Cancer catecholamine conundrum.

Exercise, psychosocial stress, and drugs such as adrenergic agonists and antagonists increase the concentrations of catecholamines and/or alter adrenergic signaling. Intriguingly, exercise studies universally suggest that catecholamines are cancer-inhibiting whereas cancer stress studies typically report the opposite, whereas ß-blocker studies show variable effects. Here, we term variable effects of catecholamines in cancer the cancer catecholamine conundrum. Variable effects of catecholamines can potentially be explained by variable expression of nine adrenergic receptor isoforms and by other factors including catecholamine effects on cancer versus immune or endothelial cells. Future studies on catecholamines and cancer should seek to understand the mechanisms that explain variable effects of catecholamines in cancer to utilize beneficial or block detrimental effects of catecholamines in cancer patients.

[Quality of indications in cystic lesions of the pancreas]. / Indikationsqualität bei zystischen Läsionen des Pankreas.

Cystic tumors of the pancreas (PCN) have increasingly gained importance in the clinical routine as they are frequently diagnosed as an incidental finding due to the continuous improvement in cross-sectional imaging. A differentiation is made between non-neoplastic and neoplastic cysts, whereby the latter has a tendency to malignant transformation to a varying extent. Therefore, they can be considered as precursor lesions of pancreatic cancer (PDAC). In addition to a detailed patient history and examination, imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) with fine needle aspiration (FNA) are used for the differential diagnosis. The indications for surgical resection of these lesions are based on the current European guidelines from 2018; however, the content is not evidence-based but relies on knowledge and recommendations from experts. According to these consensus recommendations asymptomatic serous cystic neoplasms (SCN) are serous lesions with a low tendency for malignant transformation and can be monitored. In contrast resection is warranted for all mucinous cystic neoplasms (MCN) >4 cm and all solid pseudopapillary neoplasms (SPN). Intraductal papillary mucinous neoplasms (IPMN), which are differentiated into main duct (MD-IPMN) and branch duct type (BD-IPMN) IPMN based on the position in the pancreatic duct system, should be resected as MD-IPMN and mixed type (MT)-IPMN. The risk of malignant transformation in BD-IPMN is variable and depends on risk factors, which are defined clinically and by imaging morphology. The treatment management is therefore carried out on an individual basis following risk estimation. In order to quantify the quality of indications in PCN and thereby also contributing to optimized medical care, prospective long-term studies are urgently needed.

[Surgery for isolated local recurrence and metachronous oligometastasis in pancreatic cancer]. / Chirurgie bei isoliertem Lokalrezidiv und metachroner Oligometastasierung beim Pankreaskarzinom.

BACKGROUND: Most patients with pancreatic cancer suffer a relapse, which occurs either locally or systemically in the sense of liver and the lung metastases. Surgery for pancreatic cancer has become more radical due to the increased use of multimodal treatment concepts; however, the role of surgery in cases of recurrence remains controversial. OBJECTIVE: This review summarizes the surgical treatment options for isolated local recurrence and metachronous oligometastatic pancreatic cancer. MATERIAL AND METHODS: A selective literature search was carried out and the current evidence for surgical treatment is summarized. RESULTS: There are currently no randomized studies on surgery for metastatic pancreatic cancer. Currently available data, however, show that after surgery long-term survival of up to 32-47 months after metastasectomy can be achieved, especially in patients with local recurrence or isolated pulmonary metastases with low morbidity and mortality. Individualized treatment concepts including surgical resection after initial systemic therapy seem promising even for liver metastases. The greatest survival benefits are consistently shown for all localizations in patients with a long as possible disease-free interval after the first operation. CONCLUSION: The treatment of isolated local recurrence or metachronous oligometastatic pancreatic cancer is an interdisciplinary challenge that should be performed in specialized pancreatic treatment centers only. Surgical resection embedded in a multimodal treatment concept can be meaningful in selected cases.

Neurotrophic tropomyosin receptor kinase (NTRK) and nerve growth factor (NGF) are not expressed in Caucasian patients with biliary tract cancers: pooled data from three independent cohorts.

BACKGROUND: Neuronal signaling has been implicated in the pathophysiology of multiple malignancies. In biliary tract cancers (BTCs), tumor cell expression of nerve growth factor (NGF) and its receptor neurotrophic tropomyosin receptor kinase (NTRK) has been reported in Asian patients and linked to inferior clinical outcome. Furthermore, NTRK fusions have emerged as a promising target in various cancers. Expression patterns of these markers in Caucasian patients remain unknown. METHODS: In this study, 106 patients with BTCs were included. Immunohistochemistry for pan-NTRK and NGF-beta was performed on > 90 samples of this cohort. Additionally, samples from two independent cohorts, incorporating 254 cases, were used to confirm the findings of the original cohort. RESULTS: While expression of pan-NTRK and NGF-beta was readily detectable in peri-tumoral nerves, these markers were not detectable in malignant epithelial cells in our cohort. CONCLUSIONS: In a large cohort of Caucasian patients with BTC, NTRK and NGF-beta were not detectable, underscoring potential differences between Caucasian and Asian patient populations.

The CR-POSSUM Risk Calculator Predicts Failure of Enhanced Recovery after Colorectal Surgery.

AIMS: To determine predictors of failed enhanced recovery after surgery (ERAS) in patients after elective colorectal surgery. METHODS: A cohort of 55 patients undergoing elective colorectal surgery was monitored prospectively. Perioperative care was based on a previously established protocol for ERAS. Pre-, intra-, and postoperative parameters were analyzed to elicit predictors of ERAS failure. ERAS failure was defined as prolonged hospital stay (> 7 days). The risk calculator CR-POSSUM was evaluated for its clinical utility. RESULTS: Body mass index (BMI) or the American Society of Anesthesiologists score (ASA) was not associated with ERAS failure on univariate analysis, but patients that failed ERAS were significantly older (64 y vs 54 y ; p = 0.023). Prolonged length of stay (> 7 days) was also associated with an open approach (p = 0.009), intraoperative nasogastric tube placement (p = 0.005), blood loss > 500 ml (p = 0.008), stoma formation (p = 0.006) and insertion of more than one intraabdominal drain during surgery (p = 0.005). Postoperative continuation of intravenous fluids (p = 0.027), reinsertion of urinary catheter (p = 0.045) and postoperative ileus (p = 0.020) were also strongly associated with delayed discharge on univariate analysis. After multivariate analysis the preoperative parameters CR-POSSUM score (p = 0.022), increasing BMI (p = 0.014) and preoperative albumin level (p = 0.031) were all independently associated with failure of ERAS. CONCLUSIONS: A variety of perioperative factors contribute to failure of ERAS in routine practice. CR-POSSUM can help to identify patients at risk for possible failure of ERAS. This may help to optimize avoidable factors, or accommodate those patients likely to require a longer post-operative stay.

The CR-POSSUM Risk Calculator Predicts Failure of Enhanced Recovery after Colorectal Surgery.

AIMS: To determine predictors of failed enhanced recovery after surgery (ERAS) in patients after elective colorectal surgery. METHODS: A cohort of 55 patients undergoing elective colorectal surgery was monitored prospectively. Perioperative care was based on a previously established protocol for ERAS. Pre-, intra-, and postoperative parameters were analyzed to elicit predictors of ERAS failure. ERAS failure was defined as prolonged hospital stay (> 7 days). The risk calculator CR-POSSUM was evaluated for its clinical utility. RESULTS: Body mass index (BMI) or the American Society of Anesthesiologists score (ASA) was not associated with ERAS failure on univariate analysis, but patients that failed ERAS were significantly older (64 y vs 54 y; p = 0.023). Prolonged length of stay (>7 days) was also associated with an open approach (p = 0.009), intraoperative nasogastric tube placement (p = 0.005), blood loss > 500 ml (p = 0.008), stoma formation (p = 0.006) and insertion of more than one intraabdominal drain during surgery (p = 0.005). Postoperative continuation of intravenous fluids (p = 0.027), reinsertion of urinary catheter (p = 0.045) and postoperative ileus (p = 0.020) were also strongly associated with delayed discharge on univariate analysis. After multivariate analysis the preoperative parameters CR-POSSUM score (p = 0.022), increasing BMI (p = 0.014) and preoperative albumin level (p = 0.031) were all independently associated with failure of ERAS. CONCLUSIONS: A variety of perioperative factors contribute to failure of ERAS in routine practice. CR-POSSUM can help to identify patients at risk for possible failure of ERAS. This may help to optimize avoidable factors, or accommodate those patients likely to require a longer post-operative stay.