Patrick G. Jackson

Intraperitoneal macrophages and tumor immunity: A review.

The macrophage (Mϕ) is considered the first line of defense in immune response to foreign invaders. Increasing evidence suggests that Mϕs also play an important role against neoplastic cells. Mϕs exposed to supraphysiologic concentrations of CO2 are suppressed. As surgeons apply newer minimally invasive techniques to oncologic therapies, it is important to evaluate the impact of these techniques on host‐tumor interactions. We review the current understanding of Mϕ biology with specific attention on cytotoxicity in addition to tumor immunity. Although systemic immune function is better preserved after laparoscopy than laparotomy, peritoneal Mϕs show reduced function after CO2 pneumoperitoneum than exposure to air. Mϕs have shown cytotoxicity to syngeneic cancer cells and may play an important role in tumor surveillance. The impairment in Mϕ function after CO2 exposure may have an effect on outcome after oncologic surgery. In our understanding, Mϕs help destroy neoplastic cells. As CO2 impairs Mϕ activity, laparoscopy may significantly alter the host‐tumor interaction. J. Surg. Oncol. 2000:75:146–155.

Predictors of outcome in 100 consecutive laparoscopic antireflux procedures.

BACKGROUNDnPublished success rates for surgical intervention in gastroesophageal reflux disease exceed 90%. The goal of this study was to determine if any preoperative factors could accurately predict postoperative symptom relief.nnnMETHODSnOne hundred consecutive patients undergoing laparoscopic antireflux surgery completed a detailed preoperative questionnaire, and underwent endoscopy, manometry, and 24-hour esophageal pH monitoring. Two surgeons performed all procedures in a standardized fashion. At least 2 months following operative intervention, a single interviewer, blinded to all preoperative information and procedure performed, recorded Visick and Gastroesophageal Reflux Disease-Health-Related Quality of Life scores for all patients. All follow-up was performed within 3 years of antireflux procedure.nnnRESULTSnThe surgical success rate, as defined by Visick scores of 1-2, was 91%. Three variables were predictive of postoperative success: age <50, presence of typical symptoms at presentation, and complete resolution of symptoms with acid suppression therapy.nnnCONCLUSIONnThe study shows that surgical strategies can reproducibly control gastroesophageal reflux disease symptoms in more than 90% of patients. The optimal surgical candidate is a patient under the age of 50 whose typical symptoms completely resolve with acid suppression therapy.

Brainstem sites controlling the lower esophageal sphincter and crural diaphragm in the ferret: A neuroanatomical study

The lower esophageal sphincter (LES) and the crural diaphragm (CD) surrounding the esophagogastric junction are key components of the gastroesophageal reflex mechanism, which engages the vago-vagal brainstem circuitry. Although both components work in conjunction to prevent gastroesophageal reflux, little is known about the brain area(s) where this integration takes place. The aims of this study were to: (1) trace the brainstem circuitry associated with the CD and the LES, and (2) determine possible sites of convergence. Experiments were done in adult male ferrets. Under isoflurane anesthesia, recombinant strains of the transneuronal pseudorabies virus (PRV-151 or PRV-Bablu) or the monosynaptic retrograde tracer cholera toxin beta-subunit (CTb) were injected into either the CD or the LES. Following a survival period of 5-7 days, animals were euthanized, perfused and their brains removed for dual-labeling immunofluorescence processing. In animals injected with recombinants of PRV into the CD and the LES, distinct labeling was found in various brainstem nuclei including: area postrema, DMV, nucleus tractus solitarius (NTS), medial reticular formation (MRF) and nucleus ambiguous (NA). Double-labeled cells were only evident in the DMV, NTS and MRF. Injections of CTb into the CD or the LES resulted in retrograde labeling only in the DMV. These findings demonstrate the presence of a direct projection from the DMV to the CD. They further suggest that the neuronal connections responsible for CD or LES function are contained in circuitries that, though largely independent, may converge at the level of DMV, NTS and MRF.

Stereotactic Body Radiation Therapy (sbrt) Combined With Chemotherapy for Unresected Pancreatic Adenocarcinoma.

Objectives: The role of radiation therapy in the management of unresectable pancreatic cancer is controversial. One concern about concurrent chemoradiation relates to the timing of chemotherapy. In contrast to conventional radiation therapy, stereotactic body radiation therapy (SBRT) delivers high doses in a shorter duration resulting in minimal disruption in chemotherapy. Here, we report our results of patients treated with SBRT and chemotherapy for inoperable pancreatic cancer. Materials and Methods: Thirty-eight patients treated with SBRT and chemotherapy for locally advanced, borderline resectable, and medically inoperable pancreatic cancer at our institution from January 2008 to December 2012 were included in this retrospective analysis. Treatment was delivered in 5 fractions of 5 or 6 Gy per fraction over 5 days. Toxicities were scored using the Common Terminology Criteria for Adverse Events version 3. Survival was calculated using the Kaplan-Meier method. Results: The median age was 70 years (range, 45 to 90 y). Eastern Cooperative Oncology Group performance status ranged from 0 to 3. Thirty-four patients received concurrent chemotherapy. Four patients received sequential chemotherapy. Median overall survival was 14.3 months and median progression-free survival was 9.2 months from diagnosis. From radiation, overall survival and progression-free survival were 12.3 and 6.8 months, respectively. The overall local control rate was 79%. Acute toxicity was minimal. Severe late SBRT-related toxicities included 1 grade 3 gastric outlet obstruction, 1 grade 4 biliary stricture, and 1 grade 5 gastric hemorrhage. Conclusions: SBRT combined with chemotherapy for unresectable pancreatic cancer is convenient, feasible, and generally well tolerated. Outcomes of SBRT combined with chemotherapy compare favorably to results obtained with chemotherapy and conventional radiation therapy.

Subdiaphragmatic Vagotomy With Pyloroplasty Ameliorates the Obesity Caused by Genetic Deletion of the Melanocortin 4 Receptor in the Mouse

Background/Objectives: We tested the hypothesis that abolishing vagal nerve activity will reverse the obesity phenotype of melanocortin 4 receptor knockout mice (Mc4r−/−). Subjects/Methods: In two separate studies, we examined the efficacy of bilateral subdiaphragmatic vagotomy (SDV) with pyloroplasty in the prevention and treatment of obesity in Mc4r−/− mice. Results: In the first study, SDV prevented >20% increase in body weight (BW) associated with this genotype. This was correlated with a transient reduction in overall food intake (FI) in the preventative arm of the study. Initially, SDV mice had reduced weekly FI; however, FI normalized to that of controls and baseline FI within the 8-week study period. In the second study, the severe obesity that is characteristic of the adult Mc4r−/− genotype was significantly improved by SDV with a magnitude of 30% loss in excess BW over a 4-week period. Consistent with the first preventative study, within the treatment arm, SDV mice also demonstrated a transient reduction in FI relative to control and baseline levels that normalized over subsequent weeks. In addition to the accompanying loss in weight, mice subjected to SDV showed a decrease in respiratory exchange ratio (RER), and an increase in locomotor activity (LA). Analysis of the white fat-pad deposits of these mice showed that they were significantly less than the control groups. Conclusions: Altogether, our data demonstrates that SDV both prevents gain in BW and causes weight loss in severely obese Mc4r−/− mice. Moreover, it suggests that an important aspect of weight reduction for this type of monogenic obesity involves loss of signaling in vagal motor neurons.