CA 19-9, equivalent to Sialyl Lewis antigen, is a well-known tumor marker in pancreatic cancer. At the initial step of the biosynthesis of CA 19-9, N-acetylglucosamine-beta1,3-galactosyltransferase (beta3Gal-T) transfers galactose to N-acetylglucosamine (GlcNAc). Recently, beta3Gal-T5 has been presumed to be related to the formation of the type 1 chain in an in vitro experiment in terms of kinetic enzyme characterization. The purpose of this study was to investigate which beta3Gal-T is related to the synthesis of CA 19-9 in human pancreatic cancer tissues.We examined beta;3Gal-T1, T2, T3, T4, and beta;3Gal-T5 mRNA expressions in 13 noncancerous and cancerous tissues of the human pancreas using real-time polymerase chain reaction, and compared those gene expression levels with the immunoreactivity of CA 19-9 and its precursor DUPAN-2 in cancerous tissues.Beta;3Gal-T5 gene expression significantly augmented in cancerous tissues, when compared with the adjacent noncancerous tissues. Additionally, there was a good correlation between BETA;3GAL-T5 gene transcription levels and immunohistochemical grades of CA 19-9 or its precursor DUPAN-2 in cancerous tissues. However, no correlation was observed between beta;3Gal-T1, T2, T3, and beta;3Gal-T4 gene expression levels and CA 19-9 or DUPAN-2 immunoreactive grades in cancerous tissue.beta3Gal-T5 is presumed to be responsible for the synthesis of CA 19-9 in pancreatic cancer tissue.
79 Background: Chemotherapy with panitumumab is expected to be well tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). However, skin toxicities are its most common adverse events. The aim of this trial was to evaluate the efficacy and safety of pre-emptive antibiotic treatment with clarithromycin (CAM) to prevent panitumumab skin toxicities. Methods: We conducted a phase lll, multicenter, open-label, randomized clinical trial on mCRC patients treated with pani- tumumab. Eligible patients were randomly assigned 1:1 to pre-emptive antibiotic and control groups. In the pre-emptive group, CAM administration (200 mg twice per day) continued daily through the panitumumab treatment period. The control regimen consisted of skin care only. The primary end point was the incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period. Results: Of 156 enrolled patients, 78 received pre-emptive antibiotic treatment, and 78 received reactive treatment. The number and incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period were 16 (21.3%) and 41 (54.7%) for the pre-emptive and control groups, respectively (HR, 0.32; 95% CI, 0.17–0.56). There was almost no difference in the rate of other adverse events between the two groups, but the incidence of grade ≥ 3 diarrhea in the pre-emptive group was high, at 8% vs. 1.3% in the control group. There were no treatment-related deaths. Conclusions: Prophylactic oral CAM together with relatively simple skin care was found to be effective in suppressing the development of grade ≥ 2 skin toxicities induced by panitumumab. Clinical trial information: UMIN000011485.
Our recent study of the gene expression profile in thyroid carcinoma showed an overexpression of osteonectin mRNA, an extracellular matrix protein, in an anaplastic carcinoma. To confirm this, we measured the expression levels of osteonectin mRNA in 84 thyroid normal and tumor tissues, including five anaplastic carcinomas by realtime quantitative reverse-transcription PCR. Increased expression of osteonectin mRNA was observed in anaplastic carcinoma tissue. However, in five anaplastic carcinoma cell lines, no increase was observed in the expression levels of osteonectin mRNA. These findings suggest the possibility that increased expression of osteonectin mRNA in anaplastic carcinoma tissue may be due to its overexpression in stromal cells, but not in anaplastic carcinoma cells.
A 63-year-old man visited our hospital complaining of brown urine. A physical examination showed jaundice of the skin and conjunctiva bulbar. Blood tests showed elevated serum levels of bilirubin and hepatobiliary enzymes. A type 2-like mass lesion was found near the papilla of Vater during the endoscopic retrograde cholangiopancreatography and was histologically proven to be a well-differentiated adenocarcinoma. A diagnosis of obstructive jaundice due to primary duodenal cancer arising near the papilla of Vater was made. After the jaundice was decreased by endoscopic biliary stenting, a pancreatoduodenectomy was performed. A histopathological examination of the resected specimen concerning the location and manner of invasion of cancer cells revealed that the cancer arose from the duodenal mucosa near the papilla of Vater.
Peritoneal lymphomatosis is an extremely rare presentation of non-Hodgkin lymphoma. We report a case of peritoneal lymphomatosis diagnosed by single-port laparoscopic biopsy. A 70-year-old woman presented to our hospital with a 2-day history of increasing abdominal distension. Abdominal CT and positron emission tomography/CT(PET-CT)demonstrated extensive disseminated disease with marked thickening of the peritoneal surfaces, and a large omental cake with large volume ascites. Under the diagnosis of peritoneal carcinoma, single-port laparoscopic biopsy was performed. Pathological and immunohistochemical examination revealed diffuse large B-cell lymphoma presenting as peritoneal lymphomatosis. She was treated with a combination chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, and prednisolone(R- CHOP), and no recurrence was reported for 1 year and 6 months. Single-port laparoscopic biopsy was minimally invasive, and helpful for an urgent and accurate diagnosis and treatment of the disseminated peritoneal disease.
Single-site laparoscopic interval appendectomy (SLIA) for severe complicated appendicitis after conservative treatment (CT) to ameliorate inflammation and eradicate the abscess should be safer and less invasive than emergency appendectomy (EA). However, only a few reports have been published regarding SLIA.We retrospectively collected data on 264 consecutive patients admitted to Kinan Hospital for treatment of appendicitis between 2012 and 2018. The safety and feasibility of SLIA and its perioperative outcomes for severe complicated appendicitis were investigated.A total of 61 patients were included in this study, 25 of whom underwent CT and 36 EA. Among the 25 patients who underwent CT, 23 (92.0%) succeeded; a total of 16 patients (69.5%) underwent SLIA. Compared to the EA group, the SLIA group had less bleeding (median volume 8.5 vs 50 mL, P = .005) and lower rate of expansion surgery (0% vs 27.8%, P = .022). Although the postoperative hospital stay was shorter in the SLIA group than in the EA group (9 vs 12 days, P = .008), the total hospital stay, including the CT period, was longer in the SLIA group than in the EA group (24 vs 12 days, P < .001).SLIA is safe, feasible, and less invasive than EA and may provide the advantages of minimally invasive surgery even if appendicitis is severe. SLIA may be a promising option for complicated appendicitis in select cases despite its disadvantage of prolonging the hospital stay.
It is well known that chronic inflammatory conditions involving the bile ducts predispose to the development of bile duct carcinoma, although the relationship between chronic inflammation and malignant transformation is unclear. In this study, by combining immunohistochemistry and computer imaging techniques, we quantified and compared the cyclooxygenase-2 (COX-2) protein expression levels of epithelial cells according with their histopathological backgrounds. This technique revealed that the highest levels of COX-2 were expressed in bile duct carcinoma cells, mainly in cytoplasm, and the expression pattern was homogenous and abundant. Moderate levels of COX-2 protein expression were also observed in noncancerous epithelial cells with inflammatory reaction, but the staining intensity was heterogeneous among the positive cells exhibiting inflammation. In contrast, only scattered weak reactivity of COX-2 protein was observed in the noncancerous bile duct epithelial cells without inflammatory reaction. Moreover, bile duct epithelial cells in primary sclerosing cholangitis (PSC) showed very strong expression of COX-2 protein, that was comparable with carcinoma cells. On the other hand, primary biliary cirrhosis (PBC) epithelial cells showed moderate levels of COX-2 expression. In addition, specific COX-2 inhibitors, JTE-522 and NS-398, directly inhibited the growth of 4 bile duct carcinoma and 1 gall bladder carcinoma cell lines that expressed COX-2 protein, in vitro. These data suggest that COX-2 expression might regulate carcinogenesis of bile duct epithelial cells in inflammatory regions and tumor progression in this cancer. The data also suggest that COX-2 selective inhibitors might have therapeutic effects not only on bile duct carcinoma, but other hepatobiliary carcinomas.
The safety and feasibility of the chemotherapy for super-elderly patients over 85 years old have not been clarified yet. We report an extremely aged patient with recurrent rectal cancer that was successfully treated with chemotherapy. A 85-year-old woman underwent Hartmann procedure for rectal cancer. Nine months after surgery, CT scan revealed liver metastases in S5 and S7. We administered capecitabine plus bevacizumab chemotherapy. Liver metastases were disappeared after 6 courses. Although grade 2 hypertension was appeared, no other adverse event occurred. However, due to lung metastases, we attempted irinotecan plus bevacizumab as second line treatment. After 10 courses, general fatigue was gradually developed, so we changed the frequency of chemotherapy from biweekly to triweekly administration. The patient's performance status score has been kept 0, and she has been under treatment as an outpatient for 3 years. The chemotherapy for extremely aged patients with recurrent colorectal cancer was suggested to be safe and feasible under the adequate dose reduction and interval adjustment.
A 72-year-old man with ascending colon cancer was admitted to our hospital. Right hemicolectomy and lymph node dissection(D3)were performed. The pathological diagnosis was signet-ring cell carcinoma, T4a(SE), N2b, M1a(LYM), Stage Ⅳ, R0, Cur B. Capecitabine was administered after surgery. Subcutaneous bleeding, thrombocytopenia, and a rapid increase in tumor marker levels occurred 9 months after surgery. He had already developed disseminated intravascular coagulation and was admitted to our hospital immediately. CT scan revealed metastasis in the thoracic vertebrae. Bone scintigraphy demonstrated multiple abnormal areas of uptake in the costal bones and the thoracic and lumber vertebrae. We made a final diagnosis of disseminated carcinomatosis of the bone marrow by histopathological examination. Unfortunately, before starting chemotherapy, his general condition deteriorated, and he died 14 days after hospitalization. We present here a case of colon cancer with disseminated carcinomatosis of the bone marrow.
