The Influence of Fed State Lipolysis Inhibition on the Intraluminal Behaviour and Absorption of Fenofibrate from a Lipid-Based Formulation

The bioavailability of lipophilic drugs may or may not be increased when administered with food due to increased solubilisation in fed state gastrointestinal (GI) fluids. The in vivo interplay between drug solubilisation, lipid phase digestion and drug absorption is complex and remains poorly understood. This study aimed to investigate the role of fed state GI lipolysis on the intraluminal behaviour and absorption of fenofibrate, formulated as the lipid-based formulation Fenogal. Therefore, a crossover study was performed in healthy volunteers using orlistat as lipase inhibitor. Fenofibrate concentrations were determined in the proximal jejunum and linked to simultaneously assessed systemic fenofibric acid concentrations. Inhibition of lipolysis by orlistat resulted in a faster onset of absorption in 4 out of 6 volunteers, reflected by a decrease in systemic Tmax between 20 and 140 min. In addition, the increase of undigested lipids present in the small intestine upon orlistat co-administration sustained drug solubilisation for a longer period, resulting in higher fenofibrate concentrations in the jejunum and improved absorption in 5 out of 6 volunteers (median AUC0–8h 8377 vs. 5832 μM.min). Sustaining drug solubilisation in the lipid phase may thus contribute to the absorption of lipophilic drugs. More research into the different mechanisms underlying lipophilic drug absorption from fed state media at different levels of digestion is warranted.

Diagnosis and endoscopic intervention in rare MALT lymphoma of the proximal jejunum

Summary: Extranodal lymphoma from the marginal zone mucosa-associated lymphoid tissue (MALT lymphoma) is one of the primary extranodal non-Hodgkin‘s lymphomas with low degrees of malignancy but with the risk of spreading to distant locations in the body. B-lymphomas are sometimes associated with other diseases (eg. Helicobacter pylori and Campylobacter jejuni infections or inflammatory bowel disease). B-lymphomas may manifest with a variety of clinical signs, from dyspeptic syndrome with malabsorption and weight loss to ileus or massive gastrointestinal bleeding. Dia­gnosis is based on the clinical condition and the results of laboratory tests and imaging techniques, while endoscopy is the essential procedure for visualizing the tumor mass and collecting a bio­psy sample to determine the definitive histopathological dia­gnosis. MALT lymphoma treatment is managed by oncologists and includes chemotherapy and/or radiotherapy, with resection indicated in rare cases. In this case report we present an elderly female patient who was referred to our IBD centre for non-specific abdominal pain with a positive fecal occult blood test. Computed tomography (CT) examination was used before endoscopy and showed an infiltration of the splenic flexure by an unspecified mass, a subsequent colonoscopy showed intact mucosa of the colon, including the terminal ileum. In the second reading of the CT scan the location of the infiltrate was identified more specifically as the area of the proximal jejunum and jejunal mesentery. Subsequent upper endoscopy revealed a stenosing exulcerated tumor in the proximal jejunum, with the stenosis impassable even for a pediatric colonoscope. The dia­gnosis of MALT lymphoma was confirmed by a histological examination of the bio­psied tissue. A follow-up upper endoscopy was performed after the patient had completed her oncological treatment (chemotherapy in combination with radiotherapy), showing the presence of stenosis at the proximal jejunum, still impassable for the endoscope. In clinical terms, the patient experienced weight loss, which was to some extent caused by intermittent pseudo-obstruction when on a solid diet, therefore we decided to enrich her oral intake with high-calorie sip feed. The next follow-up CT scan of the abdomen showed a regression of the infiltrate, but the stenosis of the proximal jejunum, about 7 centimeters long, persisted. To respect the patient‘s wishes, no surgical resection of the stenotic section of the intestine was performed, but we proceeded with endoscopic dilatation of the stenotic section of the jejunum with a balloon. After the first two endoscopic dilatations of the stenotic area the patient experienced a temporary improvement in solid food tolerance. Because of restenosis, a third endoscopic dilatation was performed, with the development of complications that included short-term circulatory instability with abdominal pain and eventually required an urgent surgical solution. Key words: marginal zone B-cell lymphoma – stenosis – dilatation – intestinal perforation – jejunum – MALT

Rapunzel syndrome: an uncommon tale of a long hairy tail - case report and review of literature

Trichobezoar is a rare clinical entity in which a ball of hair accumulates within the alimentary tract. When the tail of the trichobezoar extends into the small intestine, this condition is called Rapunzel syndrome (RS). A 14-year-old female presented with pain abdomen and vomiting for 2 weeks, and a history of trichotillomania and trichophagia, and an epigastric lump. A contrast enhanced computerized tomography (CECT) of the abdomen showed a grossly distended stomach with a heterogeneous mass containing trapped air with underlying normal mucosa suggestive of trichobezoar, with its tail extending into the proximal jejunum suggestive of RS. During laparotomy, a giant trichobezoar was seen in the stomach with its tail extending beyond the duodenum into the proximal jejunum. The entire specimen was delivered out intact. On follow up, she has no surgical complications, and was on behaviour therapy. Trichobezoars form when ingested hair strands become retained in the folds of the gastric mucosa and becomes entangled, forming a ball too large to exit the stomach. Trichotillomania and trichophagia are seen in many of these patients. Patients present with abdominal pain, vomiting, gastric outlet obstruction, and an epigastric mass. In the case of RS, complete removal without breakage and distal migration is important. RS should be considered as a differential diagnosis in a young girl with abdominal pain, vomiting, anaemia and upper abdominal lump. Early diagnosis prevents complications. Surgical removal is treatment of choice. Trichobezoar often coexists with psychiatric illness. Psychiatric evaluation, counselling and treatment are helpful in preventing recurrence.

Dysgeusia Due to Zinc Deficiency After Pancreaticoduodenectomy Requiring Continuous Intravenous Zinc Supplementation: a Case Report and Literature Review

Background: Zinc is mainly absorbed in the duodenum and proximal jejunum, which are removed during pancreaticoduodenectomy (PD). Little is known about the adverse oral events and skin disorders caused by zinc deficiency after PD. Herein, we reviewed studies regarding the development of zinc deficiency after PD and presented the case of a patient with zinc deficiency after PD, who required home intravenous zinc replacement.Case presentation: A 73-year-old woman with glossitis, taste disorder, and acrodermatitis enteropathica-like eruption on her fingers presented to the Division of Dentistry and Oral Surgery 69 days after PD. Her serum zinc level markedly decreased to 30 μg/dL. Oral zinc administration was inadequate to treat hypozincemia after PD; therefore, multi-trace elements were injected intravenously under readmission. Her serum zinc levels recovered, and the lesions gradually improved. Furthermore, a central venous port was implanted to maintain normal serum zinc levels, and she continued self-injecting zinc at home.Conclusion: Zinc deficiency after PD rarely occurs. The clinical oncologist community, including dentists responsible for the oral care of cancer patients, should be aware of dysgeusia associated with zinc deficiency after cancer surgery, as well as that induced by chemotherapy or head and neck radiation therapy.

CASE REPORT OF GASTRO-INTESTINAL STROMAL TUMOR (GIST)

GISTs are the most common sarcomatous tumors of GI tract, usually found in stomach and duodenum. Mostly GISTs arise as a de novo. Frequently present with hematemesis, melena and abdominal pain but sometimes diagnosed incidentally. CECT abdomen with pelvis is important to see the origin and extension of the tumor and to assess for metastasis. A 52 year old male admitted for left sided abdominal pain for 7 to 8 year and on examination lump is palpable in epigastrium, umbilical and left hypochondriac region. CT abdomen suggestive of mass arising from proximal jejunum. The patient underwent a surgical resection with free margins and had an uneventful recovery.

A Rare Case of Chronic Suppurative Appendicitis in Neonatal Presenting as Intestinal Malrotation

Neonatal appendicitis (NA) is an extremely rare acute abdomen condition, moreover, if it is a chronic suppurative one. The definite risk factor of NA is barely unknown. The signs and symptoms are often nonspecific and appear after perforation occurs. Most of the cases were found unexpectedly during surgery suspected as other diagnoses. A 7-day-old male neonate presenting lethargic and hypoglycemia since 1 st day of life. Patient drunk breast milk right after since he was born. Meconium was produced <24 h. On the 3 rd day of hospitalization, he experienced bilious vomiting and abdominal distension, so nasogastric tube was installed. Physical examination revealed decreased bowel sound. Investigation showed leucocytosis, slightly increased procalcitonin and abdominal X-ray showed that gas distribution lasted until third part of duodenum followed by minimal gas distribution in the distal part of duodenum. The patient was suspected as distal duodenum stenosis or proximal jejunum. Intraoperatively, it was found that there was second part duodenum malrotation and open Ladd’s procedure was done. During Ladd’s procedure, a perforated appendix was also found. The histopathology result revealed that it was a chronic suppurative appendicitis. Patient was discharged in good condition 20 days after surgery. NA is a rare condition with nonspecific signs and symptoms which was usually found accidentally during surgery suspected as other diagnoses.

Nanoparticulate Drug Delivery Strategies to Address Intestinal Cytochrome P450 CYP3A4 Metabolism towards Personalized Medicine

Drug dosing in clinical practice, which determines optimal efficacy, toxicity or ineffectiveness, is critical to patients’ outcomes. However, many orally administered therapeutic drugs are susceptible to biotransformation by a group of important oxidative enzymes, known as cytochrome P450s (CYPs). In particular, CYP3A4 is a low specificity isoenzyme of the CYPs family, which contributes to the metabolism of approximately 50% of all marketed drugs. Induction or inhibition of CYP3A4 activity results in the varied oral bioavailability and unwanted drug-drug, drug-food, and drug-herb interactions. This review explores the need for addressing intestinal CYP3A4 metabolism and investigates the opportunities to incorporate lipid-based oral drug delivery to enable precise dosing. A variety of lipid- and lipid-polymer hybrid-nanoparticles are highlighted to improve drug bioavailability. These drug carriers are designed to target different intestinal regions, including (1) local saturation or inhibition of CYP3A4 activity at duodenum and proximal jejunum; (2) CYP3A4 bypass via lymphatic absorption; (3) pH-responsive drug release or vitamin-B12 targeted cellular uptake in the distal intestine. Exploitation of lipidic nanosystems not only revives drugs removed from clinical practice due to serious drug-drug interactions, but also provide alternative approaches to reduce pharmacokinetic variability.

Outcomes Assessment between Hand Sewn and Stapled Intestinal Anastomosis

Objective: This study was conducted at the Department of Surgery of Liaquat University of Medical & Health Sciences, Jamshoro, Sindh, Pakistan for comparing the effectiveness of both methods: hand sewn and stapled intestinal anastomosis and to find a better comparatively to be more efficient. Methods: A total of 70 patients were encompassed who underwent intestinal anastomoses from proximal jejunum to 2/3rd of proximal distal rectum. All patients were assigned to two different groups A and B each encompassing of 35 cases. In group A, the single layer continuous and in group B single layer patients intervallic serosubmucosal anastomosis was made by implementing the stitches approximately 6 mm at a distance integrating around 5.5 mm of the gut in its stretched direction axis evading individual mucosa. The patients were observed post operatively for anastomotic fiasco such as leakage. Results: Fourteen (14) out of 35 (2.5%) patients in group A developed anastomotic leakage . In group B, the interrupted serosubmucosal anastomoses were made in 26 patients in emergency and remaining were operated schedule wise. Five (7%) patients exhibited anastomotic leakage in group B. In group A, the continuous leakage in serousubmucosal anastomosis was 2.5% while in group B interrupted serousubmucosal anastomosis was 7%. Conclusion: It has observed in past studies that single layer interrupted stitches leakage is higher as compared to continuous. It is clear that anastomotic failure in group A is greater than group B but it not considerably substantial and hence both are remarkably efficient.

Case Report: Concurrent Occurrence of Abdominal Double Expressor Lymphoma and Jejunum Follicular Lymphoma

Double expressor lymphoma (DEL), defined as overexpression of BCL2 and MYC, is an aggressive subtype of diffuse large B cell lymphoma (DLBCL). Here we report a case of a 64-year-old female diagnosed with abdominal DEL transformed from jejunum follicular lymphoma (FL). 18F-fluorodeoxyglucose (FDG)-positron emission tomography showed diffuse accumulation of FDG into the peritoneum and small bowel wall. Double balloon-assisted enteroscopy revealed whitish submucosal tumors in the proximal jejunum. Aggregation of atypical lymphocytes positive for CD20, CD79a, and BCL2 was seen in the jejunal biopsy samples. These atypical lymphocytes were monoclonal since cell surface expression of Ig light chains was limited to κ chain by flow-cytometry. Thus, immunohistochemical and flowcytometric analyses data were consistent with FL of the jejunum. Neoplastic lymphocytes obtained from ascites were positive for CD10, CD20, CD79a, BCL2, and BCL6. Fluorescence in situ hybridization (FISH) showed formation of BCL2/IgH fusion gene and extra copies of MYC, the former of which is a characteristic chromosomal abnormality of FL. These genetic alterations and protein expression profiles of ascitic fluid cells were consistent with those of DEL transformed from FL. Given that a significant population of patients with indolent FL of the gastrointestinal tract developed into aggressive DLBCL, it is likely that primary FL of the jejunum transformed into the abdominal aggressive DEL in this case. This case is unique in that concurrent occurrence of FL and DEL was confirmed by immunohistochemical and FISH analyses and that abdominal DEL transformed from jejunal FL was highly suspected.