Reassessment of the clinical significance of portal-superior mesenteric vein invasion in borderline resectable pancreatic cancer.

OBJECTIVE: The principal objective of this study is to clarify the prognostic significance of borderline resectable pancreatic cancer (BRPC). The second objective is to evaluate the prognostic impact of the depth of pathological venous invasion. METHODS: The study included 122 pancreatic cancer patients who underwent curative surgery. All computed tomography scans of the patients were retrospectively interpreted and classified according to the NCCN guidelines, version 1.2016, as resectable (-) or borderline resectable (+) in each arterial (BR-A) and venous (BR-PV) involvement. RESULTS: The overall survival (OS) rate was significantly higher in BR-A(-) patients (n = 94) than in BR-A(+) patients (n = 28) (P = 0.001), whereas there was no difference between BR-PV(-) (n = 101) and BR-PV(+) patients (n = 21) (P = 0.257). In a multivariate analysis, the independent predictors of OS included BR-A(+) (P = 0.002), lymph node metastasis (P = 0.008), pathological venous invasion (P = 0.003), and adjuvant chemotherapy (P = 0.001). Of 39 patients who underwent venous resection, no significant difference was observed between BR-PV(-) (n = 20) and BR-PV(+) patients (n = 19) in resection rate, lymph node metastasis, the presence of extrapancreatic nerve invasion, recurrence rate, frequency of initial recurrence at a liver or local site, and OS. Pathological venous invasion was significantly deeper in BR-PV(+) patients. However, the depth of invasion was not associated with OS. CONCLUSION: The definition of venous involvement in the current guidelines predicted the depth of pathological venous invasion but not OS in BRPC patients. Further prospective, randomized studies are needed to establish treatment strategies for BRPC patients with isolated venous involvement.

Preliminary study on the clinical application of augmented reality neuronavigation.

OBJECTIVE: To develop an augmented reality (AR) neuronavigation system with Web cameras and examine its clinical utility. METHODS: The utility of the system was evaluated in three patients with brain tumors. One patient had a glioblastoma and two patients had convexity meningiomas. Our navigation system comprised the open-source software 3D Slicer (Brigham and Women's Hospital, Boston, Massachusetts, USA), the infrared optical tracking sensor Polaris (Northern Digital Inc., Waterloo, Canada), and Web cameras. We prepared two different types of Web cameras: a handheld type and a headband type. Optical markers were attached to each Web camera. We used this system for skin incision planning before the operation, during craniotomy, and after dural incision. RESULTS: We were able to overlay these images in all cases. In Case 1, accuracy could not be evaluated because the tumor was not on the surface, though it was generally suitable for the outline of the external ear and the skin. In Cases 2 and 3, the augmented reality error was ∼2 to 3 mm. CONCLUSION: AR technology was examined with Web cameras in neurosurgical operations. Our results suggest that this technology is clinically useful in neurosurgical procedures, particularly for brain tumors close to the brain surface.

Mineral trioxide aggregate inhibits osteoclastic bone resorption.

Mineral trioxide aggregate (MTA), a commonly used endodontic repair material, is useful for both basic and clinical research, and the effect of MTA on osteoblast differentiation has been well-defined. However, the effects of MTA on osteoclastic bone resorption are not fully understood. Hence, the aim of this study is to examine the effect of MTA solution in the regulation of osteoclast bone-resorbing activity using osteoclasts formed in co-cultures of primary osteoblasts and bone marrow cells. MTA solution dose-dependently reduced the total area of pits formed by osteoclasts. The reduction of resorption induced by 20% MTA treatment was due to inhibition of osteoclastic bone-resorbing activity and had no effect on osteoclast number. A 20% MTA solution disrupted actin ring formation, a marker of osteoclastic bone resorption, by reducing phosphorylation and kinase activity of c-Src, and mRNA expressions of cathepsin K and mmp-9. A high concentration of MTA solution (50%) induced apoptosis of osteoclasts by increasing the expression of Bim, a member of the BH3-only (Bcl-2 homology) family of pro-apoptotic proteins. Taken together, our results suggest that MTA is a useful retrofilling material for several clinical situations because it both stimulates osteoblast differentiation and inhibits bone resorption.

Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension.

BACKGROUND: Portal venous thrombosis (PVT) is a potentially fatal complication following splenectomy. Its mechanisms and risk factors are poorly understood, especially in patients with cirrhosis and portal hypertension. This study investigated risk factors for PVT following splenectomy in such patients. METHODS: All consecutive patients with cirrhosis who underwent splenectomy in Kyushu University Hospital between 1998 and 2004 were included in this retrospective study. They were divided into two groups based on the presence or absence of postoperative PVT. Preoperative and operative factors were compared, and the relationships between formation of PVT and its independent variables were analysed. In some cases, portal venous flow was measured before and after splenectomy using duplex Doppler ultrasonography. RESULTS: PVT developed after surgery in 17 (24 per cent) of 70 patients studied. Multivariable analysis showed that increased splenic vein diameter and low white cell count were significant independent risk factors for PVT. Portal venous flow after splenectomy was greatly reduced in the PVT group, but not in patients without PVT. CONCLUSION: Large splenic vein diameter and low white cell count are independent risk factors for PVT after splenectomy in patients with cirrhosis and portal hypertension.

Factors related to the advantageous effects of wearing a wetsuit during swimming at different submaximal velocity in triathletes.

This study was designed to compare the effects of wetsuit (WS) to swimsuit (SS) at identical relative velocities in a swimming flume. Thirteen triathletes performed a continuous progressive swimming test and submaximal steady state swimming tests with a WS and with a SS. Maximal oxygen uptake (VO2max) and the associated velocity at which the VO2max was achieved (VVO2max) were determined during the continuous progressive tests. Two 5 min swims (at 60% VVO2max (V(60%)) and 80% VVO2max (V(80%))) were then conducted to measure VO2max, blood lactate concentration (LA), rating of perceived exertion (RPE), the energy cost of swimming (Cs), stroke rate (SR) and stroke length (SL). No difference was found in VO2max, but VVO2max with a WS was 5.4% higher than with a SS. VO2 with a WS was lower than with a SS alone at V(60%), but not at V(80%). Cs with a WS was lower by 14.4% at V(60%) and 7.5% at V(80%) than with a SS. No differences were found in LA and RPE between suit conditions during both submaximal swims. Wearing a WS did not affect SL, but SR tended to be higher in a WS for both submaximal velocities. These results suggest that the benefits of wearing a WS are not only improvement in swimming performance and propulsion efficiency, but reduction in gross energy consumption in the swimming portion of triathlon races. Furthermore, when wearing a WS, incremental changes in SR rather than SL are associated with improved swimming performance.

Early experiences of endoscopic procedures in general surgery assisted by a computer-enhanced surgical system.

We performed a variety of complete total endoscopic general surgical procedures, including colon resection, distal gastrectomy, and splenectomy, successfully with the assistance of the da Vinci computer-enhanced surgical system. The robotic system allowed us to manipulate the endoscopic instruments as effectively as during open surgery. It enhanced visualization of both the operative field and precision of the necessary techniques, as well as being less stressful for the endoscopic operating team. This technological innovation can therefore help surgeons overcome many of the difficulties associated with the endoscopic approach and thus has the potential to enable more precise, safer, and more minimally invasive surgery in the future.

[Current status and future of surgical robotic systems].

In this review, we are commenting the current status and the future of surgical robotic systems. AESOP is a voice-controlled laparoscope manipulator that enables the "Solo-surgery". ZEUS is a master-slave manipulator that is characterized by its simplicity and lightness. da Vinci is another master-slave manipulator that has more range of freedom, therefore a surgeon can perform the operation with fewer difficulties. The technological development of high-quality and real-time 3D simulation, minimization of scopes and power saving techniques made these surgical robots realized. Although many pending matters such as lack of safety guideline or lack of accuracy of sensor/monitor have been raised in current surgical robotics, the development of the technologies may promise to resolve such matters in the future.

Defective mitogen-activated protein kinase (ERK2) signaling in gastric mucosa of portal hypertensive rats: potential therapeutic implications.

Portal hypertensive (PHT) gastropathy is a frequent, serious complication of liver cirrhosis. PHT gastric mucosa has numerous abnormalities such as reduced mucosal potential differences, reduced surface oxygenation, and increased susceptibility to injury caused by alcohol, aspirin, and other noxious factors. Because such mucosal injury is initially mediated by oxygen free radicals, and because mitogen-activated protein (MAP) kinase (ERK2) protects against cellular stress and induces cell proliferation, we postulated that oxidative stress-induced ERK2 activation is defective in PHT gastric mucosa. Here we show that in PHT gastric mucosa, ERK2 activation by oxidative stress is impaired. This impairment is mediated by overexpression of MAP kinase phosphatase-1 (MKP-1), which results from the underlying and continual oxidative state associated with portal hypertension, and is ameliorated by inhibiting MKP-1. Furthermore, we found that supplementing vitamin E, a free radical scavenger, reduces the oxidative state in PHT gastric mucosa, normalizes MKP-1 expression, and thereby reverses impairment of oxidative stress-induced ERK2 activation. Finally, we show that orally administered vitamin E completely reverses the increased susceptibility of PHT gastric mucosa to alcohol injury. Our findings point to a new molecular and mechanistic basis for PHT gastropathy and provide a new therapeutic modality for protection of PHT gastric mucosa.

Human mast cell progenitors in peripheral blood from atopic subjects with high IgE levels.

BACKGROUND: It remains unclear whether the number of circulating mast cell progenitors is increased in patients with atopic diseases. Distinct genotypes are reported to affect mast cell/basophil activation. OBJECTIVE: We compared the number and function of mast cell progenitors present in the peripheral blood from donors with normal IgE (IgE < 400 U/mL) and those with atopic dermatitis accompanied by high serum IgE (IgE > 5000 U/mL). METHODS: Purified peripheral blood cells were cultured in serum-free methylcellulose containing stem cell factor (SCF), IL-6 plus IL-3. Fresh methylcellulose containing the cytokines was layered over every 2 weeks. The cultured mast cells were retrieved from the methylcellulose and were functionally analysed. RESULTS: Mast cell colonies were distinguished at 6 weeks of culture as other colony types had been degenerated. The number of mast cell colony-forming cells varied depending on donors and was not significantly increased in peripheral blood from the hyper-IgE atopic patients. A significant inversed correlation was found between the number of mast cells per one colony and the ages of donors. The cultured mast cells derived from atopic patients and those from normal IgE donors equally expressed Fc epsilon RI and released histamine through Fc epsilon RI, although IL-4 priming in vitro markedly enhanced the function of mast cells regardless of donors. CONCLUSIONS: These results indicate that the number of circulating mast cell progenitors may be regulated by unknown individual factors unrelated to IgE levels. Mast cell function may be regulated largely by environmental factors, such as IL-4, but not determined by their progenitors' genotypes.

Carcinoma of the colon metastatic to the lower gingiva.

A case of carcinoma of the colon that metastasized to the lower gingiva is described. The patient who had carcinoma of the colon developed a proliferating lesion at the site of a recent tooth extraction. A few days later, the primary site of the malignancy appeared. The clinical features in such cases were reviewed in studies by others, most of which were of oral and dental surgery. Thus, because of our case, gastroenterologists should consider the possibility of gingival metastasis from malignant disease such as colorectal cancer.

A comparison of an open and laparoscopic appendectomy for patients with liver cirrhosis.

Liver cirrhosis is a critical factor contributing to morbidity and mortality in abdominal surgery, because patients with cirrhosis have a particularly high risk of developing bleeding, infection, and ascites. Laparoscopic appendectomy (LA) recently has gained a lot of attention around the world; however, comparisons between the benefits of LA and those of conventional open appendectomy (OA) for patients with liver cirrhosis have yet to be sufficiently compiled. In the present retrospective study, 40 patients with liver cirrhosis who were diagnosed with acute appendicitis before surgery underwent an appendectomy (OA in 25 patients and LA in 15 patients). This study focused on the operative time, amount of postoperative pain, use of analgesics, the restart of a normal diet, number of complications, length of hospital stay, and cost-effectiveness of the procedure in such patients. The amount of postoperative pain and the length of hospital stay were significantly smaller in the LA group. The mean values of the serum C-reactive protein on postoperative days 1, 3, and 7 were significantly less in the LA group. The number of wound infections and wound bleeding was also less in the LA group. The difference in the total cost of hospitalization was not significant. The cost of the operation was greater in the LA group than in the OA group, whereas the hospitalization cost in the LA group was less than that in the OA group. The results of this study suggest that LA may be superior to OA for the treatment of postoperative pain and postoperative complications for patients with liver cirrhosis. Long-term follow-up studies are still necessary, however, to determine any possible decrease in the number of late complications.

Immunohistochemical localization of vascular endothelial growth factor in the rat portal hypertensive gastropathy.

BACKGROUND AND AIMS: Portal hypertensive gastropathy (PHG) is now recognized to be a distinct entity. Recently, angiogenesis has been noticed as a key factor in clarifying the pathophysiology of various diseases. Angiogenesis in the PHT of explored gastric mucosa has yet to be explored. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. The aim of the present study was thus to investigate whether the hypoxic state exists in PHG, and whether VEGF appears more strongly in PHG than in normal gastric mucosa and, if so, what exactly is the role of the hypoxic state and VEGF in PHG. METHODS: At 1, 3, 7 and 14 days after either a portal ligation or sham operation, the portal venous pressure, the gastric mucosal blood flow volume and the blood gas were measured and, the expression of VEGF and antiproliferating cell nuclear antigen (PCNA) in gastric mucosal specimens was immunohistochemically assessed. RESULTS: The portal pressure (PP) and the gastric mucosal blood flow (GMBF) in the PHT rats were significantly greater than in the control (CTR). Both the SaO2 and PaO2 of the arterial blood gas were lower in the PHT rats than in the control rats. The percentage of VEGF expression in the PHG was found to be higher than that in the control gastric mucosa. The percentage of PCNA expression in the PHG was higher than that in the control gastric mucosa. CONCLUSION: The levels of SaO2 and PaO2 were lower in the PHT rats. There is a possibility that a kind of portal hypertensive gastric change may trigger an enhanced histochemical expression of VEGF. The increased activity of VEGF may have a possibility of the hypoxic gastric mucosal state caused by the presence of active congestion. This damaged mucosal state 'PHG' may thus facilitate the fragility in PHG and such lesions may be slow and insidious, which may therefore lead to sudden and severe anemia, thus causing massive and sometimes fatal hemorrhaging.

[A boy diagnosed SLE after Staphylococcus aureus infection over a long period].

We encountered a 13-year-old boy with SLE who showed specific pathophysiology. The affected child was hospitalized because of long-standing cutaneous empyesis considered to be Staphylococcus aureus infection, followed by manifestation of meningoencephalitis-like symptoms. On a close check up, the patient was diagnosed as having SLE complicated with interstitial lupus nephritis and verrucosis of the left ventricle. Besides the findings, the blastogenesis of the patient's lymphocyte was low against stimulation of sac-1 which connects with the Fc portion of lgG, one of the constituent proteins of Staphylococcus. Moreover, anti-phospholipid antibodies turned positive during immunosuppressive therapy and subcutaneous abscess due to Pseudomonas aeruginosae developed concurrently at about the same time, which posed difficulties in the treatment. The affected child had had Staphylococcus aureus infections over a long period of time before diagnosis of SLE and was susceptible to bacterial infections due to Pseudomonas aeruginosae during the treatment. The clinical course of this case was considered important in presuming the complex immunologically abnormal condition of SLE in childhood.

The therapeutic strategies in performing emergency surgery for gastroduodenal ulcer perforation in 130 patients over 70 years of age.

BACKGROUND/AIMS: Gastroduodenal ulcer is a very common illness in Japan. As the number of elderly persons in Japan increases the same as in Europe and America, the number of such patients requiring a gastroduodenal emergency operation has also increased. Regarding the complications of peptic ulcer, a perforation remains the most important fatal complication. The aim of this study is to investigate the operative risk factors and the long-term recurrence rates and to define the optimal surgical procedures in emergency situations in elderly patients. METHODOLOGY: From April 1988 through March 1997, 130 patients over 70 years of age with a perforated gastroduodenal ulcer (a duodenal ulcer perforation in 50 patients and a gastric ulcer perforation in 80 patients) were operated on in an emergency situation in our clinic. We investigated the following items; medical illness, preoperative risk factor, optimal surgical procedure, postoperative organ failure and the cumulative recurrence-free rates after surgical treatment. RESULTS: A significant correlation with mortality was observed in patients with established comorbidity in the following organs: lung (P = 0.03), heart (P = 0.02), kidney (P = 0.04), and diabetes (P = 0.03). The highest postoperative mortality rate was recorded in patients who underwent a simple closure of a duodenal ulcer perforation (4 patients; 26.7%), while the lowest postoperative mortality rate was recorded in patients who underwent a simple closure and vagotomy of a duodenal ulcer perforation (3 patients; 12.5%). In gastric ulcers, the mortality rate in patients with a gastrectomy was significantly higher than in patients with a simple closure. The practical application of the three risk factors (preoperative shock, delay to surgery over 24 hours, and medical illness) was shown by the progressive rise in the mortality rate with the increasing number of risk factors. Based on the 5 postoperative years after treating a perforated duodenal ulcer, the cumulative recurrence rate after a simple closure (63.6%) was significantly higher than that after a simple closure and vagotomy (38.1%) (n = 0.02) or after gastrectomy (0%) (P < 0.001). At 5 years postoperatively, the cumulative recurrence rate after a simple closure (41.2%) was significantly higher than that after a gastrectomy (15.9%) (P < 0.01). CONCLUSIONS: In conclusion, in an emergency situation, elderly patients are in a highly unfavorable prognostic condition due to their advanced age, and comorbidity, which thus leads to poorer results, not only worldwide, but also in Japan. Based on our findings, in duodenal ulcer cases, a simple closure and vagotomy is recommended because of its low mortality and minimal stress, except for cases with a giant perforation measuring over 20 mm in diameter at the perforation hole or with severe duodenal stenosis. In stomach ulcer cases, a gastrectomy may be recommended because of its low recurrence rate.

Portal hypertensive gastric mucosa has reduced activation of MAP kinase (ERK2) in response to alcohol injury: a key to impaired healing?

Portal hypertensive (PHT) gastric mucosa has increased susceptibility to injury and impaired mucosal healing. Because our previous study showed that ulcer-induced activation of mitogen-activated protein (MAP) kinase (ERK) plays a pivotal role in gastric mucosal healing, we investigated whether ERK activation is altered in PHT gastric mucosa following alcohol injury. We studied ERK2 phosphorylation and activity and expression of MAP kinase phosphatase-1 (MKP-1) in gastric mucosa of PHT and sham-operated (SO) normal rats both at baseline and following alcohol injury. In SO gastric mucosa, ERK2 phosphorylation and activity were significantly increased time-dependently following alcohol injury: by 221% and 137%, respectively at 24 h vs. baseline. In contrast, in PHT gastric mucosa following alcohol injury, neither ERK2 phosphorylation nor activity was increased versus baseline. In PHT gastric mucosa, MKP-1 mRNA and protein expression were increased at baseline versus SO rats and were increased further following alcohol injury with values higher by 20%-40% at each study time versus SO rats. Because ERK2 is crucial for mucosal healing, reduced ERK2 activation resulting from the overexpression of MKP-1 might be the basis for the impaired mucosal healing in PHT gastric mucosa.

Hyperbilirubinemia induced by endoscopic variceal ligation for esophageal varices in a patient with primary biliary cirrhosis: a case report.

We describe the case of a 51-year-old woman with primary biliary cirrhosis who developed hyperbilirubinemia with transient liver dysfunction after undergoing endoscopic variceral ligation to control hemorrhaging from esophageal varices. After undergoing a variceal ligation, the serum total bilirubin increased from 4.0 mg/dL to 9.5 mg/dL, and the degree of liver failure worsened. She finally had to undergo a liver transplant. We discuss the mechanism of hyperbilirubinemia after endoscopic variceal ligation.

Despite activation of EGF-receptor-ERK signaling pathway, epithelial proliferation is impaired in portal hypertensive gastric mucosa: relevance of MKP-1, c-fos, c-myc, and cyclin D1 expression.

Portal hypertensive (PHT) gastric mucosa has increased susceptibility to injury and impaired mucosal healing. Our previous study demonstrated increased ERK activation and MAP kinase phosphatase-1 (MKP-1) overexpression in PHT gastric mucosa. However, it remains unknown which tyrosine kinase receptors are involved in ERK activation and whether ERK activation results in increased cell proliferation. We examined whether EGF receptor (EGF-R) is involved in ERK activation and whether ERK activation triggers epithelial proliferation in PHT gastric mucosa. In gastric mucosa of PHT and sham-operated (SO) rats we studied: (1) EGF-R mRNA and protein expression as well as phosphorylation and membrane protein tyrosine kinase (PTK) activity; (2) ERK2 phosphorylation and activity; (3) MKP-1 mRNA and protein; (4) c-fos, c-myc and cyclin D1 mRNAs, and gastric epithelial proliferation. In PHT gastric mucosa: (1) EGF-R mRNA, protein and phosphorylation and membrane PTK activity were all significantly increased by 38%, 49%, 43% and 49%, respectively; (2) ERK2 phosphorylation and activity were significantly increased by 40% and 50 %, respectively; (3) MKP-1 mRNA and protein expression were significantly increased by 27% and 34%, respectively. In contrast, (4) c-fos, c-myc, and cyclin D1 mRNAs expression were all significantly decreased in PHT gastric mucosa by 36%, 33%, and 49%, respectively, and cell proliferation was significantly lower that in SO rats (11% in PHT vs. 18% in SO). These results suggest that in PHT gastric mucosa, ERK activation is mediated through EGF-R upregulation, but the gastric epithelial proliferation is impaired, possibly by MKP-1 overexpression, leading to reduction of c-fos, c-myc and cyclin D1.

Surgical strategy and outcomes for epileptic patients with focal cortical dysplasia or dysembryoplastic neuroepithelial tumor.

PURPOSE: The purpose of this study was to clarify and compare the influence of surgical strategy on relief from seizures in patients with focal cortical dysplasia (FCD) and those with dysembryoplastic neuroepithelial tumor (DNT). METHODS: Six patients with FCD and five patients with DNT, all of whom underwent surgical resection for medically intractable epilepsy, were compared in terms of presurgical seizure types and frequency, location of lesions, magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) with 99mTc-ECD, scalp electroencephalogram (EEG), and long-term video-EEG recording. Prolonged subdural recordings and intraoperative electrocorticograms (ECoG) were analyzed. The influences of surgical strategies on seizure outcomes were retrospectively analyzed. RESULTS: In all the FCD patients, ictal SPECT revealed hyperperfusion in the regions where MRI showed FCD. Interictal epileptiform activity and ictal seizure onset on ECoG performed with subdural electrodes were localized on the FCD itself. In contrast, the tumors of all the DNT patients were depicted as hypoperfuse areas on interictal SPECT scans. Ictal SPECT in one DNT patient showed hyperperfusion in the area enclosing the tumor. Interictal spiking in all DNT patients and ictal seizure onset in two DNT patients were not in the lesions themselves but in an area enclosing the lesion. All but one patient with FCD who underwent total lesionectomy became seizure free. All DNT patients who underwent resection of the epileptogenic cortex associated with lesionectomy became seizure free or achieved a 90% reduction in seizures. CONCLUSIONS: FCD has intrinsic epileptogenicity, whereas DNT is encompassed by epileptogenic cortical areas. Therefore, total lesionectomy is an essential strategy for FCD, whereas resection of the epileptic focus associated with lesionectomy of a DNT lesion is necessary to control seizures.