Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results

OBJECTIVE: To evaluate retrospectively the long-term results of an approach consisting of performing surgery in every patient in whom radical removal of all metastatic disease was technically feasible. SUMMARY BACKGROUND DATA: The indications for surgical resection for liver metastases from colorectal cancer remain controversial. Several clinical risk factors have been reported to influence survival. METHODS: Between March 1980 and December 1997, 235 patients underwent hepatic resection for metastatic colorectal cancer. Survival rates and disease-free survival as a function of clinical and pathologic determinants were examined retrospectively with univariate and multivariate analyses. RESULTS: The overall 3-, 5-, 10-, and 15-year survival rates were 51%, 38%, 26%, and 24%, respectively. The stage of the primary tumor, lymph node metastasis, and multiple nodules were significantly associated with a poor prognosis in both univariate and multivariate analyses. Disease-free survival was significantly influenced by lymph node metastasis, a short interval between treatment of the primary and metastatic tumors, and a high preoperative level of carcinoembryonic antigen. The 10-year survival rate of patients with four or more nodules (29%) was better than that of patients with two or three nodules (16%), and similar to that of patients with a solitary lesion (32%). CONCLUSIONS: Surgical resection is useful for treating liver metastases from colorectal cancer. Although multiple metastases significantly impaired the prognosis, the life expectancy of patients with four or more nodules mandates removal.     

Extended Left Hepatectomy by Severing All Major Hepatic Veins with Reconstruction of the Right Hepatic Vein

Curative liver resection is technically challenging when multiple liver metastases from colon cancer involve the confluence of the three major hepatic veins. We report two cases of successful extended left hemihepatectomy achieved by severing all of the major hepatic veins together with the wall of the inferior vena cava, to resect liver metastases from colon cancer. Reconstruction of the right hepatic vein was done after unroofing the right anterior area of the liver with a direct anastomosis of the right hepatic vein. We did not need to perform total vascular exclusion or portovenous shunting during the liver transection. This simple and safe method can increase the surgical indications for previously unresectable tumors.     

Surgical treatment of intrahepatic cholangiocarcinoma: four patients surviving more than five years.

BACKGROUND. To find the rational surgical strategy for the treatment of intrahepatic cholangiocarcinoma (ICC), clinical features of ICC were studied in 20 patients who underwent hepatic resection in the National Cancer Center Hospital from 1980 to 1990. METHODS. According to the morphologic pattern, we classified the ICCs into two subcategories, mass-forming and infiltrating, which correlated with their biologic behavior. RESULTS. Of 10 patients who underwent hepatectomy for mass-forming ICC, three survived more than 5 years without recurrence. The 1-, 3-, and 5-year survival rates were 59.3%, 44.4%, and 44.4%, respectively. Of 10 patients who underwent hepatectomy for infiltrating ICC, one survived more than 5 years without recurrence. The 1-, 3-, and 5-year survival rates were 72.0%, 27.0%, and 27.0%, respectively. The pathologic findings and recurrences indicated that the salient feature of the mass-forming type was its tendency for intrahepatic metastasis especially near a main lesion, and of the infiltrating type was the infiltrative spread via Glisson's capsule and hilar lymph nodal metastasis. CONCLUSIONS. An anatomic and extensive liver resection should be performed for mass-forming ICC, whereas a hepatectomy with excision of the extrahepatic bile duct and hilar lymph nodal dissection is recommended for infiltrating ICC.     

Plasma interleukin-6 and tumor necrosis factor-alpha can predict coronary endothelial dysfunction in hypertensive patients.

Coronary endothelial function is impaired in hypertension; however, the severity of this impairment varies among patients. We aimed to identify the predictors of coronary endothelial dysfunction among clinical variables related to hypertension and atherosclerosis. Twenty-seven untreated, uncomplicated essential hypertensive patients and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using (15)O-water positron emission tomography (PET) at rest and during a cold pressor test (CPT). Coronary vascular resistance (CVR) during CPT was used as a marker of coronary endothelial function. Serum low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, malondialdehyde-LDL, homeostasis model assessment, high-sensitivity C-reactive protein (hs-CRP), and plasma interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were also measured. CVR during CPT was significantly higher in hypertensive patients than in healthy controls (114+/-26 vs. 94+/-12 mmHg/[mL/g/min]; p<0.05). By univariate analysis, CVR during CPT was correlated with LDL cholesterol (r=0.38, p<0.05), IL-6 (r=0.46, p<0.02), and TNF-alpha (r=0.39, p<0.05) in hypertensive patients. By multivariate analysis, IL-6 and TNF-alpha were significant independent predictors of CVR during CPT. Elevated plasma IL-6 and TNF-alpha levels were independent predictors of coronary endothelial dysfunction in hypertensive patients. These results suggest that plasma IL-6 and TNF-alpha might be useful for identifying the high risk subgroup of hypertensive patients with coronary endothelial dysfunction and provide an important clue to link systemic inflammation to the development of coronary atherosclerosis.     

Preoperative identification of intraoperative blood loss of more than 1,500?mL during elective hepatectomy

Background

Despite recent advances in surgical techniques, hepatectomies remain one of the most hemorrhagic procedures in abdominal surgery. It is important to identify preoperatively patients who are at high risk of suffering massive intraoperative blood loss.

Methods

The clinical records of 251 patients who underwent an elective hepatectomy for liver tumors between September 2007 and December 2009 were reviewed retrospectively. A multivariate logistic regression analysis of preoperative factors potentially influencing intraoperative blood loss was performed. We set the cut-off value of the amount of blood loss for safe hepatectomy as less than 1,500?mL because no patients with blood loss of less than 1,500?mL received blood transfusion in this study. A scoring system to predict blood loss of more than 1,500?mL was constructed and validated in a cohort of 59 subsequent patients.

Results

Intraoperative blood loss of more than 1,500?mL was recognized in 35 of 251 patients (13.9%). Prothrombin activity?<?70%, non-peripheral location of the tumor, involvement of hepatic veins, body mass index????23.0, and major hepatectomy were independently associated with intraoperative blood loss of more than 1,500?mL. The score was calculated by assigning 1 point for each of the 5 risk factors. The area under the receiver operating characteristic curve (AUC) was 0.814 (95% CI 0.731?C0.898). This scoring system was highly predictive in the subsequent validation group of 59 patients (AUC?=?0.839, 95% CI 0.710?C0.969).

Conclusion

This predictive scoring system is considered to be useful for identifying before hepatectomy those patients with a high risk of intraoperative blood loss of more than 1,500?mL.     

Pediatric liver failure with massive sinusoidal infiltration of histiocytes

Histiocytic neoplasms, such as Langerhans cell histiocytosis (LCH) and disseminated juvenile xanthogranuloma (JXG), can involve the liver and sometimes cause liver failure. We aimed to classify non-LCH histiocytic proliferating disorders that do not exhibit typical disseminated JXG histology. We examined four pediatric patients who presented with liver failure and splenomegaly. Two patients with liver cirrhosis without cholestasis underwent liver transplantation (LT). The other two patients presented with giant cell hepatitis causing neonatal/infantile acute liver failure (ALF). The infantile ALF patient also underwent LT. Liver dysfunction developed after LT in all three transplant cases and the grafts exhibited massive sinusoidal infiltration of histiocytes with hemophagocytosis, similar to the native liver. The neonatal ALF patient was treated with an LCH-type chemotherapy regimen, and is alive and well at 18 months. Infiltrating histiocytes were positive for CD68 and CD163, and negative for CD1a, CD207, and S-100 protein. The BRAF V600E mutation was not present. Liver histological findings were not consistent with conventional disseminated JXG or LCH, although the histological findings in other organs overlapped those of well-known histiocytic neoplasms. The histological and immunohistochemical findings of infiltrating histiocytes suggest that these four cases constituted a disseminated JXG-like systemic disease.     

Characteristics of earlier atherosclerotic involvement in adolescent patients with Kawasaki disease and coronary artery lesions: significance of gray scale median on B-mode ultrasound

ObjectiveTo test the hypothesis that textural changes in the carotid intima–media complex (IMC) detected by B-mode ultrasound are associated with the difference of remodeling process in earlier atherosclerotic involvement in patients with Kawasaki disease (KD) and coronary artery lesions (CALs).MethodsEighteen patients with KD and CALs (mean age 17.2 years), 17 patients with heterozygous familial hypercholesterolemia (FH) (mean age 16.9 years) and 15 age-matched healthy controls (Cont) were assessed and compared for carotid intima–media thickness (CIMT), elastic property (E_p), and first- and second-order statistics.ResultsKD showed significantly higher gray scale median (GSM) than FH and Cont. KD and FH showed significantly higher CIMT, entropy and lower angular second moment than Cont, but no significant difference was found between KD and FH.ConclusionHigher GSM in KD may indicate alteration of tissue components and heterogeneity of IMC, suggesting the development of arteriosclerotic vascular remodeling after vasculitis. This is distinct from that of atherosclerosis with lower GSM often observed in FH.     

Regulation of Inhibitory Synaptic Plasticity in a Purkinje Neuron

Inhibitory synapses on Purkinje cells show synaptic plasticity such as rebound potentiation (RP), which seems to contribute to refined information processing in the cerebellar cortex. Recent progress in the study on regulation mechanism of RP is reported. RP is induced by depolarization of a Purkinje cell and expressed as the increased postsynaptic responsiveness to GABA. RP might work as a homeostatic mechanism to maintain activity of a Purkinje cell sensing the strength of heterosynaptic excitatory inputs. However, there is a homosynaptic mechanism to regulate RP. RP is suppressed by the GABAergic transmission occurring during depolarization. Elaborate molecular regulation mechanism of RP induction, including GABA(B) receptors, Ca(2+), cyclic adenosine 3',5'-monophosphate (cAMP), kinases such as Ca(2+)- and calmodulin-dependent kinase II and protein kinase A, and protein phosphatases such as PP1 and PP2B, has been clarified. Application of systems biological analyses combined with electrophysiological experiments has revealed a critical role of phosphodiesterase 1 in determination of the Ca(2+) signal to induce RP.     

Muscle biopsy findings predictive of malignancy in rare infiltrative dermatomyositis

Objective

The characteristic pathological muscular findings of polymyositis (PM) and dermatomyositis (DM) have been shown to reflect their different pathogeneses. Here, we characterized the muscle biopsy findings of PM and DM patients with or without malignancy.

Methods

We evaluated the muscle biopsy findings of 215 consecutive PM and DM patients admitted to our hospital between 1970 and 2009. Pathology of the lesion biopsy sections was classified into 3 types: endomysial infiltration-type, perivascular infiltration-type, and rare-infiltrative-type.

Results

There was no difference between the muscle pathology of PM patients with and without malignancy. However, the incidence of rare-infiltrative type muscle pathology in DM patients with malignancy was significantly higher than in those without such tumors (p = 0.0345).

Conclusion

The incidence of rare-infiltrative type muscle pathology may be a predictive marker of DM with malignancy.     

Estimation of radiation tolerance to high LET heavy ions in an anhydrobiotic insect, Polypedilum vanderplanki

PURPOSE: Anhydrobiotic larvae of Polypedilum vanderplanki are known to show an extremely high tolerance against a range of stresses. We have recently reported that this insect withstands exposure to high doses of gamma-rays (linear energy transfer [LET] 0.2 keV/microm). However, its tolerance against high LET radiation remains unknown. The aim of this study is to characterize the tolerance to high-LET radiations of P. vanderplanki. MATERIALS AND METHODS: Larval survival and subsequent metamorphoses were compared between anhydrobiotic (dry) and non-anhydrobiotic (wet) samples after exposure to 1 - 7000 Gy of three types of heavy ions delivered from the azimuthally varying field (AVF) cyclotron with LET values ranging from 16.2 - 321 keV/microm. The tolerance against 4He ions was also compared among three chironomid species. RESULTS: At all LET values measured, dry larvae consistently showed greater radiation tolerance than hydrated larvae, perhaps due to the presence of high concentrations of the disaccharide trehalose in anhydrobiotic animals, and the radiation-induced damage became evident at lower doses as development progressed. Relative biological effectiveness (RBE) values based on the median inhibitory doses reached a maximum at 116 keV/microm (12C), and the maximum RBE clearly increased as development progressed. Lower D0 (dose to reduce survival from relative value 1.00 - 0.37 on the exponential part of the survival curve), and higher Dq (quasi-threshold dose) were found in individuals exposed to 4He ions, compared to gamma-rays, and in P. vanderplanki larvae compared to non-anhydrobiotic chironomids. CONCLUSION: Anhydrobiosis potentiates radiation tolerance in terms of larval survival, pupation and adult emergence of P. vanderplanki exposed to high-LET radiations as well as to low-LET radiation. P. vanderplanki larvae might have more efficient DNA damage repair after radiation than other chironomid species.