[A Case of Extrahepatic Bile Duct Carcinoid Tumor Involving Diagnostic Difficulties].

A patient in his 60s had undergone laparoscopic anterior resection for the treatment of carcinoma of the rectum in February 2016. Histopathologic examination revealed the lesion as a pT2(MP)n(-)M0, fStage Ⅰrectal cancer. One year post-surgery, contrast-enhanced computed tomography(CT)revealed enhancement of parts of the intrapancreatic distal bile ducts. Magnetic resonance cholangiopancreatography(MRCP)showed filling defects at the same site. Magnetic resonance imaging( MRI)with an endorectal coil(ERC)was then performed to identify reproducible bile duct filling defects. Neither cytology nor biopsy yielded any findings that definitely indicated malignancy. Intraductal ultrasonography(IDUS)led to the suspicion of a nonepithelial tumor or an enlarged lymph node. Repeated biopsies via ERC were performed based on the absence of evidence of malignancy and revealed the presence of some atypical cells within the lesions. Although no definitive diagnosis could be made, the patient was scheduled for surgery in June 2017 after obtaining his consent. Upon taping of the common bile duct during surgery, a tumor was palpable on the dorsal aspect of the pancreas. The bile duct tumor was completely excised and submitted for intraoperative diagnosis; the pancreatic dorsal aspect appeared to be totally split. There was no evidence of atypia in the neoplasm, which was therefore considered to be benign; however, malignancy could not be completely ruled out because the patient had presented with elevated serum levels of carbohydrate antigen(CA)19-9 once before the operation. After intraoperative consultation with the patient's family members, who were reluctant to provide consent for pancreaticoduodenectomy, we completed the operation with resection of the bile duct tumor, followed by choledochojejunostomy. The tumor was found to be chromogranin A(+), cluster of differentiation(CD)56(+/-), CA19-9(+, solely ductal structure), carcinoembryonic antigen(CEA)(+, solely ductal structure), and intranuclear p53(-), with an MIB- 1 index of<2%. With regard to neuroendocrine markers, a region that could potentially have been a carcinoid tumor, based on the findings on hematoxylin and eosin(HE)staining, and a lumenized superficial region showed positivity in toto. Therefore, the lesion as a whole was diagnosed as a G1 carcinoid neuroendocrine tumor(NET). However, the superficial lumenized layer was positive for both CA19-9 and CEA; therefore, the tumor was thought to concurrently have epithelial characteristics. The lateral stumpwas negative, while the status of the ablated region remained unclear. After discussing the histopathologic examination results with the patient and his family members, the patient's follow-upwas decided to consist of periodic checkups without any further surgical intervention. The patient has since remained free of recurrence. Carcinoid tumor of the bile duct is extremely rare but should be considered in cases involving bile duct tumors that show enhancement on imaging prior to surgery and for which no definitive diagnosis can be established despite repeated biopsy explorations.

[A Case of Complete Response to Computed Tomography-Guided Celiac Plexus Neurolysis of Pain Associated with Postoperative Recurrence of Colon Cancer].

The patient was a man in his 40s, who had undergone laparoscopic ileocecal resection with lymph node dissection(D3)for cecal cancer in January 2012. Histopathological examination of the resected specimens had revealed StageⅡ primary tumor with subserosal invasion and positive metastasis in 1-3 regional lymph nodes(pT2[SS]n1[+]). The pathological stage was Ⅲa(fStage Ⅲa), and the tumor showed RAS gene mutation. The patient was administered 5 cycles of postoperative adjuvant chemotherapy with oral tegafur/uracil(UFT)in combination with calcium folinate(UZEL). Abdominal computed tomography( CT)performed 1.5 years postoperatively revealed liver metastasis, and a laparoscopic partial hepatectomy was performed in August 2015. In addition, a node in the greater omentum, located in the inferior surface of the liver, was also resected. Histopathological examination of the resected specimens revealed peritoneal metastasis, based on the identification of the same type of adenocarcinoma as the colon cancer. The patient was given 8 cycles of adjuvant chemotherapy with capecitabine and oxaliplatin(CapeOX). Then, he presented with colonic ileus, caused by recurrent dissemination, and underwent a laparoscopic transverse colectomy in October 2015. Multiple perineal disseminations were found intraoperatively, and chemotherapy was initiated with irinotecan plus tegafur/gimeracil/oteracil(S-1)plus bevacizumab(IRIS/BV)for the recurrent and unresectable disease. After 27 cycles of this regimen, lung metastasis was detected; in addition, progression of the para-aortic node metastasis around the celiac plexus was also observed, and the patient was considered as having pro- gressive disease(PD). Treatment with trifluridine/tipiracil(TAS102)was started in September 2017. Prior to the initiation of this regimen, the dose of opioid rescue medication previously started for back and abdominal pain was rapidly increased. Accordingly, the base dose was increased, but the pain could not be controlled, and the major pain was consistently located along the area of innervation in the celiac plexus. Therefore, celiac plexus neurolysis(CPN)was performed as a local therapy. A CT-guided injection technique was used to administer urografin, bupivacaine, and absolute ethanol to complete the procedure. The patient was discharged without major complications, and the base opioid dose was gradually reduced. Since the patient did not require any rescue medication during daytime on some days, the reduction of the base opioid dose was significantly effective in improving the patient's quality of life(QOL). In patients with pain possibly caused by metastasis to the para-aortic nodes, this local therapy technique may be considered.

[A Case of Advanced Breast Cancer in Which Marked Improvement of Joint Pain Was Obtained with Stepwise Dose Reduction of Trastuzumab Emtansine (T-DM1)].

A 51-year-old woman had previously received treatment for breast cancer at another hospital but had refused early and aggressive treatment. Therefore, she was treated with symptomatic therapy. As her disease progressed, the patient wished to receive palliative care, and was transferred to a palliative care hospital. However, based on her general condition, it was determined that aggressive treatment should not be abandoned, and she was referred to our hospital for treatment. During her initial visit, the patient was found to have left breast cancer with chest wall invasion, right breast metastasis, multiple liver and lung metastases, left pleural effusion accompanied by pleural dissemination, and left upper limb edema. There was no evidence of bone metastases. The patient's pain was managed with oral oxycodone sustained-release tablets (320 mg daily), using high-dose (80 mg) oral oxycodone hydrochloride hydrate as rescue medication. The results of immunohistochemical testing, confirmed by her previous hospital, were ER (-), PgR (-) and HER2/neu positive. First-line treatment was initiated with paclitaxel (PTX) plus trastuzumab (Tmab), and the response was rated as stable disease (SD). During the course of treatment, she developed drug-induced interstitial pneumonia, which was probably caused by the taxane. Therefore, the first-line treatment was discontinued and T-DM1 was initiated as second-line treatment. However, beginning with cycle 3 of the T-DM1 treatment, the patient began complaining of joint pain, mainly in the upper limbs. Therefore, the dose of oxycodone sustained-release tablets was increased to 600 mg per day. However, the patient's joint pain showed no improvement and it was considered unlikely that the pain was due to bone metastases. It was suspected that the pain was an adverse reaction to T-DM1, and the dose of T-DM1 was reduced by one step in cycle 7 of treatment. This resulted in a dramatic improvement of the patient's symptoms. Since oxycodone sustained-release tablets was being used at a high dose, sleepiness caused by the drug interfered with her activities of daily living. Consequently, as part of an opioid rotation scheme, topical fentanyl citrate was used concomitantly, and the initial daily oxycodone sustained-release tablets dose of 600 mg was reduced to 40 mg and administered in combination with fentanyl citrate (12mg). These findings suggest that uncontrollable joint pain can occur as an adverse reaction to T-DM1.

3'-Azido-2',3'-dideoxynucleoside 5'-triphosphates inhibit telomerase activity in vitro, and the corresponding nucleosides cause telomere shortening in human HL60 cells.

Telomerase adds telomeric DNA repeats to the ends of linear chromosomal DNA. 3'-Azido-3'-deoxythymidine 5'-triphosphate (AZTTP) is a known telomerase inhibitor. To obtain more selective and potent inhibitors that can be employed as tools for studying telomerase, we investigated the telomerase-inhibitory effects of purine nucleosides bearing a 3'-down azido group: 3'-azido-2',3'-dideoxyguanosine (AZddG) 5'-triphosphate (AZddGTP), 3'-azido-2',3'-dideoxy-6-thioguanosine (AZddSG) 5'-triphosphate (AZddSGTP), 3'-azido-2',3'-dideoxyadenosine (AZddA) 5'-triphosphate (AZddATP) and 3'-azido-2',3'-dideoxy-2-aminoadenosine (AZddAA) 5'-triphosphate (AZddAATP). Of these, AZddGTP showed the most potent inhibitory activity against HeLa cell telomerase. AZddGTP was significantly incorporated into the 3'-terminus of DNA by partially purified telomerase. However, AZddGTP did not exhibit significant inhibitory activity against DNA polymerases alpha and delta, suggesting that AZddGTP is a selective inhibitor of telomerase. We also investigated whether long-term treatment with these nucleosides could alter telomere length and growth rates of human HL60 cells in culture. Southern hybridization analysis of genomic DNA prepared from cells cultured in the presence of AZddG and AZddAA revealed reproducible telomere shortening.