The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS)

Objective: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. Summary Background Data: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. Methods: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. Results: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. Conclusions: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies.</p

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Estudio de la fisiopatología de las alteraciones de la contractilidad in vitro del colon sigmoide en pacientes con diverticulosis

El objetivo de esta tesis ha sido estudiar la fisiopatología de las alteraciones de la contractilidad in Vitro del colon sigmoide en pacientes con enfermedad diverticular asintomática (diverticulosis). Se han llevado a cabo estudios fisiológicos in vitro mediante técnicas de baño de órganos y microelectrodos, estudios histológicos e inmunohistoquímicos y de biología molecular y expresión génica (expresión relativa de mRNA - qRT-PCR) en tejido de colon sigma procedente de resecciones quirúrgicas en pacientes con y sin diverticulosis (DS). El objetivo del primer estudio, consistió en evaluar la motilidad espontánea, el potencial de membrana en reposo (RMP) y el efecto de la estimulación de las MNs inhibitorias y excitatorias en colon sigmoide humano de pacientes con DS comparado con muestras procedentes del grupo control. Además se llevaron a cabo estudios histológicos e inmunohistológicos para valorar si los cambios a nivel de motilidad in Vitro y electrofisiológicos se correlacionaban con cambios estructurales en las capas musculares, plexo mientérico o células Intersticiales de Cajal (ICCs). Nuestros resultados indican que la motilidad espontánea (contracciones rítmicas espontáneas (CRE) está muy reducida en pacientes con DS (amplitud y área bajo la curva). La respuesta a la estimulación eléctrica de campo también fue diferente en los pacientes con DS, las contracciones en ON (fruto de la estimulación de MNs excitatorias) fueron mayores (amplitud) en estos pacientes. También fueron mayores la latencia de las contracciones en OFF y el potencial post-unión inhibitorio (fruto de la estimulación de MNs inhibitorias). Las muestras de pacientes con DS también presentaron un RMP más hiperpolarizado. Sin embargo, no se observaron diferencias a nivel histológico (capas musculares, estructuras neurales y gliales del plexo mientérico, densidad de ICCs). Estos hallazgos sugieren que hay cambios fisiológicos que preceden no sólo a los síntomas sino también a los principales cambios histológicos descritos en esta enfermedad. El objetivo del segundo estudio, fue caracterizar los cambios a nivel de neurotransmisión inhibitoria observados con anterioridad. En éste confirmamos las diferencias en la motilidad in Vitro observadas previamente (disminución de la motilidad espontánea e incremento de la latencia de las contracciones) y demostramos que estas diferencias se deben fundamentalmente a un incremento de la liberación de óxido nítrico (NO), tanto espontánea, como inducida por el estímulo de MNs inhibitorias, ya que después de la incubación con L-NNA, un inhibidor de la n-NOS (enzima de síntesis del NO), la motilidad espontánea incrementó sólo en el grupo de pacientes con DS. Además hubo una reducción casi total de la latencia en ambos grupos después de adición de L-NNA. Mediante estudios moleculares detectamos un aumento de la expresión relativa de n-NOS sin cambios significativos en la expresión relativa de i-NOS, P2Y1R o en el marcador neuronal PGP9.5. Esto sugiere que las alteraciones en la vía inhibitoria en estadios iniciales se deben principalmente a un incremento en la síntesis y liberación de NO y al subsiguiente incremento de respuestas inhibitorias mediadas por NO. El tercer objetivo de esta tesis fue evaluar el efecto fármacológico in Vitro de diversos espasmolíticos utilizados habitualmente en la práctica clínica para tratar las alteraciones motoras de los pacientes con enfermedad diverticular. Hemos estudiado el efecto del Bromuro de otilonio y de la N-butil-hioscina sobre las contracciones en ON. Los resultados obtenidos sugieren que aunque ambos espasmolíticos son de utilidad en estos pacientes, ambos presentan una menor eficacia y una potencia ligeramente menor en pacientes con DS. Como conclusión final, esta Tesis Doctoral pone de manifiesto que los pacientes con DS presentan una alteración de la contractilidad in vitro tanto en las contracciones espontáneas como en las inducidas por la estimulación de las motoneuronas del plexo mientérico, ya en la fase asintomática de la enfermedad. Los cambios presentes a nivel de la neurotransmisión inhibitoria son fundamentalmente de la vía nitrérgica.The aim of this Doctoral Thesis was to study the pathophysiology of the contractility alterations of the sigmoid colon, in vitro, in patients with asymptomatic diverticulosis (DS). To do this we used organ bath technique and microelectrodes, histological and immunohistochemical studies and molecular biology (mRNA relative gene expression qRT-PCR) with tissue from the human sigmoid colon of patients with and without DS undergoing surgery for colorectal cancer. The aim of the first study was to evaluate spontaneous contractility, resting membrane potential and the effect of inhibitory and excitatory enteric motor neuron stimulation, in samples from patients with DS compared with a control group. For this reason, histological and immunohistochemical studies were performed to determine whether changes observed in electrophysiologic and contractility studies in vitro correlate with structural changes in muscular layer, myenteric plexus or interstitial cells of Cajal (ICCs). Our results demonstrated that spontaneous motility (spontaneous rhythmic phasic contractions) was greatly reduced in patients with DS (amplitude and area under the curve). Electrical field stimulation (EFS), also differed between groups, and induced neurally-mediated, enhanced ON contractions (related to excitatory motor neurons - amplitude) in DS patients. EFS also increased the duration of latency of OFF contractions. The resting membrane potential of smooth muscle cells was hyperpolarized as was the amplitude of the inhibitory junction potential (related to the stimulation of inhibitory motor neurons). However, no histological differences were observed (muscular layers, neural and glial structural elements of myenteric plexus and ICCs density). These findings suggest that there are physiological changes that precede not only the symptoms but also the main histological changes described in this disease. The aim of the second study was to characterize the changes in the inhibitory neurotransmission observed previously. In this study we confirmed the differences in motility previously observed in vitro (decreased spontaneous motility and increased latency of contractions) and showed that these differences are mainly due to an increase in the release of nitric oxide (NO), both spontaneous and induced by the stimulation of inhibitory motor neurons. After incubation with L-NNA, an n-NOS inhibitor, the spontaneous motility increased only in the group of patients with DS. In addition there was an almost total reduction of latency in both groups after addition of L-NNA. Using molecular studies, we detected a relative increase in n-NOS expression without significant changes in the relative expression of i-NOS, P2Y1R or in the neuronal marker PGP9.5. This suggests that, in early stages of the disease, alterations in the inhibitory pathway are mainly due to an increase in synthesis and release of NO and the subsequent increase in inhibitory responses mediated by NO. The third aim of this doctoral thesis was to evaluate the in vitro pharmacological effect of several spasmolytic treatments commonly used in clinical practice to treat motor abnormalities in patients with diverticular disease. We studied the effect of Otilonium bromide and N-butyl-hyoscine on ON contractions. The results suggest that although both spasmolytics are useful in patients with asymptomatic diverticulosis, both show a lower efficacy and a slightly lower potency compared with controls. As a final conclusion, this doctoral thesis demonstrates that patients with diverticulosis have an in vitro contractility impairment that affects both spontaneous contractions and those induced by stimulation of the motor neurons of the myenteric plexus, present in early stages of the disease. The changes presented in inhibitory neurotransmission are primarily due to the nitrergic pathwa

Estudio de la fisiopatología de las alteraciones de la contractilidad in vitro del colon sigmoide en pacientes con diverticulosis

El objetivo de esta tesis ha sido estudiar la fisiopatología de las alteraciones de la contractilidad in Vitro del colon sigmoide en pacientes con enfermedad diverticular asintomática (diverticulosis). Se han llevado a cabo estudios fisiológicos in vitro mediante técnicas de baño de órganos y microelectrodos, estudios histológicos e inmunohistoquímicos y de biología molecular y expresión génica (expresión relativa de mRNA - qRT-PCR) en tejido de colon sigma procedente de resecciones quirúrgicas en pacientes con y sin diverticulosis (DS). El objetivo del primer estudio, consistió en evaluar la motilidad espontánea, el potencial de membrana en reposo (RMP) y el efecto de la estimulación de las MNs inhibitorias y excitatorias en colon sigmoide humano de pacientes con DS comparado con muestras procedentes del grupo control. Además se llevaron a cabo estudios histológicos e inmunohistológicos para valorar si los cambios a nivel de motilidad in Vitro y electrofisiológicos se correlacionaban con cambios estructurales en las capas musculares, plexo mientérico o células Intersticiales de Cajal (ICCs). Nuestros resultados indican que la motilidad espontánea (contracciones rítmicas espontáneas (CRE) está muy reducida en pacientes con DS (amplitud y área bajo la curva). La respuesta a la estimulación eléctrica de campo también fue diferente en los pacientes con DS, las contracciones en ON (fruto de la estimulación de MNs excitatorias) fueron mayores (amplitud) en estos pacientes. También fueron mayores la latencia de las contracciones en OFF y el potencial post-unión inhibitorio (fruto de la estimulación de MNs inhibitorias). Las muestras de pacientes con DS también presentaron un RMP más hiperpolarizado. Sin embargo, no se observaron diferencias a nivel histológico (capas musculares, estructuras neurales y gliales del plexo mientérico, densidad de ICCs). Estos hallazgos sugieren que hay cambios fisiológicos que preceden no sólo a los síntomas sino también a los principales cambios histológicos descritos en esta enfermedad. El objetivo del segundo estudio, fue caracterizar los cambios a nivel de neurotransmisión inhibitoria observados con anterioridad. En éste confirmamos las diferencias en la motilidad in Vitro observadas previamente (disminución de la motilidad espontánea e incremento de la latencia de las contracciones) y demostramos que estas diferencias se deben fundamentalmente a un incremento de la liberación de óxido nítrico (NO), tanto espontánea, como inducida por el estímulo de MNs inhibitorias, ya que después de la incubación con L-NNA, un inhibidor de la n-NOS (enzima de síntesis del NO), la motilidad espontánea incrementó sólo en el grupo de pacientes con DS. Además hubo una reducción casi total de la latencia en ambos grupos después de adición de L-NNA. Mediante estudios moleculares detectamos un aumento de la expresión relativa de n-NOS sin cambios significativos en la expresión relativa de i-NOS, P2Y1R o en el marcador neuronal PGP9.5. Esto sugiere que las alteraciones en la vía inhibitoria en estadios iniciales se deben principalmente a un incremento en la síntesis y liberación de NO y al subsiguiente incremento de respuestas inhibitorias mediadas por NO. El tercer objetivo de esta tesis fue evaluar el efecto fármacológico in Vitro de diversos espasmolíticos utilizados habitualmente en la práctica clínica para tratar las alteraciones motoras de los pacientes con enfermedad diverticular. Hemos estudiado el efecto del Bromuro de otilonio y de la N-butil-hioscina sobre las contracciones en ON. Los resultados obtenidos sugieren que aunque ambos espasmolíticos son de utilidad en estos pacientes, ambos presentan una menor eficacia y una potencia ligeramente menor en pacientes con DS. Como conclusión final, esta Tesis Doctoral pone de manifiesto que los pacientes con DS presentan una alteración de la contractilidad in vitro tanto en las contracciones espontáneas como en las inducidas por la estimulación de las motoneuronas del plexo mientérico, ya en la fase asintomática de la enfermedad. Los cambios presentes a nivel de la neurotransmisión inhibitoria son fundamentalmente de la vía nitrérgica.The aim of this Doctoral Thesis was to study the pathophysiology of the contractility alterations of the sigmoid colon, in vitro, in patients with asymptomatic diverticulosis (DS). To do this we used organ bath technique and microelectrodes, histological and immunohistochemical studies and molecular biology (mRNA relative gene expression qRT-PCR) with tissue from the human sigmoid colon of patients with and without DS undergoing surgery for colorectal cancer. The aim of the first study was to evaluate spontaneous contractility, resting membrane potential and the effect of inhibitory and excitatory enteric motor neuron stimulation, in samples from patients with DS compared with a control group. For this reason, histological and immunohistochemical studies were performed to determine whether changes observed in electrophysiologic and contractility studies in vitro correlate with structural changes in muscular layer, myenteric plexus or interstitial cells of Cajal (ICCs). Our results demonstrated that spontaneous motility (spontaneous rhythmic phasic contractions) was greatly reduced in patients with DS (amplitude and area under the curve). Electrical field stimulation (EFS), also differed between groups, and induced neurally-mediated, enhanced ON contractions (related to excitatory motor neurons - amplitude) in DS patients. EFS also increased the duration of latency of OFF contractions. The resting membrane potential of smooth muscle cells was hyperpolarized as was the amplitude of the inhibitory junction potential (related to the stimulation of inhibitory motor neurons). However, no histological differences were observed (muscular layers, neural and glial structural elements of myenteric plexus and ICCs density). These findings suggest that there are physiological changes that precede not only the symptoms but also the main histological changes described in this disease. The aim of the second study was to characterize the changes in the inhibitory neurotransmission observed previously. In this study we confirmed the differences in motility previously observed in vitro (decreased spontaneous motility and increased latency of contractions) and showed that these differences are mainly due to an increase in the release of nitric oxide (NO), both spontaneous and induced by the stimulation of inhibitory motor neurons. After incubation with L-NNA, an n-NOS inhibitor, the spontaneous motility increased only in the group of patients with DS. In addition there was an almost total reduction of latency in both groups after addition of L-NNA. Using molecular studies, we detected a relative increase in n-NOS expression without significant changes in the relative expression of i-NOS, P2Y1R or in the neuronal marker PGP9.5. This suggests that, in early stages of the disease, alterations in the inhibitory pathway are mainly due to an increase in synthesis and release of NO and the subsequent increase in inhibitory responses mediated by NO. The third aim of this doctoral thesis was to evaluate the in vitro pharmacological effect of several spasmolytic treatments commonly used in clinical practice to treat motor abnormalities in patients with diverticular disease. We studied the effect of Otilonium bromide and N-butyl-hyoscine on ON contractions. The results suggest that although both spasmolytics are useful in patients with asymptomatic diverticulosis, both show a lower efficacy and a slightly lower potency compared with controls. As a final conclusion, this doctoral thesis demonstrates that patients with diverticulosis have an in vitro contractility impairment that affects both spontaneous contractions and those induced by stimulation of the motor neurons of the myenteric plexus, present in early stages of the disease. The changes presented in inhibitory neurotransmission are primarily due to the nitrergic pathwa

Microfracture-coagulation for the real robotic liver parenchymal transection

The use of the robotic approach in liver surgery is exponentially increasing. Although technically the robot introduces several innovative features, the instruments linked with the traditional laparoscopic approach for the liver parenchymal transection are not available, which may result in multiple technical variants that may bias the comparative analysis between the different series worldwide. A real robotic approach, minimally efficient for the liver parenchymal transection, with no requirement of external tool, available for the already existing platforms, and applicable to any type of liver resection, counting on the selective use of the plugged bipolar forceps and the monopolar scissors, or "microfracture-coagulation" (MFC) transection method, is described in detail. The relevant aspects of the technique, its indications and methodological basis are discussed

Cycle Threshold Values in the Context of Multiple RT-PCR Testing for SARS-CoV-2

Purpose: Discharge or follow up of confirmed coronavirus disease 2019 (COVID-19) cases depend on accurate interpretation of RT-PCR. Currently, positive/negative interpretations are based on amplification instead of quantification of cycle threshold (Ct) values, which could be used as proxies of patient infectiousness. Here, we measured Ct values in hospitalized confirmed COVID-19 patients at different times and its implications in diagnosis and follow up. Patients and Methods: Observational study between March 17th-May 12th, 2020 using multiple RT-PCR testing. A cohort of 118 Hispanic hospitalized patients with confirmed COVID-19 diagnosis in a reference hospital in Quito, Ecuador. Multiple RT-PCR tests were performed using deep nasal swab samples and the assessment of SARS-CoV-2 genes N, RdRP, and E. Results: Patients’ median age was of 49 years (range: 24– 91) with a male majority (62.7%). We found increasing levels of Ct values in time, with a mean Ct value of 29.13 (n = 61, standard deviation (sd) = 5.55) for the first test and 34.38 (n = 60, sd = 4), 35.52 (n = 20, sd = 2.85), and 36.12 (n = 6, sd = 3.28), for the second, third, and fourth tests, respectively. Time to RT-PCR lack of amplification for all tests was of 34 days while time to RT-PCR Ct values > 33 was of 30 days. Conclusion: Cycle thresholds can potentially be used to improve diagnosis, management and control. We found that turnover time for negativity can be large for hospitalized patients and that 11% cases persisted with infectious Ct values for more time than the current isolation recommendations

The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS)

Objective: To develop and update evidence- and consensus-based guidelines on laparoscopic and robotic pancreatic surgery.Summary Background Data: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update.Methods: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, the AGREE II-GRS tool for methodological guideline quality assessment, and external validation by a Validation Committee.Results: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the two-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic and 31 on general MIPS covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. Conclusions: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy- makers and medical societies