarcinoma (RA) demonstrates longer OS and CSS in all and non-AC stage II patients, with no difference in OS and CSS for AC stage II patients. Propensity score matching analyses yielded similar results. Stratified analysis found that AC both improve OS of RA and RMA patients. Age, gender, pathologic T stage, regional nodes examined, and tumor size were identified as independent prognostic factors for RMA patients without AC. A nomogram was constructed to generate risk scores and categorize RMA patients into three subgroups based on these scores. KM curves revealed AC benefits for moderate and high-risk groups but not for the low-risk group. The external validation cohort yielded similar results. Conclusions: In summary, our study suggests that, compared to stage II RA patients, stage II RMA patients benefit more from AC after NCR. AC is recommended for moderate and high-risk stage II RMA patients after NCR, whereas low-risk patients do not require AC.

Elevated postoperative carcinoembryonic antigen guides adjuvant chemotherapy for stage II colon cancer: a multicentre cohort retrospective study.

Most clinical doctors rely on high-risk factors recommended by guidelines to decide whether to undergo adjuvant chemotherapy for stage II colon cancer. However, these high-risk factors do not include postoperative carcinoembryonic antigen (CEA). This study aims to explore the elevation of postoperative CEA as a risk factor, in addition to other high-risk factors, to guide adjuvant chemotherapy for patients with stage II colon cancer. A retrospective analysis was conducted on stage II colon cancer patients who underwent curative surgery at Yunnan Cancer Hospital and The Sixth Affiliated Hospital of Sun Yat-Sen University from April 2008 to January 2019. Patients were classified into three groups based on high-risk factors recommended by guidelines and postoperative CEA levels: low-risk with normal postoperative CEA, low-risk with elevated postoperative CEA and high-risk. COX regression analysis was used to identify independent prognostic factors affecting patients' recurrence free survival (RFS). The Kaplan-Meier method was used to create the patients' RFS curve. The restricted cubic spline (RCS) curve was used to assess the correlation between postoperative CEA and RFS on a continuous scale. Among 761 patients, there were 444 males (62.01%), with a median [IQR] age of 58.0 (18.0-88.0) years. A group of 425 high-risk patients had a 3-year RFS of 82.2% (95% CI 78.5-86.1%), while a group of 291 low-risk patients had a 3-year RFS of 89.7% (95% CI 86.1-93.5%). There was a statistically significant difference between the two groups (HR 1.83; 95% CI 1.22-2.74; P = 0.0067). Among them, the 3-year RFS of 261 low-risk patients with normal postoperative CEA was 93.6% (95% CI 90.5-96.8%), while the 3-year RFS of 30 low-risk patients with elevated postoperative CEA was 57.3% (95% CI 41.8-71.4%). There was a significant difference compared to the 3-year RFS of 425 high-risk patients (overall log-rank P < 0.0001). The multivariate analysis adjusted by the COX proportional hazards model showed that low-risk patients with elevated postoperative CEA patients (HR 14.95, 95% CI 4.51-49.63, P < 0.0001) was independently associated with a 3-year RFS. The restricted cubic spline model showed that in stage II colon cancer patients with tumor diameter > 1.955 ng/mL, the risk of postoperative recurrence increased with increasing postoperative CEA levels. Patients with elevated postoperative CEA levels have a significantly increased risk of recurrence. They should be included as high-risk factors to guide adjuvant chemotherapy for stage II colon cancer.