Treatment of delayed pancreatic fistula associated with anastomosis breakdown after pancreaticoduodenectomy using percutaneous interventions.

We here present a rare case of development of a postoperative pancreatic fistula and breakdown of the pancreaticojejunal anastomosis 8 months after pancreaticoduodenectomy. A 70-year-old man underwent pancreaticoduodenectomy for distal cholangiocarcinoma and initially recovered well. However, 8 months later, he developed abdominal pain and distention and was admitted to our institution with suspected pancreatitis. On the 17th day of hospitalization, he suddenly bled from the jejunal loop and a fluid collection was detected near the pancreaticojejunal anastomosis site. The fluid collection was drained percutaneously. Subsequent fistulography confirmed breakdown of the pancreaticojejunal anastomosis. Considering the patient's overall condition and the presence of postoperative adhesions, we decided to manage him conservatively. An additional drain tube was placed percutaneously from the site of the anastomotic breakdown into the lumen of the jejunum, along with the tube draining the fluid collection, creating a completely new fistula. This facilitated the flow of pancreatic fluid into the jejunum and was removed 192 days after placement. During a 6-month follow-up, there were no recurrences of pancreatitis or a pancreatic fistula. This case highlights the efficacy of percutaneous drainage and creation of an internal fistula as a management strategy for delayed pancreatic fistula and anastomotic breakdown following pancreaticoduodenectomy.

Gastric cancer complicated by paraneoplastic neurological syndrome which presented with extremity numbness: a case report.

BACKGROUND: Paraneoplastic neurological syndromes refer to a group of neurological disorders, which occur as distant effects of malignant tumors and are not caused by metastasis, nutritional disorders, or side effects of antitumor drugs. CASE PRESENTATION: A 70-year-old woman complained of a 1-month history of extremity numbness. Upon presentation to our hospital, she had worsening numbness, and experienced staggering and falling. Physical examination revealed diminished tendon reflexes in both lower limbs, stocking and glove-type abnormal sensation, and left-sided dominant high-steppage gait due to weakness of the bilateral tibialis anterior muscles. Blood tests indicated anemia, and upper gastrointestinal endoscopy revealed gastric cancer, leading to laparoscopic distal gastrectomy. A nerve conduction velocity test showed demyelinating peripheral neuropathy. Further blood tests and imaging studies ruled out nutritional disorders, such as vitamin deficiency, diabetes-related diseases, connective tissue diseases, and central nervous system metastasis, leading to the suspicion of paraneoplastic neurological syndrome. After laparoscopic distal gastrectomy, the progression of symptoms stopped, and with intravenous high-dose immunoglobulin and steroid therapy, the symptoms improved to only minor numbness in the peripheral limbs as of the 18-month follow-up. As of the 2-year follow-up, there has been no cancer recurrence or metastasis. CONCLUSIONS: When paraneoplastic neurological syndrome is suspected, early diagnosis and a multidisciplinary approach, including surgical treatment, are important before irreversible neurological damage occurs.

Pancreatic morphological abnormality that was challenging to differentiate from an ectopic pancreas: a case report.

BACKGROUND: Protrusion of the lateral contour of the pancreatic head is a pancreatic morphological abnormality, which is known as rare shape atypia. We present a rare case of protrusion of the lateral contour of the pancreatic head, which was challenging to distinguish from an ectopic pancreas. CASE PRESENTATION: The patient was a 40-year-old man with a history of acute pancreatitis that occurred twice in the past. He complained of epigastric pain since the day before the visit; his blood workup showed high serum amylase level and a CT scan revealed a 25-mm-large mass with contrast effect from the anterior wall of the gastric pylorus to the duodenum and increased surrounding fatty tissue density. Endoscopic ultrasonography revealed a mass lesion in the gastric pylorus with continuity with the gastric wall and suspected partial continuity with the pancreatic head. Thus, the possibility of pancreatic morphological abnormality or an ectopic pancreas was considered. Following which, resection was attempted and intraoperative findings showed a wide extension of the pancreatic parenchyma from the pancreatic head to the anterior wall of the gastric pylorus to the duodenal bulb. Since the patient only had mild pancreatitis, the resection was judged to be too invasive and was completed by exploratory laparoscopy. CONCLUSIONS: Even if the findings on preoperative CT are suspicious for an ectopic pancreas or tumor, a pancreatic morphological abnormality, such as a protrusion of the lateral contour of the pancreatic head, should be included in the differential diagnosis.

[A case of gastric mixed neuroendocrine-non-neuroendocrine neoplasm that developed five years after pancreatic neuroendocrine tumor treatment].

We present a case of 63-year-old male patient who underwent subtotal stomach-preserving pancreaticoduodenectomy for pancreatic neuroendocrine tumor (NET) G2. He had been followed up for three years and had no signs of recurrence postoperatively. Five years after surgery, he had abdominal pain. Upper gastrointestinal endoscopy showed a gastric tumor. Laparoscopic distal gastrectomy was performed without postoperative complications. The histopathological findings of the resected specimen were consistent with mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN). The immunohistochemical characteristics of the gastric MiNEN lesion were different from those of the pancreatic NET lesion resected five years ago, suggesting that those lesions were heterochronous.

[A Case of Surgical Resection of a Combined Hepatocellular and Cholangiocarcinoma with Hemobilia from Intraductal Tumor Thrombus].

We report a case of combined hepatocellular and cholangiocarcinoma with hemobilia. A 65-year-old man was admitted to our hospital because of pain in the right hypochondralrigion. Abdominal ultrasonography revealed bile duct dilatation in the lateral segment of liver and blood test findings showed elevation of the hepatobiliary enzyme, so ERC was performed and hemorrhage from the duodenal papilla was observed. In cholangiography, dilation of the left hepatic bile duct and filling defect were observed, and in the peroral cholangioscopy, a hemorrhagic papillary elevated lesion was identified in the left hepatic bile duct and diagnosed as adenocarcinoma as a result of biopsy. Left hepatectomy with caudate lobe, extrahepatic bile duct resection, lymph node dissection was performed by diagnosis of intrahepatic cholangiocarcinoma. In the resected specimen, tumor size was 16 mm, which was found in the left hepatic duct and invasived into the liver parenchyma. Histopathological examination revealed a combined hepatocellular and cholangiocarcinoma. Gemcitabin was administered as adjuvant chemotherapy for 8 months, but 1 year and 8 months after the operation, it recurred in the liver. Gemcitabin was administered, but it became PD, now it has changed to S-1 and it is SD for 2 years.

[Four Cases of Gastrointestinal Perforation Associated with Bevacizumab].

Four cases of gastrointestinal perforation associated with bevacizumab(BEV)were examined. Case 1: A 82-year-old male received FOLFIRI plus BEV for recurrent liver metastasis after rectal cancer resection. A lower esophageal perforation occurred 22 days after BEV administration and drainage was performed. Case 2: A 69-year-old female received FOLFOX4 plus BEV for unresectable rectal cancer and liver and lung metastasis. A rectal perforation occurred 6 days after BEV administration and suturing closure of the hole and colostomy was performed. Case 3: A 69-year-old female, received carboplatin(CBDCA) plus pemetrexed(PEM)plus BEV for unresectable left lung cancer and adrenal gland and lymph node metastasis. A small intestinal perforation occurred 15 days after BEV administration and ileocecal resection and primary anastomosis was performed. Case 4: A 73-year-old female received CBDCA plus PEM plus BEV for unresectable left lung carcinoma and pleural metastasis. A diverticulum of sigmoid colon perforation occurred 30 days after BEV administration and suturing closure of the hole and colostomy was performed. When we observe fever, abdominal pain, elevation of the inflammatory reaction after BEV administration, we should immediately examine gastrointestinal perforation.

[A case of complete response to multiple liver metastasis of gastric cancer after discontinuation of S-1 administration].

An 80-year-old man was diagnosed with advanced gastric cancer and underwent distal gastrectomy. Although the pathological Stage of the cancer was III A, he refused adjuvant chemotherapy. One year later, CT revealed multiple liver metastases. Therefore, he was started with S-1 administration and a complete response was obtained at 10 months after starting S-1 administration. He has maintained a complete response for 22 months after S-1 discontinuation.

Anoikis induction and inhibition of peritoneal metastasis of pancreatic cancer cells by a nuclear factor-κB inhibitor, (-)-DHMEQ.

The transcription factor nuclear factor-κB (NF-κB) plays a crucial role in pancreatic cancer (PC) progression. NF-κB is also involved in resistance to anoikis, a special type of apoptosis induced when cells are detached from the extracellular matrix or other cells. Anoikis resistance is related to the metastatic abilities of tumor cells; however, little is known about anoikis induction as it relates to inhibition of PC metastasis by NF-κB inhibitors. Here we used a specific NF-κB inhibitor, (-)-dehydroxymethylepoxyquinomicin (DHMEQ), to investigate anoikis induction and peritoneal metastasis suppression following NF-κB inhibition. We transduced Gluc, a secretory form of luciferase, into a PC cell line, AsPC-1 (AsPC-1-Gluc), for our in vivo experiments. (-)-DHMEQ induced anoikis in AsPC-1-Gluc cells as measured by cell survival assays and flow cytometry. The DNA-binding activity of p65 was enhanced immediately after cell detachment from culture dishes in ELISA assays. Some antiapoptotic proteins such as cellular inhibitor of apoptotic protein-1 were consequently upregulated on Western blots. (-)-DHMEQ prevented this increase in p65 activity and the subsequent expressions of antiapoptotic molecules. In a murine xenograft model, anoikis-resistant PC cell lines tended to metastasize to the peritoneum more than anoikis-sensitive cells, suggesting a correlation between anoikis sensitivity and peritoneal metastasis. (-)-DHMEQ successfully inhibited peritoneal metastasis of AsPC-1-Gluc cells. We monitored metastasis inhibition by ex vivo chemiluminescent detection of Gluc secreted from tumor cells into murine plasma and by in vivo imaging. Our results suggest that (-)-DHMEQ inhibited peritoneal dissemination by preventing anoikis resistance of PC cells.

Recurrence of primary squamous cell carcinoma of the ileum diagnosed by elevation of serum SCC: report of a case.

Primary squamous cell carcinoma of the intestine is extremely rare. This report describes a patient with primary squamous cell carcinoma of the small intestine. A 72-year-old Japanese woman was referred to our hospital because of a diagnosis of intestinal obstruction. She underwent laparotomy owing to the diagnosis of mechanical intestinal obstruction due to a pelvic mass after conservative treatment. The affected ileum was resected, and histopathological examination revealed proliferation of differentiated squamous cell carcinoma at the submucosal area with no adenocarcinoma component. At the 4th month after the operation, the level of serum squamous cell carcinoma (SCC) antigen was elevated. At 6 months after the operation, the serum SCC value was further elevated, and enhanced CT revealed two new pelvic tumors with enhancement at the mesentery and free space. A second laparotomy was performed 8 months after the operation. Histopathological examination showed differentiated squamous cell carcinoma as in the first operation. The level of serum SCC decreased at the 28th postoperative day. Chemotherapy including carboplatin and paclitaxel was performed as an adjuvant regimen. The patient has experienced no recurrence of squamous cell carcinoma for 55 months.

Inhibition of nuclear factor-kappaB suppresses peritoneal dissemination of gastric cancer by blocking cancer cell adhesion.

Currently, patients with peritoneal dissemination of gastric cancer must accept a poor prognosis because there is no standard effective therapy. To inhibit peritoneal dissemination it is important to inhibit interactions between extracellular matrices (ECM) and cell surface integrins, which are important for cancer cell adhesion. Although nuclear factor-kappa B (NF-κB) is involved in various processes in cancer progression, its involvement in the expression of integrins has not been elucidated. We used a novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), to study whether NF-κB blocks cancer cell adhesion via integrins in a gastric cancer dissemination model in mice and found that DHMEQ is a potent suppressor of cancer cell dissemination. Dehydroxymethylepoxyquinomicin suppressed the NF-κB activity of human gastric cancer cells NUGC-4 and 44As3Luc and blocked the adhesion of cancer cells to ECM when compared with the control. Dehydroxymethylepoxyquinomicin also inhibited expression of integrin (α2, α3, ß1) in in vitro studies. In the in vivo model, we injected 44As3Luc cells pretreated with DHMEQ into the peritoneal cavity of mice and performed peritoneal lavage after the injection of cancer cells. Viable cancer cells in the peritoneal cavities were evaluated sequentially by in vivo imaging. In mice injected with DHMEQ-pretreated cells and lavaged, live cancer cells in the peritoneum were significantly reduced compared with the control, and these mice survived longer. These results indicate that DHMEQ could inhibit cancer cell adhesion to the peritoneum possibly by suppressing integrin expression. Nuclear factor-kappa B inhibition may be a new therapeutic option for suppressing postoperative cancer dissemination.

In vivo far-red luminescence imaging of a biomarker based on BRET from Cypridina bioluminescence to an organic dye.

We aimed to develop a far-red luminescence imaging technology for visualization of disease specific antigens on cell surfaces in a living body. First, we conjugated a far-red fluorescent indocyanine derivative to biotinylated Cypridina luciferase. This conjugate produced a bimodal spectrum that has long-wavelength bioluminescence emission in the far-red region as a result of bioluminescence resonance energy transfer. To generate a far-red luminescent probe with targeting and imaging capabilities of tumors, we then linked this conjugate to an anti-human Dlk-1 monoclonal antibody via the biotin-avidin interaction. This far-red luminescent probe enabled us to obtain high-resolution microscopic images of live, Dlk-1-expressing Huh-7 cells without an external light source, and to monitor the accumulation of this probe in tumor-bearing mice. Thus this far-red luminescent probe is a convenient analytical tool for the evaluations of monoclonal antibody localization in a living body.

[Case report--postoperative continuous intraarterial infusion of small doses of 5-FU successfully controlled residual tumor and liver metastasis of stage IV gastric cancer].

A sixty-eight-year-old man was operated on for Stage IV gastric cancer with total gastrectomy and D3 lymph node dissection. The right gastric artery was filled with tumor thrombosis, but tumor tissue was left on the cut stump. Intraoperative ultrasonic liver scanning revealed the suspected metastatic images. Mitomycin C 20 mg dissolved in glue was then pasted at the artery cut stump. Although intraarterial infusion of adriamycin 20 mg, systemic methotrexate + 5-FU alternative therapy and daily medication of UFT-E 400 mg were administered, liver metastasis developed in follow-up CT scans 6 months later. Since 9 months after operation,continuous intraarterial infusion of 5-FU 250 mg/24 hours for 7 days was given biweekly, and was repeated 44 times for the next 27 months. This chemotherapeutic modality purged the liver metastasis. The patient has now survived 7 years 3 months with no therapy.

A novel leflunomide derivative, FK778, for immunosuppression after kidney transplantation in dogs.

BACKGROUND: Leflunomide and its metabolite, A77 1726, interfere with pyrimidine metabolism and exert potent immunosuppression in experimental organ transplantation. However, clinical use of the agents has been restrained because of an extended half-life. FK778, one synthetic malononitrilamide derived from A77 1726, is synthesized to overcome this problem while maintaining similar therapeutic efficacy. METHODS: Immunosuppressive effect, pharmacokinetics, and adverse events of FK778, as a single drug treatment or combination with tacrolimus or cyclosporine, were determined in a canine kidney transplantation model. The agents were daily administered orally to the animals for 90 days after surgery. Animal survival, pharmacokinetics, biochemistry, hematology, and histopathology were evaluated. RESULTS: FK778 at 4 mg/kg prolonged median survival of the control animals from 10 days to 30.5 days. Administration of 4 mg/kg FK778 with 0.3 mg/kg tacrolimus or 10 mg/kg cyclosporine increased median survival to 75.5 days and 50.5 days, respectively. In combined treatments, trough levels of FK778 at 4 mg/kg ranged between 40 microg/mL and 100 microg/mL after 1 month. Vomiting and diarrhea were common in animals given FK778. Bone marrow suppression was seen at higher doses. CONCLUSIONS: FK778 is a promising new immunosuppressant that may be used in combination with current standard drugs in organ transplantation.