Surgical management of intraductal papillary mucinous tumor of the pancreas

BACKGROUND: Intraductal papillary mucinous tumor (IPMT) is a type of pancreatic cystic neoplasm. IPMT consists of intraductal papillary mucinous adenoma (benign IPMT) and intraductal papillary mucinous carcinoma (malignant IPMT). Preoperative diagnosis of malignancy is difficult; the invasiveness and metastatic character are not well known. The purpose of the study was to evaluate the optimal diagnostic and therapeutic strategy of IPMT. METHODS: Medical charts of 38 patients with final diagnosis of IPMT in Kyoto University Hospital were retrospectively reviewed. Preoperative imaging, mode of operation, and clinical and histopathologic findings were analyzed. RESULTS: In 38 IPMTs, imaging of localization was correct in 82% by computed tomography, 90% by ultrasonography, 70% by endoscopic retrograde cholangiopancreatography, 100% by magnetic resonance cholangiopancreatography, and 100% by endoscopic ultrasonography. Evaluation of malignancy by endoscopic ultrasonography resulted in sensitivity and specificity of 81% and 78%, respectively. Pylorus-preserving pancreaticoduodenectomy was preferably performed in 20 of 38 patients with IPMT. Twenty-two patients had histologically malignant disease. Half of them had an invasive component in the adjacent stroma. One case of malignant IPMT showed lymph node metastasis, and the patient had no recurrence after pancreaticoduodenectomy with regional lymphadenectomy. No case was diagnosed as margin positive; however, 27% showed a dysplasia with atypia in the epithelial cells of the cut edge of the pancreas. One patient with negative atypia at the cut edge of the pancreas developed a recurrent tumor in the remnant pancreas. CONCLUSIONS: The preoperative diagnosis of malignancy is difficult, and 50% of malignant IPMT showed an invasive component. Thus, radical resection of the pancreas with regional lymph node dissection should be the choice of treatment. Lymph node metastasis and intraductal distant invasion should be carefully managed in the surgical treatment of these lesions.     

Intracystic papillary carcinoma in the male breast. A case report

Male breast cancer is a rare disease with an incidence between 0.5% and 2.4% of that in women. We report a case of intracystic papillary carcinoma of the breast in a 75-year-old Japanese man. The macroscopic features of the carcinoma could be accurately demonstrated by pneumocystography and ultrasonography preoperatively.     

昆藻调脂口服液治疗脂肪肝的临床研究

目的：观察昆藻调脂口服液治疗脂肪肝的临床疗效。方法：运用昆藻调脂口服液治疗脂肪肝患者71例（治疗组），并与对照组（东宝肝泰片）治疗脂肪肝患者64例作对照，通过治疗前后观察ALT、ALP、GGT、TG、TC、LDL-C、HDL-C及B超积分变化等各项指标，分析昆藻调脂口服液的临床疗效。结果：昆藻调脂口服液能显著改善患者的脂肪肝B超影像，改善和恢复肝功能，降低TG、TC、LDL—C，升高HDL—C，其总有效率为83％，显著优于对照组61％（P〈0．05）。结论：昆藻调脂口服液是治疗脂肪肝的有效方剂。     

Trojan p16 peptide suppresses pancreatic cancer growth and prolongs survival in mice.

PURPOSE: The tumor suppressor gene p16INK4A is inactivated frequently in a large number of human cancers, and many investigators have attempted to restore the function of p16 using the p16 wild-type gene and viral vectors. In this study, we treated the tumor-bearing animals with the p16-derived synthetic peptide coupled with the Antennapedia carrier sequence, which we designated as Trojan p16 peptide. EXPERIMENTAL DESIGN: Injections (i.p.) of the Trojan p16 peptide (100 microg/mouse/day) were given for 3 weeks in the AsPC-1 and BxPC-3 s.c. tumor models. Tumor growth, histopathology, and TUNEL staining of the tumor and toxicity of the animals were evaluated. To examine its influence on the survival of tumor-bearing mice, Trojan p16 was administered in the AsPC-1 peritoneal dissemination model. RESULTS: In the AsPC-1 s.c. tumor model, a significant growth inhibition was obtained by the Trojan p16 treatment when compared with the three control treatments, i.e., vehicle, unconjugated form of p16, or Trojan peptide alone. Tumor growth inhibition was almost complete in the BxPC-3 tumor, a relatively slow growing tumor. Neither hematological cytotoxicity or body weight loss were observed. Histopathology of the BxPC-3 s.c. tumor in the Trojan p16 treatment group revealed marked vacuole formation and apoptotic death of cancer cells. In the AsPC-1 peritoneal dissemination model, the survival curve of mice treated with Trojan p16 was significantly longer than that of control. CONCLUSIONS: These results provide evidence that the Trojan p16 peptide system, a gene-oriented peptide coupled with a peptide vector, functions for experimental pancreatic cancer therapy.     

Effect of Accessory Cells on Stimulation of Murine T-Cell Leukemia with Antibodies to the CD3/T Cell Antigen Receptor Complex

Stimulation of EL4 and RL  

     

Multiple endocrine neoplasia type 1 gene mutations in sporadic gastrinomas in Japan

The molecular mechanisms responsible for the development and/or progression of gastrinomas are largely unknown. Studies involving sporadic enteropancreatic neuro-endocrine tumors suggest that mutations in the MEN1 gene occur in some tumors and probably play an important role in their pathogenesis. In this study, we examined whether somatic mutations in the MEN1 gene are also responsible for sporadic gastrinomas and correlate with clinical manifestations of gastrinomas in Japanese patients. Genomic DNA was extracted from paraffin-embedded gastrinoma tissues from 12 patients. Nucleotide sequences in the MEN1 genes were determined by direct sequencing. We identified 6 mutations in 7 out of 12 examined gastrinomas (58%). The identified mutations were 1 non-sense, 2 missense, 1 deletion leading to frame shifts, 1 insertion and 1 splicing mutation. Identical mutations were found in three gastrinoma tissues. The age at surgery, the rate of hepatic metastasis, and tumor status were not significantly different in the 2 groups. This study demonstrates that alterations in the MEN1 gene are involved in about half of all sporadic gastrinomas, although no correlation between the presence of mutations and location and clinical phenotype or severity of disease has been found.     

Effects of valsartan and perindopril combination therapy on left ventricular hypertrophy and aortic arterial stiffness in patients with essential hypertension

Objective To compare the effects of combined therapy of an angiotensin II receptor blocker (ARB; valsartan) and an angiotensin converting enzyme inhibitor (ACEI; perindopril) on blood pressure (BP), metabolic profiles, plasma brain natriuretic peptide (BNP) levels, echocardiographic findings, and aortic pulse wave velocity (PWV) with those of respective monotherapy in never-treated patients with essential hypertension.Methods This was a prospective randomized trial, in which there were 31 patients with essential hypertension and left ventricular hypertrophy (LVH) who visited the outpatient clinic of Oita Red Cross Hospital (14 women and 17 men; mean±SD age, 59±5 years). Each patient was randomly assigned to receive valsartan (160 mg/day, V group, n=10), perindopril (8 mg/day, P group, n=11), or a combination of valsartan (80 mg/day) and perindopril (4 mg/day, V+P group, n=10) for 40 weeks. Ambulatory BP monitoring (ABPM), echocardiographic findings, metabolic findings, plasma BNP levels, and brachial-ankle PWV (baPWV) were evaluated before and after the 40-week therapy.Results The baseline and post-therapeutic BP levels were similar among the three groups. At baseline ABPM, non-dipping was observed in 80, 82, and 80% in the V, P, and V+P groups, respectively. Each 40-week therapy regimen comparably reduced ABP. The plasma BNP levels (P<0.0001 for each), left ventricular mass index (LVMI) (P<0.01 for each), and PWV values (P<0.0001 for each) were also reduced. However, when compared with either V or P group, the percentage reduction in LVMI (P<0.05 and P<0.005, respectively), BNP (P<0.05 for each), and baPWV values (P<0.005 and P<0.001, respectively) was greater in the V+P group.Conclusions Our findings suggest that, when compared with each monotherapy, perindopril and valsartan combination therapy exerts greater beneficial effects regarding the regression of LVH, reduction in BNP, and improvement of PWV in a selected group of essential hypertensive patients with LVH and high prevalence of non-dipping patterns.     

A randomized multicenter trial comparing resection and radiochemotherapy for resectable locally invasive pancreatic cancer

BACKGROUND: Though the outcome of resection for locally invasive pancreatic cancer is still poor, it has gradually improved in Japan, and the 5-year survival is now about 10%. However, the advantage of resection over radiochemotherapy has not yet been confirmed by a randomized trial. We conducted this study to compare surgical resection alone versus radiochemotherapy without resection for locally invasive pancreatic cancer using a multicenter randomized design. METHODS: Patients with pancreatic cancer who met our preoperative criteria for inclusion (pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric artery or the common hepatic artery, or without distant metastasis) underwent laparotomy. Patients with operative findings consistent with our criteria were randomized into a radical resection group and a radiochemotherapy group (200 mg/m(2)/day of intravenous 5-fluorouracil and 5040 cGy of radiotherapy) without resection. The 2 groups were compared for mean survival, hazard ratio, 1-year survival, quality of life scores, and hematologic and blood chemical data. RESULTS: Twenty patients were assigned to the resection group and 22 to the radiochemotherapy group. There was 1 operative death. The surgical resection group had better results than the radiochemotherapy group as measured by 1-year survival (62% vs 32 %, P=.05), mean survival time (>17 vs 11 months, P < .03), and hazard ratio (0.46, P=.04). There were no differences in the quality of life score or laboratory data apart from increased diarrhea after surgical resection. CONCLUSIONS: Locally invasive pancreatic cancer without distant metastases and major arterial invasion appears to be best treated by surgical resection.     

Experience of long-term synbiotic therapy in seven short bowel patients with refractory enterocolitis

Background/Purpose

Probiotic and prebiotic therapies are potent new strategies to treat various intestinal diseases, including inflammatory bowel disease and viral and bacterial infections. Synbiotics is defined as the combined use of probiotics and prebiotics and is expected to have a stronger effect on intestinal diseases than probiotics or prebiotics alone, but there has been no report of its clinical application. The authors designed a protocol for synbiotic therapy composed of Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides and preliminarily ascertained its clinical effects in humans.

Methods

This protocol of synbiotic therapy was applied for more than 1 year to 7 malnourished patients with short bowels who suffered from refractory enterocolitis.

Results

The therapeutic protocol improved the intestinal bacterial flora (inducing the domination by anaerobic bacteria and suppressing the residence of pathogenic bacteria) and increased short chain fatty acids in the feces (from 27.8 to 65.09 μmol/g wet feces). All patients but 1 accelerated their body weight gain, and 5 patients showed increased serum rapid turnover proteins.

Conclusions

This protocol for synbiotic therapy might be a potent modulator of intestinal flora and a promising strategy to treat short bowel patients with refractory enterocolitis.