[A Case of Thrombotic Thrombocytopenic Purpura in a Patient Undergoing FOLFOX6 plus Panitumumab Therapy for Unresectable Recurrent Rectal Cancer with a Rapidly Progressive Course].

A 71-year-old male patient began FOLFOX6 plus panitumumab treatment for unresectable recurrent rectal cancer. He developed thrombocytopenia after 2 courses of treatment and therefore a platelet transfusion was performed. The day after transfusion, the patient developed jaundice and hematuria. His lactate dehydrogenase levels had increased and a peripheral blood smear review revealed the presence of schistocytes. Anti-ADAMTS13 antibodies were present, and there was a reduction in ADAMTS13 activity. The patient was diagnosed with thrombotic thrombocytopenic purpura and treated with a plasma exchange. The day after the plasma exchange, his clinical condition rapidly worsened and he died. Thrombocytopenia due to chemotherapy often appears as myelosuppression. If conditions such as jaundice, indirect bilirubinemia, or hematuria appear during the course of chemotherapy, this condition must be considered as a differential diagnosis.

Daikenchuto stimulates colonic motility after laparoscopic-assisted colectomy.

BACKGROUND/AIMS: Paralytic ileus after laparoscopic-assisted surgery often occurs. We investigated whether daikenchuto (DKT), a traditional Japanese herbal medicine, improves intestinal motility in patients undergoing laparoscopic-assisted colectomy for colon cancer. METHODOLOGY: Fifty-four patients who underwent colectomy at Iwate Medical University Hospital between October 2010 and March 2012 were randomized to either the DKT group (7.5 g/day, p.o.) or the control group (lactobacillus preparation, 3g/day, p.o.). Primary endpoints included time to first flatus, bowel movement, and tolerance of diet after extubation. Secondary endpoints were WBC count, C-reactive protein (CRP) level, length of hospital stay, and postoperative ileus. Colonic transit time was measured using radiopaque markers and abdominal radiographs. RESULTS: Fifty-one patients (DKT, 26 vs. control, 25) were included in the per-protocol analysis. The DKT group had significantly faster time until first flatus (67.5 +/- 13.6h vs. 77.9 +/- 11.8h, P < 0.01) and bowel movement (82.9 +/- 17.8h vs. 99.5 +/- 18.9h, P < 0.01) and colonic transit time (91.9 +/- 19.8h vs. 115.2 +/- 12.8 h, P < 0.05). There were no significant intergroup differences in secondary endpoints and adverse events. CONCLUSIONS: DKT accelerates colonic motility in patients undergoing laparoscopic-assisted colectomy for colon cancer.

Laparoscopic-assisted proctocolectomy with prolapsing technique for familial adenomatous polyposis.

PURPOSE: The role of laparoscopic total proctocolectomy (TPC) and ileal pouch-anal anastomosis (IPAA) for familial adenomatous polyposis (FAP) has been controversial, given its technical difficulty of selecting the appropriate distal transection line and achieving safe anastomosis. We herein describe our initial experience with the prolapsing technique for laparoscopic-assisted TPC and IPAA (J-pouch) in the treatment of FAP. METHODS: A consecutive series of patients with FAP undergoing laparoscopic-assisted TPC with IPAA were identified from a prospectively collected database between June 2004 and February 2012. Medical records were reviewed for patient demographics, operative outcomes, and follow-up. RESULTS: The surgery was successfully completed in all 6 patients without any conversion to open surgery. The median operating time was 279 minutes (range, 240 to 386 min) and the median blood loss was 17.5 mL (range, 5 to 161 mL). No patient required blood transfusion. The median length of diet resumption and postoperative hospital stay were 7 days (range, 6 to 10 d) and 15 days (range, 13 to 21 d), respectively. A postoperative complication, wound infection, occurred in 1 patient. No anastomotic leakages or small bowel obstructions occurred. At a median follow-up of 59 months (range, 14.2 to 107.5 mo), no carcinoma had developed at the pouch or at the anastomotic site. Sexual function and fertility were unchanged as compared with preoperatively in 2 male patients. None of the patients experienced night-time incontinence or had to use a pad. CONCLUSIONS: Our limited experience suggests that this prolapsing technique helps prevent problems with laparoscopic-assisted TPC and IPAA for FAP patients.

[A case of unresectable multiple liver metastases of colorectal cancer in which ALTA(ZION), used to control internal hemorrhoidal bleeding, enabled administration of bevacizumab].

Our patient was a 58-year-old woman with internal bleeding hemorrhoids who was undergoing FOLFOX6 treatment for unresectable multiple hepatic metastases of colorectal cancer. Response evaluation after 6 courses showed stable disease (SD), but side effects necessitated a change in regimen. Hemorrhoidal bleeding had also increased, and hemorrhoid-sclerosing therapy with ALTA(ZION)injections was administered. Because no bleeding was evident after treatment and the clinical course was uneventful, chemotherapy with bevacizumab was restarted. No hemorrhoidal bleeding occurred after bevacizumab administration, and the patient is currently continuing chemotherapy. In patients with advanced cancer who have bleeding internal hemorrhoids that cannot be controlled with conservative treatment, hemorrhoid-sclerosing therapy using ALTA appears to offer an effective treatment variation that enables the use of bevacizumab in cases with limited available therapeutic regimen options.

[A case of neuroendocrine carcinoma of esophagus with a remarkable response to chemo-radiotherapy].

A 69-year-old man visited our hospital with complaints of hoarseness and dysphagia. Computed tomography showed wall thickening in the middle thoracic esophagus, tracheal invasion, and para-aorta lymph node swelling. An esophagoscopy revealed an elevated lesion in the middle portion of the esophagus, which was pathologically diagnosed as neuroendocrine carcinoma, stage IV: T4N3M1. Two courses of concurrent chemoradiotherapy using cisplatin and etoposide were performed, followed by 4 courses of combined chemotherapy with carboplatin and etoposide. The patient showed clinical complete remission.

DNA hypomethylation at the CpG island is involved in aberrant expression of the L1 cell adhesion molecule gene in colorectal cancer.

The L1 cell adhesion molecule (L1CAM) has been identified as a target gene of beta-catenin-TCF signaling in colorectal cancer (CRC) and associated with aggressive tumor behavior such as invasion and metastasis. We investigated the methylation status at the L1CAM gene promoter and/or L1CAM mRNA/protein expression in 4 CRC cell lines and 71 primary CRCs. Aberrant L1CAM expression was immuno histochemically observed in 31 (43.7%) of 71 cases, and correlated with advanced stage and presence of lymph node and distant metastases (P<0.05). Treatment with a demethylating agent induced L1CAM mRNA/protein expression in two cell lines lacking L1CAM expression. Bisulfite-modified genome sequencing suggested that DNA methylation status at core promoter and putative TCF-binding sites within the L1CAM promoter was correlated with L1CAM mRNA/protein expression in 4 CRC cell lines. Using the crypt isolation followed by bisulfite-modified genome sequencing and methylation-specific PCR methods, we confirmed that the DNA hypomethylation at core promoter and putative TCF-binding sites was well correlated with the aberrant L1CAM protein expression in primary CRC samples. These results suggest that DNA hypomethylation at the L1CAM CpG islands might induce L1CAM aberrant expression and contribute to the acquisition of aggressive tumor behavior in CRC.

Angiotensin II and epidermal growth factor receptor cross-talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines.

AIM: The cross-talk pathway between angiotensin II (AngII) and the epidermal growth factor receptor (EGFR) mediated by epidermal growth factor (EGF)-like ligands cleaved by a disintegrin and metalloprotease (ADAM) has been elucidated in several cell types. Even though the liver is a representative angiotensinogen-producing organ, such cross-talk has never been elucidated in hepatocellular carcinomas (HCCs). We investigated whether AngII exerted a mitogenic effect on HCC cell lines through the AngII-EGFR cross-talk pathway. METHODS: We determined the expression and/or phosphorylation status of AngII receptor type 1 (AGTR1), ADAM9, ADAM17, ERK1/2, STAT3, AKT and EGFR in five HCC cell lines using Western blotting. Proliferation and invasion activities were measured by ATP and Matrigel invasion assays, respectively. RESULTS: AGTR1 was expressed ubiquitously in HCC cell lines. EGFR expression in HepG2 was relatively weaker than that in the remaining HCC cell lines. The phosphorylation status of EGFR, ERK1/2, STAT3 and AKT was upregulated by AngII treatment in two EGFR-overexpressing cell lines (Huh7 and PLC/PRF/5), but not in HepG2 (showing weak EGFR expression). AngII stimulation significantly accelerated proliferation and invasion activities in Huh7 and PLC/PRF/5, and was inhibited by pretreatment with an ADAM inhibitor. A selective AGTR1 blocker significantly repressed proliferation activity in both cell lines, but did not significantly repress the invasion activity. Both chemical agents and neutralizing antibodies against ADAMs (ADAM9 and ADAM17) and EGF-like ligands suppressed EGFR transactivation and/or subsequent phosphorylation of ERK1/2, STAT3 and AKT. CONCLUSION: These results suggest that AngII-EGFR cross-talk signaling mediated by ADAMs is involved in the proliferation and invasion activities of several HCC cell lines.

Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines.

Alterations of several microRNA (miRNA) have been linked to cancer development and its biology. To search for unique miRNA that might play a role in the development of anaplastic thyroid carcinoma (ATC), we examined the expression of multiple miRNA and their functional effects on target genes in human thyroid carcinoma cell lines. We quantitatively evaluated the expression of multiple miRNA in 10 ATC and five papillary thyroid carcinoma (PTC) cell lines, as well as primary tumors from 11 thyroid carcinoma patients (three ATC and eight PTC), using the stem-loop-mediated reverse transcription real-time polymerase chain reaction method. We also examined the target gene specificity of unique miRNA that showed differences in expression between ATC and PTC cell lines. One miRNA, miR-138, was significantly downregulated in ATC cell lines in comparison with PTC (P < 0.01). Eleven miRNA (including miR-138) potentially targeting the human telomerase reverse transcriptase (hTERT) gene were totally downregulated in both ATC and PTC cell lines in comparison with normal thyroid tissues. A tendency for an inverse correlation between miR-138 and hTERT protein expression was observed in the thyroid cancer cell lines, although this failed to reach significance (r = -0.392, P = 0.148). We demonstrated that overexpression of miR-138 induced a reduction in hTERT protein expression, and confirmed target specificity between miR-138 and the hTERT 3'-untranslated region by luciferase reporter assay. These results suggest that loss of miR-138 expression may partially contribute to the gain of hTERT protein expression in ATC, and that further multiple miRNA targeting hTERT mRNA might be involved in the development of thyroid carcinoma.