Somatic mutations of epidermal growth factor receptor in colorectal carcinoma.

PURPOSE: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non-small cell lung carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA. EXPERIMENTAL DESIGN: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction and PCR, we examined EGFR mutations by sequencing genomic DNA. RESULTS: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma. CONCLUSIONS: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these tumors may be susceptible to gefitinib treatment.     

Perioperative management for total en bloc spondylectomy--the effects of preoperative embolization and hypotensive anesthesia

We retrospectively evaluated the effects of preoperative embolization and hypotensive anesthesia on total en bloc spondylectomy (TES) for solitary spinal metastases. In ten patients (treatment group), feeding arteries of spinal metastases were embolized preoperatively and controlled hypotensive anesthesia was induced during operation. In other ten patients (control group), these treatments were not applied. Intraoperative blood loss as well as the amount of blood transfused in the treatment group were significantly lower than those in the control group. Moreover, postoperative platelet counts in the treatment group were significantly higher than those in the control group. These findings indicate that embolization of feeding arteries of metastases and hypotensive anesthesia decrease intraoperative blood loss and may prevent postoperative complications in TES.     

Morvan Syndrome Converted from Isaacs' Syndrome after Thymectomy with Positivity for Both Anti-LGI1 and Anti-CASPR2 Antibodies

Anti-voltage-gated potassium channel complex antibodies-mediated disorder includes Isaacs'' syndrome, which is characterized by neuromyotonia, and Morvan syndrome, which is characterized by neuromyotonia, encephalopathy and autonomic dysfunction. We herein report a patient with Morvan syndrome that converted from Isaacs'' syndrome after thymectomy. The patient first presented with myospasm in all extremities and positivity for both anti-leucine-rich glioma inactivated 1 (LGI1) and anti-contactin-associated protein like 2 (CASPR2) antibodies and subsequently developed encephalopathy after thymectomy, which was successfully improved by immunotherapy. This is the first case of Morvan syndrome wherein thymectomy worsened Isaacs'' syndrome, suggesting that immunotherapy should be considered for Isaacs'' syndrome accompanied by positivity for both anti-LGI1 and anti-CASPR2 antibodies to prevent worsening to Morvan syndrome.     

Hepatitis B Virus Infection Predicts Extrahepatic Metastasis After Hepatic Resection in Patients With Large Hepatocellular Carcinoma

Background Although extrahepatic metastasis occurs rarely after hepatic resection for hepatocellular carcinoma (HCC), the prognosis of these patients is extremely poor. Predictors of extrahepatic metastasis have not been fully investigated. Methods To identify predictors of extrahepatic metastasis after resection, we retrospectively investigated 77 patients with HCC tumors >50 mm in diameter who underwent hepatic resection. We investigated correlations between postoperative extrahepatic metastasis and clinicopathologic factors as well as extrahepatic metastasis-free survival rate by log rank test and predictors of extrahepatic metastasis by univariate and multivariate logistic regression models. Results Hepatitis B surface antigen (HBs-Ag) was found in 25 (32.5%) of 77 patients, and extrahepatic metastasis occurred in 26 (33.8%). Patients with extrahepatic metastasis showed better liver function and a high occurrence of HBs-Ag positivity than those without. The 5-year extrahepatic metastasis-free survival rate was worse in patients with HBs-Ag positivity, larger tumors (≥70 mm), higher alfa-fetoprotein level (≥300 ng/mL), and lower indocyanine green retention rate at 15 minutes (ICGR₁₅) (<15%) than in those without. By univariate logistic regression analysis, HBs-Ag positivity, larger HCC tumor (≥70 mm), lower ICGR₁₅ (<15%), and lower preoperative lymphocyte count (<1000/mm³) were predictors of extrahepatic metastasis (P < .1). By multivariate analysis, HBs-Ag positivity was an independent predictor of postoperative extrahepatic metastasis (P = .04). Conclusions In patients positive for HBs-Ag, radiologic examination of extrahepatic organs should be performed as a part of the postoperative surveillance. Hepatitis B virus infection may promote establishment of extrahepatic metastasis.     

Surgical outcomes of nephron-sparing surgery for renal tumors

PURPOSE: We retrospectively assessed the surgical outcomes of nephron-sparing surgery (NSS) for patients with renal tumors. PATIENTS AND METHODS: From 1985 to March 2001, a total of 99 NSSs were performed on 94 patients with renal tumors. The patients were divided into three groups. Group I comprised of 22 patients who underwent imperative surgeries for renal cell carcinoma (RCC). The tumors were found in 18 patients bilaterally (including 8 patients with von Hippel-Lindau disease), in 3 with solitary kidney, and in 1 with chronic renal failure. The mean +/- standard deviation of patient age and tumor diameter was 46 +/- 23 years and 36 +/- 23 mm, respectively. Twenty-three in situ NSSs were performed on 18 patients in Group I, and the remaining 4 patients were treated with 3 simultaneous operations for bilateral renal tumors with or without 2 ex vivo surgeries. Group II consisted of 49 patients who had small RCCs with the normal contralateral kidney and underwent NSSs (elective indication). The mean age and tumor diameter was 54 +/- 10 years and 28 +/- 11 mm, respectively. Group III consisted of 23 patients with non-RCC tumor (10 angiomyolipomas, 8 cystic tumors, 2 adenomas, 2 metastatic tumors, and 1 degenerative lesion), all of whom were treated with NSS. The mean age and tumor diameter was 47 +/- 14 years and 41 +/- 29 mm, respectively. RESULTS: In Group I, 3 patients died of cancer including 2 patients who had had multiple lung metastases preoperatively. The five-year tumor specific survival rate was 87.3% with a postoperative follow-up of 49 +/- 36 months. In Group II, there were few peri-operative complications or no local recurrence at follow-up of 52 +/- 38 months. A patient developed lung metastasis, which was removed surgically with no evidence of recurrence at 159 months after NSS. Postoperative renal scintigraphy on 35 patients showed well-preserved renal function of the operated kidney. Improvement in surgical techniques resulted in less-invasive surgery in 22 operations during the last 4 years. The patients of Group III were also operated uneventfully, although 1 experienced postoperative bleeding. In 12 patients with solitary kidney (11 in Group I and 1 in Group III) serum creatinine level increased transiently, decreased to 1.3 times of preoperative values within 3 months, and almost recovered at 1-year follow-up. CONCLUSION: Excellent outcomes in cancer control and preservation of renal function support the validity of nephron-sparing surgery to treat renal tumors. The candidate patients may include those with bilateral kidney tumors, tumor occuring in the solitary kidney or small renal cell carcinomas with the normal contralateral kidney. Earlier detection of small lesions and less invasive surgical techniques will facilitate a wider indication of NSS.     

Bilateral carotid stenting for bilateral carotid artery stenosis improved vascular dementia

We report a case of bilateral internal carotid artery (ICA) stenosis treated with stenting. A 78-year-old man suffered from vascular dementia and left hemiparesis, and, by magnetic resonance angiogram (MRA), was diagnosed as having bilateral ICA stenosis. Cerebral angiogram showed severe, bilateral ICA stenosis (right; 88%, left; 93%) and xenon single photon emission tomography (SPECT) showed severely decreased cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). We performed bilateral carotid angioplasty with self-expanding stents. Both CBF and CVR were improved bilaterally after the operation. The patient was discharged without neurological deficits. Carotid stenting may be an alternative treatment for severe ischemia caused by severe, bilateral ICA stenosis.