Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer.

The present review demonstrates the major tumor suppressor genes, including TP53, CDKN2A and SMAD4, associated with pancreatic cancer. Each gene's role, prevalence and impact on tumor development and progression are analyzed, focusing on the intricate molecular landscape of pancreatic cancer. In addition, this review underscores the prognostic significance of specific mutations, such as loss of TP53, and explores some potential targeted therapies tailored to these molecular signatures. The findings highlight the importance of genomic analyses for risk assessment, early detection and the design of personalized treatment approaches in pancreatic cancer. Overall, this review provides a comprehensive analysis of the molecular intricacies of pancreatic tumors, paving the way for more effective and tailored therapeutic interventions.

Posthemithyroidectomy Hypothyroidism: Updated Meta-Analysis of Risk Factors and Rates of Remission.

INTRODUCTION: The aim of this study was to determine the incidence and risk factors for hypothyroidism, both clinical and subclinical, following hemithyroidectomy in preoperatively euthyroid patients, as well as hypothyroidism remission and its time of remission. MATERIALS AND METHODS: A search was performed in Medline (via PubMed), Web of Science, and the Cochrane Library using the keywords "hemithyroidectomy + postoperative + hypothyroidism" and "hemithyroidectomy + hormone supplementation". RESULTS: Fifty-four studies with a total of 9,999 patients were included. After a mean follow-up interval of 48.2 mo, the pooled hypothyroidism rate was 29%. The subclinical hypothyroidism rate was 79% of patients with hypothyroidism (18 studies). Moreover, a meta-analysis of 12 studies indicated a pooled hypothyroidism remission rate after hemithyroidectomy of 42% (95% CI: 24%-60%). Older patient age (MD = -2.54, 95% CI = -3.99, -1.10, P = 0.0006), female gender (OR = 0.69, 95% CI = 0.58, 0.82, P < 0.0001), higher preoperative thyroid-stimulating hormone levels (MD = -0,81, 95% CI = -0.96, -0.66, P < 0.00001), pathological preoperative anti-thyroid peroxidase antibodies (OR = 0.37, 95% CI = 0.24, 0.57, P < 0.00001) and anti-thyroglobulin antibodies (OR = 0.52, 95% CI = 0.36, 0.75, P = 00,005), and right-sided hemithyroidectomy (OR = 0.54, 95% CI = 0.43, 0.68, P < 0.00001) were associated with postoperative hypothyroidism development. In metaregression analysis, Asia presented a significantly higher hypothyroidism rate after hemithyroidectomy (34.6%, 95% CI = 29.3%-9.9%), compared to Europe (22.9%, 95% CI = 16.2%-29.5%, P = 0.037) and Canada (1.8%, 95% CI = -22.6%-26.2%, P = 0.013). CONCLUSIONS: Hypothyroidism is a frequent and significant postoperative sequela of hemithyroidectomy, necessitating individualization of treatment strategy based on the underlying disease as well as the estimated risk of hypothyroidism and its risk factors.

Scoping review for the SAGES EAES joint collaborative on sustainability in surgical practice.

BACKGROUND: Surgical care in the operating room (OR) contributes one-third of the greenhouse gas (GHG) emissions in healthcare. The European Association of Endoscopic Surgery (EAES) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) initiated a joint Task Force to promote sustainability within minimally invasive gastrointestinal surgery. METHODS: A scoping review was conducted by searching MEDLINE via Ovid, Embase via Elsevier, Cochrane Central Register of Controlled Trials, and Scopus on August 25th, 2023 to identify articles reporting on the impact of gastrointestinal surgical care on the environment. The objectives were to establish the terminology, outcome measures, and scope associated with sustainable surgical practice. Quantitative data were summarized using descriptive statistics. RESULTS: We screened 22,439 articles to identify 85 articles relevant to anesthesia, general surgical practice, and gastrointestinal surgery. There were 58/85 (68.2%) cohort studies and 12/85 (14.1%) Life Cycle Assessment (LCA) studies. The most commonly measured outcomes were kilograms of carbon dioxide equivalents (kg CO2eq), cost of resource consumption in US dollars or euros, surgical waste in kg, water consumption in liters, and energy consumption in kilowatt-hours. Surgical waste production and the use of anesthetic gases were among the largest contributors to the climate impact of surgical practice. Educational initiatives to educate surgical staff on the climate impact of surgery, recycling programs, and strategies to restrict the use of noxious anesthetic gases had the highest impact in reducing the carbon footprint of surgical care. Establishing green teams with multidisciplinary champions is an effective strategy to initiate a sustainability program in gastrointestinal surgery. CONCLUSION: This review establishes standard terminology and outcome measures used to define the environmental footprint of surgical practices. Impactful initiatives to achieve sustainability in surgical practice will require education and multidisciplinary collaborations among key stakeholders including surgeons, researchers, operating room staff, hospital managers, industry partners, and policymakers.

Perspectives on sustainability among surgeons: findings from the SAGES-EAES sustainability in surgical practice task force survey.

BACKGROUND: Surgical care significantly contributes to healthcare-associated greenhouse gas emissions (GHG). Surgeon attitudes about mitigation of the impact of surgical practice on environmental sustainability remains poorly understood. To better understand surgeon perspectives globally, the Society of American Gastrointestinal and Endoscopic Surgeons and the European Association for Endoscopic Surgery established a joint Sustainability in Surgical Practice (SSP) Task Force and distributed a survey on sustainability. METHODS: Our survey asked about (1) surgeon attitudes toward sustainability, (2) ability to estimate the carbon footprint of surgical procedures and supplies, (3) concerns about the negative impacts of sustainable interventions, (4) willingness to change specific practices, and (5) preferred educational topics and modalities. Questions were primarily written in Likert-scale format. A clustering analysis was performed to determine whether survey respondents could be grouped into distinct subsets to inform future outreach and education efforts. RESULTS: We received 1024 responses, predominantly from North America and Europe. The study revealed that while 63% of respondents were motivated to enhance the sustainability of their practice, less than 10% could accurately estimate the carbon footprint of surgical activities. Most were not concerned that sustainability efforts would negatively impact their practice and showed readiness to adopt proposed sustainable practices. Online webinars and modules were the preferred educational methods. A clustering analysis identified a group particularly concerned yet willing to adopt sustainable changes. CONCLUSION: Surgeons believe that operating room waste is a critical issue and are willing to change practice to improve it. However, there exists a gap in understanding the environmental impact of surgical procedures and supplies, and a sizable minority have some degree of concern about potential adverse consequences of implementing sustainable policies. This study uniquely provides an international, multidisciplinary snapshot of surgeons' attitudes, knowledge, concerns, willingness, and preferred educational modalities related to mitigating the environmental impact of surgical practice.

Sustainability in surgical practice: a collaborative call toward environmental sustainability in operating rooms.

BACKGROUND: The healthcare system plays a pivotal role in environmental sustainability, and the operating room (OR) significantly contributes to its overall carbon footprint. In response to this critical challenge, leading medical societies, government bodies, regulatory agencies, and industry stakeholders are taking measures to address healthcare sustainability and its impact on climate change. Healthcare now represents almost 20% of the US national economy and 8.5% of US carbon emissions. Internationally, healthcare represents 5% of global carbon emissions. US Healthcare is an outlier in both per capita cost, and per capita greenhouse gas emission, with almost twice per capita emissions compared to every other country in the world. METHODS: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and the European Association for Endoscopic Surgery (EAES) established the Sustainability in Surgical Practice joint task force in 2023. This collaborative effort aims to actively promote education, mitigation, and innovation, steering surgical practices toward a more sustainable future. RESULTS: Several key initiatives have included a survey of members' knowledge and awareness, a scoping review of terminology, metrics, and initiatives, and deep engagement of key stakeholders. DISCUSSION: This position paper serves as a Call to Action, proposing a series of actions to catalyze and accelerate the surgical sustainability leadership needed to respond effectively to climate change, and to lead the societal transformation towards health that our times demand.

Global 30-day morbidity and mortality of surgery for perforated peptic ulcer: GRACE study.

BACKGROUND: There is little international data on morbidity and mortality of surgery for perforated peptic ulcer (PPU). This study aimed to understand the global 30-day morbidity and mortality of patients undergoing surgery for PPU and to identify variables associated with these. METHOD: We performed an international study of adults (≥ 18 years) who underwent surgery for PPU from 1st January 2022 to 30th June 2022. Patients who were treated conservatively or had an underlying gastric cancer were excluded. Patients were divided into subgroups according to age (≤ 50 and > 50 years) and time from onset of symptoms to hospital presentation (≤ 24 and > 24 h). Univariate and Multivariate analyses were carried out to identify factors associated with higher 30-day morbidity and mortality. RESULTS:  1874 patients from 159 centres across 52 countries were included. 78.3% (n = 1467) of the patients were males and the median (IQR) age was 49 years (25). Thirty-day morbidity and mortality were 48.5% (n = 910) and 9.3% (n = 174) respectively. Median (IQR) hospital stay was 7 (5) days. Open surgery was performed in 80% (n = 1505) of the cohort. Age > 50 years [(OR = 1.7, 95% CI 1.4-2), (OR = 4.7, 95% CI 3.1-7.6)], female gender [(OR = 1.8, 95% CI 1.4-2.3), (OR = 1.9, 95% CI 1.3-2.9)], shock on admission [(OR = 2.1, 95% CI 1.7-2.7), (OR = 4.8, 95% CI 3.2-7.1)], and acute kidney injury [(OR = 2.5, 95% CI 1.9-3.2), (OR = 3.9), 95% CI 2.7-5.6)] were associated with both 30-day morbidity and mortality. Delayed presentation was associated with 30-day morbidity [OR = 1.3, 95% CI 1.1-1.6], but not mortality. CONCLUSIONS: This study showed that surgery for PPU was associated with high 30-day morbidity and mortality rate. Age, female gender, and signs of shock at presentation were associated with both 30-day morbidity and mortality.

Perioperative nutritional assessment and management of patients undergoing gastrointestinal surgery.

Malnutrition is a major issue in gastrointestinal perioperative situations, as only 40% of malnourished patients are finally treated. This literature review investigates the inconsistencies regarding the diagnostic approach to both preoperative and postoperative patients and the various underlying causes, as well as the efficiency of the various therapeutic regimens. A literature search was conducted until August 2023 in MEDLINE and Scopus. Clinical studies involving perioperative nutritional assessment in adult gastrointestinal surgery patients during the last 10 years were included in the present review. Finally, 19 articles were included in the study. Preoperative nutritional therapy is increasingly recognized as a key component of surgical care. Malnourished patients who are hospitalized and operated on, have significantly worse clinical results. Gastrointestinal postoperative malnutrition coexists with metabolic stress, as patients usually suffer from minor chronic inflammations; therefore, postoperative malnutrition is the result of a combination of the effects of inflammation and a lack of food intake. Postoperative malnutrition leads to prolonged hospitalizations and hospital complications and therefore the need to treat it is essential. There are many recognized tools for detecting malnutrition. However, all tools showed inconsistent results regarding their validity. Per os feeding after surgery, and dietary supplements when necessary, have been recommended. Therefore, it is very important to reduce malnutrition and define clear strategies towards that direction.

Malignant Bowel Obstruction: A Retrospective Multicenter Cohort Study.

BACKGROUND: Malignant bowel obstruction (MBO) is a serious clinical entity that requires surgical intervention in almost 50% of cases. However, overall survival remains low even for operable cases. The aim of the present study was to investigate the correlation between patients' characteristics, perioperative details, histopathological results and postoperative outcomes of patients who were operated on due to MBO. METHODS: A retrospective search of patients who were operated on due to MBO in a university and a rural hospital was conducted. Patients' characteristics, perioperative details, histopathological results and postoperative outcomes were reported. Univariable and multivariable analysis was performed. RESULTS: Seventy patients were included with a mean age of 76.1 ± 10.6 years. The 30-day mortality rate was 18.6%, the Intensive Care Unit (ICU) admission rate was 17.1% and the mean length of stay (LOS) was 12.4 ± 5.7 days. Postoperative 30-day mortality was associated with increased age, known malignant recurrence, microscopically visible metastatic foci and defunctioning stoma creation. Colorectal malignancy type, sigmoid obstruction and primary anastomosis were correlated with decreased 30-day mortality. In addition, operation at the university hospital led to increased LOS, while stoma creation led to decreased LOS. Finally, ICU admission rates were increased for operations at university hospitals, at least one comorbidity, known malignant recurrence and longer preoperative waiting interval, whereas they were decreased for colorectal primary malignancy type. CONCLUSIONS: Surgery due to MBO leads to increased morbidity and mortality. Therefore, prospective studies are needed to highlight inter-patient differences regarding the best individualized therapeutic strategy.

The Impact of Mechanical Bowel Preparation and Oral Antibiotics in Colorectal Cancer Surgery (MECCA Study): A Prospective Randomized Clinical Trial.

Background: Colorectal cancer surgery has been associated with surgical site infections (SSIs), leading to an increase in postoperative morbidity, length of stay and total cost. The aim of the present randomized study was to investigate the relationship between the preoperative administration of oral antibiotic therapy and SSI rate, as well as other postoperative outcomes in patients undergoing colorectal cancer surgery. Material and Methods: Patients who underwent colorectal cancer surgery in a university surgical department were included in the present study. Patients were randomized into two groups using the "block randomization" method. The intervention group received three doses of 400 mg rifaximin and one dose of 500 mg metronidazole per os, as well as mechanical bowel preparation the day before surgery. The control group underwent only mechanical bowel preparation the day before surgery. The study has been registered in ClinicalTrials.gov (NCT03563586). Results: Two hundred and five patients were finally included in the present study, 97 of whom received preoperative antibiotic therapy per os (intervention group). Patients of this group demonstrated a significantly lower SSI rate compared with patients who did not receive preoperative antibiotic therapy (7% vs. 16%, p = 0.049). However, preoperative antibiotic administration was not correlated with any other postoperative outcome (anastomotic leak, overall complications, readmissions, length of stay). Conclusions: Preoperative antibiotic therapy in combination with mechanical bowel preparation seemed to be correlated with a lower SSI rate after colorectal cancer surgery.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: An individual participant data meta-analysis.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGCs) of the pancreas is a rare neoplasm that accounts for less than 1% of all pancreatic malignancies. The aim of this study was to review the literature regarding UC-OGC, and to highlight its biological behavior, clinicopathologic characteristics, prognosis, and therapeutic options. A systematic review of the literature in PubMed/Medline and Scopus databases was performed (last search October 31st, 2023) for articles concerning pancreatic UC-OGC in the adult population. Fifty-seven studies met the inclusion criteria, involving 69 patients with a male-to-female ratio of 1.1:1 and a mean age of 62.96. Main symptoms included abdominal pain (33.3%), jaundice (14.5%), weight loss (8.7%), while fourteen patients (20.3%) were asymptomatic. Surgical resection was performed in 88.4% of cases. Survival rates at one, three, and five years were 58%, 44.7%, and 37.3% respectively. Sex, age, size (cut-off of 4 cm), location, and adjuvant treatment did not significantly affect patient survival. UC-OGC of the pancreas is a rare subtype of undifferentiated pancreatic carcinoma with a better prognosis than conventional pancreatic ductal adenocarcinoma or undifferentiated carcinoma without giant cells. The establishment of a dedicated patient registry is imperative to further delineate the optimal treatment for this uncommon clinical entity.