Transcriptome-guided resolution of tumor microenvironment interactions in pheochromocytoma and paraganglioma subtypes.

BACKGROUND: Pheochromocytomas and paragangliomas (PCPG) are rare catecholamine-secreting endocrine tumors deriving from chromaffin cells of the embryonic neural crest. Although distinct molecular PCPG subtypes have been elucidated, certain characteristics of these tumors have yet to be fully examined, namely the tumor microenvironment (TME). To further understand tumor-stromal interactions in PCPG subtypes, the present study deconvoluted bulk tumor gene expression to examine ligand-receptor interactions. METHODS: RNA-sequencing data primary solid PCPG tumors were derived from The Cancer Genome Atlas (TCGA). Tumor purity was estimated using two robust algorithms. The tumor purity estimates and bulk tumor expression values allowed for non-negative linear regression to predict the average expression of each gene in the stromal and tumor compartments for each PCPG molecular subtype. The predicted expression values were then used in conjunction with a previously curated ligand-receptor database and scoring system to evaluate top ligand-receptor interactions. RESULTS: Across all PCPG subtypes compared to normal samples, tumor-to-tumor signaling between bone morphogenic proteins 7 (BMP7) and 15 (BMP15) and cognate receptors ACVR2B and BMPR1B was increased. In addition, tumor-to-stroma signaling was enriched for interactions between predicted tumor-originating delta-like ligand 3 (DLL3) and predicted stromal NOTCH receptors. Stroma-to-tumor signaling was enriched for interactions between ephrins A1 and A4 with ephrin receptors EphA5, EphA7, and EphA8. Pseudohypoxia subtype tumors displayed increased predicted stromal expression of genes related to immune-exhausted T-cell response, including those for inhibitory receptors HAVCR2 and CTLA4. CONCLUSION: The current exploratory study predicted stromal and tumor through compartmental deconvolution and yielded previously unrecognized interactions and putative biomarkers in PCPG.

Disparities in Treatment for Gallbladder Carcinoma: Does Treatment Site Matter?

BACKGROUND AND PURPOSE: Current treatment guidelines for gallbladder cancer range from simple cholecystectomy to regional hepatic resection. Treatment patterns for radical resection and adjuvant chemotherapy vary. We aim to determine if there is any disparity in treatment or difference in survival between academic versus community treatment centers. METHODS: The National Cancer Database (NCDB) was queried from 2004 to 2014 for gallbladder carcinoma. Cases were stratified into treatment sites as "Community Cancer Center" (CCC) or "Academic Cancer Center" (ACC). Propensity score matching was performed for patient demographics, TNM stage, resection type, and administration of adjuvant chemotherapy. The primary outcome included 30-day mortality, 90-day mortality, and overall survival. RESULTS: There are similar frequencies of radical versus simple resection and administration of adjuvant chemotherapy between ACC and CCC. When propensity-matched for resection type, cases treated at ACC have lower 30-day mortality (4.1% vs. 6.9%) and 90-day mortality (13.2% vs. 18.5%) and increased 5-year overall survival (26.2% vs. 22.4%) (p < 0.01). After propensity matching for adjuvant chemotherapy, cases at ACC have lower 30-day mortality (4.12% vs. 7.71%) and 90-day mortality (13.22% vs. 19.19%) and increased overall survival (13.6% vs. 11.0%) (p < 0.01). DISCUSSION AND CONCLUSIONS: While treatment patterns for gallbladder cancer at ACC and CCC were similar, there was a decrease in 30-day and 90-day mortality and improved overall survival associated with patients treated at ACC. Treatment site may have an impact in the surgical outcomes of gallbladder cancer patients. This disparity warrants further research.

The utility of the MELD score in predicting mortality following liver resection for metastasis.

BACKGROUND: The MELD score has been demonstrated to be predictive of hepatectomy outcomes in mixed patient samples of primary and secondary liver cancers. Because MELD is a measure of hepatic dysfunction, prior conclusions may rely on the high prevalence of cirrhosis observed with primary lesions. This study aims to evaluate MELD score as a predictor of mortality and develop a risk prediction model for patients specifically undergoing hepatic metastasectomy. METHODS: ACS-NSQIP 2005-2013 was analyzed to select patients who had undergone liver resections for metastases. A receiver operating characteristic (ROC) analysis determined the MELD score most associated with 30-day mortality. A literature review identified variables that impact hepatectomy outcomes. Significant factors were included in a multivariable analysis (MVA). A risk calculator was derived from the final multivariable model. RESULTS: Among the 14,919 patients assessed, the mortality rate was 2.7%, and the median MELD was 7.3 (range = 34.4). A MELD of 7.24 was identified by ROC (sensitivity = 81%, specificity = 51%, c-statistic = 0.71). Of all patients above this threshold, 4.4% died at 30 days vs. 1.1% in the group ≤7.24. This faction represented 50.1% of the population but accounted for 80.3% of all deaths (p < 0.001). The MVA revealed mortality to be increased 2.6-times (OR = 2.55, 95%CI 1.69-3.84, p < 0.001). A risk calculator was successfully developed and validated. CONCLUSIONS: MELD>7.24 is an important predictor of death following hepatectomy for metastasis and may prompt a detailed assessment with the provided risk calculator. Attention to MELD in the preoperative setting will improve treatment planning and patient education prior to oncologic liver resection.

A comparison of laparoscopic and open appendectomy.

BACKGROUND AND OBJECTIVES: To compare laparoscopic appendectomy with traditional open appendectomy. METHODS: Seventy-one patients requiring operative intervention for suspected acute appendicitis were prospectively compared. Thirty-seven patients underwent laparoscopic appendectomy, and 34 had open appendectomy through a right lower quadrant incision. Length of surgery, postoperative morbidity and length of postoperative stay (LOS) were recorded. Both groups were similar with regard to age, gender, height, weight, fever, leukocytosis, and incidence of normal vs. gangrenous or perforated appendix. RESULTS: Mean LOS was significantly shorter for patients with acute suppurative appendicitis who underwent laparoscopic appendectomy (2.5 days vs. 4.0 days, p < 0.01). Mean LOS was no different when patients classified as having gangrenous or perforated appendicitis were included in the analysis (3.7 days vs. 4.1 days, P = 0.11). The laparoscopy group had significantly longer surgery times (72 min vs. 58 min, p < 0.001). There was no significant difference in the incidence of postoperative morbidity. CONCLUSIONS: Laparoscopic appendectomy reduces LOS as compared with the traditional open technique in patients with acute suppurative appendicitis. The longer operative time for the laparoscopic approach in our study is likely related to the learning curve associated with the procedure and did not increase morbidity.

Implementing a smoking cessation program for your patients.

PAs can improve the health of their patients by promoting healthy life-styles. By integrating a smoking cessation program into a surgical practice, the authors were able to achieve a cessation rate of 64% at 6 months and 1 year. The method, which includes screening, education, motivation, and follow-up, is applicable to any type of practice.

Bioavailability of medication after laparoscopic cholecystectomy.

Bioavailability of medication after laparoscopic cholecystectomy has not been studied previously. There is concern about the ability of patients to tolerate oral medication postoperatively and the optimal timing of hospital discharge. In this study, each subject received 20 mg/kg acetaminophen (po) preoperatively, with a repeat dose at 6 (group 1), 12 (group 2), or 24 h (group 3) postoperatively. Serum levels were obtained 40 and 90 min after each ingestion. Bioavailability of medication was significantly decreased (p < 0.01) 6 h (group 1) and 12 h (group 2) postoperatively. Bioavailability returned to baseline by 24 h after laparoscopic cholecystectomy (group 3). This study indicates that oral medication should be used judiciously during the first 12 h after laparoscopic surgery.

Trocar site tumor recurrence after laparoscopic-assisted colectomy.

As a variety of procedures become technically feasible with laparoscopic techniques, it becomes increasingly important to appropriately select the patients who will benefit from the laparoscopic approach. We report the case of a patient with Dukes C2 colon cancer treated by laparoscopic-assisted sigmoid colectomy who subsequently developed an abdominal wall recurrence at a trocar site scar. The case raises some concerns about the use of the laparoscopic technique in the surgical management of colon cancer.

Bioavailability of medication delivered via nasogastric tube is decreased in the immediate postoperative period.

BACKGROUND: A study was performed to determine bioavailability of medication delivered via nasogastric tube in patients after abdominal surgery. METHODS: Acetaminophen (20 mg/kg) was administered to each patient per os at least 48 hours prior to abdominal surgery and via nasogastric tube 3 hours postoperatively. The nasogastric tube was clamped for 30 minutes after drug administration, prior to resuming suction. Serum levels of acetaminophen were measured 0, 40, and 90 minutes after each dose. RESULTS: Acetaminophen levels were significantly lower (P < 0.001) when the drug was administered via nasogastric tube postoperatively. CONCLUSIONS: Decreased bioavailability of medications delivered via nasogastric tube may have important clinical implications and should be taken into consideration during the postoperative period.

Documentation of abdominal exploration during laparoscopic cholecystectomy.

UNLABELLED: To assess the documentation of intraperitoneal exploration and events during laparoscopic cholecystectomy, we reviewed 200 dictated operative reports from eight different institutions. The 200 laparoscopic cholecystectomies were performed by 40 different surgeons on 158 female patients and 42 male patients. A description of the gallbladder was included in 134 (67%) reports and not mentioned in 66 (33%) reports. Fifty-four (27%) reports did not mention any intraperitoneal findings away from the gallbladder. Another 36 (18%) of the reports contained only a general comment indicating that no abnormalities were seen in the abdomen (excluding the gallbladder). The other 110 (55%) reports mentioned at least one specific site or finding in the abdomen other than the gallbladder. The most commonly mentioned sites were the liver, bowel, and stomach. Only 42 (21%) operative notes described what happened to the gallbladder contents: 30 described spillage of bile and/or gallstones and 12 stated that no spillage occurred. CONCLUSIONS: Laparoscopic cholecystectomy operative notes have often lacked a description of gallbladder appearance, documentation of abdominal exploration, and/or documentation of complete removal of the gallbladder and its contents.

Erythropoetin accelerates hematocrit recovery in post-surgical anemia.

UNLABELLED: We evaluated the role of recombinant human erythropoietin (RHE) for treatment of severe postsurgical anemia (Hct < 25%) in 40 Jehovah's Witness (JW) patients refusing transfusion. Twenty patients (group E) received RHE either at a loading dose of 300 U/kg iv 3 times/week for 1 week followed by 150 U/kg 3 times/week in accordance with an IRB approved protocol (N = 13), or at a dose of 100 U/kg 3 times/week for humanitarian reasons (N = 7). This group was compared to 20 similar JW patients who did not receive RHE (group C). All patients received iron restoration and nutritional support. Non-parametric analysis (Mann-Whitney) was used because of sample size. Entry hematocrit was similar for both groups: H(E)(0) = 15.8% +/- 1.1 SEM (8.5-23.4) vs HC (0) = 12.8% +/- 0.9 SEM (7.3-20.6), P = 0.09. After one week, hematocrit was significantly higher in group E (H(E)(1)) = 19.3 +/- 1.1 vs HC(1) = 12.5% +/- 0.9, P < 0.0005) as was the increase in hematocrit for group E (3.6% +/- 0.9 for E vs -0.4% +/- 0.8 for C, P < 0.005). Hematocrit change in Week 2 showed an increase for both groups (2.9 +/- 0.6 for E vs 4.9% +/- 1.2 for C, P = 0.12). CONCLUSIONS: Hct recovery shows a 1-week lag in severely anemic postsurgical patients treated without RHE. Exogenous RHE appears to accelerate hematocrit recovery in the first week. Use of RHE in the immediate postoperative period may help avoid or reduce homologous blood transfusion.

Preoperatively assessing and planning blood use for elective vascular surgery.

Few guidelines exist for determining transfusion needs and strategies, namely, the appropriate use of autologous versus homologous blood for elective vascular surgery. To address this deficiency, we have developed and used an algorithm based on an analysis of the procedure, maximum surgical blood ordering schedule, patient status, and patient suitability for autologous alternatives. Data were derived from consecutive major vascular procedures done at our hospital from 1991 to 1992. The algorithm helps the surgeon assess transfusion need and patient suitability for autologous predonation and aids in selecting appropriate transfusion alternatives. Using this algorithm during the past year with 120 patients, we simplified transfusion decisions, reduced homologous blood use (to only 4.2%), and reduced wasting of autologous blood to less than 5% of the units predonated. We believe that the use of this algorithm will aid the vascular surgeon in choosing appropriate alternatives to allogeneic blood transfusion, thereby reducing the patient's exposure to risk. The algorithm should also reduce wasting of autologous blood.

A survey of preferred approach to inguinal hernia repair: laparoscopic or inguinal incision?

The recent interest in laparoscopic surgery has raised some concerns that large numbers of surgeons were recommending this "minimally invasive" approach in procedures such as inguinal herniorrhaphy before the availability of adequate data regarding safety and benefits. To determine current experience and preference levels for laparoscopic inguinal herniorrhaphy (LH), we conducted a mail survey of New Jersey surgeons. Of 531 respondents, 430 (81%) preferred a traditional inguinal incision approach over a laparoscopic approach (8%). Of 344 general surgeon respondents, 227 (66%) had experience with laparoscopic cholecystectomy, but only 56 (16%) had experience with LH. This latter group had performed only an average of 9.2 laparoscopic herniorrhaphies, with a median of five cases. Most of these 56 surgeons with LH experience indicated a preference for inguinal incision herniorrhaphy although 19 surgeons who had performed 10 or more LH cases showed a slight preference for LH (11 to 8). The primary reasons for choosing LH included "less pain" and "quicker recovery." The primary reasons for choosing inguinal incision herniorrhaphy included having a "better known procedure" and avoiding general anesthesia. Our survey indicates that the laparoscopic approach to inguinal hernia repair has currently accumulated few proponents in the surgical community since many surgeons are waiting for more data on the procedure.

Perfluorocarbons as blood substitutes: the early years. Experience with Fluosol DA-20% in the 1980s.

Clinical testing of perfluorocarbons (PFC) as blood substitutes began in the early 1980's in the form of Fluosol DA-20% (FDA), a mixture of perfluorodecalin and perfluorotripropylamine emulsified with Pluronic F68. We have treated 55 patients (Treatment (T) = 40; Control (C) = 15) with intravenous infusions of 30 cc/kg of FDA as part of either a randomized, clinical trial or a humanitarian protocol. All patients were Jehovah's Witnesses who refused blood transfusion and were severely anemic (mean hemoglobin = 4.6 g/d). FDA successfully increased dissolved or plasma oxygen content (P1O2 in ml/dl), but not overall oxygen content (T group: P1O2 baseline = 1.01 +/- .27, P1O2 12hrs = 1.58 +/- .47 [p = < .0001, t-test]; P1O2 12 hrs: T = 1.58 +/- .47, C = 1.00 +/- .31, p = < .0002, t-test). This effect persisted for only 12 hours post infusion, and had no apparent effect on survival. FDA is an ineffective blood substitute because of low concentration and short half-life. Improved emulsion design may resolve these problems, thereby producing a more effective agent. Our discussion will include a review of our data plus a summary of other reports of FDA efficacy as a blood substitute.

Elective vascular surgery without transfusion.

Although blood transfusion has helped make major vascular surgery possible, it has done so at a potential cost to our patients. Allogeneic red cell transfusions subject patients to the risks of transfusion reactions, disease transmission, and immunomodulation. These risks can be avoided in the majority of our patients through a better understanding of transfusion practices and the use of multiple alternatives to allogeneic blood.

Pancreatic cystogastrostomy by combined upper endoscopy and percutaneous transgastric instrumentation.

Minimally invasive endoscopic and radiologic techniques have been reported for internal gastric drainage of pancreatic pseudocysts but these have significant technical limitations. A purely endoscopic approach to cystogastrostomy provides limited access for instrumentation and hemostasis. Radiologically-guided percutaneous techniques cannot regularly provide an adequately wide cystogastrostomy opening. Reported is a patient who had a pancreatic cystogastrostomy performed using a minimally invasive surgical approach combining upper endoscopy and percutaneous transgastric surgical instrumentation. The upper endoscope essentially served as a camera. A percutaneous endoscopic gastrostomy tube served as a port for inserting laparoscopic instruments into the stomach. The laparoscopic instruments were used to create a 1.5 cm cystogastrostomy opening similar in size to what could be created by an open abdominal approach. The laparoscopy instruments provided good tactile feedback and excellent hemostatic control. Avoiding an open abdominal procedure shortened postoperative recovery and reduced patient discomfort. Although the pseudocyst recurred once, the same procedure was performed again and there has not been a recurrence for 10 months. The authors conclude that this minimally invasive surgical procedure provides an excellent alternative approach for internal drainage of selected pancreatic pseudocysts.

Immediate breast reconstruction after mastectomy.

Immediate breast reconstruction after mastectomy can be performed safely with a low incidence of complications. There is no evidence that reconstruction with a submuscular implant interferes with subsequent oncologic care, followup, or outcome for patients.

Safety of teaching laparoscopic cholecystectomy to surgical residents.

As laparoscopic cholecystectomy evolves into the "standard" method for gallbladder removal, it has become necessary for surgical residents to safely acquired the necessary skills to perform the procedure. To determine the safety of this procedure in the hands of residents, the authors evaluated the first 100 attempted laparoscopic cholecystectomies performed by a resident in the role of "surgeon." Ninety-one of the 100 procedures were successfully completed laparoscopically and 9 required conversion to laparotomy: 5 technically difficult cases, 2 common duct explorations, and 2 for intraoperative complications. At Cooper Hospital in New Jersey, essentially all patients requiring cholecystectomy are first attempted laparoscopically. Seventy-seven patients had chronic cholecystitis and 23 had acute disease. Twenty-two patients had intraoperative cholangiograms and two had laparoscopic common bile duct exploration. For the laparoscopically-completed procedures, average operative time was 91 min and showed a downward trend as each resident gained experience. Three (3%) major complications occurred: one colon laceration, one common bile duct injury, and one postoperative bile collection. For the 91 laparoscopically-completed procedures, 53 patients were discharged on postoperative day 1 and 20 on postoperative day 2. Average postoperative hospitalization was 1.7 days. Overall, these results were comparable to those reported in the literature by attending and private surgeons. The authors conclude that laparoscopic cholecystectomy can be performed safely by supervised residents acting as primary surgeon with outcomes similar to those obtained by trained attending surgeons.

Arterial vasopressin for control of bleeding from a stapled intestinal anastomosis. Report of two cases.

Postoperative bleeding from a stapled intestinal anastomosis is a rare complication. In previously reported cases, the bleeding either ceased spontaneously or required reoperation for direct control. We report two cases in which the bleeding was controlled using an intra-arterial vasopressin infusion. To our knowledge, this technique has not been previously reported for management of this problem. We had initial concerns about creating ischemia at the anastomosis, which could lead to disruption. Neither patient demonstrated subsequent problems with the anastomosis. Intra-arterial vasopressin infusion appears to be an effective method for controlling bleeding from a stapled intestinal anastomosis and can avert the need for reoperation.

Transfusion guidelines for cardiovascular surgery: lessons learned from operations in Jehovah's Witnesses.

Patients undergoing cardiovascular surgery are among the top users of homologous blood transfusion (HBT). Awareness of the risks of disease transmission and immune system modulation from HBT has prompted us to find alternatives such as autologous predonation (APD) and intraoperative autotransfusion (IAT). However, these latter options are not appropriate for all patients. We reviewed our experience with 59 Jehovah's Witness patients who underwent 63 elective cardiovascular procedures without either HBT or APD to determine the safety of operation without these modalities and to develop revised maximum surgical blood-ordering schedule guidelines for cardiovascular surgery. Estimated blood loss averaged 870 ml, but one third to one half of losses were replaced by IAT. IAT was not needed in lower extremity bypass operations in which the estimated blood loss was less than 150 ml. Three of 59 patients died (5.1%), but only one died of operative bleeding complications. We conclude that (1) elective cardiovascular operations can be done safely without the use of either HBT or APD, (2) HBT is not necessary in leg bypass procedures, and (3) maximum surgical blood-ordering schedule guidelines for HBT in major cardiovascular operations can be reduced to near zero by the use of intraoperative autotransfusion and acceptance of a postoperative hemoglobin nadir of 7.0 gm/dl.