High mechanical conditioning by tumor extracellular matrix stiffness is a predictive biomarker for anti-fibrotic therapy in HER2-negative breast cancer.

BACKGROUND: Tumor progression has been linked to stiffening of the extracellular matrix (ECM) caused by fibrosis. Cancer cells can be mechanically conditioned by stiff ECM, exhibiting a 1004-gene signature (MeCo score). Nintedanib has demonstrated anti-fibrotic activity in idiopathic pulmonary fibrosis. This study explores nintedanib's anti-fibrotic effect on breast cancer outcomes. METHODS: We present long-term follow-up and analysis of a neoadjuvant randomized Phase 2 trial in early HER2-negative breast cancer. Patients (N = 130) underwent a baseline biopsy and received 12 paclitaxel courses alone (control arm) or in combination with nintedanib (experimental arm). Tumor MeCo score was determined by RNAseq. The primary aim was to assess nintedanib's impact on event-free survival (EFS) based on MeCo scores. RESULTS: Follow-up data were retrieved from 111 patients; 75 baseline and 24 post-run-in phase samples were sequenced. After median follow-up of 9.67 years, median EFS was not statistically different between arms (P = 0.37). However, in the control arm, High versus Low MeCo patients had a statistically higher relapse risk: hazard ratio (HR) = 0.21; P = 0.0075. This risk was corrected by nintedanib in the experimental arm: HR = 0.37; P = 0.16. Nintedanib demonstrated pharmacodynamic engagement, reducing the MeCo score by 25% during the run-in phase (P<0.01). Patients with Low MeCo after run-in had the best long-term prognosis (HR = 0.087; P = 0.03). CONCLUSIONS: High MeCo is predictive of poor outcomes in HER2-negative early breast cancer, although this risk can be mitigated by nintedanib, which is able to specifically reduce mechanical conditioning.

Prognostic Value of Tumor Deposits in Patients with Colorectal Cancer.

Tumor nodules or tumor deposits (TDs) are a histopathological prognostic factor that are associated with a negative evolutionary course in patients with colorectal cancer (CRC). There are still controversial aspects of TDs, including how they should be integrated into the TNM classification system. The objective of this study was to analyze the predictive value of TDs for cancer-related survival (CRS) and time-to-recurrence survival (TTR) and to evaluate the prognostic value of TDs in patients whose tumors also presented lymph node metastasis (LNM). In this retrospective observational study, all patients treated for CRC between January 2010 and December 2020 at the same hospital were included. CRS and TTR were classified by tumor stage. The results were compared between patients whose tumors had TDs and patients whose tumors did not. A total of 1426 patients met the criteria for inclusion in the analysis. TDs were detected in 178 patients (12.5%): 60 had tumors without LNM, and 118 had LNM. Patients with TD tumors had a lower CRS at 60 months after diagnosis (42% vs. 82%; p < 0.001) and a shorter TTR (34% vs. 79%; p < 0.001). Cox multiple regression analysis revealed that the presence of TD was associated with an increased risk of death from CRC (HR: 1.820; 95% CI: 1.327-2.496) and an increased risk of recurrence (HR: 2.315; 95% CI: 1.743-3.073). In each N stage category, the CRS was significantly lower in the subgroup with TD+: in patients with N1a tumors, the CRS was 44% when TD+ vs. 70% when TD- (p = 0.019); in the N1b group it was 36% vs. 66% (p < 0.001); in the N2a group it was 34% vs. 58% (p = 0.012); and in N2b tumors it was 23% vs. 53% (p = 0.031). The present study shows that the information on the presence of TDs is complementary to that provided by LNM and allows the identification of subgroups of patients in each N stage determined by two metrics, CRS and TTR. TDs should be included in the definition of TNM system categories in patients who simultaneously present with LNM.

Effect of Tumor Regression Grade on Survival and Disease-Free Interval in Patients Operated on for Locally Advanced Rectal Cancer.

INTRODUCTION: Colorectal cancer is the fourth leading cause of cancer-related death in both men and women in our population. In this regard, rectal cancer accounts for more than half of colorectal cancer deaths, and its incidence is expected to increase in the coming years. There have been significant changes in neoadjuvant therapy regimens, with promising results, as demonstrated by the recent RAPIDO and PRODIGE23 studies. Around 40% of patients diagnosed with locally advanced rectal cancer show some degree of response to neoadjuvant treatment, with complete tumor regression observed in up to one in five patients. MATERIALS AND METHODS: Retrospective observational study. A total of 181 patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were analyzed. Clinical and pathological data were collected from the patients, including assessment of tumor regression through histopathological studies after surgery. The Mandard tumor regression grading system was used to categorize tumor response into different grades. RESULTS: The results showed a significant association between the degree of tumor regression and several important clinical outcomes. Specifically, patients with higher tumor regression had significantly better disease-free survival than those with less regression (p = 0.004). In addition, tumor regression was also correlated with the incidence of local recurrence (p = 0.018) and distant metastasis (p = 0.032). These associations suggest that tumor responsiveness to neoadjuvant therapy may influence the long-term progression of the disease. Regarding tumor deposits and the presence of lymphadenopathy, these factors were also found to be significantly associated with clinical outcomes. Patients with tumor deposits had a higher incidence of local recurrence (p = 0.025) and distant metastases (p = 0.041), while the presence of lymphadenopathy increased the risk of local recurrence (p = 0.013). These findings highlight the importance of evaluating not only tumor regression but also other pathological markers to predict prognosis and guide clinical management. CONCLUSIONS: The degree of tumor regression was not an independent predictor of survival compared to other variables such as nodal stage and presence of tumor deposits. This indicates that while tumor regression is an important factor, other elements also play a crucial role in determining the prognosis of patients with locally advanced rectal cancer. This study provides additional evidence for the importance of tumor regression, tumor deposits, and lymphadenopathy as predictors of clinical outcomes in patients with rectal cancer treated with neoadjuvant chemoradiotherapy.

Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2- advanced breast cancer: a real-world evidence cohort.

PURPOSE: Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. METHODS: A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates. RESULTS: One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15 months (interquartile range: 1-56 months). The median age at diagnosis was 49 years (range: 35-90 years). The estimated mPFS was 6.0 months (95%CI 5.3-7.8 months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18 months (8.7 months, 95%CI 6.6-11.3 months), in patients w/o visceral metastases (8.0 months, 95%CI 5.8-10.5 months), and chemotherapy-naïve in the metastatic setting (7.2 months, 95%CI 5.9-8.4 months). CONCLUSION: This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.

Acute Cholecystitis Complicating Cardiac Disease: A Cohort Study From a Tertiary Care Center in Mexico City, Mexico.

Background Acute cholecystitis (AC) presents as inflammation of the gallbladder, predominantly attributed to gallstones obstructing the cystic duct. Another notable etiology is ischemic cholecystitis, often stemming from severe illnesses that compromise blood flow to the splanchnic system. Individuals with pre-existing cardiovascular conditions or undergoing cardiopulmonary surgery encounter elevated risks of gastrointestinal pathology, leading to heightened morbidity and mortality rates. In these cases, AC stands out as a significant concern, whether it originates from gallstones or is acalculous (ischemic). Methods We conducted a single-center, retrospective cohort study at the National Medical Center in Mexico City, Mexico. We included demographic, clinical, laboratory, preoperative, intraoperative, and postoperative data. Our main objectives were to describe the characteristics of our population and identify predictors of major complications following surgery for AC in patients with heart disease. Results Our study encompassed 18 patients diagnosed with both AC and cardiac disease, with acute myocardial infarction being the leading cause of admission, constituting 38.9% of cases. The clinical presentation was characterized by right hypochondrial pain, observed in all patients, while Murphy's sign was evident in 44.4% of cases. Additionally, various non-specific symptoms were present in varying percentages across the patient cohort. Concerning imaging studies, 88% of our cohort underwent ultrasound (USG), while computed tomography (CT) was utilized in 55% of patients. Among those who had USG, the most prevalent findings were gallbladder wall thickening in 56% and perivesicular fluid in 37.5%. In patients who underwent CT scans, the predominant observations included perivesicular fluid in 66% and perivesicular fat stranding in 55%. In terms of intraoperative findings, gallbladder empyema and necrosis were the most common findings identified in 55.6% of the cases. After surgery, 61.1% had no complications or developed mild complications, while 11.1% experienced moderate to severe complications without resulting in death; the mortality rate was 27.8% in our cohort. Overall, major complications or death were present in 38.9% of our cohort. In the postoperative data analysis, the use of mechanical ventilation and vasopressors showed a significant correlation with increased morbidity and mortality. Conclusions Our study contributes valuable information to the international literature, providing insights into the complications faced by the Mexican population in the context of heart diseases, particularly among patients suffering from cholecystitis. Within individuals with cardiac disease, the occurrence of AC requiring surgical intervention is associated with heightened morbidity and mortality rates, with our cohort experiencing rates as high as 38.9%. Consistent with findings in the international literature, these results underscore the critical importance of continuing the search for novel clinical or laboratory predictors for this high-risk population. While most parameters assessed in this study did not show any correlation with major complications, exceptions were observed in postoperative vasopressors and mechanical ventilation.

Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy.

PURPOSE: Stromal tumor-infiltrating lymphocytes (sTIL) are associated with pathologic complete response (pCR) and long-term outcomes for triple-negative breast cancer (TNBC) in the setting of anthracycline-based chemotherapy. The impact of sTILs on refining outcomes beyond prognostic information provided by pCR in anthracycline-free neoadjuvant chemotherapy (NAC) is not known. EXPERIMENTAL DESIGN: This is a pooled analysis of two studies where patients with stage I (T>1 cm)-III TNBC received carboplatin (AUC 6) plus docetaxel (75 mg/m2; CbD) NAC. sTILs were evaluated centrally on pre-treatment hematoxylin and eosin slides using standard criteria. Cox regression analysis was used to examine the effect of variables on event-free survival (EFS) and overall survival (OS). RESULTS: Among 474 patients, 44% had node-positive disease. Median sTILs were 5% (range, 1%-95%), and 32% of patients had ≥30% sTILs. pCR rate was 51%. On multivariable analysis, T stage (OR, 2.08; P = 0.007), nodal status (OR, 1.64; P = 0.035), and sTILs (OR, 1.10; P = 0.011) were associated with pCR. On multivariate analysis, nodal status (HR, 0.46; P = 0.008), pCR (HR, 0.20; P < 0.001), and sTILs (HR, 0.95; P = 0.049) were associated with OS. At 30% cut-point, sTILs stratified outcomes in stage III disease, with 5-year OS 86% versus 57% in ≥30% versus <30% sTILs (HR, 0.29; P = 0.014), and numeric trend in stage II, with 5-year OS 93% versus 89% in ≥30% versus <30% sTILs (HR, 0.55; P = 0.179). Among stage II-III patients with pCR, EFS was better in those with ≥30% sTILs (HR, 0.16; P, 0.047). CONCLUSIONS: sTILs density was an independent predictor of OS beyond clinicopathologic features and pathologic response in patients with TNBC treated with anthracycline-free CbD chemotherapy. Notably, sTILs density stratified outcomes beyond tumor-node-metastasis (TNM) stage and pathologic response. These findings highlight the role of sTILs in patient selection and stratification for neo/adjuvant escalation and de-escalation strategies.

Ripe papaya pectins inhibit the proliferation of colon cancer spheroids and the formation of chemically induced aberrant crypts in rats colons.

Pectins are a class of soluble polysaccharides that can have anticancer properties through several mechanisms. This study aimed to characterize the molecular structure of water-soluble fractions (WSF) derived from ripe and unripe papayas and assess their biological effects in two models: the 3D colon cancer spheroids to measure cell viability and cytotoxicity, and the in vivo model to investigate the inhibition of preneoplastic lesions in rats. WSF yield was slightly higher in ripe papaya, and both samples mainly consisted of pectin. Both pectins inhibited the growth of colon cancer HT29 and HCT116 spheroids. Unripe pectin disturbed HT29/NIH3T3 spheroid formation, decreased HCT116 spheroid viability, and increased spheroid cytotoxicity. Ripe pectin had a more substantial effect on the reduction of spheroid viability for HT29 spheroids. Furthermore, in vivo experiments on a rat model revealed a decrease in aberrant crypt foci (ACF) formation for both pectins and increased apoptosis in colonocytes for ripe papaya pectins. The results suggest potential anticancer properties of papaya pectin, with ripe pectin showing a higher potency.

Single metachronous bone metastasis following rectal adenocarcinoma: A case report.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related mortality in developed countries. While its incidence in early stages has increased due to screening programs, a significant number of patients experience the development of metastases either at the time of diagnosis or during follow-ups. Unlike certain other types of cancer, such as breast, prostate, or lung cancer, where bone tissue is a common site for secondary dissemination, CRC primarily spreads to the lymph nodes, liver and lungs. The occurrence of bone metastases from CRC is rare and usually coincides with tumor involvement in other locations. Risk factors for bone metastases include the location of the primary tumor, the age of the patients, KRAS mutations and the degree of tumor differentiation. Unlike metastases to the liver and lungs, bone metastases tend to be symptomatic, affecting the patient's quality of life and resulting in a poorer prognosis with shorter survival rates. The approach to patient management needs to be personalized. The present study describes the of a patient who underwent surgery for stage IV rectal adenocarcinoma and later developed a metastasis in the costal wall 79 months post-intervention, with no evidence of recurrence at other sites.

Spontaneous cervical hematoma caused by giant parathyroid adenoma in an elderly patient: A case report.

Spontaneous cervical hematoma usually occurs as a consequence of extracapsular bleeding from a parathyroid gland, generally due to the presence of an adenoma (giant adenoma), glandular hyperplasia, cystic component, or, less frequently, due to the existence of a carcinoma. The hematoma can be confined to the cervical compartment or extend to the mediastinum, potentially causing airway compression. Despite this, the recommended management in hemodynamically stable patients consists of surveillance and hospital monitoring with delayed surgery after a few weeks. On the other hand, in those patients with airway compromise and instability, emergency surgery, consisting of cervicotomy and drainage, is mandatory. The present study describes the case of a 78-year-old patient with a medical history of high blood pressure, non-insulin-dependent diabetes mellitus, dyslipidemia, moderate aortic stenosis, chronic kidney disease and sarcoidosis under pharmacological treatment who attended the emergency department due to symptoms of neck pain, an increase in soft tissue, and dyspnea on moderate exertion with an evolution leading to respiratory failure. This was secondary to a diagnosis of spontaneous cervical hematoma that required urgent surgical intervention. The results of histopathological analysis revealed that a giant parathyroid adenoma was responsible for the bleeding. The patient had a complicated post-operative period with a prolonged admission to the intensive care unit.

Malignant Bowel Obstruction Due to Intraluminal Metastasis of Endometrial Adenocarcinoma Located in the Sigmoid Colon After Nine Years of Follow-Up.

Endometrial adenocarcinoma is currently the most common malignant tumor of the female genital tract. In the early stages, surgical or radiotherapy treatment offers high survival rates and excellent prognosis, although late recurrences have been described. Recurrences of endometrial adenocarcinoma are more frequent in the vaginal vault; however, implants are sometimes detected in the serosa of the colon and rectum, resulting in extrinsic compression. Here, we present the case of a 77-year-old patient with a clinical history of hysterectomy, lymphadenectomy, and double adnexectomy for endometrial adenocarcinoma (International Federation of Gynecology and Obstetrics (FIGO) Ia). Nine years after the initial treatment, she presented an endoluminal recurrence in the sigmoid colon, which is exceptional. The patient underwent surgery by performing an oncological sigmoidectomy. The immunohistochemical study revealed the tumor origin as metastasis of endometrial adenocarcinoma. The patient had a favorable postoperative period, subsequently receiving adjuvant therapy and being disease-free after 18 months of follow-up.

Gallbladder Volvulus in an Elderly Patient: A Case Report and Review of Literature.

Gallbladder volvulus is an uncommon cause of acute cholecystitis that results from the rotation of the gallbladder about its mesentery along the axis of the cystic pedicle. We present the case of an 87-year-old woman with acute abdominal pain in the right upper quadrant that began two days prior with no additional symptoms. The physical examination showed a large abdominal eventration on the right side and tenderness. A CT scan showed a distended gallbladder outside its liver bed and with a twist on its cystic pedicle, suggesting a gallbladder volvulus. Abdominal ultrasonography complementary revealed the gallbladder outside its vesicular fossa with incipient changes of acute cholecystitis but without evidence of gallstones. With the diagnosis of acute abdomen secondary to gallbladder volvulus, an emergency cholecystectomy was performed. The exact etiology of the gallbladder volvulus is unknown, although anatomical variants that predispose to its appearance have been described. The clinical presentation is similar to acute cholecystitis, so preoperative diagnosis can be challenging for both surgeons and radiologists and is often misdiagnosed. This is one of the few cases diagnosed with preoperative imaging techniques. Once diagnosed, the appropriate treatment is emergency cholecystectomy. Early diagnosis and surgical treatment are important before it progresses to necrosis, perforation, biliary peritonitis, and hemodynamic instability. Gallbladder volvulus is an uncommon condition. A high index of suspicion is required because the preoperative diagnosis is unusual. Once the diagnosis is established, the treatment is fundamentally surgical.

Expert design thinking workshops to analyze users' perceived applicability of NUTRI-ONCOCARE algorithm to prevent and treat malnutrition in cancer patients under routine clinical practice conditions in Spain: the ALLIANCE study.

PURPOSE: NUTRI-ONCOCARE algorithm has been developed to identify and treat patients with solid tumors who are at risk of malnutrition. The present study is aimed at analyzing users' opinion about this new tool and at assessing whether it is perceived as useful to achieve the behavioral change required for a successful integration of nutritional assessment into routine cancer care. METHODS: Design thinking Double Diamond process was applied. A multidisciplinary team composed of ten potential end-users (four oncologists, three endocrinologists, one nutritionist, and two hospital pharmacists) participated in three different workshops aiming to analyze the different tasks included within the NUTRI-ONCOCARE algorithm. RESULTS: Users agreed on the need to perform nutritional assessment around cancer diagnosis and through the course of the disease using standardized tools included in hospital nutritional protocols and involving healthcare professionals with nutrition expertise. Nutritional evaluation and intervention should be individual and comprehensive, considering not only nutritional parameters but also patients' functional status. According to participants' opinion, the implementation of nutritional screening in routine clinical practice is limited by the lack of time and staff to conduct nutritional assessments, the low level of nutrition expert participation, and the poor support provided by hospital managers, which are often unaware of nutrition's impact in cancer care. CONCLUSIONS: Experts recognized the importance of considering nutritional status in cancer patients and identified the opportunity provided by the NUTRI-ONCOCARE algorithm for this purpose, as it meets main requirements for being used routinely in clinical practice.

Differences in Colorectal Cancer Survival Based on Primary Tumor Location: Retrospective Study from a Single Institution.

Objective: The location of the primary tumor in colorectal cancer (CRC) could be a prognostic factor related to survival. However, its usefulness has not been sufficiently analyzed. The results in patients with tumors in initial stages are very limited, and there are descriptive parameters of survival that have not been analyzed in detail. In this study, the relationship between primary tumor location and survival in CRC patients was analyzed. Materials And Methods: This was a retrospective observational study. All patients treated consecutively for CRC between January 2005 and December 2019 in the same hospital center were included. Overall survival (OS), cancer-related survival (CRS), time to recurrence (TTR), relapse-free survival (RFS) and postrecurrence survival (PRS) were analyzed, and the results were classified by tumor stage. The results were compared among patients with right colon (RS), left colon (LS) and rectal tumors. Results: In the entire cohort, patients with RS tumors had lower OS and lower CRS at 60 months after diagnosis than did patients with LS or rectal tumors. In the regression analysis, the localization of the primary tumor was an independent prognostic indicator for OS and CRS. Analysis by tumor stage showed that patients with RS stage III tumors had lower OS and lower CRS at 60 months than did patients with LS and rectal tumors (42%, 59% and 53%, respectively, p = 0.006; and 48%, 63% and 57%, respectively, p = 0.025). Additionally, patients with RS Stage IV tumors had lower OS and lower CRS at 36 months than did patients with LS and rectal tumors (9%, 24%, 24%, respectively, p < 0.001; and 10%, 24% and 24%, respectively, p < 0.001). No differences were found in TTR and RFS among patients with stage I and II RS, LS, and rectal tumors. In contrast, patients with stage RS III tumors had significantly poorer PRS (9% for RS tumors, 13% for LS tumors, and 22% for rectal tumors) (p < 0.001). Conclusion: The location of the primary tumor in patients with CRC is related to survival. The effect of laterality is more marked in patients with stage III and IV tumors. Patients with RS tumors had lower OS and CRS due to the lower survival of patients with stage IV RS tumors and lower PRS for patients with stage III tumors.

Past, present, and future of chemically induced hepatocarcinogenesis rodent models: Perspectives concerning classic and new cancer hallmarks.

Hepatocellular carcinoma (HCC), the main primary liver cancer, accounts for 5 % of all incident cases and 8.4 % of all cancer-related deaths worldwide. HCC displays a spectrum of environmental risk factors (viral chronic infections, aflatoxin exposure, alcoholic- and nonalcoholic fatty liver diseases) that result in molecular complexity and heterogeneity, contributing to a rising epidemiological burden, poor prognosis, and non-satisfactory treatment options. The emergence of HCC (i.e., hepatocarcinogenesis) is a multistep and complex process that addresses many (epi)genetic alterations and phenotypic traits, the so-called cancer hallmarks. "Polymorphic microbiomes", "epigenetic reprogramming", "senescent cells" and "unlocking phenotypic plasticity" are trending hallmarks/enabling features in cancer biology. As the main molecular drivers of HCC are still undruggable, chemically induced in vivo models of hepatocarcinogenesis are useful tools in preclinical research. Thus, this narrative review aimed at recapitulating the basic features of chemically induced rodent models of hepatocarcinogenesis, eliciting their permanent translational value regarding the "classic" and the "new" cancer hallmarks/enabling features. We gathered state-of-art preclinical evidence on non-cirrhotic, inflammation-, alcoholic liver disease- and nonalcoholic fatty liver-associated HCC models, demonstrating that these bioassays indeed express the recently added hallmarks, as well as reflect the interplay between classical and new cancer traits. Our review demonstrated that these protocols remain valuable for translational preclinical application, as they recapitulate trending features of cancer science. Further "omics-based" approaches are warranted while multimodel investigations are encouraged in order to avoid "model-biased" responses.

Real-World Use of Highly Sensitive Liquid Biopsy Monitoring in Metastatic Breast Cancer Patients Treated with Endocrine Agents after Exposure to Aromatase Inhibitors.

Endocrine-resistant, hormone receptor-positive, and HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) is largely governed by acquired mutations in the estrogen receptor, which promote ligand-independent activation, and by truncal alterations in the PI3K signaling pathway, with a broader range of gene alterations occurring with less prevalence. Circulating tumor DNA (ctDNA)-based technologies are progressively permeating the clinical setting. However, their utility for serial monitoring has been hindered by their significant costs, inter-technique variability, and real-world patient heterogeneity. We interrogated a longitudinal collection of 180 plasma samples from 75 HR+/HER2- mBC patients who progressed or relapsed after exposure to aromatase inhibitors and were subsequently treated with endocrine therapy (ET) by means of highly sensitive and affordable digital PCR and SafeSEQ sequencing. Baseline PIK3CA and TP53 mutations were prognostic of a shorter progression-free survival in our population. Mutant PIK3CA was prognostic in the subset of patients receiving fulvestrant monotherapy after progression to a CDK4/6 inhibitor (CDK4/6i)-containing regimen, and its suppression was predictive in a case of long-term benefit with alpelisib. Mutant ESR1 was prognostic in patients who did not receive concurrent CDK4/6i, an impact influenced by the variant allele frequency, and its early suppression was strongly predictive of efficacy and associated with long-term benefit in the whole cohort. Mutations in ESR1, TP53, and KRAS emerged as putative drivers of acquired resistance. These findings collectively contribute to the characterization of longitudinal ctDNA in real-world cases of HR+/HER2- mBC previously exposed to aromatase inhibitors and support ongoing studies either targeting actionable alterations or leveraging the ultra-sensitive tracking of ctDNA.

Discriminating Glioblastoma from Peritumoral Tissue by a Nanohole Array-Based Optical and Label-Free Biosensor.

In glioblastoma (GBM) patients, maximal safe resection remains a challenge today due to its invasiveness and diffuse parenchymal infiltration. In this context, plasmonic biosensors could potentially help to discriminate tumor tissue from peritumoral parenchyma based on differences in their optical properties. A nanostructured gold biosensor was used ex vivo to identify tumor tissue in a prospective series of 35 GBM patients who underwent surgical treatment. For each patient, two paired samples, tumor and peritumoral tissue, were extracted. Then, the imprint left by each sample on the surface of the biosensor was individually analyzed, obtaining the difference between their refractive indices. The tumor and non-tumor origins of each tissue were assessed by histopathological analysis. The refractive index (RI) values obtained by analyzing the imprint of the tissue were significantly lower (p = 0.0047) in the peritumoral samples (1.341, Interquartile Range (IQR) 1.339-1.349) compared with the tumor samples (1.350, IQR 1.344-1.363). The ROC (receiver operating characteristic) curve showed the capacity of the biosensor to discriminate between both tissues (area under the curve, 0.8779, p < 0.0001). The Youden index provided an optimal RI cut-off point of 0.003. The sensitivity and specificity of the biosensor were 81% and 80%, respectively. Overall, the plasmonic-based nanostructured biosensor is a label-free system with the potential to be used for real-time intraoperative discrimination between tumor and peritumoral tissue in patients with GBM.

Gastric Necrosis Due to Small Bowel Obstruction: A Case Report.

Gastric necrosis is a rare entity due to the normal anatomy of the stomach; the irrigation of the stomach is abundant and has vast collateral irrigation that prevents necrosis from happening in normal situations. Gastric ischemia doesn't happen even if arterial occlusion occurs; however, a venous occlusion caused by an increase in intragastric pressure (measured ï»¿>20 cm H2O in some experiments) that surpasses gastric venous pressure can precipitate necrosis of the stomach. Here we present the case of a 79-year-old woman with a history of chronic smoking, Alzheimer's dementia, systemic hypertension, hypothyroidism, chronic constipation, and a hysterectomy performed 25 years ago. An exploratory laparotomy was performed with the following findings: 3 liters of fecaloid fluid in the abdominal cavity, 70% necrosis of the stomach affecting major curvature and 80% of the fundus without compromising the cardia, a perforation in the anterior portion of the stomach with a diameter of 6 cm, a right femoral hernia with small bowel entrapment, intestinal obstruction with dilated small bowel; and intestinal necrosis of 7 cm of the ileum that was inside the femoral hernia. A vertical gastrectomy for the necrotic stomach and intestinal resection with termino-terminal anastomosis in the affected segment of the ileum were performed. The patient had a poor response to treatment and finally died 72 hours after surgery due to abdominal sepsis. This report shows that gastric necrosis, although rare, can be a cause of acute abdominal pain. It highlights the importance of a good clinical examination and imaging studies in detecting the causes of small bowel obstruction and offering prompt diagnosis and treatment to patients with small bowel obstruction.

Malignant adipocytic tumours: A 20­year single­centre retrospective study.

Adipocytic tumours are the most common soft tissue neoplasms. Among them, liposarcoma is the most frequent malignant neoplasm. However, to the best of our knowledge, no previously published study has assessed the evolution and oncological prognosis of the different subtypes of liposarcoma at the retroperitoneal level compared with at other locations. The present study is a retrospective observational study in which all patients were operated on between October 2000 and January 2020 with a histological diagnosis of liposarcoma. Variables, such as age, sex, location, histological type, recurrence, type of treatment and mortality, among others, were analysed. The patients were divided into two groups: Group A (retroperitoneal location) and group B (non-retroperitoneal location). A total of 52 patients with a diagnosis of liposarcoma (17 women and 35 men) and a mean age of 57.2±15.9 years were assessed. A total of 16 patients were classified into group A and 36 into group B. The OR of recurrence was 1.5 (P=0.02) for R1 vs. R0 resection in group A. The OR of recurrence in group B for R1 vs. R0 resection was 1.8 (P=0.77), whereas for R2 vs. R0 resection, the OR was 69 (P=0.011). In conclusion, 52 cases of malignant adipocytic tumours collected during 2000-2020 were analysed with the new World Health Organization classification (updated 2020). Although its recurrence potential and capacity for distant metastasis depended on each histological type, surgical treatment with unaffected margins was the main prognostic factor for survival. The present study identified differences in relation to the survival of each histological subtype and its location, finding greater survival in dedifferentiated liposarcoma, myxoid liposarcoma and pleomorphic liposarcoma located at the extraperitoneal level than in the retroperitoneal location. Resectability was not influenced by liposarcoma location.

SEOM-GEICAM-SOLTI clinical guidelines in advanced breast cancer (2022).

Advanced breast cancer represents a challenge for patients and for physicians due its dynamic genomic changes yielding to a resistance to treatments. The main goal is to improve quality of live and survival of the patients through the most appropriate subsequent therapies based on the knowledge of the natural history of the disease. In these guidelines, we summarize current evidence and available therapies for the medical management of advanced breast cancer.