Distal pancreatectomy withen bloc resection of the celiac artery for carcinoma of the body and tail of the pancreas

Summary Conclusion Combined resection of the celiac artery with a distal pancreatectomy (DP) increases the resectability and improves the overal prognosis of patients with locally advanced ductal cancer of the body and tail of the pancreas. Background Carcinoma of the body and tail of the pancreas is often unresectable because of invasion to adjacent organs. We evaluated a DP including anen bloc resection of the celiac artery (“extended”), for pancreatic cancer that had invaded the common hepatic and/or celiac arteries. Methods Six cases of an “extended” DP were compared with 19 cases of a “standard” DP for pancreatic ductal carcinoma in terms of clinical and pathologic findings, perioperative course, and long-term outcome. We also compared the survival rate of these two groups with a third group consisting of 22 patients with unresectable pancreatic ductal carcinoma. Results The mean operative time, postoperative serum aspartate aminotransferase concentration, and length of hospital stay did not significantly differ between the “extended” and “standard” DP groups. The cumulative 1- and 3-yr accumulated survival rates for the “extended,” “standard,” and unresectable groups were 40.0, 33.3, and 5.4, and 20.0, 16.6, and 0%, respectively. Statistically significant differences (p<0.01) existed between the “extended” and unresected groups.     

Tumor Location Based Segmentation in Upper-Tract Urothelial Carcinoma Impacts on the Urothelial Recurrence-Free Survival: A Multi-Institutional Database Study

Introduction and ObjectivesThe predictive impact of primary tumor location for patients with upper-tract urothelial carcinoma (UTUC) in the presence of concomitant urothelial bladder cancer, along with urothelial recurrence after the curative treatment is still contentious. We evaluated the association between precise tumor location and concomitant presence of urothelial bladder cancer and urothelial recurrence-free survival in patients with UTUC treated by radical nephroureterectomy with a bladder cuff.MethodsA total of 1,349 patients with localized UTUC (Ta-4N0M0) from a retrospective multi-institutional cohort were studied. We queried four UTUC databases. This retrospective clinical series was of patients with localized UTUC managed by nephroureter-ectomy with a bladder cuff, for whom data were from the Nishinihon Uro-Oncology Collaborative Group registries. Patients with a history of chemotherapy or radiotherapy were excluded from the study. Associations between the location of the tumor and subsequent outcome following nephroureterectomy were assessed using COX multivariate analysis. The location of the tumor was verified by pathological samples. Urothelial recurrence was defined as tumor relapse in any local urothelium, and coded apart from distant metastasis. The median follow-up was 34 months.ResultsA total of 887 patients had an evaluation of the tumor location in which 475 patients had pelvic tumors (53.6%), 96 had ureteral tumors in the U1 segment (10.8%), 87 in the U2 segment (9.8%), and 176 in the U3 segment (19.8%). There were 52 patients who had multifocal tumors (5.9%) as follows: 8 (0.9%) in the pelvis and ureter, 11 (1.2%) in U1 + U2, 1 (0.1%) in U1 + U3, 27 (3.0 %) in U2 + U3, and 6 (0.7%) in U1 + U2 + U3. In all, 145 (16.3%) had concomitant bladder tumors. Logistic regression analysis of gender, age, hydronephrosis, cytology, performance status, grade, lymphovascular invasion, pT, pN, and tumor focality showed that tumor location was associated with the presence of concomitant bladder cancer (p = 0.004, HR = 1.265). When the tumor location was stratified into 8 segments, including multifocal tumors, only the U3 segment remained as a predictor for the presence of concomitant bladder cancer (p = 0.002, HR = 2.872). Kaplan-Meier analysis for unifocal disease showed that lower ureter tumors (a combination of U2 and U3) had a worse prognosis for urothelial recurrence than pelvic tumors or upper ureteral tumors (U1) (p < 0.001 for lower ureteral tumors versus pelvic tumors, p = 0.322 for upper ureteral tumor versus pelvic tumor by log rank). Multivariate analysis showed that lower ureter remained as a prognostic factor for urothelial recurrence after adjusting for gender, age, hydronephrosis, urine cytology, lymphovascular invasion, pT, and pN (p < 0.001, HR = 1.469), and a similar tendency was found when the analysis was run for patients without concomitant bladder tumors (p = 0.003, HR = 1.446). Patients with lower ureteral tumors had a higher prevalence of deaths (HR = 2.227) compared to patients with upper ureter tumors.ConclusionsThis multi-institutional study showed that the primary tumor locations were independently associated with the presence of concomitant bladder tumors and subsequent urothelial recurrence.Key Words: Upper-tract urothelial carcinoma, Prognosis, Tumor location     

Ectopic Relapse of Anti-neutrophil Cytoplasmic Antibody-associated Pituitary Vasculitis with No Elevation of Anti-neutrophil Cytoplasmic Antibodies after Renal Remission

The relationship between anti-neutrophil cytoplasmic antibody (ANCA) titer levels and relapse risk in patients with ANCA-associated vasculitis (AAV) following clinical remission remains controversial. We herein report a case showing ectopic relapse of AAV in the pituitary with no ANCA elevation after renal remission. Magnetic resonance imaging revealed an enlarged pituitary gland. A pituitary biopsy showed geographic necrosis with multinucleated giant cells. We diagnosed this case as relapse of AAV in the pituitary. One month after rituximab therapy, the pituitary gland volume had decreased. The intensification of therapy due to the possibility of vasculitis relapse may facilitate better control of AAV.     

A new position for photoplethysmography assessment of lower leg venous function—Technical notes

A new position for photoplethysmographic (PPG) assessment of lower leg venous function is described and tested. This study aids in the selection of patients for more limited stripping operation. PPG measurements were carried out in the usual sitting position and in the supine body position on limbs with primary varicose veins. Competence of the greater saphenous vein (GSV) and incompetent perforators were evaluated by venography. Limbs with a competent GSV in the lower leg had a longer 50% venous refill time (VRT/2) in the supine body position than in the sitting position (7.6±0.6 seconds vs. 5.0±0.4 seconds,p<0.01). Limbs without incompetent perforators had a longer VRT/2 in the supine body position than in the sitting position (8.0±1.1 seconds vs. 5.1±0.3 seconds,p<0.05). PPG measurement in the supine body position gave a better separation of VRT/2s on GSV competence in the lower leg and incompetent perforators. The supine body position is recommended for assessing lower leg venous function.     

Preoperative cholangiography of the caudate lobe: Surgical anatomy and staging for biliary carcinoma

The biliary branches of the caudate lobe (B1) join the right hepatic duct, the left hepatic duct, the confluence of these ducts, and/or the right posterior segmental bile duct. Therefore, in the preoperative staging of biliary tract carcinoma it is important to delineate the anatomy of B1 and the extent of cancer spread into B1. Tube cholangiography through percutaneous transhepatic biliary drainage or selective cholangiography by percutaneous transhepatic cholangioscopy enables us to obtain fine images of B1. We have developed cholangiography in the cephalad anterior oblique position to visualize B1 more clearly and distinctly. Four separate types of biliary branches are identified in the caudate lobe: (1) A duct running from the cranial portion of the right caudate lobe along the inferior vena cava to the hepatic hilus (B1r); (2) a duct from the cranial portion of the left caudate lobe to the hepatic hilus (B1ls); (3) a duct from the left lateral part of the left caudate lobe to the hepatic hilus (B1li); and (4) a duct from the caudate process to the hepatic hilus (B1c). The findings of the root of B1 in resected patients with biliary tract carcinoma were classified into four groups: not stenotic, short segmental stenosis, long segmental stenosis, and poorly imaged. A study of 64 branches of B1 in 42 resected patients with biliary tract cancer revealed carcinoma invasion in or near the root of B1 in all patients with poorly imaged or long segmental stenosis of B1, and in 33% of those with short segmental stenosis of B1.     

Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice

Most mammals have two major olfactory subsystems: the main olfactory system (MOS) and vomeronasal system (VNS). It is now widely accepted that the range of pheromones that control social behaviors are processed by both the VNS and the MOS. However, the functional contributions of each subsystem in social behavior remain unclear. To genetically dissociate the MOS and VNS functions, we established two conditional knockout mouse lines that led to either loss-of-function in the entire MOS or in the dorsal MOS. Mice with whole-MOS loss-of-function displayed severe defects in active sniffing and poor survival through the neonatal period. In contrast, when loss-of-function was confined to the dorsal MOB, sniffing behavior, pheromone recognition, and VNS activity were maintained. However, defects in a wide spectrum of social behaviors were observed: attraction to female urine and the accompanying ultrasonic vocalizations, chemoinvestigatory preference, aggression, maternal behaviors, and risk-assessment behaviors in response to an alarm pheromone. Functional dissociation of pheromone detection and pheromonal induction of behaviors showed the anterior olfactory nucleus (AON)-regulated social behaviors downstream from the MOS. Lesion analysis and neural activation mapping showed pheromonal activation in multiple amygdaloid and hypothalamic nuclei, important regions for the expression of social behavior, was dependent on MOS and AON functions. Identification of the MOS-AON–mediated pheromone pathway may provide insights into pheromone signaling in animals that do not possess a functional VNS, including humans.Most mammals have two major olfactory subsystems―the main olfactory system (MOS) and vomeronasal system (VNS). The MOS comprises the main olfactory epithelium (MOE), in which olfactory sensory neurons detect odorants, and their projection target, the main olfactory bulb (MOB) (Fig. S1A). Although the MOS is thought to detect volatile odorants and the VNS is thought to be important for the detection of nonvolatile pheromones, evidence shows that the MOS is also involved in pheromone detection (1–8). Surgical blocking of odorant access to the MOE, but not surgical ablation of the vomeronasal epithelium (VNE), eliminates preference to odors from the opposite sex in ferrets (9, 10). In mice, chemical ablation of the MOE impairs male and female sexual behaviors (11, 12). In these experiments in which the MOE was ablated, the function of the VNS is not directly disrupted, because the VNS is activated by direct application of urine to the nostril. Thus, these results indicate that the MOS also contributes to pheromone processing and related behaviors.Nonconditional disruption of genes encoding signal transduction proteins that are required for activation of olfactory neurons, such as cyclic nucleotide-gated channel (Cnga2) or adenylyl cyclase 3, impairs several social behaviors (11, 13–15). However, complete loss of MOS function causes anosmia and severely impairs sniffing and chemoinvestigatory behaviors (11, 13, 14, 16). Chemoinvestigation and the accompanying physical contact of the nose and pheromone source are essential for VNS activation; therefore, the loss of MOS function indirectly impairs the VNS, because the VNS becomes behaviorally isolated from pheromone cues in mice (16–19).Therefore, it is useful to establish a novel animal model, in which functions of the MOS in controlling social behavior are genetically dissociated from those of the VNS to answer several fundamental questions, such as which social behaviors are regulated by the MOS or what is the difference between the MOS and VNS in regulating social behaviors? A further question is whether the MOS has its own pheromone pathway in the brain, separate from the VNS. These questions are also important for understanding pheromone-induced social behaviors in animals that do not possess a functional VNS, such as humans.In this study, we established two Cnga2 conditional knockout mouse lines with regional differences in the extent of loss-of-function in the MOS: (i) MOS-specific conditional Cnga2 knockout mice, the ΔMOS(cng) line, which had severe defects in active sniffing and poor survival through the neonatal period; and (ii) Cnga2 conditional knockout mice with loss-of-function confined to the olfactory sensory neurons in the dorsal zone, the ΔD(cng) line. The ΔD(cng) mice and the previously generated ΔD(dta) mice, in which the dorsal part of the MOB is deleted by targeted expression of the diphtheria toxin fragment-A (dta) gene (20) (Fig. 1A and Fig. S1B), maintained the ability to smell and chemoinvestigate their conspecifics. These mice therefore showed preserved pheromonal activity in the VNS, but had defects in sexual, maternal, aggressive, and risk-assessment behaviors. This functional dissection of the MOS and VNS enabled us to demonstrate social behaviors that are regulated by the MOS in a VNS-independent manner and to further characterize functional roles for the MOS-mediated pheromone pathway.Open in a separate windowFig. 1.Preserved detection of odors and pheromones in ΔD mice. (A) Strategy for generating ΔMOS(cng) mice, ΔD(dta) mice, and ΔD(cng) mice. (B) Schematic diagram for generating Cnga2 conditional knockout mice. Following Cre recombination, exon 6 is deleted resulting in a frameshift of exon 7, which contains the channel pore and cAMP binding domains. (C) Verification of homologous recombination by Southern blot analysis. The 9.1-kb band is from the wild-type allele, and the 2.7-kb band is from the targeted allele. (D) Most of the ΔMOS(cng) mice die before weaning (3–4 wk old), whereas ΔD(dta) or ΔD(cng) mice do not. The number of surviving mice at the time of weaning was divided by the expected birth number to calculate survival rate. (E) ΔD(dta), ΔD(cng), and control mice spend similar amounts of time sniffing eugenol (n = 6 for each genotype). (F) Urine habituation-dishabituation test. Graphs present total amount of time (in seconds, s) that male control (n = 8), ΔD(dta) (n = 7), and ΔD(cng) (n = 8) mice spend sniffing a piece of filter paper spotted with water or urine from male or female mice. A decrease or increase in sniffing time indicates that the mice perceive the presented odor to be same as, or different from, the previously presented odor, respectively. O-MACS^cre/+ mice were used as controls. NSE, neuron-specific enolase, pan-neuronal promoter; dta, diphtheria toxin A. Data are presented as mean + SEM or mean ± SEM; *P < 0.05; **P < 0.01; ***P < 0.001; ns, P > 0.05 (Student’s t test).     

Utility of the novel bladder preservation therapy, BOAI-CDDP-radiation (OMC-regimen), for elderly patients with invasive bladder cancer

In this study, we investigated the novel bladder preservation therapy, the balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, concomitantly with hemodialysis, along with concurrent irradiation [the 'Osaka Medical College (OMC)-regimen'] in patients >70 years of age with muscle-invasive bladder cancer. Eighty-three such patients were assigned to receive either the OMC-regimen (n=56) or cystectomy (n=27). The OMC-regimen patients who failed to achieve complete response (CR) underwent cystectomy, or secondary BOAI with gemcitabine (1600 mg). The OMC-regimen, which delivers an extremely high concentration of anti-cancer agent to the tumor site without systemic adverse effects, yielded CR in >90% (39/43) of patients with locally invasive tumors [70% (39/56) of all patients including those with T4 and N+ disease]. None of the CR patients showed recurrence after a mean follow-up of 162 (range, 35-683) weeks, and 2 patients died of unrelated causes. The 5- and 12-year overall survival rates were 92.7 and 69.5% (vs. 59.6 and 20.9% for cystectomy; P<0.0092), respectively, although the median age in the OMC-regimen group was significantly greater than that in the cystectomy group (median, 77; range, 70-98; vs. 74; 70-79; p<0.0001). No patients suffered grade III or more severe toxicities. The oldest patient, aged 98 years, successfully completed this therapy. The OMC-regimen is a useful bladder preservation strategy for elderly patients with locally invasive bladder cancer, not only for those for whom cystectomy has been indicated, but also for patients whose condition is not amenable to curative treatment and for whom palliation would otherwise seem the only option.     

Laparoscopic resection of an epidermoid cyst originating from an intrapancreatic accessory spleen: Report of a case

A 67-year-old man underwent an investigation of epigastric pain and weight loss. Preoperative imaging findings suggested the presence of a tumor, which developed as an epidermoid cyst and originated from an intrapancreatic accessory spleen; however, the possibility of malignancy could not be ruled out. We therefore performed a laparoscopic-assisted distal pancreatectomy with a splenectomy for both diagnostic and treatment purposes. Five laparoscopic ports were created. After the spleen and pancreatic tail were dissected from the retroperitoneum laparoscopically, they were pulled out through a 7-cm left subcostal incision and resected with an endoscopic linear stapler. The operative time was 227 min and the blood loss was 400 ml. The postoperative course was uneventful. The final pathological diagnosis was in agreement with the preoperative diagnosis. This case demonstrates that the minimally invasive approach of laparoscopic surgery can be used safely and successfully for difficult-to-diagnose pancreatic tumors. This is the first report describing a laparoscopic resection of an epidermoid cyst originating from an intrapancreatic accessory spleen.     

Surveillance of pathogens in outpatients with gastroenteritis and characterization of sapovirus strains between 2002 and 2007 in Kumamoto Prefecture,Japan

Infectious acute gastroenteritis is an important public health problem worldwide. A total of 639 stool specimens were tested for the presence of diarrhea pathogens. The specimens were from outpatients with acute gastroenteritis who consulted the pediatric clinic in Kumamoto Prefecture, Japan, from June 2002 to December 2007. Of these, 421 (65.9%) were positive for diarrhea pathogens. Among them were norovirus (NoV) in 260 (61.8%), sapovirus (SaV) in 81 (19.2%), rotavirus in 49 (11.6%), adenovirus in 19 (4.5%), enterovirus in 13 (3.1%), astrovirus in 9 (2.1%), kobuvirus in 1 (0.2%), and bacterial pathogens in 11 (2.6%). Mixed infection (co‐infection of viruses) was found in 22 (5.2%) of the 421 pathogen‐positive stool samples. NoV was the most prevalent pathogen throughout the study period; however, the SaV detection rate was unexpectedly high and was found to be the secondary pathogen from 2005 to 2007. Genetic analysis of SaV with 81 strains demonstrated that SaV strains belonging to genogroup IV emerged in 2007, and dynamic genogroup changes occurred in a restricted geographic area. This study showed that SaV infection is not as rare as thought previously. J. Med. Virol. 81:1117–1127, 2009. © 2009 Wiley‐Liss, Inc.