Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions.

BACKGROUND: Solid tumors such as pancreatic ductal adenocarcinoma (PDAC) comprise not just tumor cells but also a microenvironment with which the tumor cells constantly interact. Detailed characterization of the cellular composition of the tumor microenvironment is critical to the understanding of the disease and treatment of the patient. Single-cell transcriptomics has been used to study the cellular composition of different solid tumor types including PDAC. However, almost all of those studies used primary tumor tissues. METHODS: In this study, we employed a single-cell RNA sequencing technology to profile the transcriptomes of individual cells from dissociated primary tumors or metastatic biopsies obtained from patients with PDAC. Unsupervised clustering analysis as well as a new supervised classification algorithm, SuperCT, was used to identify the different cell types within the tumor tissues. The expression signatures of the different cell types were then compared between primary tumors and metastatic biopsies. The expressions of the cell type-specific signature genes were also correlated with patient survival using public datasets. RESULTS: Our single-cell RNA sequencing analysis revealed distinct cell types in primary and metastatic PDAC tissues including tumor cells, endothelial cells, cancer-associated fibroblasts (CAFs), and immune cells. The cancer cells showed high inter-patient heterogeneity, whereas the stromal cells were more homogenous across patients. Immune infiltration varies significantly from patient to patient with majority of the immune cells being macrophages and exhausted lymphocytes. We found that the tumor cellular composition was an important factor in defining the PDAC subtypes. Furthermore, the expression levels of cell type-specific markers for EMT+ cancer cells, activated CAFs, and endothelial cells significantly associated with patient survival. CONCLUSIONS: Taken together, our work identifies significant heterogeneity in cellular compositions of PDAC tumors and between primary tumors and metastatic lesions. Furthermore, the cellular composition was an important factor in defining PDAC subtypes and significantly correlated with patient outcome. These findings provide valuable insights on the PDAC microenvironment and could potentially inform the management of PDAC patients.

Neo-adjuvant therapy for pancreatic cancer: hope for the future.

INTRODUCTION: In 2018, pancreatic ductal adenocarcinoma (PDAC) was the 3rd highest cause cancer related death in the United States. Worldwide estimates in 2018 indicate 458,918 cases diagnosed with 432,242 deaths. Standard therapy for decades for localized PDAC has been to pursue surgical resection for localized disease. For the individuals who are diagnosed with localized PDAC and undergo surgical resection, historical survival has been reported to be around 24 months. While recent advancements in the use of multiagent systemic therapy has allowed for greater survival benefit, adjuvant therapy does have limitations. Recently, neo-adjuvant therapy for PDAC has become more accepted in practice. Areas covered: In this review, we will discuss the current guidelines for treatment of localized PDAC, the pros and cons of neo-adjuvant versus adjuvant therapy for PDAC, the utilization of available biomarkers for the management of PDAC, and future possibilities for clinical trials. Expert commentary: Neo-adjuvant therapy for localized PDAC has tremendous promise in leading to greater survival by treating for micro-metastatic disease along with selecting for patients for better outcomes. Further work based upon molecular insights will lead to better biomarkers for treatment assessment along with improvements in treatment.

Emergency department diagnosis of an ovarian inguinal hernia in an 11-year-old female using pointof-care ultrasound / 世界急诊医学杂志（英文）

@#Inguinal hernias affect 5% of children and are usually defined as a protrusion of intestine or omentum through abdominal wall or inguinal canal defects.[1] Inguinal hernias may contain structures other than bowel and unique cases have been documented since the early 1900's.[2–10] Ultrasound has been demonstrated to differentiate superficial swellings and has been used by radiologists to evaluate inguinal masses for decades.[1–5,11–13] Although the use of radiology-performed ultrasound for the diagnosis of congeni tal inguinal hernias containing ovaries, uterus, and fallopian tubes has been documented; the use of point-of-care ultrasound for the evaluation of the acute inguinal mass prior to reduction has not been demonstrated. Accurate identification by the emergency physician of the herniated structures may lead to earlier diagnosis, faster consultation, improve patient management, and superior patient outcomes.

Spontaneous Rupture of a Hepatic Adenoma: Diagnostic Nuances and the Necessity of Followup.

We present the case of a young female on oral contraceptives (OCs) who was diagnosed with focal nodular hyperplasia (FNH) and remained on oral contraceptives. Months later, the patient presented with acute abdominal pain and intratumoral hemorrhage in the liver. The patient was taken to the operating room (OR) and was diagnosed with a ruptured hepatic adenoma (HA). We review the key diagnostic features of FNH and HA, the different management guidelines including use of OCs, and potential surgical indications. HA compared to FNH has a significantly higher rate of sequelae despite being a benign lesion, thus providers must accurately distinguish between the two diagnoses to prevent potential morbidity and mortality.

Ultrasound-Guided Forearm Nerve Blocks: A Novel Application for Pain Control in Adult Patients with Digit Injuries.

Phalanx fractures and interphalangeal joint dislocations commonly present to the emergency department. Although these orthopedic injuries are not complex, the four-point digital block used for anesthesia during the reduction can be painful. Additionally, cases requiring prolonged manipulation or consultation for adequate reduction may require repeat blockade. This case series reports four patients presenting after mechanical injuries resulting in phalanx fracture or interphalangeal joint dislocations. These patients received an ultrasound-guided peripheral nerve block of the forearm with successful subsequent reduction. To our knowledge, use of ultrasound-guided peripheral nerve blocks of the forearm for anesthesia in reduction of upper extremity digit injuries in adult patients in the emergency department setting has not been described before.

Palliative care training in surgical oncology and hepatobiliary fellowships: a national survey of the fellows.

BACKGROUND: Surgical oncologists (SO) and hepatobiliary (HPB) surgeons frequently care for patients with advanced diseases near the end of life, yet little is known about their training, comfort, and readiness in the provision of palliative care. This study sought to assess the quality, adequacy, and extent of palliative care training and the readiness of SO and HPB fellows in delivering palliative care. METHODS: A self-administered survey was distributed to all fellows enrolled in Society of Surgical Oncology (SSO) and HPB fellowships during the 2013-2014 academic year. The survey assessed attitudes, training, experience, and readiness of fellows in caring for patients at the end of life. Descriptive analysis was performed, and Chi square, Student's t test, and the Mann-Whitney U test were used to compare mean or median values as appropriate. RESULTS: The response rate was 47.2 %, and 50.9 % of the fellows reported exposure to a palliative care specialty service during their fellowship. Of the study participants, 75 % observed their faculty discussing the side effects of surgery compared with 54 % who observed faculty communication with patients regarding end-of-life goals (p < 0.01). On the other hand, 40 % of the fellows were never observed by faculty discussing symptoms management, goals of care, or hospice referral with patients, and 56.7 % never received feedback on their palliative skills. CONCLUSION: The fellows rated the quality of their palliative care education as poor compared with other aspects of their fellowship training, implying the lack and need of palliative care teaching. Surgical oncology and HPB fellows and ultimately patients may benefit from increased clinical and didactic palliative care training.

Is local resection adequate for T1 stage ampullary cancer?

BACKGROUND: Concerns for morbidity after a pancreaticoduodenectomy (PD) has led to practitioners adopting endoscopic resection or ampullectomy in the treatment of T1 ampullary cancer (AC). It was hypothesized that survival for patients undergoing local resection of AC was inferior to those undergoing a PD. METHODS: All the data of patients with AC reported in the Surveillance, Epidemiology and End Results (SEER) database between 2004 and 2010 were collected. Five-year survival rates according to nodal disease and histological type were compared. RESULTS: There were 1916 cases of AC; 421 (22%) had T1 disease. Among those with T1 disease, 217 (51%) received endoscopic surveillance, 21 (5%) underwent local resection/ampullectomy, 20 (5%) underwent ampullectomy with regional lymphadenectomy and 163 (39%) underwent PD. For patients with complete nodal staging (PD, n = 163), 35 (22%) had metastatic disease in the nodes. Grade was significantly associated with node positivity (P = 0.007). In multivariate models, survival was improved with either an ampullectomy with regional lymphadenectomy [hazard ratio (HR) 0.19; 95% confidence interval (CI) 0.05-0.61, P < 0.005] or a PD (HR 0.23; 95% CI 0.15-0.36, P < 0.001). CONCLUSION: Patients with T1 AC have a high risk for nodal metastases especially if they are higher-grade lesions. Nodal clearance with a lymphadenectomy or a PD is essential for long-term survival in these patients.

Defining the role of adjuvant external beam radiotherapy on resected adenocarcinoma of the ampulla of vater.

The role of adjuvant radiotherapy in the treatment of ampullary carcinoma (AC) remains unclear. We hypothesized that adjuvant radiotherapy (RT) does not improve survival following resection for AC. The SEER database was queried for patients with non-metastatic AC who underwent surgery (S) from 2004 to 2010. Propensity score (PS) modeling was applied to create balanced cohorts of patients that would be equally likely to receive RT. Cox proportional hazard models were used to compare survival. Of 1,287 patients, 329 (25.6%) received adjuvant RT. Unadjusted median overall survival (OS) for patients receiving adjuvant RT compared to S alone was 27 vs. 36 months (p = 0.14). Patients receiving RT were younger (63 vs. 69 years, p < 0.001), had more advanced tumors (69 vs. 53% T3/T4, p < 0.001), and had more frequent lymph node metastasis (73 vs. 40%, p < 0.001). Adjuvant RT failed to improve both overall survival (27 vs. 29 months, p = 0.58) and disease-specific survival (36 vs. 40 months, p = 0.92) in propensity-matched cohorts, although certain imbalances remained between treatment groups. Adjuvant RT does not confer a survival benefit for patients with ampullary tumors. The lack of disease-specific survival benefit suggests that it may also not be beneficial to prevent local recurrences.

Surgical management of hepatic hemangiomas: a multi-institutional experience.

BACKGROUND: The management of hepatic hemangiomas remains ill defined. This study sought to investigate the indications, surgical management and outcomes of patients who underwent a resection for hepatic hemangiomas. METHODS: A retrospective review from six major liver centres in the United States identifying patients who underwent surgery for hepatic hemangiomas was performed. Clinico-pathological, treatment and peri-operative data were evaluated. RESULTS: Of the 241patients who underwent a resection, the median age was 46 years [interquartile range (IQR): 39-53] and 85.5% were female. The median hemangioma size was 8.5 cm (IQR: 6-12.1). Surgery was performed for abdominal symptoms (85%), increasing hemangioma size (11.3%) and patient anxiety (3.7%). Life-threatening complications necessitating a hemangioma resection occurred in three patients (1.2%). Clavien Grade 3 or higher complications occurred in 14 patients (5.7%). The 30- and 90-day mortality was 0.8% (n = 2). Of patients with abdominal symptoms, 63.2% reported improvement of symptoms post-operatively. CONCLUSION: A hemangioma resection can be safely performed at high-volume institutions. The primary indication for surgery remains for intractable symptoms. The development of severe complications associated with non-operative management remains a rare event, ultimately challenging the necessity of additional surgical indications for a hemangioma resection.

Palliation: treating patients with inoperable biliary tract and primary liver tumors.

This article summarizes the current literature in treatment of unresectable biliary tract and primary liver tumors. Locoregional therapies including radiofrequency ablation, percutaneous ethanol injection, cryoablation, microwave ablation, transarterial chemoembolization, hepatic artery infusion, radioembolization ((90)Y), and bland embolization are discussed and clinical trials compared. Palliative strategies including surgical, percutaneous, and endoscopic techniques to decompress the biliary system and improve symptoms are also summarized. Systemic chemotherapy and sorafenib used in conjunction with locoregional therapies or as sole therapeutic options are discussed.

Recognition of complications after pancreaticoduodenectomy for cancer determines inpatient mortality.

CONTEXT: While perioperative mortality after pancreaticoduodenectomy is decreasing, key factors remain to be elucidated. OBJECTIVE: The purpose of this study was to investigate inpatient mortality after pancreaticoduodenectomy in the Nationwide Inpatient Sample (NIS), a representative inpatient database in the USA. METHODS: Patient discharge data (diagnostic and procedure codes) and hospital characteristics were investigated for years 2009 and 2010. The inclusion criteria were a procedure code for pancreaticoduodenectomy, elective procedure, and a pancreatic or peripancreatic cancer diagnosis. Chi-square test determined statistical significance. A logistic regression model for mortality was created from significant variables. RESULTS: Two-thousand and 958 patients were identified with an average age of 65±12 years; 53% were male. The mean length of stay was 15±12 days with a mortality of 4% and a complication rate of 57%. Eighty-six percent of pancreaticoduodenectomy occurred in teaching hospitals. Pancreaticoduodenectomy performed in teaching hospitals in the first half of the academic year were associated with higher mortality than in the latter half (5.5% vs. 3.4%, P=0.005). On logistic regression analysis, non-surgical complications are the largest predictor of death (P<0.001) while operations in the latter half of the academic year are associated with decreased mortality (P<0.01). CONCLUSIONS: The timing of pancreaticoduodenectomy for cancer remained more predictive of mortality than age or length of stay; only complications were more predictive of death than time of year. This suggests that there remains a clinically and statistically significant learning curve for trainees in identifying complications; further study is needed to prove that identification of complications leads to a decrease in mortality rate by taking corrective actions.

Laparoscopic-assisted minithoracotomy for repair of diaphragmatic penetrating trauma.

BACKGROUND: Stable patients with thoracoabdominal penetrating or blunt trauma resulting in diaphragmatic injuries represent a challenging dilemma. Laparoscopy has emerged as the most reliable and efficient diagnostic and treatment modality for such patients. OBJECTIVE: The aim of this study was to analyze our novel surgical technique for the management of penetrating diaphragmatic injuries in stable patients. MATERIALS AND METHODS: In this retrospective study, we analyzed data that had been prospectively collected on a new surgical repair technique established at our institution. We reviewed the records of 7 hemodynamically stable trauma patients with thoracoabdominal penetrating trauma resulting in diaphragmatic injuries. RESULTS: The 7 patients (5 with stab wounds, 2 with gunshot wounds) underwent laparoscopic exploration and laparoscopic-assisted minithoracotomy for the repair of diaphragmatic injuries. The mean length of stay was 4.4 days (range, 1 to 8 d). There were no tension pneumothoraces, missed injuries, or other procedure-related complications. CONCLUSIONS: If complete laparoscopic repair is not possible, laparoscopic-assisted repair of diaphragmatic injuries using minithoracotomy is a viable option. In our 7 patients, the results were good, with no morbidity.

Effect of a pharmacist on timing of postintubation sedative and analgesic use in trauma resuscitations.

PURPOSE: Pharmacists' impact in reducing the time interval from intubation to sedative and analgesic use during trauma patient resuscitations is investigated. METHODS: A retrospective cohort study was conducted at a level 1 trauma center to compare medication-use outcomes in consecutive cases in which trauma patients underwent rocuronium-assisted rapid-sequence intubation (RSI) and subsequent sedation and analgesia with or without a pharmacist's participation on the resuscitation team. The primary and secondary outcomes were, respectively, the time to sedative provision and the time to analgesic provision after intubation. RESULTS: Relative to resuscitation cases not involving a pharmacist, the presence of the pharmacist during RSI was associated with decreased mean times to provision of postintubation sedation (9 minutes versus 28 minutes, p = 0.007) and analgesia (21 minutes versus 44 minutes, p = 0.057). The cumulative proportions of patients receiving appropriate sedation 5, 10, and 15 minutes after intubation were 11%, 26%, and 41% in the pharmacist-absent group and 33%, 53%, and 63% in the pharmacist-present group (p = 0.009, 0.008, and 0.045, respectively); for postintubation analgesic use, the corresponding figures were 9%, 14%, and 23% in the pharmacist-absent group and 17%, 30%, and 43% in the pharmacist-present group (p = 0.236, 0.066, and 0.039, respectively). CONCLUSION: The presence of a pharmacist during RSI procedures was associated with decreased times to postintubation sedative and analgesic use, indicating that pharmacist participation in trauma-resuscitation responses can facilitate appropriate drug therapy.

Morphine versus fentanyl for pain due to traumatic injury in the emergency department.

The analgesic response and safety of intravenous morphine versus fentanyl for adult trauma patients who presented to the emergency department (ED) were evaluated. Median pain reduction on the numeric rating scale (0-10; 0 = no pain and 10 = worst possible pain) after opioid administration was similar between the groups (2 vs 2; P = .67). The lowest postdose pain score was recorded sooner in the fentanyl group than in the morphine group (22 vs 47 minutes, respectively; P < .001). There were no significant differences in drug-induced adverse effects between groups. Fentanyl produced a similar but more rapid analgesic response compared with morphine in trauma patients.

Effect of paralytic type on time to post-intubation sedative use in the emergency department.

OBJECTIVE: To determine the difference between rocuronium and succinylcholine with regard to post-intubation sedative initiation in the emergency department. METHDS: This was a retrospective cohort study conducted in a tertiary care emergency department (ED) in the USA. Consecutive adult patients intubated in the ED using succinylcholine or rocuronium for paralysis were included. Data collected included patient demographics, vital signs, medications used post-intubation and times of drug administration. Patients were divided into two groups based on the type of paralytic used for rapid sequence intubation: (1) rocuronium or (2) succinylcholine. All patients received etomidate for induction of sedation. Time between intubation and post-intubation sedative use was compared between the two groups using an unpaired Student's t test. MAIN RESULTS: A total of 200 patients were included in the final analyses (100 patients in each group). There were no significant differences between the groups with regard to patient demographics, vital signs or other baseline characteristics. After intubation, 77.5% (n=155) of patients were initiated on a sedative infusion of propofol (n=148) or midazolam (n=7). The remaining patients received sedation as bolus doses only. Mean time between intubation and post-intubation sedative use was significantly greater in the rocuronium group compared with the succinylcholine group (27 min vs 15 min, respectively; p<0.001). CONCLUSIONS: Patients intubated with rocuronium had greater delays in post-intubation sedative initiation compared with succinylcholine.

Effect of epidural analgesia on postoperative complications following pancreaticoduodenectomy.

BACKGROUND: The purpose of this study was to evaluate the effect of epidural analgesia use on postoperative complications in patients undergoing pancreaticoduodenectomy. METHODS: This retrospective cohort study used the 2009 Nationwide Inpatient Sample from the Agency for Healthcare Research and Quality. Patients who underwent pancreaticoduodenectomy were grouped on the basis of whether they received epidural analgesia. The effect of epidural use on the composite end point of major complications including death was investigated using a generalized linear model. RESULTS: Overall, 8,610 cases of pancreaticoduodenectomy occurred within the United States in 2009, and 11.0% of these patients received epidural analgesia. After controlling for various potential confounders, results of the multivariate regression indicated that epidural analgesia use was associated with lower odds of composite complications including death (odds ratio, .61; 95% confidence interval, .37-.99; P = .044). CONCLUSIONS: In patients who underwent pancreaticoduodenectomy, epidural analgesia was associated with significantly lower postoperative composite complications.

Factor IX complex for the correction of traumatic coagulopathy.

BACKGROUND: Damage control resuscitation advocates correction of coagulopathy; however, options are limited and expensive. The use of prothrombin complex concentrate (PCC), also known as factor IX complex, can quickly accelerate reversal of coagulopathy at relatively low cost. The purpose of this study is to describe our experience in the use of factor IX complex in coagulopathic trauma patients. METHODS: All patients receiving PCC at our Level I trauma center over a two-year period (2008-2010) were reviewed. PCC was used at the discretion of the trauma attending for treatment of coagulopathy, reversal of coumadin, and when recombinant factor VIIa was indicated. RESULTS: Forty-five trauma patients received 51 doses of PCC. Sixty-two per cent were male and mean Injury Severity Score was 23 (± 14.87). Standard dose was 25 units per kg and mean cost per patient was $1,022 ($504-3,484). Fifty-eight per cent of patients were on warfarin before admission. Mean international normalized ratio (INR) was decreased after PCC administration (p = 0.001). Packed red blood cell transfusion was also reduced after factor IX complex (p = 0.018). Mean INR was reduced in both the nonwarfarin (p = 0.001) and warfarin (p = 0.001) groups. Packed red blood cell transfusion was less in the nonwarfarin group (p = 0.002) however was not significant in the warfarin group. Subsequent thromboembolic events were observed in 3 of the 45 patients (7%). Mortality was 16 of 45 (36%). CONCLUSION: PCC rapidly and effectively treats coagulopathy after traumatic injury. PCC therapy leads to a significant correction in INR in all trauma patients, regardless of coumadin use, and concomitant reduction in blood product transfusion. PCC should be considered as an effective tool to treat acute coagulopathy of trauma. Further prospective studies examining the safety, efficacy, cost, and outcomes comparing PCC and recombinant factor VIIa are needed.

Treatment of severe hemolytic anemia caused by Clostridium perfringens sepsis in a liver transplant recipient.

BACKGROUND: Clostridium perfringens bacteremia accompanied by extensive intravascular hemolysis is an almost inescapably fatal infection. METHODS: Case report and literature review. RESULTS: A 52-year-old man with a recent history of liver transplantation developed sepsis and severe hemolytic anemia. The patient had multiple organ dysfunction syndrome and required aggressive transfusion, antibiotics, and continuous hemodialysis. Blood cultures grew C. perfringens. With appropriate resuscitation and antibiotic treatment, the patient had a complete, although complicated recovery. CONCLUSION: This is the first reported case of a liver transplant patient developing fulminant C. perfringens sepsis with hemolysis. This infection usually kills patients within hours of presentation. Early recognition and aggressive treatment is necessary to avoid this outcome.