Study protocol: the OptiScreen-Study: optimized psycho-oncological care-from screening to intervention.

PURPOSE: Adequate, needs-oriented psycho-oncological care contributes to reducing psychological distress in cancer patients and their relatives and improving quality of life. Regarding the precise determination of objective and subjective needs, there are often discrepancies in practice between the screening instrument completed by patients, the clinical impression of the treatment team, and the judgment of the psycho-oncology team. METHODS: The present multicenter study "OptiScreen", involving three German Comprehensive Cancer Centers (Hannover, Leipzig, Dresden), aims to professionalize psychosocial screening to enable targeted and needs-based allocation to psycho-oncological support. Optimization and professionalization of the screening process will be achieved by training of oncological nursing staff to improve the targeted identification of distressed patients and provide them with needs-based psycho-oncological care. The non-randomized pre-post study will include inpatients with gastrointestinal cancers from the visceral oncology centers at the three sites. First, the comparison group (CG) will be assessed of N = 300. After completion of nursing training, the intervention group (IG) with N = 600 patients will be evaluated by validated questionnaires. RESULTS: The aim is to reduce barriers on both the patient and treatment side by promoting interdisciplinary dialogue and linking the screening with a personal consultation offer provided by the nurses, which should help to increase utilization and reduce patients' fears, shame and information deficits. CONCLUSION: It is not sufficient to establish a well-validated screening procedure, it also has to be feasible and useful in clinical practice. "OptiScreen" aims to improve the psycho-oncological care situation. In parallel, the study enables the professionalization of psycho-oncological care with the involvement of important professional groups (e.g. nursing) and thus aims to develop a "best practice model".

Do certain surgical steps increase postoperative morbidity after cytoreductive surgery and HIPEC- a retrospective analysis.

INTRODUCTION: It has been shown that cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for patients suffering from peritoneal malignancies. Despite good results, there is an ongoing debate about this treatment due to perioperative morbidity. The aim of this study is to identify relevant risk factors for an unfavorable postoperative outcome after CRS and HIPEC. MATERIALS AND METHODS: A retrospective analysis of a prospectively recorded database of all patients undergoing CRS and HIPEC between 2013 and 2020 in the Department of Surgery of the University Hospital Dresden was performed with a special focus on certain surgical steps of multivisceral resection, one- or 2- stage CRS/HIPEC and underlying diagnosis as possible risk factors for worse postoperative course. RESULTS: N = 173 CRS and HIPEC procedures were performed for various diagnoses. Relevant postoperative morbidity was 24% and 30d-mortality 1.2%. Simultaneous liver resections, preoperative hypalbuminemia and 2-staged CRS/HIPEC were significant risk factors for a worse postoperative course in multivariable analysis. Assessment of the association of simultaneous anastomoses and morbidity and mortality was inconclusive. CONCLUSION: CRS and HIPEC is a safe treatment without relevant intraoperative morbidity and mortality and acceptable postoperative outcome. One-stage CRS/HIPEC should be preferred.

Comparative Analysis of Postoperative Complications after Cytoreductive Surgery and HIPEC in Gastric Cancer.

INTRODUCTION: Patients with advanced gastric cancer (AGC) frequently show peritoneal carcinomatosis (PC). PC reduces life expectancy and quality of life. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve overall survival. Nevertheless, it has been reported that CRS and HIPEC are accompanied by an increase in postoperative complications. The purpose of this study was to investigate the complications associated with CRS and HIPEC and overall and disease-free survival. METHODS: Patients with AGC and PC, who received complete CRS and HIPEC, were included in the HIPEC group (n = 15). Patients with AGC but without PC, who received resection of the primary tumor alone, constituted the control group (n = 43). RESULTS: Patients enrolled in the HIPEC group presented with a median PCI of 7. In comparison with the control group, no differences were found in patient characteristics, risk factors, pathological findings, and operative procedures. Twenty-five percentage of the patients in both groups suffered from serious postoperative complications (CDC ≥3a). Surgical and medical complications, rate of reoperation, and mortality did not differ. Also, the recurrence pattern, median survival, and 1- and 2-year survival rates showed no differences. CONCLUSION: CRS and HIPEC do not lead to an increased postoperative morbidity and mortality in AGC with PC. Albeit the poorer prognosis of patients with PC, survival of both groups was comparable.

Does caffeine consumption affect laparoscopic skills in a motion tracking analysis? A prospective, randomized, blinded crossover trial.

BACKGROUND: Coffee can increase vigilance and performance, especially during sleep deprivation. The hypothetical downside of caffeine in the surgical field is the potential interaction with the ergonomics of movement and the central nervous system. The objective of this trial was to investigate the influence of caffeine on laparoscopic performance. METHODS: Fifty laparoscopic novices participated in this prospective randomized, blinded crossover trial and were trained in a modified FLS curriculum until reaching a predefined proficiency. Subsequently, all participants performed four laparoscopic tasks twice, once after consumption of a placebo and once after a caffeinated (200 mg) beverage. Comparative analysis was performed between the cohorts. Primary endpoint analysis included task time, task errors, OSATS score and a performance analysis with an instrument motion analysis (IMA) system. RESULTS: Fifty participants completed the study. Sixty-eight percent of participants drank coffee daily. The time to completion for each task was comparable between the caffeine and placebo cohorts for PEG transfer (119 s vs 121 s; p = 0.73), precise cutting (157 s vs 163 s; p = 0.74), gallbladder resection (190 s vs 173 s; p = 0.6) and surgical knot (171 s vs 189 s; p = 0.68). The instrument motion analysis showed no significant differences between the caffeine and placebo groups in any parameters: instrument volume, path length, idle, velocity, acceleration, and instrument out of view. Additionally, OSATS scores did not differ between groups, regardless of task. Major errors occurred similarly in both groups, except for one error criteria during the circle cutting task, which occurred significantly more often in the caffeine group (34% vs. 16%, p < 0.05). CONCLUSION: The objective IMA and performance scores of laparoscopic skills revealed that caffeine consumption does not enhance or impair the overall laparoscopic performance of surgical novices. The occurrence of major errors is not conclusive but could be negatively influenced in part by caffeine intake.

Influence of the First Wave of the COVID-19 Pandemic on Cancer Care in a German Comprehensive Cancer Center.

Introduction: During the first wave of the COVID-19 pandemic in 2020, the German government implemented legal restrictions to avoid the overloading of intensive care units by patients with COVID-19. The influence of these effects on diagnosis and treatment of cancer in Germany is largely unknown. Methods: To evaluate the effect of the first wave of the COVID-19 pandemic on tumor board presentations in a high-volume tertiary referral center (the German Comprehensive Cancer Center NCT/UCC Dresden), we compared the number of presentations of gastrointestinal tumors stratified by tumor entity, tumor stage, and treatment intention during the pandemic to the respective data from previous years. Results: The number of presentations decreased by 3.2% (95% CI -8.8, 2.7) during the COVID year 2020 compared with the pre-COVID year 2019. During the first shutdown, March-May 2020, the total number of presentations was 9.4% (-18.7, 1) less than during March-May 2019. This decrease was significant for curable cases of esophageal cancer [N = 37, 25.5% (-41.8, -4.4)] and colon cancer [N = 36, 17.5% (-32.6, 1.1)] as well as for all cases of biliary tract cancer [N = 26, 50% (-69.9, -15)] during the first shutdown from March 2020 to May 2020. Conclusion: The impact of the COVID-19 pandemic on the presentation of oncological patients in a CCC in Germany was considerable and should be taken into account when making decisions regarding future pandemics.

Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO-04 randomized phase 3 rectal cancer trial.

Peripheral blood leukocytosis and neutrophilia reflect cancer inflammation and have been proposed as prognostic immunological biomarkers in various malignancies. However, previous studies were limited by their retrospective nature and small patient numbers. Baseline peripheral blood leukocytes, neutrophils, hemoglobin, platelets, lactate dehydrogenase and carcinoembryonic antigen (CEA) were correlated with clinicopathologic characteristics, and clinical outcome in 1236 patients with rectal cancer treated with 5-FU-based preoperative chemoradiotherapy (CRT) alone or with oxaliplatin followed by surgery and adjuvant chemotherapy within the CAO/ARO/AIO-04 randomized phase 3 trial. Multivariable analyses were performed using Cox regression models. After a median follow-up of 50 months, baseline leukocytosis remained an independent adverse prognostic factor for disease-free survival (DFS; HR 1.457; 95% CI 1.163-1.825; p = 0.001), distant metastasis (HR 1.696; 95% CI 1.266-2.273; p < 0.001) and overall survival (OS; HR 1.716; 95% CI 1.264-2.329; p = 0.001) in multivariable analysis. Similar significant findings were observed for neutrophilia and high CEA levels. Conversely, treatment-induced leukopenia correlated with favorable DFS (p = 0.037), distant metastasis (p = 0.028) and OS (p = 0.012). Intriguingly, addition of oxaliplatin to 5-FU CRT resulted in a significant DFS improvement only in patients with neutrophilia and leukocytosis (p = 0.028 and p = 0.002). Our findings have important clinical implications and provide high-level evidence on the adverse prognostic role of leukocytes and neutrophils, and the impact of chemotherapy in the context of these biomarkers. These data could help guide patient stratification and should be further validated within prospective studies.

Adjuvant therapy after resection of colorectal liver metastases: the predictive value of the MSKCC clinical risk score in the era of modern chemotherapy.

BACKGROUND: Despite introduction of effective chemotherapy protocols, it has remained uncertain, if patients with colorectal cancer (CRC) liver metastases should receive adjuvant therapy. Clinical or molecular predictors may help to select patients at high risk for disease recurrence and death who obtain a survival advantage by adjuvant chemotherapy. METHODS: A total of 297 patients with potentially curative resection of CRC liver metastases were analyzed. These patients had no neoadjuvant therapy, no extrahepatic disease and negative resection margins. The primary endpoint was overall survival. Patients' risk status was evaluated using the Memorial Sloan-Kettering Cancer Center clinical risk score (MSKCC-CRS). Multivariable analyses were performed using Cox proportional hazard models. RESULTS: A total of 137 (43%) patients had a MSKCC-CRS > 2. Adjuvant chemotherapy was administered to 116 (37%) patients. Patients who received adjuvant chemotherapy were of younger age (p = 0.03) with no significant difference in the presence of multiple metastases (p = 0.72) or bilobar metastases (p = 0.08). On multivariate analysis adjuvant chemotherapy was associated with improved survival in the entire cohort (Hazard ratio 0.69; 95% confidence interval 0.69-0.98). It improved survival markedly in high-risk patients with a MSKCC-CRS > 2 (HR 0.40; 95% CI 0.23-0.69), whereas it was of no benefit in patients with a MSKCC-CRS ≤ 2 (HR 0.90; 95% CI 0.57-1.43). CONCLUSIONS: The MSKCC-CRS offers a tool to select patients for adjuvant therapy after resection of CRC liver metastases. Validation in independent patient cohorts is required.

Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial.

BACKGROUND: Neoadjuvant chemotherapy for unresectable colorectal liver metastases can downsize tumours for curative resection. We assessed the effectiveness of cetuximab combined with chemotherapy in this setting. METHODS: Between Dec 2, 2004, and March 27, 2008, 114 patients were enrolled from 17 centres in Germany and Austria; three patients receiving FOLFOX6 alone were excluded from the analysis. Patients with non-resectable liver metastases (technically non-resectable or > or =5 metastases) were randomly assigned to receive cetuximab with either FOLFOX6 (oxaliplatin, fluorouracil, and folinic acid; group A) or FOLFIRI (irinotecan, fluorouracil, and folinic acid; group B). Randomisation was not blinded, and was stratified by technical resectability and number of metastases, use of PET staging, and EGFR expression status. They were assessed for response every 8 weeks by CT or MRI. A local multidisciplinary team reassessed resectability after 16 weeks, and then every 2 months up to 2 years. Patients with resectable disease were offered liver surgery within 4-6 weeks of the last treatment cycle. The primary endpoint was tumour response assessed by Response Evaluation Criteria In Solid Tumours (RECIST), analysed by modified intention to treat. A retrospective, blinded surgical review of patients with radiological images at both baseline and during treatment was done to assess objectively any changes in resectability. The study is registered with ClinicalTrials.gov, number NCT00153998. FINDINGS: 56 patients were randomly assigned to group A and 55 to group B. One patient in each group were excluded from the analysis of the primary endpoint because they discontinued treatment before first full dose, one patient in group B was excluded because of early pulmonary embolism. A confirmed partial or complete response was noted in 36 (68%) of 53 patients in group A, and 30 (57%) of 53 patients in group B (difference 11%, 95% CI -8 to 30; odds ratio [OR] 1.62, 0.74-3.59; p=0.23). The most frequent grade 3 and 4 toxicities were skin toxicity (15 of 54 patients in group A, and 22 of 55 patients in group B), and neutropenia (13 of 54 patients in group A and 12 of 55 patients in group B). R0 resection was done in 20 (38%) of 53 patients in group A and 16 (30%) of 53 of patients in group B. In a retrospective analysis of response by KRAS status, a partial or complete response was noted in 47 (70%) of 67 patients with KRAS wild-type tumours versus 11 (41%) of 27 patients with KRAS-mutated tumours (OR 3.42, 1.35-8.66; p=0.0080). According to the retrospective review, resectability rates increased from 32% (22 of 68 patients) at baseline to 60% (41 of 68) after chemotherapy (p<0.0001). INTERPRETATION: Chemotherapy with cetuximab yields high response rates compared with historical controls, and leads to significantly increased resectability. FUNDING: Merck-Serono, Sanofi-Aventis, and Pfizer.

Hepaticojejunostomy--analysis of risk factors for postoperative bile leaks and surgical complications.

Anastomoses between the jejunum and the bile duct are an important component of many surgical procedures; however, risk factors for clinically relevant bile leaks have not yet been adequately defined. The objective of this study was to describe the incidence of bile leaks after hepaticojejunostomy and to define predictive factors associated with this risk and with surgical morbidity. Between October 2001 and April 2004, hepaticojejunostomies were performed in 519 patients in a standardized way. Patient- and treatment-related data were documented prospectively. A bile leak was defined as bilirubin concentration in the drains exceeding serum bilirubin with a consecutive change of clinical management or occurrence of a bilioma necessitating drainage. Surgical morbidity occurred in 15% of patients, the incidence of a bile leak was 5.6%. Multivariate analysis confirmed preoperative radiochemotherapy, preoperative low cholinesterase levels, biliary complications after liver transplantation necessitating a hepaticojejunostomy, and simultaneous liver resection as risk factors for bile leakages, whereas biliary complications after liver transplantation necessitating hepaticojejunostomy, simultaneous liver resection, and diabetes mellitus were significantly associated with postoperative surgical morbidity. Our results demonstrate that hepaticojejunostomy is a safe procedure if performed in a standardized fashion. The above found factors may help to better predict the risk for complications after hepaticojejunostomy.

Biofeedback versus electrostimulation in treatment of anal sphincter insufficiency.

The purpose of this study was to prospectively investigate a consecutive patient series (N = 70) with anal sphincter insufficiency and compare the efficacy of biofeedback and electrostimulation as conservative treatment options. Forty patients were treated by biofeedback training, 30 patients by electrostimulation. Patients were not specifically selected for one or the other treatment. Success was evaluated by vector volume manometry, water infusion test, time until stoma closure and clinical incontinence scores. Resting and squeeze pressure and resting and squeeze vector volume all increased significantly after biofeedback training (P < 0.05 and < 0.001). Resting pressure and squeeze vector volume only were significantly improved by electrostimulation (P < 0.05 and < 0.01). The increase in squeeze vector volume was significantly greater in the biofeedback group (P = 0.03). The estimated median time period from commencement of training until stoma closure was 9 months in the biofeedback versus 21 months in the electrostimulation group. Biofeedback training is probably superior to electrostimulation in the conservative treatment of anal sphincter insufficiency, this needs to be confirmed in a randomized study.