Identifying the optimal treatment strategy in patients with resectable non-cardia gastric cancer.

BACKGROUND: Multimodal treatment strategy including perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) has been accepted as the standard of care in gastric cancer (GC). The ideal sequence and type of therapy remain undetermined. METHOD: The National Cancer Database was examined from 2006 to 2016 to identify patients with resectable non-cardia gastric cancer. Patient outcomes were compared based on the receipt of PEC, POCR, and POC. This comparison was repeated in a sub-group of patients who received optimal treatment. Optimal treatment was defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection and standard radiation dose (45 Gy). Kaplan-Meier test, log-rank test, and multivariable analysis (MVA) were performed. RESULTS: We identified 9589 patients. Median survival was greater in the PEC group followed by POCR and POC (60.6, 42.3, and 31.2 months, respectively). On MVA, factors associated with worse overall survival included age above median (≥ 63 years), Charlson-Deyo score of ≥ 1, non-academic/research program, poorly differentiated/undifferentiated grade, positive margins, and positive lymph nodes. Both PEC and POCR were associated with improved survival when compared to POC (HR 0.78 and 0.79; p < 0.001). When compared with PEC, no significant difference was noted with POCR (HR 1.01; p = 0.987). These results were maintained in optimally treated cohort (n = 3418). CONCLUSION: In patients with resectable non-cardia gastric cancer, both perioperative chemotherapy and postoperative chemoradiation therapy were associated with improved survival when compared to postoperative chemotherapy. No difference was noted between perioperative chemotherapy and postoperative chemoradiation therapy. These results were maintained in the optimally treated cohort.

Leaks From the Tip of the J-pouch: Diagnosis, Management, and Long-term Pouch Survival.

BACKGROUND: The standard of care for surgical treatment of ulcerative colitis is restorative proctocolectomy with ileal J-pouch. Leaks from the tip of the J-pouch are a known complication, but there is a paucity of literature regarding this type of leak. OBJECTIVE: We aimed to describe the diagnosis, management, and long-term clinical outcomes of leaks from the tip of the J-pouch at our institution. DESIGN: This was a retrospective study of a prospectively maintained pouch registry. SETTING: This study was conducted at a quaternary IBD referral center. PATIENTS: Patients included those with ileal J-pouches diagnosed with leaks from the tip of the J-pouch. MAIN OUTCOME MEASURES: The main measures of outcomes were pouch salvage rate, type of salvage procedures, and long-term Kaplan-Meier pouch survival. RESULTS: We identified 74 patients with leaks from the tip of the J-pouch. Pain (68.9%) and pelvic abscess (40.9%) were the most common presentations, whereas 10.8% of patients presented with an acute abdomen. The leak was diagnosed by imaging and/or endoscopy in 74.3% of patients but only discovered during surgical exploration in 25.6% of patients. Some 63.5% of patients were diagnosed only after loop ileostomy closure, whereas 32.4% of patients were diagnosed before ileostomy closure. The most common methods used for diagnosis were pouchoscopy (31.1%) and gastrograffin enema (28.4%). A definitive nonoperative approach was attempted in 48.6% of patients but was successful in only 10.8% of patients overall. Surgical repair was attempted in 89.2% of patients, whereas 4.5% of patients had pouch excision. Salvage operations (n = 63) included sutured or stapled repair of the tip of the J (65%), pouch excision with neo-pouch (25.4%), and pouch disconnection, repair, and reanastomosis (9.5%). Ultimately' 10 patients (13.5%) required pouch excision, yielding an overall 5-year pouch survival rate of 86.3%. LIMITATIONS: This was a retrospective review; referral bias may limit the generalizability. CONCLUSIONS: Leaks from the tip of the J-pouch have variable clinical presentations and require a high index of suspicion. Pouch salvage surgery is required in the majority of patients and is associated with a high pouch salvage rate. See Video Abstract at http://links.lww.com/DCR/C50 . FUGAS DEL EXTREMO DE LA BOLSA EN J DIAGNSTICO, MANEJO Y SUPERVIVENCIA A LARGO PLAZO DE LA BOLSA: ANTECEDENTES:El estándar de atención para el tratamiento quirúrgico de la colitis ulcerosa es la proctocolectomía restauradora con bolsa ileal en J. Las fugas del extremo de la bolsa en J son una complicación conocida, pero hay escasez de literatura sobre este tipo de fuga.OBJETIVO:Describir el diagnóstico, manejo y resultados clínicos a largo plazo de las fugas del extremo de la bolsa en J en nuestra institución.DISEÑO:Estudio retrospectivo de registro de bolsa mantenido prospectivamente.ENTORNO CLINICO:Centro de referencia de enfermedad inflamatoria intestinal cuaternaria.PACIENTES:Pacientes con bolsas ileales en J diagnosticadas con fugas del extremo de la J.PRINCIPALES MEDIDAS DE VALORACIÓN:Tasa de rescate de la bolsa, tipo de procedimientos de rescate y supervivencia a largo plazo de la bolsa Kaplan-Meier.RESULTADOS:Identificamos 74 pacientes con fugas del extremo de la bolsa en J. El dolor (68,9%) y el absceso pélvico (40,9%) fueron las presentaciones más comunes, mientras que el 10,8% de los pacientes presentaron abdomen agudo. La fuga se diagnosticó por imagen y/o endoscopia en el 74,3%, pero solo se descubrió durante la exploración quirúrgica en el 25,6%. El 63,5% fueron diagnosticados solo después del cierre de la ileostomía en asa, mientras que el 32,4% lo fueron antes del cierre de la ileostomía. Los métodos más comunes utilizados para el diagnóstico fueron la endoscopia (31,1%) y el enema de gastrografín (28,4%). Se intentó un abordaje no quirúrgico definitivo en el 48,6%, pero tuvo éxito en solo el 10,8% de los pacientes en general. Se intentó la reparación quirúrgica en el 89,2% de los pacientes, mientras que en el 4,5% se realizó la escisión del reservorio. Las operaciones de rescate (n = 63) incluyeron la reparación con sutura o grapas del extremo de la J (65%), la escisión del reservorio con neo-reservorio (25,4%) y la desconexión, reparación y reanastomosis del reservorio (9,5%). Finalmente, 10 (13,5%) pacientes requirieron la escisión de la bolsa, lo que se asocio con una alta tasa de supervivencia general de la bolsa a los 5 años del 86,3%.LIMITACIONES:Revisión retrospectiva; el sesgo de referencia puede limitar la generalización.CONCLUSIONES:Las fugas del extremo de la bolsa en J tienen presentaciones clínicas variables y requieren un alto índice de sospecha. La cirugía de rescate de la bolsa se requiere en la mayoría y se asocia con una alta tasa de rescate de la bolsa. Consulte Video Resumen en http://links.lww.com/DCR/C50 . (Traducción- Dr. Ingrid Melo ).

Engineering the Nonmorphing Point of Actuation for Controlled Drug Release by Hydrogel Bilayer across the pH Spectrum.

Hydrogel-based pH-responsive bilayer actuators exhibit bidirectional actuation due to the differences in the concentration gradient developed across the thickness, the volume expansion due to swelling, and the mechanical stiffness of the layers involved. At a pH value (point), where the sum of these factors generates moments of equal magnitudes, the moments cancel each other and result in no net actuation. This pH point is termed here as a "nonmorphing point". In this work, we present a bilayer of chitosan (CS) and carboxymethyl cellulose (CMC) cross-linked with citric acid (CA) with tunable nonmorphing points across the pH spectrum by modulating the concentration and cross-linking density of the layers involved. The standard CS/CMC bilayer films took about 40 s to completely fold (clockwise) in 0.1 M HCl and 78 s to completely fold (anticlockwise) in 0.1 M NaOH. Generally, pH-responsive actuators are designed for targeted drug delivery to a specific site inside the body as they show bidirectional (clockwise/anticlockwise) actuation around a single nonmorphing point. The same pH-responsive system cannot be applied for drug release at another site with a different functioning pH. Thus, having a pH-responsive system with multiple nonmorphing points is highly desirable. Drug release experiments were performed with FITC and EtBr as model drugs loaded in CS and CMC layers. Moreover, the clockwise/anticlockwise actuation of the bilayer around the nonmorphing point can facilitate or inhibit the release of a drug. The clockwise actuation resulted in 55% FITC release and inhibited EtBr release to 4%; anticlockwise actuation resulted in 50% EtBr release and inhibited FITC release to 5%. We demonstrated morphing induced drug release by hydrogel bilayer films with tunable nonmorphing points across the pH spectrum.

Soft and elastic hollow microcapsules embedded silicone elastomer films with enhanced water uptake and permeability for mechanical stimuli responsive drug delivery applications.

Polydimethylsiloxane (PDMS) film with significantly enhanced water permeability and uptake was prepared by incorporating spherical elastic hollow microcapsules (eHMCs) in it. eHMCs were prepared through O/W/O emulsification method. Water permeability and uptake of the film increased significantly in proportion to the amount of embedded eHMCs while minimizing the changes in elastic characteristics and transparency of PDMS. The release rate of loaded water soluble model drug from the eHMC-embedded PDMS film could be controlled by the magnitude of uniaxial mechanical stimulus applied over the film and initial drug loading amount, with negligible release of drug from the film in the absence of external stimulation. Thus, these biocompatible and elastic composite PDMS films are potentially useful, including as an easily accessible and instantly effective way of controlling hydrophilic drug release using the mechanical stimulus as well as a soft elastomer with enhanced water uptake and permeability.

Mechanical stimuli responsive and highly elastic biopolymer/nanoparticle hybrid microcapsules for controlled release.

Mechanical stimulus is one of the universally accessible physical ways of triggering the drug release from their carriers. Hollow microcapsules made of polyelectrolyte multilayers by conventional methods are not elastic enough to respond to a large and repetitive mechanical deformation. Here, hybrid hollow capsules comprising alternating layers of inorganic colloidal particles and biopolymers were prepared by the layer-by-layer approach followed by freezing-assisted crosslinking of polymer layers. The size of the capsule was controllable by the size of sacrificial cores. These hybrid capsules were mechanically more stable and recover faster than polyelectrolyte capsules, and could be recovered elastically even after large and repetitive deformation up to 98% relative to their original dimensions. Drugs in a wide range of molecular weight up to 70 kDa Mw could be loaded into the hollow hybrid microcapsules and the release of loaded contents from these hybrid capsules could be controlled through the deformation by applying a weak force such as a finger pressing on them. Mechanical stimuli-responsive delivery of model drugs was demonstrated on a monolayer of these hybrid capsules.