Impact of Concomitant Thiopurine on the Efficacy and Safety of Filgotinib in Patients with Ulcerative Colitis: Post hoc Analysis of the Phase 2b/3 SELECTION Study

BACKGROUND AND AIMS: SELECTION is the first study to assess the impact of concomitant thiopurine and other immunomodulator [IM] use on the efficacy and safety of a Janus kinase inhibitor, filgotinib, in patients with ulcerative colitis. METHODS: Data from the phase 2b/3 SELECTION study were used for this post hoc analysis. Patients were randomized [2:2:1] to two induction studies [biologic-naive, biologic-experienced] to filgotinib 200 mg, 100 mg, or placebo. At week 10, patients receiving filgotinib were re-randomized [2:1] to continue filgotinib or switch to placebo until week 58 [maintenance]. Outcomes were compared between subgroups with and without concomitant IM use. RESULTS: At week 10, a similar proportion of patients in +IM and -IM groups treated with filgotinib 200 mg achieved Mayo Clinic Score [MCS] response [biologic-naive: 65.8% vs 66.9%; biologic-experienced: 61.3% vs 50.5%] and clinical remission [biologic-naive: 26.0% vs 26.2%; biologic-experienced: 11.3% vs 11.5%]. At week 58, a similar proportion of patients in +IM and -IM groups treated with filgotinib 200 mg achieved MCS response [biologic-naive: 74.2% vs 75.0%; biologic-experienced: 45.5% vs 61.4%] and clinical remission [biologic-naive: 51.6% vs 47.4%; biologic-experienced: 22.7% vs 24.3%]. The probability of protocol-specified disease worsening during the maintenance study in patients treated with filgotinib 200 mg did not differ between +IM and -IM groups [p = 0.6700]. No differences were observed in the incidences of adverse events between +IM and -IM groups in induction/maintenance studies. CONCLUSIONS: The efficacy and safety profiles of filgotinib treatment in SELECTION did not differ with or without concomitant IM use

A Case of Ischemic Colonic Stenosis of the Splenic Flexure

Ischemic colitis is characterized by lesions arising from colonic ischemia. The treatment of choice is surgery, and resection of the affected segment is often life saving. This study presents a case of segmental ischemic colonic stenosis of the splenic flexure. A 70-year-old woman was admitted to our hospital with abdominal pain and distension. Physical examination revealed mild tenderness of the left-upper abdomen but no peritoneal signs. A computed tomography scan demonstrated a thickening of the splenic flexure of the colon with active inflammation. A gastrografin enema revealed a 5-cm-long tight stricture at the left transverse colon, which suggested a subileus. Surgery for segmental ischemic colonic stenosis was performed because the stricture did not respond to treatment. Pathological examination revealed features typical of ischemic colitis, including ulceration and segmental colonic stenosis of the splenic flexure, but revealed no evidence of tumors, lymph node swelling, or vascular disorder

A Case of Single-Incision Laparoscopic Surgery for Lipoma of the Terminal Ileum

A 52-year-old woman presented with a right lower abdominal mass, lower abdominal pain, and distension in July 2011. She had myasthenia gravis, but did not have any surgical history. Clinical examination showed a right lower abdominal mass, abdominal distension, decreased bowel sounds, and rebound tenderness in the lower abdomen. Abdominal computed tomography showed an intussusception involving the ileocecal junction. A gastrografin enema image of the colon showed a 30-mm filling defect in the ascending colon. The patient underwent resection of the intussuscepted intestine by single-incision laparoscopic surgery (SILS). The resected specimen contained a round tumor measuring 35 × 35 × 20 mm, which was diagnosed histopathologically as lipoma of the terminal ileum. The patient remains asymptomatic eight months after surgery

A Case of Gallstone Ileus

A 57-year-old woman was admitted to our hospital with abdominal pain and vomiting. Her abdomen was distended, and obstructive bowel sounds were discovered on examination. Diffuse abdominal tenderness was present, but no palpable masses were apparent. Abdominal computed tomography confirmed a large gallstone obstructing the small bowel. Colonoscopy revealed a large gallstone lodged at the terminal ileum, which was subsequently fragmented using electronic hydraulic lithotripsy (EHL). The patient has remained asymptomatic for over 3 years of follow-up after the EHL treatment. Here, we present this case of small intestinal obstruction caused by a large gallstone in the lower ileum

Gut Cryptopatches Direct Evidence of Extrathymic Anatomical Sites for Intestinal T Lymphopoiesis

AbstractAthymic cytokine receptor γ chain mutant mice that lack the thymus, Peyer's patches, cryptopatches (CP), and intestinal T cells were reconstituted with wild-type bone marrow cells. Bone marrow–derived TCR− intraepithelial lymphocytes (IEL) first appeared within villous epithelia of small intestine overlying the regenerated CP, and these TCR− IEL subsequently emerged throughout the epithelia. Thereafter, TCR+ IEL increased to a comparable number to that in athymic mice and consisted of TCRγδ and TCRαβ IEL. In gut-associated lymphoid tissues of wild-type mice, only CP harbored a large population of c-kithighIL-7R+CD44+Thy-1+/−CD4+/−CD25low/−αEβ7−Lin− (Lin, lineage markers) lymphocytes that included cells expressing germline but not rearranged TCRγ and TCRβ gene transcripts. These findings provide direct evidence that gut CP develop progenitor T cells for extrathymic IEL descendants

Anastomotic Recurrence due to Tumor Implantation using the Double Stapling Technique after Curative Surgery for Sigmoid Colon Cancer

Recurrence at the site of a stapled anastomosis is generally believed to result from the luminal implantation of viable cancer cells during stapling. We report a 57-year-old woman who underwent radical surgery for sigmoid colon cancer and developed anastomotic recurrence ten months after the initial operation. Her serum carcinoembryonic antigen (CEA) levels were within normal limits during the postoperative follow-up. The patient subsequently underwent a partial colon resection for the anastomotic recurrence. The clinicopathological findings revealed that possible tumor cell implantation caused the recurrence. We encountered a case of anastomotic recurrence due to possible tumor implantation after curative surgery for sigmoid colon cancer. Follow-up colonoscopy was more helpful for the diagnosis of anastomotic recurrence than CEA monitoring

Strangulation Caused by a Small Bowel Epiploic Appendage: Report of a Case

While many recent cases of colonic epiploic appendage causing acute abdomen have been reported, such appendages of the small bowel are extremely rare. We present a 59-year-old woman in whom a small bowel epiploic appendage caused volvulus. She presented with abdominal pain and vomiting in the absence of previous abdominal operations. A diagnosis of small bowel obstruction from strangulation was made. Laparotomy disclosed bloody peritoneal fluid and a closed loop of strangulated small intestine. An adherent band composed of an epiploic appendage and intestine had completely encircled a loop of jejunum, leading to obstruction. This band was released, and approximately 80 cm of gangrenous bowel was resected. Four epiploic appendages 5–6 cm in length were attached to the ileum at the mesenteric border, beginning at a point 70 cm proximal to the terminal ileum