Localized Disease Research Articles

Pathological complete response of locally advanced triple-negative breast cancer: case report

Background. Triple-negative breast cancer is the most aggressive molecular subtype among breast malignancies. Due to the high proliferative activity of tumor cells and the lack of targets for targeted therapy, neoadjuvant chemotherapy plays the main role in complex treatment of this subtype. The optimal time to start neoadjuvant chemotherapy is defined as less than 8 weeks. Delays in time to treatment initiation may adversely affect treatment outcomes, as well as cause local or systemic disease progression. Achieving complete pathological response after neoadjuvant chemotherapy reduces the relative risk of relapse by more than 70 %, which, in turn, leads to a significant improvement in long-term survival of these patients. Description of the clinical case. A 32-year-old woman came to the clinic 15 months after being diagnosed with triple-negative breast cancer. The patient was treated with alternative medicine methods for 15 months, and upon admission to the hospital, the patient had pronounced local tumor growth with massive decay, tumor lysis syndrome and nutritional disorders. We decided to perform neoadjuvant chemotherapy: 12 cycles of weekly paclitaxel + carboplatin, followed by 4 cycles of dose-dense doxorubicin + cyclophosphamide. Chemotherapy resulted in a significant reduction in tumor size and improvement of health status of the patient. There were no clinically significant side effects requiring hospitalization or dose reduction. Upon completion of neoadjuvant treatment, the patient underwent mastectomy. The histological examination revealed a complete pathological response of the primary tumor and regional lymph nodes. The patient underwent adjuvant external beam radiation therapy. The patient is alive 3 years after diagnosis and 1.5 years after treatment completion. She plans delayed breast reconstruction with contralateral breast augmentation. Conclusion. This is a rare case of locally advanced triple-negative breast cancer with pathological complete response to neoadjuvant chemotherapy 15 months after diagnosis.

Outcomes following extended resection of radiation-induced angiosarcoma of the breast: a sarcoma unit experience and systematic review.

Radiation-induced angiosarcoma (RIAS) of the breast is a rare tumour with high rate of local recurrence. The aim of this study is to evaluate the outcome of radical resections. A retrospective analysis of all patients who underwent extended surgical resection for RIAS of the breast between 2013 and 2022. Included were patients who underwent radical resection, including complete resection of previously irradiated skin and underlying fascia of pectoralis major. Post-operative and long-term oncological outcomes were than analysed. A systematic review was performed using the MEDLINE database in the last 20 years. Twenty-two (n = 22) patients met the inclusion criteria. The median length of the specimen was 220 mm (range, 120-377 mm). At a median follow-up of 33.5 months (range, 7.9-102.4), 3 (13.6%) patients had both local and metastatic lung disease and 1 (4%) patient with only lung metastasis. The estimated 3- and 5-year OS was 81.1% and 57.9%, respectively. The estimated 3- and 5-year DSS was 91.7% and 65.5%, respectively. The estimated 3- and 5-year DFS rate were both 75.2%. The systematic review identified 17 studies with a recurrence rate ranging from 33% to 100%. Treatment of RIAS of the breast with an up-front locally extended approach is associated with a low rate of local recurrence compared with the reported literature.

The impact of preoperative treatments on the immune environment of rectal cancer.

To improve local disease control, the use of preoperative radiotherapy either alone or combined with chemotherapy has become standard practice in rectal cancer, but it is unclear how these treatments modify the antitumoral immune response. We aimed to evaluate tumor histopathologic features and the prognostic effect of host immune response in rectal cancer with variable treatment modalities. Ninety-five rectal cancers with short-course radiotherapy (SRT), 97 with long-course chemoradiotherapy (CRT), and 154 without preoperative treatments, were evaluated for histopathologic features including Crohn's-like reaction (CLR). CD3+ and CD8+ immunohistochemistry and tumor cells were analyzed from tumor tissue microarray samples to calculate T-cell densities and G-cross function values to estimate cancer cell-T-cell co-localization (proximity score). We found that lymphocyte densities were diminished after SRT, but CLR was scarcer after CRT. Proximity score and CLR density were prognostic for survival in cancer without preoperative treatments and could be combined into an enhanced prognostic score (immune grade). In the irradiated tumors, CLR density remained prognostic while the impact of T-cell infiltration was insufficient alone. In multivariable analysis, the immune grade proved to be an independent prognostic factor for survival. In conclusion, the immune contexture of rectal cancer harbors prognostic significance even after preoperative radiotherapy.

FP2.5 - Predictors for anastomotic leak (AL) in inflammatory bowel disease (IBD) patients and its associated postoperative (PO) complications; A cohort of a single institution experience

Abstract Introduction IBD patients are highly susceptible to PO morbidities. This study aimed to look at the predictors of AL and the associated morbidities during hospital stays to increase the awareness of these patients. Methods A 5-year retrospective study in DGH. All variables were evaluated:patient-dependent (Age, Gender, BMI, ethnic group, comorbidities),disease-dependent (type of IBD, disease location, disease duration), surgery-dependent (duration, CEPOD type, approach, type of resection),Postoperative(CRP level, VTE, ITU admission, LOS, complications).All data were analysed using SPSS22, and Chi-square test. Results 131 patients were admitted for IBD resection. Median age 37 years. 76 (58%) were female, Chron’s disease was 98 (74.8%). 101 (77.1%) were done laparoscopically, 87 (66.4%)were elective, and the median LOS was 7days.63 (48.1%) has bowel anastomosis and 15 (23.8%) have AL. The median CRP on PO day3 for AL patients was 118. There was no significant association between PO day3CRP and IBD type with AL (P=0.4, 0.7); however, DVT and PE were associated with AL (P=0.001 and 0.039). Patients with AL had a high tendency for ITU admission with longer LOS (P=0.000).Long stays were seen in patients with leaks post-emergency than elective resections (P=0.047, 0.112). AL was associated with chest infection (P=0.001), collection (P=0.006),wound infection (p=0.000), and a higher rate of re-operation within 30 days (p=0.019). Conclusion PO day3CRP is not an independent predictor for AL. Our cohort of IBD patients who had bowel anastomosis showed a significant correlation between VTE and AL.AL was associated with chest and wound infections, high chance of a long ITU stay and subsequently, a long hospital stay. IBD patients with AL are vulnerable to VTE so need high care on these regards.

EP230 - A Closed Loop Audit for Peri-Operative Outcomes Comparing Laparoscopic and Robotic-Assisted Nephroureterectomy for Upper Tract Transitional Cell Carcinoma

Abstract Introduction Transitional cell carcinoma (TCC) of the upper urinary tract (localised high-risk disease) is treated with a radical nephroureterectomy (RNU). Evidence shows laparoscopic and robotic-assisted RNU have similar oncological outcomes to open RNU, but improved peri-operative outcomes, namely length of stay (LOS) and time to mitomycin C (MMC) – given to reduce bladder recurrence. Standard The European Association of Urology (EAU) Guidelines suggest MMC instillation should occur 2-10 days after RNU. Aim To determine if this standard was being met in a single tertiary centre following laparoscopic RNU, and if the expansion of the robotics service has improved this and other peri-operative outcomes. Methods Retrospective data was collected from patient notes and collated in an excel spreadsheet for descriptive statistical analysis. Results The first loop analysed laparoscopic procedures (n = 36). The average LOS was 5 days (SD = 3.7±) and the average time to MMC was 14 days (SD = 6.7±). Bladder recurrence occurred in 41% (n = 14) of this cohort, over an average follow up time of 30.6 months. The second loop analysed robotic-assisted procedures (n = 33). The average LOS was 4 days (SD = 2.23±) and the average time to MMC was 2 days (SD = 0.57±). Bladder recurrence occurred in 30% (n = 8) of this cohort, over an average follow up time of 13 months. Conclusion Both procedures are safe and effective with satisfactory oncological outcomes. By expanding the robotics service, the average LOS and time to MMC decreased. Disease recurrence was higher in the laparoscopic cohort, but the follow-up period was longer.

Review of Intranasal Active Pharmaceutical Ingredient Delivery Systems.

In recent decades, there has been an increased interest in the development of intranasal delivery systems for active pharmaceutical ingredients (APIs) not only for treating local nasal diseases but also for treating systemic diseases, central nervous system (CNS) disorders, and vaccine delivery. The nasal cavity possesses a unique set of anatomical characteristics for delivering active pharmaceutical ingredients, but there are several limitations that recent research in the field of the intranasal administration of APIs aims to overcome. For the effective delivery of nasal preparations, active pharmaceutical ingredients are incorporated into various micro- and nanosystems. Some of the most commonly encountered API delivery systems in the scientific literature include liposomal systems, polymer particles with mucoadhesive properties, in situ gels, nano- and microemulsions, and solid lipid particles. This article provides a review of research on the development of nasal preparations for treating local nasal cavity diseases (in particular, for antibiotic delivery), systemic diseases (analgesics, drugs for cardiovascular diseases, antiviral and antiemetic drugs), CNS disorders (Alzheimer's disease, Parkinson's disease, epilepsy, schizophrenia, depression), and vaccine delivery. The literature data show that active research is underway to reformulate drugs of various pharmacotherapeutic groups into a nasal form.

Clinical characteristics and outcomes of Brazilian patients with duodenal-type follicular lymphoma: a multicenter retrospective study

Duodenal-type follicular lymphoma (DFL) is a rare subtype classified by the 5th edition of the WHO and international consensus classifications of lymphoid neoplasms, typically presenting as localized disease with favorable outcomes. This multicenter retrospective study examines 53 Brazilian DFL patients with a median age of 58.2 years (33–85), with males comprising 50% (n = 27). According to Lugano GI tract classification, 40 patients (75%) were stage I. Median follow-up was 2.9 years (range 0.1–11). Incidental diagnosis occurred in 28 patients (52.8%) during routine endoscopy; 24 patients (45%) presented mild gastrointestinal symptoms. Treatments included watchful waiting (32 patients, 60.4%), rituximab monotherapy (15 patients, 28.3%), radiotherapy (three patients, 5.7%), and chemoimmunotherapy (three patients, 5.7%). Three patients experienced disease progression; watchful waiting showed three spontaneous remissions. No deaths occurred during follow-up. This study, the first from Latin America, demonstrates a good prognosis across treatments, highlighting Watchful waiting’s effectiveness.

A new surgical strategy for T4 stage posterior buccal carcinoma: anatomical unit resection

Objective: To investigate the effect of anatomical unit resection on the overall survival rate of patients with T4 stage posterior buccal carcinoma. Methods: We conducted a retrospective study on 79 patients with T4 stage posterior buccal squamous cell carcinoma underwent radical surgery for buccal mucosa cancer and reconstruction with free anterolateral thigh flap in the Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital, Central South University from March 2014 to December 2019. The 74 patients were males and the 5 patients were females, aged from 28 to 72 years old. The 40 patients in control group underwent traditional extended resection (1.5-2.0 cm safe margin), and 39 patients in the experimental group underwent anatomical unit resection. The clinicopathological parameters of patients were collected and followed up regularly. The overall survival rate was assessed by Log-rank and Cox proportional risk regression model. Multivariate analysis was performed by linear regression model. Results: There were significant differences between experimental group and control group in overall survival rates (61.53% vs 27.50%, χ2=6.624, P=0.010) and local disease control rates (74.36% vs 27.50%, χ2=17.350, P<0.001). Multiple linear regression analysis showed that local disease control rate was significantly correlated with anatomical unit resection (t=3.880, P<0.001) and lymph node metastasis (t=2.619, P=0.011), and also Cox proportional hazards regression model analysis identified that overall survival rate was significantly correlated with anatomical unit resection (Z=2.421, P=0.016) and lymph node metastasis (Z=2.793, P=0.005). Conclusion: For posterior buccal carcinoma with multiple anatomical units involved, anatomical unit resection can significantly reduce local recurrence and improve overall survival rate of patients.

Selection of X-ray Tube Settings for Relative Bone Density Quantification in the Knee Joint of Cats Using Computed Digital Absorptiometry.

Bone mineral density (BMD) varies with aging and both systemic and local diseases; however, such evidence is lacking in feline medicine. This may be due to the need for general anesthesia in cats for direct BMD measurements using dual-energy X-ray absorptiometry (DXA) or quantitative computed tomography (QCT). In this study, computed digital absorptiometry (CDA), an indirect relative BMD-measuring method, was optimized to select an X-ray tube setting for the quantitative assessment of the feline knee joint. The knee joints of nine cats were radiographically imaged and processed using the CDA method with an aluminum density standard and five X-ray tube settings (from 50 to 80 kV; between 1.2 and 12 mAs). The reference attenuation of the X-ray beam for ten steps (S1-S10) of the density standard was recorded in Hounsfield units (HU), compared between X-ray tube settings, and used to determine the ranges of relative density applied for radiograph decomposition. The relative density decreased (p < 0.0001) with an increase in kV and dispersed with an increase in mAs. Then, the percentage of color pixels (%color pixels), representing ranges of relative density, was compared among S1-S10 and used for the recognition of background artifacts. The %color pixels was the highest for low steps and the lowest for high steps (p < 0.0001), regardless of X-ray tube settings. The X-ray tube setting was considered the most beneficial when it effectively covered the lowest possible HU ranges without inducing background artifacts. In conclusion, for further clinical application of the CDA method for quantitative research on knee joint OA in cats, 60 kV and 1.2 mAs settings are recommended.

Does the Primary Tumor Site Drive Biology for Patients With Synovial Sarcoma?

We evaluated survival outcomes by primary tumor site in synovial sarcoma (SS) patients with localized and metastatic disease at diagnosis. We conducted a retrospective review of 504 SS patients diagnosed from 1974 to 2020. Kaplan-Meier method, log-rank test, and Cox-proportional hazards regression were used. Among 504 patients, 401 (79.6%) presented with localized disease, and 103 (20.4%) with metastases. For patients with localized disease, (1) 5-year OS by tumor site was as follows: 80% (95% CI, 67%-89%) for head/neck, 30% (95% CI, 18%-42%) for intrathoracic, 51% (95% CI, 35%-65%) for abdomen/pelvis, 71% (95% CI, 62%-79%) for proximal-extremity, and 83% (71%, 91%) for distal-extremity. (2) On multivariable analysis, tumor site (compared with proximal-extremity: intrathoracic tumors [HR: 1.95; 95% CI, 1.22-3.16]; hand/foot [HR: 0.52; 95% CI, 0.28-0.97]), tumor size (compared with <5cm, 5-10cm [HR: 1.80; 95% CI, 1.14-2.85]; ≥10cm [HR: 4.37; 95% CI, 2.69-7.11]), and use of neo/adjuvant radiation (HR: 0.54; 95% CI, 0.37-0.79) remained significantly associated with OS. For patients with metastatic disease, (1) 5-year OS was 12% (95% CI, 6%-21%) and (2) the only factor that remained significantly associated with OS on multivariable analysis was surgical resection for the primary tumor (HR: 0.14; 95% CI, 0.08-0.26). The primary tumor location plays a significant role in predicting outcomes for patients with localized SS. Even though patients present with metastatic disease, surgical resection of the primary tumor improves their survival. These findings are critical for patient counseling and designing a personalized treatment plan that reflects the corresponding outcomes.

Therapeutic Treatment Options for In-Transit Metastases from Melanoma.

In-transit metastases (ITM) in melanoma present a significant therapeutic challenge due to their advanced stage and complex clinical nature. From traditional management with surgical resection, ITM treatment has evolved with the advent of systemic therapies such as immune checkpoint inhibitors and targeted therapies, which have markedly improved survival outcomes. This study aims to review and highlight the efficacy of both systemic and locoregional treatment approaches for ITM. Methods include a comprehensive review of clinical studies examining the impact of treatments like immune checkpoint inhibitors, targeted therapies, Isolated Limb Perfusion, and electrochemotherapy. The results indicate that combining systemic therapies with locoregional treatments enhances both local disease control and overall survival rates. The introduction of modern immunotherapies has not diminished the effectiveness of locoregional therapies but rather improved patient outcomes when used in conjunction. The conclusions emphasize that a multidisciplinary approach integrating systemic and locoregional therapies offers a promising strategy for optimizing the management of ITM in melanoma patients. This integrated treatment model not only improves survival rates but also enhances the quality of life for patients, suggesting a shift in standard care practices toward more comprehensive therapeutic regimens.

Ocular adnexal lymphoma - a retrospective study and review of the literature.

To review the characteristics of all Slovenian patients with ocular adnexal lymphoma (OAL) in the period of 24 years with the aim of evaluating demographic data, lymphoma location and type, disease stage, treatment modality, local control rate and survival rate. All patients with histologically diagnosed OAL in the main tertiary centre of Slovenia, Eye Hospital, University Medical Centre Ljubljana, who were treated at Institute of Oncology Ljubljana were included in the study. Patients' data were collected from October 1995 through April 2019. Seventy-four patients were included in the study having a median age of 68 years at diagnosis. The majority of lymphomas were of B-cell origin (98.6%). The most frequent type was the extranodal marginal zone B-cell lymphoma (MALT) (71.6%). Orbital lymphomas were diagnosed in 56 cases (75.7%) and conjunctival in 18 cases (24.3%). Ocular manifestation was the first sign of the disease in 78.4% of patients and in 67.6% of patients ocular adnexa were the only disease location. Fifty-one patients (68.9%) were treated with radiotherapy, 7 patients (9.4%) with systemic treatment, 5 patients (6.8%) with combined radiotherapy and systemic treatment and in 11 patients, biopsy and active surveillance strategy was applied (14.9%). Local control of the disease was achieved in 96.6% of treated patients. Median overall survival of the whole study group has not been reached yet. Five-year overall survival rate was 80.1% (95% CI 68.1% - 88.5%) and 5-year lymphoma specific survival rate was 87.2% (95% CI 83.2%-91.2%). OALs comprise a group of heterogeneous diseases with variable outcomes depending predominately on the patient's age and lymphoma type, with low grade lymphomas carrying good prognosis even in elderly patients.

Unveiling molecular clues: Exploring IFNγ, IL-10, and MMP7 blood levels in gastric carcinoma patients

Objective: Gastric carcinoma is a leading cause of morbidity and mortality worldwide. Early detection can help reduce mortality rates. Biomarkers are being investigated globally for their potential in disease screening, monitoring, and follow-up in various cancers. However, currently, there is insufficient data on the role of biomarkers in gastric carcinoma. Material and Methods: This single center case control study was conducted from June 2018 to March 2021 from South India. Blood samples were collected from 85 patients diagnosed with gastric carcinoma and 85 apparently healthy individuals serving as the control group. The samples were collected in a fasting state. The serum levels of biomarkers interferon gamma (IFNγ), interleukin 10 (IL-10), and matrix metalloproteinase 7 (MMP7) were measured using enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Additionally, the levels of biomarkers were compared within the gastric cancer group based on disease location, stage, and histotype. Results: The serum levels of IFNγ and IL-10 were found to be significantly elevated in gastric carcinoma patients compared to the healthy control group. Both biomarkers exhibited high sensitivity and specificity in detecting carcinoma of the stomach. However, there was no significant difference in the serum level of MMP7 between gastric cancer patients and control group. Conclusion: IFNγ and IL-10 show promise as potential molecular biomarkers for the detection of gastric carcinoma. Further, well designed studies, involving larger and more diverse populations matched for stage and histological types, are necessary to establish the screening and monitoring utility of these biomarkers in gastric carcinoma.

Local Anesthetic Systemic Toxicity in Pregnancy: A Retrospective Cohort Analysis.

Introduction Local anesthetic systemic toxicity (LAST) is a rare complication of regional anesthesia. Pregnancy is a risk factor due to gestational physiologic changes. Labor and disorders of pregnancy can mask or delay symptoms of LAST, slowing appropriate intervention. This study examines LAST within a larger cohort and identifies features that help distinguish LAST in pregnant women from LAST in nonpregnant patients. Methods The TriNetX database was used to compare pregnant and nonpregnant patients with LAST from 2013 to 2023. Cohorts were matched on age, race, obesity status, diabetes, metabolic disorders, local anesthetic type, and cardiovascular, liver, kidney, and respiratory disease. Outcomes included prodromal symptoms of LAST and symptoms of cardiac and central nervous system excitation and depression. Results Matching occurred for 276 pregnant and 276 nonpregnant patients. Pregnant cohorts had a significantly higher risk of cardiac depression (risk ratio (RR)=1.96 (95% confidence interval (CI): 1.44-2.66), p<0.01) and significantly lower risk of cardiac excitation (RR=0.38 (95% CI: 0.22-0.63), p<0.01), prodromal symptoms (RR=0.17 (95% CI: 0.09-0.33), p<0.01), central nervous system excitation (RR=0.44 (95% CI: 0.21-0.90), p=0.02), and central nervous system depression (RR=0.24 (95% CI: 0.13-0.48), p<0.01) than nonpregnant cohorts. Conclusion Pregnant patients with LAST were more likely to exhibit cardiac depression and less likely to manifest prodromal symptoms, cardiac excitation, and central nervous system excitation and depression than nonpregnant patients. Physiological changes during pregnancy and prompt detection and treatment may explain these differences. These findings highlight the variable nature of LAST and how pregnancy may influence its clinical presentation.

Racial disparities in thyroid cancer outcomes: A systematic review

IntroductionRacial disparities in surgical outcomes are well described, but a paucity of literature exists examining trends in outcomes of thyroid cancer. We performed a systematic review of studies on thyroid cancer outcomes to better delineate the impact of race. MethodsA comprehensive search strategy was performed in several academic databases for articles on thyroid cancer and surgical outcomes in accordance with PRISMA guidelines. A total of 1771 abstracts were reviewed. Abstracts were screened by two independent reviewers with disagreements resolved by a third. Studies that were based in the United States, included single center, unique data, focused on outcomes of differentiated thyroid cancer, were performed on adults >18 years old, and reported race in their results were included. Chi square statistics with Yates correction were calculated on the compiled data. The protocol was registered on PROSPERO (CRD42022300021). ResultsTwelve studies met inclusion criteria with data on 7,221patients. Among the included studies, our study consists of 67 ​% White patients, 22 ​% Black patients, 7 ​% Hispanic patients, and 3 ​% Asian patients. Extrathyroidal extension was observed in 8.4 ​% (n ​= ​13) of White patients. In comparison to White patients, Black (18.4 ​%, n ​= ​21, p ​= ​0.024) and Hispanic patients (28.3 ​%, n ​= ​30, p ​< ​0.001) had a higher incidence of extrathyroidal extension, while a similar incidence was observed in Asian patients (14.0 ​%, n ​= ​8, p ​= ​0.336). Compared to White patients (22.2 ​%, n ​= ​34), Black (12.4 ​%, n ​= ​13, p ​= ​0.065), Hispanic (16.0 ​%, n ​= ​15, p ​= ​0.301), and Asian (18.4 ​%, n ​= ​9, p ​= ​0.709) patients had a similar incidence of T1a stage. White patients had 10.1 ​% (n ​= ​54) recurrence rates, and Black (13.5 ​%, n ​= ​7, p ​= ​0.595), Hispanic (10.5 ​%, n ​= ​2, p ​= ​1.000), and Asian (11.1 ​%, n ​= ​3, p ​= ​1.000) patients had similar recurrence rates. ConclusionsRace is seldom reported in outcomes on studies of thyroid cancer. From our analysis we conclude that non-White patients may have a higher risk of more advanced local disease at presentation. More data with granular detail on race is necessary to better understand racial disparities in thyroid cancer outcomes and how to alleviate them.

Metastatic pheochromocytoma and paraganglioma: Integrating tumor biology in clinical practice

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors derived from chromaffin cells in the autonomic nervous system. Depending on their location, these tumors are capable of excessive catecholamine production, which may lead to uncontrolled hypertension and other life-threatening complications. They are associated with a significant risk of metastatic disease and are often caused by an inherited germline mutation.Although surgery can cure localized disease and lead to remission, treatments for metastatic PPGL (mPPGL)—including chemotherapy, radiopharmaceutical agents, multikinase inhibitors, and immunotherapy used alone or in combination— aim to control tumor growth and limit organ damage.Substantial advances have been made in understanding hereditary and somatic molecular signaling pathways that play a role in tumor growth and metastasis. Treatment options for metastatic disease are rapidly evolving, and this paper aims to provide a brief overview of the management of mPPGL with a focus on therapy options.

Endoscopic Skipping, Stricturing, and Penetrating Complications in Crohn's Disease on Tandem Ileo-colonoscopy and Cross-sectional Imaging: A Retrospective Cohort Study.

Crohn's disease (CD) is characterized by discontinuous inflammation. Failure to identify skipping lesions of the terminal ileum (TI) or transmural changes can lead to incorrect management. Eligible adult patients with CD undergoing ileo-colonoscopy and computed tomography enterography or magnetic resonance enterography within 6 months. We determined the prevalence of endoscopic skipping (normal ileum on colonoscopy but proximal small bowel inflammation on cross-sectional imaging), skip lesions (discontinuous inflammation along the gastrointestinal tract identified on cross-sectional imaging), structuring, and penetrating complications. Among 202 patients, 45 (22.3%) had endoscopic skipping proximal to TI intubation. Fifty patients (24.5%) had small bowel skip lesions, primarily in the ileum. Strictures were identified in 34 patients (16.8%) through both imaging and ileo-colonoscopy, in 21 patients (10.4%) solely through cross-sectional imaging, and in 3 patients (1.5%) solely through ileo-colonoscopy. Approximately 36.2% of stricturing cases would be missed without cross-sectional imaging. Penetrating complications, including abscesses (2.5%) and various fistula types (4.9%), were detected in 15 (7.4%) patients. Ileo-colonoscopy missed detection of active CD in approximately one-fifth of cases due to more proximal disease location. Stricturing disease might be missed in more than a third of cases if cross-sectional imaging is not performed.

Radiological and pathological predictors of post-operative upstaging of breast ductal carcinoma in situ (DCIS) to invasive ductal carcinoma and lymph-nodes metastasis; a potential algorithm for node surgical de-escalation

Background/aimDuctal carcinoma in situ is considered a local disease with no metastatic potential, thus sentinel lymph node biopsy (SLNB) may be deemed an overtreatment. SLNB should be reserved for patients with invasive cancer, even though the risk of upstaging rises to 25 %. We aimed to identify clinicopathological predictors of post-operative upstaging in invasive carcinoma. MethodsWe retrospectively analyzed patients with a pre-operative diagnosis of DCIS subjected to breast surgery between January 2017 to December 2021, and evaluated at the Breast Unit of PTV (Policlinico Tor Vergata, Rome). ResultsOut of 267 patients diagnosed with DCIS, 33(12.4 %) received a diagnosis upstaging and 9(3.37 %) patients presented with sentinel lymph node (SLN) metastasis. In multivariate analysis, grade 3 tumor (OR 1.9; 95 % CI 1.2–5.6), dense nodule at mammography (OR 1.3; 95 % CI 1.1–2.6) and presence of a solid nodule at ultrasonography (OR 1.5; 95 % CI 1.2–2.6) were independent upstaging predictors. Differently, the independent predictors for SLNB metastasis were: upstaging (OR 2.1.; 95 % CI 1.2–4.6; p = 0.0079) and age between 40 and 60yrs (OR 1.4; 95 % CI 1.4–2.7; p = 0.027).All 9 patients with SLN metastasis received a diagnosis upstaging and were aged between 40 and 60 years old. ConclusionWe identified pre-operative independent predictors of upstaging to invasive ductal carcinoma. The combined use of different predictors in an algorithm for surgical treatments of DCIS could reduce the numbers of unnecessary SLNB.

AAV-mouse DNase I sustains long-term DNase I expression invivo and suppresses breast cancer metastasis.

Neutrophil extracellular traps (NETs) have been implicated in the pathology of various inflammatory conditions. In cancer, NETs have been demonstrated to induce systemic inflammation, impair peripheral vessel and organ function and promote metastasis. Here we show that the plasma level of NETs is significantly higher in patients with metastatic breast cancer compared to those with local disease, or those that were considered cured at a 5-year follow-up, confirming NETs as interesting therapeutic targets in metastatic breast cancer. Administration of DNase I is one strategy to eliminate NETs but long-term treatment requires repeated injections and species-specific versions of the enzyme. To enhance administration and therapeutic efficacy, we have developed an adeno-associated virus (AAV) vector system for delivery of murine DNase I and addressed its potential to counteract cancer-associated pathology in the murine MMTV-PyMT model for metastatic mammary carcinoma. The AAV vector is comprised of capsid KP1 and an expression cassette encoding hyperactive murine DNase I (AAV-mDNase I) under the control of a liver-specific promotor. This AAV-mDNase I vector could support elevated expression and serum activity of murine DNase I over at least 8 months. Neutrophil Gelatinase-Associated Lipocalin (NGAL), a biomarker for kidney hypoperfusion that is upregulated in urine from MMTV-PyMT mice, was suppressed in mice receiving AAV-mDNase I compared to an AAV-null control group. Furthermore, the proportion of mice that developed lung metastasis was reduced in the AAV-mDNase I group. Altogether, our data indicate that AAV-mDNase I has the potential to reduce cancer-associated impairment of renal function and development of metastasis. We conclude that AAV-mDNase I could represent a promising therapeutic strategy in metastatic breast cancer.

The Landmark Series: Multimodal Management of Oligometastatic Sarcoma.

The concept of "oligometastatic" disease suggests the presence of intermediate states between localized disease and widespread metastases, which may be potentially treatable with curative therapeutic strategies. Metastases local therapy (MLT) can be accomplished through various techniques such as stereotactic ablative radiotherapy (SABR), radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, or surgical metastasectomy. The incorporation of MLT in the multidisciplinary treatment of patients with metastatic sarcoma is complex. Retrospective studies support consideration of MLT for selected patients based on factors such as patient condition, disease biology, histologic type, and disease burden. Decisions regarding type and timing of MLT should be made after multidisciplinary discussion including radiation oncologists, surgical and orthopedic oncologists, medical oncologists, and interventional radiology to explore all options before treatment decsions. All MLT techniques have advantages and disadvantages and should be performed in centers specialized in the care of complex oncology patients where various options can be explored concurrently or sequentially for each patient. Future studies evaluating quality of life and patient-reported outcomes are necessary to adequately align patient goals and optimal outcomes. This article reviews the medical scenarios that may benefit the use of MLT, evaluates the distinct advantages and disadvantages associated with these various techniques, and analyzes the findings from pivotal series to provide a comprehensive understanding of its role in clinical practice.