Psychological Benefits of a Preoperative Educational Bridging Program for Bariatric Surgery: Does Face-to-Face versus Videoconference-based delivery make a difference?

INTRODUCTION: Short educational programs prior to metabolic and bariatric surgery (MBS) provide information to prepare patients adequately for surgery and subsequent changes. Our knowledge of the beneficial effects of these programs on stabilizing and improving mental health of patients with obesity awaiting surgery is incomplete. The objective of this study was to assess the effects of a group-based educational program before MBS on three key factors: i) patients' mental health, ii) the program's perceived helpfulness from the patients' perspective, and iii) the effectiveness of delivering the program online via videoconferencing. METHODS: Validated questionnaires for anxiety, depression, stress, and quality of life before and after the program were assessed. Additionally, participants' perspectives of benefits were assessed. Two subgroups, one participating in face-to-face classes, the other participating online via videoconferencing, were compared. RESULTS: Three hundred five patients with obesity waiting for MBS participated in the program. The dropout rate was 3%. On mean average, symptoms of anxiety (-1.1 units (SD 4.6), p < 0.001), depression (-0.9 units (SD 4.6), p < 0.001), and stress (-4.6 units (SD 15.6), p < 0.001) improved, while physical quality of life (+1.7 (SD 9.7), p = 0.016) and body weight (-0.3 kg (SD 8.7), p = 0.57) remained stable. Patients perceived the program as very beneficial. The results were similar between delivery methods (face-to-face versus videoconferencing). CONCLUSION: The educational program proved to be effective in bridging the gap in preoperative preparation while also stabilizing participants' mental health. In addition, participants perceived the program as supportive. Online participation via video conferencing can be offered as an equivalent option to face-to-face classes.

Peritoneal regression grading score (PRGS): first evidence for independent predictive and prognostic significance.

Objectives: The peritoneal regression grading score (PRGS) is a four-tied pathologic score measuring tumor regression in biopsies from patients with peritoneal metastasis (PM) receiving chemotherapy. Methods: This retrospective analysis of a prospective registry (NCT03210298) analyses 97 patients with isolated PM under palliative chemotherapy. We examined the predictive value of the initial PRGS for overall survival (OS) and the prognostic value of PRGS in repeated peritoneal biopsies. Results: The 36 (37.1 %) patients with an initial mean PRGS≤2 had a longer median OS (12.1 months, CI 95 % 7.8-16.4) vs. 8.0 months (CI 95 % 5.1-10.8 months) in 61 (62.9 %) patients with PRGS≥3 (p=0.02) After stratification, the initial PRGS was an independent predictor of OS (Cox-regression, p<0.05). Out of 62 patients receiving≥two chemotherapy cycles, 42 (67.7 %) had a histological response (defined as a lower or stable mean PRGS in successive therapy cycles), and 20 (32.3 %) progressed (defined as an increasing mean PRGS). PRGS response was associated with a longer median OS (14.6 months, CI 5-95 % 6.0-23.2) vs. 6.9 (CI 5-95 % 0.0-15.9) months. PRGS response was prognostic in the univariate analysis (p=0.017). Thus, PRGS had both a predictive and prognostic significance in patients with isolated PM receiving palliative chemotherapy in this patient cohort. Conclusions: This is the first evidence for the independent predictive and prognostic significance of PRGS in PM. These encouraging results need validation in an adequately powered, prospective study.

Effects of Lifestyle and Educational Bridging Programs before Bariatric Surgery on Postoperative Weight Loss: A Systematic Review and Meta-Analysis.

OBJECTIVE: To fulfill the requirements for bariatric surgery, patients often need to participate in mandatory preoperative lifestyle interventions. Currently, the efficacy of multi-month preoperative lifestyle intervention programs on body mass index (BMI) reduction from the start of the program (T0) through the immediate preoperative time point (T1) to 1 year post-surgery (T2) and how the amount of preoperative BMI reduction affects postoperative outcome (T1 to T2) is unclear. The aim of this meta-analysis was to analyze the effects of preoperative lifestyle interventions on BMI 1 year post-surgery. METHOD: A systematic literature search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Randomized controlled trials that implemented preoperative lifestyle interventions lasting 1-8 months before bariatric surgery were included. The BMI of the intervention group was compared with that of a control group before participation in the preoperative lifestyle interventions (T0), after completion of the program before surgery (T1), and 1 year post-surgery (T2). Finally, the impact of successful BMI reduction at T1 on BMI at T2 was analyzed. RESULTS: N = 345 patients derived from 4 studies undergoing preoperative lifestyle interventions reduced their BMI at T1 by 1.5 units compared to the control group (95% CI: -2.73, -0.28). One year post-surgery, both groups had lost comparable BMI points. The influence of reduced BMI at T1 on weight status at T2 is unclear due to the lack of available studies. Other endpoints and subgroup analyses were rarely examined. CONCLUSIONS: Preoperative lifestyle interventions reduce BMI before bariatric surgery more effectively than usual care. These differences are not detectable 1 year post-surgery. Although a short-term energy reduction period before surgery is clearly important to minimize surgery risks, it is currently unclear whether, and if so, under what circumstances, participation in a preoperative lifestyle intervention is beneficial.

Treatment of Acute Mesenteric Ischemia: Individual Challenges for Interventional Radiologists and Abdominal Surgeons.

Background: Acute mesenteric ischemia (AMI) is a life-threatening condition resulting from occlusion of the mesenteric arterial vessels. AMI requires immediate treatment with revascularization of the occluded vessels. Purpose: to evaluate the technical success, clinical outcomes and survival of patients receiving endovascular treatment for AMI followed by surgery. Material and Methods: A search of our institution's database for AMI revealed 149 potential patients between 08/2016 and 08/2021, of which 91 were excluded due to incomplete clinical data, insufficient imaging or missing follow-up laparoscopy. The final cohort included 58 consecutive patients [(median age 73.5 years [range: 43−96 years], 55% female), median BMI 26.2 kg/m2 (range:16.0−39.2 kg/m2)]. Periinterventional imaging regarding the cause of AMI (acute-embolic or acute-on-chronic) was evaluated by two radiologists in consensus. The extent of AMI and the degree of technical success was graded according to a modified TICI (Thrombolysis in Cerebral Infarction scale) score (TICI-AMI) classification (0: no perfusion; 1: minimal; 2a < 50% filling; 2b > 50%; 2c: near complete or slow; 3: complete). Lab data and clinical data were collected, including the results of follow-up laparoscopy. Non-parametric statistics were used. Results: All interventions were considered technically successful. The most common causes of AMI were emboli (51.7%) and acute-on-chronic thrombotic occlusions (37.9%). Initial imaging showed a TICI-AMI score of 0, 1 or 2a in 87.9% (n = 51) of patients. Post-therapeutic TICI-AMI scores improved significantly with 87.9% of patients grade 2b and better. Median lactate levels reduced from 2.7 (IQR 2.0−3.7) mg/dL (1−18) to 1.45 (IQR 0.99−1.90). Intestinal ischemia was documented in 79.1% of cases with resection of the infarcted intestinal loops. In total, 22/58 (37.9%) patients died during the first 30 days after intervention and surgery. According to CIRSE criteria, we did not observe any SAE scores of grade 2 or higher. Conclusions: AMI is a serious disease with high lethality within the first 30 days despite optimal treatment. However, interventional revascularization before surgery with resection of the infarcted bowel can save two out of three of critically ill patients.

Role of Rendezvous-Procedure in the Treatment of Complications after Laparoscopic Sleeve Gastrectomy.

INTRODUCTION: Laparoscopic sleeve gastrectomy is one of the most commonly performed bariatric procedures worldwide with good results, high patient acceptance, and low complication rates. The most relevant perioperative complication is the staple line leak. For the treatment of this complication, endoscopic negative pressure therapy has proven particularly effective. The correct time to start endoscopic negative pressure therapy has not been the subject of studies to date. METHODS: Twelve patients were included in this retrospective data analysis over three years. Endoscopic negative pressure therapy was carried out using innovative open pore suction devices. Patients were treated with simultaneous surgery and endoscopy, so called rendezvous-procedure (Group A) or solely endoscopically, or in sequence surgically and endoscopically (Group B). Therapy data of the procedures and outcome measures, including duration of therapy, therapy success, and change of treatment strategy, were collected and analysed. RESULTS: In each group, six patients were treated (mean age 52.96 years, 4 males, 8 females). Poor initial clinical situation, time span of endoscopic negative pressure therapy (Group A 31 days vs. Group B 18 days), and mean length of hospital stay (Group A 39.5 days vs. Group B 20.17 days) were higher in patients with rendezvous procedures. One patient in Group B died during the observation time. DISCUSSION: Rendezvous procedures for patients with staple line leaks after sleeve gastrectomy is indicated for serious ill patients with perigastric abscesses and in need of laparoscopic lavage. The one-stage complication management with the rendezvous procedure seems not to result in an obvious advantage in the further outcome in patients with staple line leaks after laparoscopic sleeve gastrectomy.

Endoscopic Negative Pressure Therapy (ENPT) Is Superior to Stent Therapy for Staple Line Leak After Sleeve Gastrectomy: a Single-Center Cohort Study.

PURPOSE: Staple line leak (SLL) is a serious complication after sleeve gastrectomy (SG). Common endoscopic treatment options include self-expandable metallic stent (SEMS), endoscopic internal drainage (EID), and endoscopic closure. The endoscopic negative pressure therapy (ENPT) is a promising treatment option combining temporary sealing of the defect with drainage of the inflammatory bed. In this study, we compare the outcome of ENPT and SEMS for the treatment of SLL following SG. MATERIALS AND METHODS: A retrospective cohort of 27 patients (21 females) treated at a single center for SLL after SG was included. ENPT was primary therapy for 14 patients and compared with 13 patients treated primarily using SEMS. RESULTS: ENPT was associated with a significant reduction of hospital stay (19 ± 15.1 vs. 56.69 ± 47.21 days, p = 0.027), reduced duration of endoscopic treatment (9.8 ± 8.6 vs. 44.92 ± 60.98 days, p = 0.009), and shorter transabdominal drain dwell time (15 (5-96) vs. 45 (12-162) days, p = 0.014) when compared to SEMS. Whereas endoscopic management was successful in 12/14 (85.7%) of patients from the ENPT group, SEMS was successful in only 5/13 (38.5%) of patients (p = 0.015). Furthermore, ENPT was associated with a significant reduction of endoscopic adverse events compared with SEMS (14.3% vs. 76.92% p = 0.001). CONCLUSION: Compared with SEMS, ENPT is effective and safe in treating SLL after SG providing higher success rates, shorter treatment duration, and lower adverse events rates.

Impact of Resection Volume/Stapler Firings-Ratio on Perioperative Complications and Weight Loss After Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Major postoperative morbidity after laparoscopic sleeve gastrectomy (LSG) is often related to staple line leaks (SLL). Of note, a recent study suggested a central role of the absolute numbers of stapler firings as a predictive factor for postoperative morbidity due to SLL. In addition, a larger gastric remnant volume could be responsible for lower weight loss after LSG, and nevertheless, the gastric resection volume (GRV) is strictly related to the residual volume. METHODS: Prospectively, collected data of 384 consecutive patients with complete follow-up at 12 months after LSG at our institution were retrospectively analyzed. Patients were stratified according to three different variables (i.e., number of stapler firings, GRV, and GRV/stapler firings-ratio), and respective impact on postoperative complications and weight loss was analyzed. RESULTS: High absolute number of stapler firings was linked to increased intraoperative and postoperative bleeding and prolonged hospitalization, but was not associated with SLL, transfusion rate or revisional procedures. Absolute GRV showed no impact on both complications and outcome after LSG. Interestingly, higher ratio of GRV/stapler firings was not only linked to decreased intraoperative bleeding and shorter hospital stay but also to higher Excess Body Mass Index Loss (EBMIL) at 12 months after LSG. CONCLUSIONS: Here, we introduce GRV/stapler firings-ratio as a simple predictive factor for identifying patients at risk for postoperative complications and impaired weight loss that is superior compared with absolute number of stapler firings or GRV alone.

Pyogenic Liver Abscesses Caused by Acute Appendicitis: Frequency and Diagnostic and Therapeutic Recommendations.

Background: Pyogenic liver abscesses (PLA) are caused by biliary diseases or hematogenous spreading of mostly intra-abdominal infections. Liver abscesses resulted in hematogenous spreading of infections via the portal vein, such as abscesses caused by acute appendicitis. Pyogenic liver abscesses associated with appendicitis have rarely been described in the literature, especially in adults. The standard therapeutic procedures for liver abscesses are broad-spectrum antibiotic therapy and percutaneous drainage. Surgery for liver abscesses is required in cases of unsuccessful processes. Patients and Methods: A retrospective analysis of patients with liver abscesses between January 2005 and June 2013 was performed. Parameters investigated included demographics, etiologies of abscesses, treatment modalities, and germ spectrum including antibiotic profile. Five cases of PLA caused by appendicitis were reviewed in detail. Results: During the study period, 49 patients with PLA and 1,986 patients with acute appendicitis were treated in our hospital. Twenty-one patients with PLA were treated with antibiotic agents and computed tomography (CT)-guided drainage. Liver resections were necessary in 29 of the patients with PLA. In five patients with PLA, abscesses were caused by an acute appendicitis (9.4% of all PLA, 0.25% of all appendicitis operations). Diagnosis of appendicitis as cause of PLA was made during surgery for liver resections in three patients. Previous imaging was not clear in all cases of PLA caused by appendicitis. The most common pre-operative symptoms in patients with PLA caused by appendicitis were fever and right upper quadrant tenderness. Discussion: Pyogenic liver abscesses caused by acute appendicitis are rare. In the study period of eight and one-half years nearly 2,000 cases of acute appendicitis were treated and five of these patients developed liver abscesses (0.25%). Pyogenic liver abscesses should be considered in patients with unusual high infectious parameters, septic symptoms, and detection of unknown liver lesions.

Gut Microbiota, Probiotics and Psychological States and Behaviors after Bariatric Surgery-A Systematic Review of Their Interrelation.

The gastrointestinal (GI) microbiota plays an important role in health and disease, including brain function and behavior. Bariatric surgery (BS) has been reported to result in various changes in the GI microbiota, therefore demanding the investigation of the impact of GI microbiota on treatment success. The goal of this systematic review was to assess the effects of BS on the microbiota composition in humans and other vertebrates, whether probiotics influence postoperative health, and whether microbiota and psychological and behavioral factors interact. A search was conducted using PubMed and Web of Science to find relevant studies with respect to the GI microbiota and probiotics after BS, and later screened for psychological and behavioral parameters. Studies were classified into groups and subgroups to provide a clear overview of the outcomes. Microbiota changes were further assessed for whether they were specific to BS in humans through the comparison to sham operated controls in other vertebrate studies. Changes in alpha diversity appear not to be specific, whereas dissimilarity in overall microbial community structure, and increases in the abundance of the phylum Proteobacteria and Akkermansia spp. within the phylum Verrucomicrobia after surgery were observed in both human and other vertebrates studies and may be specific to BS in humans. Human probiotic studies differed regarding probiotic strains and dosages, however it appeared that probiotic interventions were not superior to a placebo for quality of life scores or weight loss after BS. The relationship between GI microbiota and psychological diseases in this context is unclear due to insufficient available data.

Reprogramming of Mesothelial-Mesenchymal Transition in Chronic Peritoneal Diseases by Estrogen Receptor Modulation and TGF-ß1 Inhibition.

In chronic peritoneal diseases, mesothelial-mesenchymal transition is determined by cues from the extracellular environment rather than just the cellular genome. The transformation of peritoneal mesothelial cells and other host cells into myofibroblasts is mediated by cell membrane receptors, Transforming Growth Factor ß1 (TGF-ß1), Src and Hypoxia-inducible factor (HIF). This article provides a narrative review of the reprogramming of mesothelial mesenchymal transition in chronic peritoneal diseases, drawing on the similarities in pathophysiology between encapsulating peritoneal sclerosis and peritoneal metastasis, with a particular focus on TGF-ß1 signaling and estrogen receptor modulators. Estrogen receptors act at the cell membrane/cytosol as tyrosine kinases that can phosphorylate Src, in a similar way to other receptor tyrosine kinases; or can activate the estrogen response element via nuclear translocation. Tamoxifen can modulate estrogen membrane receptors, and has been shown to be a potent inhibitor of mesothelial-mesenchymal transition (MMT), peritoneal mesothelial cell migration, stromal fibrosis, and neoangiogenesis in the treatment of encapsulating peritoneal sclerosis, with a known side effect and safety profile. The ability of tamoxifen to inhibit the transduction pathways of TGF-ß1 and HIF and achieve a quiescent peritoneal stroma makes it a potential candidate for use in cancer treatments. This is relevant to tumors that spread to the peritoneum, particularly those with mesenchymal phenotypes, such as colorectal CMS4 and MSS/EMT gastric cancers, and pancreatic cancer with its desmoplastic stroma. Morphological changes observed during mesothelial mesenchymal transition can be treated with estrogen receptor modulation and TGF-ß1 inhibition, which may enable the regression of encapsulating peritoneal sclerosis and peritoneal metastasis.

MRI-guided percutaneous thermoablation in combination with hepatic resection as parenchyma-sparing approach in patients with primary and secondary hepatic malignancies: single center long-term experience.

BACKGROUND: Combination therapy using hepatic resection (HR) and intra-operative thermal ablation is a treatment approach for patients with technically unresectable liver malignancies. The aim of this study was to investigate safety, survival and local recurrence rates for patients with technically unresectable liver tumors undergoing HR and separate percutaneous MR-guided thermoablation procedure as an alternative approach. METHODS: Data from all patients with primary or secondary hepatic malignancies treated at a single institution between 2004 and 2018 with combined HR and MR-guided percutaneous thermoablation was collected and retrospectively analyzed. Complications, procedure related information and patient characteristics were collected from institutional records. Overall survival and disease-free survival were estimated using the Kaplan-Meier method. RESULTS: A total of 31 patients (age: 62.8 ± 9.1 years; 10 female) with hepatocellular carcinoma (HCC; n = 7) or hepatic metastases (n = 24) were treated for 98 hepatic tumors. Fifty-six tumors (mean diameter 28.7 ± 23.0 mm) were resected. Forty-two tumors (15.1 ± 7.6 mm) were treated with MR-guided percutaneous ablation with a technical success rate of 100%. Local recurrence at the ablation site occurred in 7 cases (22.6%); none of these was an isolated local recurrence. Six of 17 patients (35.3%) treated for colorectal liver metastases developed local recurrence. Five patients developed recurrence at the resection site (16.1%). Non-local hepatic recurrence was observed in 18 cases (58.1%) and extrahepatic recurrence in 11 cases (35.5%) during follow-up (43.1 ± 26.4 months). Ten patients (32.3%) developed complications after HR requiring pharmacological or interventional treatment. No complication requiring therapy was observed after ablation. Median survival time was 44.0 ± 7.5 months with 1-,3-, 5-year overall survival rates of 93.5, 68.7 and 31.9%, respectively. The 1-, 3- and 5-year disease-free survival rates were 38.7, 19.4 and 9.7%, respectively. CONCLUSION: The combination of HR and MR-guided thermoablation is a safe and effective approach in the treatment of technically unresectable hepatic tumors and can achieve long-term survival.

Endoscopic negative pressure therapy with open-pore film drainage and open-pore polyurethane sponge drainage for iatrogenic perforation of the esophagus.

BACKGROUND: Management of iatrogenic esophageal perforation (IEP) is challenging. Endoscopic negative pressure therapy (ENPT) is an emerging and effective tool for the treatment of gastrointestinal and anastomotic leaks. We have used ENPT as first-line therapy for IEP since 2017. The aim of this study was to present our results with this strategy in patients with IEP. METHODS: Nine patients were treated with ENPT for IEP between August 2017 and August 2019. Their treatment characteristics, including duration of therapy, strategy used, and outcomes, were analyzed. Treatment included ENPT with open-pore film drainage (OFD) and open-pore polyurethane foam drainage (OPD). RESULTS: Early diagnosis (< 24 hours) of IEP occurred in four patients. After a mean (standard deviation) of 19.0 (13.5) days of ENPT, 6.4 (3.4) endoscopies, and 38.1 (40.3) days of hospitalization, endoscopic treatment was effective and successful in all of the patients. Additional video-assisted thoracic surgery (VATS) was done in four patients. CONCLUSIONS: ENPT is an effective new method for the management of IEP. ENPT with OFD and OPD can be combined with minimally invasive operative methods for sepsis control in IEP.

shRNA-mediated inhibition of PhosphoGlycerate Kinase 1 (PGK1) enhances cytotoxicity of intraperitoneal chemotherapy in peritoneal metastasis of gastric origin.

BACKGROUND: Phosphoglycerate kinase 1 (PGK1) plays metabolic, kinase and translational roles in Peritoneal metastasis (PM) of gastric origin and is associated with chemoresistance. Silencing PGK1 might potentiate the effect of chemotherapy. METHODS: In an orthoptic xenograft nude mice model, human gastric cancer cells (MKN45) were grown in 22 donor animals. Solid tumors were then grafted into the gastric subserosa of 102 recipient animals and allowed to grow for 10 days. Animals were randomized into 7 groups: Five test groups: 1) Mitomycin C (MMC), 2) MMC and small hairpin RNA silencing of PGK1 with an adenoviral vector (Adv-shPGK1), 3) 5-fluorouracil (5-FU), 4) 5-FU and Adv-shPGK1, 5) Adv-shPGK1 alone; two control groups: 1) Sham (NaCl 0.9%), 2) empty viral vector. Intraperitoneal therapy was administered on postoperative day (POD) 11 and 18. Animals were sacrificed at POD 21, analysis was blinded to therapy. RESULTS: Adding Adv-shPGK1 to 5-FU reduced the number (0.23 ± 0.43 vs. 1.36 ± 1.00, p = 0.005) and weight (0,005 ± 0.012 mg vs. 0.05 ± 0.08 mg, p = 0.002) of PM as compared to 5-FU alone. The effect of adding Adv-shPGK1 to MMC did not reach statistical significance. Mortality was not increased by adding Adv-shPGK1 to chemotherapy but was increased by Adv-shPGK1 alone as compared to sham. CONCLUSION: In this experimental model, combined therapy with chemotherapy and Adv-shPGK1 improves control of PM of gastric origin as compared to chemotherapy alone and might counteract chemoresistance of PM. A systemic toxicity of Adv-shPGK1 cannot be excluded.

Endoscopic Vacuum Therapy for Staple Line Leaks after Sleeve Gastrectomy.

PURPOSE: Management of staple line leaks (SLL) after sleeve gastrectomy (SG) is challenging. The aim of this study was to evaluate the effectiveness of a novel endoscopic vacuum therapy (EVT) modality in the management of sleeve leaks. MATERIALS AND METHODS: Eight patients were treated with EVT for SLL. Therapy data and outcome measures including duration of therapy, therapy success, and change of treatment strategy were collected and analyzed. RESULTS: During the study period, SLL occurred in 1.6% of patients who underwent SG. After 9.8 ± 8.6 days of EVT, 3.3 ± 2.2 endoscopies, and 19 ± 15.1 days of hospitalization, endoscopic treatment using EVT was successful in seven out of eight patients (87.5%). CONCLUSIONS: EVT is an effective method for the management of staple line leaks after sleeve gastrectomy. The use of the intraluminal open-pore film drainage (OFD) could be considered as an advantageous modality of EVT, regarding placement and complications.

Overcoming Drug Resistance by Taking Advantage of Physical Principles: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).

Theoretical considerations as well as comprehensive preclinical and clinical data suggest that optimizing physical parameters of intraperitoneal drug delivery might help to circumvent initial or acquired resistance of peritoneal metastasis (PM) to chemotherapy. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel minimally invasive drug delivery system systematically addressing the current limitations of intraperitoneal chemotherapy. The rationale behind PIPAC is: 1) optimizing homogeneity of drug distribution by applying an aerosol rather than a liquid solution; 2) applying increased intraperitoneal hydrostatic pressure to counteract elevated intratumoral interstitial fluid pressure; 3) limiting blood outflow during drug application; 4) steering environmental parameters (temperature, pH, electrostatic charge etc.) in the peritoneal cavity for best tissue target effect. In addition, PIPAC allows repeated application and objective assessment of tumor response by comparing biopsies between chemotherapy cycles. Although incompletely understood, the reasons that allow PIPAC to overcome established chemoresistance are probably linked to local dose intensification. All pharmacological data published so far show a superior therapeutic ratio (tissue concentration/dose applied) of PIPAC vs. systemic administration, of PIPAC vs. intraperitoneal liquid chemotherapy, of PIPAC vs. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) or PIPAC vs. laparoscopic HIPEC. In the initial introduction phase, PIPAC has been used in patients who were quite ill and had already failed multiple treatment regimes, but it may not be limited to that group of patients in the future. Rapid diffusion of PIPAC in clinical practice worldwide supports its potential to become a game changer in the treatment of chemoresistant isolated PM of various origins.

Cachexia Anorexia Syndrome and Associated Metabolic Dysfunction in Peritoneal Metastasis.

: Patients with peritoneal metastasis (PM) of gastrointestinal and gynecological origin present with a nutritional deficit characterized by increased resting energy expenditure (REE), loss of muscle mass, and protein catabolism. Progression of peritoneal metastasis, as with other advanced malignancies, is associated with cancer cachexia anorexia syndrome (CAS), involving poor appetite (anorexia), involuntary weight loss, and chronic inflammation. Eventual causes of mortality include dysfunctional metabolism and energy store exhaustion. Etiology of CAS in PM patients is multifactorial including tumor growth, host response, cytokine release, systemic inflammation, proteolysis, lipolysis, malignant small bowel obstruction, ascites, and gastrointestinal side effects of drug therapy (chemotherapy, opioids). Metabolic changes of CAS in PM relate more to a systemic inflammatory response than an adaptation to starvation. Metabolic reprogramming is required for cancer cells shed into the peritoneal cavity to resist anoikis (i.e., programmed cell death). Profound changes in hexokinase metabolism are needed to compensate ineffective oxidative phosphorylation in mitochondria. During the development of PM, hypoxia inducible factor-1α (HIF-1α) plays a key role in activating both aerobic and anaerobic glycolysis, increasing the uptake of glucose, lipid, and glutamine into cancer cells. HIF-1α upregulates hexokinase II, phosphoglycerate kinase 1 (PGK1), pyruvate dehydrogenase kinase (PDK), pyruvate kinase muscle isoenzyme 2 (PKM2), lactate dehydrogenase (LDH) and glucose transporters (GLUT) and promotes cytoplasmic glycolysis. HIF-1α also stimulates the utilization of glutamine and fatty acids as alternative energy substrates. Cancer cells in the peritoneal cavity interact with cancer-associated fibroblasts and adipocytes to meet metabolic demands and incorporate autophagy products for growth. Therapy of CAS in PM is challenging. Optimal nutritional intake alone including total parenteral nutrition is unable to reverse CAS. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) stabilized nutritional status in a significant proportion of PM patients. Agents targeting the mechanisms of CAS are under development.

Staging laparoscopy and Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for peritoneal metastasis: safe access to the abdomen.

BACKGROUND: Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is an innovative drug delivery technique. Most common indication is palliative therapy of peritoneal metastasis of gastrointestinal and gynecological origin in the salvage situation. Access to the abdomen is the critical step of the procedure, since most patients had previous surgery. Potential pitfalls include non-access because of adhesions, bowel access lesions and postoperative subcutaneous toxic emphysema. METHODS: We propose a technique, the "finger-access technique" that might prevent largely these pitfalls. A minilaparotomy of 3 cm is performed in the midline, a finger introduced into the abdomen and a 5-mm double-balloon trocar (no Hasson trocar) is placed under finger protection at some distance of the first incision. The fascia of the minilaparotomy, not the skin, is then closed. The abdomen is insufflated with CO2 and tightness is controlled with saline solution in the minilaparotomy. A second 10-12 mm trocar is then introduced under videoscopic control. The first trocar is then visualized through the second one to exclude a bowel lesion during first access. RESULTS AND CONCLUSIONS: In our hands, this access technique has shown to be safe and effective.

Resistance to anoikis in transcoelomic shedding: the role of glycolytic enzymes.

Detachment of cells from the extracellular matrix into the peritoneal cavity initiates a cascade of metabolic alterations, leading usually to cell death by apoptosis, so-called anoikis. Glycolytic enzymes enable the switch from oxidative phosphorylation to aerobic glycolysis and allow resistance to anoikis of shed tumour cells. These enzymes also have moonlighting activities as protein kinases and transcription factors. Phosphoglycerate kinase (PGK) and pyruvate kinase are the only glycolytic enzymes generating ATP in the hexokinase pathway. Hypoxia, EGFR activation, expression of K-Ras G12V and B-Raf V600E induce mitochondrial translocation of phosphoglycerate kinase 1 (PGK1). Mitochondrial PGK1 acts as a protein kinase to phosphorylate pyruvate dehydrogenase kinase 1 (PDHK1), reducing mitochondrial pyruvate utilization, suppressing reactive oxygen species production, increasing lactate production and promoting tumourigenesis. PGK1 also plays a role as a transcription factor once transported into the nucleus. Resistance to anoikis is also facilitated by metabolic support provided by cancer-associated fibroblasts (CAFs). Our series of experiments in-vitro and in the animal model showed that PGK1 knock-out or inhibition is effective in controlling development and growth of peritoneal metastasis (PM) of gastric origin, establishing a causal role of PGK1 in this development. PGK1 also increases CXCR4 and CXCL12 expression, which is associated with a metastatic phenotype and plays a role in the metastatic homing of malignant cells. Thus, PGK1, its modulators and target genes may be exploited as therapeutic targets for preventing development of PM and for enhancing cytotoxic effects of conventional systemic chemotherapy.

Ursodeoxycholic Acid for 6 Months After Bariatric Surgery Is Impacting Gallstone Associated Morbidity in Patients with Preoperative Asymptomatic Gallstones.

BACKGROUND: Obesity is a predisponing factor for gallstone formation with a prevalence > 10% in patients undergoing gastric bypass procedure. Although there is a strong recommendation for concomitant cholecystectomy in patients with symptomatic gallstones, the evidence level for patients with asymptomatic gallstones is weak. According to recent literature, up to 21% of asymptomatic gallstones become symptomatic after bariatric surgery. Secondary prophylaxis with ursodeoxycholic acid (UDCA), which is altering the composition and excretion of the bile acid pool, was the objective of this study. METHODS: Retrospective analysis of the patient records of all patients undergoing laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SGx) at our center between January 2007 and October 2017. RESULTS: We enrolled a total of 704 patients with routine preoperative ultrasound. In 61 patients, asymptomatic gallstones were detected and these patients were treated with UDCA for 6 months after bariatric surgery. One patient developed a single episode of symptoms 3 months after SGx, which did not require surgery. One patient developed chronic cholecystitis and underwent cholecystectomy 6 months after SGx. All other patients (n = 59; 96.8%) remained asymptomatic under UDCA therapy. CONCLUSION: UDCA for 6 months after bariatric surgery seems to reduce the incidence of gallstone-associated morbidity when compared to the current literature. Thus, our results call the concept of prophylactic concomitant cholecystectomy in patients with asymptomatic gallstones into question while at the same time paving the way for a future clinical trial.