Pathological Tumor Research Articles

Robotic Partial Nephrectomy for Treating Renal Masses: Outcomes and Complications.

Partial nephrectomy is the preferred treatment for renal tumors <7 cm. Robot-assisted laparoscopic approach is a minimally invasive method that offers advantages for resecting complex tumors. Here, we conducted a descriptive retrospective analysis of the first robotic partial nephrectomies (RPNs) performed at our center. A retrospective cohort of 94 patients who consecutively underwent RPN at our center between November 2012 and December 2022 was investigated. Baseline patient data, tumor characteristics, intraoperative variables, pathological tumor analysis, and postoperative complications at 30 days were analyzed. The patients were followed up for a median of 25.3 months. Baseline values included a median age of 63 years and a median body mass index (BMI) of 28.1. Intraoperative variables comprised a median surgical time of 150 min and a median warm ischemia time of 16 min. The mean postoperative creatinine level was 1 mg/dL. The median tumor size was 41.9 mm, with a median PADUA score of 8 and a median RENAL score of 8. Resected tumors were predominantly cT1a (58.5%) and cT1b (39.3%), while the positive margin rate was 21.3%. A total of 19.2% of the patients experienced Clavien-Dindo complications, of which 11% were Clavien-Dindo I; 66.7%, Clavien-Dindo II; And 22.2%, Clavien-Dindo IIIb. However, no Clavien-Dindo IIIa or IV complications were reported. RPN is an effective and safe technique for treating solid renal masses, demonstrating a low complication rate and adequate oncologic control locally and distally.

The prognostic impact of EpCAM and p53 expressions in infiltrating duct carcinoma of the breast and their association with the clinicopathological prognostic parameters

Background Breast cancer is the most common cause of cancer death among women worldwide. Adhesion molecule EpCAM is an important player in carcinogenesis; however, its exact biological role is not clear. Tumor suppressor gene p53 maintains genomic stability. In malignant cells, its function can be compromised by various mechanisms such as mutations, alteration of p53 regulators, and alteration of p53 target genes. This study aimed to find the relationship between epithelial cell adhesion molecule (EpCAM) and p53 expressions on one hand and clinicopathological factors of prognostic importance in breast cancer on the other hand and find any correlations between EpCAM and p53 markers. Materials and methods Immunohistochemical staining with EpCAM and p53 was studied on 42 cases of infiltrating duct carcinoma. Results A significant association was found between EpCAM and tumor size (P=0.049), tumor grade (P=0.005), lymph node status (P=0.043), pathological tumor stage; pathological tumor stage (P=0.027), and lymphovascular invasion (P=0.048). However, EpCAM was negatively associated with estrogen receptor (P=0.007), progesterone receptor (P=0.031), and human epidermal growth factor receptor 2/neu (P=0.025) expressions. Expression of p53 was positively associated with tumor size (P=0.025), tumor grade (P=0.002), lymph node status (P=0.05), pathological tumor stage (P=0.041), and lymphovascular invasion (P=0.043), while negatively associated with estrogen receptor (P=0.029), progesterone receptor (P=0.043), and human epidermal growth factor receptor 2/neu (P=0.039) expressions. A positive association was found between EpCAM and p53 expressions and triple-negative breast cancer (P=0.007 and 0.029, respectively). There was a positive association between EpCAM and p53 (P=0.007). Conclusion EpCAM and p53 expressions are good markers of predicting poorer outcomes in breast cancer patients. There is a positive association suggesting a combined prognostic value in breast cancer and it may confirm the binding of p53 with the EpCAM gene to regulate its function.

Systemic Inflammatory Response Following Preoperative Chemoradiotherapy Can Affect Oncologic Outcomes in MSI-H/dMMR Rectal Cancer.

Systemic inflammatory response (SIR) is a crucial determinant of disease progression and survival in patients with colorectal cancer. This study investigated the prognostic relevance of changes in the platelet count on survival and the predictive value of changes in the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) on the pathological tumor response to preoperative chemoradiotherapy (CRT) in patients with microsatellite instability-high (MSI-H) rectal cancer. From 2011 to 2022, data of 46 consecutive patients with MSI-H rectal cancer who were treated with preoperative CRT followed by curative surgery at Kyungpook National University Chilgok Hospital (Daegu, South Korea) were retrospectively analyzed. A 235 cut-off value was used to define whether PLR was high or low. Any change in the PLR or NLR was calculated on the basis of subtracting the pre-CRT PLR or NLR from the post-CRT values. Both pre-CRT and post-CRT values of the NLR and PLR were not significantly associated with clinical outcomes. Simple logistic regression analysis showed that a change in the PLR following CRT was not significantly associated with survival outcomes; however, patients who maintained a high change in the PLR following CRT showed significantly better pathologic T-stage. No statistically significant association was noted between changes in the platelet count and clinical outcomes of patients. The results suggested that changes in the PLR following CRT are associated with pathologic T-stage of the group. However, the SIR markers showed no prognostic values on the survival outcomes of the patients with MSI-H/mismatch repair-deficient (dMMR) locally advanced rectal cancer (LARC).

A Large Tuberculous Abscess Mimicking an Abdomino-pelvic Cystic Mass: A Case Report

Introduction: Tuberculosis can involve any part of the gastrointestinal tract or the peritoneum and is the sixth most frequent site of extrapulmonary involvement. The pseudotumoral form is relatively rare and several predisposing factors are mentioned, a significant differential diagnostic problem with malignant tumor pathology is exposed , often considered first when encountering an abdominal or pelvic mass in the context of overall deterioration. Presentation of case: We report a rare case of a huge retroperitoneal TB abscess mimicking an abdomino-pelvic cystic mass. Discussion: Abdominal tuberculosis represents 1 to 2% of all locations and 31 to 58% of abdominal locations. The pseudotumoral form is relatively rare and are uncommon in immunocompetent patients. Tuberculosis abscess can present with variable radiologic features. It is difficult to differentiate it from malignant pathologies. Invasive explorations, such as laparoscopy or laparotomy, play a crucial role in confirming the diagnosis. Peritoneal cavity exploration may reveal whitish granulations, peritoneal nodules, peritoneal hyperemia, filamentous peritoneal adhesions, and intestinal adhesions. Histological examination of biopsies are the key to the diagnosis. The treatment of peritoneal tuberculosis relies on a combined therapy of antitubercular drugs . Conclusion: As TB remains endemic in our country and with the continued increase in multidrug-resistant TB infections, it is important to know various presentations and diagnosis forms features of extrapulmonary TB including TB abscess as the treatment remains basically the same combining anti-tuberculosis drugs and the recourse to surgery.

The effect of resection of gliomas of the primary motor and sensory cortex on functional recovery and seizure outcome: A 10-year retrospective study.

Gliomas, the most common primary brain tumors, pose surgical challenges in eloquent cortex regions due to potential deficits affecting patients' quality of life (QOL) and increased mortality risk. This study investigates motor and sensory recovery postresection of Rolandic cortex gliomas in 40 patients, alongside seizure outcomes and the efficacy of intraoperative techniques such as awake craniotomy. This was a 10-year monocentric retrospective study based on the experience of a neurosurgeon in the resection of Rolandic gliomas and its impact on 40 patients' QOL in a period from 2011 to 2020. The primary outcomes were tumor recurrence and the efficacy of the surgery defined as survival status, seizure status, and sensory and motor neurological deficits. Data collection included demographic, tumor, and surgical outcome variables. The extent of resection (EOR) was classified as gross total resection (GTR) (EOR ≥95%) or subtotal resection (EOR <95%). Statistical analysis involved descriptive statistics and inferential tests for outcome comparisons. Patients were aged an average of 42.3 ± 14 years and distributed between 72.5% of males and 27.5% of females. The most common presentation was seizures (65%). The tumor was located in the frontal lobe at 65%, the motor at 75%, and the top tumor pathology was oligodendroglioma (42.5%). The recurrence rate in the study was 20% (8 of 40), and the 1-year survival rate was 92.5%. After the resection, significant improvement was shown in Karnofsky's performance status (P = 0.007), in normal daily activities (P = 0.001), in fine motor skills (P = 0.020), and work hobbies (P = 0.046). No statistically significant improvement was shown in seizures and deficit rates. Recurrence was not associated with the demographic characteristics, clinical presentation, tumor-related characteristics (location, area, side, and mutation), tumor resection, and adjuvant treatment (P > 0.05). GTR of Rolandic gliomas can be achieved with the use of meticulous stimulation mapping, and complete functional recovery is attainable despite common belief.

CASE REPORT: AN UNUSUAL CHEST WALL TUMOR REVEALING EXTRAPULMONARY THORACIC ACTINOMYCOSIS IN A CHILD

Actinomycosis is a granulomatous, suppurativebacterial condition caused by Actinomycesisraelii.The thoracic localization is rare it can simulate a neoplastic pathology or tuberculosis. We report one case of unusual presentation a 9-year-old girl. Admitted for the appearance of inflammatory pain of the right shoulder evolving for 6 months in a febrile context, marked by the appearance of a dorsal tumefaction. Radiological examination showed an osteolytic tissue mass of the lateral chest wall with pulmonary nodules and mediastinal lymphadenopathy. An Anatomopathological examination of the biopsy of the dorsal mass showed a histiocytic inflammatory reaction around grains of actinomycosis, allowing the diagnosis of thoracic-pulmonary actinomycosis. The patient was then put on antibiotic treatment with a good evolution. Thoracic actinomycosis is a rare infectious pathology, it can be radiologically divided into the chest wall involvement type, parenchymal type, the airway type including bronchiectasis, and the endobronchial form. The clinico-radiologicalpictureismisleading and maysimulate a tumoral or tubercular pathology, hence the need to repeat biopsies in search of characteristics of actinomyce.

Synaptopodin-2 Isoforms Have Specific Binding Partners and Display Distinct, Muscle Cell Type-Specific Expression Patterns.

Synaptopodin-2 (SYNPO2) is a protein associated with the Z-disc in striated muscle cells. It interacts with α-actinin and filamin C, playing a role in Z-disc maintenance under stress by chaperone-assisted selective autophagy (CASA). In smooth muscle cells, SYNPO2 is a component of dense bodies. Furthermore, it has been proposed to play a role in tumor cell proliferation and metastasis in many different kinds of cancers. Alternative transcription start sites and alternative splicing predict the expression of six putative SYNPO2 isoforms differing by extended amino- and/or carboxy-termini. Our analyses at mRNA and protein levels revealed differential expression of SYNPO2 isoforms in cardiac, skeletal and smooth muscle cells. We identified synemin, an intermediate filament protein, as a novel binding partner of the PDZ-domain in the amino-terminal extension of the isoforms mainly expressed in cardiac and smooth muscle cells, and demonstrated colocalization of SYNPO2 and synemin in both cell types. A carboxy-terminal extension, mainly expressed in smooth muscle cells, is sufficient for association with dense bodies and interacts with α-actinin. SYNPO2 therefore represents an additional and novel link between intermediate filaments and the Z-discs in cardiomyocytes and dense bodies in smooth muscle cells, respectively. In pathological skeletal muscle samples, we identified SYNPO2 in the central and intermediate zones of target fibers of patients with neurogenic muscular atrophy, and in nemaline bodies. Our findings help to understand distinct functions of individual SYNPO2 isoforms in different muscle tissues, but also in tumor pathology.

Patency and disease-free status after oncovascular resection of truncal malignancies with major vascular invasion

BackgroundWith advances in current therapies, more patients are currently surgical candidates for oncologic resections that were previously deemed unresectable owing to vascular invasion. We analyzed our institution's outcomes of patients undergoing oncovascular resection of truncal malignancies with vascular invasion to identify factors associated with vascular reconstruction complications and oncologic recurrence. MethodsA retrospective chart review of all adult patients between January 1, 2002, and June 1, 2022, who underwent a surgical resection of a neoplasm at Northwestern Memorial Hospital and required vascular surgery intraoperative assistance was performed. Data on patient demographics, tumor anatomy and pathology, operative details, and clinical outcomes were extracted. Primary end points included 30-day and 1-year mortality, and 1-year primary patency of the vascular reconstruction. Secondary end points included vascular reintervention and tumor recurrence, both local and metastatic disease. ResultsA total of 104 patients (43.3% females) with a mean age of 58 years were included in the study. The median follow-up was 22.1 months (range, 0-207 months). The most common tumor pathology included advanced renal cell carcinoma (n = 58) and soft tissue and primary vascular sarcomas (n = 24). Vascular procedures included 98 venous interventions and 6 arterial interventions. The overall 30-day mortality was 1% and 1-year mortality was 14.4%. Primary vascular patency at 1 year among patients with ≥12 months of follow-up was 98.5%. No patients underwent a vascular reintervention. In total, 34 patients (38%) developed recurrent malignant disease (23.5% local and 76.5% metastatic) during the study period. The median time to tumor recurrence was 11.4 months (range, 1.2-100.0 months). ConclusionsOncovascular resections of truncal tumors involving major vascular structures can be performed safely with a low incidence of vascular complications; tumor recurrence remains the major contributor to morbidity. Further investigation of the factors associated with tumor recurrence in these patients may help to refine surgical techniques.

Factors associated with gastrointestinal stromal tumor rupture and pathological risk: A single-center retrospective study.

Gastrointestinal stromal tumor (GIST) is a rare gastrointestinal mesenchymal tumor with potential malignancy. Once the tumor ruptures, regardless of tumor size and mitotic number, it can be identified into a high-risk group. It is of great significance for the diagnosis, treatment, and prognosis of GIST if non-invasive examination can be performed before surgery to accurately assess the risk of tumor. To identify the factors associated with GIST rupture and pathological risk. A cohort of 50 patients with GISTs, as confirmed by postoperative pathology, was selected from our hospital. Clinicopathological and computed tomography data of the patients were collected. Logistic regression analysis was used to evaluate factors associated with GIST rupture and pathological risk grade. Pathological risk grade, tumor diameter, tumor morphology, internal necrosis, gas-liquid interface, and Ki-67 index exhibited significant associations with GIST rupture (P < 0.05). Gender, tumor diameter, tumor rupture, and Ki-67 index were found to be correlated with pathological risk grade of GIST (P < 0.05). Multifactorial logistic regression analysis revealed that male gender and tumor diameter ≥ 10 cm were independent predictors of a high pathological risk grade of GIST [odds ratio (OR) = 11.12, 95% confidence interval (95%CI): 1.81-68.52, P = 0.01; OR = 22.96, 95%CI: 2.19-240.93, P = 0.01]. Tumor diameter ≥ 10 cm, irregular shape, internal necrosis, gas-liquid interface, and Ki-67 index ≥ 10 were identified as independent predictors of a high risk of GIST rupture (OR = 9.67, 95%CI: 2.15-43.56, P = 0.01; OR = 35.44, 95%CI: 4.01-313.38, P < 0.01; OR = 18.75, 95%CI: 3.40-103.34, P < 0.01; OR = 27.00, 95%CI: 3.10-235.02, P < 0.01; OR = 4.43, 95%CI: 1.10-17.92, P = 0.04). Tumor diameter, tumor morphology, internal necrosis, gas-liquid, and Ki-67 index are associated with GIST rupture, while gender and tumor diameter are linked to the pathological risk of GIST. These findings contribute to our understanding of GIST and may inform non-invasive examination strategies and risk assessment for this condition.

Impact of Tumor Size on Survival Outcome in Esophageal Squamous Cell Carcinoma After Esophagectomy Following Neoadjuvant Chemotherapy.

Large tumor size is a prognostic factor in esophageal squamous cell carcinoma (ESCC). However, the effect of tumor size on outcomes following neoadjuvant chemotherapy (NAC) has not been evaluated. This study aimed to assess the influence of tumor size on prognosis of patients undergoing esophagectomy after NAC. This study was made up of 272 patients who underwent esophagectomy after NAC at Kobe University Hospital. We evaluated the pathological tumor size and determined the cutoff level for tumor size using receiver operating characteristics analysis to the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. The patients were categorized into two groups: patients with tumor sizes ≥ 36 mm and < 36 mm. Deep pathological tumor invasion and worse histological response to NAC were associated with tumor size ≥ 36 mm. In patients with pT0-1, pT2, and pT4 ESCC, no significant differences in overall survival (OS) rates were observed between the two groups. In patients with pT3, OS of the tumor size ≥ 36 mm group was significantly worse than that of the tumor size < 36 mm group (p < 0.0001). Multivariate analysis in pT3 patients revealed tumor size ≥ 36 mm was an independent risk factor for OS. The 5-year OS rate was 10% in patients with tumor size ≥ 36 mm pT3 ESCC with pathological lymph node metastasis (p < 0.0001). Tumor size ≥ 36 mm is an independent risk factor for poorer survival in pT3 patients. Furthermore, tumor size ≥ 36 mm with pathological lymph node metastasis in pT3 patients was associated with very poor survival.

The clinical impact of ureteroscopy for upper tract urothelial carcinoma: A multicenter study.

With the development of kidney-sparing surgery and neoadjuvant chemotherapy, ureteroscopic biopsy (URSBx) has become important for the management of upper tract urothelial carcinoma (UTUC). We retrospectively analyzed data from 744 patients with UTUC who underwent radical nephroureterectomy (RNU), stratified into no ureteroscopy (URS), URS alone, and URSBx groups. Intravesical recurrence-free survival (IVRFS) was examined using the Kaplan-Meier method. We conducted Cox regression analyses to identify risk factors for IVR. We investigated differences between clinical and pathological staging to assess the ability to predict the pathological tumor stage and grade of RNU specimens. Kaplan-Meier curves and multivariate Cox regression revealed significantly more IVR and inferior IVRFS in patients who underwent URS and URSBx. Superficial, but not invasive, bladder cancer recurrence was more frequent in the URS and URSBx groups than in the no URS group. Clinical and pathological staging agreed for 55 (32.4%) patients. Downstaging occurred for 48 (28.2%) patients and clinical understaging occurred for 67 (39.4%) patients. Upstaging to muscle-invasive disease occurred for 39 (35.8%) of 109 patients with ≤cT1 disease. Clinical and pathological grading were similar for 72 (42.3%) patients. Downgrading occurred for 5 (2.9%) patients, and clinical undergrading occurred for 93 (54.7%) patients. URS and URSBx instrumentation will be risk factors for superficial, but not invasive, bladder cancer recurrence. Clinical understaging/undergrading and upstaging to muscle-invasive disease occurred for a large proportion of patients with UTUC who underwent RNU. These data emphasize the challenges involved in accurate UTUC staging and grading.

Predictive factors of axillary lymph node involvement in Tunisian women with early breast cancer.

Axillary lymph node involvement (ALNI) is associated with an increased risk of local recurrence and poor prognosis in early breast cancer. The determination of the risk of positive axillary lymph node contributes to therapeutic decisions. The aim of this study was to identify clinicopathological predictive factors of axillary lymph node metastases in patients with early breast cancer. We included patients with clinical T0, T1 andT2 invasive breast carcinoma who underwent resection of the primary tumor and axillary staging by sentinel lymph node biopsy and/or axillar lymph node dissection between 2012 and 2018. Of the 135patients included, 41.5% had ALNI. Regarding univariate analysis, clinical factors correlated with positive ALNM were clinical tumour size>30mm, clinical tumour stage, clinical number of tumours, clinical axillary nodal status and nodal status on ultrasound. Pathologic factors associated with nodal involvement were pathologic tumour stage, tumour grade SBR, number of foci, lymphovascular invasion, perineural invasion and Ki67>20%.In multivariate logistic regression, clinical axillary nodal status, pathologic tumour stage and lymphovascular invasion (LVI) remained as independent predictors of ALNI. Based on these results, we suggest that clinical axillary nodal status, pathologic tumour stage and LVI are predictive factors for ALNM in Tunisian women with early breast cancer.

Assessing Clinical Relevance of Gastric Cancer Cell Lines as Tumor Models by Identifying Key Genes and miRNAs involved in EMT Metastasis Pathway

Cancer cell lines are in-vitro cancer cell models that continue to divide and proliferate under controlled laboratory conditions. They are used in medical research to study tumor pathology and for testing therapeutics efficacy. Despite their extensive application, significant differences in genetic and transcriptomic expression exist between cell lines and tumor cells. The purpose of this study was to identify the relevance of gastric cancer cell lines as suitable models for gastric tumor research. Using a two-tiered bioinformatics approach- a comparison between the gastric tumor and the gastric cancer cell line was performed using functional genomics data available in the literature to identify the common Differentially Expressed Genes (DEGs). The study revealed differential expression of a total 380 genes common in both gastric cancer cell lines and tumor samples. Interestingly, four of these genes were identified as the Epithelial Mesenchymal Transition (EMT) markers, involved in the accelerated metastasis, of which two genes with discrete over-expression patterns, namely- ITGB1 and TGFB1 were selected for further analysis. Their survival analysis revealed their key role in gastric cancer severity, evident by the regressed survival rate of gastric cancer patients upon their overexpression. A total of nine tumor-suppressor miRNAs relevant to ITGB1 and TGFB1 were also identified. In conclusion, our findings indicate that inspite of various genetic and transcriptomic deviations, the tumor and cell line exhibit comparable expression patterns. The data obtained would be useful to implore the druggability of these targets with a goal of improved translational rates.

Medical and management approaches to the examination of hereditary cancer syndrome patients and their relatives

Introduction. Genetic testing has become the part of the practice of providing specialized cancer care. This allows not only detecting the further tactics for patient management, but also identifying a risk group for the occurrence of malignant neoplasms (MNP). However, there are still no algorithms for dispensary monitoring of healthy carriers of mutations, which determined the relevance of our study.&#x0D; The purpose of the study was to propose an organizational model for the work of the office of hereditary tumor pathology (HTP) based on the analysis of our own experience in identifying patients with hereditary oncological syndromes and their relatives as potent carriers of mutations associated with an increased risk of occurring MNP.&#x0D; Materials and methods. Genetic testing was carried out in two thousand two hundred seventy six patients (residents of Moscow) with breast, gastrointestinal tract, and ovarian cancer.&#x0D; Results. 714 patients out of 2276 MNP patients had mutations associated with an increased risk of developing cancer. Further, 277 relatives of these patients were invited, and mutations were detected in 143 (51.7%). Based on these data, an management model of the HTP office was proposed as part of the Outpatient Oncology Center (OOC), and the need for specialists to work in the HTP office per 100 thousand people was determined — &#x0D; 0.06 oncologist’s rate, 0.03 doctor’s rate-genetics and 0.03 psychologist rates.&#x0D; Limitations. This study did not include patients who did not meet the selection criteria, as well as persons under 18 years of age or who isn’t resident of Moscow.&#x0D; Conclusion. The introduction of genetic testing of patients’ relatives into practice will allow forming risk groups for subsequent dispensary observation, early detection of tumor and precancerous pathology.

Texture analysis of apparent diffusion coefficient maps: can it identify nonresponse to neoadjuvant chemotherapy for additional radiation therapy in rectal cancer patients?

Neoadjuvant chemotherapy (NCT) alone can achieve comparable treatment outcomes to chemoradiotherapy in locally advanced rectal cancer (LARC) patients. This study aimed to investigate the value of texture analysis (TA) in apparent diffusion coefficient (ADC) maps for identifying non-responders to NCT. This retrospective study included patients with LARC after NCT, and they were categorized into nonresponse group (pTRG 3) and response group (pTRG 0-2) based on pathological tumor regression grade (pTRG). Predictive texture features were extracted from pre- and post-treatment ADC maps to construct a TA model using RandomForest. The ADC model was developed by manually measuring pre- and post-treatment ADC values and calculating their changes. Simultaneously, subjective evaluations based on magnetic resonance imaging assessment of TRG were performed by two experienced radiologists. Model performance was compared using the area under the curve (AUC) and DeLong test. A total of 299 patients from two centers were divided into three cohorts: the primary cohort (center A; n = 194, with 36 non-responders and 158 responders), the internal validation cohort (center A; n = 49, with 9 non-responders) and external validation cohort (center B; n = 56, with 33 non-responders). The TA model was constructed by post_mean, mean_change, post_skewness, post_entropy, and entropy_change, which outperformed both the ADC model and subjective evaluations with an impressive AUC of 0.997 (95% confidence interval [CI], 0.975-1.000) in the primary cohort. Robust performances were observed in internal and external validation cohorts, with AUCs of 0.919 (95% CI, 0.805-0.978) and 0.938 (95% CI, 0.840-0.985), respectively. The TA model has the potential to serve as an imaging biomarker for identifying nonresponse to NCT in LARC patients, providing a valuable reference for these patients considering additional radiation therapy.

A predictive model and rapid multi-dynamic algorithm developed based on tumor-stroma percentage in gastric cancer: a retrospective, observational study.

Tumor-stroma percentage (TSP) is a prognostic risk factor in numerous solid tumors. Despite this, the prognostic significance of TSP in gastric cancer (GC) remains underexplored. Through the development of a personalized predictive model and a semi-automatic identification system, our study aimed to fully unlock the predictive potential of TSP in GC. We screened GC patients from Shanghai General Hospital (SGH) between 2012 and 2019 to develop and validate a nomogram. Univariate and multivariate Cox proportional hazards regression analyses were employed to identify independent prognostic factors influencing the prognosis for GC patients. The nomogram was further validated externally by using a cohort from Bengbu Medical College (BMC). All patients underwent radical gastrectomy, with those diagnosed with locally advanced GC receiving adjuvant chemotherapy. The primary outcome measured was overall survival (OS). The semi-automatic identification of the TSP was achieved through a computer-aided detection (CAD) system, denoted as TSP-cad, while TSP identified by pathologists was labeled as TSP-visual. A total of 813 GC patients from SGH and 59 from BMC were enrolled in our study. TSP-visual was identified as an adverse prognostic factor for OS in GC and was found to be associated with pathological Tumor Node Metastasis staging system (pTNM) stage, T stage, N stage, perineural invasion (PNI), lymphovascular invasion (LVI), TSP-visual, tumor size, and other factors. Multivariate Cox regression using the training cohort revealed that TSP-visual (hazard ratio [HR], 2.042; 95% confidential interval [CI], 1.485-2.806; P < 0.001), N stage (HR, 2.136; 95% CI, 1.343-3.397; P = 0.010), PNI (HR , 1.791; 95% CI, 1.270-2.526; P = 0.001), and LVI (HR, 1.482; 95% CI, 1.021-2.152; P = 0.039) were independent predictors. These factors were incorporated into a novel nomogram, which exhibited strong predictive accuracy for 5-year OS in the training, internal validation, and external validation cohorts (area under the curve = 0.744, 0.759, and 0.854, respectively). The decision curve analysis of the nomogram and concordance indexes across the three cohorts outperformed the traditional pTNM (P < 0.05). Additionally, TSP-cad assessment using a rapid multi-dynamic algorithm demonstrated good agreement with TSP-visual. The novel nomogram based on TSP could effectively identify individuals at risk of a poor prognosis among patients with GC. TSP-cad is anticipated to enhance the evaluation process of TSP.

Cancer-related fatigue trajectories up to 5 years after curative treatment for oesophageal cancer

BackgroundWhether cancer-related fatigue develops differently after curative-intended oesophageal cancer treatment and the related modifiable factors are unclear.MethodsThis population-based and longitudinal cohort included 409 oesophageal cancer patients who underwent curative oesophagectomy in 2013–2020 in Sweden. The main outcome was cancer-related fatigue trajectories with measurements at 1, 1.5, 2, 2.5, 3, 4 and 5 years postoperatively by validated EORTC QLQ-FA12 questionnaire, and analysed using growth mixture models. Weighted logistic regressions provided odds ratios (OR) with 95% confidence intervals (95% CI) for underlying sociodemographic, clinical, and patient-reported outcome factors in relation to the identified trajectories.ResultsTwo distinct overall cancer-related fatigue trajectories were identified: low level of persistent fatigue and high level of increasing fatigue, with 64% and 36% of patients, respectively. The odds of having high level of fatigue trajectory were increased by Charlson comorbidity index (≥ 2 versus 0: OR = 2.52, 95% CI 1.07–5.94), pathological tumour Stage (III–IV versus 0-I: OR = 2.52, 95% CI 1.33–4.77), anxiety (OR = 7.58, 95% CI 2.20–26.17), depression (OR = 15.90, 95% CI 4.44–56.93) and pain (continuous score: OR = 1.02, 95% CI 1.01–1.04).ConclusionsLong-term trajectories with high level of increasing cancer-related fatigue and the associated modifiable factors were identified after oesophageal cancer treatment. The results may facilitate early identification and targeted intervention for such high-risk patients.

Decoding the basis of histological variation in human cancer.

Molecular abnormalities that shape human neoplasms dissociate their phenotypic landscape from that of the healthy counterpart. Through the lens of a microscope, tumour pathology optically captures such aberrations projected onto a tissue slide and has categorized human epithelial neoplasms into distinct histological subtypes based on the diverse morphogenetic and molecular programmes that they manifest. Tumour histology often reflects tumour aggressiveness, patient prognosis and therapeutic vulnerability, and thus has been used as a de facto diagnostic tool and for making clinical decisions. However, it remains elusive how the diverse histological subtypes arise and translate into pleiotropic biological phenotypes. Molecular analysis of clinical tumour tissues and their culture, including patient-derived organoids, and add-back genetic reconstruction of tumorigenic pathways using gene engineering in culture models and rodents further elucidated molecular mechanisms that underlie morphological variations. Such mechanisms include genetic mutations and epigenetic alterations in cellular identity codes that erode hard-wired morphological programmes and histologically digress tumours from the native tissues. Interestingly, tumours acquire the ability to grow independently of the niche-driven stem cell ecosystem along with these morphological alterations, providing a biological rationale for histological diversification during tumorigenesis. This Review comprehensively summarizes our current understanding of such plasticity in the histological and lineage commitment fostered cooperatively by molecular alterations and the tumour environment, and describes basic and clinical implications for future cancer therapy.

Evaluation of Conservative Breast Surgery After Neoadjuvant Chemotherapy in Early Breast Cancer

Background: The breast cancer is a frequent type of cancers. It is associated with high mortality related to cancer in women. The treatment options transferred from radical surgery to less invasive operations. This was attributed to surgical advance and available neoadjuvant chemotherapy. Objective: This work aimed to evaluate the conservative breast surgery feasibility and outcome for early breast cancer received neoadjuvant chemotherapy (NACT) for downstaging. Patients and Methods: Thirty women (30) with early breast cancer were included between November 2022 and May 2023. All women were assessed in systematic manner by history, clinical, laboratory and radiological investigations before chemotherapy, before and after surgery. A true cut biopsy was drawn to estimate the histopathological nature. All surgeries were performed one and half months after the last session of NACT. A regular postoperative follow up was carried out up to six months. Any complications were recorded. Effect of NACT on the tumor grading was the primary outcome, while cosmetic results and patient satisfaction were the secondary outcomes. Results: Complications were in the form of wound infection, seroma and hematoma in 6.7%, 13.3% and 3.3% respectively. These were mild and treated conservatively. The excellent cosmetic result was achieved for 80.0% and excellent patient satisfaction was recorded for 60.0%. The effect of chemotherapy showed significant improvement of clinical and pathological post chemotherapy tumor size values when compared to clinical tumor size values before chemotherapy, the T1 grade (≤2cm) increased from 50% to 66.7%, while the T2 grade (&gt; 2cm &lt;5 cm) decreased from 50% to33.3%. Conclusion: NACT was associated with excellent response regarding tumor size reduction, negativity of lymph nodes as well as pathological response of early breast cancer, before breast conservation surgery (BCS). The BCS after NACT could be considered as a safe option with acceptable aesthetic outcome.

The effect of NBS1 heterozygous inactivating mutation in a model of 7,12-dimethylbenz[a]anthracene-induced carcinogenesis in mice

BACKGROUND: The creation of new experimental models carrying various heterozygous inactivating mutations in DNA repair genes and their carcinogenesis studies could expand our understanding of the spectrum of possible neoplasms that patients with such mutations are at risk of developing.&#x0D; AIM: The study of the effect of NBS1 inactivating heterozygous mutation (с.1971insT, p.Arg658Stop) in a model of 7,12-dimethylbenz[a]anthracene (DMBA) induced carcinogenesis in mice.&#x0D; MATERIALS AND METHODS: Carcinogenesis was induced in 2-month-old female mice with and without NBS1 heterozygous mutation by intragastric administration of 7,12-DMBA (dose of 50 mg/kg once a week, for 8 weeks) on a high-fat diet. Lifetime observation was conducted, and parameters of lifespan and carcinogenesis were evaluated.&#x0D; RESULTS: NBS1 inactivating heterozygous mutation had no significant effect on the incidence of tumor pathology induced by 7,12-DMBA, but somewhat accelerated the rate of tumor development and, consequently, the death of animals. The presence of the mutation increased the sensitivity to carcinogen toxic effect, which was expressed in a statistically significant increase in death rate (by 35%) in the early stages of the study. The mean lifespan in female NBS1 mutant mice was reduced by 14% compared to mutation-free animals.&#x0D; CONCLUSION: Carrying NBS1 inactivating heterozygous mutation (с.1971insT, p.Arg658Stop) worsens the prognosis of survival in the model of chemically induced 7,12-DMBA carcinogenesis in mice.