Laparoscopic distal pancreatectomy is more cost-effective than open resection: results from a Swedish randomized controlled trial.

BACKGROUND: Laparoscopic distal pancreatectomy is being implemented worldwide. The aim of this study was to perform a cost-effectiveness analysis from a health care perspective. METHODS: This cost-effectiveness analysis was based on the randomized controlled trial LAPOP, where 60 patients were randomized to open or laparoscopic distal pancreatectomy. For the follow-up of two years, resource use from a health care perspective was recorded, and health-related quality of life was assessed using the EQ-5D-5L. The per-patient mean cost and quality-adjusted life years (QALYs) were compared using nonparametric bootstrapping. RESULTS: Fifty-six patients were included in the analysis. The mean health care costs were lower, €3863 (95% CI: -€8020 to €385), for the laparoscopic group. Postoperative quality of life improved with laparoscopic resection and resulted in a gain in QALYs of 0.08 (95% CI: -0.09 to 0.25). The laparoscopic group had lower costs and improved QALYs in 79% of bootstrap samples. With a cost-per-QALY threshold of €50 000, 95.4% of the bootstrap samples were in favour of laparoscopic resection. CONCLUSION: Laparoscopic distal pancreatectomy is associated with numerically lower health care costs and improvements in QALYs compared with the open approach. The results support the ongoing transition from open to laparoscopic distal pancreatectomies.

Quality of life after open versus laparoscopic distal pancreatectomy: long-term results from a randomized clinical trial.

BACKGROUND: Pancreatic surgery is rapidly transitioning towards minimally invasive methods. Positive results have been published regarding the safety and efficacy of laparoscopic distal pancreatectomy, but postoperative quality of life after operation remains relatively unexplored. The aim of this study was to assess the long-term quality of life after open versus laparoscopic distal pancreatectomy. METHODS: A long-term analysis of quality-of-life data after laparoscopic and open distal pancreatectomy based on the LAPOP trial (a single-centre, superiority, parallel, open-label, RCT in which patients undergoing distal pancreatectomy were randomized 1 : 1 to either the open or laparoscopic approach). Patients received the quality-of-life questionnaires QLQ-C30 and PAN26 before surgery and at 5-6 weeks, 6 months, 12 months, and 24 months after surgery. RESULTS: Between September 2015 and February 2019, a total of 60 patients were randomized, and 54 patients (26 in the open group and 28 in the laparoscopic group) were included in the quality-of-life analysis. A significant difference was observed in six domains in the mixed model analysis, with better results among patients who underwent laparoscopic surgery. At the 2-year measurement, a statistically significant difference between groups was seen in three domains, and a clinically relevant difference of 10 or more was seen in 16 domains, with better results among the patients who underwent laparoscopic resection. CONCLUSION: Considerable differences were shown in postoperative quality of life after laparoscopic compared with open distal pancreatectomy, with better results among the patients who had undergone laparoscopic resection. Of note, some of these differences persisted up to 2 years after surgery. These results strengthen the ongoing transition from open to minimally invasive pancreatic surgery for distal pancreatectomy. Registration number: ISRCTN26912858 (http://www.controlled-trials.com).

High Infiltration of CD68+/CD163- Macrophages Is an Adverse Prognostic Factor after Neoadjuvant Chemotherapy in Esophageal and Gastric Adenocarcinoma.

Tumor-associated macrophages (TAMs) have emerged as key players in tumor immunology but demonstrate a continuum of functional states being either tumor suppressive or promoting. Moreover, chemotherapeutic agents have been shown to alter the tumor microenvironment. Perioperative chemotherapy is a standard treatment option for resectable esophageal and gastric (EG) adenocarcinoma. The aim of this study was to investigate the influence of neoadjuvant chemotherapy (NAC) on TAMs to improve the prognostication and treatment course for these patients. The study cohort comprised 148 patients, all of whom were diagnosed with resectable EG adenocarcinoma and treated with NAC. Immunohistochemistry was applied to assess the total infiltration and infiltration into tumor nests (TN) of CD68+/CD163-, CD68+/CD163+, and MARCO+ TAMs, on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. In pre-NAC specimens, high CD68+/CD163+ infiltration into TN was an unfavorable prognostic factor. No association was found between TAM density in PT pre-NAC and histopathological regression. The density of CD68+/CD163+ TAMs was increased in PT post-NAC, while the density of MARCO+ TAMs was decreased. CD68+/CD163- TAM density was not altered. In post-NAC specimens, higher total as well as TN infiltration of CD68+/CD163- TAMs were adverse prognostic factors. In conclusion, these results suggest that NAC may alter certain TAM subsets in EG adenocarcinoma, along with their functional properties and thus their prognostic value.

Plasma MMP-1 Expression as a Prognostic Factor in Colon Cancer.

BACKGROUND: Matrix metalloproteinases (MMP) are involved in the local and distant invasiveness of colorectal cancer. This study investigates the prognostic value of circulating matrix metalloproteinase levels in patients with colon cancer. METHODS: A cohort of 152 patients was followed for more than 10 years. The correlation of plasma levels of MMP-1,-2, -7, -8, and -9 and survival was investigated. RESULTS: A high level of MMP-1 in circulating plasma was associated with a poorer prognosis in colon cancer (HR 2.0, 95% CI 1.1-3.9) in multivariate analysis regarding 5-year cancer-specific survival. This was further seen in regard of 10-year cancer-specific survival. CONCLUSIONS: Measurement of plasma MMP-1 concentration in patients planned for radical colon cancer surgery might be of importance when discussing prognosis and selection of patients for oncological treatment and postsurgery surveillance.

Laparoscopic versus open distal pancreatectomy (LAPOP): study protocol for a single center, nonblinded, randomized controlled trial.

BACKGROUND: Earlier nonrandomized studies have suggested that laparoscopic distal pancreatectomy (LDP) is advantageous compared with open distal pancreatectomy (ODP) regarding hospital stay, blood loss, and recovery. Only one randomized study has been conducted showing reduced time to functional recovery after LDP compared with ODP. METHODS: LAPOP is a prospective randomized, nonblinded, parallel-group, single-center superiority trial. Sixty patients with lesions in the pancreatic body or tail that are found by a multidisciplinary tumor board to need surgical resection will be randomized to receive LDP or ODP. The primary outcome variable is postoperative hospital stay, and secondary outcomes include functional recovery (defined as no need for intravenous medications or fluids and as the ability of an ambulatory patient to perform activities of daily life), perioperative bleeding, complications, need for pain medication, and quality of life comparison. DISCUSSION: The LAPOP trial will test the hypothesis that LDP reduces postoperative hospital stay compared with ODP. TRIAL REGISTRATION: ISRCTN, 26912858 . Registered on 28 September 2015.

Stability of matrix metalloproteinase-9 as biological marker in colorectal cancer.

Matrix metalloproteinases (MMPs) are believed to be of importance in the growth and spread of colorectal cancer (CRC). MMP-9 level has been suggested as a biological predictor of prognosis in CRC as well as in other types of cancer such as breast and cervical cancer. The purpose of this study was to investigate the stability over time of MMP-9 in cryopreserved plasma, colorectal tumor tissue extract and macroscopically tumor-free colon mucosa tissue extract samples. Plasma and tissue samples were taken from patients at primary CRC surgery and analyzed for MMP-9. Aliquots of samples from the same patients were stored at - 80 °C pending analysis. These aliquots were analyzed using identical methods after storage periods of nine (plasma) and twelve (tissue) years. No significant difference in plasma MMP-9 concentration was seen between baseline samples and those after 9 years of cryopreservation (median values 9.9 and 9.7 ng/mL, respectively; p > 0.05). MMP-9 levels in the tumor-free tissue extracts had increased to baseline (median values 7.1 and 8.1 ng/mL, respectively; p < 0.01). MMP-9 levels in the tumor tissue extracts had also increased significantly (median values 89.9 and 133.5 ng/mL, respectively; p < 0.01). We have demonstrated that MMP-9 levels in frozen citrated plasma are stable if stored at - 80 °C, whereas MMP-9 levels in extracts from tumor tissue and tumor-free intestinal mucosa appear to increase with time. We conclude that MMP-9 levels in cryopreserved plasma may be considered stable over time and are thus suitable for comparison purposes in consecutive series.

[Orally administered infection prophylaxis in elective colorectal surgery]. / Peroral infektionsprofylax vid allmän­­kirurgiska ingrepp bör utvärderas mer - Trimetoprim­sulfametoxazol kombinerat med metronidazol tycks fungera vid kolorektal kirurgi ­ om det ges vid rätt tid.

Orally administered infection prophylaxis in elective colorectal surgery  Orally administered trimethoprim-sulfamethoxazole and metronidazole given at a defined time point at least two hours before elective colorectal surgery can be used as prophylaxis with a small increase in superficial surgical site infections (SSI), if motivated by other benefits such as environmental concerns. However, in upper malignant or bariatric surgery it should be used only in study form. Further, the methods of infection surveillance have a great potential to be improved.

Validation of surgical site infection registration in colorectal surgery.

BACKGROUND: Surgical site infection (SSI) represents almost 40% of nosocomial infections. Risk for SSI is most prominent following colorectal surgery. There is no Swedish standard SSI classification or surveillance. We have failed to find validation of SSI surveillance programs presently in use. This study investigates SSI registration routines at Halmstad County Hospital, Sweden (HCH) as well as Swedish surgery departments' SSI classification and reporting practices. METHODS: We requested information regarding SSI surveillance routines from all surgical departments performing colorectal surgery in Sweden. The reliability of SSI data collected routinely at HCH between 1999 and 2008 was approximated by comparing routine reports with data from a prospective study on infection prophylaxis. We calculate how much the reported SSI frequency must change for detection with current surveillance routines. RESULTS: In all, 36 of 56 surgical departments answered a questionnaire; 24 have active SSI registration. Most commonly, SSI is detected with a combination of postoperative control in the outpatient unit and review of medical records after discharge. The department of surgery at HCH reported, from 1999 to 2008, an average SSI rate of 12.7% including emergency surgery. Compared to prospective registration, the routine provided a sensitivity of 0.56 and a specificity of 1.0. A reported frequency of 26% is required to detect a statistically significant increase in SSI. CONCLUSION: Swedish hospital SSI rates cannot be compared, there is neither uniform SSI surveillance nor classification system. The SSI monitoring routine explored in this study is uncertain. Methods must be developed further to obtain reliable data.

Levels of matrix metalloproteinases differ in plasma and serum - aspects regarding analysis of biological markers in cancer.

BACKGROUND: There are inconsistencies in the use of serum or plasma when analysing the matrix metalloproteinases (MMPs) as diagnostic or prognostic markers. The purpose of this study was to compare the concentration of MMP-1, -2, -7, -8, -9 and -13 in serum vs plasma samples. METHODS: Blood samples were obtained from sixty-five men and women. Samples were analysed for levels of MMPs in corresponding citrate plasma and serum. RESULTS: All MMPs expressed higher concentration in serum compared with plasma (P<0.01). There were no differences between genders. CONCLUSIONS: Present study demonstrated significant differences regarding concentrations of some MMPs using plasma vs serum. We conclude that future studies regarding MMPs as biological markers in cancer should consider the use of citrate plasma instead of serum.

Orally Administered Trimethoprim-Sulfamethoxazole and Metronidazole as Infection Prophylaxis in Elective Colorectal Surgery.

BACKGROUND: This randomized clinical trial evaluated orally administered trimethoprim-sulfamethoxazole and metronidazole (TSM) in elective colorectal surgery as prophylactic for post-operative surgical site infections (SSI). METHODS: Patients undergoing elective colorectal resection were evaluated for inclusion. Randomized subjects received either orally administered TSM or intravenously administered cefuroxime and metronidazole (control group, CXM). The primary endpoint was the rate of SSI. RESULTS: A total of 1073 subjects were randomized to either control (540) or TSM (533). 486 patients in the TSM group and 499 in the control group were followed-up with after 4 weeks. Thirty-seven (3.8%) patients were afflicted by SSI at discharge from hospital and 69 (7.0%) at follow-up four weeks after surgery. After four weeks, the rate of incisional SSI was 7.0% in the TSM group and 3.6% in the control group (p=0.022). For organ/space SSI and the other complications monitored in the study, no differences were observed between the groups. CONCLUSION: Orally administered TSM as prophylaxis before elective colorectal surgery results in a low rate of organ/space SSI but an increased rate of incisional SSI compared with intravenously administered cefuroxime and metronidazole. Thus, when considering orally administered TSM, because of environmental concerns or for economic reasons, the slightly increased infection rate has to be kept in mind.

Activated protein C-protein C inhibitor complex, activation peptide of carboxypeptidase B and C-reactive protein as predictors of severe acute pancreatitis.

INTRODUCTION: The concentration of carboxypeptidase B activation peptide (CAPAP) is proposed to be a predictor of severe acute pancreatitis. The activated protein C (APC)-protein C inhibitor (PCI; APC-PCI) complex in plasma could be useful in detecting the hypercoagulative condition in severe acute pancreatitis. METHOD: In this prospective study, mild (n = 50) and severe (n = 9) cases of acute pancreatitis were compared with respect to levels of CAPAP and APC-PCI, and sorted in time intervals from onset of symptoms to sampling. The peak values of the C-reactive protein (CRP) within the 1st week were also compared. RESULTS: CRP detected the severe cases with a sensitivity of 0.89 and a specificity of 0.74 (cut-off level 200 mg/l). In the interval 0-72 h, CAPAP could predict the severity of the disease in serum and urine (sensitivity 0.52/0.29, specificity 0.73/0.93, cut-off 2 nM/60 nM). The level of APC-PCI in plasma could predict the severe condition in the interval 0-24 h after the onset of symptoms (sensitivity 0.6, specificity 0.66, cut-off level 0.54 microg/l). CONCLUSION: Of the parameters explored, CRP is still the best biochemical marker to distinguish between severe and mild acute pancreatitis. CAPAP could be useful in combination with other tests, but the APC-PCI complex's diagnostic time interval is too short to be used in the clinical routine.

Does glyceryl nitrate prevent post-ERCP pancreatitis? A prospective, randomized, double-blind, placebo-controlled multicenter trial.

OBJECTIVE: Acute pancreatitis is the most dreaded complication of ERCP. Two studies have shown a significant effect of glyceryl nitrate (GN) in preventing post-ERCP pancreatitis (PEP). We wanted to evaluate this promising effect in a larger study with a realistically precalculated incidence of PEP. DESIGN/PATIENTS: A randomized, double-blind, placebo-controlled multicenter study including patients from 14 European centers was performed. A total of 820 patients were entered; 806 were randomized. INTERVENTION: The active drug was transdermal GN (Discotrine/Minitran, 3M Pharma) 15 mg/24 hours; placebo (PL) was an identical-looking patch applied before ERCP. A total of 401 patients received GN; 405 received PL. RESULTS: Forty-seven patients had PEP (5.8%), 18 (4.5%) in the GN group and 29 (7.1%) in the PL group. The relative risk reduction of PEP in the GN group of 36% (95% CI, 11%-65%) compared with the PL group was not statistically significant (P = .11). Thirteen had mild pancreatitis (4 in the GN group, 9 in the PL group), 26 had moderate pancreatitis (9 in the GN group, 17 in the PL group), and 8 had severe pancreatitis (5 in the GN group, 3 in the PL group). Headache (P < .001) and hypotension (P = .006) were more common in the GN group. Significant variables predictive of PEP were not having biliary stones extracted; hypotension after ERCP; morphine, propofol, glucagon, and general anesthesia during the procedure; or no sufentanil during the procedure. CONCLUSIONS: The trial showed no statistically significant preventive effect of GN on PEP. Because of a considerable risk of a type II error, an effect of GN may have been overlooked. (ClinicalTrials.gov ID: NCT00121901.).