Localized Cancer Research Articles

Quality of Life Outcomes in Breast Cancer Patients Receiving Chemotherapy With or Without Radiation Therapy

PurposeUnderstanding quality of life (QOL) implications of individual components of breast cancer treatment is important as systemic therapies continue to improve oncologic outcomes. We hypothesized that adjuvant radiation therapy does not significantly impact QOL domains in breast cancer patients undergoing chemotherapy. MethodsData was drawn from three prospective studies in women with localized breast cancer being treated with chemotherapy from March 2014 to December 2019. Patient-reported measures were collected at baseline (pretreatment) and post-treatment using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) measure, which consists of 5 subscales. Changes in mean QOL scores in patients who received radiotherapy were compared to those who did not using a one-sided noninferiority method. Statistical significance was determined below 0.05 to meet noninferiority. ResultsIn a sample of 175 patients, 131 were treated with radiation and 44 had no radiation. The sample consisted mostly of stage I-II breast cancer (78%) with hormone receptor positive (59%) disease, receiving either neoadjuvant (36%) or adjuvant chemotherapy (64%). Mean change in QOL for the group treated with radiation compared to no radiation was noninferior with respect to Physical Well-Being (P = .0027), Social/Family Well-Being (P = .0002), Emotional Well-Being (P = .0203), FACIT-Fatigue Subscale (P = .0072), and the Total FACIT-F score (P = .0005); however, mean change in QOL did not meet noninferiority for Functional Well-Being (P = .0594). ConclusionPatient-reported QOL from baseline to post-treatment, using the Total FACIT-F score, was noninferior in patients treated with versus without radiation therapy. This finding, in addition to individualized QOL subscales, provides important information in the informed decision-making process when discussing the effects of locoregional radiation on QOL in localized breast cancer patients treated with chemotherapy.

Renal cancer: signaling pathways and advances in targeted therapies.

Renal cancer is a highlyheterogeneous malignancy characterized by rising global incidence and mortalityrates. The complex interplay and dysregulation of multiple signaling pathways,including von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), Hippo-yes-associated protein (YAP), Wnt/ß-catenin, cyclic adenosine monophosphate (cAMP), and hepatocyte growth factor (HGF)/c-Met, contribute to theinitiation and progression of renal cancer. Although surgical resection is thestandard treatment for localized renal cancer, recurrence and metastasiscontinue to pose significant challenges. Advanced renal cancer is associatedwith a poor prognosis, and current therapies, such as targeted agents andimmunotherapies, have limitations. This review presents a comprehensiveoverview of the molecular mechanisms underlying aberrant signaling pathways inrenal cancer, emphasizing their intricate crosstalk and synergisticinteractions. We discuss recent advancements in targeted therapies, includingtyrosine kinase inhibitors, and immunotherapies, such as checkpoint inhibitors.Moreover, we underscore the importance of multiomics approaches and networkanalysis in elucidating the complex regulatory networks governing renal cancerpathogenesis. By integrating cutting-edge research and clinical insights, this review contributesto the development of innovative diagnostic and therapeutic strategies, whichhave the potential to improve risk stratification, precision medicine, andultimately, patient outcomes in renal cancer.

An exploratory analysis of the impact of area-level exposome on geographic disparities in aggressive prostate cancer

Numbers of aggressive prostate cancer (aPC) cases are rising, but only a few risk factors have been identified. In this study, we introduce a systematic approach to integrate geospatial data into external exposome research using aPC cases from Pennsylvania. We demonstrate the association between several area-level exposome measures across five Social Determinants of Health domains (SDOH) and geographic areas identified as having elevated odds of aPC. Residential locations of Pennsylvania men diagnosed with aPC from 2005 to 2017 were linked to 37 county-/tract-level SDOH exosome measures. Variable reduction processes adopted from neighborhood-wide association study along with Bayesian geoadditive logistic regression were used to identify areas with elevated odds of aPC and exposome factors that significantly attenuated the odds and reduced the size of identified areas. Areas with significantly higher odds of aPC were explained by various SDOH exposome measures, though the extent of the reduction depended on geographic location. Some areas were associated with race (social context), health insurance (access), or tract-level poverty (economics), while others were associated with either county-level water quality or a combination of factors. Area-level exposome measures can guide future patient-level external exposome research and help design targeted interventions to reduce local cancer burden.

Assessing the safety of bladder-preserving therapy as an alternative to surgical intervention in elderly patients with muscle invasive bladder cancer.

There is interest in using bladder-preserving therapy as an alternative definitive therapy for muscle invasive bladder cancer in certain high-risk groups such as the elderly. To determine if bladder-preserving therapy represents a safer alternative to surgical intervention in elderly patients with muscle invasive bladder cancer. We surveyed the Surveillance, Epidemiology and End Results database (SEER) for cases of non-metastasized malignant bladder cancer in patients aged 80+. Survival outcomes with radical cystectomy (RC) with or without chemotherapy were compared to those after chemotherapy and radiation without cystectomy. We performed log-rank tests and Kaplan-Meier and cox regression and hazard analyses before and after propensity score matching. A total of 2995 patients were identified, with 49.98% treated with RC only, 8.65% treated with RC/chemotherapy, and 41.37% treated with chemotherapy and radiation without RC. Median overall survival for the RC only, RC/chemotherapy and chemotherapy/radiation groups were 31.4, 44.1, and 24.6 months, respectively. On multivariate analysis, hazard ratios (reference: RC/chemotherapy group) were RC Only (HR = 1.408 (95% CI 1.188-1.669), p < 0.0001) and chemotherapy/radiation (HR = 1.650 (95% CI 1.390-1.959), p < 0.0001). After matching the chemotherapy/radiation and RC/chemotherapy groups, the former continued to show survival hazard (HR = 1.744 (95% CI 1.414-2.155), p < 0.0001). Octogenarians should be offered definitive local therapy for their localized bladder cancer including RC and chemotherapy. Bladder-sparing alternatives should be reserved for patients unfit for surgery.

The Association of Metformin, Other Antidiabetic Medications, and Statins with the Prognosis of Hepatocellular Carcinoma in Patients with Type 2 Diabetes: A Retrospective Cohort Study.

This study aimed to explore whether the prediagnostic use of metformin and statins is associated with the prognosis of patients with hepatocellular carcinoma (HCC) and type 2 diabetes. We identified 1383 eligible individuals who had both type 2 diabetes and HCC diagnosed between 1998 and 2017 from several Finnish registers. Cox models were fitted for cause-specific and all-cause mortality in relation to the use of antidiabetic medications and statins prior to the HCC diagnosis. Prediagnostic metformin use was associated with decreased overall mortality (hazard ratio 0.84, 95% confidence interval 0.74-0.94) compared with nonuse in patients with type 2 diabetes. Similarly, slightly decreased HCC mortality and other-cause mortality were observed among metformin users. The results were inconclusive regarding metformin use and both overall and HCC mortality among patients with localized HCC. No discernible contrast between statin users and nonusers was found in overall mortality nor HCC mortality in either the whole cohort or patients with localized cancer.

Pathological response and survival outcomes after neoadjuvant chemotherapy with radical cystectomy in octogenarians for muscle-invasive bladder cancer: an observational database study

BackgroundNeoadjuvant chemotherapy (NAC) with radical cystectomy (RC) is the preferred first-line treatment for localized muscle-invasive bladder cancer (MIBC). In recent years, octogenarians have been undergoing RC uneventfully, but studies showed older adults receive NAC less often. We studied the utilization and effect of RC with or without NAC in octogenarians and compared survival outcomes between responders and non-responders.MethodsIn our retrospective study using the National Cancer Database (NCDB), we identified octogenarians with MIBC and urothelial histology who underwent RC with or without NAC between 2004 and 2018. The NAC cohort included patients who underwent RC with NAC, and the non-NAC cohort included those with or without adjuvant chemotherapy. The NAC cohort was subcategorized into responders and non-responders based on surgical pathology. Patients with comorbidity index > 1 were not included, thereby excluding patients with possible renal impairment. After propensity-matching, we compared the overall survival (OS) between NAC and non-NAC cohorts and responders and non-responders.Results33924 patients underwent RC, and 3056 octogenarians met our selection. Among them, 396 received NAC, and 2660 did not receive NAC. Among those who received NAC, 112(28.3%) experienced downstaging, and 223(56.4%) exhibited upstaging or no change (p < 0.001). After propensity-matching, the median OS of the NAC and non-NAC cohorts were 51.6 months and 31.3 months, respectively (p<0.001). Similarly, the median OS of responders and non-responders were 89.4 months and 26.5 months, respectively(p < 0.0001).ConclusionIn our study, we observed that NAC with RC for MIBC may help to improve OS among healthy octogenarians. Similarly, responders had better OS than non-responders.

Chitosan/Hyaluronate Complex-Coated Electrospun Poly(3-hydroxybutyrate) Materials Containing Extracts from Melissa officinalis and/or Hypericum perforatum with Various Biological Activities: Antioxidant, Antibacterial and In Vitro Anticancer Effects.

The present study aimed to fabricate innovative fibrous materials with various biological activities from poly(3-hydroxybutyrate), sodium hyaluronate (HA), chitosan (Ch), Melissa officinalis (MO), Hypericum perforatum (HP) extract, or a combination of both extracts. Electrospinning or electrospinning followed by dip coating and the subsequent formation of a polyelectrolyte complex were the methods used to prepare these materials. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) were applied for investigating the morphology of materials, their thermal characteristics, and their surface chemical composition. The composition and design of the mats had an influence on the in vitro release behavior of the main bioactive compounds present in the MO and HP extracts incorporated in the materials. It was found that as-created materials comprising a combination of both extracts and a Ch/HA complex exerted higher antioxidant activity than that of (non-)coated MO-containing mats and Ch/HA-coated mats containing HP. The novel materials manifested antibacterial efficacy towards the pathogenic bacteria S. aureus and E. coli, as evidenced by the performed microbiological screening. Furthermore, the mats possessed a great growth inhibitory effect on HeLa cancer cells but had a less pronounced effect on the growth of normal mouse BALB/3T3 fibroblasts. The loading of both extracts in the mats and the formation of coating led to the enhancement of the in vitro anticancer and antibacterial activities of the materials. Thus, the novel materials have potential for use in local cancer therapy as well as for use as wound dressings.

Survival among 148 patients with an incidentally detected appendiceal tumours at surgery for acute appendicitis: a population-based cohort follow-up study.

To investigate the long-term prognosis of appendiceal tumours incidentally detected at appendicectomy for suspicion of benign appendicitis. A retrospective register-based single centre cohort study was carried out, using data from the local acute appendicectomy quality register of cases operated on at the Department of Surgery, South General Hospital, Stockholm, Sweden. The local colorectal cancer register was also used to identify appendix tumours. The study period was between January 2004 and January 2023. Survival was calculated according to the Kaplan-Meier method. A total of 11,888 patients were registered in the acute acute appendicectomy register, 54% males and 46% females, median age 32 (Q1 = 21, Q3 = 47) (with 33.7% were 41 years or older). From the appendicectomy and colorectal registers 148 (1.2% of the total cohort) appendiceal tumours were found; 60% in females and 40% in males, median age 56 (Q1 = 43, Q3 = 70) (with 78.4% being 41 years or older). Tumours found were: Low grade Appendiceal Mucinous Neoplasms (LAMN, N = 64); Neuroendocrine Tumours (NET N = 24); adenocarcinomas or other form of carcinomas (N = 57); and adenomas (N = 3). The overall 5-year survival in patients operated for LAMN was 96.8%, for NET 93.3% and for adenocarcinoma 69.7%. The overall 5-year survival for all tumour patients was 85.7%. For the younger patients (< 51 years) with LAMN and NET, almost all survived to the end of follow-up. Survival of patients in the carcinoma group was statistically significantly lower than for the LAMN and NET groups, especially in females 51 years or older. In the group of tumour patients undergoing surgery (n = 146), primary surgery was laparoscopic in 47% and open in 52%. Two patients did not undergo surgery due to widespread disease. In 64% of cases operation was acute, whereas it was delayed and/or planned in 34%. Most procedures were laparoscopic appendicectomy 36%, followed by open appendicectomy 30%, right-sided hemicolectomy 14.6% (open 11.6% and laparoscopic 3%, acute operation 5.5%), ileocaecal resection 5% (acute operation 3.4%), and staging laparoscopy 7%. In 38% of the operated patients the tumour was discovered incidentally at histopathology examination. Two patients had CRS and HIPEC as the initial operation. Forthy-three per cent of the 146 tumour patients operated underwent a second procedure: CRS and HIPEC in 23.3% and right-sided hemicolectomy in 13.6% (laparoscopic 8.2% open 5.4%). Survival was high for patients with incidentally detected appendiceal LAMN or NET, but not so for carcinoma. Survival was lower in the carcinoma group older than 50 years, especially those sick and females.

Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: A study protocol of a randomized phase II/III trial (STELLAR II study).

For patients with locally advanced rectal cancer, previous STELLAR studies have shown that a new adjuvant treatment paradigm of short-course radiotherapy followed by neoadjuvant chemotherapy can achieve pathological complete response rates superior to those of standard care; however, the 3-year DFS is inferior to neoadjuvant concurrent radiotherapy. Recent studies have shown that immune checkpoint inhibitors may improve the prognosis of rectal cancer and have good synergy with radiotherapy. Therefore, neoadjuvant chemotherapy combined with immune checkpoint inhibitors after a short course of radiotherapy has the potential to further improve complete response rates and prognosis. The STELLAR II study is a multicentre, open label, two-arm randomized, phase II/III trial of short-course radiotherapy followed by neoadjuvant chemotherapy concurrent with immunotherapy for locally advanced rectal cancer. A total of 588 patients with locally advanced rectal cancer (LARC) will be randomly assigned to the experimental and control groups. The experimental group will receive short-course radiotherapy and neoadjuvant chemotherapy in combination with sindilizumab, while the control group will receive short-course radiotherapy and neoadjuvant chemotherapy. Both groups will subsequently receive either total rectal mesenteric resection or a watch & wait (W&W) strategy. The phase II primary endpoint is the complete remission rate, and the secondary endpoints include grade 3-4 adverse events, perioperative complications, R0 resection rate, overall survival, local recurrence rate, distant metastasis rate and quality of life score. A seamless phase II/III randomized controlled design will be used to investigate the effectiveness and safety of the TNT strategy with the addition of immunotherapy. The trial opened, and the first patient was recruited on 31 August 2022. Trial registration number and date of registration: ClinicalTrials.gov NCT05484024, 29 July 2022. The STELLAR II trial will prospectively evaluate the efficacy of TNT treatment strategies that incorporate immune checkpoint inhibitors. The trial will yield important information to guide routine management of patients with local advanced rectal cancer.

Questionnaire survey on cervical cancer screening and HPV awareness among patients at a local cancer center in Japan

BackgroundThe incidence of cervical intraepithelial neoplasia is increasing in Japan. Although human papillomavirus (HPV) vaccination and cancer screening are crucial in preventing cancer-related mortality, the cervical cancer screening rate in Japan was only approximately 43.6% in 2022. This study aimed to conduct an epidemiological analysis of cervical cancer by collecting data from individual patients.MethodsA questionnaire survey was administered to patients who visited our hospital between January 2017 and July 2023 owing to abnormal cervical cytological findings or a cancer diagnosis. Patients answered questions regarding their history of cervical cancer screening as well as their knowledge of HPV and cervical cancer.ResultsDuring the study period, 471 patients participated in the survey, with 35 declining to participate. Patients with Stage 1b1–4b primarily sought medical attention due to self-reported symptoms (P < 0.001); however, they were less likely to have undergone cervical cancer screening (P < 0.001). Additionally, older patients were less likely to be aware of the association of HPV with cervical and other cancers. Notably, 28 of the 129 patients with stage 1b1–4b cancer underwent cervical cancer screening within 2 years. The tumor location within the endocervical canal emerged as a significant factor contributing to the difficulty for an accurate diagnosis of precancerous or cervical cancer during cervical screening. Furthermore, non- squamous cell carcinoma (SCC) histology was another possible factor.ConclusionsOur findings suggest the need to widely disseminate information regarding the significance of cancer screening to increase cancer screening rates. Moreover, establishing strategies for improving the accuracy of detecting lesions during screening for non-SCC and endocervical canal tumors is crucial.

Introducing Neoadjuvant Immunotherapy for Colorectal Cancer: Advancing the Frontier.

To give surgeons a review of the current and future use of neoadjuvant immunotherapy in patients with localized colorectal cancer. Immunotherapy has revolutionized the standard of care in oncology and improved survival outcomes in several cancers. However, the applicability of immunotherapy is still an ongoing challenge. Some cancer types are less responsive to immunotherapy, and the heterogeneity in responses within cancer types is poorly understood. Clinical characteristics of the patient, the timing of immunotherapy in relation to surgery, diversities in the immune responses, clonal heterogeneity, different features of the tumor microenvironment, and genetic alterations are some factors among many that may influence the efficacy of immunotherapy. In this narrative review, we describe the major types of immunotherapy used to treat localized colorectal cancer. Furthermore, we discuss the prediction of response to immunotherapy in relation to biomarkers and radiological assessment. Finally, we consider the future perspectives of clinical implications and response patterns, as well as the potential and challenges of neoadjuvant immunotherapy in localized colorectal cancer. Establishing mismatch repair status at the time of diagnosis is central to the potential use of neoadjuvant immunotherapy, in particular immune checkpoint inhibitors, in localized colorectal cancer. To date, efficacy is primarily seen in patients with deficient mismatch repair status and POLE mutations, although a small group of patients with proficient mismatch repair does respond. In conclusion, neoadjuvant immunotherapy shows promising complete response rates, which may open a future avenue of an organ-sparing watch-and-wait approach for a group of patients.

Characterization and optimization of colon specific nanosponges immobilized polymeric microbeads formulation for the combined delivery of 5-fluorouracil and curcumin

Introductionand purpose: Site-specific delivery systems are highly advantageous for local cancer treatment as they allow a more significant delivery of the drug to the tumor with minimal systemic side effects. Furthermore, combination therapy is a promising approach that attracts more attention in cancer treatment due to its synergistic effects. In this work, nanosponges immobilized polymeric microbeads for colon-specific delivery systems were developed for a drug combination of 5-fluorouracil and curcumin to treat colorectal cancer. MethodsSodium alginate and low molecular chitosan polymers were used to create microbead-based formulations containing curcumin-encapsulated nanosponges and 5-fluorouracil. To improve curcumin's low solubility, Diphynylacarbonate (DPC) hyper cross-linking of β-CD was used to create curcumin-loaded β-CD nanosponges that further incorporated in the polymeric microbeads along with free 5-fluorouracil. ResultsThe optimized microbeads were spherical with a mean particle size of 1.1 ± 0.05 mm. The produced beads were subsequently coated with a multilayer coating of ethyl cellulose and Eudragit S100 polymers, which functioned as pH-dependent and time-dependent coatings to ensure drug delivery to the colon. The developed formulation (Coated MB5) showed controlled release of the drug and sustained cytotoxic effect. The release profiles of 5-fluorouracil and curcumin from Coated MB5 were best described by zero-order followed by first-order release functions. About 66.4 % of 5-FU and 73.1 % of curcumin were released for 24 h. In vivo roentgenographic evaluation in a rabbit model indicated that the optimized coated microbeads successfully reached the colon 7–9 h after administration. ConclusionsAs a prospective colon-specific drug delivery system, a successful formulation (Coated MB5) was developed for the combined delivery of 5-fluorouracil and curcumin. More in vivo studies are needed to demonstrate the therapeutic efficacy of optimized formulations and their potential to improve colorectal cancer therapy by providing a more targeted administration of combination medicines with fewer undesirable side effects.

Recent Advances of Neoadjuvant Immunotherapy for Urothelial Bladder Cancer.

Urothelial bladder cancer is one of the most common malignant tumors of the urinary system, which accounts for 90~95% of urothelial carcinoma. Despite the current standard neoadjuvant management for localized urothelial MIBC (T2-4cN0M0) is cisplatin-based chemotherapy before radical cystectomy, there still had poor performances and less overall survival benefits in patients with localized urothelial MIBC. Moreover, nearly half of MIBC patients were ineligible for receiving cisplatin because of chronic kidney disease and performance status. Although immunotherapy, immune checkpoint inhibitors (ICIs) has been identified as first or second-line treatments for localized and metastasis bladder cancer based on less adverse reactions and favorable outcomes, neoadjuvant immunotherapy had rarely used for the treatment of these patients because of less large-scale clinical randomized studies and limited outcomes. Therefore, we reviewed the advances of efficacy and safety with neoadjuvant immunotherapy for urothelial bladder cancer depended on published articles and clinical studies, which could provide more theoretical evidences and promising strategy for clinical therapeutic development.

Feasibility of weekly cisplatin and radiotherapy for localized anal cancer – A Danish anal cancer group report

BackgroundChemoradiotherapy (CRT) with flourouracil and mitomycin is the standard treatment for squamous cell carcinomas of the anus (SCCA), however the associated acute toxicity often hinders compliance. Although weekly cisplatin is a well-established treatment for other squamous cell carcinomas, it has not been explored in SCCA. PurposeTo investigate if radiotherapy (RT) with weekly cisplatin is a feasible option for SCCA and to report the acute toxicity. Material/methodsPatients were treated with RT and weekly cisplatin 40 mg/m2 between 1998–2020. Retrospective data from medical records (n=65) and prospectively collected data from an observational study (n=51) comprising physician assessed toxicity (NCI-CTCAE 4.0), patient-reported outcomes (EORTC-QlQC30 + CR29) baseline, mid-therapy, end of treatment and 2–4 weeks post-treatment were included. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. ResultsWe included 116 patients. T-stages were T1:4%, T2: 71%, T3: 17%, T4: 8% and 47% has N+ disease. RT doses were 53.75–64 Gy/45–51.2 Gy and the mean cumulative dose of cisplatin was 307.5 mg. The median overall treatment time was 43 days. Within 6 months after CRT 88.9 % had complete response. The median follow-up time was 4.5 years and 5-year DFS and OS were 77% (95%CI 68.7;84.5%) and 86.4% (95%CI 78.3;91.7%), respectively. Hospitalization occured in 20% with 2.6% being admitted due to febrile neutropenia. Hematological toxicity was low with 13.7% grade 3 and 3.9% grade 4. Anal pain, skin, gastrointestinal and urogenital toxicity were mild. ConclusionRT and weekly cisplatin for SCCA showed good outcome results and an acceptable acute toxicity profile.

Electrospun amygdalin and Inula helenium extract-loaded polylactic acid (PLA)/Polyvinylpyrrolidone (PVP) nanofibrous patches for colon cancer treatment: Fabrication, characterization and antitumour effect results

In this study, 75PLA/25PVP nanofibrous loaded with amygdalin (AMG) and Inula helenium (I.H) extract were produced by electrospinning method in order to prevent local colon cancer recurrence, and the effect of the produced nanofibrous on the HCT-116 cell line was examined in vitro. When the scanning electron microscopy (SEM) images were examined, the fiber diameter of the 75PLA/25PVP group was measured as 443.74 ± 79 nm, but the addition of I.H and AMG caused a thickening effect on the fiber diameters. Drug release results show the controlled release period of 75PLA/25PVP/I.H and 75PLA/25PVP/AMG loaded nanofibrous patches within 180 h. Slowly degrading nanofibrous remained durable for up to 25 days. When the in vitro cytotoxicity results were analyzed, all nanofibrous were found to be effective in inducing cytotoxicity against HCT-116 colon cancer cells. The most effective group is the group in which I.H extract and AMG drug are loaded onto the nanofibrous together. AMG drug and I.H plant extract showed effects on the colon cancer cell line in in vitro experiments. Considering all the results I.H and AMG loaded nanofibrous can be implanted into solid tumor cells in order to reduce the risk of local recurrence of cancer after surgery in colon cancer.

Incidence of Pancreatic Leakage in Isolated Biliary Limb Roux-en-Y Reconstruction in Whipple Procedure

Abstract Background Whipple is currently the procedure of choice in the treatment of localized pancreatic cancer. Isolated Roux-en-Y loop pancreaticojejunostomy was proposed as a method of reconstruction following pancreaticoduodenectomy. The idea is to isolate the bile from pancreatic secretions to minimize pancreatic enzyme activation and ultimately pancreatic fistula formation. It was also proposed that if a pancreatic fistula develops, it will be a pure fistula and thereby more benign as opposed to a mixed pancreatic fistula containing bile. Objective To estimate the incidence of pancreatic fistula in patients undergoing isolated Roux-en- Y hepaticojejunostomy reconstruction following pancreaticoduodenectomy. Patients and Methods In this prospective observational study, our aim is to calculate the incidence of post-operative pancreatic fistula in 20 patients that underwent Roux-en-Y isolated biliary limb reconstruction following pancreaticoduodenectomy for the treatment of pancreatic cancer. The study includes patients that underwent this procedure at Ain Shams University Hospitals in the period between January 2021 and July 2022 with a post-operative follow up period of 3 weeks. Patients were diagnosed with pancreatic cancer using MRI or CT scans with some of them also undergoing endoscopic US with biopsy. They were then admitted to one of the two main Ain Shams University Hospitals for pre-operative preparation. Results Our study did no estimate post-operative complications such as delayed gastric emptying and wound infection. Pancreaticoduodenectomy is a major surgery that carries a significant burden in terms of morbidity and mortality. Post-operative pancreatic fistula can be fatal as it can lead to vascular pseudoaneurysms that may fatally rupture. The idea behind using isolated biliary limb roux-en-y reconstruction is to alleviate the morbidity caused by post-operative pancreatic fistula. Conclusion Further comparative studies with a higher number of patients are recommended to assess and compare the value of isolated biliary limb reconstruction when compared to conventional reconstruction.

Evolving Management of Breast Cancer in the Era of Predictive Biomarkers and Precision Medicine.

Breast cancer is the most common cancer among women in the world as well as in the United States. Molecular and histological differentiation have helped clinicians optimize treatments with various therapeutics, including hormonal therapy, chemotherapy, immunotherapy, and radiation therapy. Recently, immunotherapy has become the standard of care in locally advanced triple-negative breast cancer and an option across molecular subtypes for tumors with a high tumor mutation burden. Despite the advancements in personalized medicine directing the management of localized and advanced breast cancers, the emergence of resistance to these therapies is the leading cause of death among breast cancer patients. Therefore, there is a critical need to identify and validate predictive biomarkers to direct treatment selection, identify potential responders, and detect emerging resistance to standard therapies. Areas of active scientific and clinical research include novel personalized and predictive biomarkers incorporating tumor microenvironment, tumor immune profiling, molecular characterization, and histopathological differentiation to predict response and the potential emergence of resistance.

1211 Patterns of Recurrences After Mastectomy for Invasive Breast Cancer and DCIS Followed by Immediate Breast Reconstruction: 13-Year Follow-Up from a Single institution

Abstract Aim A retrospective review was conducted at a single centre to analyse the patterns of recurrence in IBR. Method Between January 2009 and December 2021, 347 patients who had IBR for either invasive (244) or DCIS (125), were analysed retrospectively. The study included patients who received implants without ADM (10.8%), ADM with +implant (69%), Latissimus Dorsi flap +/- implant (18.1%), and deep inferior epigastric perforator-free flaps (2.5%). Results During the study period, 29 patients developed recurrence over a median period of 74 months (ranging from 24 to 125 months). Two patients had local cancer recurrence only (0.5%), 5 patients had local recurrence associated with distant or regional metastasis, (1.4%) and 19 cases with distal metastasis were identified (8.3%). The study found an overall survival rate of 96.4% and a disease-free survival rate of 91.7%. The most familiar sites of recurrence in breast cancer are distal recurrence, (Bone being the most common site), followed by local recurrence. Discussion This rate is in line with the expected range, assuming a standard of recurrence of 1% per year. Nevertheless, it is crucial to acknowledge the possibility of selection bias, as patients with advanced diseases and significant comorbidities may not have been offered IBR. Conclusions Based on the findings of the study, it can be inferred that mastectomy with (IBR) is a safe option for mastectomy.

Circulating Lipid Profiles Associated With Resistance to Androgen Deprivation Therapy in Localized Prostate Cancer.

Intense androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPIs) before radical prostatectomy (RP) produced favorable pathologic responses in approximately 20% of patients. The molecular reason for the low rate of response remains unclear. Lipid metabolism is known to influence androgen receptor signaling and ARPI efficacy. The aim of the study was to identify circulating lipid profiles associated with ADT/ARPI resistance in localized prostate cancer. Two independent experimental approaches were used. Experiment 1: Post hoc analysis of the association between plasma lipidomic profiles and ADT/ARPI response was performed on patients (n = 104) from two phase II trials of neoadjuvant ADT/ARPI. Response to ADT/ARPI was defined by pathologic response. Experiment 2: Patient-derived tumor explants from RP (n = 105) were cultured in enzalutamide for 48 hours. Explant response to enzalutamide was evaluated against pre-RP plasma lipidomic profiles (n = 105) and prostate tissue lipidomic profiles (n = 36). Response was defined by Ki67 (cell proliferation marker) fold difference between enzalutamide and vehicle-treated explants. In both experiments, associations between lipid profiles and ADT/ARPI response were analyzed by latent class analysis. Pretreatment plasma lipid profiles classified each experimental cohort into two groups with differences in ADT/ARPI response rates. The response rates of the groups were 9.6% versus 29% in experiment 1 (chi-squared test P = .012) and 49% versus 70% in experiment 2 (chi-squared test P = .037). In both experiments, the group with a higher incidence of ADT/ARPI resistance had higher plasma levels of sphingomyelin, glycosylceramides, free fatty acids, acylcarnitines, cholesterol esters, and alkyl/alkenyl-phosphatidylcholine and lower plasma levels of triacylglycerols, diacylglycerols, and phosphoethanolamine (t-test P < .05). Pretreatment circulating lipid profiles are associated with ADT/ARPI resistance in localized cancer in both human cohorts and explant models.

Cancer of the Larynx-20-Year Comparative Survival and Mortality Analysis by Age, Sex, Race, Stage, Grade, Cohort Entry Time-Period, Disease Duration and ICD-O-3 Topographic Primary Sites-Codes C32.0-9: A Systematic Review of 43,103 Cases for Diagnosis Years 1975-2017: (NCI SEER*Stat 8.3.9).

.-Laryngeal malignancy, "voice box" cancer, is uncommon with 12,620 estimated new cases and 3770 deaths in the United States in 2021,1 and represents only 6.2% of all respiratory system malignancies. The most significant risk factors are alcohol and tobacco consumption. Almost all cases (98%) of laryngeal cancer arise in the squamous epithelium, and in this analysis more than 75% are of well-or-moderately differentiated histopathology (Grades I&II). Local stage cancer (SEER Historic Staging) was more common than regional and distant stages combined (55.3% vs 44.7%). Tumors may arise above, below or at the level of the vocal folds and are described as supraglottic (encompassing the epiglottis, false vocal cords, ventricles, aryepiglottic fold and arytenoids), the glottis (encompassing the true vocal cords and the anterior and posterior commissures), and the subglottic region. In the National Cancer Institute's Surveillance, Epidemiology, End-Results (NCI-SEER) Data Research, 9 Registries, Nov 2019 Sub (1975-2017),2 laryngeal cancer occurred more commonly in men than in women, 80.7% vs 19.3%, respectively with a 4.2 to 1 ratio. Additionally, there are racial disparities with African Americans presenting at a younger age and having a higher incidence and mortality than Caucasians. In the 1975-2017 period, overall median patient age was 64.4 years with White Americans-64.8 years and Black Americans-61.5 years. Unfortunately, the 5-year relative survival rate has declined 4%, and excess death rate has risen 13% since 1975 with overall incidence declining.As a consequence, observed median survival is approximately 6.5-years for the total study-period pinpointing the need for further specialty research. This study follows the World Health Organization International Classification of Diseases for Oncology-3rd Edition (ICD-O-3)3 topographical identification, coding, labeling and listing of 43,103 patient-cases accessible for analysis in the United States National Cancer Institute's Surveillance, Epidemiology and End Results program (NCI SEER Research Data, 9 Registries, 1975-2017). These are located in 6 primary anatomical sites: C32.0-Glottis, C32.1-Supraglottis, C32.2-Subglottis, C32.3-Laryngeal cartilage, C32.8-Overlapping lesion of larynx, C32.9-Larynx, NOS. .-To update short- and long-term mortality and survival indices, and identify changing risk patterns for laryngeal cancer patients in a retrospective US population-based analysis, 1975-2017, using prognostic data stratified by ICD-O-3 Primary Site, age, sex, race, stage, histologic grade, two cohort entry time-periods (1975-1996 to 1997-2017), and disease duration to 20-years. .-SEER*Stat v8.3.94 software (built March 12, 2021) was used to access SEER Research Data, 9 Registries, Nov. 2019 submission (1975-2017). For displaying risk, general methods and standard double decrement life table methodologies for converting and displaying ICD-O-3 coded laryngeal cancer primary site annual data to aggregate average annual mortality and survival units in durational-intervals of 0-1, 1-2, 2-5, 0-5, 5-10, 10-15, and 15-20 years were employed. The reader is referred to the "Registrar Staging Assistant (SEER*RSA)" for local-regional-distant Extent of Disease (EOD) sources used in the development of staging descriptions, and Summary Stage 2018 Coding Manual v2.0 released September 1, 2020. Cancer staging & grading procedural explanations, statistical significance and 95% confidence levels5 are described in previous Journal of Insurance Medicine articles6,7 and other publications.8,9 Poisson confidence intervals at the 95% level based on the number of observed deaths are used in this study but not displayed here to conserve space on the mortality tables. Excluded were all death certificate only and those alive with no survival time. .-Total SEER annual age-adjusted incidence rates from 1980 to 2017 have diminished from 5.25 patient-cases/100,000/year to 2.59/100,000 per year, and in the same period annual age-adjusted US death rates declined from 1.61 deaths/100.000/year to 0.91 deaths/100,000/year (Ref. 10, CSR Tables 12.5-6), However, in the 0-5-year disease durational interval for all staged cases in both cohort time-periods (Table 5), excess death rates (EDR) rose from 80 per 1000 persons per year in the 1975-96 cohort, to 89 per 1000 persons per year in the 1997-17 cohort, (a 10% rise in excess mortality in 42 years). Further, in the 5-10-year disease durational interval, EDR rose from 39 per 1000 persons per year to 45 per 1000 persons per year with corresponding cohort declines in cumulative survival ratios (SR), and overall declines in median observed and relative survival times in the later cohort (not shown). The epidemiologic burden of malignancy is >4-fold higher in males and increases in parallel with aging, peaking after 65 years. The most significant risk factors for laryngeal cancer are tobacco and alcohol consumption. .-Although annual incidence and mortality rates from 1980 to 2017 have diminished, there is no concomitant improvement in larynx cancer survival (SR) and mortality (EDR) indices, with rising mortality and diminishing survival in all staged cases at 5-years disease duration between the 1975-96 and 1997-2017 analytic cohorts. Larynx cancer remains a burdensome clinical, social, and public health challenge.