Adjuvant 5-fluorouracil and portal vein infusion chemotherapy followed by gemcitabine for pancreatic cancer.

BACKGROUND: Although adjuvant gemcitabine (GEM) monotherapy improves the overall survival (OS) of patients with resected pancreatic cancer, its efficacy requires further improvement. This multicenter, phase II study investigated the efficacy of adjuvant portal vein infusion (PVI) chemotherapy followed by GEM therapy in patients with resected pancreatic cancer. METHODS: 5-fluorouracil (250 mg/day) and heparin (2000 IU/day) PVI chemotherapy were combined with systemic administration of mitomycin C (4 mg; days 6, 13, 20, and 27) and cisplatin (10 mg; days 7, 14, 21, and 28) for 4 weeks (PI4W), followed by GEM (1000 mg/m2; days 1, 8, and 15 every 4 weeks for 6 months). The primary endpoint was relapse-free survival (RFS) and the secondary endpoints were OS and treatment completion. RESULTS: Between November 2010 and August 2013, 53 patients who underwent complete resection were enrolled, including 30, 20, and 3 patients who underwent pancreaticoduodenectomies and distal and total pancreatectomies, respectively. In total, 51 (96.2%) patients underwent R0 resection, of whom 3, 2, 12, 35, 0, and 1 had stages IA, IB, IIA, IIB, III, and IV cancer, respectively, and 47 (88.7%) patients completed PI4W. The median RFS was 22.0 months (1-, 3-, 5, and 10 years RFS: 64.9%, 38.1%, 38.1%, and 38.1%, respectively), whereas the median OS was 32.0 months (1-, 3-, 5, and 10 years OS:86.6%, 47.2%, 44.4%, and 44.4%, respectively). CONCLUSION: Treatment with PI4W followed by GEM for 6 months after surgery may be beneficial in patients undergoing curative resection of pancreatic cancer.

Investigating the early diagnosis of pancreatic cancer by surveillance of patients with "K-sign" of the pancreas by computed tomography: A prospective study.

BACKGROUND: We previously conducted a retrospective study investigating pancreatic morphological abnormalities that lead to early diagnosis of pancreatic cancer (PC) using computed tomography (CT). We reviewed 41 of 308 PC patients between 2011 and 2017 who had previously undergone CT to look for morphological changes leading to cancer development. In 24 patients (58.5%), a K-shaped constriction of the pancreas ("K-sign") was observed before the appearance of cancer. This study aimed to investigate whether an early PC diagnosis is possible by prospective CT follow-up of patients with the K-sign. METHODS: We investigated PC development through prospective surveillance of patients exhibiting K-signs identified on CT. RESULTS: Of approximately 87 000 CT scans performed between April 2019 and August 2022, the K-sign was observed in 54 patients. A total of 30 patients provided informed consent and were subsequently monitored using CT. Five patients (16.7%) were diagnosed with PC and underwent surgery after 3-24 months follow-up. Pathologically, four of five patients (80%) were diagnosed with early-stage pancreatic cancer (stage 0-IA). All patients exhibited defects in acinar structure, fibrous tissue, fat replacement, and inflammatory cells, suggesting their potential involvement in PC development. CONCLUSION: The detection and surveillance of the K-sign may be helpful for early PC diagnosis.

Efficacy and safety of endovascular therapy for delayed hepatic artery post-pancreatectomy hemorrhage: development of extrahepatic collateral circulation and complications of post endovascular therapy.

BACKGROUND: Endovascular therapy (ET) for delayed hepatic artery post-pancreatectomy hemorrhage (HA-PPH) may require complete hepatic artery occlusion (HAO). Nonetheless, the development of extrahepatic collateral circulation (EHC) and the relationship between radiological factors (EHC, portal vein stenosis, and HAO) and adverse hepatic events after ET remain unclear. This study aimed to evaluate the efficacy and safety of ET for delayed PPH and examine the development of EHC. METHODS: A total of 19 ET cases for delayed HA-PPH were reviewed. Hepatic adverse events, portal vein stenosis, HAO, and mortality rate after ET were evaluated. Moreover, EHC from the left gastric artery (LGA), right inferior phrenic artery (RIPA), left inferior phrenic artery (LIPA), right internal thoracic artery (RITA), left internal thoracic artery (LITA), renal artery (RA), omental artery (OA), intercostal artery (IA), and branch of superior mesenteric artery (BSMA) was assessed using angiogram and computed tomography angiography (CTA). RESULTS: All cases were successfully treated using transcatheter arterial embolization (n = 17) and stent-graft placement (n = 2) without mortality. EHC from the LGA (8/19), RIPA (10/19), LIPA (4/19), and RITA (3/19) was observed on post-ET CTA. The incidence of hepatic adverse events was significant in the group with both HAO and portal vein stenosis (p < 0.001) and absence of EHC from LIPA and RITA (p < 0.05). CONCLUSION: ET for delayed HA-PPH might be effective and safe. While avoiding both HAO and portal vein stenosis is important, the development of EHCs from LIPA and RITA may prevent hepatic adverse events after ET.

Percutaneous transhepatic coil and cover technique with small system for the extrahepatic portal vein hemorrhage after pancreaticoduodenectomy.

Post-pancreaticoduodenectomy hemorrhage is a life-threatening complication that usually occurs in skeletonized arteries. Venous hemorrhage is a rarer complication, and surgical management is often challenging. We herein report the case of an 80-year-old man who suffered from prolonged pancreatic fistula and long-term drainage tube placement, which could cause late post-pancreaticoduodenectomy hemorrhage from the confluence of the splenic and extrahepatic portal veins. An intrahepatic posterior portal venous branch was percutaneously punctured, and the splenic vein was embolized using coils and a vascular plug. A balloon-expandable covered stent was also placed from the superior mesenteric vein to the main portal vein to cover the confluence, which required a system as small as 8-F. Portal venography revealed good patency without extravasation. Thereafter, antithrombotic and antibacterial treatments were successfully administered without any additional interventions. He remained well without any evidence of thrombosis or indolent infection 19 months after endovascular treatment. The endovascular coil and cover technique with prolonged adjuvant therapy is a feasible alternative for managing such critical situations.

Successful biliary stent placement using balloon enteroscopy-assisted ERCP in a patient with rare surgically altered anatomy who underwent Roux-en-Y reconstruction twice.

Highlight Nakadai and colleagues report a case of successful endoscopic biliary drainage in a patient with rare surgically altered anatomy after undergoing Roux-en-Y reconstruction twice. Balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography can be the first choice for patients with such complex surgically altered anatomy, especially in those without biliary dilation.

Independent predictors of secondary invasive pancreatic remnant tumors after initial resection of an intraductal papillary mucinous neoplasm: a nationwide large-scale survey in Japan.

PURPOSE: There is no standardized surveillance protocol after intraductal papillary mucinous neoplasm (IPMN) resection. We report the findings of a large-scale survey in Japan, investigating the independent predictors of secondary invasive tumors by analyzing the epidemiology of secondary tumors of the remnant pancreas after initial IPMN resection. METHODS: An institutional questionnaire about the remnant pancreas after pancreas resection was distributed at the 41st Annual Meeting of the Japanese Society of Pancreatic Surgery in Tokyo. We retrospectively analyzed the patient data including pathological diagnosis, postoperative outcomes, and evaluation methods. RESULTS: Redo pancreatectomy was performed for secondary disease in 213 (1.4%) of a total 15,777 patients. Eighty-eight of these 213 patients had undergone initial resection of IPMN. The types of secondary tumors after IPMN resection significantly depended on those of the primary tumors. Through short-interval and long-term follow-up, most of the secondary tumors were detected within 1-4 years. Logistic regression analysis revealed that the initial pathological diagnosis of invasive IPMN was an independent predictor of secondary invasive tumors in the remnant pancreas. CONCLUSION: Primary invasive IPMN proved to be a significant predictor of secondary invasive IPMN. Both short-interval and long-term follow-up may help to determine the prognosis of patients after IPMN resection.

Successful treatment of esophagopleural fistula following pulmonary resection for primary lung cancer: a case report.

BACKGROUND: We report a rare case of esophagopleural fistula (EPF) developing during the postoperative period after pulmonary resection for primary lung cancer. CASE PRESENTATION: A 71-year-old male who underwent video-assisted thoracoscopic right lower lobectomy with lymph node dissection for primary lung cancer developed severe stabbing pain in his right shoulder and high fever 3 days after the operation. The fever persisted, the cough became more productive, and a plain chest X-ray showed slight a few infiltrative opacities in the right lung field. Intravenous antibiotic therapy was initiated. The patient developed a right pneumothorax 5 days after the operation, and contaminated discharge from the right chest tube was noted. A chest computed tomography showed right-sided empyema, while bronchoscopic examination revealed no evidence of a bronchopleural fistula. Open-window thoracostomy (OWT) was performed. Finally, 2 days after the OWT, the patient was diagnosed as having an EPF, because the right chest cavity was found to be contaminated with food materials. Ample purification of the right chest cavity was achieved by repeated dressing changes, and the EPF was finally closed by omentopexy. The post-surgical course was uneventful. Five weeks after the omentopexy, an esophagogram revealed no leakage of the contrast medium from the esophageal wall. The patient was discharged 13 weeks after the omentopexy. CONCLUSION: While EPF following pulmonary resection is a rare complication, it can lead to critical situations and the diagnosis is difficult. Prompt OWT and omentopexy were found to be effective treatment procedures for EPF following lung surgery.

Anaplastic carcinoma of the pancreas: Case report and literature review of reported cases in Japan.

We report a case of a 64-year-old woman with anaplastic carcinoma of the pancreas (ACP) with cyst formation and review 60 ACP cases reported in Japan. In 20% of cases, laboratory tests revealed severe anemia (hemoglobin level < 10.0 g/dL) and elevated leucocyte counts (> 12000/mm3), which were likely attributable to rapid tumor growth, intratumoral hemorrhage, and necrosis. Elevated serum CA19-9 levels were observed in 55% of cases. Cyst-like structures were observed on imaging in 47% of cases, and this finding appears to reflect subsequent cystic degeneration in the lesion. Macroscopically, hemorrhagic necrosis was observed in 77% of cases, and cyst formation was observed in 33% of cases. ACP should be considered when diagnosing pancreatic tumors with a cyst-like appearance, especially in the presence of severe anemia, elevated leucocyte counts, or elevated serum CA19-9 levels.

Two cases of cystic artery pseudoaneurysm rupture due to acute cholecystitis with gallstone impaction in the neck.

A cystic artery aneurysm is a rare cause of hemobilia. Herein, we report two cases of acute cholecystitis with a ruptured cystic artery pseudoaneurysm. Two patients (a 69-year-old man and an 83-year-old man) were admitted to our hospital because of acute cholecystitis with gallstone impaction in the neck. Percutaneous transhepatic gallbladder drainage (PTGBD) was performed for both patients. After a few days of PTGBD, gallbladder hemorrhage was observed. Abdominal angiography showed cystic artery aneurysm. A transcatheter arterial embolization was therefore performed, followed by an open cholecystectomy.

Functional consequences of Wnt-induced dishevelled 2 phosphorylation in canonical and noncanonical Wnt signaling.

Dishevelled (Dvl) proteins are intracellular effectors of Wnt signaling that have essential roles in both canonical and noncanonical Wnt pathways. It has long been known that Wnts stimulate Dvl phosphorylation, but relatively little is known about its functional significance. We have previously reported that both Wnt3a and Wnt5a induce Dvl2 phosphorylation that is associated with an electrophoretic mobility shift and loss of recognition by monoclonal antibody 10B5. In the present study, we mapped the 10B5 epitope to a 16-amino acid segment of human Dvl2 (residues 594-609) that contains four Ser/Thr residues. Alanine substitution of these residues (P4m) eliminated the mobility shift induced by either Wnt3a or Wnt5a. The Dvl2 P4m mutant showed a modest increase in canonical Wnt/ß-catenin signaling activity relative to wild type. Consistent with this finding, Dvl2 4Pm preferentially localized to cytoplasmic puncta. In contrast to wild-type Dvl2, however, the P4m mutant was unable to rescue Wnt3a-dependent neurite outgrowth in TC-32 cells following suppression of endogenous Dvl2/3. Earlier work has implicated casein kinase 1δ/ε as responsible for the Dvl mobility shift, and a CK1δ in vitro kinase assay confirmed that Ser(594), Thr(595), and Ser(597) of Dvl2 are CK1 targets. Alanine substitution of these three residues was sufficient to abrogate the Wnt-dependent mobility shift. Thus, we have identified a cluster of Ser/Thr residues in the C-terminal domain of Dvl2 that are Wnt-induced phosphorylation (WIP) sites. Our results indicate that phosphorylation at the WIP sites reduces Dvl accumulation in puncta and attenuates ß-catenin signaling, whereas it enables noncanonical signaling that is required for neurite outgrowth.

[A study of the efficacy of high-dose toremifene in advanced and recurrent breast cancer].

Recently, many patients have been treated with aromatase inhibitors(AI), either in an adjuvant setting or as a treatment for recurrence. The efficacy and safety of high-dose toremifene(HD-TOR)were evaluated in 18 patients with advanced/recurrent breast cancer. Twelve of the 18 patients had received AI just prior to the study treatment. The clinical benefit rate was 56%(PR: 28%, long SD: 28%). Progression-free median survival was 5. 5 months. Adverse events were mild and toremifene was well-tolerated. The results suggest that HD-TOR should be considered early on as a second-line treatment, or as a later treatment option for AI-resistant breast cancer.

Wnt signaling in liver cancer.

Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide. As in many other types of cancer, aberrant activation of the canonical Wnt/beta-catenin signaling pathway is an important contributor to tumorigenesis. In HCC this frequently occurs through mutations in the N-terminal region of beta-catenin that stabilize the protein and permit an elevated level of constitutive transcriptional activation by beta-catenin/TCF complexes. In this article we review the abundant evidence that Wnt/beta-catenin signaling contributes to liver carcinogenesis. We also discuss what is known about the roles of Wnt signaling in liver development, regeneration, and stem cell behavior, in an effort to understand the mechanisms by which activation of the canonical Wnt pathway promotes tumor formation in this organ. The Wnt/beta-catenin pathway presents itself as an attractive target for developing novel rational therapies for HCC, a disease for which few successful treatment strategies are currently available.

Antitumor effect induced by dendritic cell (DC)-based immunotherapy against peritoneal dissemination of the hamster pancreatic cancer.

Establishing a method to control peritoneal dissemination is one of the most pressing issues in the postsurgical treatment of pancreatic cancer. In the present study, we investigated the effect of dendritic cell (DC)-based immunotherapy on peritoneal disseminations of hamster pancreatic cancer cells, PGHAM-1. After the orthotopically inoculation of 2 x 10(6) PGHAM-1 cells, DC pulsed with PGHAM-1-derived tumor lysates, DC alone or PBS as a vehicle was injected intraperitoneally (i.p.) three times at weekly intervals. The group treated with DC or DC+lysate was found to have smaller disseminated tumors than the vehicle-treated. In addition, mean survival time in the DC+lysate groups was significantly longer than the PBS group. These findings suggested that DC-based immunotherapy might be efficient for the treatment of peritoneal disseminations of the pancreatic cancer.

Intraductal growth of a nonfunctioning endocrine tumor of the pancreas.

Intraductal growth of nonfunctioning endocrine tumors of the pancreas may be very rare, and our survey of literature shows only two cases have been described. We report a case of a 43-year-old man with a nonfunctioning endocrine tumor of the pancreas that uniquely grew within the lumen of the main pancreatic duct (MPD) without ductal involvement and completely obstructed the MPD. Endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) were very helpful to delineate the intraductal growth of the tumor and to determine the resection line of the pancreas. A nonfunctioning pancreatic endocrine tumor is important to consider on differential diagnoses when complete obstruction of the MPD is demonstrated on ERCP. It is speculated that the tumor originated from precursor cells of the pancreatic duct or islet cells adjacent to the MPD and slowly proliferated within the lumen of the MPD.

Structure and characterization of hamster IL-12 p35 and p40.

Complementary DNAs coding for two subunits of hamster interleukin-12 (IL-12), p35 and p40, were cloned from a hamster dendritic cell (DC) cDNA library. The cloning demonstrated that hamster IL-12 consisted of a p35 subunit with 216 amino acid (aa) residues and a p40 subunit with 327 aa. Structural comparison of hamster p35 and p40 at the protein level showed the highest homologies with each counterpart of sigmodon (hispid cotton rat). The gene expressions of hamster IL-12 p35 and p40 in bone marrow (BM) cells cultured in the presence of mouse granulocyte macrophage-colony-stimulating factor (mGM-CSF) and IL-4 were up-regulated during culture. Immunoblot analysis of 293 cells transfected with hamster p35 and p40 expression vectors suggested the presence of a covalently linked p35/p40 heterodimer. Furthermore, supernatant from the 293 cells transfected with both expression vectors induced the up-regulation of interferon-gamma (IFN-gamma) mRNA in hamster splenocytes, indicating that the p35/p40 heterodimer IL-12 protein present in the supernatant was functional. These results suggest that the vectors containing hamster IL-12 cDNA might be suitable tools for developing an immunotherapeutic approach against experimental cancer in a hamster model.