Performance of a modified three-level classification in stratifying open liver resection procedures in terms of complexity and postoperative morbidity.

BACKGROUND: Traditional classifications for open liver resection are not always associated with surgical complexity and postoperative morbidity. The aim of this study was to test whether a three-level classification for stratifying surgical complexity based on surgical and postoperative outcomes, originally devised for laparoscopic liver resection, is superior to classifications based on a previously reported survey for stratifying surgical complexity of open liver resections, minor/major nomenclature or number of resected segments. METHODS: Patients undergoing a first open liver resection without simultaneous procedures at MD Anderson Cancer Center (Houston cohort) or the University of Tokyo (Tokyo cohort) were studied. Surgical and postoperative outcomes were compared among three grades: I (wedge resection for anterolateral or posterosuperior segment and left lateral sectionectomy); II (anterolateral segmentectomy and left hepatectomy); III (posterosuperior segmentectomy, right posterior sectionectomy, right hepatectomy, central hepatectomy and extended left/right hepatectomy). RESULTS: In both the Houston (1878 patients) and Tokyo (1202) cohorts, duration of operation, estimated blood loss and comprehensive complication index score differed between the three grades (all P < 0·050) and increased in stepwise fashion from grades I to III (all P < 0·001). Left hepatectomy was associated with better surgical and postoperative outcomes than right hepatectomy, extended right hepatectomy and right posterior sectionectomy, although these four procedures were categorized as being of medium complexity in the survey-based classification. Surgical outcomes of minor open liver resections also differed between the three grades (all P < 0·050). For duration of operation and blood loss, the area under the curve was higher for the three-level classification than for the minor/major or segment-based classification. CONCLUSION: The three-level classification may be useful in studies analysing open liver resection at Western and Eastern centres.

ANTECEDENTES: Las clasificaciones tradicionales de la resección hepática abierta (open liver resection, OLR) por número de segmentos resecados, no siempre se asocian con la complejidad quirúrgica y la morbilidad postoperatoria. El objetivo de este estudio fue comprobar si una clasificación de 3 niveles para estratificar la complejidad quirúrgica en función de los resultados quirúrgicos y postoperatorios, ideada originalmente para la resección hepática laparoscópica, es superior a las clasificaciones basadas en una encuesta descrita previamente para estratificar la complejidad quirúrgica de los procedimientos de OLR, nomenclatura menor/mayor, o número de segmentos resecados. MÉTODOS: Se estudiaron pacientes sometidos a una primera OLR sin otros procedimientos quirúrgicos concomitantes en el hospital MD Anderson (cohorte de Houston) o en la Universidad de Tokio (cohorte de Tokio). Se compararon los resultados quirúrgicos y postoperatorios entre 3 grados: I (resección limitada para el segmento anterolateral o posterosuperior y seccionectomía izquierda); II (segmentectomía anterolateral y hepatectomía izquierda); III (segmentectomía posterosuperior, seccionectomía posterior derecha, hepatectomía derecha, hepatectomía central y hepatectomía ampliada izquierda/derecha). RESULTADOS: En ambas cohortes de Houston (n = 1.878) y Tokio (n = 1.202), el tiempo operatorio, las pérdidas estimadas de sangre, y el índice de complejidad integral (comprehensive complication index) variaba en los 3 grados (todos P < 0,05) y aumentaba paso a paso desde los grados I a III (todos P < 0,05). La hepatectomía izquierda se asociaba con mejores resultados quirúrgicos y postoperatorios que la hepatectomía derecha, hepatectomía derecha ampliada, y seccionectomía posterior derecha, aunque estos cuatro procedimientos fueron categorizados como de complejidad intermedia en la clasificación basada en la encuesta. Los resultados quirúrgicos de las OLRs menores también variaron en los 3 grados (todos P < 0,05). Para el tiempo operatorio y la pérdida sanguínea, el área bajo la curva fue mayor para la clasificación de 3 niveles en el estudio actual, que para la clasificación menor/mayor o la clasificación basada en los segmentos. CONCLUSIÓN: La clasificación en 3 niveles puede ser útil en estudios que analizan las resecciones hepáticas abiertas en centros occidentales y orientales.

Hepatectomy for hepatocellular carcinoma after perioperative management of portal hypertension.

BACKGROUND: Indications for hepatectomy in patients with hepatocellular carcinoma (HCC) who have portal hypertension (PH) have been controversial. Some studies have concluded that PH is a contraindication to hepatectomy, whereas others have suggested that perioperative prophylactic management (PPM) can help overcome complications after hepatectomy associated with PH. The objective of this retrospective study was to assess the short- and long-term outcomes after hepatectomy for HCC in patients with PH, with or without PPM. METHODS: Records were reviewed of consecutive patients who underwent hepatectomy for HCC, with or without PPM of PH, in a single institution from 1994 to 2015. Patients were divided into three groups: those who received PPM for PH (PPM group), patients who had PH but did not receive PPM (no-PPM group) and those without PH (no-PH group). RESULTS: A total of 1259 patients were enrolled, including 123 in the PPM group, 181 in the no-PPM group and 955 in the no-PH group. Three- and 5-year overall survival rates were 74·3 and 53·1 per cent respectively in the PPM group, 69·2 and 54·9 per cent in the no-PPM group, and 78·1 and 64·2 per cent in the no-PH group (P = 0·520 for PPM versus no PPM, P = 0·027 for PPM versus no PH, and P < 0·001 for no PPM versus no PH). Postoperative morbidity and mortality rates were 26·0 and 0·8 per cent respectively in the PPM group, 29·8 and 1·1 per cent in the no-PPM group, and 20·3 and 0 per cent in the no-PH group. CONCLUSION: The present study has demonstrated acceptable outcomes among patients with HCC who received appropriate management for PH in an Asian population. Enhancement of the safety of hepatic resection through use of PPM may provide a rationale for expansion of indications for hepatectomy in patients with PH.

Use of a Right Lateral Sector Graft in Living Donor Liver Transplantation Is Feasible, but Special Caution Is Needed With Respect to Liver Anatomy.

Right lateral sector (RLS) grafting has been introduced to enlarge the potential donor pool for living donor liver transplantation (LDLT); however, evidence of its feasibility is limited. Data from 437 LDLTs carried out between 2000 and 2013 were analyzed retrospectively. LDLTs using a right liver graft (n = 251) were compared with those using a RLS graft (RLSG; n = 28). No donor mortality occurred, and the major complication rates were similar between the two groups. Postoperative liver function preservation was better in the RLSG donors. Concerning the recipients, the mortality and overall survival rates were similar between the two groups. The complication rate for the recipients was higher when more than two arterial or biliary anastomoses were necessary. A systematic literature search identified four reports on LDLT using RLSGs. Among 66 LDLTs, including the present series, there were no cases of donor death, and the rates of major and minor complications in the donors were 6% and 29%, respectively. The major complication and overall mortality rates in the recipients were 29% and 6%, respectively. LDLT using an RLSG is feasible, with an acceptable survival rate among the recipients.

Sinistral portal hypertension after pancreaticoduodenectomy with splenic vein ligation.

BACKGROUND: Splenic vein ligation may result in sinistral (left-sided) portal hypertension and gastrointestinal haemorrhage. The aim of this study was to analyse the pathogenesis of sinistral portal hypertension following splenic vein ligation in pancreaticoduodenectomy. METHODS: Patients who underwent pancreaticoduodenectomy for pancreatic cancer between January 2005 and December 2012 were included in this retrospective study. The venous flow pattern from the spleen and splenic hypertrophy were examined after surgery. RESULTS: Of 103 patients who underwent pancreaticoduodenectomy with portal vein resection, 43 had splenic vein ligation. There were two predominant venous flow patterns from the spleen. In the varicose route (27 patients), flow from the spleen passed to colonic varices and/or other varicose veins. In the non-varicose route, flow from the spleen passed through a splenocolonic collateral (14 patients) or a spontaneous splenorenal shunt (2 patients). The varicose route was associated with significantly greater splenic hypertrophy than the non-varicose route (median splenic hypertrophy ratio 1·52 versus 0·94; P < 0·001). All patients with the varicose route had colonic varices, and none had a right colic marginal vein at the hepatic flexure. CONCLUSION: Pancreaticoduodenectomy with splenic vein ligation may lead to sinistral portal hypertension. To avoid the development of varices, it is important to preserve the right colic marginal vein. Reconstruction of the splenic vein should be considered if the right colic marginal vein is divided.

Contrast-enhanced intraoperative ultrasonography using perfluorobutane microbubbles for the enumeration of colorectal liver metastases.

BACKGROUND: Intraoperative ultrasonography (IOUS) is considered the standard for the identification of liver metastases. Use of lipid-stabilized perfluorobutane microbubbles as an ultrasound contrast agent may improve this. The value of contrast-enhanced IOUS (CE-IOUS) in enumerating colorectal liver metastases was studied here. METHODS: CE-IOUS was performed in consecutive resections for colorectal liver metastases in 2007-2010. All patients underwent preoperative computed tomography. Magnetic resonance imaging was not carried out routinely. Conventional intraoperative examination including IOUS, and CE-IOUS with peripherally injected contrast were performed. The histopathological findings and 6-month follow-up images were used as the reference standard. RESULTS: The study group of 102 patients had a total of 315 lesions identified on preoperative imaging (2·4 lesions per operation; 129 operations). Conventional intraoperative examination including IOUS identified 350 lesions (2·7 per operation). CE-IOUS identified 370 lesions (2·9 per operation). The sensitivity, specificity and accuracy of CE-IOUS were 97·1, 59·1 and 93·2 per cent respectively. The CE-IOUS findings altered the surgical plan in 19 operations (14·7 per cent). CONCLUSION: CE-IOUS provided additional information to that obtained using contemporary preoperative imaging and conventional intraoperative examinations.

Randomized clinical trial of the effect of a saline-linked radiofrequency coagulator on blood loss during hepatic resection.

BACKGROUND: Use of a saline-linked radiofrequency coagulator (dissecting sealer) has been suggested to reduce blood loss during hepatic resection. A randomized clinical trial was conducted to assess the effects of using the device on the amount of blood loss. METHODS: Patients scheduled to undergo hepatic resection were randomly assigned to either use of the dissecting sealer or the clamp crushing method. The primary outcome measure was blood loss during liver parenchymal division. Multivariate analysis was also performed. RESULTS: Ninety-four consecutive patients underwent hepatic resection and 40 patients were assigned to each group. There were no significant differences between the dissecting sealer and clamp crushing groups in blood loss during liver parenchymal division (median 373 versus 535 ml; P = 0.252) or total intraoperative blood loss (665 versus 733 ml; P = 0.450). Multivariate analysis revealed that use of the dissecting sealer offered no protection against blood loss compared with the clamp crushing method (odds ratio 1.17 (95 per cent confidence interval 0.39 to 3.53); P = 0.777), whereas number of resections, thoracotomy and type of resection had a significant effect. CONCLUSION: Use of a dissecting sealer offered no substantial benefit over the clamp crushing method in reducing blood loss during hepatic resection.

Purification and properties of a proteinaceous toxin from the brackishwater clam (Corbicula japonica).

Water extracts from the brackishwater clam (Corbicula japonica) are lethal to mice upon i.v. injection. Further mouse assays confirmed that the toxicity exhibits a regional variation but no seasonal or sexual variations. The C. japonica toxin was purified from foot muscle, the most toxic tissue, successively by hydrophobic chromatography on Phenyl Sepharose, gel filtration on Sephacryl S-200, hydrophobic FPLC on Phenyl Superose and cation-exchange FPLC on Mono S. The purified toxin had an i.v. LD50 of 11 microg/kg against mice. It was a weakly basic protein (pI 7.7) with a mol. wt of 23,000 and was rich in Gly, Glx and Asx but devoid of Met. Analysis of the purified toxin by a protein sequencer afforded no N-terminal amino acid. In addition to C. japonica, two species of freshwater clams belonging to the genus Corbicula, C. leana and C. sandai, were newly found to be toxic, although much less potent than C. japonica. Despite the difference in anatomical distribution of toxins among the three species of Corbicula clams, both C. leana and C. sandai toxins were closely similar in stability and mol. wt to the C. japonica toxin.

Differential regulation of prolactin release and lactotrope proliferation during pregnancy, lactation and the estrous cycle.

The proestrous surge of prolactin (PRL) secretion and subsequent proliferation of lactotropes at estrus have been suggested to be induced by a common hypothalamic hormone. We investigated changes in lactotrope proliferation at other reproductive stages of female rats when PRL secretion was stimulated. To assess proliferative activity of lactotropes, incorporation of 5-bromo-2'-deoxyuridine (BrdU) into DNA was measured by double immunostaining for PRL and BrdU. BrdU-labeling indices, determined by BrdU injections at 10.00 h, revealed low levels of proliferative activity of lactotropes at the reproductive stages including diestrus, days 6 and 13 of pregnancy, and day 6 of lactation while high levels were detected on estrus and the day of parturition. When BrdU-labeling indices were determined at 3-hour intervals through day 6 of pregnancy to find an increase in lactotrope proliferation which might occur at times other than 10.00 h, proliferative activity of lactotropes remained at low levels with a slight increase in the afternoon. Such a diurnal change as observed in early pregnancy was not detected on day 13 of pregnancy. In contrast, short-interval determinations of BrdU-labeling indices during a period from day 20 of pregnancy to day 2 of lactation revealed a marked increase in proliferative activity on the day of parturition with a peak at 18.00 h, which was comparable to that observed at estrus. To investigate involvement of ovarian steroids in suppression of lactotrope proliferation as observed during early pregnancy and lactation, ovariectomized and pup-removed lactating rats were given one of treatment combinations of estradiol and suckling. In pup-removed lactating rats, estradiol treatment alone induced neither a PRL surge nor an increase in BrdU-labeling indices. Suckling stimuli, which were effective in increasing serum PRL concentrations irrespective of estradiol treatment, elicited a marked increase in BrdU-labeling indices in the presence of estradiol but not in its absence. These results suggest that proliferative activity of rat lactotropes does not necessarily correlate with PRL secretion during pregnancy and lactation. In contrast to PRL release, lactotrope proliferation requires both a hypophysiotropic stimulatory input from the hypothalamus and a sensitizing action of estradiol, an observation which may account for the fact that proliferation does not occur during pregnancy and lactation in spite of elevated PRL release.

[A patient with epilepsy, congenital alopecia and mental retardation: combination of atypical absence in waking and nocturnal partial seizure].

We report a 7-year-old girl with epilepsy, congenital alopecia, and mental retardation. She was hairless at birth. Very scanty hair, eyebrows and eyelashes appeared at 2 years of age. Developmental delay was first recognized at 6 years. Nocturnal partial seizures occurred at 4 years, and atypical absence in waking at 6 years. Electroencephalogram showed spike-waves in the centrotemporal area which increased and developed into a generalized continuous spike and wave complexes upon sleeping at the age of 7 years 1 month. Ictal electroencephalogram in atypical absence showed generalized 3 c/s spike and wave complexes. Skin biopsy of the scalp showed scanty, immature hair follicles and immature sebaceous glands. Whether this case is related to ectodermal dysplasia is unclear.

[Epileptogenesis of acute encephalitis and acute encephalopathy: epilepsy with its onset in the acute phase and without a latent period].

Epileptogenesis was evaluated in 60 patients with acute encephalitis and in 10 patients with acute encephalopathy. Forty-seven patients have been seizure-free during for more than three years' follow-up (Group III). On the other hand, 23 patients developed epilepsy. Among them, 18 patients developed epilepsy after a latent period of 1 month to 2 3/12 years (Group I). In Group I, a younger age of the onset, a long period of disturbed consciousness and a high activity of CSF neuron-specific enolase (NSE) was associated with refractory epilepsy. The other five patients had continuous seizures from the acute phase of encephalitis without a latent period (Group II). They had more than 2 types of partial motor seizures which occurred frequently during the acute phase of encephalitis. The NSE activity in the CSF of patients in Group II was less than 50 ng/ml, being similar to those in Group III. The epilepsy in Group II, however, was the most refractory. The reason for the development of this continuous refractory epilepsy remained obscure.

Involvement of phosphoinositide-3-kinase and p70 S6 kinase in regulation of proliferation of rat lactotrophs in culture.

Phosphoinositide-3-kinase (PI-3K) and p70 S6 kinase (p70S6k) are suggested as important molecules for mediating mitogenic actions of growth factors and cytokines in a variety of cell types. The purpose of the present study was to investigate whether these kinases were involved in mediation of the mitogenic actions of not only the growth factor insulin but also cyclic adenosine monophosphate (cAMP) and estrogen on rat cultured lactotrophs. Treatment with wortmannin or LY294002, a PI-3K inhibitor, or rapamycin, a p70S6k inhibitor, decreased basal levels of 5-bromo-2-deoxyuridine (BrdU)-labeling indices of lactotrophs in a dose-dependent manner. These inhibitors were effective in blocking an increase in BrdU-labeling indices induced by insulin. LY294002 and rapamycin also suppressed an increase in BrdU-labeling indices induced by forskolin, an adenylate cyclase activator, or dibutyryl cAMP, a membrane-permeable cAMP analog, as well as that induced by estradiol, a physiologic extracellular activator of lactotroph proliferation. However, the dibutyryl cAMP-, but not insulin-induced proliferation, acquired a resistance to LY294002 and rapamycin by pretreatment with bromocriptine, a dopaminergic agonist that is able to suppress lactotroph proliferation. These results suggest that the mitogenic actions of cAMP and estradiol on rat lactotrophs are mediated by PI-3K and p70S6k, and that dopaminergic inhibition modifies the PI-3K and p70S6k dependence of the regulation of lactotroph proliferation.

Distribution of prolactin-releasing peptide-immunoreactive neurons in the rat hypothalamus.

A newly identified hypothalamic peptide whose specific receptors are present in the anterior pituitary gland is a selective and potent stimulator of prolactin secretion and is therefore termed prolactin-releasing peptide (PRP). We investigated the distribution of PRP-containing neurons in the hypothalamus of female rats by immunocytochemical techniques. Immunocytochemistry using a specific antibody raised to PRP revealed that PRP-immunoreactive perikarya were located in the posteroventral part of the dorsomedial nucleus of the hypothalamus. PRP-immunoreactive nerve terminals were present in high concentrations in a region ventral to the bed nucleus of the stria terminalis, but scarcely observed in the external layer of the median eminence in which well known hypothalamic hormones such as growth hormone-releasing hormone and somatostatin were abundantly detected. This specific distribution in the hypothalamus suggests a novel route of the hypophysiotropic action of PRP.

Mitogen-activated protein kinase-dependent stimulation of proliferation of rat lactotrophs in culture by 3',5'-cyclic adenosine monophosphate.

Intracellular cAMP regulates cell proliferation as a second messenger of extracellular signals in a number of cell types. We investigated, by pharmacological means, whether an increase in intracellular cAMP levels changes proliferation rates of lactotrophs in primary culture, whether there are interactions between signal transduction pathways of cAMP and the growth factor insulin, and where the dopamine receptor agonist bromocriptine acts in the cAMP pathway to inhibit lactotroph proliferation. Rat anterior pituitary cells, cultured in serum-free medium, were treated with cAMP-increasing agents, followed by 5-bromo-2'-deoxyuridine (BrdU) to label proliferating pituitary cells. BrdU-labeling indices indicative of the proliferation rate of lactotrophs were determined by double immunofluorescence staining for PRL and BrdU. Treatment with forskolin (an adenylate cyclase activator) or (Bu)2cAMP (a membrane-permeable cAMP analog) increased BrdU-labeling indices of lactotrophs in a dose- and incubation time-dependent manner. The cAMP-increasing agents were also effective in increasing BrdU-labeling indices in populations enriched for lactotrophs by differential sedimentation. The stimulatory action of forskolin was observed, regardless of concentrations of insulin that were added in combination with forskolin. Inhibition of the action of endogenous cAMP by H89 or KT5720, a protein kinase A inhibitor, attenuated an increase in BrdU-labeling indices by insulin treatment. On the other hand, the specific mitogen-activated protein kinase inhibitor PD98059, which was effective in blocking the mitogenic action of insulin, markedly suppressed the forskolin-induced increase in BrdU-labeling indices. (Bu)2cAMP antagonized not only inhibition of BrdU labeling indices but also changes in cell shape induced by bromocriptine treatment, although forskolin did not have such an antagonizing effect. These results suggest that: 1) intracellular cAMP plays a stimulatory role in the regulation of lactotroph proliferation; 2) cAMP and insulin/mitogen-activated protein kinase signalings require each other for their mitogenic actions; and 3) the antimitogenic action of bromocriptine is, at least in part, caused by inhibition of cAMP production.

Enhancement by 1-oleoyl-2-docosahexaenoyl phosphatidylcholine of long-term potentiation in the rat hippocampal CA1 region.

We reported previously that administration of 1-oleoyl-2-docosahexaenoyl-sn-glycero-3-phosphorylcholine (ODHPC), a kind of phosphatidylcholine, enhanced discriminatory shock avoidance learning in rats. Since long-term potentiation (LTP) of the hippocampus has been suggested to be a physiological substrate of some forms of memory, we investigated the effects of ODHPC on LTP in the rat hippocampal CA1 region. LTP in the amplitude of population spikes in the CA1 region was induced by tetanic stimulation in anesthetized rats. ODHPC significantly increased magnitudes of LTP in a dose-dependent manner when injected intraperitoneally 20 min before inducing LTP. However, administration of 1,2-dioleoyl-sn-glycero-3-phosphorylcholine, in which only docosahexaenoyl residue of ODHPC was replaced with oleoyl residue, did not affect LTP. These results suggest that ODHPC enhances hippocampal LTP by its specific conformation.

Electrical stimulation of the lower midbrain around retrorubral field decreases temperatures of brown fat and rectum in anesthetized Wistar rats.

To investigate a neuronal mechanism controlling heat production of brown adipose tissue (BAT), ventral regions of the lower midbrain was stimulated by rectangular electric current (0.1 ms, 1 mA, 5-50 Hz) while recording temperatures of the interscapular BAT (IBAT), rectum and arterial blood pressure in urethane-anesthetized Wistar rats at room temperature of 24-26 degrees C. Unilateral stimulation (10 Hz) for 5 min to the midbrain around the retrorubral field decreased temperatures of IBAT (0.33 +/- 0.03 degrees C, n = 33) and rectum (0.10 +/- 0.01 degrees C). The response was reversed when procaine (10%, 800 nl) was injected into the same locus. The results support the hypothesis that a tonic inhibitory mechanism for metabolic heat production locates around the retrorubral field.

D2 dopamine-receptor-mediated inhibition of proliferation of rat lactotropes in culture is accompanied by changes in cell shape.

Dopaminergic agonists are effective in vivo in inhibiting lactotrope proliferation and prolactin (PRL)-secreting pituitary tumors. The purpose of the present study was to demonstrate in vitro actions of dopaminergic agents on proliferation and cell shape of rat lactotropes. Anterior pituitary cells cultured with serum-free, chemically defined medium were treated with dopaminergic agents and were labeled with 5-bromo-2'-deoxyuridine (BrdU) for 3 h before the end of culture. BrdU-labeling indices indicative of the proliferation rate of lactotropes were determined by double immunofluorescence staining for BrdU and PRL. Treatment with dopamine for 21 h decreased BrdU-labeling indices of lactotropes in a dose-dependent manner with a nadir at 3 x 10(-7) M. The inhibitory action of 10(-5) M dopamine appeared 15 h after the initiation of treatment and became pronounced with time up to 33 h. The dopamine action was mimicked by treatment with the D2 receptor agonist bromocriptine at concentrations over 10(-9) M. Phase-contrast microscopy revealed that the flat polygonal cell shape of cultured lactotropes had changed to a round refractive cell shape after treatment with dopamine or bromocriptine, and that these changes in cell shape exactly paralleled those in the BrdU-labeling index. The changes in cell shape of lactotropes were accompanied by changes in subcellular distribution of actin filaments. Pretreatment with 10(-7) M eticlopride, a D2 receptor antagonist, blocked the dopamine- or bromocriptine-induced changes in both BrdU-labeling index and cell shape. These results suggest that (1) the in vitro experimental system established in the present study is a good model for studying the mechanism of the antiproliferative action of dopamine and (2) D2-receptor-mediated inhibition of proliferation of lactotropes in serum-free culture is closely related to changes in actin organization and cell shape.