Sunitinib-induced hyperammonemic encephalopathy in metastatic gastrointestinal stromal tumors: A case report.

BACKGROUND: Sunitinib, a multi-targeted tyrosine kinase inhibitor (TKI), has been approved for the salvage treatment of gastrointestinal stromal tumors (GIST). Hyperammonemic encephalopathy is a rare but severe complication of sunitinib use. Here, we present the case of a 66-year-old male with metastatic GIST without underlying liver cirrhosis who developed sunitinib-induced hyperammonemic encephalopathy. CASE SUMMARY: A 66-year-old male with metastatic GIST was admitted because of reduced consciousness. Imatinib was administered as the first-line systemic therapy. He experienced repeated episodes of peritonitis due to tumor perforation, and surgery was performed. Progressive disease was confirmed based on increased liver metastasis, and sunitinib was initiated as a salvage treatment. However, 23 d after the third course of sunitinib, he presented to the emergency room with an episode of altered consciousness and behavioral changes. Based on the patient clinical history and examination findings, sunitinib-induced encephalopathy was suspected. Sunitinib was discontinued, and the patient was treated for hyperammonemia. The patient had a normal level of consciousness four days later, and the serum ammonia level gradually decreased. No further neurological symptoms were reported in subsequent follow-ups. CONCLUSION: TKI-induced hyperammonemic encephalopathy is potentially life-threatening. Patients receiving TKIs experiencing adverse reactions should undergo systemic evaluation and prompt treatment.

[A Case of Fournier's Gangrene during Second-Line IRIS plus Bevacizumab Chemotherapy for Rectal and Anal Canal Cancer].

A 52-year-old man diagnosed with Stage ⅢA rectal and anal canal cancer underwent abdominal perineal resection using Miles's method. Two years later, local recurrence and lung metastases were detected using contrasted CT imaging. First-line chemotherapy of XELOX was administered for 4 months until the disease progressed and lung metastases developed. After 4 courses of second-line IRIS plus bevacizumab chemotherapy, fever and swelling of the right buttock appeared; he visited and was admitted to our hospital. A CT scan revealed a pelvic abscess which resulted in septic shock. Swelling and pain extended to the right scrotum, and acute necrotizing fasciitis was suspected, and emergency surgery was performed. An incision was made from the right buttock to the right scrotum, bloody purulent drainage with a foul odor was observed, and a diagnosis of Fournier's gangrene was made. Although typical CT findings such as emphysema due to gas-producing bacteria were not observed in this case, early diagnosis and intervention of systemic management including early surgical drainage and operation were effective. For pelvic infections occurring during bevacizumab chemotherapy, Fournier's gangrene should considered for differential diagnosis, even if CT findings are atypical.

[A Case of Superior Vena Cava Syndrome Due to Recurrent Breast Cancer Effectively Treated by Trastuzumab Deruxtecan].

A 64-year-old female underwent Bt+Ax surgery due to ER(-), PR(-), HER2(+), ycT3N1M0, Stage ⅢA right breast cancer. After cancer recured in the chest wall, whole-breast radiation therapy was performed, followed by ddAC, and T- DM1. After 12 courses of T-DM1, CT scan and physical findings showed no evidence of metastases, so chemotherapy was suspended with strict follow-up. Seven months later, a chest wall recurrence with pleural dissemination was found and 9 courses of PER plus HER plus eribulin therapy was administered until disease progression. T-DM1 was re-administered but disease progressed after 2 courses accompanied by SVC syndrome due to 8 cm mediastinal lymph node metastasis which caused respiratory discomfort and face edema. We administered T-DXd and after the first course respiratory symptoms vanished, and after 3 courses lymph node metastasis shrunk extremely in the CT imaging. SVCS is one of the oncologic emergencies, in which palliative radiotherapy may be typically selected for the relief of symptoms, and intravascular stents are used in urgent cases. Surprisingly, we experienced a case of SVC syndrome caused by breast cancer metastasis, effectively treated by T-DXd.

Focal neuroendocrine carcinoma mixed with adenocarcinoma of the gallbladder with aggressive lymph node metastasis in a patient who did not meet the mixed neuroendocrine-non-neuroendocrine neoplasm criteria.

A 70-year-old Japanese woman who was treated for interstitial pneumonia (IP) with steroid therapy developed cholecystitis. A serial computed-tomography (CT) imaging showed irregular thickness of the fundus wall of the gallbladder and two rapidly enlarged lymph nodes (LNs): number (no.) 12 and no. 8a. Positron-emission tomography-computed tomography (PET-CT) scan showed an abnormal uptake at the site of the gallbladder tumor and those LNs. We subsequently performed open radical cholecystectomy and LN dissection of the no. 12 and 8a LNs, following complete remission of IP. The histology showed gallbladder adenocarcinoma, with a single focus of neuroendocrine carcinoma (NEC) component of less than 30%; Ki-67 index > 80%, synaptophysin (Syn) (+), chromogranin A (CgA) (+), and clusters of differentiation (CD) 56 (+) (T2bN1M0, Stage IIIB). LN no. 8a was diffusely metastatic with NEC components. LN no. 12c, which was adjacent to the cystic duct, revealed necrosis without apparent tumor cells, but was highly suspicious for tumor necrosis. The final diagnosis was adenocarcinoma of the gallbladder with focal NEC (< 30%), which did not meet the criteria for mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN). Postoperatively, she completed 4 cycles of adjuvant chemotherapy for NEC (Cisplatin plus Etoposide), and no recurrence was observed after 12 months.

[A Case of an Advanced Intrahepatic Cholangiocarcinoma Effectively Treated by Conversion Surgery after Neoadjuvant Chemotherapy of Gemcitabine, Cisplatin and S-1].

A 61-year-old male suffered from intrahepatic cholangiocarcinoma in S7 lesion(90 mm diameter), diagnosed by hepatic tumor biopsy. As PET-CT showed para-aortic lymph node metastasis(cT3N1M1, cStage ⅣB), and judged to be unresectable, he received neoadjuvant chemotherapy of gemcitabine, cisplatin, and S-1(GCS). After 7 courses of GCS, CT showed partial response of the primary tumor and PET-CT showed decreased accumulation of FDG at para-aortic lymph node. Resectability was reexamined and the patient underwent S7 extended subsegmentectomy as conversion surgery. Furthermore, after the surgery, he received adjuvant chemotherapy of S-1 for 6 months, and he remained relapse-free for the next 2 years. Cholangiocarcinoma is one of the most poorly prognosed type cancer. Conversion surgery for unresectable intrahepatic cholangiocarcinoma is frequently reported, but there are still few reports of GCS as neoadjuvant chemotherapy. Here, we report a case of unresectable intrahepatic cholangiocarcinoma that was successfully treated with GCS and underwent conversion surgery.

[Incidence of Secondary Malignancy of Chronic Myeloid Leukemia during Treatment of Breast Cancer with Hormone Therapy].

It is expected that the number of long-term breast cancer survivors will increase owing to the improvements in chemotherapy and irradiation, while the risk of double cancers, including secondary malignancy, may become an issue. There are many unclear points in the treatment policy with regard to when a secondary malignancy occurs or the primary cancer relapses during the management of a secondary malignancy. A 54-year-old woman who was diagnosed with ER/PgR-positive HER2 negative breast cancer Stage ⅢB received neoadjuvant chemotherapy FEC and docetaxel followed by breast surgery, adjuvant hormone therapy, and radiation therapy. Chronic myeloid leukemia diagnosed by the abnormal findings of leukocytosis and bone marrow aspiration emerged after 3 years of the diagnosis of the first breast cancer. After 3 years of imatinib therapy that achieved a major molecular response(MMR)of CML, a recurrence of sacral metastasis of breast cancer was revealed by MRI. The combination of imatinib and hormone or S-1 chemotherapy could be maintained without serious adverse events after the relapse of the primary cancer.

[A Case of Advanced Esophageal Cancer Discovered Due to Suffocation, Which Was Invasive to the Trachea and Internal Carotid Artery and Treated by Chemotherapy].

A 51-year-old male presented with dyspnea due to upper airway obstruction. We decided to perform a cricothyroidotomy due to difficulty in performing orotracheal intubation. A CT scan revealed a massive tumor infiltrating into the right side of the neck, which penetrated the internal carotid artery. An upper gastrointestinal tract endoscopy was performed, and the patient was diagnosed with advanced esophageal cancer(stage Ⅳ, cT4N4M0). We initiated palliative chemotherapy of FOLFOX as first-line chemotherapy. After the fourth course, the patient was evaluated as having progressive disease(PD)due to regrowth of lymph node metastasis around the lower esophagus. Although we changed the treatment to nivolumab as second-line chemotherapy, there was a gradual exacerbation of airway obstruction, and the head and upper limb edema emerged due to superior vena cava syndrome. After the first course of nivolumab, we diagnosed the patient as having clinically PD. After the first course of docetaxel(DTX)as third-line chemotherapy, he suddenly died of massive hemorrhage caused by the intubation tube on day 136. Airway management is difficult to perform in patients with a poor response to chemotherapy due to obstruction by a tumor. On the other hand, excessive response to chemotherapy is also associated with a risk of massive hemorrhage due to arterial perforation, as observed in this case.

[A Case of Ipsilateral Breast Tumor Recurrence(IBTR)after Breast-Conserving Surgery Which Successfully Resected after Chemotherapy Using Carboplatin plus Gemcitabine].

A 39-year-old woman underwent partial mastectomy with sentinel lymph node biopsy for right triple negative breast cancer(T2N0M0, Stage ⅡA). Six months later, ipsilateral breast tumor recurrence(IBTR)was observed and paclitaxel plus bevacizumab therapy was started, but anaphylactoid symptoms appeared and the patient was discontinued. Subsequently, eribulin was started, but the IBTR was increased ineffectively. At that point, IBTR had progressed, apparently unresectable, with no distant metastases. We predicted from the patient's background that the patient may be associated with BRCA1 gene mutation and was sensitive to the platinum salts. Carboplatin plus gemcitabine was selected and 6 courses were performed. After the 6 courses, the IBTR were remarkably reduced and resectable, and mastectomy with axillary lymph node dissection were performed. One year after the operation, contralateral breast cancer develop and found to be hereditary breast and ovarian cancer syndrome (HBOC) by Genetic test. About 6 years have passed since local recurrence, but no distant metastases have been observed.

[A Case of Recurrent Premenopausal Hormone Receptor Positive Breast Cancer with Liver, Lung and Bone Metastasis Successfully Treated with Endocrine Therapy].

Here we report a 48-year-old female with recurrent breast cancer. She had received chest muscle-conserving mastectomy and lymph node dissection at another hospital, diagnosed as pStage ⅡB, T2N1M0 premenopausal left endocrine positive/ HER2 negative breast cancer at the age of 45. Although postoperative adjuvant therapy was started with LH-RH agonist plus tamoxifen, and chest radiation, tamoxifen therapy was intolerantly discontinued due to severe adverse events of hot flash after 1 year later. Three years later, she presented with back pain and was referred to our hospital. As PET-CT revealed recurrence of multiple bone and lung metastases and solitary liver metastasis which did not seem to be life-threatening, palliative radiation therapy and endocrine therapy with leuprorelin and anastrozole(LA)were started. Eighteen months later, PET-CT showed complete disappearance of liver and lung metastases and remarkable regression of bone metastases except for the right sciatic bone. LA therapy could be maintained for a total of 30 months until metastatic recurrence on liver and bone emerged. LA endocrine therapy may be effective for patients with premenopausal hormone-positive breast cancer even if the difficult situation such as tamoxifen intolerance.

A Phase II Study of Regorafenib With a Lower Starting Dose in Patients With Metastatic Colorectal Cancer: Exposure-Toxicity Analysis of Unbound Regorafenib and Its Active Metabolites (RESET Trial).

BACKGROUND: Regorafenib demonstrated survival benefits as salvage therapy for patients with metastatic colorectal cancer. However, severe toxicities frequently occurred early in the treatment with the standard dose (160 mg/day), resulting in a dose reduction or interruption. To improve the tolerability and maintain sufficient efficacy, we conducted a phase II study of regorafenib with a lower starting dose (120 mg/day). PATIENTS AND METHODS: Regorafenib was initiated at 120 mg/day, and the dosage was increased to 160 mg/day on day 15 of the first cycle for patients who had met the dose escalation criteria. The primary endpoint was the disease control rate (DCR). The pharmacokinetics of the total and unbound regorafenib and its active metabolites (M2, M5) were assessed. RESULTS: A total of 70 patients were enrolled from September 2016 to December 2017. Only 6 patients achieved dose escalation to 160 mg on day 15 as planned. For the 68 evaluable patients, the DCR was 32.4% (95% confidence interval, 21.5%-44.8%), which was less than the threshold (30%) of our statistical hypothesis. The serum concentrations of total regorafenib for patients whose dose was escalated to 160 mg/day were significantly lower than those of the patients whose dose was not escalated (median, 3978 vs. 7244 nM; P = .027). The serum unbound concentrations of the sum of regorafenib and the active metabolites correlated significantly with the maximum grade of regorafenib-related symptomatic adverse events in the first cycle (11,138 vs. 19,096 pM; P = .035). CONCLUSION: Regorafenib with a low starting dose of 120 mg/day did not achieve the expected DCR. A relationship of unbound exposure with toxicity was found.

Female Functional Constipation Is Associated with Overactive Bladder Symptoms and Urinary Incontinence.

This noninterventional cross-sectional study aims to assess the association between functional constipation (FC) and urinary symptoms in female patients with no treatment for urination and defecation. The Rome III criteria for evaluation of defecation, Overactive Bladder Symptom Score (OABSS) for evaluation of urinary symptoms, and clinical features were investigated in 145 female patients. Latent FC and moderate to severe overactive bladder (OAB) were defined on the basis of positivity for two or more of the Rome III criteria and an OABSS ≥ 6 with OABSS Q3 ≥ 2, respectively. In 60 latent FC patients, the OABSS was higher (5.0 versus 3.2, p = 0.001), and concurrent moderate to severe OAB symptoms and OAB with urinary incontinence were more frequent than those in 85 nonlatent FC patients (33.3 versus 10.6%, p = 0.001, and 31.7 versus 7.1%, p < 0.001). Multivariate analysis demonstrated that moderate to severe OAB symptoms were a significant associated factor of latent FC (odds ratio (OR) = 4.125, p = 0.005), while latent FC was the only associated factor of moderate to severe OAB and OAB with urinary incontinence (OR = 4.227, p = 0.005 and OR = 4.753, p = 0.004). In conclusion, moderate to severe OAB symptoms are correlated with FC. Moreover, FC is related to moderate to severe OAB symptoms and to OAB with urinary incontinence.

Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells.

Cancer-associated fibroblasts contribute to cancer progression that is caused by epithelial-mesenchymal transition (EMT). Recently, mesenchymal stem cells (MSCs) were found to be the major candidate involved in the development of tumor-promoting cancer stroma. Here we report that α-smooth muscle actin-positive myofibroblast-like cells originating from MSCs contribute to inducing EMT in side population cells of pancreatic cancer. More importantly, MSC-derived myofibroblasts function to maintain tumor-initiating stem cell-like characteristics, including augmenting expression levels of various stemness-associated genes, enhancing sphere- forming activity, promoting tumor formation in a mouse xenograft model, and showing resistance to anticancer drugs. Furthermore, both γ-secretase inhibitor and siRNA directed against Jagged-1 attenuated MSC-associated E-cadherin suppression and sphere formation in pancreatic cancer side population cells. Thus, our results suggest that MSC-derived myofibroblasts play important roles in regulating EMT and tumor-initiating stem cell-like properties of pancreatic cancer cells through an intermediating Notch signal.

Suppression of myeloid cell leukemia-1 (Mcl-1) enhances chemotherapy-associated apoptosis in gastric cancer cells.

BACKGROUND: Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that regulates apoptosis sensitivity in a variety of cell types. Here we evaluate the roles of Mcl-1 in chemotherapy-associated apoptosis in gastric cancer cells. In addition, our study examined whether Mcl-1 contributed to apoptosis resistance in so-called cancer stem cell (CSC)-like populations in gastric cancer. METHODS: Seven gastric cancer cell lines were used. The expression of Mcl-1 was assessed by either real-time polymerase chain reaction or Western blot analysis. Apoptosis was quantitated by morphological observation and caspase activity measurement. Adenovirus-mediated RNA interference (RNAi) technology was used to knockdown the expression of Mcl-1. The release of cytochrome c was evaluated by subcellular fractionation and immunoblot analysis. To identify and isolate the CSC-like populations, we used the CSC-associated cell surface marker CD44 and flow cytometry. RESULTS: Six out of the 7 gastric cancer cell lines overexpressed Mcl-1 protein. These Mcl-1-expressing cell lines were relatively resistant to chemotherapeutic agents such as 5-fluorouracil (5-FU) and cisplatin (CDDP). Depletion of Mcl-1 protein by RNAi technology effectively sensitized the cells to anticancer drug-induced mitochondrial cytochrome c release, caspase activation, and apoptosis. In addition, vast amounts of Mcl-1 mRNA were expressed in CD44-positive CSC-like cells. Mcl-1 suppression enhanced the apoptosis in CD44-positive cells to a level equivalent to that in CD44-negative cells, suggesting that Mcl-1 mediates chemotherapy resistance in CSC-like populations. CONCLUSION: These results suggest that Mcl-1 mediates the resistance to apoptosis in gastric cancer cells by blocking the mitochondrial pathway of cell death. Mcl-1 depletion appears to be an attractive strategy to overcome chemotherapy resistance in gastric cancer cells.

Second-line chemotherapy for refractory small cell neuroendocrine carcinoma of the esophagus that relapsed after complete remission with irinotecan plus cisplatin therapy: Case report and review of the literature.

Small cell esophageal carcinoma is a type of small cell neuroendocrine carcinoma (SCNEC). SCNEC follows an aggressive clinical course and has a poor prognosis despite multidisciplinary therapies. A standard therapeutic strategy, including surgery, radiation and first-/second-line chemotherapy, has not yet been established for SCNEC. We present a case of SCNEC of the esophagus. A 66-year-old male with SCNEC as extensive disease was treated with 60 mg/m(2) cisplatin on day 1 plus 60 mg/m(2) irinotecan on days 1, 8 and 15 every 4 weeks (IP) with successful complete remission. After the sixth course of IP, increasing pro-gastrin-releasing peptide (ProGRP) and nonspecific enolase (NSE) levels and intense fluorodeoxyglucose (FDG) avidity in a lymph node around the celiac artery (SUV(max), 8.3) indicated a refractory relapse of the disease. The patient was treated with three courses of amrubicin (AMR, 35 mg/m(2)) administered intravenously for 3 consecutive days every 3 weeks as a second-line chemotherapy. The ProGRP and NSE levels returned to the normal range 1 month after the initiation of second-line chemotherapy. However, the ProGRP and NSE levels were elevated after the third course of AMR, and PET-CT revealed progressive disease with liver metastasis and extended lymph node metastasis. As the patient remained asymptomatic, paclitaxel (100 mg/m(2)) was started as third-line chemotherapy. Patients with SCNEC of the esophagus with extensive disease should be treated with aggressive chemotherapy rather than surgery or radiation monotherapy. In the present case, tumor markers such as ProGRP and NSE were predictive of relapse and PET-CT was used to detect relapse. Further research is required to identify and exploit promising agents for resistant SCNEC.

Phase I study of combination chemotherapy consisting of paclitaxel, cisplatin, and S-1 in patients with unresectable gastric cancer (KOGC-02).

BACKGROUND: Triplet combination chemotherapy has the potential to improve the prognosis of patients with unresectable gastric cancer. We conducted a phase I trial of triplet combination chemotherapy consisting of paclitaxel, cisplatin, and S-1 (PCS) for unresectable gastric cancer. PATIENTS AND METHODS: Patients with metastatic or incurable disease were enrolled. S-1 was administered on days 1-14. Paclitaxel and cisplatin were infused on days 1 and 15. The starting doses of paclitaxel and cisplatin were 100 and 20 mg/m(2), respectively. Dose levels of paclitaxel and cisplatin were escalated as follows: 120 and 20 mg/m(2), respectively (level 2); 120 and 30 mg/m(2), respectively (level 3). End-points: Dose-limiting toxicities included grade 3 nausea, vomiting, and general fatigue, and grade 4 febrile neutropenia. The maximum tolerated dose and recommended dose were established at level 3 and level 2, respectively. CONCLUSION: Although further clinical trials are recommended to more thoroughly evaluate safety and efficacy, PCS appears to be an excellent candidate for a standard treatment strategy for unresectable gastric cancer.

Chemoresistance is associated with cancer stem cell-like properties and epithelial-to-mesenchymal transition in pancreatic cancer cells.

BACKGROUND: The aim of this study was to evaluate whether apoptosis-resistant cancer cells have cancer stem cell (CSC)-like properties. MATERIALS AND METHODS: Panc-1 pancreatic cancer cells were incubated in the presence of 5-fluorouracil (5-FU) for 24 h, and further incubated without 5-FU for 28 days. To assess the capacity of self-renewal, surviving cells were planted for sphere-forming assay. Epithelial-to-mesenchymal transition (EMT) was induced with TGF-ß, then mRNA expression was evaluated by real-time PCR for E-cadherin, SNAIL, and vimentin. The E-Cadherin protein levels were also examined by immunoblot analysis. The Local invasion ability was analyzed by Matrigel invasion assay. RESULTS: The frequency of cells that were capable of initiating spheres was higher in 5-FU-pre treated cells, which also overexpressed stem cell marker genes, OCT4 and NANOG. Matrigel invasion activity of apoptosis-resistant Panc-1 cells was greater than that of control Panc-1 cells. CONCLUSION: Apoptosis-resistant cancer cells have CSC-like properties, i.e., able to initiate sphere formation, express stem cell genes, and respond to EMT stimulation.

Colon neoplastic cells do not originate from bone marrow-derived cells after sex-mismatched bone marrow transplantation.

BACKGROUND: Although previous studies indicate that gastrointestinal (GI) cancer may originate from cells recruited from bone marrow (BM) in mice, whether similar phenomena occur in humans is controversial. In the current study, we evaluated two female patients who developed colonic adenocarcinoma more than 10 years after gender-mismatched BM transplantation, and followingly underwent successful endoscopic mucosal resection. MATERIALS AND METHODS: Fluorescent in situ hybridization (FISH) analysis was used to determine whether the tumours contained donor-derived BM cells. RESULTS: Approximately 1.2% of the tumour cells contained Y-chromosome-positive signals, and a comparable percentage of normal colonic epithelial cells close to the tumour also contained Y-chromosome-positive signals. CONCLUSION: These results do not support the concept that GI cancer can originate from BM-derived cells.

Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1/HMGB2) antibodies and anti-Saccharomyces cerevisiae antibodies (ASCA): accuracy in differentially diagnosing UC and CD and correlation with inflammatory bowel disease phenotype.

BACKGROUND: The development of a supportive diagnostic method has long been required to differentially diagnose ulcerative colitis (UC) and Crohn's disease (CD). Several antibodies circulate in the sera of patients with inflammatory bowel disease. We previously identified the high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1 and HMGB2) as novel antigens of perinuclear type anti-neutrophil cytoplasmic antibodies (pANCA) and discovered anti-HMGB1/HMGB2 antibodies in sera from patients with UC. Here, we evaluated the ability of anti-HMGB1/HMGB2 antibodies combined with anti-Saccharomyces cerevisiae antibodies (ASCA) to differentially diagnose UC and CD. METHODS: We measured titers of anti-HMGB1/HMGB2 antibodies and ASCA in the sera of 213 patients with UC and 93 with CD, using enzyme-linked immunosorbent assays. RESULTS: Among the patients with UC, 26.8% were positive for anti-HMGB1/HMGB2 antibodies, with 85.0% specificity towards CD and a positive predictive value of 80.3%. Corticosteroids significantly suppressed the titer of anti-HMGB1/HMGB2 antibodies. Among the patients with CD, 24.7% were positive for ASCA, with 96.2% specificity towards UC and a positive predictive value of 74.2%. Interestingly, the positivity rate of anti-HMGB/HMGB2 antibodies was higher (35.7%) in patients with the ileitis type of CD than in patients with CD in the colon (6.2%; significant difference, P < 0.01). The specificity of anti-HMGB1/HMGB2 antibodies in UC for CD in the colon was 93.8%. CONCLUSIONS: CD in the colon and UC can be differentially diagnosed using anti-HMGB/HMGB2 antibodies combined with ASCA.

5-aminosalicylic acid mediates expression of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase to suppress colorectal tumorigenesis.

BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme that produces prostaglandin E2 (PGE2) and plays an important role in colorectal tumor growth. In addition, recent researches focused on 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades PGE2. Here we determined the effect of 5-aminosalicylic acid (5-ASA) on COX-2 and 15-PGDH expression and investigated its preventive effect for colorectal cancer (CRC). MATERIALS AND METHODS: HT-29 cells were used in the in vitro experiments. c-Ha-ras transgenic mice were employed in order to explore the chemopreventive effects. Western blotting analysis was performed and the protein expression of COX-2 and 15-PGDH was quantified. RESULTS: 5-ASA significantly suppressed COX-2 expression and induced 15-PGDH expression in HT-29 cells. In the transgenic mice, oral 5-ASA intake reduced the incidence of colorectal tumor formation and the tumor size. Furthermore, we observed a down-regulation of COX-2 and an up-regulation of 15-PGDH in the tissue from colons of these mice. CONCLUSION: 5-ASA exerts a preventive effect against colorectal tumor development through mediation of COX-2 and 15-PGDH expression.

[A case of metastatic esophageal cancer - endoscopic resection of the primary site following systemic chemotherapies].

A 64-year-old male presented with discomfort in the chest. His endoscopic examination and CT scan showed esophageal cancer with multiple liver metastases. A total of ten courses of systemic chemotherapy by 5-fluorouracil (5-FU) (800 mg for five days) and cisplatin (CDDP) (80 mg/day on the first day of the week for four weeks) were performed, and liver and lymph node metastases disappeared. The primary lesion was the only site detected positive by PET scan. After a concurrent chemoradiation therapy, salvage endoscopic mucosal resection (EMR) was performed on the remainder of the primary site and the patient gained a complete response (CR). We report this case because, although the mean survival time of advanced esophageal cancer is less than one year, this patient responded to chemotherapy and gained complete response by salvage EMR. This patient has had no recurrence for four years since his initial diagnosis.