Minimally invasive robot-assisted and laparoscopic distal pancreatectomy in a pan-European registry a retrospective cohort study.

BACKGROUND: International guidelines recommend monitoring of the use and outcome of minimally invasive pancreatic surgery (MIPS). However, data from prospective international audits on minimally invasive distal pancreatectomy (MIDP) are lacking. This study examined the use and outcome of robot-assisted (RDP) and laparoscopic (LDP) distal pancreatectomy in the E-MIPS registry. MATERIALS AND METHODS: Post-hoc analysis in a prospective audit on MIPS, including consecutive patients undergoing MIDP in 83 centers from 19 European countries (01-01-2019/31-12-2021). Primary outcomes included intraoperative events (grade 1: excessive blood loss, grade 2: conversion/change in operation, grade 3: intraoperative death), major morbidity, and in-hospital/30-day mortality. Multivariable logistic regression analyses identified high-risk groups for intraoperative events. RDP and LDP were compared in the total cohort and in high-risk groups. RESULTS: Overall, 1672 patients undergoing MIDP were included; 606 (36.2%) RDP and 1066 (63.8%) LDP. The annual use of RDP increased from 30.5% to 42.6% (P<0.001). RDP was associated with fewer grade 2 intraoperative events compared to LDP (9.6% vs. 16.8%, P<0.001), with longer operating time (238 vs. 201 minutes,P<0.001). No significant differences were observed between RDP and LDP regarding major morbidity (23.4% vs. 25.9%, P=0.264) and in-hospital/30-day mortality (0.3% vs. 0.8%, P=0.344). Three high-risk groups were identified; BMI>25 kg/m2, previous abdominal surgery, and vascular involvement. In each group, RDP was associated with fewer conversions and longer operative times. CONCLUSION: This European registry-based study demonstrated favorable outcomes for MIDP, with mortality rates below 1%. LDP remains the predominant approach, whereas the use of RDP is increasing. RDP was associated with less conversions and longer operative time, including in high-risk subgroups. Future randomized trials should confirm these findings and assess cost differences.

Have a vital end-user been overlooked? Developing a shared decision intervention for patients with potential pancreatic cancer regarding the choice of surgery.

Objective: To develop a patient decision aid facilitating shared decision making for patients with potential pancreatic cancer deciding about no treatment, surgical or medical treatment. Methods: Based on a user-centred design by Wittemann et al., we developed a shared decision making intervention in three phases: 1) Understanding decision needs 2) Development of a patient decision aid (PtDA) based on a generic template 3) Assessment of the intervention from interviews with patients (n = 11), relatives (n = 11), nurses (n = 4) and surgeons (n = 2) analysed with thematic analysis, and measuring patients' perceptions of choice of options with the Decisional Conflict Scale. Results: Results showed varying experiences with the use of the PtDA, with surgeons not finding PtDA useful as it was impractical and constraining with patients' conversations. There was no difference in patients' perceptions in choosing options for those being presented vs those patients not being presented for the PtDA. Conclusion: The format and structure of the PtDA was not feasible for the surgeons as fundamental users in the present clinic. Innovation: This study highlights the urgent need to consider clinical context before introducing a predefined tool and shows the importance of a multistakeholder approach. Research should focus on finding means to successful implement shared decision making.

Robotic Distal Pancreatectomy: A Novel Standard of Care? Benchmark Values for Surgical Outcomes From 16 International Expert Centers.

BACKGROUND AND OBJECTIVE: Robotic distal pancreatectomy (DP) is an emerging attractive approach, but its role compared with laparoscopic or open surgery remains unclear. Benchmark values are novel and objective tools for such comparisons. The aim of this study was to identify benchmark cutoffs for many outcome parameters for DP with or without splenectomy beyond the learning curve. METHODS: This study analyzed outcomes from international expert centers from patients undergoing robotic DP for malignant or benign lesions. After excluding the first 10 cases in each center to reduce the effect of the learning curve, consecutive patients were included from the start of robotic DP up to June 2020. Benchmark patients had no significant comorbidities. Benchmark cutoff values were derived from the 75th or the 25th percentile of the median values of all benchmark centers. Benchmark values were compared with a laparoscopic control group from 4 high-volume centers and published open DP landmark series. RESULTS: Sixteen centers contributed 755 cases, whereof 345 benchmark patients (46%) were included the analysis. Benchmark cutoffs included: operation time ≤300 minutes, conversion rate ≤3%, clinically relevant postoperative pancreatic fistula ≤32%, 3 months major complication rate ≤26.7%, and lymph node retrieval ≥9. The comprehensive complication index at 3 months was ≤8.7 without deterioration thereafter. Compared with robotic DP, laparoscopy had significantly higher conversion rates (5×) and overall complications, while open DP was associated with more blood loss and longer hospital stay. CONCLUSION: This first benchmark study demonstrates that robotic DP provides superior postoperative outcomes compared with laparoscopic and open DP. Robotic DP may be expected to become the approach of choice in minimally invasive DP.

Long-term results after resection of primary duodenal adenocarcinoma: A retrospective cohort study.

BACKGROUND: Radical resection of duodenal adenocarcinoma (DA) offers the possibility of cure. The outcome after operation and adjuvant therapy is mainly based on small numbers due to the low incidence of the disease. We examined the long-term outcome after surgical treatment of DA. MATERIAL AND METHODS: This was a retrospective cohort study including all patients undergoing curatively intended resection for histologically confirmed DA at a single University hospital. Long-term survival was examined by the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox proportional hazards regression analysis was applied to adjust for confounding. RESULTS: A total of 96 patients were included. The median follow-up was 3.7 years (IQR 2.9-4.3), during which 18 patients (18.5%) had recurrence and 35 (36.5%) patients had died. The 3- and 5-year overall survival was 66.3% (55.6-76.9%) and 58.2% (46.2-70.2%), respectively. In the multivariable analysis, adjuvant therapy was associated with decreased mortality (HR 0.29, CI 0.11-0.76, P = 0.011) whereas positive lymph node ratio >0.20 was associated with increased mortality. CONCLUSION: Radical operation for DA has a median overall 5-year-survival of more than 50%. The indication for adjuvant chemotherapy remains to be addressed.

Assessment of sarcopenia in patients with upper gastrointestinal tumors: Prevalence and agreement between computed tomography and dual-energy x-ray absorptiometry.

BACKGROUND & AIMS: Sarcopenia is associated with an increased risk of complications to treatment and lower survival rates in patients with cancer, but there is a lack of agreement on cut-off values and assessment methods. We aimed to investigate the prevalence of sarcopenia assessed by dual-energy x-ray absorptiometry (DXA) and computed tomography (CT) as well as the agreement between the methods for identification of sarcopenia. METHODS: This cross-sectional study pooled data from two studies including patients scheduled for surgery for gastrointestinal tumors. We assessed sarcopenia using two different cut-off values derived from healthy young adults for DXA and two for CT. Additionally, we used one of the most widely applied cut-off values for CT assessed sarcopenia derived from obese cancer patients. The agreement between DXA and CT was evaluated using Cohen's kappa. The mean difference and range of agreement between DXA and CT for estimating total and appendicular lean soft tissue were assessed using Bland-Altman plots. RESULTS: In total, 131 patients were included. With DXA the prevalence of sarcopenia was 11.5% and 19.1%. Using CT, the prevalence of sarcopenia was 3.8% and 26.7% using cut-off values from healthy young adults and 64.1% using the widely applied cut-off value. The agreement between DXA and CT in identifying sarcopenia was poor, with Cohen's kappa values ranging from 0.05 to 0.39. The mean difference for estimated total lean soft tissue was 1.4 kg, with 95% limits of agreement from -8.6 to 11.5 kg. For appendicular lean soft tissue, the ratio between DXA and CT was 1.15, with 95% limits of agreement from 0.92 to 1.44. CONCLUSIONS: The prevalence of sarcopenia defined using DXA and CT varied substantially, and the agreement between the two modalities is poor.

[Minimally invasive surgery for malignant diseases in pancreas].

Unlike most other abdominal procedures, pancreatic resection for malignant tumours is still predominantly performed as open surgery. However, recent published randomised trials suggest that a laparoscopic approach is safe and may offer advantages in the early postoperative period. Likewise, early reports of robot-assisted pancreatic resection suggest advantages. This reveiw describes the current status of minimally invasive pancreatic surgery for malignant tumours, including both laparoscopic and robot-assisted approaches for pancreaticoduodenectomy and distal pancreatectomy.

Preoperative TruCulture® whole blood cytokine response predicts post-operative inflammation in pancreaticoduodenectomy patients-A pilot cohort study.

Major surgery is associated with substantial morbidity and mortality with early post-operative adverse events (POAE) occurring in 30% of patients within the first 30 days. The underlying pathogenesis is multifactorial, including immune dysfunction and increased inflammatory response to surgery. We investigated preoperative immune function by the TruCulture® whole blood technique in a cohort of patients undergoing pancreaticoduodenectomy (PD), hypothesizing that patients developing inflammatory POAE defined as leucocytosis, fever or high (above median) area under the curve (AUC) C-reactive protein (CRP) the first post-operative week would display perturbed preoperative immune function. Sixty-two adult patients were screened, 30 included and 11 excluded post-inclusion due to other surgical procedures than PD and post-operative complications directly attributed to surgery, leaving 19 patients for analysis of preoperative immune function. Patients developing leucocytosis (n = 5, 26%) had lower Toll-like receptor (TLR)-3-stimulated IL-12p40 and higher Candida Albicans (TLR1/2/4/6, Dectin-1)-stimulated TNF-α, compared to patients without leucocytosis (all P < .05). Patients developing fever (n = 7, 37%) had lower TLR7/8-stimulated IFN-γ and patients with high AUC CRP (n = 9, 47%) had lower TLR3-stimulated IFN-γ and IL-6 and lower TLR7/8-stimulated IL-10 (all P < .05), compared to patients without fever or low CRP, respectively. In conclusion, patients with inflammatory POAE displayed lower preoperative stimulated IL-12p40, IFN-γ, IL-6 and IL-10 and higher TNF-α response, compared to patients without inflammatory POAE. This finding suggests that TruCulture is a feasible immunologic screening tool in surgical patients, with a potential for preoperative identification of patients at increased risk for inflammatory POAE, allowing for risk-based intervention trials.

[Segmental reversal of the small bowel as treatment of short bowel syndrome in adults]. / Segmentel vending af tyndtarmen til behandling af voksne patienter med korttarmssyndrom.

Short bowel syndrome is the result of extensive surgical resection, inherited defects or loss of functional absorbing intestine. Parenteral nutrition is associated with high economical expenses, increased morbidity and decreased quality of life. Intestinal transplantation is associated with high morbidity and mortality rates. Segmental reversal of the small bowel can prolong the transit time in the small bowel and in many cases permanently end parenteral nutrition dependency. Segmental reversal of the small bowel should be integrated in the surgical treatment of adults with short bowel syndrome.

[Possibly improved treatment of colorectal cancer by sentinel lymph node mapping]. / Mulig forbedret behandling af kolorektal cancer med sentinel lymph node-diagnostic.

Prognosis for colorectal cancer is dependent on radical surgical intervention. Chemotherapy in patients with advanced disease has improved the survival. A considerable proportion of the patients going through radical surgery will subsequently relapse. Adjuvant chemotherapy is reserved for patients with lymph node metastases, why undetected malignant lymph nodes will result in understaging and exclusion from the possible benefit of adjuvant chemotherapy. With sentinel lymph node mapping it may be possible to detect and resect more malignant lymph node and maybe even avoid extensive resections.

Short Hospital Stay after Laparoscopic Colorectal Surgery without Fast Track.

Purpose. Short hospital stay and equal or reduced complication rates have been demonstrated after fast track open colonic surgery. However, fast track principles of perioperative care can be difficult to implement and often require increased nursing staff because of more concentrated nursing tasks during the shorter hospital stay. Specific data on nursing requirements after laparoscopic surgery are lacking. The purpose of the study was to evaluate the effect of operative technique (open versus laparoscopic operation), but without changing nurse staffing or principles for peri- or postoperative care, that is, without implementing fast track principles, on length of stay after colorectal resection for cancer. Methods. Records of all patients operated for colorectal cancer from November 2004 to December 2008 in our department were reviewed. No specific patients were selected for laparoscopic repair, which was solely dependent on the presence of two specific surgeons at the same time. Thus, the patients were not selected for laparoscopic repair based on patient-related factors, but only on the simultaneous presence of two specific surgeons on the day of the operation. Results. Of a total of 540 included patients, 213 (39%) were operated by a laparoscopic approach. The median hospital stay for patients with a primary anastomosis was significantly shorter after laparoscopic than after conventional open surgery (5 versus 8 days, P < 0.001) while there was no difference in patients receiving a stoma (10 versus 10 days, ns), with no changes in the perioperative care regimens. Furthermore there were significant lower blood loss (50 versus 200 mL, P < 0.001) and lower complication rate (21% versus 32%, P = 0.006) in the laparoscopic group. Conclusion. Implementing laparoscopic colorectal surgery in our department resulted in shorter hospital stay without using fast track principles for peri- and postoperative care in patients not receiving a stoma during the operation. Consequently, we aimed to reduce hospitalisation without increasing cost in nursing staff per hospital bed. Length of stay was not reduced in patients receiving a stoma pointing at this group for specific intervention in the future. Furthermore, the complication rate was reduced in the laparoscopic group.

Dendritic cell vaccination of patients with metastatic colorectal cancer.

Colorectal cancer is with more than 4000 new cases every year the third most common cancer in Denmark. Metastases are most often found in the liver, and 20-25% of the patients have synchronous metastases to the liver at time of primary diagnosis. Other frequent sites for metastases are lungs and lymph nodes. Without treatment the median survival for patients with metastatic colorectal cancer is 7-9 months. Patients receiving systemic or regional chemotherapy now have a median survival of approximately 20 months. Up to 40% of the patients undergoing intended curative surgery subsequently relapse with local or distant disease, and approximately 80% of the relapses appear within the first 3 years. If the cancer metastasises, and the chances of radical surgery are eliminated, the prognosis is poor. The aim of the present study was to evaluate the clinical and immunological effects of treating patients with disseminated colorectal cancer with a dendritic cell based cancer vaccine (MelCancerVac). The vaccine consisted of dendritic cells generated from autologous mononuclear cells pulsed with an allogeneic tumor cell lysate, selected for its high expression of cancer associated antigens. A clinical phase I study evaluating tolerability and toxicity of the treatment was established. Six patients with progressive disease were included and the analysis revealed that the treatment was well tolerated and not associated with toxicity. A subsequent clinical phase II study evaluating the activity of the treatment with CT-scan based measurements of tumors (RECIST), self reported quality of life (SF-36), and clinical evaluation was established. Out of twenty included patients with progressive disease, seventeen received intervention with the vaccine. Stable disease was achieved in four patients and two of these remained stable throughout the entire study period. Quality of life remained for most parameters included in the evaluation high and stable. The immunological consequences of the treatment were evaluated with plasma- and serum-levels of inflammatory and non-inflammatory markers (the following 10 cytokines: GM-CSF, INF-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNF-alpha, and in addition the inflammatory chemokines MIP-1beta, Eotaxin and IP-10) and biomarkers CEA and TIMP-1. These analyses showed that the vaccine induced increasing levels of Th1 cytokines such as GM-CSF, TNF-alpha, IFN-gamma, and IL-2 in patients achieving stable disease. Patients with progressive disease had increasing levels of CEA and TIMP-1, while patients achieving stable disease maintained relatively stable levels. Conclusively, treatment with this dendritic cell based cancer vaccine was non-toxic and safe, clinical response in terms of stable disease was achieved in 24% of the patients, and the patients maintained a high quality of life during treatment. The immunological analyses indicated that the treatment resulted in favourable anticancer responses in the patients' immune system in terms of polarisation towards a Th1 dominated response potentially directed against tumor cells. Since no partial or complete responses were observed and since the number of patients was relatively low these results have to be interpreted with caution. Moreover, phase II study designs do not lead to final conclusions regarding clinical efficacy, which must be validated in larger prospective, randomised and controlled studies.

[Laparoscopic versus right-sided hemicolectomy in cancer of colon therapy]. / Laparoskopisk versus åben højresidig hemikolektomi til behandling af koloncancer.

INTRODUCTION: In Denmark, we are still debating whether a laparoscopic approach is beneficial for patients scheduled for right-sided hemicolectomy. The aim of this study was to compare the outcome of laparoscopic versus open resection for right-sided colon cancer. MATERIAL AND METHODS: Using the Danish Colorectal Cancer Group (DCCG) database, we identified two groups each with 42 patients who underwent either laparoscopic right hemicolectomy (LRH) or open right hemicolectomy (ORH). The two groups were compared with respect to demographic data, length of hospital stay, number of glands harvested, blood loss, surgical complications and mortality. RESULTS: The length of hospital stay was significantly shorter in the LRH group than in the ORH group (five vs. six, p = 0.023). Furthermore, the number of lymph nodes harvested was significantly larger in the LRH group than in the ORH group (23 vs. 15, p < 0.001). We found fewer anastomotic leaks (three vs. five), fewer patients with postoperative complications including anastomotic leaks (eight vs. 14) and lower operation-related mortality (zero vs. three). None of these differences were statistically significant. CONCLUSION: LRH is comparable to ORH with regards to morbidity, mortality and blood loss. Furthermore, LRH is associated with a shorter hospital stay and a higher radical lymph node harvest than ORH. The results and the thesis that LRH will result in fewer hernias and better cosmetic outcomes makes LRH a promising surgical procedure.

Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination.

INTRODUCTION. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. MATERIAL AND METHODS. Plasma and serum samples were collected prior to vaccination and continuously during treatment. GM-CSF, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-4, IL-8, IL-1b, IL-5, IL-10, IL-12, MIP-1b, IP-10 and Eotaxin were analyzed in a multiplex assay with a Luminex 100 instrument. CEA and TIMP-1 were analysed on ELISA platforms. RESULTS. Patients achieving stable disease showed increasing levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5. Patients with progressive disease showed significant increase in CEA and TIMP-1 levels, while patients with stable disease showed relatively unaltered levels. CONCLUSION. The increased levels of key pro-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine.

Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine.

Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based on dendritic cells pulsed with an allogenic tumor cell lysate. Twenty patients with advanced colorectal cancer were consecutively enrolled. Dendritic cells (DC) were generated from autologous peripheral blood mononuclear cells and pulsed with allogenic tumor cell lysate containing high levels of cancer-testis antigens. Vaccines were biweekly administered intradermally with a total of 10 vaccines per patient. CT scans were performed and responses were graded according to the RECIST criteria. Quality of life was monitored with the SF-36 questionnaire. Toxicity and adverse events were graded according to the National Cancer Institute's common Toxicity Criteria. Four patients were graded with stable disease. Two remained stable throughout the entire study period. Analysis of changes in the patients' quality of life revealed stability in the subgroups: 'physical function' (p=0.872), 'physical role limitation' (p=0.965), 'bodily pain' (p=0.079), 'social function' (p=0.649), 'emotional role limitation' (p=0.252) and 'mental health' (p=0.626). The median survival from inclusion was 5.3 months (range 0.2-29.2 months) with one patient still being alive almost 30 months after inclusion in the trial. Treatment with this DC-based cancer vaccine was safe and non-toxic. Stable disease was found in 24% (4/17) of the patients. The quality of life remained for most categories high and stable throughout the study period.

[Routine second look endoscopy after bleeding ulcers]. / Rutinemaessig second look-endoskopi efter blødende ulcus.

Treatment of peptic duodenal and gastric ulcers has improved in efficiency and become less invasive. There is still a considerable risk of re-bleeding (15-20%) and the mortality remains high (5-14%). A Danish study from 2000 showed that scheduled second look endoscopy (SLE) the day after the primary intervention decreased the re-bleeding rate. Studies have questioned this and suggest that SLE decreases the risk of re-bleeding, but do not reduce mortality. Since SLE is debated and a recent national survey found a variable practice, the evidence has been reviewed critically.

[Effect of 10-minute apnoea on hiccups--a meta analysis]. / Effekt på hikke af ti minutters apnø--en metaanalyse.

INTRODUCTION: Hiccups are well-known to most people. In most cases, hiccups are limited to a short period of time, but in some cases, they persist for days, weeks, months and even years. Many interventions have been proposed and tested, but the most effective is probably long periods of apnoea. The aim of this article was to determine the effect of 10-minute apnoea on hiccups. MATERIAL AND METHODS: PubMed, the Cochrane Library databases and Web of Science were searched for randomised controlled trials examining the effect of apnoea on hiccups. The main outcome measure was total absence of hiccups for at least two days after intervention. RESULTS: We found no randomised controlled trials testing extensive apnoea as an intervention against hiccups. CONCLUSIONS: In spite of massive positive empirical experience with the effect of long apnoea periods on hiccups, there is no solid scientific evidence confirming this effect. To determine the clinical effect, it is necessary to perform large double-blinded, randomised, placebo-controlled crossover trials.

[Changes in personnel performing gastroenterologic tests, with special emphasis on endoscopy]. / Opgaveglidning inden for gastroenterologien med saerligt fokus på endoskopi.

In the gastroenterologic field, there has been an increasing need for endoscopy. With future screening programs, the number of endoscopies performed will further increase. In Denmark endoscopies are performed primarily by doctors, but soon the number of endoscopies done will exceed the capacities of the doctors who perform them. International experience with nurse endoscopists has shown good results, with safety, sensitivity and specificity comparable to doctors'. This paper discusses the possibilities for nurses' performing endoscopy.

[Dendritic cell-based cancer vaccine]. / Dendritcellebaseret cancervaccine.

The varieties of treatments for patients with cancer have increased rapidly during the last few years. One of the newer ways to treat cancer patients is by immune therapy using tumor antigen pulsed dendritic cell-based vaccination. Phase I and II trials have shown effectiveness in generating an immunologic response and have in some cases shown clinical responses with tumour regression. This paper describes some of the possibilities and perspectives for dendritic cell vaccines for cancer patients.