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BACKGROUND: Patients with locally advanced or metastatic colorectal cancer (CRC) display heterogeneous responses to standard-of-care therapy. Robust preclinical models of malignancy in the form of patient-derived tumor organoids (PDTOs) have recently come to the fore in tailoring patient care to a personalized medicine level. This study aimed to review the literature systematically regarding PTDOs and gauge their impact on precision medicine in the management of CRC. METHODS: A PRISMA-compliant systematic review of the MEDLINE, EMBASE, Web of Science, and Cochrane Library databases was performed. The results were categorized based on the primary objective of the individual studies as follows: organoid use in predicting effective hyperthermic intraperitoneal chemotherapy (HIPEC), systemic chemotherapy in CRC, or neoadjuvant chemoradiotherapy in rectal cancer. RESULTS: The literature search found 200 publications, 16 of which met the inclusion criteria. Organoid models of primary and metastatic CRC have been increasingly used to assess clinical responses to standard therapy. Marked heterogeneity exists, matching the responses observed in clinical practice with ex vivo drug and radiation screening. Repeated correlation between organoid and patient sensitivity to forms of HIPEC, systemic chemotherapy, and chemoradiotherapy has been observed. CONCLUSION: Patient-derived tumor organoids are the latest tool in predictive translational research. Current organoid-based studies in precision medicine have shown their great potential for predicting the clinical response of patients to CRC therapy. Larger-scale, prospective data are required to fully support this exciting avenue in cancer care.
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Neoplasias do Colo , Neoplasias Retais , Humanos , Organoides , Medicina de Precisão , Estudos ProspectivosRESUMO
Penile squamous cell carcinoma (SCC) is a rare and aggressive urological malignancy. Advanced penile SCC requires multimodal management, including surgery and systemic therapy. Given its rarity, there have been few substantial advances in our understanding of the molecular and genomic drivers of penile SCC, especially for patients with relapsed or advanced disease. In this review, we discuss the molecular and genomic landscape of penile SCC, clinical trials in progress and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a platform for investigation and validation of new molecular pathways for testing of therapeutics.
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Neoplasias Penianas/etiologia , Neoplasias Penianas/terapia , Animais , Biomarcadores Tumorais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/terapia , Tomada de Decisão Clínica , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Humanos , Masculino , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Neoplasias Penianas/diagnóstico , TranscriptomaRESUMO
Spigelian hernias are an uncommon type of primary ventral hernia and are defined as a defect in the Spigelian aponeurosis (fascia). Herein, we present an uncommon case of Spigelian hernia to highlight the potential complications of these hernias and the need for surgical management. This is a case report of an 86-year-old gentleman presenting post-fall with an acute rib fracture and an incidental Spigelian hernia seen on a CT trauma pan scan. The Spigelian hernia surgical treatment was planned for elective management due to the anesthetic risks associated with an elderly patient and acute rib fractures. Ultimately, the patient developed a large bowel obstruction secondary to the Spigelian hernia and required emergency operative management to relieve the obstruction. The patient had an uncomplicated recovery following his emergency surgery. This case report highlights the importance of assessing anesthetic risks versus surgical risks when it comes to surgical planning. Clinicians should recognize occult hernias and continue ongoing clinical reviews with a high index of suspicion, as symptoms of Spigelian hernia obstruction might be non-specific.
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BACKGROUND: The development of peritoneal metastases (PM) in patients with colorectal cancer (CRC) connotates a poor prognosis. Circulating tumour (ctDNA) is a promising tumour biomarker in the management CRC. This systematic review aimed to summarize the role of ctDNA in patients with CRC and PM. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a systematic review of the literature until June 2022 was performed. Studies reporting on the utility of ctDNA in colorectal PM were included. A total of eight eligible studies were identified including a total of 167 patients. RESULTS: The findings from this review suggest an evolving role for ctDNA in CRC with PM. ctDNA can be isolated from both plasma and peritoneal fluid, with peritoneal fluid preferred as the liquid biopsy of choice with higher mutation detection rates. Concordance rates between tissue and plasma/peritoneal ctDNA mutation detection can vary, but is generally high. ctDNA has a potential role in monitoring anti-EGFR treatment response and resistance, as well as in predicting future prognosis and recurrence. The detection of ctDNA in plasma of patients with isolated PM is also possibly suggestive of occult systemic disease, and patients exhibiting such ctDNA positivity may benefit from systemic treatment. Limitations to ctDNA mutation detection may include the size of peritoneal lesions, as well as the fact that PM poorly shed ctDNA. CONCLUSION: While these findings are promising, further large-scale studies are needed to better evaluate the utility of ctDNA in this subset of patients.
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Neoplasias Colorretais , Doenças Peritoneais , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/secundário , Prognóstico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , MutaçãoRESUMO
IntroductionAnastomotic leak (AL) is a serious complication following colorectal surgery. This study aimed to identify factors associated with the development of AL and analyze its impact on survival.Materials and MethodsAll consecutive adult colorectal cancer resections with curative intent and anastomosis formation were included from a prospectively maintained bi-national database between 2007 and 2020. The primary outcome measure was the rate of AL. The secondary outcome measure was 5-year overall survival (OS).ResultsThere were 7566 eligible patients. The rate of AL was 2.3% and 4.4% in patients with colon and rectal cancer respectively. AL was a significant independent predictor of reduced 5-year OS in patients who underwent curative surgery for rectal cancer (Odds ratio 1.999, p = 0.017). Emergency surgery (p = 0.013), surgery at a public hospital (p < 0.01), and an open surgical approach (p = 0.002) were all significantly associated with a higher risk of AL in patients with colon cancer, with higher rates of AL noted in left colectomies as compared to right hemicolectomies (6.8% vs 1.6%, p < 0.05). In rectal cancer patients, ultra-low anterior resections had the highest risk of AL (4.6%), and associations were found with neoadjuvant chemotherapy (p = 0.011), surgery in a public hospital (p = 0.019), and an open approach (p = 0.035). Anastomosis formation technique (hand-sewn vs stapled) did not impact on rate of AL.DiscussionClinicians should be cognizant of the predictive factors for AL and consider early intervention for patients at risk of this.
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Cirurgia Colorretal , Neoplasias Retais , Adulto , Humanos , Fístula Anastomótica/etiologia , Fatores de Risco , Colo/cirurgia , Anastomose Cirúrgica/métodos , Neoplasias Retais/cirurgia , Estudos RetrospectivosRESUMO
<br><b>Introduction:</b> Anastomotic leak (AL) is a serious complication following colorectal surgery.</br> <br><b>Aim:</b> The aim of this study was to identify factors associated with the development of AL and to analyze its impact on survival.</br> <br><b>Materials and methods:</b> All consecutive adult colorectal cancer resections performed between 2007 and 2020 with curative intent and anastomosis formation were included from a prospectively maintained database. The primary outcome measure was the rate of AL. The secondary outcome measure was 5-year overall survival (OS).</br> <br><b>Results:</b> There were 6837 eligible patients. The rate of AL was 2.2% and 4.0% in patients with colon and rectal cancer, respectively. AL was a significant independent predictor of reduced 5-year OS in patients who underwent curative surgery for rectal cancer (odds ratio 2.293, p = 0.009). Emergency surgery (p = 0.015), surgery at a public hospital (p = 0.002), and an open surgical approach (p = 0.021) were all associated with a significantly higher risk of AL in patients with colon cancer, with higher rates of AL noted in left colectomies as compared to right hemicolectomies (4.4% <i>vs.</i> 1.3%, p < 0.001). In rectal cancer patients, AL was associated with neoadjuvant chemoradiotherapy (p = 0.038) and male gender (p = 0.002). The anastomosis formation technique (hand-sewn <i>vs.</i> stapled) did not impact the rate of AL (p = 0.116 and p = 0.198 with colon and rectal cancer, respectively).</br> <br><b>Discussion:</b> Clinicians should be cognizant of the predictive factors for AL and should consider early intervention for at-risk patients.</br>.
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BACKGROUND: To analyze the long-term outcomes and prognostic value of hematological parameters in anal cancer patients receiving intensity-modulated radiation therapy (IMRT). MATERIALS: Hospital records of consecutive patients with anal squamous cell carcinoma who received curative-intent IMRT according to a standardized contouring protocol between 2010 and 2020 were reviewed. Locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Coverage of locoregional recurrences by the initial IMRT volumes were assessed. The prognostic value of pretreatment blood counts for PFS and OS were determined using Cox regression analysis. RESULTS: A total of 166 patients were analyzed with a median follow-up of 3.3 years. Forty-six percent and 54% of patients had Stage I-II and IIIA-B cancers, respectively. The 5-year LRFS, DMFS, PFS and OS were 81%, 89%, 65% and 76% respectively. Grade ≥ 3 toxicity occurred in 5% of patients. Of all patients who relapsed, 70% had only locoregional recurrence as first site of failure. Ninety percent of locoregional recurrences were in-field. Hemoglobin, neutrophil and platelet counts were associated with PFS on univariable analysis, but only cancer stage and p16 status remained prognostic on multivariable analysis. Patients with more advanced cancer stages also had higher baseline neutrophil counts. Performance status and neutrophil counts were prognostic for OS on multivariable analysis. CONCLUSION: This study affirms the long-term efficacy and safety of IMRT. Treatment resistance, rather than radiation geographic miss, is a major issue underpinning locoregional recurrences. Pretreatment blood counts were not validated to be independently prognostic for disease recurrence.
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Neoplasias do Ânus , Radioterapia de Intensidade Modulada , Neoplasias do Ânus/radioterapia , Intervalo Livre de Doença , Humanos , Recidiva Local de Neoplasia , Prognóstico , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos RetrospectivosRESUMO
In this case, we describe a unique case of large renal hydronephrosis in a 79-year-old Indian male patient who had initially presented with 3 months of progressive dysphagia and loss of weight. His dysphagia was initially thought to be related to the atypical diagnosis of achalasia and was being considered for an elective laparoscopic Heller myotomy. On performing CT of the abdomen, a large renal mass was discovered. However, predicament remained regarding the exact aetiology of this renal mass. This case highlights a tremendously intriguing case of dysphagia with an underlying aetiology that has not been reported elsewhere previously.