Total Neoadjuvant Therapy Significantly Increases Complete Clinical Response.

BACKGROUND: Increased experience with total neoadjuvant therapy for rectal cancer suggests significantly more tumor regression and increased rates of complete clinical response as measured by pathological complete response and clinical complete response. OBJECTIVE: This study aimed to assess outcomes after total neoadjuvant therapy versus standard neoadjuvant chemoradiotherapy for patients with locally advanced rectal cancer. DESIGN: This is a retrospective cohort study. SETTINGS: A database of patients with rectal cancer from 2015 to 2019 at a large integrated health care system was reviewed. PATIENTS: Demographics of the 2 groups revealed no significant difference in clinical stage or patient characteristics. Of 465 patients, 66 patients underwent total neoadjuvant therapy and 399 underwent standard neoadjuvant chemoradiotherapy. Fifty-six patients underwent consolidation chemotherapy, and 10 underwent induction chemotherapy. MAIN OUTCOME MEASURES: Complete clinical response, disease-free survival, proctectomy-free survival, and organ preservation rates were the main outcome measures. RESULTS: Complete clinical response was achieved in 36 patients (58.1%) versus 59 patients (14.8%; p < 0.001), favoring the total neoadjuvant therapy group. Three-year overall survival was similar between groups (85.6% standard neoadjuvant chemoradiotherapy versus 86.0% total neoadjuvant therapy). Three-year distant metastasis-free survival was 67.4% in the total neoadjuvant therapy group compared to 77.7% in the standard neoadjuvant chemoradiotherapy group. Three-year proctectomy-free survival was 44% in the total neoadjuvant therapy group compared to 6% in the standard neoadjuvant chemoradiotherapy group. Twenty-two patients (37.3% of complete clinical responders) in the standard neoadjuvant chemoradiotherapy group elected to pursue organ preservation, whereas 31 patients (86.1% of complete clinical responders) from the total neoadjuvant therapy group chose organ preservation. LIMITATIONS: This study is limited by its retrospective nature with a shorter follow-up of 3 years. CONCLUSIONS: Total neoadjuvant therapy for rectal cancer significantly increased complete clinical response. This allowed patients to have greater organ preservation with no significant difference in overall survival or disease control. See Video Abstract at http://links.lww.com/DCR/B934 . LA TERAPIA NEOADYUVANTE TOTAL AUMENTA SIGNIFICATIVAMENTE LA RESPUESTA CLNICA COMPLETA: ANTECEDENTES:La mayor experiencia con la terapia neoadyuvante total para el cáncer de recto sugiere una regresión tumoral significativamente mayor y mayores tasas de respuesta clínica completa, medidas por respuesta patológica completa y respuesta clínica completa.OBJETIVO:Este estudio evaluó los resultados después de la terapia neoadyuvante total versus la quimiorradioterapia neoadyuvante estándar para pacientes con cáncer de recto localmente avanzado.DISEÑO:Este es un estudio de cohorte retrospectivo.ESCENARIO:Se revisó una base de datos de pacientes con cáncer de recto de 2015 a 2019 en un sistema de salud integrado grande.PACIENTES:La demografía de los dos grupos no revela diferencias significativas en el estadio clínico o las características de los pacientes. De 465 pacientes, 66 pacientes recibieron terapia neoadyuvante total y 399 quimiorradioterapia neoadyuvante estándar. Cincuenta y seis se sometieron a quimioterapia de consolidación mientras que 10 pacientes a quimioterapia de inducción.PRINCIPALES MEDIDAS DE RESULTADO:Se midieron la respuesta clínica completa, la sobrevida libre de enfermedad, la sobrevida libre de proctectomía y las tasas de preservación de órgano.RESULTADOS:Se logró una respuesta clínica completa en 36 pacientes (58.1 %) frente a 59 pacientes (14.8 %) (p < 0,001) a favor del grupo de terapia neoadyuvante total. La sobrevida general a tres años fue similar entre los grupos (85.6 % quimiorradioterapia neoadyuvante estándar frente a 86.0 % terapia neoadyuvante total). La sobrevida libre de metástasis a distancia a los tres años fue del 67.4 % en el grupo de terapia neoadyuvante total y del 77.7 % en el grupo de quimiorradioterapia neoadyuvante estándar. La sobrevida sin proctectomía a los tres años fue del 44 % en el grupo de terapia neoadyuvante total frente al 6 % en el grupo de quimiorradioterapia neoadyuvante estándar. Veintidós pacientes (37.3 % con respuesta clínica completa) en el grupo de quimiorradioterapia neoadyuvante estándar optaron por la preservación de órgano, mientras que 31 pacientes (86.1 % respuesta clínica completa) del grupo de terapia neoadyuvante total eligieron la preservación de órgano.LIMITACIONES:Este estudio es un estudio retrospectivo con un seguimiento más corto de 3 años.CONCLUSIONES:La terapia neoadyuvante total para el cáncer de recto aumentó significativamente la respuesta clínica completa. Esto permitió a los pacientes tener una mayor preservación de órgano sin diferencias significativas en la sobrevida general o el control de la enfermedad. Consulte Video Resumen en http://links.lww.com/DCR/B934 . (Traducción-Dr. Jorge Silva Velazco ).

Surgical approach to pediatric mediastinal masses based on imaging characteristics.

BACKGROUND: Pediatric mediastinal masses may be resected using an open or video-assisted thoracoscopic surgery (VATS) approach. We sought to define the preoperative imaging findings predicting amenability to VATS. METHODS: This multicenter retrospective study of pediatric patients undergoing either VATS or open surgical mediastinal mass resection between 2008 and 2018 evaluated the preoperative imaging descriptors associated with VATS. Postoperative endpoints included length of stay (LOS), 30-day readmission, 90-day mortality and complication rates. RESULTS: Mediastinal mass resection was performed in 33 patients. Median tumor size was 6 cm, and 51.5% had anterior mediastinal tumors. The 23 (69.7%) patients who underwent VATS were significantly older (144 months vs 32, P = 0.01) and larger (33.6 kg vs 13.8 P = 0.03). Preoperative imaging characteristics in VATS included "well circumscribed", "smooth margins" and "cystic", while the open surgery group were "heterogeneous" and "coarse calcification". The open group had more germ cell tumors (60.0% vs 13.0%, P = 0.16) but no difference in malignancy. VATS patients had shorter LOS (2 days vs 6.5, P = 0.24). Readmission, complication and mortality rates were similar. CONCLUSIONS: Pediatric patients with apparent malignancy frequently underwent open resection compared with the thoracoscopic group, although final malignant pathology was similar. Equivalent outcomes and shorter LOS should favor a minimally invasive approach. LEVEL OF EVIDENCE: Level III.

Cryoablation is associated with shorter length of stay and reduced opioid use in pectus excavatum repair.

PURPOSE: The use of intercostal nerve cryoablation (INC) is becoming increasingly common in patients undergoing pectus excavatum (PE) repair. This study sought to evaluate the use of INC compared to traditional use of thoracic epidural (TE). METHODS: A retrospective review of 79 patients undergoing PE repair with either INC or TE from May 2009 to December 2019 was conducted. The operations were performed by four surgeons who worked together at four different hospitals and have the same standardized practice. The primary outcome measure was hospital length of stay (LOS). Secondary variables included surgical time, total operating room time, operating room time cost, total hospital cost, inpatient opioid use, long-term opioid use after discharge, and postoperative complications. RESULTS: LOS decreased to 2.5 days in the INC group compared to 5 days in the TE group (p < 0.0001). Surgical time was increased in the INC group, but there was no difference in total OR time. The INC group experienced significantly lower hospital costs. Total hospital opioid administration was significantly lower in INC group, and there was a significant decrease in long-term opioid use in the INC group. CONCLUSIONS: INC is a newer modality that decreases LOS, controls pain, and results in overall cost savings. We recommend that INC be included in the current practice for postoperative pain control in PE patients undergoing Nuss procedure.

Cryoablation is associated with shorter length-of-stay and reduced opioid use after the Ravitch procedure.

PURPOSE: The use of intercostal nerve cryoablation (INC) is becoming increasingly common in patients undergoing pectus repair. This study sought to evaluate the use of INC compared to traditional use of thoracic epidural (TE) in patients undergoing the modified Ravitch procedure. METHODS: A retrospective review of 37 patients undergoing the modified Ravitch repair with either INC or TE from March 2009 to July 2021 was conducted. The operations were performed by four surgeons who worked together at four different hospitals and have the same standardized practice. The primary outcome measure was hospital length of stay (LOS). Secondary variables included surgical time, total operating room time, operating room time cost, total hospital cost, inpatient opioid use, long term opioid use after discharge, and post-operative complications. RESULTS: LOS decreased to 2.8 days in the INC group compared to 6 days in the TE group (p<0.0001). Surgical time and total OR time was increased in the INC group. The INC group experienced significantly lower hospital costs (p<0.01). Total hospital opioid administration was significantly lower in INC group, and there was a significant decrease in long term opioid use in the INC group (p<0.0001). CONCLUSIONS: INC is a newer modality that decreases LOS, controls pain, and results in overall cost savings for patients undergoing the modified Ravitch procedure. We recommend that INC be included in the current practice for postoperative pain control in pectus disorder patients undergoing the modified Ravitch procedure.

Same day discharge for pectus excavatum-is it possible?

PURPOSE: The use of intercostal nerve cryoablation (INC) has been an effective modality for treating pain in patients undergoing pectus excavatum (PE) repair. This study sought to evaluate if PE patients undergoing Nuss procedures with INC and intercostal nerve block (INB) could safely be discharged the same day of surgery. METHODS: A prospective study with IRB approval of 15 consecutive patients undergoing PE Nuss repair with INC, INB, and an enhanced recovery after surgery (ERAS) protocol was conducted. The primary outcome measure was hospital length of stay (LOS) in hours. Secondary variables included same day discharge, postoperative complications, emergency department (ED) visits, urgent care (UC) visits, opioid use, and return to the operating room (OR). RESULTS: LOS averaged 11.9 h amongst 15 patients. Ten patients (66.7%) went home on postoperative day (POD) 0, and the rest went home on POD 1. No patients stayed in the hospital due to pain. Reasons for failure to discharge included urinary retention, drowsiness, vomiting, and anxiety, but not pain. No patients were readmitted to the ED. One patient visited UC for constipation. One patient had bar migration requiring return to the OR for revision. Ten (66.7%) patients did not use opioids after discharge. CONCLUSIONS: Same day discharge is feasible and safe in PE patients undergoing Nuss procedure with INC and INB. INC with INB can adequately control pain without significant complications. Same day discharge can be safely considered for PE patients undergoing Nuss procedure with INC with INB. TYPE OF STUDY: Prognosis study LEVEL-OF-EVIDENCE RATING: Level II.

Same-day discharge following the Nuss repair: A comparison.

PURPOSE: Intercostal Nerve Cryoablation (INC) has significantly improved pain control following the Nuss repair of pectus excavatum (PE). This study sought to evaluate patients undergoing the Nuss repair with INC compared to the Nuss repair with an ERAS protocol, INC, and intercostal nerve blocks (INB). METHODS: In June 2020, a new protocol was implemented involving surgery, anesthesia, nursing, physical therapy, and child life with the goal of safe same day discharge for patients undergoing the Nuss repair. They were compared to a control group who underwent the Nuss repair with INC alone in 2017-2019. The primary outcome measure was hospital length of stay (LOS) in hours, secondary outcomes were number of patients discharged on postoperative day (POD) 0, and returns to the emergency department (ED), urgent care (UC), and operating room (OR). RESULTS: The characteristics between the groups were the same (Table 1). The mean LOS was 11.8 h in the INB group versus 58.2 h in the INC group, p < 0.01. 10 of 15 patients in the INB group went home on POD 0 (average of 5.5 h postop), versus 0 patients in the INC only group, p < 0.01. Five patients in the INB stayed overnight. Two patients stayed owing to anxiety, one owing to urinary retention, one owing to nausea, and one owing to drowsiness. None stayed for pain control. Four patients in the INC group returned to the ED for pain control, versus 0 in the INB group, and 1 patient in the INB returned to UC for constipation. CONCLUSIONS: The majority of patients undergoing the Nuss repair of PE with a multidisciplinary regimen of pre and postoperative nursing education, precise intraoperative anesthesia care, performance of direct vision INB and INC, as well as careful surgery can go home on the day of surgery without adverse outcomes or unanticipated returns to the hospital. LEVEL-OF-EVIDENCE: Level II.

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice.

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).

miRNA signature associated with outcome of gastric cancer patients following chemotherapy.

BACKGROUND: Identification of patients who likely will or will not benefit from cytotoxic chemotherapy through the use of biomarkers could greatly improve clinical management by better defining appropriate treatment options for patients. microRNAs may be potentially useful biomarkers that help guide individualized therapy for cancer because microRNA expression is dysregulated in cancer. In order to identify miRNA signatures for gastric cancer and for predicting clinical resistance to cisplatin/fluorouracil (CF) chemotherapy, a comprehensive miRNA microarray analysis was performed using endoscopic biopsy samples. METHODS: Biopsy samples were collected prior to chemotherapy from 90 gastric cancer patients treated with CF and from 34 healthy volunteers. At the time of disease progression, post-treatment samples were additionally collected from 8 clinical responders. miRNA expression was determined using a custom-designed Agilent microarray. In order to identify a miRNA signature for chemotherapy resistance, we correlated miRNA expression levels with the time to progression (TTP) of disease after CF therapy. RESULTS: A miRNA signature distinguishing gastric cancer from normal stomach epithelium was identified. 30 miRNAs were significantly inversely correlated with TTP whereas 28 miRNAs were significantly positively correlated with TTP of 82 cancer patients (P<0.05). Prominent among the upregulated miRNAs associated with chemosensitivity were miRNAs known to regulate apoptosis, including let-7g, miR-342, miR-16, miR-181, miR-1, and miR-34. When this 58-miRNA predictor was applied to a separate set of pre- and post-treatment tumor samples from the 8 clinical responders, all of the 8 pre-treatment samples were correctly predicted as low-risk, whereas samples from the post-treatment tumors that developed chemoresistance were predicted to be in the high-risk category by the 58 miRNA signature, suggesting that selection for the expression of these miRNAs occurred as chemoresistance arose. CONCLUSIONS: We have identified 1) a miRNA expression signature that distinguishes gastric cancer from normal stomach epithelium from healthy volunteers, and 2) a chemoreresistance miRNA expression signature that is correlated with TTP after CF therapy. The chemoresistance miRNA expression signature includes several miRNAs previously shown to regulate apoptosis in vitro, and warrants further validation.