Decreased mebrofenin uptake in patients with non-colorectal liver tumors requiring liver volume augmentation-a single-center analysis.

BACKGROUND: Posthepatectomy liver failure (PHLF) remains a life-threatening complication after hepatectomy. To reduce PHLF, a preoperative assessment of liver function is indispensable. For this purpose, 99mTc-mebrofenin hepatobiliary scintigraphy with SPECT (MSPECT) can be used. The aim of the current study was to evaluate the predictive value of MSPECT for PHLF in patients with non-colorectal liver tumors (NCRLT) compared to patients with colorectal liver metastasis (CRLM) undergoing extended liver resection. METHODS: We included all patients undergoing extended liver resections via two-stage procedures between January 2019 and December 2021 at the University Medical Center Hamburg-Eppendorf, Germany. All patients received a preoperative MSPECT. RESULTS: Twenty patients were included. In every fourth patient, PHLF was observed. Four patients had PHLF grade C. There were no differences between patients with CRLM and NCRLT regarding PHLF rate and future liver remnant (FLR) volume. Patients with CRLM had higher mebrofenin uptake in the FLR compared to those with NCRLT (2.49%/min/m2 vs. 1.51%/min/m2; p = 0.004). CONCLUSION: Mebrofenin uptake in patients with NCRLT was lower compared to those patients with CRLM. However, there was no difference in the PHLF rate and FLR volume. Cut-off values for the mebrofenin uptake might need adjustments for different surgical indications, surgical procedures, and underlying diseases.

Adjusting the RAPID score with 2 additional variables significantly increases its predictive value in patients with empyema.

Pleural empyema is a serious condition leading to a significant burden on health care systems due to protracted hospitalisations. Treatment ranges from non-surgical interventions such as antibiotic therapy and chest tube placement to thoracoscopic or open surgery. Various risk factors which impact outcomes have been investigated. The RAPID (renal, age, purulence, infection source, and dietary factors) score is a clinical risk score which identifies patients at risk of death and may be used to formulate individual treatment strategies accordingly. All patients undergoing surgical interventions for empyema at a major tertiary medical centre in Germany from 2017 to 2020 were analysed. The aim was to identify perioperative risk factors which significantly impact treatment outcomes but are currently not included in the RAPID score. 245 patients with pleural empyema surgically treated at the Department of General, Visceral and Thoracic Surgery at the University Medical Centre, Hamburg, Germany (admitted from January 2017 to April 2020) were retrospectively analysed. All patients which received either minimally invasive or open thoracic surgery were included. Epidemiological as well as perioperative data was analysed to identify risk factors which impact long-term overall outcomes. 90-day mortality rate was the primary endpoint. The mean age was 59.4 years with a bimodal distribution. There was a male predominance across the cohort (71.4% compared to 28.6%), with no significant differences across ages below or above 60 years. 53 (21.6%) patients died within the first 90 days. Diabetes type 1 and 2, renal replacement therapy, immunosuppression, postoperative bleeding, intraoperative transfusion as well as microbiologically confirmed bacterial invasion of the pleura all led to higher mortality rates. Higher RAPID scores accurately predicted higher 90-day mortality rates. Modifying the RAPID score by adding the comorbidities diabetes and renal replacement therapy significantly increased the predictive value of the score. We demonstrated various perioperative and patient related risk-factors not included in the RAPID score which negatively impact postoperative outcome in patients receiving surgical treatment for pleural empyema. These should be taken into consideration when deciding on the best course of treatment. If confirmed in a prospective study including non-surgical patients with a significantly larger cohort, it may be worth considering expanding the RAPID score to include these.

[Perioperative fluid management]. / Perioperatives Volumenmanagement.

An appropriate perioperative infusion management is pivotal for the perioperative outcome of the patient. Optimization of the perioperative fluid treatment often results in enhanced postoperative outcome, reduced perioperative complications and shortened hospitalization. Hypovolemia as well as hypervolemia can lead to an increased rate of perioperative complications. The main goal is to maintain perioperative euvolemia by goal-directed therapy (GDT), a combination of fluid management and inotropic medication, to optimize perfusion conditions in the perioperative period; however, perioperative fluid management should also include the preoperative and postoperative periods. This encompasses the preoperative administration of carbohydrate-rich drinks up to 2 h before surgery. In the postoperative period, patients should be encouraged to start per os hydration early and excessive i.v. fluid administration should be avoided. Implementation of a comprehensive multimodal, goal-directed fluid management within an enhanced recovery after surgery (ERAS) protocol is efficient but the exact status of indovodual items remains unclear at present.

International consensus guidelines for surgery and the timing of intervention in chronic pancreatitis.

BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a complex inflammatory disease with pain as the predominant symptom. Pain relief can be achieved using invasive interventions such as endoscopy and surgery. This paper is part of the international consensus guidelines on CP and presents the consensus guideline for surgery and timing of intervention in CP. METHODS: An international working group with 15 experts on CP surgery from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 20 statements generated from evidence on 5 questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available for each statement. To determine the level of agreement, the working group voted on the 20 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: Strong consensus was obtained for the following statements: Surgery in CP is indicated as treatment of intractable pain and local complications of adjacent organs, and in case of suspicion of malignant (cystic) lesion; Early surgery is favored over surgery in a more advanced stage of disease to achieve optimal long-term pain relief; In patients with an enlarged pancreatic head, a combined drainage and resection procedure, such as the Frey, Beger, and Berne procedure, may be the treatment of choice; Pancreaticoduodenectomy is the most suitable surgical option for patients with groove pancreatitis; The risk of pancreatic carcinoma in patients with CP is too low (2% in 10 year) to recommend active screening or prophylactic surgery; Patients with hereditary CP have such a high risk of pancreatic cancer that prophylactic resection can be considered (lifetime risk of 40-55%). Weak agreement for procedure choice in patients with dilated duct and normal size pancreatic head: both the extended lateral pancreaticojejunostomy and Frey procedure seems to provide equivalent pain control in patients. CONCLUSIONS: This international expert consensus guideline provides evidenced-based statements concerning key aspects in surgery and timing of intervention in CP. It is meant to guide clinical practitioners and surgeons in the treatment of patients with CP.

[Fluorescence angiography for esophageal anastomoses : Perfusion evaluation of the gastric conduit with indocyanine green]. / Fluoreszenzangiographie bei Ösophagusanastomosen : Perfusionsbeurteilung des Magenschlauchs mit Indocyaningrün.

BACKGROUND: The incidence of esophageal cancer continues to increase. Despite increasing experience in esophageal surgery and perioperative management, anastomotic leakage remains a frequent and severe complication. OBJECTIVE: The aim of this article is to demonstrate the current role of fluorescence angiography (FA) with indocyanine green (ICG) in the assessment of esophageal anastomoses. The main focus is on the evaluation of the perfusion situation. MATERIAL AND METHODS: A systematic search was carried out in PubMed and Medline on FA and ICG, especially with respect to current subjective and objective interpretation approaches of FA against the background of own research. RESULTS: The rate of anastomotic leakage remains high despite modern surgical procedures. Assessment of neoesophageal perfusion with FA can significantly reduce the rate of anastomotic leakage. At present, FA is mostly subjectively applied in small case studies. The study situation is heterogeneous. Randomized studies do not so far exist. CONCLUSION: The use of FA with ICG is suitable for evaluation of perfusion of the gastric tube. The implementation is simple and can be standardized. Prospective, randomized trials and objective quantification are needed in the future in order to clarify the potential of the technique.

A hairy cavity: endoscopic therapy of a presacral recurrence of a complex pilonidal sinus.

BACKGROUND: Recently, minimally invasive techniques to avoid radical excisions of the pilonidal sinus with long-lasting secondary wound healing were developed. We describe a rare case of an intrapelvic, pararectal recurrence of a pilonidal sinus, who was innovatively treated with flexible endoscopy. CASE PRESENTATION: A 43-year-old Caucasian man presented with an intrapelvic, pararectal recurrence of a primarily wide-stretched pilonidal sinus, originally located in the sacrococcygeal region and spreading laterally to the gluteal region and intrapelvic to the presacral area. No connection to the bowel was evident. Up until presentation in the endoscopic department, a total of five attempts of surgical resection were performed, always confirming the diagnosis of a pilonidal sinus. Endoscopic therapy consisted of a combination of debridement, laser ablation and endoscopic vacuum therapy. After completion of APC and VAC therapy, the patient irrigated the abscess cavity for a further 2 weeks with a rinsing syringe. The resulting deep scar at the gluteal fistula was resected after secondary wound healing was completed. Two years after the end of the therapy, no recurrence was evident. CONCLUSION: Flexible endoscopy is, with its multiple therapeutic applications, an effective tool even in very complex inflammatory fistula and abscesses. Correctly indicated, it is with its minimally invasive character an excellent alternative to open surgical approaches.

[Standardized access options for colorectal surgery with the da Vinci Xi system]. / Standardisierte Zugangsoptionen für die kolorektale Chirurgie mit dem Da-Vinci-Xi-System.

BACKGROUND: Performing colorectal surgery with previous da Vinci system generations presented some limitations that caused uncertainty for surgeons as they began to apply robotic technologies. The da Vinci Xi system is designed to overcome these limitations and to enable multiquadrant colorectal surgery. OBJECTIVE: The design concept of the da Vinci Xi system and the standardized access for colorectal surgery are explained. MATERIAL AND METHODS: The da Vinci Xi system applies an overhead boom that maximizes the arm workspace, minimizes interference and makes the port placement universal for standardized access. Colorectal approaches have been validated in numerous cadaver models confirming the reproducibility of the standardized access. RESULTS: Standardized access with a straight-line port placement is possible in all colorectal applications. For right-sided hemicolectomy, a transverse abdominal approach as well as a suprapubic port placement are possible. Utilizing the same principles, left-sided colectomy, sigmoid colectomy and low anterior resections can be performed. Proctocolectomy is enabled through boom rotation and a second docking. Only minor arm-to-arm interferences occurred and were easily manageable by the bedside assistant. None of the approaches required rearrangement of the patient cart or swapping arms to different port locations. CONCLUSION: The da Vinci Xi system enables a standardized access for colorectal surgery through a universal straight-line port placement. Learning this standard principle once enables the surgeon to apply it to all colorectal surgeries and shorten the learning curve as well as minimizing stress for both novices and experienced robotic surgeons learning a new surgical robotic platform.

Robot-Assisted Oesophagectomy: Recommendations Towards a Standardised Ivor Lewis Procedure.

A considerable number of reports have been published on the feasibility, techniques, and early postoperative results of robotic-assisted oesophageal surgery. However, these are mostly smaller case series, suggesting that the robot-assisted Ivor Lewis procedure is still in the implementation phase and far from being standardised. Oesophageal surgeons from seven robotic university centres in Germany, experienced in both minimally invasive and robot-assisted minimally invasive surgery, took part in a workshop on robot-assisted surgery. An intensive exchange of opinions and experiences, followed by a step-by-step re-enactment of the operation in a cadaver lab, enabled us to develop a standardised robot-assisted Ivor Lewis surgical workflow, which is presented here. Systematic and objective comparison of experiences and results using a robot-assisted Ivor Lewis procedure has made it possible to develop a standardised surgical workflow that is now clinically applied in our centres. It is hoped that standardisation of this procedure will help to maintain patient safety, prevent medical errors, and facilitate the learning curve, while introducing robotic surgery into a centre.

What predicts the outcome in patients with intestinal ischemia? A single center experience.

BACKGROUND: Acute mesenteric ischemia (AMI) is associated with a mortality of 60-80%. Early diagnosis and rapid treatment have a decisive influence on therapy. The aim of this study was to evaluate the prognostic value of AMI markers on mortality, in order to better anticipate the clinical course and to initiate therapeutic steps at an early stage. STUDY DESIGN: An analysis from our prospective database of 302 consecutive patients with AMI who were treated surgically in the Department of General Surgery between February 2003 and October 2014 was performed. Uni- and multivariate analysis of risk factors for mortality have been performed in the total cohort and in two subgroups according to their stay in intensive care unit (ICU) at the time of AMI diagnosis. RESULTS: Of the 302 patients with AMI, 115 were in ICU at the time of diagnosis. Totally, 203 patients underwent computed tomography scan (CT-scan) of the abdomen for diagnosis and 68% of them showed specific signs of AMI. A total of 63 (21%) embolectomies were performed during the surgical procedure. The post-operative mortality rate was 68% (204 patients). Among survivors, 85 (87%) patients developed a short bowel syndrome in the post-operative course. Multivariate analysis showed a significant association between mortality and preoperative lactate>3mmol/L, C-reactive protein>100mg/L and ICU stay at the time of AMI diagnosis. CONCLUSION: Mortality of patients with AMI remains high. Elevated lactate, elevated C-reactive protein and ICU stay are factors associated with increased mortality. Their presence in a patient with suspicion of AMI should trigger a multidisciplinary management in emergency.

Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.

[Evidence for standard surgical procedures: appendicitis, diverticulitis and cholecystitis]. / Evidenz für chirurgische Standardverfahren: Appendizitis, Divertikulitis und Cholezystitis.

BACKGROUND: Acute appendicitis, cholecystitis and sigmoid diverticulitis are the most common inflammatory visceral surgical emergencies. According to the principles of evidence-based medicine, treatment methods and surgical indications should be constantly questioned and validated by high-quality clinical studies. OBJECTIVE: To identify and classify the current evidence on surgical treatment of acute appendicitis, cholecystitis and sigmoid diverticulitis. MATERIAL AND METHODS: Targeted literature search in Medline, the Cochrane Library and study registers (clinicaltrials.gov). RESULTS AND CONCLUSION: The indications for surgery are changing due to increasing numbers of high-quality clinical studies. Conservative treatment seems to be feasible in the early stages. In contrast, many surgical steps have not yet been sufficiently validated. Furthermore, there is a great need for high-quality, prospective randomized clinical trials, so that promotion of studies and the study culture in surgery should continue to be of greatest interest.

Evaluation of the MDACC clinical classification system for pancreatic cancer patients in an European multicenter cohort.

BACKGROUND: The MDACC group recommends to extend the current borderline classification for pancreatic cancer into three groups: type A patients with resectable/borderline tumor anatomy, type B with resectable/borderline resectable tumor anatomy and clinical findings suspicious for extrapancreatic disease and type C with borderline resectable and marginal performance status/severe pre-existing comorbidity profile or age>80. This study intents to evaluate the proposed borderline classification system in a multicenter patient cohort without neoadjuvant treatment. METHODS: Evaluation was based on a multicenter database of pancreatic cancer patients undergoing surgery from 2005 to 2016 (n = 1020). Complications were classified based on the Clavien-Dindo classification. χ2-test, Kaplan-Meier estimator and Cox regression hazard model were used for statistical analysis. RESULTS: Most patients (55.1%) were assigned as type A patients, followed by type C (35.8%) and type B patients (9.1%). Neither the complication rate, nor the mortality rate revealed a correlation to any subgroup. Type B patients had a significant worse progression free (p < 0.001) and overall survival (p = 0.005). Type B classification was identified as an independent prognostic marker for progression free survival (p = 0.005, HR 1.47). CONCLUSION: The evaluation of the proposed classification in a cohort without neoadjuvant treatment did not justify an additional medical borderline subgroup. A new subgroup based on prognostic borderline patients might be the main target group for neoadjuvant protocols in future.

Evaluation of the robotic approach concerning pitfalls in rectal surgery.

INTRODUCTION: The feasibility and advantages of robotic rectal surgery (RRS) in comparison to conventional open or laparoscopic rectal resections have been postulated in several reports. But well-known challenges and pitfalls of minimal invasive rectal surgery have not been evaluated by a prospective, multicenter setting so far. Aim of this study was to analyze the perioperative outcome of patients following RRS especially in regard to the pitfalls such as obesity, male patients and low tumors by a European multicenter setting. METHODS: This prospective study included 348 patients undergoing robotic surgery due to rectal cancer in six major European centers. Clinicopathological parameters, morbidity, perioperative recovery and short-term outcome were analyzed. RESULTS: A total of 283 restorative surgeries and 65 abdominoperineal resections were carried out. The conversion rate was 4.3%, mean blood loss was 191 ml, and mean operative time was 315 min. Postoperative complications with a Clavien-Dindo score >2 were observed in 13.5%. Obesity and low rectal tumors showed no significant higher rates of major complications or impaired oncological parameters. Male patients had significant higher rates of major complications and anastomotic leakage (p = 0.048 and p = 0.007, respectively). DISCUSSION: RRS is a promising tool for improvement of rectal resections. The well-known pitfalls of minimal-invasive rectal surgery like obesity and low tumors were sufficiently managed by RRS. However, RRS showed significantly higher rates of major complications and anastomotic leakage in male patients, which has to be evaluated by future randomized trials.

Blood fibrinogen levels discriminate low- and high-risk intraductal papillary mucinous neoplasms (IPMNs).

BACKROUND: The risk assessment of intraductal papillary mucinous neoplasms (IPMN) to either guide patients to surgical resection or watchful waiting is still under debate. Additional markers to better separate low and high-risk lesions would improve patient selection. METHODS: Patients who underwent pancreatic resections for IPMNs between January 2008 and December 2012 with available blood samples were selected and retrospectively assessed. Data on cyst characteristics such as cyst size, duct relation and main-duct dilatation were collected and plasma fibrinogen levels were measured. RESULTS: A total of 73 patients fulfilled the inclusion criteria by pancreatic resection for pathologically confirmed IPMN and available blood sample. Histologically, IPMNs were classified as low-grade and borderline in 52 (71.2%, group 1) and as high-grade and invasive in 21 (28.8%, group 2) of all cases. Fibrinogen levels showed significant differences between the two groups (group 1: mean 3.62 g/L (SD ± 1.14); group 2: mean 4.49 g/L (SD ± 1.57); p = 0.027). A ROC-curve analysis calculated cut-off value of 4.71 g/L separated groups 1 and 2 (p = 0.008). Fibrinogen levels remained as the only significant factor in multivariable analysis, cyst size and duct relation were not significant. CONCLUSION: Blood fibrinogen differed between low and high risk IPMNs and therefore, the use of fibrinogen as an additional discriminator in the pre-operative risk assessment of IPMNs should be further evaluated.

MALDI imaging mass spectrometry reveals multiple clinically relevant masses in colorectal cancer using large-scale tissue microarrays.

For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer, we applied Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) to a tissue micro array containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. Fifteen out of 27 IMS signals revealed a significant association with survival. For seven signals (m/z 654, 776, 788, 904, 944, 975 and 1013) the absence and for eight signals (m/z 643, 678, 836, 886, 898, 1095, 1459 and 1477) the presence were associated with decreased life expectancy, including five masses (m/z 788, 836, 904, 944 and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these five masses resulted in a three-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale tissue micro arrays to simultaneously identify and validate clinically useful molecular marker. Copyright © 2017 John Wiley & Sons, Ltd.

HRG/HER2/HER3 signaling promotes AhR-mediated Memo-1 expression and migration in colorectal cancer.

Colorectal cancer (CRC) is a complex disease with still unsatisfactory prognosis even in western societies, although substantial progress has been made in pre-screening programs, surgical techniques and targeted therapy options. Mediator of motility-1 (Memo-1) was previously recognized as an important effector of cell migration downstream of receptor tyrosine kinase signaling in breast cancer. This study identified Memo-1 as frequently overexpressed in CRC and established a close link between extracellular HER2 activation, AhR/ARNT transcriptional activity and Memo-1 expression. Dissection of the hMemo-1 gene promoter using reporter assays and chromatin IP techniques revealed recruitment of Aryl hydrocarbon receptor (AhR)/Aryl hydrocarbon receptor nuclear-translocator (ARNT) complex, which positively influenced Memo-1 expression in cancer cells. We found that Memo-1 depletion negatively influenced the cellular actin network and that its expression is required for HER2-mediated cell migration and invasion. Moreover, analyses of Memo-1 expression in primary CRC revealed correlation with clinical parameters that point to Memo-1 as a new prognostic factor of aggressive disease in CRC patients. Altogether, these observations demonstrate that Memo-1 is an important downstream regulator of HER2-driven CRC cell migration and invasion through connecting extracellular signals from membrane to the cytoskeletal actin network.

A rheological model for immersed corrugated elastic plates.

The influence of surface imperfections on the propagation of guided waves in an immersed elastic plate can be interpreted by means of a rheological model. The corrugated surface is modeled by a very thin interface, similar to a Jones spring model, which replaces the continuity boundary conditions at the liquid - corrugated solid-plate interface. As the surrounding liquid is considered to be perfect, only one complex stiffness is used for the model of Jones. The selection of the plate guided mode and the test frequency are motivated by the detectability and non-interference with other modes. The spring stiffness is obtained by a best fit procedure, between the analytical solution and the results obtained by the finite elements method (FEM). One way ensuring the agreement of the two approaches, rheological and FEM, is to consider angular resonances provided by the transmission coefficients. Small changes in the parameters of the roughness keep the positions of the angular resonances of the plate practically unchanged, while at the same time large variations of the half width of the transmission coefficient curve is observed. The effect of corrugation parameters on the guided modes in the plate can be predicted by using the rheological model with the deduced spring complex stiffness.

[Pancreatic anastomosis in operative treatment of chronic pancreatitis]. / Pankreasanastomosen bei operativer Versorgung der chronischen Pankreatitis.

Chronic pancreatitis (CP) is an irreversible, inflammatory process, which is characterized by progressive fibrosis of the pancreas and leads to abdominal pain, endocrine and exocrine insufficiency. Surgical therapy is indicated by the absence of pain relief and local complications. The target of the surgical approach is to relieve the pancreatic and bile ducts and resection of the fibrotic and calcified parenchyma. Drainage procedures, such as the Partington-Rochelle method, are used in patients with isolated congestion of the pancreatic duct without further organ complications, such as inflammatory processes of the pancreatic head; however, patients with CP often have an inflammatory swelling of the pancreatic head. In this case classical pancreatoduodenectomy (PD) or organ-sparing duodenum-preserving pancreatic head resection (DPPHR) with its various techniques (e.g. Beger, Frey, Bern and V­shape) can be applied. Due to similar long-term results PD should be carried out in cases of suspicion or detection of malignancies and DPPHR for treatment of CP.