Intraperitoneal drug delivery systems for peritoneal carcinomatosis: Bridging the gap between research and clinical implementation.

Several abdominal-located cancers develop metastasis within the peritoneum, what is called peritoneal carcinomatosis (PC), constituting a clinical challenge in their therapeutical management, often leading to poor prognoses. Current multidisciplinary strategies, including cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC), demonstrate efficacy but have limitations. In response, alternative strategies are explored in the drug delivery field for intraperitoneal chemotherapy. Controlled drug delivery offers a promising avenue, maintaining localized drug concentrations for optimal PC management. Drug delivery systems (DDS), including hydrogels, implants, nanoparticles, and hybrid systems, show potential for sustained and region-specific drug release. The present review aims to offer an overview of the advances and current designs of DDS for PC chemotherapy administration, focusing on their composition, main characteristics, and principal experimental outcomes, highlighting the importance of biomaterial rationale design and in vitro/vivo models for their testing. Moreover, since clinical data for human subjects are scarce, we offer a critical discussion of the gap between bench and bedside in DDS translation, emphasizing the need for further research.

The Role of Systematic Lymphadenectomy in Low-Grade Serous Ovarian Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the role of systematic lymphadenectomy in low-grade serous ovarian cancer (LGSOC) and determine its impact on clinical outcomes in overall survival (OS) and disease-free survival (DFS) terms. METHODS: A comprehensive, systematic computer literature search on PubMed was performed using the following Medical Subject Headings (MeSH) terms: "low grade serous ovarian cancer" AND/OR "lymphadenectomy" AND/OR "staging" AND/OR "ovarian cancer" AND/OR "cytoreduction". Separate searches were performed with MeSH terms on MEDLINE and EMBASE to extract all the relevant literature available. We included only patients with histologically confirmed LGSOC. RESULTS: Three studies were considered in the quantitative analysis. Systematic lymphadenectomy in LGSOC failed to provide a significant OS or PFS benefit in LGSOC when compared to no lymphadenectomy in the entire (all the stages) population (for OS: HR = 1.15, 95% CI [0.42, 3.18] I2 = 84% and for PFS: HR = 1.46, 95% CI [0.63, 3.41], I2 = 71%), nor did it in the subtype analysis regarding FIGO stages. For FIGO early-stage I-II LGSOC, the DFS data were pooled (HR = 1.48, 95% CI [0.58, 3.78], I2 = 75%). In patients with advanced-stage (FIGO II-IV), we also failed to prove survival benefit for lymphadenectomy in OS (HR = 1.74, 95% CI [0.87, 3.48], I2 = 11%) or DFS (HR = 1.48, 95% CI [0.58, 3.78], I2 = 75%) compared to no lymphadenectomy. CONCLUSION: More extensive prospective research is mandatory to understand the real impact of lymphadenectomy on survival in LGSOC. The existing literature does not provide strong evidence.

Standardizing Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer Treatment: Navigating Complexities and Charting the Path Forward.

The incorporation of hyperthermic intraperitoneal chemotherapy (HIPEC) into the treatment landscape for ovarian cancer has invoked a spectrum of emotions, ranging from enthusiastic anticipation to cautious skepticism [...].

Antiperistaltic Transverse Coloplasty: A Salvage Procedure in Extensive Bowel and Colorectal Resections to Avoid Intestinal Failure.

INTRODUCTION: After extensive small and colon resections, quality of life can be affected. We propose the antiperistaltic transverse coloplasty as a solution that allows for preservation of the transverse colon after both right and left colectomies while achieving a tension-free colorectal anastomosis slowing the transit and increasing the absorption time, resulting in better stool consistency and quality of life compared with an ileorectal anastomosis. METHODS: This technique was performed in a 41-year-old woman with Goblet cell adenocarcinoma of the appendix with peritoneal metastasis. The transverse colon is rotated anticlockwise over the axis of the middle colic vessels toward the left parietocolic flank and relocated to the usual position of the descending colon. RESULTS: After 1 year of follow-up, the patient led a normal life without parenteral nutrition with five bowel movements per day and a weight gain of 15%. CONCLUSIONS: The use of an antiperistaltic transverse coloplasty may be worthwhile to perform in cases of extensive bowel resections during cytoreductive surgery leading to short-bowel syndrome to avoid a permanent stoma or intestinal failure and improve patient outcomes.

Simultaneous Surgical Approach with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients with Concurrent Peritoneal and Liver Metastases of Colon Cancer Origin.

Background: Simultaneous liver resection and peritoneal cytoreduction with hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial today. The aim of the study was to analyze the postoperative outcomes and survival of patients with advanced metastatic colon cancer (peritoneal and/or liver metastases). Methods: Retrospective observational study from a prospective maintained data base. Patients who underwent a simultaneous peritoneal cytoreduction and liver resection plus HIPEC were studied. Postoperative outcomes and overall and disease free survival were analyzed. Univariate and multivariate analyses were performed. Results: From January 2010 to October 2022, 22 patients operated with peritoneal and liver metastasis (LR+) were compared with 87 patients operated with peritoneal metastasis alone (LR-). LR+ group presented higher serious morbidity (36.4 vs. 14.9%; p: 0.034). Postoperative mortality did not reach statistical difference. Median overall and disease free survival was similar. Peritoneal carcinomatosis index was the only predictive factor of survival. Conclusions: Simultaneous peritoneal and liver resection is associated with increased postoperative morbidity and hospital stay, but with similar postoperative mortality and OS and disease free survival. These results reflect the evolution of these patients, considered inoperable until recently, and justify the trend to incorporate this surgical strategy within a multimodal therapeutic plan in highly selected patients.

Challenges in precision medicine in pancreatic cancer: A focus in cancer stem cells and microbiota.

Pancreatic cancer adenocarcinoma (PDAC) is a lethal disease, with the lowest 5-years survival rate of all cancers due to late diagnosis. Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in PDAC is currently neglectable. The reasons for this dismal situation are mainly the absence of effective early diagnostic biomarkers and therapy resistance. PDAC cancer stem cells (PDAC-SC), which are regarded as essential for tumor initiation, relapse and drug resistance, are highly dependent on their niche i.e. microanatomical structures of the tumor microenvironment. There is an altered microbiome in PDAC patients embedded within the highly desmoplastic tumor microenvironment, which is known to determine therapeutic responses and affecting survival in PDAC patients. We consider that understanding the communication network that exists between the microbiome and the PDAC-SC niche by co-culture of patient-derived organoids (PDOs) with TME microbiota would recapitulate the complexity of PDAC paving the way towards a precision oncology treatment-response prediction.

Cribado de neoplasia intraepitelial anal en pacientes con infección por virus de la inmunodeficiencia humana / Anal intraepithelial neoplasia screening in patients with human immunodeficiency virus infection

Introducción: la incidencia de cáncer anal ha aumentadoen los últimos años, por lo que el cribado y la detecciónprecoz de la neoplasia intraepitelial anal (AIN) en pacientesde riesgo son una necesidad.Métodos: se realizó un estudio observacional descriptivode pacientes homosexuales (HSH) o mujeres con neoplasiacervical intraepitelial grado III (CIN III), con infección porvirus de la inmunodeficiencia humana (PVIH), incluidos enun programa de cribado de detección de AIN entre marzode 2016 y septiembre de 2019.Resultados: se realizaron 695 citologías anales, 156 conresultados de lesión de bajo grado (LSIL) o lesión de altogrado (HSIL) (22,4 %), y 116 anoscopias de alta resolución(HRA), el 75,3 % de los pacientes con citología alterada. Sehan obtenido 403 biopsias, el 84 % de ellas patológicas; 197biopsias evidenciaron AIN I (49 %) y 96, AIN II y III (24 %); 44eran condilomas (11 %); y el 16 %, mucosa normal.Conclusión: la alta prevalencia de lesiones premalignas y lamejoría del estadiaje de las lesiones tras tratamiento recomienda dicho protocolo. (AU)

Insights behind the Relationship between Colorectal Cancer and Obesity: Is Visceral Adipose Tissue the Missing Link?

Colorectal cancer (CRC) is a major health problem worldwide, with an estimated 1.9 million new cases and 915,880 deaths in 2020 alone. The etiology of CRC is complex and involves both genetic and lifestyle factors. Obesity is a major risk factor for CRC, and the mechanisms underlying this link are still unclear. However, the generalized inflammatory state of adipose tissue in obesity is thought to play a role in the association between CRC risk and development. Visceral adipose tissue (VAT) is a major source of proinflammatory cytokines and other factors that contribute to the characteristic systemic low-grade inflammation associated with obesity. VAT is also closely associated with the tumor microenvironment (TME), and recent evidence suggests that adipocytes within the TME undergo phenotypic changes that contribute to tumor progression. In this review, we aim to summarize the current evidence linking obesity and CRC, with a focus on the role of VAT in tumor etiology and progression.

Anal intraepithelial neoplasia screening in patients with human immunodeficiency virus infection.

INTRODUCTION: the incidence of anal cancer has increased in recent years, making screening and early detection of anal intraepithelial neoplasia (AIN) a necessity in patients at risk. METHODS: a descriptive observational study of homosexual patients (MSM) or women with cervical intraepithelial neoplasia (CIN) III, with human immunodeficiency virus (HIV) infection, included in an AIN detection screening program was carried out between March 2016 and September 2019. RESULTS: we have performed 695 anal smears, 156 with results of LSIL (low-grade lesion) or HSIL (high-grade lesion) (22.4 %), and 116 high resolution anoscopy (HRA), 75.3 % of patients with altered cytology. We have 403 biopsies, being 84 % pathological, 197 biopsies of AIN I (49 %), 96 of AIN II and III (24 %), 44 condylomas (11 %) and the rest (16 %), normal mucosa. CONCLUSION: the high prevalence of premalignant lesions and the improvement in the staging of lesions after treatment recommend this protocol.

Revisión del diagnóstico y manejo del quiste hidatídico hepático / Review of diagnosis and management of hydatid cyst of the liver

La hidatidosis es una zoonosis causada por el estado larvario de Echinococcus. Los seres humanos son huéspedes intermediarios accidentales, donde produce lesiones quísticas, principalmente en hígado y pulmón. Suele ser asintomática, por lo que se suele detectar de forma incidental. Los síntomas se deben a la expansión del quiste y/o a la reacción inflamatoria. El signo más frecuente es la hepatomegalia. No produce alteraciones analíticas específicas pero existeninmunodiagnósticos que pueden complementar su estudio, siendo la detección de anticuerpos el método de elección. Aunque la ecografía es la principal técnica para su diagnóstico, la tomografía brinda información más precisa respecto a sus características y relaciones anatómicas. Actualmente hay varias opciones terapéuticas. El tratamiento con albendazol, combinado o no con prazicuantel, es útil en los quistes pequeños (< 5 cm) sin complicaciones. Solo el 30 % de los quistes desaparecen con tratamiento médico exclusivo. La cirugía está indicada en los quistes hepáticos grandes (> 10 cm), con riesgo de ruptura y/o complicados; el abordaje laparoscópico está poco generalizado. La técnica radical (quistoperiquistectomía total) es preferible dado el menor riesgo postoperatorio de infecciones abdominales, fístulas biliares y morbilidad global. Las técnicas conservadoras son adecuadas en las áreas endémicas donde la cirugía la realizan cirujanos no especializados. La PAIR (punción-aspiración-inoculación-reaspiración) es una técnica innovadora que representa una alternativa a la cirugía. Está indicada en los pacientes inoperables y/o que rechazan la cirugía, en caso de recidiva tras la cirugía y cuando hay ausencia de respuesta al tratamiento médico. En los casos en que se demuestran quistes quiescentes o inactivos no complicados, se puede realizar una vigilancia activa sin tratamiento. (AU)

A review of the diagnosis and management of liver hydatid cyst.

Hydatidosis is a zoonosis caused by Echinococcus in the larval stage. Humans are accidental intermediary hosts where cystic lesions develop, primarily in the liver and the lungs. It is usually asymptomatic, hence it often represents an incidental finding. Symptoms result from cyst expansion and/or host inflammatory reaction. Hepatomegaly is the most common sign. Hydatidosis induces no specific changes in lab tests but immunodiagnostics are available that may complement its study, with antibody detection being the modality of choice. While ultrasound is the main diagnostic technique, tomography offers more accurate information regarding both characteristics and anatomical relations. A number of therapy options are presently available. Treatment with albendazole, whether combined or not with praziquantel, is useful for smaller, uncomplicated cysts (< 5 cm). Only 30 % of cysts disappear with medical treatment alone. Surgery is indicated for bigger liver cysts (> 10 cm), and cysts at risk of rupture and/or complicated cysts. The laparoscopic approach is scarcely widespread. The radical technique (total cystopericystectomy) is preferable because of its lower risk for postoperative abdominal infection, biliary fistula, and overall morbidity. Conservative techniques are appropriate in endemic areas where surgery is performed by nonspecialist surgeons. PAIR (puncture-aspiration-injection-reaspiration) is an innovative technique representing an alternative to surgery. It is indicated for inoperable cases and/or patients who reject surgery, for recurrence after surgery, and for lack of response to medical treatment. Active surveillance without treatment may be indicated for quiescent or inactive, uncomplicated liver cysts.

Organoids: An Emerging Tool to Study Aging Signature across Human Tissues. Modeling Aging with Patient-Derived Organoids.

The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans, and cell cultures. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. An organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging, and to design personalized approaches for the prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging, paving the way to personalized interventions targeting the biology of aging.

Abdominal metastatic melanoma invading the transverse colon and stomach.

Gastrointestinal melanoma metastases are not uncommon, with the jejunum and ileum being the most common locations (58 %), followed by the stomach (26 %), colon (22 %), duodenum (12 %), and rectum (5 %).

Laparoscopy technique in the setting of peritoneal metastases to avoid port site relapse.

BACKGROUND: Laparoscopy is indicated in many patients with abdominal and pelvic malignancy. If cancer cells are present within the peritoneal space, there is a possibility for port site metastases to develop. METHODS: The pathophysiology for occurrence of port site metastases was reviewed. Technical modifications to reduce the incidence of these abdominal wall sites for disease progression were suggested. RESULTS: Evacuation of all gases and all fluid from the peritoneal space through the trocars prior to their removal will reduce the contamination of the tissue surrounding the port site by intraperitoneal cancer cells. If port sites are confined to the midline, they can be removed as part of a midline abdominal incision if metastases occur. If port site metastases occur through lateral port sites, the rectus abdominus muscle may need to be widely excised to achieve negative margins. CONCLUSION: Technical modifications of laparoscopy in patients with peritoneal metastases may reduce incidence of this iatrogenic dissemination of cancer.