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.

Effect of platelet inhibition with perioperative aspirin on survival in patients undergoing curative resection for pancreatic cancer: a propensity score matched analysis.

BACKGROUND: The importance of platelets in the pathogenesis of metastasis formation is increasingly recognized. Although evidence from epidemiologic studies suggests positive effects of aspirin on metastasis formation, there is little clinical data on the perioperative use of this drug in pancreatic cancer patients. METHODS: From all patients who received curative intent surgery for pancreatic cancer between 2014 and 2016 at our institution, we identified 18 patients that took aspirin at time of admission and continued to throughout the inpatient period. Using propensity score matching, we selected a control group of 64 patients without aspirin intake from our database and assessed the effect of aspirin medication on overall, disease-free, and hematogenous metastasis-free survival intervals as endpoints. RESULTS: Aspirin intake proved to be independently associated with improved mean overall survival (OS) (46.5 vs. 24.6 months, *p = 0.006), median disease-free survival (DFS) (26 vs. 10.5 months, *p = 0.001) and mean hematogenous metastasis-free survival (HMFS) (41.9 vs. 16.3 months, *p = 0.005). Three-year survival rates were 61.1% in patients with aspirin intake vs. 26.3% in patients without aspirin intake. Multivariate cox regression showed significant independent association of aspirin with all three survival endpoints with hazard ratios of 0.36 (95% CI 0.15-0.86) for OS (*p = 0.021), 0.32 (95% CI 0.16-0.63) for DFS (**p = 0.001), and 0.36 (95% CI 0.16-0.77) for HMFS (*p = 0.009). CONCLUSIONS: Patients in our retrospective, propensity-score matched study showed significantly better overall survival when taking aspirin while undergoing curative surgery for pancreatic cancer. This was mainly due to a prolonged metastasis-free interval following surgery.

[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.

[Learning from aviation - how to increase patient safety in surgery]. / Kann die Chirurgie wirklich von der Luftfahrt lernen?

During the last years attempts have been made to draw lessons from aviation to increase patient safety in medicine. In particular similar conditions are present in surgery as pilots and surgeons may have to support high physical and mental pressure. The use of a few safety instruments from aviation is feasible in an attempt to increase safety in surgery. First a "root caused" accident research may be established. This is achievable by morbidity and mortality conferences and critical incident reporting systems (CIRS). Second, standard operating procedures may assure a uniform mental model of team members. Furthermore, crew resource management illustrates a strategy and attitude concept, which is applicable in all situations. Safety instruments from aviation, therefore, seem to have a high potential to increase safety in surgery when properly employed.

Transmediastinal gunshot wounds: a prospective study.

OBJECTIVE: To evaluate admission systolic blood pressure (SBP) in the emergency center (EC) as a means by which patients with transmediastinal gunshot wounds (TM-GSWs) can be triaged to the operating room versus further diagnostic evaluation. METHODS: A prospective case series presenting concurrent data collected for 68 consecutive patients with TM-GSWs admitted to one urban trauma center over a 4.5-year period. For purposes of analysis, patients were assigned to the following groups based on SBP in the EC: group I, SBP > 100 mm Hg; group II, SBP from 60 to 100 mm Hg; group III, SBP < 60 mm Hg. RESULTS: The management and outcomes of 68 patients with a mean age of 29 years were evaluated. For patients in group I (n = 20), TM-GSW was diagnosed by findings on x-ray film for 15 patients (75%), at physical examination for 4 patients (20%), and at operation for 1 patient (5%). Indications for immediate operation were found in five patients (25%), whereas further diagnostic evaluation prompted operation for three additional patients. Only one patient developed persistent hypotension from neurogenic shock. There were two deaths from late complications. In patients in group II (n = 16), TM-GSW was diagnosed by findings on x-ray film for 9 patients (56%), at physical examination for 5 patients (31%), and at operation for 2 patients (13%). Six patients with persistent hypotension had indications for immediate operation, whereas further diagnostic evaluation in the remaining patients, who became hemodynamically normal during resuscitation, prompted operation in an additional two patients. There were two intraoperative deaths. For the patients in group III (n = 32), six patients with signs of life underwent immediate operation with one intraoperative death, seventeen patients required EC thoracotomy with 100% mortality, and nine patients were pronounced dead in the EC without an attempt at operation. CONCLUSION: The diagnosis of TM-GSW for patients in groups I and II is confirmed by finding at physical examination and on chest x-ray films in 90% of cases. In the absence of obvious bleeding, patients with TM-GSWs and SBP > 100 mm Hg may safely undergo further diagnostic evaluation. Sixty percent of such patients did not require an operation. All patients with TM-GSWs and SBP < 60 mm Hg (group III) require immediate operation. For patients with TM-GSWs, SBP from 60 to 100 mm Hg (group II), and without obvious bleeding, it is the response to resuscitation and the results of further diagnostic evaluation that determine the need for operation. Fifty percent of such patients did not require operation.

Iliac vessel injury: operative physiology related to outcome.

BACKGROUND: Fifty-three patients treated at a level I trauma center with iliac vessel injury were studied to determine if body temperature and acid-base status in the operating room predicts outcome. METHODS: Records were reviewed for demographics, mechanism of injury, body temperature, acid-base status, operative management, and outcome. Statistical methods included Student's t test, odds ratio determination, and chi-square analysis to determine statistical significance. RESULTS: Fifty-three patients (47 male, 6 female) sustained 92 iliac vascular injuries (36 arterial, 56 venous). Mortality was 34%, with 72% of deaths due to shock within 24 hours. Physiologic parameters differed significantly between survivors and nonsurvivors. Odds ratio identified six conditions; the number present predicted outcome. CONCLUSIONS: (1) There are significant differences between initial and final operating room temperature and acid-base status in survivors versus nonsurvivors with iliac vessel injury. Conditions for odds ratio can be calculated and correlated with outcome. (2) A patient with two or more conditions should be considered for an abbreviated laparotomy to allow for reversal of "physiologic failure."

The length of hospital stay after an unnecessary laparotomy for trauma: a prospective study.

OBJECTIVE: To record length of hospital stay (LOS) for patients for whom unnecessary laparotomies for trauma (no repair, no drain) were performed. The influence of complications and associated injuries on the LOS would be studied. DESIGN: Prospective case series. MATERIALS AND METHODS: Data were recorded concurrently for consecutive patients on whom unnecessary laparotomies for trauma were performed at a trauma center. MEASUREMENTS AND MAIN RESULTS: The main and secondary outcome measures were LOS and the influence of complications or associated injuries on the LOS, respectively. From 1988 until 1991, unnecessary laparotomies for trauma were performed on 254 patients. The overall mean LOS was 8.1 days (median, 6 days; range, 1-80 days), whereas the overall mean LOS for 81 patients who had no associated injuries and on whom completely negative laparotomies were performed was 4.7 days (median, 5 days; range, 2-8 days). Complications occurred in 41.3% of the patients and increased the mean LOS from 5 days (no complication) to 9 days (complication) (p = 0.0002). Associated injuries occurred in 43.7% of the patients and increased the mean LOS from 5.3 days (no associated injury) to 11.7 days (associated injury) (p = 0.0001). CONCLUSIONS: Unnecessary laparotomies for trauma resulted in a significant LOS. The presence of a complication or an associated injury significantly prolonged the LOS. Current efforts to reduce the incidence of these unnecessary procedures and minimize the occurrence of complications are worthwhile.

Unnecessary laparotomies for trauma: a prospective study of morbidity.

OBJECTIVE: Despite advances in diagnostic techniques, unnecessary laparotomies (no repairs/no drains) are still performed in trauma centers. The true risks of such procedures are unclear. Our hypothesis was that the overall incidences of complications after an unnecessary laparotomy for trauma that have been reported in the literature were significant underestimates because of flaws in study design. To test our hypothesis, a prospective study to record all perioperative complications in patients undergoing an unnecessary laparotomy for trauma was performed. DESIGN: Prospective case series. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were perioperative complications. An unnecessary laparotomy was performed in 254 patients who sustained trauma. The mechanism of injury was a penetrating wound in 98% of the patients. Complications occurred in 41.3% of the patients (n = 105) and included atelectasis (15.7%), postoperative hypertension that required medical treatment (11.0%), pleural effusion (9.8%), pneumothorax (5.1%), prolonged ileus (4.3%), pneumonia (3.9%), surgical wound infection (3.2%), small bowel obstruction (2.4%), urinary infection (1.9%), and others. Complication rates for patients who did (n = 111) and did not (n = 143) have an associated injury were 61.3% and 25.9%, respectively (p = 0.0001). Complications occurred in 19.7% of 81 patients who did not have an associated injury and who did not have intraperitoneal or retroperitoneal penetration. The mortality rate for the entire series was 0.8% and was unrelated to the unnecessary laparotomies. CONCLUSIONS: Unnecessary laparotomies for trauma result in a significant morbidity when complications are recorded prospectively. Current efforts to reduce the incidence of these unnecessary procedures without increasing that of missed injuries are obviously worthwhile.

Rapid right atrial cannulation for fluid infusion during resuscitative emergency department thoracotomy.

A simple rapid technique for cannulating the right atrium during a resuscitative Emergency Department thoracotomy (EDT) for exsanguinating trauma is described. Following the thoracotomy and pericardiotomy, an ordinary Foley urinary bladder balloon catheter is inserted into the right atrial appendage for rapid, large volume normothermic blood and fluid infusion. A method for simplifying this maneuver, as well as the potential complications of over-resuscitation with myocardial distention and fluid overload, myocardial cooling, air embolism, and tricuspid valve occlusion are discussed. We recognize that this technique is radical and applicable to only a limited subset of severely injured patients, for example, victims of non-cardiac penetrating trauma who arrive at the hospital moribund or who arrest in the emergency center.

Gunshot wounds to the right thoracoabdomen: a prospective study of nonoperative management.

Dissatisified with our unnecessary laparotomy rate in patients with gunshot wounds (GSWs) to the right thoracoabdomen (RTA), a prospective study was designed to test the hypothesis that hemodynamically stable patients without peritonitis could be managed without a surgical procedure. From 1990 through 1993, 13 consecutive patients with a GSW between the right nipple, costal margin, right posterior axillary line, and anterior midline were studied. No patient had or developed more than local wound tenderness. All patients had a right hemothorax treated with a chest tube. Computed tomographic (CT) scanning of the RTA was performed within 8 hours of admission in 12 of the 13 patients, and the following injuries were noted: pulmonary contusion (12), hepatic laceration (seven), spinal cord transection (two), and a renal laceration (one). Follow-up CT scans, 3 to 14 days after injury, in six of the seven patients with hepatic wounds showed partial or complete resolution of the injury in all. In one patient, an associated renal injury was unchanged on the follow-up CT scan. Mean length of hospitalization for the 11 patients who did not have an injury to the spinal cord was 5.1 days (3-8 days). Complications included atelectasis (four), a small persistent pneumothorax (two), and pneumonia (one).(ABSTRACT TRUNCATED AT 250 WORDS)

Hot tar burns: twenty-seven hospitalized cases.

Between July 1, 1984, and December 31, 1991, 27 consecutive patients required admission to the Grady Memorial Hospital Burn Unit for care of hot tar burns. This group represented 1.4% of all admissions to this burn unit. Injuries occurred at the workplace and occurred mostly during the summer. They most commonly involved the patient slipping while carrying a bucket of hot tar. Ninety-six percent were male. The mean age was 33.7 years. Mean burn size was 13.1% total body surface area. Burn topography centered on the upper extremities and hands. Forty-one percent required a surgical procedure for their burn. Mean hospitalization time for survivors was 16.6 days. The survival rate was 92.6%. Both of the patients who died had large burns and/or preexisting medical problems. Hot tar burns occur under predictable circumstances, appear to be preventable, and have accounted for only a small fraction of all admissions to this burn unit.