Evaluation of Ki-67 and p53 expression in primary and repeated liver metastases of GISTs

There has been little research evaluating changes related to tumor cell proliferation between primary and metastatic tumors of gastrointestinal tumors in the same case. We herein report the case of a 50-year-old woman with a gastric gastrointestinal stromal tumor (GIST), who developed metastatic liver tumors three times in the 7 years after proximal gastrectomy for GIST. The primary and all the metastatic liver tumors, except the second, showed fascicular/storiform architecture and the short spindle cell type. The diffuse epithelioid cell proliferation was observed in the second metastatic liver tumor. Although the immunostaining pattern with respect to GIST differentiation markers had been preserved in the primary tumor as well as in all of the metastatic tumors, the latter showed weaker positivity of both Ki-67 and p53 than the primary GIST. The primary tumor showed diffuse positive p53, and the highest value of Ki-67 labeling index (LI) among them. The metastatic liver tumors showed focal, negative or sporadic positive appearances of p53, however, Ki-67 LI were scattering among them. Immunohistochemical assessment of Ki-67 LI and p53 might be useful for evaluating changes related to tumor cell proliferation between primary and metastatic tumors of GISTs.     

Two-staged hepato-pancreatoduodenectomy and interventional pancreaticojejunostomy

Two-staged pancreatoduodenectomy, including exteriorization of the pancreatic juice and second-look pancreaticojejunostomy, has been recommended for high-risk patients to avoid pancreatic leakage, which often causes intra-abdominal hemorrhage. We present a new technique of interventional pancreaticojejunostomy under both fluoroscopy and endoscopy without second-look laparotomy. A 77-year-old woman with local recurrence and liver metastasis from colon cancer underwent hepato-pancreatoduodenectomy with the external drainage of pancreatic juice via the pancreatic duct tube without pancreaticojejunostomy. Two months later, the jejunum was punctured with the insertion of a 5-F needle-knife into the pancreatic fistula during endoscopic observation of jejunal lumen, followed by the insertion of two 0.35-inch guidewires into the jejunum and the pancreatic fistula. Finally, a 10-Fr stenting tube was placed between the jejunum and the pancreatic fistula. No complications developed.     

Extracellular and Intracellular Regulation of Biliary Lecithin Hydrophobicity

Bromosulfophthalein and papaverine have beendemonstrated to inhibit biliary lipid secretion withoutaffecting secretion of bile salts in normal rats,so-called uncoupling. Bromosulfophthalein inhibits the capacity of intracanalicular bile saltmicelles to induce biliary lipid secretion, andpapaverine inhibits vesicular transport within thehepatocyte. We compared the effects ofbromosulfophthalein and papaverine on biliary lipid secretion in normalSprague-Dawley rats and Eizai hyperbilirubinuria rats.The fatty acyl chain saturation in biliary lecithinincreased during bromosulfophthalein infusion and decreased during papaverine infusion inSprague-Dawley rats. Bromosulfophthalein had no effecton biliary lipid secretion in Eizai rats, whilepapaverine induced uncoupling. The degree of fatty acylchain saturation in biliary lecithin was unchangedduring bromosulfophthalein infusion, but decreased withpapaverine in Eizai rats. We deduce that selection ofbiliary lecithin species occurs at various points in the lipid transport pathway at intracellularand intracanalicular sites.     

Successful bridge therapy of gilteritinib to cord blood transplantation in relapsed acute myeloid leukemia after bone marrow transplantation

The FMS-related tyrosine kinase 3 (FLT3) internal tandem duplication mutations (FLT3-ITD) positive acute myeloid leukemia (AML) is a disease with a dismal outcome. Gilteritinib is a second-generation FLT3 inhibitor with activity against ITD and high affinity toward the FLT3 receptor, thereby showing therapeutic potential for relapsed/refractory FLT3-mutated AML. Bone marrow transplantation (BMT) from a human leukocyte antigen (HLA) identical sibling donor was performed in a 38-year-old Japanese male with FLT3-ITD positive AML. Neutrophil engraftment (>0.5 × 10⁹/L) was achieved on day 16, and bone marrow remission was revealed on day 32. The patient's AML relapsed hematologically four months after BMT and was resistant to salvage chemotherapy. Gilteritinib was administered and the patient achieved non-remission but ‘stable disease’ status according to the response criteria. During administration, liver damage was observed but controllable. The patient received cord blood transplantation (CBT) as the second hematopoietic stem cell transplantation (HSCT) three months after relapse and achieved second remission. There was no evidence of recurrence of AML four months after CBT. This case demonstrates that gilteritinib can control FLT3-ITD positive AML that relapsed early after initial HSCT and can bridge to second HSCT.     

Renal cell carcinoma with unusual metastasis to the gallbladder

Gallbladder involvement in patients with renal cell carcinoma (RCC) is extremely rare. We present a report of a 61-year-old man with a synchronous RCC metastasis to the gallbladder presenting as an intraluminal polypoid mass simulating primary gallbladder carcinoma. Enhanced abdominal computed tomography demonstrated a well-enhanced polypoid lesion in the gallbladder. Intraoperative rapid pathological examination of the gallbladder tumor showed clear cell-type cancerous cells. Microscopically, tumor cells of both the resected kidney and gallbladder had round uniform nuclei, clear cytoplasm, and well-defined cytoplasmic borders, forming alveolar patterns. Immunohistochemically, the tumor cells were negative for cytokeratin 7 (CK7) and carcinoembryonic antigen (CEA), which is usually positive in primary clear cell carcinoma of the gallbladder. Therefore, the final diagnosis was RCC with a synchronous gallbladder metastasis.