Efficacy and Safety of Endoscopic Removal for Asymptomatic Common Bile Duct Stones in Comparison with Symptomatic Stones.

OBJECTIVE: Endoscopic removal is recommended for common bile duct stones (CBDs). However, in patients with asymptomatic CBDs, follow-up without treatment may be recommended because of the increased complication risks associated with asymptomatic CBDs removal. The objective of our study was to investigate the efficacy and safety of CBDs removal in asymptomatic patients. METHODS: Consecutive patients with naive papilla who underwent endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of CBDs from April 2016 to August 2020 were retrospectively analyzed. We compared the efficacy and safety of CBDs removal in asymptomatic and symptomatic patients. RESULTS: We enrolled 300 patients, 53 asymptomatic and 247 symptomatic patients. Endoscopic CBDs removal was successful in all patients, except one symptomatic patient. However, the complete stone removal rate in a single session was significantly higher in the asymptomatic group than that in the symptomatic group. ERCP-related complications did not differ between the asymptomatic and symptomatic patients. The incidence of post-ERCP pancreatitis was similar and liver cirrhosis was the only significant risk factor for pancreatitis. CONCLUSION: Complication risks associated with endoscopic CBDs removal was not significantly different between asymptomatic and symptomatic patients. Liver cirrhosis was a significant risk factor of ERCP-related pancreatitis.

Effects of Culture Conditions (Microplate and Solvent) on in vitro Antifungal Activity of Caspofungin Against Candida Species.

Effects of the type of microplates and solvent for preparation of caspofungin (CPFG) on antifungal susceptibility testing of CPFG against clinical isolates of Candida albicans, Candida glabrata, and Candida krusei (20 strains each) by broth microdilution method according to the Clinical and Laboratory Standards Institute were evaluated. When CPFG was dissolved in water, MICs against the three Candida species decreased 3.1-6.0-fold in surface-untreated microplates compared to those in treated microplates. When CPFG was dissolved in dimethyl sulfoxide, MICs against the three Candida species decreased 1.3-2.5-fold in surface-untreated microplates compared to those in treated microplates. Differences in MICs according to the type of solvent did not exceed the difference for one dilution interval (0.5-2-fold MIC ratio) regardless of whether the microplate surface was treated or not. These findings suggest that differences in CPFG MICs may depend mainly on the type of surface treatment of assay microplates.

A Case of Endoscopic Mucosal Resection of Carcinoma in Adenoma at the Minor Duodenal Papilla.

Here, we describe a case of minor papillary adenocarcinoma in adenoma that was treated with endoscopic mucosal resection (EMR). In a 67-year-old woman, sigmoid colon cancer was incidentally detected on preoperative upper gastrointestinal endoscopy. Endoscopy revealed a slightly elevated lesion at the minor duodenal papilla. The findings of a histopathologic examination were suggestive of adenocarcinoma. Computed tomography and magnetic resonance images identified a minute tumor, whereas endoscopic ultrasonography revealed that the tumor did not spread to the pancreas. We performed EMR of this lesion. There were no complications, and relapse has not occurred in 3 years. Cases of minor papillary adenocarcinoma treated with EMR are quite rare.

[Pharmacological and clinical effects of letermovir (Prevymis®), a novel anti-human cytomegalovirus prophylactic drug].

Letermovir is an anti-human cytomegalovirus (HCMV) drug with a novel mechanism of action. Virological characterization and sequence analysis of resistant viruses indicate that the viral DNA terminase complex is the target of this compound. Unlike currently marketed anti-HCMV drugs, which act via inhibition of the viral DNA polymerase, the terminase inhibitor interferes with viral DNA cleavage and packaging of monomeric genome units into capsids. Letermovir has potent anti-HCMV activity, with 50% effective concentration of single-digit nanomolar against most clinical HCMV isolates in cell-culture models of infection. Besides its excellent in vitro inhibitory activity against laboratory and clinical HCMV isolates, letermovir exhibits activity against virus strains resistant to the currently approved anti-HCMV drugs. Letermovir is specific for human cytomegalovirus but lacks inhibitory activity against major pathogenic viruses including other Herpesviridae. In a xenograft mouse infection model, the 50% and 90% effective doses of the letermovir were 3 and 8 mg/kg/day, respectively. HCMV infection and disease in recipients of allogeneic hematopoietic stem cell transplant (HSCT) is a serious disease leading to significant morbidity and mortality. In the Phase 3 trial, the preventive effect of clinically significant HCMV infection by oral or intravenous administration of letermovir in allogeneic HSCT patients was confirmed, and letermovir was well tolerated with no suggestions of myelotoxicity or nephrotoxicity.

Successful Endoscopic Removal of a Biliary Stent with Stent-Stone Complex after Long-Term Migration.

A 49-year-old man was referred to our hospital for an abnormality of the hepatobiliary enzyme. The patient was diagnosed with primary sclerosing cholangitis 9 years ago, and he had a biliary stent with a string placed as an inside stent. We attempted to remove the stent 6 months later, but the string was cut off, so the stent could not be removed. Removal was attempted again, but the patient cancelled the outpatient appointments. During the examination performed at the present visit, we discovered that the biliary stent had migrated into the bile duct, and a stone had formed around the stent. We attempted to remove the stent-stone complex by endoscopic retrograde cholangiopancreatography, but it was difficult; thus, we decided to implant a new biliary stent and remove the other stent later. When we performed endoscopic retrograde cholangiopancreatography again 2 days later, the bile duct axis was linearized thanks to the additional stent, enabling us to grab the migrated stent with stent-stone complex using grasping forceps and to successfully pull it out. By implanting an additional plastic stent temporarily, we were able to straighten the biliary axis and endoscopically remove the biliary stent that migrated and caused the development of stent-stone complex in a 2-staged approach.

Comparison between Endoscopic Treatment and Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis.

BACKGROUND: Treatment of recurrent chronic obstructive pancreatitis is pancreatic duct decompression with endoscopic drainage (endoscopic pancreatic stenting [EPS] with extracorporeal shockwave lithotripsy [ESWL]) or surgical drainage. Despite the recent popularization of endoscopic drainage, treatment or stent removal is difficult in many patients. We compared the efficacy, safety, and medical cost of endoscopic and surgical treatments. PATIENTS AND METHODS: We retrospectively compared the treatment course and medical cost of hospitalization between 41 patients who had undergone pancreatic stenting between 2006 and 2010 (EPS group) and 10 patients who had undergone surgery for poor control of pancreatitis between 2001 and 2005 (surgical drainage group). RESULTS: No intergroup differences were observed in causes, symptoms, disease duration, smoking history, or endocrine and exocrine functions. The technical success rate was 100% in both groups, and pain had improved in all of the patients in both groups. The incidences of complications did not differ significantly, and the mortality rate was 0% in both groups. The rehospitalization rate was significantly higher in the EPS group (78%) than that in the surgical drainage group (20%; P<0.01). This was considered attributable to rehospitalization for stent replacement. The effects to improve endocrine and exocrine functions were not different between the two groups before and after treatment, and the current condition was maintained in 80% or more of the patients. For the entire EPS group, the mean hospitalization period was 18 days and the mean medical cost of hospitalization was 2,133,330 yen. For the entire surgical drainage group, the mean hospitalization period was 23 days and the mean medical cost of hospitalization was 2,246,548 yen, thus indicating no significant differences between the two groups. CONCLUSIONS: Although both endoscopic and surgical treatments achieved high symptom control and safety rates, re-hospitalization is required for stent replacement, which leads to poor cost-effectiveness, particularly in patients in whom stent removal is difficult. Endoscopic treatment for severe pancreatic duct stenosis will need to be advanced and evaluated in the future.

Conversion surgery for an initially unresectable, locally advanced pancreatic cancer after induction chemotherapy and carbon-ion radiotherapy: a case report.

BACKGROUND: Pancreatic cancer has a very high mortality rate worldwide, and about 30-40% of all patients have extensive vascular involvement at initial diagnosis that precludes surgical intervention. Here, we describe our experience in a patient with locally advanced pancreatic cancer (LAPC) who underwent R0 conversion surgery after undergoing a combination of chemotherapy and carbon-ion radiotherapy (CIRT), which led to long-term relapse-free survival (23 months). CASE PRESENTATION: A 41-year-old woman presented a month ago with epigastralgia referred to our facility and was subsequently diagnosed with pancreatic cancer cStage III (Ph, TS2 (35 mm), cT4, cCH1, cDU1, cS1, cRP1, cPL1, cVsm0, cAsm1, cN0, cM0) that was also categorized as an unresectable LAPC. She immediately underwent 3 cycles of induction chemotherapy (gemcitabine + nanoparticle albumin-bound (nab-) paclitaxel) followed by CIRT with concurrent gemcitabine. Although significant shrinkage of the primary tumor occurred, frequent cholangitis due to duodenal stenosis of unknown etiology prevented continued chemotherapy, and 9 months after the first visit, she underwent a radical, subtotal, stomach-preserving, pancreaticoduodenectomy (SSPPD). Histopathologic examination of the resected tissue revealed a R0 resection with a histological response of Evans grade IIB. She was administered an almost full dose of S-1 as adjuvant chemotherapy for 6 months and has shown no signs of recurrence in 23 months. CONCLUSIONS: We report a first case of successful conversion surgery for an initially unresectable LAPC after rapid induction GEM + nab-PTX chemotherapy followed by CIRT. Rapid induction GEM + nab-PTX chemotherapy followed by CIRT for LAPC might be a safe and effective treatment option.

An Intra-Abdominal Desmoid Tumor, Embedded in the Pancreas, Preoperatively Diagnosed as an Extragastric Growing Gastrointestinal Stromal Tumor.

A 45-year-old woman was found to have a pancreatic tumor by abdominal ultrasound performed for a medical check-up. Abdominal contrast-enhanced computed tomography showed a hypovascular tumor measuring 30 mm in diameter in the pancreatic tail. Endoscopic ultrasound-guided fine needle aspiration was performed. An extragastric growing gastrointestinal stromal tumor was thereby diagnosed preoperatively, and surgical resection was planned. Laparoscopic surgery was attempted but conversion to open surgery was necessitated by extensive adhesions, and distal pancreatectomy, splenectomy, and partial gastrectomy were performed. The histological diagnosis was an intra-abdominal desmoid tumor. A desmoid tumor is a fibrous soft tissue tumor arising in the fascia and musculoaponeurotic tissues. It usually occurs in the extremities and abdominal wall, and only rarely in the abdominal cavity. We experienced a case with an intra-abdominal desmoid tumor that was histologically diagnosed after laparotomy, which had been preoperatively diagnosed as an extragastric growing gastrointestinal stromal tumor. Although rare, desmoid tumors should be considered in the differential diagnosis of intra-abdominal tumors. Herein, we report this case with a literature review.

A Serous Cystic Neoplasm of the Pancreas Coexisting with High-Grade Pancreatic Intraepithelial Neoplasia Mimicking an Intraepithelial Papillary Mucinous Neoplasm: A Case Report.

Serous cystic neoplasms of the pancreas are rare exocrine pancreatic neoplasms, most of which are benign and do not communicate with the pancreatic duct. Pancreatic intraepithelial neoplasm (PanIN) is considered a precursor of ductal adenocarcinoma that is microscopically recognized in pancreatic ducts. A 67-year-old Japanese woman presented with a 10-mm multilocular cystic lesion at the pancreatic body. Magnetic resonance pancreatography showed stenosis of the main pancreatic duct at the pancreatic body and dilatation of the distal side of the main pancreatic duct. Furthermore, communication between the cystic lesion and the main pancreatic duct was suspected based on magnetic resonance pancreatography findings. Distal pancreatectomy was performed under the preoperative diagnosis of intraductal papillary mucinous neoplasm. Histologically, the cystic lesion was lined with a non-atypical cuboidal or flat epithelium with clear cytoplasm and was thus diagnosed as a serous cystic neoplasm. High-grade PanIN lesions with stromal fibrosis were observed at the main and branch pancreatic ducts. Histological examination revealed no communication between the serous cystic neoplasm and the pancreatic ducts. Immunohistochemically, the epithelium of the serous cystic neoplasm showed positive anti-von Hippel-Lindau antibody staining, whereas the epithelium of the PanIN showed negative staining. A serous cystic neoplasm coexisting with another pancreatic neoplasm is rare. When dilatation of the main or branch pancreatic ducts coexists with a serous cystic neoplasm, as in this case, the lesion clinically mimics an intraductal papillary mucinous neoplasm.

Laparoscopic splenopancreatectomy for an endocrine tumor with cystic changes: a case report.

The biological behavior of a cystic pancreatic endocrine neoplasm is less aggressive than that of pancreatic neuroendocrine neoplasms, and its prognosis is better. Limited surgery should be considered for cystic pancreatic endocrine neoplasms that are not accompanied preoperatively by lymph node or distant metastasis.

Undifferentiated carcinoma of the ampulla of Vater.

Undifferentiated carcinoma of the ampulla of Vater is a rare disease with unclear and clinical characteristics and prognosis. Here, we report the case of a 61-year-old man with undifferentiated carcinoma of the ampulla of Vater. He presented to our hospital with an increase in hepatobiliary system enzymes that was detected during a health check-up. Imaging and endoscopy demonstrated a tumor with ulcer in the ampulla of Vater, which was diagnosed as a carcinoma by biopsy. No distant metastasis was observed. Subtotal stomach-preserving pancreaticoduodenectomy was performed. Undifferentiated carcinoma was confirmed based on the presence of small round atypical cells with the formation of a solid alveolar lesion on histopathological examination and immunohistochemical staining that was positive for CAM 5.2 but negative for chromogranin A and synaptophysin. The tumor infiltrated the duodenum, but not the pancreas; no lymph node metastasis was observed. However, liver metastases were detected 2 months postoperatively. Chemotherapy was performed, and the tumor size temporality decreased; however, it grew in size again, and the patients subsequently died of the primary disease 15 months postoperatively. Undifferentiated carcinoma of the ampulla of Vater is a very rare histological type. More number of cases is necessary to clarify optimal treatment.

Carcinosarcoma of the ampulla of Vater: a case report and literature review.

BACKGROUND: Carcinosarcoma of the ampulla of Vater is extremely rare, and to the best of our knowledge, this is the third reported study. CASE PRESENTATION: The patient was a 73-year-old man, who presented with a chief complaint of dark urine. After a work-up, we suspected duodenal papillary cancer and performed a subtotal stomach-preserving pancreaticoduodenectomy with lymph node dissection. Immunohistochemically, the sarcomatous atypical cells were diffusely positive for cytokeratin AE1&3 and vimentin and focally positive for α-smooth muscle actin; these cells were also negative for desmin, CD34, DOG1, c-kit, and S100. From these findings, we diagnosed the patient with so-called carcinosarcoma. There was no lymph node metastasis. CONCLUSIONS: Carcinosarcoma of the ampulla of Vater has a poor prognosis, and lymph node metastases are often seen. For the complete cure of carcinosarcoma of the ampulla of Vater, resection with the dissection of the lymph nodes may be necessary.

Bile duct carcinoma associated with congenital biliary dilatation in a 16-year-old female: a case report and literature review.

We encountered a very rare case of bile duct carcinoma associated with congenital biliary dilatation (CBD) in a 16-year-old female who was admitted to our hospital because of right upper abdominal pain and vomiting. Abdominal computed tomography demonstrated a cystic dilatation of the common bile duct measuring 7 cm in diameter and two enhanced tumors 4 cm in diameter located in the inferior bile duct and middle bile duct. Magnetic resonance cholangiopancreatography clearly demonstrated a cystic dilatation of the extrahepatic bile duct (Todani's CBD classification: type 4-A). Endoscopic retrograde cholangiopancreatography also revealed two tumors. Biopsy results of one of the tumors confirmed adenocarcinoma. Excision of the perihilar bile duct and subtotal stomach-preserving pancreaticoduodenectomy with dissection of the major lymph nodes were performed. A postoperative histopathologic examination revealed a well-differentiated tubular adenocarcinoma, which remained within the mucosal layer, and no lymph node metastasis was found. The postoperative course was uneventful, and the patient was discharged 10 days after surgery and has remained disease-free for 21 months.

Discovery of Novel Indazole Derivatives as Highly Potent and Selective Human ß3-Adrenergic Receptor Agonists with the Possibility of Having No Cardiovascular Side Effects.

Novel indazole derivatives were prepared and evaluated for their biological activity and cardiovascular safety profile as human ß3-adrenergic receptor (AR) agonists. Although the initial hit compound 5 exhibited significant ß3-AR agonistic activity (EC50 = 21 nM), it also exhibited agonistic activity at the α1A-AR (EC50 = 219 nM, selectivity: α1A/ß3 = 10-fold). The major metabolite of 5, which was an oxidative product at the indazole 3-methyl moiety, gave a clue to a strategy for improvement of the selectivity for ß3-AR agonistic activity versus α1A-AR agonistic activity. Thus, modification of the 3-substituent of the indazole moiety effectively improved the selectivity to develop compound 11 with potent ß3-AR agonistic activity (EC50 = 13 nM) and high selectivity (α1A/ß3 = >769-fold). Compound 11 was also inactive toward ß1 and ß2-ARs and showed dose dependent ß3-AR mediated relaxation of marmoset urinary bladder smooth muscle, while it did not obviously affect heart rate or blood pressure (iv, 3 mg/kg) in anesthetized rats.

Risk factors for migration, fracture, and dislocation of pancreatic stents.

Aim. To analyze the risk factors for pancreatic stent migration, dislocation, and fracture in chronic pancreatitis patients with pancreatic strictures. Materials and Methods. Endoscopic stent placements (total 386 times) were performed in 99 chronic pancreatitis patients with pancreatic duct stenosis at our institution between April 2006 and June 2014. We retrospectively examined the frequency of stent migration, dislocation, and fracture and analyzed the patient factors and stent factors. We also investigated the retrieval methods for migrated and fractured stents and their success rates. Results. The frequencies of stent migration, dislocation, and fracture were 1.5% (5/396), 0.8% (3/396), and 1.2% (4/396), respectively. No significant differences in the rates of migration, dislocation, or fracture were noted on the patient factors (etiology, cases undergoing endoscopic pancreatic sphincterotomy, location of pancreatic duct stenosis, existence of pancreatic stone, and approach from the main or minor papilla) and stent factors (duration of stent placement, numbers of stent placements, stent shape, diameter, and length). Stent retrieval was successful in all cases of migration. In cases of fractured stents, retrieval was successful in 2 of 4 cases. Conclusion. Stent migration, fracture, and dislocation are relatively rare, but possible complications. A good understanding of retrieval techniques is necessary.

A case of pancreatic intraepithelial neoplasia that was difficult to diagnose preoperatively.

A 63-year-old female patient presented to a local physician with pain in her back and epigastric region. An abdominal computed tomography (CT) scan revealed a pancreatic tumor, and the patient was referred to our hospital. Multiple imaging studies that included ultrasonography (US), CT, MRI, and endoscopic US revealed a cystic lesion 3-4 cm in size with node-like projections in the body of the pancreas. The distal main pancreatic duct was also found to be dilated. Endoscopic retrograde pancreatography revealed an irregular stenosis of the main pancreatic duct proximal to the cystic lesion, and malignancy was suspected. The patient was preoperatively diagnosed with pancreatic ductal carcinoma concomitant with intraductal papillary mucinous carcinoma, and a distal pancreatectomy was performed. Rapid pathological diagnosis during surgery revealed positive surgical margins for pancreatic intraepithelial neoplasia (PanIN). Further resection was performed twice, her surgical margin was positive and total pancreatectomy was ultimately conducted. Histopathological findings revealed diffuse microinvasive cancerous lesions corresponding to PanIN-2 (moderate dysplasia) to PanIN-3 (carcinoma in situ) throughout the pancreas. PanIN involves microlesions of the ductal epithelium that may precede pancreatic cancer. Ascertaining changes in PanIN using images provided by diagnostic modalities such as CT and US is challenging. Ductal stenosis and distal cystic lesions resulting from atrophy and fibrosis of pancreatic tissue were noted around PanIN. Considering the possibility of PanIN, a precancerous lesion during differential diagnosis will help to improve early detection and prognosis for patients with pancreatic cancer.

Relationship between pain and plasma amino acid levels in chronic pancreatitis.

OBJECTIVE: Our aim was to investigate the relationship between imbalances of plasma amino acids and pain in chronic pancreatitis (CP). METHODS: Thirty patients with alcoholic CP in an exocrine-insufficient state were examined. We divided them between diet and control group. Diet group ingested 80 g/300 kcal of the elemental diet "Elental®". This diet of 300 kcal/day was administered for two months. Selected clinical and laboratory values were compared between both groups before and after diet. Pain was observed and compared using a visual analog scale (VAS). RESULTS: There was no significant difference in the BMI between both groups before and after diet. The serum albumin level in diet group after diet was significantly higher than in control group (P=0.036). There was no significant difference in HbA1c between both groups before and after diet. The total amino acid concentration was significantly higher in diet group after diet than in control group (P=0.033). The concentrations of serum histidine and methionine in diet group after diet were significantly higher than in control group (histidine, P=0.022; methionine, P=0.026). The concentration of serum glutamate in diet group after diet was significantly lower than in control group (P=0.027). The balance of amino acids in diet group was normalized after the Elental® was ingested. The VAS score was significantly lower in diet group after diet than in control group (P=0.018). CONCLUSION: These amino acid levels and pancreatic pain were improved by the elemental diet. The pancreatic pain may be related to these amino acid imbalances.

A case study of a collision tumor composed of cancers of the bile duct and pancreas.

In this case report, we describe the extremely rare case of a collision tumor comprising cancers of the bile duct and the pancreas. A 70-year-old man was referred to our hospital with a diagnosis of obstructive jaundice. He was diagnosed with pancreatic head cancer, and we performed a pancreaticoduodenectomy with lymph node dissection. At laparotomy, there were two palpable masses in the vicinity of the confluence of the cystic duct and the head of the pancreas. The resected specimen demonstrated tumors at the confluence of the cystic duct and in the pancreatic head. Histopathological examination demonstrated a moderately differentiated tubular adenocarcinoma in the pancreatic head and a well-differentiated tubular adenocarcinoma at the confluence of the cystic duct. Immunostaining was negative for p53 and MUC6 in the pancreatic head tumor; however, immunostaining was positive for both in the tumor located at the confluence of the cystic duct. The two tumors were histologically different and were diagnosed as collision cancer caused by the collision of the bile duct and pancreatic cancers.

Accessory Pancreatic Duct-Portal Vein Fistula: A Rare Complication of Chronic Pancreatitis during Endoscopic Retrograde Cholangiopancreatography.

Pancreatitis, hemorrhage and perforation are the most frequent complications associated with endoscopic retrograde cholangiopancreatography (ERCP). We report a rare case of accessory pancreatic duct-portal vein fistula, which occurred during ERCP in a patient with chronic pancreatitis. To our knowledge, this is the first report of accessory pancreatic duct-portal vein fistula created during ERCP by the use of a guide wire.