What is the optimum post treatment surveillance imaging protocol for low grade appendiceal mucinous neoplasms and pseudomyxoma peritoneii?

Appendiceal mucinous neoplasms are rare and can be associated with the development of disseminated peritoneal disease known as pseudomyxoma peritonei (PMP). Mucinous tumours identified on appendicectomy are therefore followed up to assess for recurrence and the development of PMP. In additional, individuals who initially present with PMP who are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are followed up to assess for recurrence. However, despite the concerted efforts of multiple expert groups, the optimal imaging follow-up protocol is yet to be established. The purpose of this paper is to review the available evidence for imaging surveillance in these populations to identify the optimum post-resection imaging follow-up protocol.

Are women breaking the glass ceiling? A gendered analysis of the duration of sick leave in Spain.

We study the gender gap in the duration of sick leave in Spain by splitting this duration into two types of days - those which are related to biological characteristics and those derived from behavioral reasons. Using the Statistics of Accidents at Work for 2011-2019, we found that women presented longer standard durations (i.e., purely attached to physiological reasons) compared to men. However, when estimating individuals' efficiency as the ratio between actual and standard durations, we found that women were more inefficient at lower levels of income, whereas in case of men, this occurred at higher levels of income. These results were reinforced when considering that men and women do not recover from the same injury at the same rate. Women were more efficient than men across all the compensation distribution, especially at higher income levels.

Ensemble-GNN: federated ensemble learning with graph neural networks for disease module discovery and classification.

SUMMARY: Federated learning enables collaboration in medicine, where data is scattered across multiple centers without the need to aggregate the data in a central cloud. While, in general, machine learning models can be applied to a wide range of data types, graph neural networks (GNNs) are particularly developed for graphs, which are very common in the biomedical domain. For instance, a patient can be represented by a protein-protein interaction (PPI) network where the nodes contain the patient-specific omics features. Here, we present our Ensemble-GNN software package, which can be used to deploy federated, ensemble-based GNNs in Python. Ensemble-GNN allows to quickly build predictive models utilizing PPI networks consisting of various node features such as gene expression and/or DNA methylation. We exemplary show the results from a public dataset of 981 patients and 8469 genes from the Cancer Genome Atlas (TCGA). AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/pievos101/Ensemble-GNN, and the data at Zenodo (DOI: 10.5281/zenodo.8305122).

LAMPPrimerBank, a manually curated database of experimentally validated loop-mediated isothermal amplification primers for detection of respiratory pathogens.

PURPOSE AND METHODS: The emergence of coronavirus disease 2019 (COVID-19) has once again affirmed the significant threat of respiratory infections to global public health and the utmost importance of prompt diagnosis in managing and mitigating any pandemic. The nucleic acid amplification test (NAAT) is the primary detection method for most pathogens. Loop-mediated isothermal amplification (LAMP) is a rapid, simple, sensitive, and specific epitome of isothermal NAAT performed using a set of four to six primers. Primer design is a fundamental step in LAMP assays, with several complexities and experimental screening requirements. To address this challenge, an online database is presented here. Its workflow comprises three steps: literature aggregation, data curation, and database and website implementation. RESULTS: LAMPPrimerBank ( https://lampprimerbank.mathematik.uni-marburg.de ) is a manually curated database dedicated to experimentally validated LAMP primers, their peculiarities of assays, and accompanying literature, with a primary emphasis on respiratory pathogens. LAMPPrimerBank, with its user-friendly web interface and an open application programming interface, enables the accelerated and facile exploration, comparison, and exportation of LAMP primer sequences and their respective information from the massively scattered literature. LAMPPrimerBank currently comprises LAMP primers for diagnosing viral, bacterial, and fungal respiratory pathogens. Additionally, to address the challenge of false-positive results generated by nonspecific amplifications, LAMPPrimerBank computationally predicted and visualized the sizes of LAMP products for recorded primer sets in the database. CONCLUSION: LAMPPrimerBank, as a pioneering database in the rapidly expanding field of isothermal NAAT, endeavors to confront the two challenges of the LAMP: primer design and discrimination of false-positive results.

Appendiceal Mucinous Neoplasms: From Clinic to Pathology and Prognosis.

Appendiceal mucinous neoplasms have been classified differently over time causing confusion when comparing results between working groups in this field and establishing a prognosis of the disease. A historical perspective of the different classification systems of these tumors is essential for the understanding of the evolution of concepts and histopathological definitions that have led up to the present moment. We carried out a systematic review of the pathological classifications of appendiceal mucinous tumors and how they have included the new criteria resulting from clinical and pathological research. The latest classifications by PSOGI and AJCC 8th edition Cancer Staging have made a great effort to incorporate the new pathological descriptions and develop prognostic groups. The introduction of these new classification systems has posed the challenge of verifying how they adapt to our casuistry and which one defines best the prognosis of our patients. We reclassified our series of patients treated for mucinous appendiceal tumors with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy following the PSOGI and the AJCC 8th edition criteria and concluded that both classifications correspond well with the OS and DFS of these patients, with some advantage relative to the PSOGI classification due to a better histopathological description of the different groups.

Correlation between PSOGI pathological classification and survival outcomes of patients with pseudomyxoma peritonei treated using cytoreductive surgery and HIPEC: national referral centre experience and literature review.

Objectives: The Peritoneal Surface Oncology Group International (PSOGI) consensus subdivided pseudomyxoma peritonei (PMP) into four groups according to histopathological features. The aim of this paper is to report survival outcomes after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) from a national referral centre and to correlate the PSOGI classification with survival. Methods: A retrospective study of a prospectively maintained database was performed. Consecutive patients treated with CRS + HIPEC for PMP of appendiceal origin were included (September-2013 to December-2021). Pathological features of the peritoneal disease were used to classify patients into the four groups proposed by PSOGI. Survival analysis was performed to evaluate the correlation of pathology on overall survival (OS) and disease-free survival (DFS). Results: Overall, 104 patients were identified; 29.6 % were reclassified as acellular mucin (AM), 43.9 % as low-grade mucinous carcinoma peritonei (LGMCP), 22.4 % as high-grade MCP (HGMCP) and 4.1 % as HGMCP with signet ring cells (HGMCP-SRC). Median PCI and rate of optimal cytoreduction were 19 and 82.7 %, respectively. Median OS and DFS were not reached, 5-year OS and DFS were 88.6(SD 0.04) % and 61.6(SD 0.06) %, respectively. Log-Rank test revealed significant differences in terms of OS and DFS across the different histological subgroups (p<0.001 in both cases). However, histology did not retain its significance in the multivariate analysis for OS or DFS (p=0.932 and p=0.872, respectively). Conclusions: Survival outcomes after CRS + HIPEC for PMP are excellent. The PSOGI pathological classification correlates with OS and DFS, but differences were not significant at multivariate analysis when adjusted for other prognostic factors.

Structural and functional analysis of the cerato-platanin-like protein Cpl1 suggests diverging functions in smut fungi.

Plant-pathogenic fungi are causative agents of the majority of plant diseases and can lead to severe crop loss in infected populations. Fungal colonization is achieved by combining different strategies, such as avoiding and counteracting the plant immune system and manipulating the host metabolome. Of major importance are virulence factors secreted by fungi, which fulfil diverse functions to support the infection process. Most of these proteins are highly specialized, with structural and biochemical information often absent. Here, we present the atomic structures of the cerato-platanin-like protein Cpl1 from Ustilago maydis and its homologue Uvi2 from Ustilago hordei. Both proteins adopt a double-Ψß-barrel architecture reminiscent of cerato-platanin proteins, a class so far not described in smut fungi. Our structure-function analysis shows that Cpl1 binds to soluble chitin fragments via two extended grooves at the dimer interface of the two monomer molecules. This carbohydrate-binding mode has not been observed previously and expands the repertoire of chitin-binding proteins. Cpl1 localizes to the cell wall of U. maydis and might synergize with cell wall-degrading and decorating proteins during maize infection. The architecture of Cpl1 harbouring four surface-exposed loop regions supports the idea that it might play a role in the spatial coordination of these proteins. While deletion of cpl1 has only mild effects on the virulence of U. maydis, a recent study showed that deletion of uvi2 strongly impairs U. hordei virulence. Our structural comparison between Cpl1 and Uvi2 reveals sequence variations in the loop regions that might explain a diverging function.

ODNA: identification of organellar DNA by machine learning.

MOTIVATION: Identifying organellar DNA, such as mitochondrial or plastid sequences, inside a whole genome assembly, remains challenging and requires biological background knowledge. To address this, we developed ODNA based on genome annotation and machine learning to fulfill. RESULTS: ODNA is a software that classifies organellar DNA sequences within a genome assembly by machine learning based on a predefined genome annotation workflow. We trained our model with 829 769 DNA sequences from 405 genome assemblies and achieved high predictive performance (e.g. matthew's correlation coefficient of 0.61 for mitochondria and 0.73 for chloroplasts) on independent validation data, thus outperforming existing approaches significantly. AVAILABILITY AND IMPLEMENTATION: Our software ODNA is freely accessible as a web service at https://odna.mathematik.uni-marburg.de and can also be run in a docker container. The source code can be found at https://gitlab.com/mosga/odna and the processed data at Zenodo (DOI: 10.5281/zenodo.7506483).

History of the discovery and development of Biomodulina T (InmunyVital®), a useful immunomodulator with a broad range of clinical applications.

Biomodulina T (InmunyVital®) is a thymic factor that modulates immune response and inflammation. Biomodulina T stimulates the differentiation, maturation and proliferation of T cells. Additionally, Biomodulina T improves the ability of T cells to produce cytokines, therefore enhancing T lymphocyte function. Biomodulina T stimulates the thymus gland and, thus, promotes the recovery of normal thymus size in children with thymic hypoplasia and restores the functions of immunosenescent T cells in aging people. In 1984 Rodriguez Martin RR established the laboratory of Biomodulators, where he created and developed an immunomodulatory thymic factor that he named "Biomodulina T." The biological activity of Biomodulina T was demonstrated in several studies. An extensive series of preclinical toxicological studies were conducted and these studies demonstrated that Biomodulina T is an active and safe thymic factor. Clinical trials were conducted with Biomodulina T in patients with immunodeficiency and infections, autoimmune diseases, older adults with recurrent respiratory infections, and cancer. In 1994, we obtained the approval of Biomodulina T as an immunomodulatory drug. This article identifies the milestones involved in the development of Biomodulina T. Since its discovery more than 35 years ago, reports show that Biomodulina T is a modulator of immune response and inflammation that is very useful for restoring the immune system in young and elderly people with immunodeficiencies, autoimmune diseases, and infections. Biomodulina T is also useful as an immunotherapeutic agent for improving immune responses in cancer and vaccines, for reversing immunosenescence and for improving healthspan in aging.

External multicentre validation of pseudomyxoma peritonei PSOGI-Ki67 classification.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignant disease. Adding of the Ki67 proliferation index to the PSOGI PMP classification provided two different subcategories of the extensive HG-PMP group (HG-PMP ≤15% and HG-PMP >15%) with different survival in a previous unicentric study. This study aims to carry out an external and multicentre validation of this new proposed classification. METHOD: It was a prospective analysis of samples from a historical and international cohort of patients. A representative area with higher cellular density was used to determine the Ki67%. The Ki67 proliferation index (%) was determined in all the HG-PMP patients. A Cox proportional hazard models and multivariable COX models were used. The Kaplan-Meier method and the two-tailed log-rank test were used to analyse the effect of different PSOGI-Ki67 categories on OS and DFS. Its predictive accuracy was analysed using Harrel's C-index and the ROC curve. The calibration was performed using the calibration plots matching. RESULTS: After exclusions, 349 patients were available for analysis. The 5-years OS were 86% for LG-PMP, 59% for HG-PMP≤15, 38% for HG-PMP>15 and 42% for SRC-PMP (p = 0.0001). The 5-years DFS were 49% for LG-PMP, 35% for HG-PMP≤15, 16% for HG-PMP>15 and 18% SRC-PMP (p = 0.0001). The discrimination capability of PSOGI-Ki67 was validated. CONCLUSION: the PSOGI-Ki67 classification discriminates and predicts the OS and DFS in patients with PMP dividing the HG-PMP category into two well-defined sub-categories. The Ki67 proliferation index should be incorporated routinely in the pathology report for these patients.

Which classification system defines best prognosis of mucinous neoplasms of the appendix with peritoneal dissemination: TNM vs PSOGI?

AIMS: Several classification systems are used for pseudomyxoma peritonei. The four-tiered classification system proposed by Peritoneal Surface Oncology Group International (PSOGI) and the two-tiered proposed by the eighth edition of the American Joint Committee on Cancer (AJCC) result from evolution in terminology and pathological insight. The aim is to evaluate the impact of PSOGI and eighth edition of the AJCC classifications on survival. METHODS: Pathological slides were reviewed from a prospectively maintained database including patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for an appendiceal mucinous neoplasm with peritoneal dissemination between January 2009 and December 2019. Patients were reclassified according to PSOGI and AJCC eighth edition criteria. Survival analysis evaluated the impact of each classification system on overall survival (OS) and disease-free survival (DFS) while the concordance-index evaluated their predictive power. RESULTS: 95 patients were identified; 21.1% were reclassified as acellular mucin, 55.8% as low-grade mucinous carcinoma peritonei, 8.4% as high-grade MCP (HGMCP) and 14 as HGMCP with signet ring cells. Median OS was not reached, 5-year OS and DFS were 86.1% and 51.5%, respectively. Multivariate analysis revealed significant associations with OS (PSOGI: HR 10.2, p=0.039; AJCC: HR 7.7, p=0.002) and DFS (PSOGI: HR 12.7, p=0.001; AJCC: HR 3.7, p<0.001). The predictive capacity of both classification systems was unacceptable for OS and DFS (concordance-index values <0.7). CONCLUSIONS: Both classification systems behaved similarly when stratifying our series into prognostic groups. The PSOGI classification provides better histopathological description, but histology alone is insufficient for adequate patient prognostication.

Vitamin D Deficiency Reduces Postthyroidectomy Protracted Hypoparathyroidism Risk. Is Gland Preconditioning Possible?

Context: Hypoparathyroidism is the most frequent complication after total thyroidectomy (PT-hypoPTH). After 1 year, most patients recover parathyroid function; however, the implicated physiologic dynamics remain unknown. Vitamin D deficiency (VDD) is the main cause of secondary hyperparathyroidism. Whether this compensatory hyperparathyroidism could influence parathyroid function recovery (PFR) in the setting of PT-hypoPTH has not been studied. Objective: This work aimed to evaluate the effect of preoperative VDD on PFR. Methods: A retrospective study was conducted with a prospectively maintained database including patients undergoing a total thyroidectomy between May 2014 and June 2019. Preoperative vitamin D (25(OH)D) less than 20 mg/mL was defined as VDD. Intact PTH less than 14 pg/mL on postoperative day 1 was defined as PT-hypoPTH. Transient PT-hypoPTH displayed PFR within the first year (early recovery: < 30 days; protracted recovery: > 30 days) whereas definite PT-hypoPTH did not. Survival analysis evaluated the effect of preoperative VDD on PFR, and a binary logistic regression model identified associated factors. Results: A total of 397 patients were identified. The observed rates of transient, protracted, and definite PT-hypoPTH were 32.9%, 15.1%, and 5.2%, respectively. Rates of VDD were higher in the early-recovery PT-hypoPTH group (55.2% vs 31.5%; P = .01). Preoperative VDD was associated with faster PFR (19 vs 35 days; P = .03) and behaved as a protective factor for protracted PT-hypoPTH (odds ratio 0.47; 95% CI, 0.25-0.881; P = .016) in the multivariable analysis. Conclusion: Preoperative VDD could act as a preconditioning factor of the parathyroid glands prior to the surgical aggression exerted against them during surgery aiding PFR. Basic research studies and prospective clinical trials are needed to explain the underlying physiological mechanisms and to provide further evidence to improve clinical management.

Complications and Mortality Rate of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: Italian Peritoneal Surface Malignancies Oncoteam Results Analysis.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy may significantly improve survival for selected patients with peritoneal surface malignancies, but it has always been criticized due to the high incidence of postoperative morbidity and mortality. METHODS: Data were collected from nine Italian centers with peritoneal surface malignancies expertise within a collaborative group of the Italian Society of Surgical Oncology. Complications and mortality rates were recorded, and multivariate Cox analysis was used to identify risk factors. RESULTS: The study included 2576 patients. The procedure was mostly performed for ovarian (27.4%) and colon cancer (22.4%). The median peritoneal cancer index was 13. Overall postoperative morbidity and mortality rates were 34% and 1.6%. A total of 232 (9%) patients required surgical reoperation. Multivariate regression logistic analysis identified the type of perfusion (p ≤ 0.0001), body mass index (p ≤ 0.0001), number of resections (p ≤ 0.0001) and colorectal resections (p ≤ 0.0001) as the strongest predictors of complications, whereas the number of resections (p ≤ 0.0001) and age (p = 0.01) were the strongest predictors of mortality. CONCLUSIONS: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is a valuable option of treatment for selected patients with peritoneal carcinomatosis providing low postoperative morbidity and mortality rates, if performed in high-volume specialized centers.

Guideline for software life cycle in health informatics.

The long-lasting trend of medical informatics is to adapt novel technologies in the medical context. In particular, incorporating artificial intelligence to support clinical decision-making can significantly improve monitoring, diagnostics, and prognostics for the patient's and medic's sake. However, obstacles hinder a timely technology transfer from research to the clinic. Due to the pressure for novelty in the research context, projects rarely implement quality standards. Here, we propose a guideline for academic software life cycle processes tailored to the needs and capabilities of research organizations. While the complete implementation of a software life cycle according to commercial standards is not feasible in scientific work, we propose a subset of elements that we are convinced will provide a significant benefit while keeping the effort within a feasible range. Ultimately, the emerging quality checks for academic software development can pave the way for an accelerated deployment of academic advances in clinical practice.

Validation of a Nomogram to Predict Recurrence in Patients with Mucinous Neoplasms of the Appendix with Peritoneal Dissemination After Cytoreductive Surgery and HIPEC.

BACKGROUND: Survival of patients affected by mucinous appendiceal neoplasms with peritoneal dissemination (PD) is mainly related to histopathological features. However, prognostic stratification is still a concern, as the clinical course of the disease is often unpredictable. The aim of this study is to construct and externally validate a nomogram predicting disease-free survival (DFS) in mucinous appendiceal neoplasms with PD treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). PATIENTS AND METHODS: Patients treated in two referral centers were included: Hospital General Universitario Gregorio Marañón, Madrid, Spain (derivation cohort) and Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy (validation cohort). Cox regression analysis identified factors associated with shorter DFS in the derivation cohort. The nomogram performance was externally evaluated in the validation cohort using concordance index and calibration plots. Histology was classified according to the Peritoneal Surface Oncology Group International (PSOGI). RESULTS: The derivation cohort included 95 patients, and the validation cohort 348. Five-year DFS rates were 51.5 and 62%, respectively. Cox regression analysis (derivation cohort) identified PSOGI histology of the peritoneal components, number of preoperative elevated tumor marker, and peritoneal disease extent, as assessed by peritoneal carcinomatosis index, to be predictors of DFS. The model's predictive capacity was higher than that of PSOGI classification alone, with respective concordance indexes of 0.702 ± 0.023 and 0.610 ± 0.018 (validation cohort). The nomogram approximated the perfect model in the calibration plots at 3- and 5-year DFS. CONCLUSIONS: An easy-to-use model that provides better prognostic stratification than histopathological features has been constructed. This nomogram may help clinicians in individualized survival predictions and informed clinical decision-making.

Relationship between the anatomical location and the selective non-operative management of penetrating stab wounds in the abdomen.

INTRODUCTION: The relationship between the anatomical location of penetrating abdominal stab wounds (SW) and the rate of selective non-operative management (SNOM) based on that location is scarcely reflected in the specialized literature. Our main objective has been to assess this rate based on the anatomical location, and our results. METHODS: Retrospective review of a prospective registry of abdominal trauma from April 1993 to June 2020. The two study groups considered were the Operative Management (OM), and the SNOM, including in this one the use of diagnostic laparoscopy. Penetrating SWs in the abdomen were classified according to anatomical location. RESULTS: We identified 259 patients who fulfilled the inclusion criteria. SNOM was applied in 31% of the patients with a success rate of 96%, and it was more frequent in the lumbar, flank, and thoraco-abdominal regions; within the anterior abdomen it was more applicable in the RH, followed by the LH and epigastrium, respectively. An unnecessary laparotomy was done in 21% of patients, with the highest number in the epigastrium. Taking into account the unnecessary laparotomies and the rates of successful SNOM, 70.5% of lumbar, 66.5% of epigastric, 62% of flank, and 59% of RH penetrating SW could have been managed without a laparotomy. CONCLUSIONS: SNOM of penetrating SW in the abdomen has been safer and more applicable in those located in the lumbar, flank, epigastric, and RH regions.

Relación entre la localización anatómica y el manejo selectivo no operatorio de las heridas por arma blanca penetrantes en abdomen / Relationship between the anatomical location and the selective non-operative management of penetrating stab wounds in the abdomen

Introducción: La localización anatómica de las heridas por arma blanca (HAB) penetrantes en abdomen y su relación con el manejo selectivo no operatorio (MSNO) tiene escaso reflejo en la literatura especializada. Nuestro objetivo principal ha sido valorar la tasa de MSNO en función de esa localización anatómica, y sus resultados. Métodos: Revisión retrospectiva del registro prospectivo de trauma abdominal desde abril de 1993 hasta junio de 2020. Los dos grupos a estudio fueron manejo operatorio (MO) y MSNO, incluyendo en este último grupo el uso de laparoscopias exploradoras como método diagnóstico. Se clasificaron las HAB penetrantes en abdomen en función de su localización anatómica. Resultados: Identificamos 259 pacientes que cumplían los criterios de inclusión. El MSNO se aplicó en el 31% de los pacientes, con una tasa de éxito del 96,5%. En las HAB de las regiones lumbares, flancos y toracoabdominales fue donde se optó más frecuentemente por este manejo; y en el abdomen anterior fue más aplicable en el hipocondrio derecho (HD), seguido del hipocondrio izquierdo (HI) y epigastrio. Se realizó una laparotomía innecesaria en el 21%, con la cifra más alta en el epigastrio. Teniendo en cuenta los porcentajes de MSNO y laparotomías evitables en cada región, el 70,5% de las HAB lumbares, el 66,5% de las epigástricas, el 62% de flancos y el 59% de HD se podrían haber manejado con éxito sin laparotomía. Conclusiones: El MSNO de las HAB penetrantes en abdomen ha resultado más seguro y aplicable en las localizadas en las regiones lumbares, flancos, epigastrio e HD (AU)

Introduction: The relationship between the anatomical location of penetrating abdominal stab wounds (SW) and the rate of selective non-operative management (SNOM) based on that location is scarcely reflected in the specialized literature. Our main objective has been to assess this rate based on the anatomical location, and our results. Methods: Retrospective review of a prospective registry of abdominal trauma from April 1993 to June 2020. The two study groups considered were the Operative Management (OM), and the SNOM, including in this one the use of diagnostic laparoscopy. Penetrating SWs in the abdomen were classified according to anatomical location. Results: We identified 259 patients who fulfilled the inclusion criteria. SNOM was applied in 31% of the patients with a success rate of 96%, and it was more frequent in the lumbar, flank, and thoraco-abdominal regions; within the anterior abdomen it was more applicable in the RUQ, followed by the LUQ and epigastrium, respectively. An unnecessary laparotomy was done in 21% of patients, with the highest number in the epigastrium. Taking into account the unnecessary laparotomies and the rates of successful SNOM, 70,5% of lumbar, el 66,5% of epigastric, 62% of flank, and 59% of RUQ penetrating SWs could have been managed without a laparotomy. Conclusions: SNOM of penetrating SWs in the abdomen has been safer and more applicable in those located in the lumbar, flank, epigastric, and RUQ regions (AU)

Systemic metastases from low-grade and high-grade pseudomyxoma peritonei: Treatments and outcomes.

BACKGROUND: The metastasizing potential of pseudomyxoma peritonei (PMP) is largely unknown. We assessed incidence, impact on prognosis, treatments, and outcomes of systemic metastases after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: A prospective database of 327 patients undergoing CRS/HIPEC for PMP of appendiceal origin was reviewed. PMP was graded according to the Peritoneal Surface Oncology Group International (PSOGI) classification. Haematogenous metastases, and non-regional lymph-node involvement were considered as systemic metastases. RESULTS: After a median follow-up of 74.8 months (95% confidence interval [CI] = 68.0-94.8), systemic metastases occurred in 21 patients. Eleven patients were affected by low-grade PMP, and ten by high-grade PMP. Metastatic disease involved the lung (n = 12), bone (n = 1), liver (n = 4), distant nodes (n = 3), both lung and distant nodes (n = 1). Systemic metastases independently correlated with PSOGI histological subtypes (P = 0.001), and incomplete cytoreduction (P = 0.026). Median OS was 139.0 months (95%CI = 56.6-161.9) for patients who experienced systemic metastases, and 213.8 months (95%CI = 148.7-not reached) for those who did not (P = 0.159). Eight of eleven patients who had curative-intent surgery are presently alive at a median of 52.5 months (range 2.0-112.7). Seven are disease-free at a median of 27.4 months (range 2.0-110.4). At multivariate analysis, PSOGI histological subtypes (P = 0.001), completeness of cytoreduction (P = 0.001), and preoperative systemic chemotherapy (P = 0.020) correlated with poorer survival. Systemic metastases did not (P = 0.861). CONCLUSIONS: After CRS/HIPEC, systemic metastases occur in a small but clinically relevant number of patients, and the risk increases with incomplete cytoreduction and aggressive histology. In selected patients, surgical resection of metastatic disease can result in long survival.

Relevance of pneumoperitoneum in the conservative approach to complicated acute diverticulitis. A retrospective study identifying risk factors associated with treatment failure.

BACKGROUND: The aim of this study is to evaluate the relevance of pneumoperitoneum on the success rate of non-operative management (NOM) of patients with complicated acute diverticulitis (AD), and the risk factors associated with failure. METHODS: Observational retrospective cohort study of patients attended at the emergency department for AD from January 2015-August 2019. Patient demographics, blood tests, radiological data and initial treatment strategies were registered. NOM, based on intravenous antibiotics (ATB) and bowel rest, was defined as unsuccessful when emergency surgery (ES) and/or infection-related death took place. Patients initially treated with ES were excluded. Analysis was done with the IBM SPSS statistics 23.0.0.2 software. RESULTS: According to modified Hinchey and WSES criteria, 99 (12%) of 826 AD episodes were complicated, with pneumoperitoneum on the CT scan in 89 (90.5%). NOM was undertaken in 93 (94%) cases, with a 91.5% success rate. Multivariate analysis revealed ASA class III-IV, and the presence of fluid collections >3 cm in diameter, but not distant free air, to be associated with NOM failure. However, the success rate of NOM was significantly higher in patients with pericolic pneumoperitoneum (98.5%) than in those with distant free air (80%) (P=0.02). Risk factors of NOM failure were an advanced age, high CRP and WBC values, and the presence of free fluid in >2 abdominal quadrants. CONCLUSIONS: NOM in hemodynamically stable patients with complicated AD is a safe and feasible approach, even in the context of distant free air. Nevertheless, patients with isolated pericolic air did better in our series.