Impact and utility of follicular lymphoma GELF criteria in routine care: an Australasian Lymphoma Alliance study.

Follicular Lymphoma (FL) treatment initiation is largely determined by tumor burden and symptoms. In the pre-rituximab era, the Group d'Etude des Lymphomes Folliculaires (GELF) developed widely adopted criteria to identify high tumor burden FL patients to harmonize clinical trial populations. The utilization of GELF criteria (GELFc) in routine therapeutic decision-making is poorly described. This multicenter retrospective study evaluated patterns of GELFc at presentation and GELFc utilization in therapeutic decision-making in newly diagnosed, advanced stage rituximab-era FL. Associations between GELFc, treatment given, and patient survival were analyzed in 300 eligible cases identified between 2002-2019. 163 (54%) had ≥1 GELFc at diagnosis. The presence or cumulative number of GELFc did not predict PFS in patients undergoing watch-and-wait (WW) or those receiving systemic treatment. Of interest, in patients with ≥1 GELFc, 16/163 (10%) underwent initial watch-and-wait (comprising 22% of the watchand- wait cohort). In those receiving systemic therapy +/- radiotherapy, 74/215 (34%) met no GELFc. Our data suggest clinicians are using adjunctive measures to make decisions regarding treatment initiation in a significant proportion of patients. By restricting FL clinical trial eligibility only to those meeting GELFc, reported outcomes may not be applicable to a significant proportion of patients treated in routine care settings.

Poor outcomes for trial-ineligible patients receiving polatuzumab for relapsed/refractory diffuse large B-cell lymphoma in routine care: An Australian Lymphoma and Related Diseases Registry project.

Polatuzumab vedotin (Pola) is an approved therapy in combination with rituximab and bendamustine for relapsed or refractory diffuse large B-cell lymphoma (RR-DLBCL) based on positive results of the landmark phase II randomised G029365 trial. However, trial results for many approved novel therapies in RR-DLBCL have not been replicated in routine care cohorts, as RR-DLBCL patient populations are heterogeneous and trial eligibility is increasingly restrictive. We evaluated outcomes from pola ± bendamustine and rituximab in patients with RR-DLBCL enrolled in a compassionate access program with no alternative treatment options identified via the Australasian Lymphoma and Related Diseases Registry according to their eligibility for the original phase II published study. Of 58 eligible patients, 74% met the criteria deeming them ineligible for the G029365 original study at the time of pola's commencement. Median progression-free survival and overall survival in our cohort were 2.3 and 3.5 months, respectively. In contrast to the landmark trial cohort, more of our patients ceased therapy prior to completion, the majority due to progressive disease and only 8/58 received any subsequent treatment. Dismal outcomes in this Australian real-world population demonstrate trial eligibility is challenging to meet, and newer treatments can be difficult to deliver in routine care. Clinically applicable results from therapeutic studies require trial cohorts to reflect representative clinical populations wherever possible, and more research is required to address the benefit of novel agents in the increasing majority who are ineligible for modern studies.

How Does Resident Participation Alter the Outcome of Surgery for Pectus Excavatum?

BACKGROUND: General surgery resident participation in the operating room is critical in training the next generation of surgeons. As of yet, the impact of resident participation on outcomes of surgery for pectus excavatum and many complex subspecialty operations has not been well studied. METHODS: A multi-institutional retrospective study of patients undergoing operative repair for pectus excavatum was performed. All relevant data were analyzed (IRB 11144). RESULTS: Two hundred and fourteen patients underwent operative correction (195 Nuss, 19 Ravitch). There were 185 males. Average age at repair was 14.7 years with a Haller index of 4.5. Average surgery time was 144 minutes (57-255) for the Nuss procedure and 263 minutes (141-373) for the Ravitch procedure. The presence of a second pediatric surgeon reduced the surgery time from 170 to 135 minutes (p < 0.01) and the presence of residents increased the time from 129 to 155 minutes (p < 0.01) for the Nuss procedure. One hundred and fifty patients had a single bar and 57 patients had 2 bars (28%). Average length of stay was 4.96 days (3-11). Long-term follow-up averaged 1737 days (42-3894). There were few complications and no difference in complication rate or length of stay between groups. Ninety nine percent of patients deemed the repair excellent and no patients required revision. CONCLUSIONS: Resident participation increases operative time, but with no demonstrable effect on hospital stay or long-term outcomes. Complication rates are low regardless of operating team composition. Thus, continuing to allow resident involvement, especially in subspecialty operations such as the Nuss and Ravitch procedures, may be worthwhile for resident education and surgical experience.

Minimally Invasive Repair of Pediatric Morgagni Hernias Using Transfascial Sutures with Extracorporeal Knot Tying.

BACKGROUND: Morgagni hernias are rare, with a reported incidence of 2% to 5% of congenital diaphragmatic hernias. OBJECTIVES: To review a laparoscopic technique to repair Morgagni hernias in pediatric patients. METHODS: Retrospective chart review of pediatric patients who underwent minimally invasive repair of a Morgagni hernia from November 2009 to September 2017 within a defined population. RESULTS: During an 8-year period, 15 patients with Morgagni hernias were identified. Four patients with Morgagni hernias were excluded because they had open repairs. Eleven Morgagni hernias were repaired through a completely minimally invasive approach. Three repairs were completed using a soft-tissue patch (Gore-Tex patch, W L Gore & Associates Inc, Flagstaff, AZ). All minimally invasive repairs were completed with transfascial sutures using an endoscopic suturing device (Endo Close, Covidien/Medtronic, Fridley, MN) and 2-0 nonabsorbable synthetic sutures with extracorporeal knot tying. Median follow-up was 40 months (range = 2.6 months to 7.3 years). No patients had postoperative pectus excavatum defects. There were no recurrences. CONCLUSION: Morgagni hernias are amenable to minimally invasive repair with this simple technique. With large defects, synthetic patches should be used. Recurrences are rare, and morbidity is low.

A new technique in complex chest wall reconstruction: Open reduction and internal fixation.

BACKGROUND: Reconstruction of complex chest wall deformities is a surgical challenge. A new technique can improve long-term outcomes and result in high patient satisfaction. METHODS: A multicenter study was conducted on pediatric patients undergoing complex chest wall reconstruction between September 2015 and January 2018. The evolution of the technique using open reduction and internal fixation (ORIF) with SternaLock® and RibFix® to repair chest wall deformities is described. RESULTS: Seventeen patients underwent complex chest wall reconstruction with ORIF. Eight patients had severe or recurrent pectus excavatum, five patients had pectus carinatum, and four patients had complex chest wall fractures or other anomalies causing significant chronic pain. Up to three SternaLock® plates and four RibFix® plates were used for each procedure. Median length of hospital stay after surgery was four days. Median follow-up time was 12 months (range 2-30). There were no postsurgical complications. There was 100% patient satisfaction in postoperative recovery and cosmesis. CONCLUSION: ORIF using SternaLock® and RibFix® is an effective method of reconstructing complex chest wall deformities. This technique improves physical stability without the requirement of a subsequent surgery and enhances overall patient satisfaction. High volume centers should integrate this novel approach for challenging chest wall reconstruction. TYPE OF STUDY: Treatment study: case series. LEVEL OF EVIDENCE: Level IV.

Thoracoscopic versus open repair of tracheoesophageal fistulas and rates of vocal cord paresis.

BACKGROUND/PURPOSE: The purpose of this study was to investigate the rates of vocal cord paresis/paralysis (VCP) in patients treated for esophageal atresia (EA) with and without fistula performed thoracoscopically versus open. METHODS: A retrospective review of EA cases performed from 2008 to 2014 in an integrated health care system was performed. RESULTS: A total of 31 cases of EA were performed by 6 surgeons at 4 different institutions. Seventeen cases were performed thoracoscopically, whereas 14 cases were performed open. In the thoracoscopic group, the average gestational age (weeks) of the patient was significantly higher 38.3 vs. 35.2 (p=0.016) as well as the average birth weight (grams) 2843 vs. 2079 (p=0.005). There was no difference in the postoperative length of stay, rates of anastomotic stricture, leak, or tracheomalacia. There were 10 cases of vocal cord paresis, 9 from the thoracoscopic group and one from the open group (p=0.007). Of the 10 cases of VCP, 6 were unilateral (left sided) and 4 were bilateral. Of the 10 cases, 6 resolved, 2 resulted in permanent paralysis, and 2 are currently still being evaluated. CONCLUSIONS: Thoracoscopic repair of EA appears to have higher rates of VCP. The results are thought to be from thoracoscopic dissection of the esophagus high into the thoracic inlet.

A comparison of laparoscopic and open Nissen fundoplication and gastrostomy placement in the neonatal intensive care unit population.

INTRODUCTION: The aim of this study was to compare outcomes after laparoscopic and open techniques for Nissen fundoplication and gastrostomy placement in the neonatal intensive care unit (NICU) population. METHODS: The medical records for NICU inpatients who underwent laparoscopic and open Nissen fundoplication and gastrostomy placement from August 2002 to August 2008 were reviewed after Institutional Review Board approval. Each technique was compared with regard to operative time, estimated blood loss, postoperative 24-hour narcotic requirements, time to goal feeds, and complication rates. Analysis of variance was used to determine statistical significance. Data are quoted as mean +/- SEM. RESULTS: Fifty-seven NICU patients underwent fundoplication and gastrostomy placement (25 laparoscopic and 32 open). The time to goal feeds was significantly shorter for the laparoscopic group (4.3 +/- 0.4 vs 6.1 +/- 0.6 days, P = .04). The 24-hour postoperative narcotic requirement was significantly lower in the laparoscopic group (0.24 +/- 0.05 vs 0.55 +/- 0.08 mg/kg, P = .007). Operation times (111 +/- 5 [open] vs 113 +/- 5 minutes, P = .76) and estimated blood loss (13 +/- 2 [open] vs 11 +/- 1 mL, P = .33) were comparable for both groups. CONCLUSION: Laparoscopic and open techniques for Nissen fundoplication with gastrostomy placement are safe and appropriate treatment methods with equivalent operating times for the treatment of gastroesophageal reflux in the NICU population.

A rare cause of vaginal bleeding in a 7-month-old female infant.

Ovarian sex cord stromal tumor (OSCST), sclerosing type, is an extremely rare ovarian tumor. Sex hormone production by OSCST can result in isosexual or heterosexual precocious puberty in younger patients. We present a case of a 7-month-old female infant found to have a sclerosing-type OSCST that presented with vaginal bleeding and very prominent vellus hair at the mons pubis. This represents the youngest patient reported in the literature with this subset of OSCST.

Modulation of the inflammatory response and apoptosis using epidermal growth factor and hepatocyte growth factor in a liver injury model: a potential approach to the management and treatment of cholestatic liver disease.

BACKGROUND/PURPOSE: The major side effect of total parenteral nutrition is liver injury leading to liver failure. This study was designed to assess specific growth factors in modulating the hepatic response in an ANIT-induced liver-injury model. METHODS: Sprague-Dawley rats were divided into four groups: control (n = 5), liver-injury control (alpha-naphthylisothiocyanate [ANIT], 100 mg/kg, n = 8), ANIT + epidermal growth factor (EGF, 150 mug/kg per day, n = 10), and ANIT + hepatocyte growth factor (HGF, 250 mug/kg per day, n = 9). Rats were given intraperitoneal injections of saline (control) or ANIT and implantation of an osmotic mini-pump for 7 days of continuous intravenous saline (liver injury control), EGF, or HGF. Seven and 14 days later, liver biopsies were obtained and evaluated for interleukin (IL)-6 and tumor necrosis factor alpha expression by immunofluorescent staining, and for apoptosis, by the terminal transferase dUTP nick end labeling (TUNEL) technique. All animals were euthanized at 14 days. RESULTS: Epidermal growth factor (P < .025) and HGF (P < .001) groups induced less IL-6 expression at day 14 compared to liver-injury controls. In addition, the interval decrease in IL-6 expression between days 7 and 14 was greater in EGF (P < .001) and HGF (P < .001) groups compared to liver-injury controls. At day 14, HGF also demonstrated decreased tumor necrosis factor alpha expression (P < .005). Apoptotic activity was significantly less for the EGF (P < .011) and HGF (P < .0012) groups. CONCLUSION: Epidermal growth factor and HGF modulated the hepatic inflammatory response and apoptotic index in this established liver-injury model and may diminish or prevent liver damage in patients with total parenteral nutrition-induced liver injury.

Biocatalytic synthesis of a nanostructured and crystalline bimetallic perovskite-like barium oxofluorotitanate at low temperature.

Silicatein, an enzymatic biocatalyst from the marine sponge Tethya aurantia, is demonstrated to catalyze and template the hydrolysis/condensation of the molecular precursor BaTiF6 at low temperature to form nanocrystalline BaTiOF4, an orthorhombic oxofluorotitanate. The kinetics of hydrolysis and growth were studied in-situ via pH profiling and quartz crystal microbalance (QCM) techniques. The composition and structure of the resulting BaTiOF4 microstructures on the silicatein surface were characterized using FT-IR spectroscopy, X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, scanning electron microscopy, transmission electron microscopy, and selected area electron diffraction. The silicatein-mediated hydrolysis/condensation of BaTiF6 generates nanocrystalline BaTiOF4 (a high-temperature intermediate to BaTiO3) at 16 degrees C without any added acid or base, and the growth is templated along the protein filaments into floret microstructures. The unique combination of silicatein and the single-source molecular precursor has allowed a multimetallic perovskite-like material to be biocatalytically synthesized, in vitro, for the first time.