Gene Expression Profile Prospectively Predicts Peritoneal Relapse After Curative Surgery of Gastric Cancer

Background

Peritoneal relapse is the most common pattern of tumor progression in advanced gastric cancer. Clinicopathological findings are sometimes inadequate for predicting peritoneal relapse. The aim of this study was to identify patients at high risk of peritoneal relapse in a prospective study based on molecular prediction.

Methods

RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly, we constructed a molecular prediction system and validated its robustness and prognostic validity by 500 times multiple validation by repeated random sampling in a retrospective set of 56 (38 relapse-free and 18 peritoneal-relapse) patients. Secondly, we applied this prediction to 85 patients of the prospective set to assess predictive accuracy and prognostic validity.

Results

In the retrospective phase, repeated random validation yielded ~68% predictive accuracy and a 22-gene expression profile associated with peritoneal relapse was identified. The prediction system identified patients with poor prognosis. In the prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis of peritoneal-relapse-free survival showed a significant difference between the “good signature group” and “poor signature group” (log-rank p = 0.0017). Multivariate analysis by Cox regression hazards model identified the molecular prediction as the only independent prognostic factor for peritoneal relapse.

Conclusions

Gene expression profile inherent to primary gastric cancer tissues can be useful in prospective prediction of peritoneal relapse after curative surgery, potentially allowing individualized postoperative management to improve the prognosis of patients with advanced gastric cancer.     

Long-Term Characteristics of 5-Year Survivors After Liver Resection for Colorectal Metastases

Background We investigated factors affecting 5-year survival in patients undergoing hepatic resection for colorectal cancer metastases, including events long after initial hepatectomy. Although retrospective studies have demonstrated survival benefit of hepatectomy for metastatic colorectal cancer, few have included sufficient 5-year survivors to identify survival-related factors throughout the clinical course. Methods We divided 156 patients with hepatectomy for colorectal cancer metastases into 5-year survivors (n = 64) and patients dying before 5 years after hepatectomy (n = 92). Clinicopathologic data were compared retrospectively with respect to long-term outcome. Results By multivariate analysis, large liver tumors (adjusted relative risk, 2.029; P = .011), short tumor doubling time (1.809; P = .026), and origin from poorly differentiated primary adenocarcinoma (12.632; P = .001) compromised survival, whereas initial treatment-related variables did not. Although no difference was seen in initial treatment-related variables between 5-year survivors with recurrence after hepatectomy and patients dying before 5 years, repeat surgery was used more frequently in survivors (P < .001), typically with adjuvant chemotherapy. Conclusions Reoperations for each recurrence of metastases, followed by additional chemotherapy, frequently resulted in long survival.     

Idiopathic retroperitoneal fibrosis diagnosed by CT-guided needle biopsy: a case report

A 72-year-old man was admitted to another hospital because of general fatigue and dyspnea secondary to renal insufficiency. Abdominal computed tomography (CT) and magnetic resonance imaging showed left atrophic kidney, right hydronephrosis, and an intra-pelvic mass of soft-tissue density located anterior to the sacrum, involving the right ureter at the level between the 5th lumber vertebra and the sacrum. He was referred to our hospital after percutaneous nephrostomy was constructed into right kidney. CT-guided needle biopsy revealed the idiopathic retroperitoneal fibrosis, leading us to give him steroid therapy. Three weeks later, radiographic findings showed a remarkable reduction of the mass and the improvement of the right ureteral stricture.     

The effects of arginine and selective inducible nitric oxide synthase inhibitor on pathophysiology of sepsis in a CLP model

BACKGROUND: Sepsis is an arginine-deficient state and is associated with overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). It has been indicated that low plasma levels of arginine are related to high mortality rates in sepsis. Arginine, however, is also known to be a precursor of NO. Therefore, administration of arginine in septic patients remains controversial. We examined the effects of co-administration of arginine and aminoguanidine, a selective iNOS inhibitor, on sepsis, using rat models. METHOD: Sepsis was induced in rats by cecal ligation and puncture (CLP). Effects of separate and combined administration of arginine and aminoguanidine were investigated by comparing plasma levels of arginine, expressions of heme oxygenase (HO)-1 and HO-2 in liver and lung, and nitrite + nitrate (NOx) excretion in urine, as well as neuroendocrine responses in urine in the early phase of sepsis. Seven-day survival rates were also examined. RESULTS: A combination of arginine and aminoguanidine recovered the plasma level of arginine at 6 h post-CLP, decreased expression of HO-1 in liver and lung at 24 h post-CLP, decreased urinary excretion of epinephrine, norepinephrine, dopamine, and 17-hydroxycorticosteroid in the first 24 h post-CLP, and increased 7-d survival. CONCLUSION: It is demonstrated that administration of arginine together with the selective iNOS inhibitor in the early phase of sepsis restores plasma arginine, reduces oxidative stress by probably maintaining NO derived from constitutive NOS, and attenuates neuroendocrine stress responses. This co-administration may be a beneficial treatment approach against sepsis.     

Relationship between serum ferritin levels and tumour status in patients with renal cell carcinoma

OBJECTIVE: To assess the relationship between serum ferritin levels (a useful marker for diagnosing and staging renal cell carcinoma, RCC) and tumour status in RCC of 相似文献   

Surgical treatment for popliteal artery entrapment syndrome

PURPOSE: This study was a retrospective review of 11 limbs of 10 patients with popliteal artery entrapment syndrome (PAES) treated surgically in a 20-yr period. METHODS: The patients were aged 34.7 +/- 17.4 SEM yr. Arteriographic findings varied, showing medial deviation in two limbs, poststenotic dilatation in four limbs and occlusion of the popliteal artery in five limbs. In addition, computed tomographic (CT) scanning showed positive findings of PAES in all the limbs. RESULTS: The surgical procedures consisted of musculotendonous section (MTS) with autogenous saphenous vein (ASV) graft in seven limbs, MTS and ASV patch angioplasty with or without thromboendarterectomy in three limbs, and MTS alone in one limb. All the ASV grafts were found to be patent during the postoperative follow-up period (10.9 +/- 4.0 yr). CONCLUSION: CT scanning was demonstrated to be the most sensitive diagnostic modality for PAES, and MTS with or without ASV grafting method was considered to be the best surgical procedure for PAES.     

Implications of MYCN amplification in patients with stage 4 neuroblastoma who undergo intensive chemotherapy

Background/Purpose

This study aims to clarify the implications of MYCN amplification in patients with high-risk neuroblastomas treated with 2 different regimens of induction chemotherapy established by the Japan Study Group for Advanced Neuroblastoma.

Methods

Between 1985 and 2003 in Japan, 392 patients with stage 4 neuroblastomas who were older than 12 months were treated with 2 regimens of induction chemotherapy (the combination of cyclophosphamide [CTX], cisplatin [CDDP], pirarubicin, and vincristine or etoposide). Regimen 91A3 or 98A3 (A3) (CTX 2400 mg/m², CDDP 125 mg/m²) was a higher dose combination of CTX and CDDP than regimen 85A1 or 91A1 (A1) (CTX 1200 mg/m², CDDP 90 mg/m²). The 392 cases were classified into 3 groups (A, 1 copy; B, 2-9 copies; C, more than 10 copies) based on the MYCN amplification status by a Southern blot analysis.

Results

The 5-year overall survival rate (5-YS) was 41.1% for all 392 cases. Regarding the MYCN amplification status, the 5-YS was 46.6% for A group (n = 227), 22.7% for B group (n = 26), and 36.0% for C group (n = 139). A flouresence in situ hybridization analysis showed the presence of the cells with more than 10 copies in cases with 2 to 9 copies based on the Southern blot findings. Of the 227 patients in a group, the 5-YS was 46.7% for the 70 cases treated by A3 and 47.0% for 154 cases treated by A1 (nonsignificant). The 5-YS of the 210 patients with stem cell transplantation (SCT) (51.%) was significantly better than that of the 127 patients without SCT (41.1%) (P < .05).

Conclusions

Regarding the MYCN amplification status, the tumor aggressiveness might thus be different between 2 and 9 copies and a single copy of MYCN. In neuroblastomas with 2 and 9 copies of MYCN based on a Southern blot analysis, the MYCN amplification status should be analyzed using the flouresence in situ hybridization method. Induction chemotherapy followed by SCT according to the Japan Study Group for Advanced Neuroblastoma protocol improved the outcome of neuroblastomas with MYCN amplification; however, obtaining a further improvement in the long-term survival of stage 4 neuroblastomas may therefore require the development of an even more effective treatment modality.     

Intrahepatic biliary cysts in children with biliary atresia who have had a Kasai operation

Purpose

In patients with biliary atresia who had undergone a Kasai operation, treatment of intrahepatic biliary cysts (IBCs), particularly when complicated by cholangitis, is often difficult because the clinical implications and the course of IBCs are unclear. Thus, to determine the best treatment guideline, the morphology of IBCs, the clinical course, and the outcomes of such patients were evaluated.

Patients and Methods

A total of 44 patients with type III biliary atresia who underwent a Kasai operation from 1977 to 2005 were postoperatively examined for IBC by using ultrasonography and computed tomography. We classified the IBCs based on their number and shape.

Results

Intrahepatic biliary cysts developed in 12 of 54 patients. Three patients with solitary simple cysts and 1 patient with multiple simple cysts had no history of cholangitis. Two patients with multiple simple cysts had cholangitis at the time of IBC diagnosis and were treated with percutaneous transhepatic cholangiodrainage (PTCD). Patients with simple IBCs did not develop persistent cholangitis and their prognosis depended largely on their liver function; 3 of 6 patients remained healthy without cholangitis, whereas 3 patients required liver transplantation (LT) because of progressive liver failure or worsening hepatopulmonary syndrome, and not severe cholangitis. On the other hand, all 6 patients with multiple complicated IBCs had persistent cholangitis, eventually requiring LT. Even after bile flow to the intestine was reestablished after PTCD, both IBCs and cholangitis recurred. These patients required LT because of severe cholangitis.

Conclusions

Intrahepatic biliary cysts without cholangitis are not a source of infection and require no treatment. Simple IBCs with cholangitis can be controlled by antibiotics and/or PTCD. Patients with multiple complicated IBCs have a poor prognosis, requiring LT to control cholangitis. Although PTCD can control cholangitis in these patients as they wait for LT, PTCD does not alleviate it—LT is the final solution.     

Spontaneous closure of dural arteriovenous fistula after performing diagnostic angiography

The pathogenesis and clinical treatment of dural arteriovenous fistulas (DAVF) has been well established. However, only 15 cases of spontaneous closure of DAVFs have been reported. We describe a case of spontaneous closure of a DAVF. A 60-year-old male presented with pulsatile tinnitus. Selective cerebral angiography revealed a left posterior DAVF fed by the left occipital artery and the middle meningeal artery, which drained into the left transverse sinus and sigmoid sinus. Following the initial angiography, the patient exhibited vomiting with transient disorientation and amnesia. These symptoms, along with the tinnitus, disappeared by the following day. Seven days after the initial angiography, a second angiography was performed that revealed the complete disappearance of the DAVF. Previous reports have described a long period of closure for DAVFs following initial diagnosis. Possible mechanisms for spontaneous closure of DAVFs include the development of scar tissue or a sinus thrombosis that leads to occlusion of the DAVF In this case, the DAVF closure may have been due to a sinus thrombosis induced by sinus stenosis, since occlusion of the draining sinuses coincided with the spontaneous closure of the DAVF. In cases of non-traumatic DAVF without cortical venous reflex that do not present severe symptoms, a prudent course of treatment is necessary since there is a chance of spontaneous closure of the DAVF occuring.     

The high prevalence of colorectal neoplasms in preoperative patients with abdominal aortic aneurysm or peripheral artery disease.

OBJECTIVE: In Japan, the incidence of both colorectal carcinoma and vascular disease is increasing. We screened preoperative patients with abdominal aortic aneurysm (AAA) or peripheral artery disease (PAD) for colorectal cancer. DESIGN OF STUDY: This study was retrospective and cross-sectional. MATERIALS: The subjects were 492 patients admitted for elective surgery of AAA or PAD. METHODS: The patients underwent immunochemical faecal occult blood tests (FOBT) before operation, and those with positive results underwent investigations for colorectal neoplasm. We compared the results with that of screening programmes performed on the general population. RESULTS: Of the 408 patients that underwent FOBT, 104 (25.5%) were positive. After colonoscopy, six (1.5%) had colorectal carcinoma and 16 (3.9%) had advanced adenoma. These values were several folds higher than that for the general population in Japan. CONCLUSIONS: Patients with AAA or PAD carry a high risk for colorectal neoplasm.