Diaphragmatic Hernia Repair After Esophagectomy: Technical Report and Lessons After a Series of Cases.

Introduction: Diaphragmatic hernia (DH) repair after esophagectomy is infrequent and technically challenging. Such hernias are mostly asymptomatic and have an estimated incidence of around 2.5%. Controversy continues over suture versus mesh cruroplasty. This article reports a series of cases and a description of the technique, showing this type of procedure being performed in the medical literature and its results. Methods: A DH was diagnosed, and repair was performed in eight out of 328 esophagectomies. All of them were performed through the following steps: (1) Pulling the hernia content down properly without handling the intestinal segment directly to not promote serosal lesions; (2) Lysis of adhesions-this should be done close to the diaphragmatic pillar, with precaution toward the vessels running in the epiplon and near the greater gastric curvature; and (3) Closure of the diaphragmatic hiatus achieved with anterior and posterior sutures. Mesh repair was performed across the DH defects that measured more than 5.5 cm. Results: The patients constituted five men (62.5%) with a mean age of 61.6 years. The main DH-related symptom was abdominal pain, reported by four patients (50%). The other symptoms mentioned were dyspnea (37.5%), thoracic pain (25%), and dysphagia (25%). The mean hospitalization period was 17.5 days and was related to the restoration of the respiratory function. Most of the DH repairs were performed by adopting a laparoscopic approach. Conclusions: DH is a rare complication following esophagectomy with most of the symptomatic manifestations. However, its repair is feasible and safe, with low morbidity (only respiratory complications) and no mortality.

Solid-State Characterization of Different Crystalline Forms of Sitagliptin.

Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase-4, used for the treatment of type 2 diabetes mellitus. The crystal structure of active pharmaceutical solids determines their physical and chemical properties. The polymorphism, solvates and hydrates can influence the free energy, thermodynamic parameters, solubility, solid-state stability, processability and dissolution rate, besides directly affecting the bioavailability. Thus, the physicochemical characterization of an active pharmaceutical ingredient is required to guarantee the rational development of new dosage forms. In this context, we describe herein the solid-state characterization of three crystalline forms of sitagliptin: sitagliptin phosphate monohydrate, sitagliptin phosphate anhydrous and sitagliptin base form. The investigation was carried out using differential scanning calorimetry (DSC), thermogravimetry (TG)/derivative thermogravimetry (DTG), spectroscopic techniques, X-ray powder diffraction (XRPD) and morphological analysis by scanning electron microscopy. The thermal analysis revealed that during the dehydration of sitagliptin phosphate monohydrate (Tpeak = 134.43 °C, ΔH = -1.15 J g-1) there is a characteristic crystalline transition event, which alters the physicochemical parameters of the drug, such as the melting point and solubility. The crystalline behavior of sitagliptin base form differs from that of sitagliptin phosphate monohydrate and sitagliptin phosphate anhydrous, mainly with regard to the lower temperature of the fusion event. The melting point (Tpeak) values obtained were 120.29 °C for sitagliptin base form, 206.37 °C for sitagliptin phosphate monohydrate and 214.92 °C for sitagliptin phosphate anhydrous. In relation to the thermal stability, sitagliptin phosphate monohydrate and sitagliptin phosphate anhydrous showed a slight difference; however, both are more thermostable than the base molecule. Therefore, through this study it was possible to establish the most suitable crystalline form of sitagliptin for the development of a safe, effective and appropriate pharmaceutical dosage form.

Physico-chemical solid-state characterization of omeprazole sodium: thermal, spectroscopic and crystallinity studies.

The physical characterization of active pharmaceutical substances is crucial to the successful development of the final drug product. The different solid forms and variations in the degree of crystallinity can lead to significantly different physical and chemical properties, including color, morphology, stability, dissolution and bioavailability. In the case of omeprazole sodium (OMS), its chemical structures contain a specific number of water molecules (hydrate). The behavior of pharmaceutical hydrates has become the object of increasing attention over the past decade, primarily due to the potential impact of hydrates on the development process and dosage form performance. The present study was designed to characterize and evaluate the crystallinity of omeprazole sodium, dehydrated omeprazole sodium (DOMS) and omeprazole free base (OM) using a variety of techniques including thermal analysis (thermogravimetry/derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC)), diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, scanning electron microscopy (SEM) and X-ray powder diffraction (XRPD). Furthermore, an NMR spectroscopy study was also carried out to clarify the conformation and crystal structure.