Classification of recurrent esophageal cancer after radical esophagectomy with two- or three-field lymphadenectomy

BACKGROUND: Although patients with recurrent diseases have a very poor prognosis, appropriate pretreatment classification for management of recurrent esophageal cancers has yet to be identified. The patterns of recurrence following radial esophagectomy were retrospectively assessed, and evaluated for possible adaptation as a novel classification of recurrent esophageal cancer. PATIENTS AND METHODS: One hundred and sixty thoracic esophageal cancer patients (142 men; 18 women), who underwent radical esophagectomy without preoperative treatment, were studied. RESULTS: Recurrence occurred in 59 (36.8%) patients. The relationship between recurrence and clinicopathological features revealed significant associations between recurrence and age at surgery (p<0.05), tumor (p<0.0001), lymph node (p<0.0001) and metastatic status (p<0.01), pathological stage (p<0.0001) and lymph node dissection (p<0.0001). Locoregional recurrence occurred in 13 (22%) patients, distant in 30 (51%) and mixed in 16 (27%). Mixed recurrence occurred the fastest and showed the poorest prognosis. A novel classification for recurrent esophageal cancer was proposed based on the clinical findings. Univariate analysis of the prognostic factors for post-recurrent survival revealed a significant association with distant organ recurrence (p<0.05). CONCLUSION: Mixed recurrence had a poorer outcome than other recurrences. The proposed classification of clinical findings for recurrent esophageal cancer was shown to be useful; however, further studies with a larger number of recurrent esophageal cancers are required for stage grouping of the proposed classification.     

Predictors of response to chemo-radiotherapy and radiotherapy for esophageal squamous cell carcinoma

BACKGROUND: The sensitivity of tumors to chemotherapy and radiotherapy differs from one case to another and may be influenced by the expression of biological molecules. The presence of six potential predictive markers in esophageal squamous cell carcinoma (ESCC) was investigated and the data obtained were related to the response of the tumors to chemo-radiotherapy and radiotherapy. MATERIALS AND METHODS: Biopsy specimens were obtained from 61 patients with ESCC before treatment with chemo-radiotherapy (31 patients) or radiotherapy (30 patients). External radiotherapy was delivered by a two-field technique to a total of 60-70 Gray. Concurrent chemotherapy consisted of cisplatin or nedaplatin and 5-fluorouracil administered intravenously. The patients were examined before and after treatment by endoscopy, esophagography and computed tomography. The clinical response was classified as effective (> 50% decrease in primary lesion), or ineffective. Immunohistochemical staining for p53, p21, bax, bcl2, heat-shock protein (Hsp) 27 and Hsp70 was performed on the biopsy specimens before therapy. RESULTS: The primary tumor response was effective in 73.8% (45/61) and ineffective in 26.2% (16/61) of patients. Tumors with p53-positive expression were less sensitive than p53-negative tumors (p = 0.033). p21-positive patients (p = 0.027), and Hsp27-negative (p = 0.0057) and Hsp70-negative patients (p = 0.010) were all good responders. Neither bcl2 nor bax expression was related to the efficacy of therapy. Multivariate analysis revealed that Hsp27 was the most reliable predictor of the effect of chemo-radiotherapy and radiotherapy among the four potential markers. p53-negative and Hsp70-negative patients had a more favorable prognosis than p53- and Hsp70-positive patients (p = 0.039, p = 0.038, respectively). CONCLUSION: Expression of Hsp27 was a good predictor of the response of ESCC to chemo-radiotherapy and radiotherapy.     

Progress in endoscopic surgery for breast cancer

Breast conserving surgery has become the commonest surgery for breast cancer in Japan. And the cosmetic results have become more and more important. The main characteristics of endoscopy assisted surgery for breast cancer can realize radical resection and immediate reconstruction from a small skin incision and inconspicuous scars. Because the endoscopy-assisted surgery assures not only higher curativity but also better cosmetic results, the indications will increase more and more.     

Phase I study of radioimmunotherapy with an anti-CD20 murine radioimmunoconjugate ((90)Y-ibritumomab tiuxetan) in relapsed or refractory indolent B-cell lymphoma

We conducted a phase I study to evaluate the safety and efficacy of radioimmunotherapy with yttrium-90-ibritumomab tiuxetan (Y2B8) in Japanese patients with relapsed or refractory indolent B-cell lymphoma. Indium-111-labeled ibritumomab tiuxetan (In2B8; 3.5 or 5 mCi [129.5 or 185 MBq]) was administered on day 1, followed by serial gamma-camera imaging to investigate the distribution of In2B8 in the whole body of patients and to judge the feasibility of Y2B8 administration. Y2B8 with a dose of 0.3 mCi/kg (11.1 MBq/kg) or 0.4 mCi/kg (14.8 MBq/kg) was administered on day 8. Grade 4 neutropenia and grade 3 thrombocytopenia were observed in three of nine of the patients evaluated for safety. Critical toxicities (prolonged thrombocytopenia or severe non-hematological toxicities) were observed in two of six patients in the 0.4 mCi/kg (14.8 MBq/kg) dose group but were not seen in any of the three patients in the 0.3 mCi/kg (11.1 MBq/kg) dose group. The non-hematological toxicities of the nine patients were of grade 2 or less, except in two patients who had been heavily treated previously. They experienced critical toxicities such as infection, diarrhea, hyponatremia and prolonged thrombocytopenia, as well as other frequent grade 2 non-hematological toxicities. Although the pharmacokinetic profiles were similar to those in the US study, one of the two patients was clarified retrospectively as showing abnormal biodistribution of In2B8 in the bone marrow, as judged by an independent third party panel of radiologists. Five of the 10 participants achieved complete responses or unconfirmed complete responses and two partial responses. In conclusion, the recommended dose of Y2B8 for the subsequent phase II study for Japanese patients is 0.4 mCi/kg (14.8 MBq/kg). This dose of radioimmunotherapy was feasible when patients with altered biodistribution of In2B8 were excluded, and it was highly effective. (Cancer Sci 2005; 96: 903-910).     

Effect of enteral nutrition of monoacetoacetin on bacterial translocation in burned rats

BACKGROUND: Bacterial translocation (BT) occurs under stress, and enteral nutrition is said to be effective in counteracting this effect. The usefulness of i.v. nutrition of monoacetoacetine (MA) under stress has been reported previously, and we studied the effect of enteral nutrition of MA as it is related to BT. METHODS: Rats were given 13.6% MA or 15% glucose (Glu) via gastrostomy, and after 4 days a 30% full-thickness burn was made. Before and after administration of the burn, we measured serum cytokines; amounts of bacteria in the mesenteric lymph node (MLN), liver, and spleen (estimation of BT); mucosal thickness of the terminal ileum; and body weight changes. To confirm the effectiveness of MA in the small intestine, we estimated succinyl-CoA:3-oxoacid CoA-transferase (SCOT) expression in the terminal ileum by immunohistochemical staining and Western blot analysis. RESULTS: At 6 hours after burn, all cytokines were lower, and BT in the MLN was inhibited significantly in the MA group. Ileal mucosal thickness was not significantly different, but mucosa was more edematous in the Glu group. At 3 days after burn injury, BT was significantly inhibited in the MLN and liver, and the ileal mucosa was significantly thicker in the MA group. Body weight loss after burn injury was significantly smaller in the MA group. SCOT expression was the strongest at 6 hours after burn injury by Western blot analysis but not by immunohistochemical staining. CONCLUSIONS: Enteral nutrition of MA may be useful for the inhibition of intestinal mucosal atrophy and the prevention of multiple organ dysfunction syndrome caused by the inhibition of BT and subsequent overproduction of cytokines.     

Fibroblast growth factor-2 promotes the repair of partial thickness defects of articular cartilage in immature rabbits but not in mature rabbits

OBJECTIVE: To investigate cartilage response to fibroblast growth factor-2 (FGF-2) with increasing age in vivo, we examined the effect of FGF-2 on partial thickness defects of immature and mature rabbits. DESIGN: Sixty-nine Japanese white rabbits (34 immature rabbits, 35 mature rabbits) were examined. We made experimental partial thickness defects in articular cartilage of the knees. Then, we injected FGF-2 into the knees eight times, immediately after surgery and every 2 days for 2 weeks. A single dose of FGF-2 was 10 ng/0.1 ml or 100 ng/0.1 ml. In the control group, 0.1 ml saline was injected on the same time schedule. The rabbits were sacrificed at intervals following surgery that ranged from 2 to 48 weeks. The specimens were stained with toluidine blue and examined microscopically. We used a modified semiquantitative scale for evaluating the histological appearance of repair. RESULTS: In immature rabbits, the cartilage repair in the FGF-2 (100 ng)-treated group was significantly better than that of the other groups. The defects were almost completely repaired with chondrocytes that showed a round to polygonal morphology, and large amounts of extracellular matrix with intense metachromatic staining. In mature rabbits, however, there was apparently no effect from FGF-2 in either group. CONCLUSIONS: Application of FGF-2 facilitated cartilage repair in partial thickness defects in immature rabbits, but not in mature ones.     

Reduction in connective tissue growth factor by antisense treatment ameliorates renal tubulointerstitial fibrosis

Connective tissue growth factor (CTGF/CCN2) is one of the candidate factors mediating fibrogenic activity of TGF-beta. It was shown previously that the blockade of CTGF by antisense oligonucleotide (ODN) inhibits TGF-beta-induced production of fibronectin and type I collagen in cultured renal fibroblasts. The in vivo contribution of CTGF in renal interstitial fibrosis, however, remains to be clarified. With the use of a hydrodynamics-based gene transfer technique, the effects of CTGF antisense ODN are investigated in rat kidneys with unilateral ureteral obstruction (UUO). FITC-labeled ODN injection via the renal vein showed that the ODN was specifically introduced into the interstitium. At day 7 after UUO, the gene expression of CTGF, fibronectin, fibronectin ED-A, and alpha1(I) collagen in untreated or control ODN-treated obstructed kidneys was prominently upregulated. CTGF antisense ODN treatment, by contrast, markedly attenuated the induction of CTGF, fibronectin, fibronectin ED-A, and alpha1(I) collagen genes, whereas TGF-beta gene upregulation was not affected. The antisense treatment also reduced interstitial deposition of CTGF, fibronectin ED-A, and type I collagen and the interstitial fibrotic areas. The number of myofibroblasts determined by the expression of alpha-smooth muscle actin was significantly decreased as well. Proliferation of tubular and interstitial cells was not altered with the treatment. These findings indicate that CTGF expression in the interstitium plays a crucial role in the progression of interstitial fibrosis but not in the proliferation of tubular and interstitial cells during UUO. CTGF may become a potential therapeutic target against tubulointerstitial fibrosis.     

Cardiovascular surgery in patients on chronic dialysis: effect of intraoperative hemodialysis

To evaluate the operative result and the perioperative management of dialysis patients undergoing elective cardiac surgery, we retrospectively reviewed consecutive adult patients with chronic renal failure dependent on maintenance dialysis. Between April 1994 and March 2002, 20 patients who underwent cardiopulmonary bypass (CPB) procedures were studied. Fourteen patients underwent isolated coronary artery bypass grafting, four valve replacements and two combined procedures. Our strategy for the chronic dialysis patients was as follows: dialysis the day before the operation, intraoperative hemodialysis (HD) during CPB, and no dialysis or hemofiltration (HF) on the operative day. Intraoperative HD produces the optimal fluid and electrolyte balance at the end of the operation. The mean interval between the end of surgery and the commencement of HD was 31.2+/-12.5 h. No patients required any hemocatharsis such as HF or HD on the day of operation. The overall operative mortality was 5.0%. There were six late deaths (30.0%). Overall, including the operative and non-cardiac death, actuarial survival rate was 85.0% at 1 year, 70.0% at 5 years, and 65.0% at 6 years. Intraoperative HD has an advantage in the postoperative period; it avoids the hemodynamic instability and the risk of heparin-associated bleeding associated with the use of HD.     

Multiple eccrine spiradenomas on the hand,forearm and head

The first case of multifocal eccrine spiradenomas on the hand, forearm and scalp is described. This case is unusual in that the tumors located on the little finger included the nail matrix and occurred in a linear/zosteriform distribution, resulting in a nail deformity. The nodules on the forearm and scalp were in a random distribution. Histologically, each tumor was highly cellular and composed of two cell types: small darkly staining basaloid cells and larger, pale cells. Ultrastructural observations often showed an intracellular lumen with numerous microvilli in larger pale-staining cells.