[A Case of Ascending Colon Cancer with Synchronous Unresectable Liver Metastasis Maintaining a Long-Term Stable Disease State after Discontinuing Chemotherapy].

A 73-year-old woman presenting with weight loss was diagnosed as having ascending colon cancer with synchronous liver metastasis. The liver metastasis was solitary but it occupied the medial and anterior segments. The size was over 9 cm in diameter and was located adjacent to the left, middle, and right hepatic veins, making it initially unresectable. Following surgical resection of the primary tumor, she received mFOLFOX6 plus bevacizumab chemotherapy, resulting in a decrease in size of the liver metastasis. During the 15 courses of chemotherapy, an allergic reaction to oxaliplatin occurred and oxaliplatin administration was stopped. Although the liver metastasis was considered to be in a stable disease state according to the RECIST criteria at the time following 32 courses of chemotherapy, we discontinued chemotherapy due to various reasons of the patient. However, the liver metastasis continues to be in the stable disease state, and has not grown for over 5 years since initiating mFOLFOX6 plus bevacizumab chemotherapy and for over 3 years since discontinuing the chemotherapy.

A comprehensive expression analysis of mucins in appendiceal carcinoma in a multicenter study: MUC3 is a novel prognostic factor.

BACKGROUND: Mucins are implicated in survival in various cancers, but there have been no report addressed on survival in appendiceal carcinoma, an uncommon disease with different clinical and pathological features from those of other colon cancers. We aimed to investigate the clinical implications of expression of mucins in appendiceal carcinoma. METHODS: Expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in cancer tissue were examined by immunohistochemistry in 108 cases of surgically resected appendiceal carcinoma. RESULTS: The following relationships of mucins with clinicopathologic factors were identified: MUC1 with positive lymphatic invasion (p = 0.036); MUC2 with histological type (mucinous carcinoma, p<0.001), superficial invasion depth (p = 0.007), negative venous invasion (p = 0.003), and curative resection (p = 0.019); MUC3 with non-curative resection (p = 0.017); MUC5AC with histological type (mucinous carcinoma, p = 0.002), negative lymphatic invasion (p = 0.021), and negative venous invasion (p = 0.022); and MUC16 with positive lymph node metastasis (p = 0.035), positive venous invasion (p<0.05), and non-curative resection (p = 0.035). A poor prognosis was related to positive lymph node metastasis (p = 0.04), positive lymphatic invasion (p = 0.02), positive venous invasion (p<0.001), non-curative resection (p<0.001), and positive expression of MUC3 (p = 0.004). In multivariate analysis, positive venous invasion (HR: 6.93, 95% CI: 1.93-24.96, p = 0.003), non-curative resection (HR: 10.19, 95% CI: 3.05-34.07, p<0.001) and positive MUC3 expression (HR: 3.37, 95% CI: 1.13-10.03, p = 0.03) were identified as significant independent prognostic factors in patients with appendiceal carcinoma. CONCLUSIONS: Expression of MUC3 in appendiceal carcinoma is an independent factor for poor prognosis and a useful predictor of outcome in patients with appendiceal carcinoma after surgery.

[Recurrent gastric volvulus resolved surgically after therapeutic percutaneous endoscopic gastrostomy in Duchenne muscular dystrophy].

A 20-year-old man with Duchenne muscular dystrophy (DMD) with recurrent gastric volvulus underwent percutaneous endoscopic gastrostomy (PEG). Four months later, he developed vomiting and consciousness disturbance. CT revealed gastric volvulus recurrence along the gastrostomy axis. Endoscopic repositioning failed and fistula perforation necessitated emergency surgery. The upper position of the stomach was twisted counter-clockwise and revolved on the gastrostomy axis sliding between the lower stomach and abdominal wall. The fistula showed necrotic perforation and was thus resected. The anterior stomach wall was fixed to the abdominal wall at 3 triangular points. Thereafter, gastric volvulus did not recur. PEG is reportedly effective for preventing gastric volvulus, but there are rare cases of postgastrostomy recurrence. This successfully managed case provides valuable clinical insights.

Value of laparoscopic appendectomy in perforated appendicitis.

BACKGROUND: The purpose of this clinical study was to evaluate the efficacy of laparoscopic appendectomy in patients with perforated appendicitis. METHODS: This study involved a total of 73 consecutive patients who had undergone appendectomy for perforated appendicitis between January 1999 and December 2004. While 39 patients underwent open appendectomy (OA) during the first 3 years, the remaining 34 patients underwent laparoscopic appendectomy (LA) during the last 3 years. RESULTS: There was no case of LA converted to OA. No significant difference was found in the operating time between the two groups. Laparoscopic appendectomy was associated with less analgesic use, earlier oral intake restart (LA, 2.6 days; OA, 5.1 days), shorter median hospital stay (LA, 11.7 days; OA, 25.8 days), and lower rate of wound infections (LA, 8.8%; OA, 43.6%). CONCLUSIONS: These results suggest that LA for perforated appendicitis is a safe procedure that may prove to have significant clinical advantages over conventional surgery.

Intense PET signal in the degenerative necrosis superimposed on chronic pancreatitis.

Although fluorine-18 deoxyglucose-positron emission tomography (FDG-PET) is a sensitive diagnostic modality in detecting malignant tumors, differential diagnosis of malignant tumors from inflammatory lesion is challenging. We experienced a case of acute degenerative necrosis superimposed on chronic pancreatitis, which was difficult to distinguish from pancreatic cancer. The patient was a 66-year-old man with a complaint of upper abdominal pain. Abdominal computed tomography revealed low-density masses in the head and body of the pancreas. FDG-PET revealed intense accumulations at the head and body of the pancreas (mean standard uptake value for the head and body pancreatic tumors was 4.1 and 6.7, respectively) corresponding to the 2 tumors detected by computed tomography. Because of a possible malignant pancreatic tumor, the patient underwent pylorus-preserving pancreatoduodenectomy. Histologic examination of the resected specimen revealed a characteristic of chronic pancreatitis in a nontumorous area. Two tumors detected by FDG-PET consisted of degenerative necrosis surrounded by granulation tissue. The amount of granulation tissue was correlated to the levels of standard uptake value. No malignant tumors were observed. This case suggests a limitation of FDG-PET in distinguishing malignant neoplastic lesions in the pancreas, especially from acute degenerative changes in chronic pancreatitis. Repetitive PET examination is recommended for the accurate diagnosis.

[A case of recurrent breast cancer with multiple lung, adrenal, inferior vena cava tumor thrombus and bone metastases successfully treated with 5'-DFUR and hormonal therapy].

A 42-year-old woman with multiple organ metastases from breast cancer was successfully treated with 5'-deoxy-5-fluorouridine (5'-DFUR) and hormonal therapy (leuprorelin+tamoxifen). She underwent radical mastectomy for advanced left breast cancer in June 1998. In September 2000, she was treated with docetaxel for multiple lung metastases, and the lesions were diagnosed as in complete remission. In June 2001, she received radiation for bone metastasis in left femoral and received a resection of subcutaneous metastases in the face. Then she received 2 courses of paclitaxel. In May 2002, she had multiple lung metastases, right adrenal metastasis, tumor thrombus in the inferior vena cava and multiple bone metastases, and was treated with cycrophosphamide, epirubicin, and 5-FU, however, they were abandoned due to severe leucopenia. Therefore, 600 mg/day of 5'-DFUR was administered from December 2002. The lesions of lung and adrenal decreased extendedly in March 2003. She was diagnosed as being in CR in March 2004, and this condition has continued to the present.

Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice.

Extrahepatic cholestasis often evokes liver injury with hepatocyte apoptosis, aberrant cytokine production, and-most importantly-postoperative septic complications. To clarify the involvement of aberrant cytokine production and hepatocyte apoptosis in impaired resistance to bacterial infection in obstructive cholestasis, C57BL/6 mice or Fas-mutated lpr mice were inoculated intraperitoneally with 10(7) colony-forming units of Escherichia coli 5 days after bile duct ligation (BDL) or sham celiotomy. Cytokine levels in sera, liver, and immune cells were assessed via enzyme-linked immunosorbent assay or real-time reverse-transcriptase polymerase chain reaction. BDL mice showed delayed clearance of E. coli in peritoneal cavity, liver, and spleen. Significantly higher levels of serum interleukin (IL) 10 with lower levels of IL-12p40 were observed in BDL mice following E. coli infection. Interferon gamma production from liver lymphocytes in BDL mice was not increased after E. coli infection either at the transcriptional or protein level. Kupffer cells from BDL mice produced low levels of IL-12p40 and high levels of IL-10 in vitro in response to lipopolysaccharide derived from E. coli. In vivo administration of anti-IL-10 monoclonal antibody ameliorated the course of E. coli infection in BDL mice. Furthermore, BDL-lpr mice did not exhibit impairment in E. coli killing in association with little hepatic injury and a small amount of IL-10 production. In conclusion, increased IL-10 and reciprocally suppressed IL-12 production by Kupffer cells are responsible for deteriorated resistance to bacterial infection in BDL mice. Fas-mediated hepatocyte apoptosis in cholestasis may be involved in the predominant IL-10 production by Kupffer cells.

NK T cells stimulated with a ligand for TLR2 at least partly contribute to liver injury caused by Escherichia coli infection in mice.

Fas ligand (Fas L) expression was induced on intrahepatic NK1.1(+) T cells in vivo after an intraperitoneal inoculation of Escherichia coli. Liver injury after E. coli infection, as assessed by serum GPT level and histological examination, was significantly reduced in Jalpha281(-/-) mice lacking NK1.1(+) T cells or in gld/gld mice bearing mutated Fas L, indicating that NK T cells at least partly contribute to E. coli-induced liver injury in a Fas/Fas L-dependent manner. Bacterial numbers in organs and cytokine levels in serum of Jalpha281(-/-) mice did not differ from those of Jalpha281(+/+) mice following E. coli infection. Intrahepatic NK1.1(+) T cells, which preferentially expressed Toll-like receptor 2 (TLR2) mRNA, responded in vitro to synthetic lipoprotein, a ligand for TLR2, by inducing Fas L expression on their surface. In a manner analogous to E. coli infection, lipoprotein and LPS could additively induce Fas L expression on NK1.1(+) T cells, leading to liver injury in vivo in normal mice but not in gld/gld mice. In conclusion, it is suggested that induction of Fas L on NK T cells in response to bacterial components such as lipoproteins plays an important role in pathogenesis of E. coli-induced liver injury in mice.

Overexpression of interleukin-15 protects against Escherichia coli-induced shock accompanied by inhibition of tumor necrosis factor-alpha-induced apoptosis.

Interleukin (IL)-15, a potent inhibitor of tumor necrosis factor (TNF)-alpha-mediated apoptosis, causes multiple organ failure during endotoxic shock. We investigated the potential role of IL-15 in protection against Escherichia coli-induced shock by using IL-15 transgenic (Tg) mice. These mice were resistant to an otherwise lethal challenge with E. coli, although bacterial burden and serum levels of TNF-alpha were similar in non-Tg mice. Apoptosis in cells of the peritoneal cavity, liver, spleen, or lung was significantly suppressed in IL-15 Tg mice after E. coli infection. Peritoneal cells from naive IL-15 Tg mice were also resistant to TNF-alpha-induced apoptosis in vitro, and neutralization of endogenous IL-15 significantly aggravated TNF-alpha-induced apoptosis. Exogenous IL-15 prevented TNF-alpha-induced apoptosis in normal mice in vitro and improved the survival rate after E. coli challenge. These results suggest that IL-15 overexpression can prevent TNF-alpha-induced apoptosis and protect against E. coli-induced shock, indicating a possible therapeutic application of IL-15 for septic shock.

CD8 alpha-deficient mice are highly susceptible to 5-fluorouracil-induced lethality.

Intestinal intraepithelial lymphocytes (i-IEL) expressing CD8 alpha are located in the intestine and may confer protection against invasion of intestinal microflora. We found that mice rendered deficient in CD8 alpha molecules by homologous recombination were susceptible to 5-fluorouracil (5-FU)-induced lethality accompanied by translocation of members of the enterobacteria. The number of i-IEL was greatly reduced on day 6 after 5-FU administration in both CD8 alpha(+/-) mice and CD8 alpha(-/-) mice, whereas the recovery of the level of i-IEL thereafter was significantly impaired in CD8 alpha(-/-) mice compared with that in CD8 alpha(+/-) mice. The ability of i-IEL to produce gamma interferon in response to immobilized T-cell receptor (TCR) alpha beta or TCR gamma delta monoclonal antibodies was significantly lower in CD8 alpha(-/-) mice than in CD8 alpha(+/-) mice. Transfer of CD8(+) i-IEL conferred significant protection against 5-FU-induced lethality in CD8 alpha(-/-) mice. The results suggest that CD8(+) i-IEL play an important role in protection against 5-FU-induced lethality with translocation of Enterobacteriaceae.