Towards Equal Access to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy and Survival in Patients with Isolated Colorectal Peritoneal Metastases: A Nationwide Population-Based Study.

BACKGROUND: Before 2016, patients with isolated synchronous colorectal peritoneal metastases (PMCRC) diagnosed in expert centers had a higher odds of undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and better overall survival (OS) than those diagnosed in referring centers. Nationwide efforts were initiated to increase awareness and improve referral networks. METHODS: This nationwide study aimed to evaluate whether the between-center differences in odds of undergoing CRS-HIPEC and OS have reduced since these national efforts were initiated. All patients with isolated synchronous PMCRC diagnosed between 2009 and 2021 were identified from the Netherlands Cancer Registry. Associations between hospital of diagnosis and the odds of undergoing CRS-HIPEC, as well as OS, were assessed using multilevel multivariable regression analyses for two periods (2009-2015 and 2016-2021). RESULTS: In total, 3948 patients were included. The percentage of patients undergoing CRS-HIPEC increased from 17.2% in 2009-2015 (25.4% in expert centers, 16.5% in referring centers), to 23.4% in 2016-2021 (30.2% in expert centers, 22.6% in referring centers). In 2009-2015, compared with diagnosis in a referring center, diagnosis in a HIPEC center showed a higher odds of undergoing CRS-HIPEC (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.02-2.67) and better survival (hazard ratio [HR] 0.80, 95% CI 0.66-0.96). In 2016-2021, there were no differences in the odds of undergoing CRS-HIPEC between patients diagnosed in HIPEC centers versus referring centers (OR 1.27, 95% CI 0.76-2.13) and survival (HR 1.00, 95% CI 0.76-1.32). CONCLUSION: Previously observed differences in odds of undergoing CRS-HIPEC were no longer present. Increased awareness and the harmonization of treatment for PMCRC may have contributed to equal access to care and a similar chance of survival at a national level.

The impact of hospital experience in bariatric surgery on short-term outcomes after minimally invasive esophagectomy: a nationwide analysis.

BACKGROUND: Minimally invasive esophagectomy (MIE) is a technically challenging procedure with a substantial learning curve. Composite volume of upper gastrointestinal (upper GI) procedures for cancer has been previously linked to postoperative outcomes. This study aimed to investigate an association between hospital experience in bariatric surgery and short-term outcomes in MIE. METHOD: Data on esophagectomy patients between 2016 and 2020 were collected from the Dutch Upper Gastrointestinal Cancer Audit, a mandatory nationwide registry. Hospitals were categorized as bariatric or non-bariatric. Multivariable logistic regression investigated short-term postoperative outcomes, adjusting for case mix. RESULTS: Of 3371 patients undergoing esophagectomy in sixteen hospitals, 2450 (72.7%) underwent MIE. Bariatric hospitals (N = 6) accounted for 1057 (43.1%) MIE. Annual volume of bariatric procedures was median 523 and esophagectomies 42. In non-bariatric hospitals, volume of esophagectomies was median 52 (P = 0.145). Overall postoperative complication rate was lower in bariatric hospitals (59.2% vs. 65.9%, P < 0.001). Bariatric hospitals were associated with a reduced risk of overall complications (aOR 0.76 [95% CI 0.62-0.92]), length of hospital (aOR 0.79 [95% CI 0.65-0.95]), and ICU stay (aOR 0.81 [95% CI 0.67-0.98]) after MIE. Surgical radicality (R0) did not differ. Lymph node yield (≥ 15) was lower in bariatric hospitals (90.0% vs. 94.7%, P < 0.001). Over the years, several short-term outcomes improved in bariatric hospitals compared to non-bariatric hospitals. CONCLUSION: In this nationwide analysis, there was an association between bariatric hospitals and improved short-term outcomes after MIE. Characteristics of bariatric hospitals that could explain this phenomenon and whether this translates to other upper GI procedures may be warranted to identify.

Patient-reported outcomes during first-line palliative systemic therapy alternated with pressurized intraperitoneal aerosol chemotherapy for unresectable colorectal peritoneal metastases: a single-arm phase II trial (CRC-PIPAC-II).

BACKGROUND: The CRC-PIPAC-II study prospectively assessed bidirectional therapy (BT) consisting of first-line palliative systemic therapy and electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC-OX) in patients with unresectable colorectal peritoneal metastases (CPM). This study describes the exploration of patient-reported outcomes (PROs). METHODS: In this phase II trial, 20 patients with isolated CPM were treated with up to three cycles of BT, each cycle consisting of two to three courses of systemic therapy, followed by ePIPAC-OX (92 mg/m2). Patients were asked to complete the EuroQoL EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-CR29 questionnaires at baseline, during the first cycle of BT, and one and four weeks after each consecutive BT cycle. PRO scores were calculated and compared between baseline and each subsequent time point using linear-mixed modeling (LMM). PROs were categorized into symptom scales and function scales. Symptom scales ranged from 0 to 100, with 100 representing the maximum symptom load. Function scales ranged from 0 to 100, with 100 representing optimal functioning. RESULTS: Twenty patients underwent a total of 52 cycles of bidirectional therapy. Most PROs (29 of 37, 78%) were not significantly affected during trial treatment. In total, only eight PROs (22%) were significantly affected during trial treatment: Six PROs (index value, global health status, emotional functioning, C30, appetite, and insomnia) showed transient improvement at different time points. Two PROs transiently deteriorated: pain initially improved during the first BT cycle [- 16, p < 0.001] yet worsened temporarily one week after the first two BT cycles (+ 20, p < 0.001; + 17, p = 0.004; respectively). Abdominal pain worsened temporarily one week after the first BT cycle (+ 16, p = 0.004), before improving again four weeks after treatment ended (- 10, p = 0.004). All significant effects on Pros were clinically significant and all deteriorations in PROs were of temporary nature. DISCUSSION: Patients undergoing BT for unresectable CPM had significant, but reversible alterations in several PROs. Most affected PROs concerned improvements and only two PROs showed deteriorations. Both deteriorated PROs returned to baseline after trial treatment and were of a temporary nature. These outcomes help to design future studies on the role of ePIPAC in the palliative setting.

Postoperative circadian patterns in wearable sensor measured heart rate: a prospective observational study.

PURPOSE: This study aimed to describe the 24-hour cycle of wearable sensor-obtained heart rate in patients with deterioration-free recovery and to compare it with patients experiencing postoperative deterioration. METHODS: A prospective observational trial was performed in patients following bariatric or major abdominal cancer surgery. A wireless accelerometer patch (Healthdot) continuously measured postoperative heart rate, both in the hospital and after discharge, for a period of 14 days. The circadian pattern, or diurnal rhythm, in the wearable sensor-obtained heart rate was described using peak, nadir and peak-nadir excursions. RESULTS: The study population consisted of 137 bariatric and 100 major abdominal cancer surgery patients. In the latter group, 39 experienced postoperative deterioration. Both surgery types showed disrupted diurnal rhythm on the first postoperative days. Thereafter, the bariatric group had significantly lower peak heart rates (days 4, 7-12, 14), lower nadir heart rates (days 3-14) and larger peak-nadir excursions (days 2, 4-14). In cancer surgery patients, significantly higher nadir (days 2-5) and peak heart rates (days 2-3) were observed prior to deterioration. CONCLUSIONS: The postoperative diurnal rhythm of heart rate is disturbed by different types of surgery. Both groups showed recovery of diurnal rhythm but in patients following cancer surgery, both peak and nadir heart rates were higher than in the bariatric surgery group. Especially nadir heart rate was identified as a potential prognostic marker for deterioration after cancer surgery.

The Metabolic Health Index Identifies Patients That Will Benefit From Metabolic Surgery.

INTRODUCTION: Metabolic syndrome is a modern world's major health hazard related to comorbidities like type 2 diabetes and cardiovascular disease. Bariatric surgery is well known to lower this health risk in patients with obesity. There is a need for an objective measure to assess the intended reduction in health hazard and indirectly the eligibility for bariatric surgery. The Metabolic Health Index (MHI) quantitatively summarizes the cumulative impact of the metabolic syndrome on health status on a scale from 1 to 6. This study describes the use of the MHI as a supportive tool in the decision for and outcome assessment of bariatric surgery. METHODS: The general usability of the MHI was tested by extending its application to patient data of five other bariatric centers in the Netherlands. Retrospective laboratory and national bariatric quality registry data of 11,501 patients were collected. RESULTS: The quantification of (improvement in) metabolic health burden as measured by the MHI was independent of the dataset that was used to derive the MHI model. Patients with MHI > 2.8 prior to surgery improved significantly more in MHI 12 mo after surgery compared to patients with MHI ≤ 2.8 (1.1 compared to 0.4 MHI points, respectively; P < 0.001). CONCLUSIONS: The MHI is robust between centers and is suitable for general use in clinical decision-making. As changes in MHI over time reflect metabolic health alterations, it is suitable as an outcome measure of surgery. An MHI cut-off value of 2.8 helps to predict the likelihood of significant improvement after surgery, independent of body mass index and known metabolic comorbidities.

Weight recurrence after Sleeve Gastrectomy versus Roux-en-Y gastric bypass: a propensity score matched nationwide analysis.

BACKGROUND: Literature remains scarce on patients experiencing weight recurrence after initial adequate weight loss following primary bariatric surgery. Therefore, this study compared the extent of weight recurrence between patients who received a Sleeve Gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB) after adequate weight loss at 1-year follow-up. METHODS: All patients undergoing primary RYGB or SG between 2015 and 2018 were selected from the Dutch Audit for Treatment of Obesity. Inclusion criteria were achieving ≥ 20% total weight loss (TWL) at 1-year and having at least one subsequent follow-up visit. The primary outcome was ≥ 10% weight recurrence (WR) at the last recorded follow-up between 2 and 5 years, after ≥ 20% TWL at 1-year follow-up. Secondary outcomes included remission of comorbidities at last recorded follow-up. A propensity score matched logistic regression analysis was used to estimate the difference between RYGB and SG. RESULTS: A total of 19.762 patients were included, 14.982 RYGB and 4.780 SG patients. After matching 4.693 patients from each group, patients undergoing SG had a higher likelihood on WR up to 5-year follow-up compared with RYGB [OR 2.07, 95% CI (1.89-2.27), p < 0.01] and less often remission of type 2 diabetes [OR 0.69, 95% CI (0.56-0.86), p < 0.01], hypertension (HTN) [OR 0.75, 95% CI (0.65-0.87), p < 0.01], dyslipidemia [OR 0.44, 95% CI (0.36-0.54), p < 0.01], gastroesophageal reflux [OR 0.25 95% CI (0.18-0.34), p < 0.01], and obstructive sleep apnea syndrome (OSAS) [OR 0.66, 95% CI (0.54-0.8), p < 0.01]. In subgroup analyses, patients who experienced WR after SG but maintained ≥ 20%TWL from starting weight, more often achieved HTN (44.7% vs 29.4%), dyslipidemia (38.3% vs 19.3%), and OSAS (54% vs 20.3%) remission compared with patients not maintaining ≥ 20%TWL. No such differences in comorbidity remission were found within RYGB patients. CONCLUSION: Patients undergoing SG are more likely to experience weight recurrence, and less likely to achieve comorbidity remission than patients undergoing RYGB.

A randomized clinical trial evaluating eHealth in bariatric surgery.

BACKGROUND: Supporting patients before, and long after, their bariatric treatment contributes a lot to successful outcome. eHealth interventions have a hypothetical benefit in addition to standard care. This could lead to increased weight loss, reduction of obesity-related diseases, patient adherence, and quality of life. This randomized controlled trial aims to evaluate the value of an eHealth platform and self-monitoring devices as additions to standard bariatric care. MATERIALS AND METHODS: Two-hundred-and-five patients who underwent primary bariatric surgery were randomized (2:1:1) to receive standard care (control group), additional access to an educational patient eHealth platform (online group), or additional access to eHealth platform as well as self-monitoring devices (device group). The platform consisted of an interactive educational environment with informational videos, dietary advice, news, and more. The self-monitoring devices used were a weight scale, blood pressure monitor, pulse oximeter, and activity bracelet. The primary endpoint was weight loss and secondary outcomes included reduction of obesity-related diseases, quality of life, and eHealth use. RESULTS: Postoperative weight loss, reduction of obesity-related diseases, frequency of consultations, and quality of life were similar between groups. Participation to the eHealth platform was high (online group 90%, device group 98%). Most frequently accessed contents were informational messages, videos, and the treatment preparation modules. The percentage of active users of the self-monitoring devices dropped from 62% in the first postoperative month to 19% after 2 years. Thirteen patients in the device group withdrew due to unwillingness to use self-monitoring devices. CONCLUSION: Participation to the eHealth intervention in addition to the standard post-bariatric guidance program was high, however, had no significant impact on clinical outcomes such as weight loss, reduction of obesity-related diseases, and quality of life. Trial registration ClinicalTrials.gov (identifier number NL56992.100.16) https://clinicaltrials.gov/ct2/show/NCT03394638.

The impact of body weight on the development of peritoneal metastases in colorectal cancer patients: results from a nationwide cohort study.

BACKGROUND: Obesity is a major global health problem and an important risk factor for colorectal cancer (CRC) is increased body weight. Obesity plays a role in the peritoneal dissemination of cancer; however, it is unclear whether this also applies for peritoneal dissemination of CRC. The purpose of this study was to provide insight in the role of obesity on the peritoneal dissemination of colorectal cancer. METHODS: Of all patients diagnosed with CRC in the Netherlands in the first half of 2015, follow-up data was completed in 2019. Weight at time of primary diagnosis was categorized as underweight, normal weight, overweight, or obese. Logistic regression modelling was used to assess the association between weight and the presence of synchronous colorectal peritoneal metastases (CPM), and Cox regression modelling was used to assess the association between weight and metachronous CPM. Patient and tumor characteristics were taken into account. The analyses were adjusted for tumor stage, nodal stage, tumor location, and tumor histology. RESULTS: In total, 6436 patients were included in this study. Two-hundred ninety-three (4.6%) patients presented with synchronous CPM at the time of primary diagnosis, while another 278 (5.1%) patients developed metachronous CPM after a median time of 16.5 months. Univariable and multivariable logistic regression modelling did not identify an effect of weight on the presence of synchronous CPM. Neither underweight (odds ratio [OR] 1.10, 95% CI 0.48-2.54), nor overweight (OR 0.96, 95% CI 0.71-1.29), or obesity (OR 0.84, 95% CI 0.56-1.26) was either positively or negatively associated with the presence of synchronous peritoneal metastases as compared to normal weight. Univariable and multivariable Cox regression modelling did not identify an effect of weight on the development of metachronous CPM. Neither underweight (HR 0.162, 95% CI 0.02-1.16), nor overweight (HR 1.07, 95% CI 0.82-1.39), or obesity (HR 1.02, 95% CI 0.73-1.16) was either positively or negatively associated with the presence of synchronous peritoneal metastases as compared to normal weight. CONCLUSION: CRC patients who are overweight or obese are not more at risk for the presence of synchronous CPM nor development of metachronous CPM than their normal-weight counterparts.

Peritoneal metastases from colorectal cancer belong to Consensus Molecular Subtype 4 and are sensitised to oxaliplatin by inhibiting reducing capacity.

BACKGROUND: Peritoneal metastases (PM) in colorectal cancer (CRC) are associated with therapy resistance and poor survival. Oxaliplatin monotherapy is widely applied in the intraperitoneal treatment of PM, but fails to yield clinical benefit. We aimed to identify the mechanism(s) underlying PM resistance to oxaliplatin and to develop strategies overcoming such resistance. EXPERIMENTAL DESIGN: We generated a biobank consisting of 35 primary tumour regions and 59 paired PM from 12 patients. All samples were analysed by RNA sequencing. We also generated a series of PM-derived organoid (PMDO) cultures and used these to design and test strategies to overcome resistance to oxaliplatin. RESULTS: PM displayed various hallmarks of aggressive CRC biology. The vast majority of PM and paired primary tumours belonged to the Consensus Molecular Subtype 4 (CMS4). PMDO cultures were resistant to oxaliplatin and expressed high levels of glutamate-cysteine ligase (GCLC) causing detoxification of oxaliplatin through glutathione synthesis. Genetic or pharmacological targeting of GCLC sensitised PMDOs to a 1-h exposure to oxaliplatin, through increased platinum-DNA adduct formation. CONCLUSIONS: These results link oxaliplatin resistance of colorectal PM to their CMS4 status and high reducing capacity. Inhibiting the reducing capacity of PM may be an effective strategy to overcome PM resistance to oxaliplatin.

Impact of the COVID-19 pandemic on surgical care in the Netherlands.

BACKGROUND: The COVID-19 pandemic caused disruption of regular healthcare leading to reduced hospital attendances, repurposing of surgical facilities, and cancellation of cancer screening programmes. This study aimed to determine the impact of COVID-19 on surgical care in the Netherlands. METHODS: A nationwide study was conducted in collaboration with the Dutch Institute for Clinical Auditing. Eight surgical audits were expanded with items regarding alterations in scheduling and treatment plans. Data on procedures performed in 2020 were compared with those from a historical cohort (2018-2019). Endpoints included total numbers of procedures performed and altered treatment plans. Secondary endpoints included complication, readmission, and mortality rates. RESULTS: Some 12 154 procedures were performed in participating hospitals in 2020, representing a decrease of 13.6 per cent compared with 2018-2019. The largest reduction (29.2 per cent) was for non-cancer procedures during the first COVID-19 wave. Surgical treatment was postponed for 9.6 per cent of patients. Alterations in surgical treatment plans were observed in 1.7 per cent. Time from diagnosis to surgery decreased (to 28 days in 2020, from 34 days in 2019 and 36 days in 2018; P < 0.001). For cancer-related procedures, duration of hospital stay decreased (5 versus 6 days; P < 0.001). Audit-specific complications, readmission, and mortality rates were unchanged, but ICU admissions decreased (16.5 versus 16.8 per cent; P < 0.001). CONCLUSION: The reduction in the number of surgical operations was greatest for those without cancer. Where surgery was undertaken, it appeared to be delivered safely, with similar complication and mortality rates, fewer admissions to ICU, and a shorter hospital stay.

COVID-19 has had a significant impact on healthcare worldwide. Hospital visits were reduced, operating facilities were used for COVID-19 care, and cancer screening programmes were cancelled. This study describes the impact of the COVID-19 pandemic on Dutch surgical healthcare in 2020. Patterns of care in terms of changed or delayed treatment are described for patients who had surgery in 2020, compared with those who had surgery in 2018­2019. The study found that mainly non-cancer surgical treatments were cancelled during months with high COVID-19 rates. Outcomes for patients undergoing surgery were similar but with fewer ICU admissions and shorter hospital stay. These data provide no insight into the burden endured by patients who had postponed or cancelled operations.

The impact of an open or laparoscopic approach on the development of metachronous peritoneal metastases after primary resection of colorectal cancer: results from a population-based cohort study.

BACKGROUND: This study aimed to assess the impact of open or laparoscopic resection of primary colorectal cancer (CRC) on the development of metachronous colorectal peritoneal metastases (CPM) in a population-based cohort. MATERIALS AND METHODS: This was a retrospective, population-based study of CRC patients who underwent open or laparoscopic resection of the primary tumour in the Netherlands between January 1st and June 30th 2015. Patients with synchronous metastases were excluded. CPM were considered metachronous if diagnosed ≥ 90 days after resection of primary CRC. Multivariable cox regression analysis was performed to correct for tumour location, histology, differentiation, and stage, nodal stage, tumour perforation, primary surgery type, and unclear resection margins. RESULTS: In total, 1516 CRC patients underwent open resection and 3236 CRC patients underwent laparoscopic resection, with a 3-year cumulative incidence of metachronous CPM of 7.3% and 3.7%, respectively (p < 0.001), after median follow-up of 42 months. Open surgical approach was significantly associated with the development of metachronous CPM: HR 1.4 [95%CI 1.1-1.8]. Other prognostic factors were mucinous adenocarcinoma histology (HR 1.6, 95%CI 1.0-2.5), T4 stage (HR 3.2, 95%CI 2.3-4.5), N1 stage (HR 2.9, 95%CI 2.1-4.0), and N2 stage (HR 4.2, 95%CI 2.9-6.1). CONCLUSIONS: Patients treated with open resection had a significantly higher risk to develop metachronous CPM than patients treated with laparoscopic resection. The mechanisms underlying this phenomenon remain unknown but might be related to differences in per-operative specimen handling, tumour spill, surgical trauma and pro-inflammatory response. This finding might imply the need for a personalized follow-up after primary resection of CRC.

Patient-reported outcomes during repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy for isolated unresectable colorectal peritoneal metastases in a multicenter, single-arm, phase 2 trial (CRC-PIPAC).

BACKGROUND: CRC-PIPAC prospectively assessed repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-OX) as a palliative monotherapy (i.e., without concomitant systemic therapy in between subsequent procedures) for unresectable colorectal peritoneal metastases (CPM). The present study explored patient-reported outcomes (PROs) during trial treatment. METHODS: In this single-arm phase 2 trial in two tertiary centers, patients with isolated unresectable CPM received 6-weekly PIPAC-OX (92 mg/m2). PROs (calculated from EQ-5D-5L, and EORTC QLQ-C30 and QLQ-CR29) were compared between baseline and 1 and 4 weeks after the first three procedures using linear mixed modeling with determination of clinical relevance (Cohen's D ≥ 0.50) of statistically significant differences. RESULTS: Twenty patients underwent 59 procedures (median 3 [range 1-6]). Several PROs solely worsened 1 week after the first procedure (index value - 0.10, p < 0.001; physical functioning - 20, p < 0.001; role functioning - 27, p < 0.001; social functioning - 18, p < 0.001; C30 summary score - 16, p < 0.001; appetite loss + 15, p = 0.007; diarrhea + 15, p = 0.002; urinary frequency + 13, p = 0.004; flatulence + 13, p = 0.001). These PROs returned to baseline at subsequent time points. Other PROs worsened 1 week after the first procedure (fatigue + 23, p < 0.001; pain + 29, p < 0.001; abdominal pain + 32, p < 0.001), second procedure (fatigue + 20, p < 0.001; pain + 21, p < 0.001; abdominal pain + 20, p = 0.002), and third procedure (pain + 22, p < 0.001; abdominal pain + 22, p = 0.002). Except for appetite loss, all changes were clinically relevant. All analyzed PROs returned to baseline 4 weeks after the third procedure. CONCLUSIONS: Patients receiving repetitive PIPAC-OX monotherapy for unresectable CPM had clinically relevant but reversible worsening of several PROs, mainly 1 week after the first procedure. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03246321; Netherlands trial register: NL6426.

Pressurized Intraperitoneal Aerosol Chemotherapy (Oxaliplatin) for Unresectable Colorectal Peritoneal Metastases: A Multicenter, Single-Arm, Phase II Trial (CRC-PIPAC).

BACKGROUND: Despite its increasing use, pressurized intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC-OX) has never been prospectively investigated as a palliative monotherapy for colorectal peritoneal metastases in clinical trials. This trial aimed to assess the safety (primary aim) and antitumor activity (key secondary aim) of PIPAC-OX monotherapy in patients with unresectable colorectal peritoneal metastases. METHODS: In this two-center, single-arm, phase II trial, patients with isolated unresectable colorectal peritoneal metastases in any line of palliative treatment underwent 6-weekly PIPAC-OX (92 mg/m2). Key outcomes were major treatment-related adverse events (primary outcome), minor treatment-related adverse events, hospital stay, tumor response (radiological, biochemical, pathological, ascites), progression-free survival, and overall survival. RESULTS: Twenty enrolled patients underwent 59 (median 3, range 1-6) PIPAC-OX procedures. Major treatment-related adverse events occurred in 3 of 20 (15%) patients after 5 of 59 (8%) procedures (abdominal pain, intraperitoneal hemorrhage, iatrogenic pneumothorax, transient liver toxicity), including one possibly treatment-related death (sepsis of unknown origin). Minor treatment-related adverse events occurred in all patients after 57 of 59 (97%) procedures, the most common being abdominal pain (all patients after 88% of procedures) and nausea (65% of patients after 39% of procedures). Median hospital stay was 1 day (range 0-3). Response rates were 0% (radiological), 50% (biochemical), 56% (pathological), and 56% (ascites). Median progression-free and overall survival were 3.5 months (interquartile range [IQR] 2.5-5.7) and 8.0 months (IQR 6.3-12.6), respectively. CONCLUSIONS: In patients with unresectable colorectal peritoneal metastases undergoing PIPAC-OX monotherapy, some major adverse events occurred and minor adverse events were common. The clinical relevance of observed biochemical, pathological, and ascites responses remains to be determined, especially since radiological response was absent.

Systemic Pharmacokinetics of Oxaliplatin After Intraperitoneal Administration by Electrostatic Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC) in Patients with Unresectable Colorectal Peritoneal Metastases in the CRC-PIPAC Trial.

BACKGROUND: Electrostatic pressurized intraperitoneal aerosol chemotherapy (ePIPAC) is a palliative treatment for unresectable peritoneal metastases from various primary cancers. However, little is known about the systemic pharmacokinetics of oxaliplatin after ePIPAC. METHODS: Twenty patients with unresectable colorectal peritoneal metastases were treated with repetitive ePIPAC monotherapy with oxaliplatin (92 mg/m2) and a simultaneous intravenous bolus of leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Samples were collected during each ePIPAC: whole blood at t = 0, t = 5, t = 10, t = 20, t = 30, t = 60, t = 120, t = 240, t = 360 and t = 1080 min for plasma and plasma ultrafiltrate concentrations; urine at t = 0, t = 1, t = 3, t = 5 and t = 7 days. Samples were analyzed using atomic absorption spectrometry. Pharmacokinetics were analyzed using nonlinear mixed-effects modeling. RESULTS: Four patients received one ePIPAC, three patients received two ePIPAC, and thirteen patients received ≥ 3 ePIPAC. The population pharmacokinetic models adequately described the pharmacokinetics of oxaliplatin after ePIPAC. The plasma ultrafiltrate Cmax of oxaliplatin reached 1.36-1.90 µg/mL after 30 min with an AUC0-24 h of 9.6-11.7 µg/mL * h. The plasma Cmax reached 2.67-3.28 µg/mL after 90 min with an AUC0-24 h of 49.0-59.5 µg/mL * h. The absorption rate constant (Ka) was 1.13/h. Urine concentrations of oxaliplatin rapidly decreased to less than 3.60 µg/mL in 90% of the samples at day 7. DISCUSSION: Systemic exposure to oxaliplatin after ePIPAC seemed comparable to that after systemic chemotherapy, as described in other literature. Since this is an indirect comparison, future research should focus on the direct comparison between the systemic exposure to oxaliplatin after ePIPAC and after systemic chemotherapy. TRIAL REGISTRATION: NCT03246321, Pre-results; ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.

The Value of an e-Health Platform in Bariatric Surgery: A Retrospective Study on the Impact on Weight Loss.

Background: In this time, where health care is getting more digitalized, opportunities open up to provide patients with additional information using e-Health. An e-Health platform was developed to increase knowledge about obesity in general, bariatric procedures, and follow-up program to achieve more weight loss. It was hypothesized that a higher e-Health usage, defined as page views per patient, leads to a higher percentage total weight loss (%TWL) at 2 years postoperatively. Materials and Methods: Accounts with available follow-up data between January 2015 and April 2018 were retrospectively reviewed. Three groups were formed based on number of page views. Results: In total, 1,098 subjects were analyzed. On average, a patient connected 12 times with an average of 51-page views per patient. At 1 year postoperatively, the %TWL was 30.7 versus 30.9 versus 31.9 (p = 0.126), and at 2 years 29.4 versus 29.8 versus 30.5 (p = 0.350) in low-active, medium-active, and high-active group, respectively. Analysis whether patients accessed the preoperative content did not show significant differences. However, patients who accessed content after surgery lost more weight than those who did not, being 30.1%TWL versus 31.7%TWL at 1 year (p = 0.006) and 28.9%TWL versus 30.4%TWL at 2 years postoperatively (p = 0.034). Pre- and postoperative quality of life did not differ between groups. Conclusion: e-Health might be a beneficial tool for weight reduction after bariatric surgery. The current platform reached a large portion of patients. Patients accessing postoperative content lost more weight at 1 and 2 years postoperatively than those who did not. Quality of life was comparable.

Gastric Bypass Versus Sleeve Gastrectomy: Patient Selection and Short-term Outcome of 47,101 Primary Operations From the Swedish, Norwegian, and Dutch National Quality Registries.

OBJECTIVE: The aim of this study was to compare the use and short-term outcome of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) in Sweden, Norway, and the Netherlands. BACKGROUND: Although bariatric surgery is performed in high volumes worldwide, no consensus exists regarding the choice of bariatric procedure for specific groups of patients. METHODS: Data from 3 national registries for bariatric surgery were used. Patient selection, perioperative data (severe complications, mortality, and rate of readmissions within 30 days), and 1-year results (follow-up rate and weight loss) were studied. RESULTS: A total of 47,101 primary operations were registered, 33,029 (70.1%) RYGB and 14,072 (29.9%) SG. Patients receiving RYGB met international guidelines for having bariatric surgery more often than those receiving SG (91.9% vs 83,0%, P < 0.001). The 2 procedures did not differ in the rate of severe complications (2.6% vs 2.4%, P = 0.382), nor 30-day mortality (0.04% vs 0.03%, P = 0.821). Readmission rates were higher after RYGB (4.3% vs 3.4%, P < 0.001).One-year post surgery, less RYGB-patients were lost-to follow-up (12.1% vs 16.5%, P < 0.001) and RYGB resulted in a higher rate of patients with total weight loss of more than 20% (95.8% vs 84.6%, P < 0.001). While the weight-loss after RYGB was similar between hospitals, there was a great variation in weight loss after SG. CONCLUSION: This study reflects the pragmatic use and short-term outcome of RYGB and SG in 3 countries in North-Western Europe. Both procedures were safe, with RYGB having higher weight loss and follow-up rates at the cost of a slightly higher 30-day readmission rate.

Structured CT reporting improves accuracy in diagnosing internal herniation after laparoscopic Roux-en-Y gastric bypass.

OBJECTIVES: To confirm that structured reporting of CT scans using ten signs in clinical practice leads to a better accuracy in diagnosing internal herniation (IH) after gastric bypass surgery, compared with free-text reporting. METHODS: In this prospective study, CT scans between June 1, 2017, and December 1, 2018, were included from a cohort of 2606 patients who had undergone laparoscopic gastric bypass surgery between January 1, 2011, and January 1, 2018. The CT scans were made for a suspicion of IH and structured reports were made using a standardised template with ten signs: (1) swirl sign, (2) small-bowel obstruction, (3) clustered loops, (4) mushroom sign, (5) hurricane eye sign, (6) small bowel behind the superior mesenteric artery, (7) right-sided anastomosis, (8) enlarged nodes, (9) venous congestion, and (10) mesenteric oedema. Furthermore, an overall impression of IH likelihood was given using a 5-point Likert scale. CT scans performed in 2011 until 2017, without structured reporting, were included for comparison. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated using two-way contingency tables; the chi-square test was used for calculating p value. Reoperation and 3-month follow-up were used as reference. RESULTS: A total of 174 CT scans with structured reporting and 289 CT scans without structured reporting were included. Sensitivity was 81.3% (95% CI, 67.7-94.8%) and 79.5% (95% CI, 67.6-91.5%), respectively (p = 0.854); specificity was 95.8% (95% CI, 92.5-99.1%) and 88.6% (95% CI, 84.6-92.6%), respectively (p = 0.016); PPV was 81.3% (95% CI, 67.7-94.8%) and 55.6% (95% CI, 43.3-67.8%), respectively (p = 0.014); NPV was 95.8% (95% CI, 92.5-99.1%) and 96.0% (95% CI, 93.5-98.6%), respectively (p = 0.909); and accuracy was 93.1% (95% CI, 88.0-96.2%) and 87.2% (95% CI, 82.7-90.7%), respectively (p = 0.045). CONCLUSION: Structured reporting for the diagnosis of internal herniation after gastric bypass surgery improves accuracy and can be implemented in clinical practice with good results. KEY POINTS: • Ten signs are used to aid CT diagnosis of internal herniation after gastric bypass surgery. • Structured reporting increases specificity and positive predictive value and thereby prevents unnecessary reoperations in patients without internal herniation. • Structured reporting by means of a standardised template can help less experienced readers.

Can Electric Nose Breath Analysis Identify Abdominal Wall Hernia Recurrence and Aortic Aneurysms? A Proof-of-Concept Study.

Introduction. This pilot study evaluates if an electronic nose (eNose) can distinguish patients at risk for recurrent hernia formation and aortic aneurysm patients from healthy controls based on volatile organic compound analysis in exhaled air. Both hernia recurrence and aortic aneurysm are linked to impaired collagen metabolism. If patients at risk for hernia recurrence and aortic aneurysms can be identified in a reliable, low-cost, noninvasive manner, it would greatly enhance preventive options such as prophylactic mesh placement after abdominal surgery. Methods. From February to July 2017, a 3-armed proof-of-concept study was conducted at 3 hospitals including 3 groups of patients (recurrent ventral hernia, aortic aneurysm, and healthy controls). Patients were measured once at the outpatient clinic using an eNose with 3 metal-oxide sensors. A total of 64 patients (hernia, n = 29; aneurysm, n = 35) and 37 controls were included. Data were analyzed by an automated neural network, a type of self-learning software to distinguish patients from controls. Results. Receiver operating curves showed that the automated neural network was able to differentiate between recurrent hernia patients and controls (area under the curve 0.74, sensitivity 0.79, and specificity 0.65) as well as between aortic aneurysm patients and healthy controls (area under the curve 0.84, sensitivity 0.83, and specificity of 0.81). Conclusion. This pilot study shows that the eNose can distinguish patients at risk for recurrent hernia and aortic aneurysm formation from healthy controls.

Mesh OR Patch for Hernia on Epigastric and Umbilical Sites (MORPHEUS-Trial): The Complete Two-year Follow-up.

OBJECTIVE: The objective of this trial was to identify a superior method for umbilical and epigastric hernia repair in terms of complications. Complications such as an extended operation duration, additional use of painkillers, reoperation, infection, seroma, extended wound care, extended hospitalization, and early recurrence were reported according to the Clavien-Dindo grading system. SUMMARY BACKGROUND DATA: Over the years mesh repair is proven the gold standard for umbilical and epigastric hernias. The question remains, which mesh should be used? METHODS: In this randomized controlled, multicenter trial, all patients ≥ 18 years with a single, symptomatic, and primary small umbilical or epigastric hernia qualified for inclusion. Flat preperitoneal polypropylene mesh repair was compared with patch repair (PROCEED Ventral Patch) (PVP). RESULTS: A total of 352 patients were randomized; 348 patients received the intervention (n = 177 PVP vs n = 171 mesh). One out of 4 suffered from any kind of complication within 2 years postoperative (27.6%). A significant difference in complications was seen, in favor of polypropylene mesh repair (P = 0.044, 22.1% mesh vs 32.5% PVP). Reoperation was performed in 19 PVP operated patients (10.7%) versus 7 patients with polypropylene mesh repair (4.0%, P = 0.021).No significant differences were seen in recurrences (n = 13, 8.4% PVP vs n = 6, 4.1% mesh, P = 0.127). CONCLUSIONS: In small epigastric and small umbilical hernia repair a flat polypropylene mesh repair was associated with a lower complication rate than PVP repair. No differences in recurrence rates were seen. Combining all complications, the preperitoneal positioned flat polypropylene mesh performed better.