Pancreatoduodenectomy with or without prophylactic falciform ligament wrap around the hepatic artery for prevention of postpancreatectomy haemorrhage: randomized clinical trial (PANDA trial).

BACKGROUND: Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels. METHODS: In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH. RESULTS: Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively). CONCLUSION: A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy. REGISTRATION NUMBER: NCT02588066 (http://www.clinicaltrials.gov).

Surgical complications and cardiovascular comorbidity - Substantial non-immunological confounders of survival after living donor kidney transplantation.

BACKGROUND: Surgical complications following kidney transplantation compromise immediate graft survival. However, the role of early surgical complications in the impairment of long-term survival is not completely established due to various other influences, such as patient comorbidities. The purpose of this study was to characterize the impact of surgical complications and overlapping patient comorbidities on graft function and survival after living donor kidney transplantation (LDKT). METHODS: Two groups of patients following LDKT between 1995 and 2014 with (n = 65) or without (n = 294) Clavien-Dindo grade 3 and 4 complications were analyzed. Type of surgical revision, graft and patient survival, general patient characteristics, pre-transplant renal function, immunosuppression, and immunological characteristics (HLA mismatch, panel-reactive antibodies, rejections) were determined. Post-transplant graft function as well as long-term graft and patient survival were quantified. RESULTS: Graft survival was 84.4/97.6% (1y), 75.2/92.7% (3y), and 62.1/87.6% (5y) with/without surgical revision, patient survival was 95.3/99.3%, 90.0/97.5%, and 84.7/93.7%, respectively. Surgical revision was required in 18%, which affected graft survival (p = 0.008) to a comparable extent as pre-existing cardiopulmonary/-vascular disease. Initially impaired graft function recovered to an equal level without complications following surgical revision. Whereas pre-existing cardiopulmonary/-vascular disease affected graft loss and patient survival, surgical revision had no particular impact on patient survival. These observations were confirmed by Cox regression. CONCLUSION: Long-term graft survival following LDKT is independently impaired by both postoperative complications and cardiovascular comorbidities. Although both factors may interact, a complication-free postsurgical course may improve graft survival, thereby reducing the need for dialysis restart and enhancing long-term recipient survival.

Partial pancreatoduodenectomy versus duodenum-preserving pancreatic head resection in chronic pancreatitis: the multicentre, randomised, controlled, double-blind ChroPac trial.

BACKGROUND: There is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery. METHODS: This randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013. FINDINGS: Between Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference -2·3, 95% CI -6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity. INTERPRETATION: No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting. FUNDING: German Research Foundation (DFG).

Donor Dopamine Does Not Affect Liver Graft Survival: Evidence of Safety From a Randomized Controlled Trial.

Treatment of donation after brain death (DBD) donors with low-dose dopamine improves the outcomes after kidney and heart transplantation. This study investigates the course of liver allografts from multiorgan donors enrolled in the randomized dopamine trial between 2004 and 2007 (clinicaltrials.gov identifier: NCT00115115). There were 264 hemodynamically stable DBDs who were randomly assigned to receive low-dose dopamine. Dopamine was infused at 4 µg/kg/minute for a median duration of 6.0 hours (interquartile range, 4.4-7.5 hours). We assessed the outcomes of 212 liver transplantations (LTs) performed at 32 European centers. Donors and recipients of both groups were very similar in baseline characteristics. Pretransplant laboratory Model for End-Stage Liver Disease score was not different in recipients of a dopamine-treated versus untreated graft (18 ± 8 versus 20 ± 8; P = 0.12). Mean cold ischemia time was 10.6 ± 2.9 versus 10.1 ± 2.8 hours (P = 0.24). No differences occurred in biopsy-proven rejection episodes (14.4% versus 15.7%; P = 0.85), requirement of hemofiltration (27.9% versus 31.5%; P = 0.65), the need for early retransplantation (5.8% versus 6.5%; P > 0.99), the incidence of primary nonfunction (7.7% versus 8.3%; P > 0.99), and in-hospital mortality (15.4% versus 14.8%; P > 0.99). Graft survival was 71.2% versus 73.2% and 59.6% versus 62.0% at 2 and 3 years (log-rank P = 0.71). Patient survival was 76.0% versus 78.7% and 65.4% versus 69.4% at 1 and 3 years (log-rank P = 0.50). In conclusion, donor pretreatment with dopamine has no short-term or longterm effects on outcome after LT. Therefore, low-dose dopamine pretreatment can safely be implemented as the standard of care in hemodynamically stable DBDs.

Isolated pulmonary metastases define a favorable subgroup in metastatic pancreatic cancer.

PURPOSE: Liver metastasis represents the first site of dissemination in >80% of metastatic pancreatic cancer (PC) patients. Pulmonary metastasis as first site of dissemination in PC is a rare event and might define a biologically distinct subgroup in metastatic PC. METHODS: Consecutive PC patients who were diagnosed or treated with isolated pulmonary metastases at our high-volume comprehensive cancer center were included in a prospectively maintained database between 2002 and 2015. Medical records and correlating computed tomography findings (CT) were retrospectively analyzed. RESULTS: A total of 40 PC patients with isolated pulmonary metastases were identified. Pulmonary metastases represented disease recurrence after initial resection of PC in 22 patients and disease progression of locally advanced pancreatic cancer in 5 patients. 14 out of 27 PC patients (56%) had received chemoradiotherapy for localized disease prior to pulmonary metastasis. Data on 1st-line treatment for pulmonary metastases was available for 38 patients: most patients (71%) received a gemcitabine-based chemotherapy regimen, 5 patients (13%) received best supportive care. After a median follow-up of 37.3 months, median survival after diagnosis of pulmonary metastasis was estimated with 25.5 months (95% CI 19.1-31.8); a significantly improved survival after diagnosis of pulmonary metastasis was observed for patients with less than 10 lung metastases (31.3 vs 18.7 months, p = 0.003) and for an unilateral localization of lung involvement (31.3 vs 21.8 months, p = 0.03). CONCLUSIONS: Our results suggest a favorable outcome of PC patients with isolated pulmonary metastases. Further research is warranted to elucidate the specific molecular characteristics of this rare subgroup.

Surgery for metastasis to the pancreas: is it safe and effective?

BACKGROUND: Pancreatic metastases are rare and only sparse data exists on treatment options. After recent advances in pancreatic surgery, metastasectomies have become promising treatment alternatives. METHODS: Twenty-six patients underwent pancreatic metastasectomy between 1991 and 2010 at our institution. Data was evaluated retrospectively. RESULTS: Renal cell carcinoma was the most common origin of pancreatic metastases (n = 16; 62%). Other primaries include gall bladder carcinoma, leiomyosarcoma, colon cancer (all n = 2), and others. The median time interval between primary tumor and pancreatic resection was 5.3 years [0-24]. Eleven pancreatic head resections (42%), fourteen distal pancreatectomies (54%), and one total pancreatectomy were performed (4%). The estimated 3- and 5-year survival rates were 73.2% and 52.3%, respectively. The estimated median overall survival was 63 months (CI: 37.8-88.1 months). There' was no perioperative death. The complication rate and relaparotomy rate was 31% and 19%, respectively. Patients suffering from synchronous metastases at the time of pancreatic surgery had a statistically significant shorter median overall survival time (11 months vs. 64 months). CONCLUSIONS: Despite the operative risk involved, we believe that pancreatic resection should be considered in selected patients with good performance status, stable disease and isolated pancreatic metastases.

Determinants and clinical significance of negative scintigraphic findings in primary hyperparathyroidism: a retrospective observational study.

AIM: In patients with recurrent primary hyperparathyroidism (pHPT) or preceding thyroid operation, scintigraphic localization of the pathological parathyroid gland is sometimes unsuccessful. Reason for diagnostic failure, and its clinical relevance is poorly understood. METHODS: This retrospective observational study in patients suffering from a pHPT evaluated independent predictors of a negative preoperative scintigraphy (SC) result, and its relevance for intraoperative outcome using logistic regression analysis. RESULTS: Among 86 pHPT patients scheduled for parathyroid operation, 63 (73%) had a history of a preceding thyroid or parathyroid operation. Preoperative SC could not identify an adenoma in 30 patients (34.9%), and in 12 patients (14.0%), the surgeon was subsequently unable to localize abnormal parathyroid tissue. Preoperative parathyroid hormone concentration was the only significant independent predictor of a negative SC finding (non-linear and indirect association). Independent from surgical history, an unsuccessful intraoperative focus localization was exclusively predicted by preoperative ultrasonographic (US) and SC findings (OR per diagnostic category 2.98; 95%-CI 1.03-8.58, p=0.043, and OR 2.26; 95%-CI: 1.10-4.63, p=0.027, respectively). Compared to exclusive US, however, the combination of SC and US significantly increased the sensitivity and predictive power to identify patients at a high risk for a complicated surgical procedure. CONCLUSION: In patients before parathyroidectomy, a low preoperative parathyroid hormone concentration is significantly associated with a high likelihood for a negative SC finding. Combining US with SC before operation significantly increases the chance to identify patients prone to negative intraoperative findings.

Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis.

Augmenter of liver regeneration (ALR) is known to support liver regeneration and to stimulate proliferation of hepatocytes. However, it is not known if ALR exerts anti-apoptotic effects in human hepatocytes and whether this protective effect is cell type specific. This is relevant, because compounds that protect the liver against apoptosis without undesired effects, such as protection of metastatic tumour cells, would be appreciated in several clinical settings. Primary human hepatocytes (phH) and organotypic cancer cell lines were exposed to different concentrations of apoptosis inducers (ethanol, TRAIL, anti-Apo, TGF-ß, actinomycin D) and cultured with or without recombinant human ALR (rhALR). Apoptosis was evaluated by the release of cytochrome c from mitochondria and by FACS with propidium iodide (PI) staining. ALR significantly decreased apoptosis induced by ethanol, TRAIL, anti-Apo, TGF-ß and actinomycin D. Further, the anti-apoptotic effect of ALR was observed in primary human hepatocytes and in HepG2 cells but not in bronchial (BC1), colonic (SW480), gastric (GC1) and pancreatic (L3.6PL) cell lines. Therefore, the hepatotrophic growth factor ALR acts in a liver specific manner with regards to both its mitogenic and its anti-apoptotic effect. Unlike the growth factors HGF and EGF, rhALR acts in a liver specific manner. Therefore, ALR is a promising candidate for further evaluation as a possible hepatoprotective factor in clinical settings.

Arterial blood flow predicts graft survival in liver transplant patients.

Proper liver perfusion is essential for sufficient organ function after liver transplantation. The aim of this study was to determine the effects of portal and arterial blood flow on liver function and organ survival after liver transplantation. The arterial and portal venous blood flow was measured intraoperatively by transit time flow measurement after reperfusion for 290 consecutive liver transplants. The graft survival, hepatic cell damage (alanine aminotransferase and aspartate aminotransferase), and liver function (prothrombin ratio and bilirubin) were determined. Grafts were stratified into groups according to arterial blood flow measurements [<100 mL/minute for arterial blood flow group I (ART I), 100-240 mL/minute for ART II, and ≥ 240 mL/minute for ART III] and portal venous blood flow measurements (<1300 mL/minute for portal venous blood flow group I and ≥ 1300 mL/minute for portal venous blood flow group II). With multivariate analysis, the impact of blood flow on graft survival was determined, and potential confounders were considered. Decreased portal venous blood flow was associated with significantly less organ survival in univariate analysis but not in multivariate analysis. In contrast, the arterial blood flow was significantly correlated with organ survival after liver transplantation in univariate and multivariate analyses [hazard rate ratio = 2.5, confidence interval = 1.6-4.1, P < 0.001, median survival = 56.6 (ART I), 82.7 (ART II), or 100.7 months (ART III)]. Moreover, low arterial blood flow resulted in impaired postoperative organ function and higher rates of primary nonfunction. Biliary complications were not affected by blood flow. Other risk factors for graft failure that were identified by multivariate analysis included retransplantation, histidine tryptophan ketoglutarate solution versus University of Wisconsin solution, and donor treatment with epinephrine. Impaired arterial blood flow after reperfusion represents a significant predictor of primary graft nonfunction and is associated with impaired graft survival. Whether the intraoperative measurement of hepatic arterial flow is predictive of graft survival should be evaluated in a prospective trial.

Enteric conversion after pancreatic transplantation: resolution of symptoms and long-term results.

PURPOSE: Bladder drainage (BD) of pancreatic transplants is associated with a unique set of complications. We intended to analyze the incidence, indications, complications and long-term results of enteric conversion procedures (EC). METHODS: Using a prospective database, 32 EC patients out of 433 simultaneous pancreas-kidney-transplant (SPK) recipients were identified. Graft and patient survival rates were compared with those after primary enteric drainage (ED). RESULTS: The mean SPK-EC interval was 5.0 yr, and the mean patient follow-up was 13.8 yr. Indications for EC were genitourinary symptoms (62.5%), duodenal complications (15.6%), graft pancreatitis (12.5%), pyelonephritis (6.3%), and metabolic acidosis (3.1%). All patients reported significant long-term resolution of symptoms. Surgical complications, reoperations, early graft loss, and 30-d mortality occurred in 31.3%, 25.0%, 6.3%, and 3.1% of cases, respectively. Pancreatic graft and patient survival rates at 1, 5, and 10 yr after SPK were comparable between EC patients and ED patients at the same institution. CONCLUSION: For the treatment of symptoms associated with BD, EC results in excellent long-term graft function and significant resolution of symptoms even years after SPK. Postoperative morbidity after EC including early reoperation and graft loss, however, has to be considered.

Co-morbidity and postsurgical outcome in patients with perforated sigmoid diverticulitis.

INTRODUCTION: It was previously reported that in patients with acute perforated diverticulitis with Hinchey categories I to III sigmoidectomy with primary anastomosis (PA) is superior to Hartmann's procedure (HP) as later closure of colostomy involves substantial morbidity. We evaluated our experience with PA for patients with perforated diverticulitis over a 10-year period and aimed to investigate whether Hinchey category or co-morbidity are more relevant for postoperative outcome. METHODS: Records of all patients treated at our institution for sigmoid diverticulitis between 1996 and 2006 were retrieved from an in-hospital database (N = 787, median age 66 years, range 30 to 94, female:male ratio 1.3:1); 73 patients who underwent immediate emergency surgery for perforated diverticulitis were included in this study. American Society of Anesthesiology (ASA) classification to gauge co-morbidity and Hinchey category for intraoperative extent of inflammation were evaluated as regards their relevance for postoperative mortality and major complications. RESULTS: 47 patients (64%) underwent sigmoid colectomy and PA, which was combined with loop ileostomy in 11 patients (15%). Sigmoid colectomy and HP was performed in 26 patients (36%). Major postoperative complications occurred in 26 patients (36%). In the PA group, 10 of 47 patients (21%) had anastomotic leakage. Three leakages occurred despite a loop ileostomy. Anastomotic leakage was independent of Hinchey category (Hinchey I: three patients, Hinchey II: four patients, Hinchey III: three patients, n.s.), but associated with co-morbidity (one patient ASA II, six patients ASA III, three patients ASA IV, P < 0.05). Total mortality was 12%. Seven patients died after HP and two patients after PA. No mortality was observed in PA patients with loop ileostomy. CONCLUSIONS: Emergency surgery for perforated sigmoid diverticulitis is associated with high morbidity and mortality rates. Anastomotic leakage was associated with patient co-morbidity rather than with intraoperative Hinchey category, suggesting that the decision to perform PA should better be based on patient's general condition rather than on intraoperative extent of inflammation.

Lean processes for optimizing OR capacity utilization: prospective analysis before and after implementation of value stream mapping (VSM).

BACKGROUND: The decision to optimize the processes in the operating tract was based on two factors: competition among clinics and a desire to optimize the use of available resources. The aim of the project was to improve operating room (OR) capacity utilization by reduction of change and throughput time per patient. SETTING: The study was conducted at Centre Hospitalier Emil Mayrisch Clinic for specialized care (n = 618 beds) Luxembourg (South). METHOD: A prospective analysis was performed before and after the implementation of optimized processes. Value stream analysis and design (value stream mapping, VSM) were used as tools. VSM depicts patient throughput and the corresponding information flows. Furthermore it is used to identify process waste (e.g. time, human resources, materials, etc.). For this purpose, change times per patient (extubation of patient 1 until intubation of patient 2) and throughput times (inward transfer until outward transfer) were measured. VSM, change and throughput times for 48 patient flows (VSM A(1), actual state = initial situation) served as the starting point. Interdisciplinary development of an optimized VSM (VSM-O) was evaluated. Prospective analysis of 42 patients (VSM-A(2)) without and 75 patients (VSM-O) with an optimized process in place were conducted. RESULTS: The prospective analysis resulted in a mean change time of (mean ± SEM) VSM-A(2) 1,507 ± 100 s versus VSM-O 933 ± 66 s (p < 0.001). The mean throughput time VSM-A(2) (mean ± SEM) was 151 min (±8) versus VSM-O 120 min (±10) (p < 0.05). This corresponds to a 23% decrease in waiting time per patient in total. CONCLUSION: Efficient OR capacity utilization and the optimized use of human resources allowed an additional 1820 interventions to be carried out per year without any increase in human resources. In addition, perioperative patient monitoring was increased up to 100%.

The formal requirements of algorithms and their implications in clinical medicine and quality management.

PURPOSE: Clinical algorithms contribute to the problem- and priority-orientated management of patients and their disease in healthcare. Algorithms are of particular importance in all aspects of emergency medicine where the fast completion of a complex problem according to a hierarchy is required. The advantages and success of this priority- and problem-orientated concept led to its expansion to other subspecialties in medicine in recent years. However, in spite of algorithms being created based on defined norms, they are frequently violated in the literature, which renders the algorithm useless in a particular case. METHODS: The present debate addresses these issues and provides the formal criteria and their necessary modification for creating sufficient clinical algorithms. In this context, we also clarify the misunderstandings between step-by-step schemes, decision trees, and algorithms, which are often used synonymously, and discuss their implications in clinical medicine and quality management. RESULTS: A clinical algorithm can easily be created with the present derivation of the algorithm by its formal mathematical function using the corresponding norms describing specific symbols for a single criterion. Some symbol modifications as well as the usage of checklists to focus on the major criteria led to a rigorous reduction of the algorithm length and results in a clearer arrangement for routine clinical use. In clinical medicine, algorithms cannot only provide a fast access for solving complex problems but must also assure a transparent protocol and democratic treatment such that every patient receives the same quality of treatment. Thus, a treatment by chance can be excluded by standardization, which might impact the overall work needed to guide patients though diagnostics and therapy and may ultimately reduce cost. Algorithms are useful not only for quality in healthcare but also for undergraduate and continuous medical education. From a more philosophical point of view, we can raise the question of whether medical pathways and thereby the medical art should be disclosed to the general public by algorithms. Hippocrates form Kos held the view in the so-called Hippocratic Oath that medical art should only be revealed to medical scholars. CONCLUSIONS: The present derivation and nomination of the formal requirements may lead to a better understanding of algorithms themselves as well as their development and generation.

Pulmonary sclerosing hemangioma in a 21-year-old male with metastatic hereditary non-polyposis colorectal cancer: report of a case.

BACKGROUND: Pulmonary sclerosing hemangioma (SH) is a rare tumor of the lung predominantly affecting Asian women in their fifth decade of life. SH is thought to evolve from primitive respiratory epithelium and mostly shows benign biological behavior; however, cases of lymph node metastases, local recurrence and multiple lesions have been described. CASE PRESENTATION: We report the case of a 21-year-old Caucasian male with a history of locally advanced and metastatic rectal carcinoma (UICC IV; pT4, pN1, M1(hep)) that was eventually identified as having hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome). After neoadjuvant chemotherapy followed by low anterior resection, adjuvant chemotherapy and metachronous partial hepatectomy, he was admitted for treatment of newly diagnosed bilateral pulmonary metastases. Thoracic computed tomography showed a homogenous, sharply marked nodule in the left lower lobe. We decided in favor of atypical resection followed by systematic lymphadenectomy. Histopathological analysis revealed the diagnosis of SH. CONCLUSIONS: Cases have been published with familial adenomatous polyposis (FAP) and simultaneous SH. FAP, Gardner syndrome and Li-Fraumeni syndrome, however, had been ruled out in the present case. To the best of our knowledge, this is the first report describing SH associated with Lynch syndrome.

Rare SARS-CoV-2 antibody development in cancer patients.

SARS-CoV-2 antibody development and immunity will be crucial for the further course of the pandemic. Until now, it has been assumed that patients who are infected with SARS-CoV-2 will develop antibodies as has been the case with other coronaviruses, like MERS-CoV and SARS-CoV. In the present study, we analyzed the development of antibodies in 77 patients with an oncologic diagnosis 26 days after positive RT-qPCR testing for SARS-CoV2. RT-qPCR and anti-SARS-CoV2-antibody methods from BGI (MGIEasy Magnetic Beads Virus DNA/RNA Extraction Kit) and Roche (Elecsys Anti-SARS-CoV-2 immunoassay) were used, respectively, according to the manufacturers' specifications. Surprisingly, antibody development was detected in only 6 of 77 individuals with a confirmed history of COVID-19. Despite multiple testing, the remaining patients did not show measurable antibody concentrations in subsequent tests. These results undermine the previous hypothesis that SARS-CoV2 infections are regularly associated with antibody development and cast doubt on the provided immunity to COVID-19. Understanding the adaptive and humoral response to SARS-CoV2 will play a key role in vaccine development and gaining further knowledge on the pathogenesis.

Landscape of Biomarkers and Actionable Gene Alterations in Adenocarcinoma of GEJ and Stomach-A Real World Data Analysis.

After several years of negative phase III trials in gastric and esophageal cancer, a significant breakthrough in the treatment of metastatic adenocarcinomas of the gastroesophageal junction (GEJ) and stomach (GC) is now becoming evident with the emerging of precision oncology and implementation of molecular targets in tumor treatment. In addition, new generation studies such as umbrella and basket trials are focused on these molecular targets, which makes an early molecular diagnosis based on IHC/ISH and NGS necessary. The required companion diagnostics of Her2neu overamplification or PD-L1 expression is based on immunohistochemistry (IHC) or additionally in situ hybridization (ISH) in case of an IHC Her2neu score of 2+. However, there are investigator-dependent differences in the assessment of Her2neu amplification and different PD-L1 scoring systems obtained by IHC/ISH. The use of high-throughput technologies such as next-generation sequencing (NGS) holds the potential to standardize the analysis and thus make them more comparable. In the presented study, real-world multigene sequencing data of 72 Caucasian patients diagnosed with metastatic adenocarcinomas of GEJ and stomach were analyzed. In the clinical companion diagnostics, we found ESCAT level I molecular targets in one-third of our patients, which directly determined the therapy. In addition, we found potential targets in 14/72 patients (19.4%) who potentially qualify for precision therapies in corresponding molecular studies. The study highlights the importance of comprehensive molecular profiling for precision treatment of GEJ/GC and indicates that a biomarker evaluation should be performed for all patients with metastatic adenocarcinomas before the initiation of first-line treatment and during second-line or subsequent treatment.

EFEMP1 expression promotes in vivo tumor growth in human pancreatic adenocarcinoma.

The progression of pancreatic cancer is dependent on local tumor growth, angiogenesis, and metastasis. EFEMP1, a recently discovered member of the fibulin family, was characterized with regard to these key elements of pancreatic cancer progression. Differential gene expression was assessed by mRNA microarray hybridization in FG human pancreatic adenocarcinoma cells and L3.6pl cells, a highly metastatic variant of FG. In vivo orthotopic tumor growth of EFEMP1-transfected FG cells was examined in nude mice. To assess the angiogenic properties of EFEMP1, vascular endothelial growth factor (VEGF) production of tumor cells, endothelial cell proliferation and migration, and tumor microvessel density were analyzed in response to EFEMP1. Further, tumor cell apoptosis, cell cycle progression, and resistance to cytotoxic agents were quantitated by propidium iodide staining and flow cytometry. In microarray hybridization, EFEMP1 was shown to be significantly up-regulated in L3.6pl cells compared with FG cells. Concordantly, EFEMP1 transfection of FG cells stimulated orthotopic and metastatic tumor growth in vivo. EFEMP1 expression resulted in a stimulation of VEGF production by tumor cells and an increased number of CD31-positive microvessels. Endothelial cell proliferation and migration were not altered by EFEMP1, indicating an indirect angiogenic effect. Further, EFEMP1 expression decreased apoptosis and promoted cell cycle progression in response to serum starvation or exposure to gemcitabine, 5-fluorouracil, and irinotecan. EFEMP1 has protumorigenic effects on pancreatic cancer in vivo and in vitro mediated by VEGF-driven angiogenesis and antiapoptotic mechanisms. Hence, EFEMP1 is a promising candidate for assessing prognosis and individualizing therapy in a clinical tumor setting.

Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications.

PURPOSE: Since the discovery of cancer cells with stem-like characteristics in hematopoietic malignancies and, more recently, in solid tumors, enormous attention has been paid to the stem-cell nature of pancreatic cancer. Among the most important properties of cancer stem cells their high capacity for tumorigenicity as well as their ability to metastasize is under special research interest today. METHODS: Here, we give a brief overview of main components used to confirm the stem-cell-like behavior of putative cancer stem cells and discuss markers and methods for identifying them in pancreatic cancer. Finally, the review provides some new suggestions as to how specifically target these cells and improve current therapy regimens. RESULTS: The cancer stem-cell hypothesis is a fundamentally different model of carcinogenesis composed of two separate but dependent on each other characteristics of stem cells--aberrant activation of their tightly regulated processes of self-renewal and differentiation and their resistance towards chemo- and radiotherapy. The cancer stem cells may further be identified based on their expression of cell surface markers or their functional characteristics. The concept of molecular targeting of such highly tumorigenic cancer cells aimed to sensitize tumors toward conventional therapies and effectively abrogate tumor growth and metastasis. CONCLUSIONS: The presence of cancer stem cells in pancreatic tumors has prognostic relevance and influences therapeutic response. Evidence suggests that metastatic potential may be conferred to these highly tumorigenic cells as well. A better understanding of the biological behavior of these cells may further improve therapeutic approaches and outcomes in patients with this devastating disease.

SARS-CoV-2 infections in cancer outpatients-Most infected patients are asymptomatic carriers without impact on chemotherapy.

Oncologic patients are regarded as the population most at risk of developing a severe course of COVID-19 due to the fact that malignant diseases and chemotherapy often weaken the immune system. In the face of the ongoing SARS-CoV-2 pandemic, how particular patients deal with this infection remains an important question. In the period between the 15 and 26 April 2020, a total of 1227 patients were tested in one of seven oncologic outpatient clinics for SARS-CoV-2, regardless of symptoms, employing RT-qPCR. Of 1227 patients, 78 (6.4%) were tested positive of SARS-CoV-2. Only one of the patients who tested positive developed a severe form of COVID-19 with pneumonia (CURB-65 score of 2), and two patients showed mild symptoms. Fourteen of 75 asymptomatic but positively tested patients received chemotherapy or chemo-immunotherapy according to their regular therapy algorithm (±4 weeks of SARS-CoV-2 test), and 48 of 78 (61.5%) positive-tested patients received glucocorticoids as co-medication. None of the asymptomatic infected patients showed unexpected complications due to the SARS-CoV-2 infection during the cancer treatment. These data clearly contrast the view that patients with an oncologic disease are particularly vulnerable to SARS-CoV-2 and suggest that compromising therapies could be continued or started despite the ongoing pandemic. Moreover the relatively low appearance of symptoms due to COVID-19 among patients on chemotherapy and other immunosuppressive co-medication like glucocorticoids indicate that suppressing the response capacity of the immune system reduces disease severity.

Perioperative fluid retention and clinical outcome in elective, high-risk colorectal surgery.

BACKGROUNDS AND AIMS: There is some controversy regarding concepts currently propagated for an optimal perioperative fluid management in colorectal surgery. We wanted to analyze the association of net intraoperative and postoperative fluid balances with postoperative morbidity and length of stay. MATERIALS AND METHODS: We performed a retrospective analysis of data collected prospectively from March 1993 through February 2005. A subgroup from 4,658 patients was studied who had undergone major elective colorectal surgery during that time. This subgroup included 198 patients with a particularly high preoperative risk profile requiring immediate postoperative intensive care unit (ICU) admission. Fluid therapy was guided by established clinical end points. Results were adjusted for various confounding variables (extent of the operative trauma, individual response to the injury, type of analgesia, underlying disease, treatment era). RESULTS/FINDINGS: After adjustment for relevant covariates, the magnitude of fluid balance was unimportant for morbidity and postoperative hospital length of stay. A high Apache II score after ICU admission, an increased perioperative blood loss, and palliative surgical procedures were associated with a significantly higher complication rate, whereas use of epidural analgesia improved morbidity and shortened hospital stay. INTERPRETATION/CONCLUSION: If guided by established standards, even large perioperative fluid retentions do not appear to be associated with a worse outcome after extended colorectal surgery. Epidural analgesia may provide a significant benefit in those high-risk patients.