Associations of body composition parameters with postoperative outcome and perineural tumour invasion after oncological pancreatic resection.

BACKGROUND: Pancreatic cancer is often accompanied by wasting conditions. While surgery is the primary curative approach, it poses a substantial risk of postoperative complications, hindering subsequent treatments. Therefore, identifying patients at high risk for complications and optimizing their perioperative general condition is crucial. Sarcopenia and other body composition abnormalities have shown to adversely affect surgical and oncological outcomes in various cancer patients. As most pancreatic tumours are located close to the neuronal control centre for the digestive tract, it is possible that neural infiltration in this area deranges bowel functions and contributes to malabsorption and malnutrition and ultimately worsen sarcopenia and weight loss. METHODS: A retrospective analysis of CT scans was performed for pancreatic cancer patients who underwent surgical tumour resection at a single high-volume centre from 2007 to 2023. Sarcopenia prevalence was assessed by skeletal muscle index (SMI), and visceral obesity was determined by the visceral adipose tissue area (VAT). Obesity and malnutrition were determined by the GLIM criteria. Sarcopenic obesity was defined as simultaneous sarcopenia and obesity. Postoperative complications, mortality and perineural tumour invasion, were compared among patients with body composition abnormalities. RESULTS: Of 437 patients studied, 46% were female, the median age was 69 (61;74) years. CT analysis revealed 54.9% of patients with sarcopenia, 23.7% with sarcopenic obesity and 45.9% with visceral obesity. Sarcopenia and sarcopenic obesity were more prevalent in elderly and male patients. Postoperative surgical complications occurred in 67.7% of patients, most of which were mild (41.6%). Severe complications occurred in 22.7% of cases and the mortality rate was 3.4%. Severe postoperative complications were significantly more common in patients with sarcopenia or sarcopenic obesity. Visceral obesity or malnutrition based on BMI alone, did not significantly impact complications. Perineural invasion was found in 80.1% of patients and was unrelated to malnutrition or body composition parameters. CONCLUSIONS: This is the first and largest study evaluating the associations of CT-based body mass analysis with surgical outcome and histopathological perineural tumour invasion in pancreatic cancer patients. The results suggest that elderly and male patients are at high risk for sarcopenia and should be routinely evaluated by CT before undergoing pancreatic surgery, irrespective of their BMI. Confirmation of the results in prospective studies is needed to assess if pancreatic cancer patients with radiographic sarcopenia benefit from preoperative amelioration of muscle mass and function by exercise and nutritional interventions.

Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia--can findings from animal models be translated to humans?

BACKGROUND: Cachexia is a multi-factorial, systemic syndrome that especially affects patients with cancer of the gastrointestinal tract, and leads to reduced treatment response, survival and quality of life. The most important clinical feature of cachexia is the excessive wasting of skeletal muscle mass. Currently, an effective treatment is still lacking and the search for therapeutic targets continues. Even though a substantial number of animal studies have contributed to a better understanding of the underlying mechanisms of the loss of skeletal muscle mass, subsequent clinical trials of potential new drugs have not yet yielded any effective treatment for cancer cachexia. Therefore, we questioned to which degree findings from animal studies can be translated to humans in clinical practice and research. DISCUSSION: A substantial amount of animal studies on the molecular mechanisms of muscle wasting in cancer cachexia has been conducted in recent years. This extensive review of the literature showed that most of their observations could not be consistently reproduced in studies on human skeletal muscle samples. However, studies on human material are scarce and limited in patient numbers and homogeneity. Therefore, their results have to be interpreted critically. More research is needed on human tissue samples to clarify the signaling pathways that lead to skeletal muscle loss, and to confirm pre-selected drug targets from animal models in clinical trials. In addition, improved diagnostic tools and standardized clinical criteria for cancer cachexia are needed to conduct standardized, randomized controlled trials of potential drug candidates in the future.

Intra-operative wound irrigation to reduce surgical site infections after abdominal surgery: a systematic review and meta-analysis.

PURPOSE: Surgical site infection (SSI) remains to be one of the most frequent infectious complications following abdominal surgery. Prophylactic intra-operative wound irrigation (IOWI) before skin closure has been proposed to reduce bacterial wound contamination and the risk of SSI. However, current recommendations on its use are conflicting especially concerning antibiotic and antiseptic solutions because of their potential tissue toxicity and enhancement of bacterial drug resistances. METHODS: To analyze the existing evidence for the effect of IOWI with topical antibiotics, povidone-iodine (PVP-I) solutions or saline on the incidence of SSI following open abdominal surgery, a systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out according to the recommendations of the Cochrane Collaboration. RESULTS: Forty-one RCTs reporting primary data of over 9000 patients were analyzed. Meta-analysis on the effect of IOWI with any solution compared to no irrigation revealed a significant benefit in the reduction of SSI rates (OR = 0.54, 95 % confidence Interval (CI) [0.42; 0.69], p < 0.0001). Subgroup analyses showed that this effect was strongest in colorectal surgery and that IOWI with antibiotic solutions had a stronger effect than irrigation with PVP-I or saline. However, all of the included trials were at considerable risk of bias according to the quality assessment. CONCLUSION: These results suggest that IOWI before skin closure represents a pragmatic and economical approach to reduce postoperative SSI after abdominal surgery and that antibiotic solutions seem to be more effective than PVP-I solutions or simple saline, and it might be worth to re-evaluate their use for specific indications.

Intraoperative Wound Irrigation for the Prevention of Surgical Site Infection After Laparotomy: A Randomized Clinical Trial by CHIR-Net.

Importance: Surgical site infections frequently occur after open abdominal surgery. Intraoperative wound irrigation as a preventive measure is a common practice worldwide, although evidence supporting this practice is lacking. Objective: To evaluate the preventive effect of intraoperative wound irrigation with polyhexanide solution. Design, Setting, and Participants: The Intraoperative Wound Irrigation to Prevent Surgical Site Infection After Laparotomy (IOWISI) trial was a multicenter, 3-armed, randomized clinical trial. Patients and outcome assessors were blinded to the intervention. The clinical trial was conducted in 12 university and general hospitals in Germany from September 2017 to December 2021 with 30-day follow-up. Adult patients undergoing laparotomy were eligible for inclusion. The main exclusion criteria were clean laparoscopic procedures and the inability to provide consent. Of 11 700 screened, 689 were included and 557 completed the trial; 689 were included in the intention-to-treat and safety analysis. Interventions: Randomization was performed online (3:3:1 allocation) to polyhexanide 0.04%, saline, or no irrigation (control) of the operative wound before closure. Main Outcome and Measures: The primary end point was surgical site infection within 30 postoperative days according to the US Centers for Disease Control and Prevention definition. Results: Among the 689 patients included, 402 were male and 287 were female. The median (range) age was 65.9 (18.5-94.9) years. Participants were randomized to either wound irrigation with polyhexanide (n = 292), saline (n = 295), or no irrigation (n = 102). The procedures were classified as clean contaminated in 92 cases (8%). The surgical site infection incidence was 11.8% overall (81 of 689), 10.6% in the polyhexanide arm (31 of 292), 12.5% in the saline arm (37 of 295), and 12.8% in the no irrigation arm (13 of 102). Irrigation with polyhexanide was not statistically superior to no irrigation or saline irrigation (hazard ratio [HR], 1.23; 95% CI, 0.64-2.36 vs HR, 1.19; 95% CI, 0.74-1.94; P = .47). The incidence of serious adverse events did not differ among the 3 groups. Conclusions and Relevance: In this study, intraoperative wound irrigation with polyhexanide solution did not reduce surgical site infection incidence in clean-contaminated open abdominal surgical procedures compared to saline or no irrigation. More clinical trials are warranted to evaluate the potential benefit in contaminated and septic procedures, including the emergency setting. Trial Registration: drks.de Identifier: DRKS00012251.

Surgical site infection prevention in abdominal surgery: is intraoperative wound irrigation with antiseptics effective? Protocol for a systematic review and meta-analysis.

INTRODUCTION: Surgical site infection (SSI) after laparotomy still represents the most frequent postoperative complicationin abdominal surgery. The effectiveness of reducing SSI rates by intra-operative irrigation of the incisional wound with antiseptic solutions or saline has been much debated, and recommendations on its use are divergent. Therefore, we aim to conduct a systematic review and meta-analysis, focusing specifically on procedures by laparotomy and considering recent evidence only. METHODS AND ANALYSIS: The systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. On 1 July 2022, PubMed/MEDLINE, Cochrane, Central Register of Controlled Trials and EMBASE were searched for the following predefined terms: (Surgical site infection) AND ((irrigation) OR (wound irrigation) OR (lavage)) AND ((abdominal surgery) OR (laparotomy). The search was limited to peer-revied publications, dating after 1 January 2000 in English or German language. Systematic reviews and meta-analyses were included for reference screening. Case reports, case series, non-systematic reviews and studies without follow-up information were excluded. The primary outcome is the rate of postoperative SSI after abdominal surgery by laparotomy. Meta-analysis is pooled using the Mantel-Haenszel method for random effects. The risk of bias in randomised studies will be assessed using the Cochrane developed RoB 2-tool, and the ROBINS-I tool for non-randomised studies. Completion of the analysis and publication is planned in March 2023. ETHICS AND DISSEMINATION: Ethical approval is not necessary for this study, as no new data will be collected. The results of the final study will be published in a peer-reviewed open-access journal. PROSPERO REGISTRATION NUMBER: CRD42022321458.

Peritoneal antiseptic irrigation to prevent surgical site infection after laparotomy for hepatobiliary or gastrointestinal surgery (PAISI)-protocol for a randomized controlled study.

BACKGROUND: Postoperative surgical site infections (SSIs) remain common after laparotomy for resections of the gastrointestinal or hepatobiliary tract. Especially organ/space infections (CDC class III SSI) can be life-threatening, require relaparotomy, intensive care or interventional drainage of intraabdominal abscesses. The PAISI study aims to investigate whether the use of prophylactic peritoneal irrigation with NaOCl/HOCl solution can reduce the SSI rates following laparotomy for resections of the gastrointestinal or hepatobiliary tract, compared to standard irrigation with physiological electrolyte solution (Ringer's solution). Secondarily, to evaluate whether the use of prophylactic peritoneal irrigation with NaOCl/HOCl solution can reduce postoperative morbidity and mortality as well as the rate of re-operations and length of hospital stay. METHODS: PAISI is a prospective, randomized, observer- and patient-blinded, monocentric, two-arm surgical study in an adaptive parallel groups design, comparing peritoneal and wound irrigation with NaOCl/HOCl (50/50ppm) solution to irrigation with Ringer's solution. The primary endpoint of the study is the SSI rate within 30 days postoperatively. Since there is no data on incidence rates from randomized clinical trials, the rates for sample size calculation were estimated according to the clinical experience at our institution. Therefore, the study design includes one unblinded look at the data by a second statistician, which will be performed after half of the patients reached the primary endpoint. This interim information will be used to check the assumptions and if needed, the sample size will be adjusted. The O'Brien-Fleming spending function is used to determine the efficacy test boundary and the non-binding futility boundary. The one-sided z-test (Group sequential test of two proportions) at the 2.5% significance level with a total of two looks at the data will have overall 80% power. DISCUSSION: The results of this study will provide high-level evidence for future research and clinical recommendations regarding the use of NaOCl/HOCl solution in abdominal surgery and provide the participating patients the opportunity of a potentially improved treatment. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00028037. Registered on 27 May 2022.

White Paper on European Patient Needs and Suggestions on Chronic Type 2 Inflammation of Airways and Skin by EUFOREA.

Background: Type 2 inflammation underlies the chronicity of disease in subgroups of patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and atopic dermatitis (AD), that often co-exist. Although several studies have investigated the unmet needs of asthma, AD and CRSwNP as such, little is known about the similarities and differences in experiences and perspectives of the current management of patients with comorbid Type 2 inflammatory diseases. Aims: To improve insight into the common and organ-specific needs of patients with Type 2 inflammation and comorbidities, allowing the formulation of recommendations to better address these needs in the future. Methodology: This qualitative study was conducted between July 2021 and December 2021 using semi-structured face-to-face or telephone interviews with patients suffering from year-long severe chronic Type 2 inflammation and at least one co-morbid inflammatory condition. Seven participating academic centers in Europe interviewed asthma (Copenhagen and Leuven), CRSwNP (London, Amsterdam and Crete) and/or AD (Oldenburg and Zurich) patients on patient characteristics, disease severity, shortcomings of current care pathways and suggestions for improvement of care. Transcripts were analyzed using an inductive thematic analysis approach. Results: Eighty-one patients with severe Type 2 inflammation and comorbidities were interviewed. Similar needs were recognized by patients with Type 2 inflammation, with both a lack of coordination in care and a lack of a real cure reported as being most frustrating. However, several needs are specific to asthma, CRSwNP and AD. Suggestions for improvement of care were generic across diseases, such as the implementation of a multidisciplinary approach, the improved facilitation of access to better treatments, the increase of general awareness on disease burden, and better educational programs for healthcare providers and patients. Of note, patients with CRSwNP also stated the need for alternatives to sinus surgery, whereas patients with asthma requested better medical care to prevent exacerbations and patients with AD would warmly welcome the reimbursement of emollients. Conclusion: Patients with asthma, CRSwNP and AD have shared unmet needs that need to be addressed by physicians, the academic community and health policy makers. This survey provides unique recommendations made by patients for the implementation of better care.

Corrigendum on: White paper on European patient needs and suggestions on chronic type 2 inflammation of airways and skin by EUFOREA.

[This corrects the article DOI: 10.3389/falgy.2022.889221.].

Plasmodium knowlesi infection in humans, Cambodia, 2007-2010.

Two cases of Plasmodium knowlesi infection in humans were identified in Cambodia by 3 molecular detection assays and sequencing. This finding confirms the widespread distribution of P. knowlesi malaria in humans in Southeast Asia. Further wide-scale studies are required to assess the public health relevance of this zoonotic malaria parasite.

Measurement of body mass by bioelectrical impedance analysis and computed tomography in cancer patients with malnutrition - a cross-sectional observational study.

Malnutrition and cachexia affects the majority of cancer patients and significantly worsens their quality of life and prognosis. However, the diagnostic criteria of malnutrition and cachexia remain a topic under constant debate. To overcome this hurdle, diagnostic tools to objectively detect and quantify the loss of muscle and fat mass are needed. Computed tomography (CT)-based measurement is currently considered the golden standard. Bioelectrical impedance analysis (BIA) is an economical, non-invasive tool but it is seen controversial in patients with cancer and malnutrition because of possible estimation errors.BIA and CT-based analysis of body mass compartments were performed 172 times in 118 cancer patients, within the nutrition program of our institution. Prevalence of malnutrition was determined according to the global leadership initiative on malnutrition criteria. Data obtained for muscle and fat mass from both BIA and CT were correlated using Pearson's ρ. All analyses were performed with an explorative significance level of 5%.45.7% of the cohort were classified as "malnourished." No significant differences were observed between the 2 groups regarding demographic data. Median body mass index, Karnofsky performance status, and nutritional risk score were lower in the malnourished group. Values for muscle and fat mass by BIA and CT were significantly lower in malnourished patients. Correlation of the measured parameters were highly significant between CT-based and BIA measurement. In the overall cohort, correlation of measured muscle mass values by CT and BIA was significant with Pearson's ρ = 0.794 (P < .01). Looking at patients without malnutrition only, Pearson's ρ was 0.754 (P < .01). The correlation of measured fat mass values was equally significant, with Pearson's ρ of 0.748 (P < .01) in the overall cohort and 0.771 (P < .01) in patients with malnutrition.To our knowledge, this is the first study comparing BIA to CT-based body mass analysis in a large cohort of cancer patients with malnutrition. The results suggest that BIA is a valid diagnostic tool for the assessment of muscle and fat mass, even in patients with malnutrition, and could be implemented for the early detection and short-term follow-up of malnutrition and cachexia.

Intraoperative wound irrigation to prevent surgical site infection after laparotomy (IOWISI): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative surgical site infection (SSI) is one of the most common hospital infections and contributes substantially to postoperative morbidity and mortality. In addition, SSIs dramatically increase the treatment cost and length of hospital stay. Following visceral surgery by laparotomy, SSI rates are especially high (14-25%). Therefore, measures to prevent SSI in this field are urgently needed. Prophylactic intraoperative wound irrigation (IOWI) of the subcutaneous soft tissue before skin closure hypothetically represents an easy and economical option to reduce SSI rates and is already frequently used in clinical practice. However, there are currently no definite recommendations on the use of IOWI since high-level evidence supporting its use is lacking. Consequently, clinical practice varies widely. Antiseptic polyhexanide (PHX)-based solutions are approved for soft-tissue wound irrigation in surgery but have not been specifically evaluated in randomized clinical trials for the prevention of SSI following laparotomy for visceral surgery. METHODS/DESIGN: The IOWISI trial is a multicentre, randomized, observer- and patient-blinded clinical trial with three parallel treatment groups, comparing IOWI with a 0.04% PHX solution to no irrigation (test 1) or saline (test 2) before skin closure after laparotomy for visceral surgery (contamination level II-IV). The primary endpoint of the trial is the SSI rate within 30 days postoperatively. Statistical analysis of the primary endpoint measure will be based on the intention-to-treat population. The global level of significance is set at 2.5% for test 1 and 5% for test 2 and the sample size (n = 540) is determined to assure a power of 94% (test 1) and 85% (test 2). DISCUSSION: The IOWISI trial will provide high-level evidence as a basis for clinical recommendations regarding the use of IOWI with PHX or saline and will potentially impact on future clinical guidelines and practice. The pragmatic trial design guarantees high external validity. TRIAL REGISTRATION: Registered at the German Clinical Trials Register, DRKS00012251 . Registered on 3 July 2017.

Parenteral nutrition during neoadjuvant chemotherapy for patients with non-metastatic gastric or esophago-gastric cancer to reduce postoperative morbidity (PERCOG): study protocol for a randomized controlled trial.

BACKGROUND: The majority of patients with gastric or esophago-gastric cancer are at risk for malnutrition. Preoperative malnutrition was shown to increase the incidence of postoperative complications following abdominal surgery. However, it remains unclear if preoperative parenteral nutritional support during neoadjuvant chemotherapy (NACT) may be effective to reduce the rate of postoperative complications in these patients. METHODS/DESIGN: The PERCOG trial is a randomized controlled multicenter observer-blinded trial, investigating if the improvement of the general condition of patients with non-metastasized gastric cancer or cancer of the esophago-gastric junction during NACT by supplemental parenteral nutrition can decrease the postoperative Comprehensive Complication Index (CCI). Statistical analysis of the primary endpoint measure (CCI on postoperative day 30) will be based on the intention-to-treat population. The global level of significance is set at 5% and the sample size (n = 150) is determined to assure a power of 80%. DISCUSSION: The results of the PERCOG trial will provide high-level evidence for clinical recommendations regarding the administration of preoperative supportive parenteral nutrition and provide all participating patients the opportunity of an improved treatment. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00009451 . Registered on 3 July 2017.

Cachexia and pancreatic cancer: are there treatment options?

Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cachexia. However, recent studies have demonstrated that multidimensional therapeutic modalities are able to alleviate pancreatic cancer-associated cachexia and ultimately improve patients' outcome. In this current review, we propose a stepwise and pragmatic approach to facilitate and standardize the treatment of cachexia in pancreatic cancer patients. This strategy consists of nutritional, dietary, pharmacological, physical and psychological methods.

Acute undifferentiated febrile illness in rural Cambodia: a 3-year prospective observational study.

In the past decade, malaria control has been successfully implemented in Cambodia, leading to a substantial decrease in reported cases. Wide-spread use of malaria rapid diagnostic tests (RDTs) has revealed a large burden of malaria-negative fever cases, for which no clinical management guidelines exist at peripheral level health facilities. As a first step towards developing such guidelines, a 3-year cross-sectional prospective observational study was designed to investigate the causes of acute malaria-negative febrile illness in Cambodia. From January 2008 to December 2010, 1193 febrile patients and 282 non-febrile individuals were recruited from three health centers in eastern and western Cambodia. Malaria RDTs and routine clinical examination were performed on site by health center staff. Venous samples and nasopharyngeal throat swabs were collected and analysed by molecular diagnostic tests. Blood cultures and blood smears were also taken from all febrile individuals. Molecular testing was applied for malaria parasites, Leptospira, Rickettsia, O. tsutsugamushi, Dengue- and Influenza virus. At least one pathogen was identified in 73.3% (874/1193) of febrile patient samples. Most frequent pathogens detected were P. vivax (33.4%), P. falciparum (26.5%), pathogenic Leptospira (9.4%), Influenza viruses (8.9%), Dengue viruses (6.3%), O. tsutsugamushi (3.9%), Rickettsia (0.2%), and P. knowlesi (0.1%). In the control group, a potential pathogen was identified in 40.4%, most commonly malaria parasites and Leptospira. Clinic-based diagnosis of malaria RDT-negative cases was poorly predictive for pathogen and appropriate treatment. Additional investigations are needed to understand their impact on clinical disease and epidemiology, and the possible role of therapies such as doxycycline, since many of these pathogens were seen in non-febrile subjects.