Preliminary study of the anatomy of the venous drainage of the intrahepatic and extrahepatic bile ducts and its relevance to the practice of hepatobiliary surgery

Background : Although there have been many studies of the arterial supply of the biliary system, attempts to study the corresponding venous drainage have been few and all have been incomplete. The purpose of the present investigation is to describe the anatomy of the venous drainage of both the intrahepatic and extrahepatic bile ducts and to determine its relevance to hepatobiliary surgery. Methods : The intrahepatic and extrahepatic venous drainage of the bile ducts was investigated in seven specimens by injecting a solution of 10% gelatin coloured with Alcian blue into the portal vein or the superior mesenteric vein to outline the venous drainage. The specimens were dissected under loop magnification and representative drawings were obtained. Results : The surface of the intrahepatic and extrahepatic bile ducts was covered by a fine venous plexus. On the surface of the supraduodenal common hepatic duct and common bile duct the venous plexus drained laterally into marginal veins, usually two in number and known as the 3 o’clock and 9 o’clock marginal veins. Inferiorly the marginal veins and the venous plexus communicated with the pancreaticoduodenal venous plexus, which in its turn drained into the posterosuperior pancreaticoduodenal vein, a branch of the superior mesenteric vein. Superiorly the marginal veins divided into a number of branches. Some branches followed the left and right hepatic ducts into the liver, communicating with the venous plexus and the adjacent branches of the portal vein. Other branches of variable size entered either segment IV or the caudate lobe or process via the hilar venous plexus. A most important finding was that even after dividing the bile duct and all communicating veins at the upper border of the duodenum, the venous plexus and the marginal veins filled normally to the level of transection. This occurred almost certainly by retrograde filling from above. Conclusion : The satisfactory results of end‐to‐end anastomosis in whole liver transplantation depends partly on the presence of adequate venous drainage. This has been amply demonstrated by the injection studies. This would indicate that the poor results of end‐to‐end repair of the bile duct after surgical trauma results from other factors such as poor technique, devascularization of the cut ends due to trauma, and carrying out the anastomosis under tension. After resection of the hilum for cholangiocarcinoma the venous drainage of the left and right hepatic ducts and their branches depends mainly on the communications between the venous plexus on the ducts and the adjacent branches of the portal vein, even at a lobular or sinusoidal level. The satisfactory results obtained after anastomosis of the left and right hepatic ducts or their branches to a Roux loop of jejunum attest to this. This applies also to the transplantation of segments II and III in paediatric patients from related adult donors and in patients receiving split liver transplants. Finally, the venous drainage at the bifurcation of the common hepatic duct has been shown to enter the caudate lobe and segment IV directly. This suggests that a hilar cholangiocarcinoma may metastasize to these segments, and perhaps partly explain the significantly better long‐term results when the caudate lobe and segment IV are resected en bloc with the cholangiocarcinoma as part of modern radical surgery for this condition.     

A phase II study of lapatinib,a dual EGFR and HER-2 tyrosine kinase inhibitor,in patients with castration-resistant prostate cancer

ObjectivesEpidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases may be involved in activation of androgen receptor and progression of prostate cancer. They represent potential therapeutic targets in prostate cancer. Lapatinib is an oral inhibitor of EGFR and HER-2. The objective of this study is to assess the preliminary clinical efficacy of lapatinib in the therapy of castration-resistant prostate cancer.MethodsIn this multicenter, open-label trial, patients with rising PSA on androgen deprivation therapy and not having received chemotherapy were eligible. They were treated with lapatinib at a dose of 1,500 mg once daily. The primary end point was a >50% confirmed PSA decline from baseline; safety, tolerability, and time to PSA progression were secondary outcomes.ResultsTwenty-nine patients enrolled in the study had a median age of 73 years and a baseline PSA of 21.6 ng/ml. Seven patients had no radiologic evidence of metastatic disease, while the remaining patients had bone or measurable disease or both. Treatment was well tolerated with only grade 3 treatment-related toxicities being diarrhea (14%) and rash (3%). One of 21 evaluable patients had >50% reduction in PSA, while another patient had 47% reduction in PSA with an ongoing duration of response of 45+ months. The median time to PSA progression was 29 days.ConclusionsLapatinib showed single agent activity in a small subset of unselected patients with castration-resistant prostate cancer, as measured by PSA. Future trials should explore a trial design with time-to-event end points and predictive biomarkers and a combination with other agents.     

Cylindroma of the breast of skin adnexal type: a study of 4 cases

Four cases of solitary cylindroma of the breast of skin adnexal type are described. The tumors were morphologically and immunophenotypically identical to their dermal counterparts. They arose in close proximity to the nipple, such as the retroareolar area of the breast and in intimate association with the lactiferous ducts, suggesting an origin from the latter structures. One case occurred in a woman with hereditary multiple cylindromatosis (Brooke-Spiegler syndrome). This is the second reported case of this hereditary syndrome with extracutaneous manifestations and the first case in which the breast is involved.     

A decision-analytic economic evaluation of valaciclovir prophylaxis for the prevention of cytomegalovirus infection and disease in renal transplantation

OBJECTIVE: This analysis evaluates the cost-effectiveness of valaciclovir prophylaxis using clinically and economically important health outcomes including graft failure, life-years, and quality-adjusted life-years (QALYs). METHODS: A Markov model was developed using a randomized, placebo-controlled trial of valaciclovir prophylaxis, together with a published epidemiological study and national renal transplant registry data. The model's population was stratified into two risk groups by donor/recipient cytomegalovirus (CMV) serostatus at transplantation: donor-positive/recipient-negative (D+R-) and recipient-positive (R+) patients. The model estimated costs and health outcomes over a 30-yr period from the perspective of Australian health care providers. RESULTS: The total health care cost was $3619 lower for D+R- patients receiving valaciclovir prophylaxis compared with those not receiving prophylaxis. D+R- patients receiving valaciclovir gained an extra 0.33 yr of life and 0.27 QALYs. R+ patients receiving valaciclovir prophylaxis gained an extra 0.07 yr of life and 0.05 QALYs, with an incremental cost of $914. This equates to $17 127 per QALY gained, which is highly cost-effective compared with other drugs and health interventions. CONCLUSIONS: Valaciclovir for the prophylaxis of CMV disease in renal transplant recipients is a cost-effective intervention, significantly reducing the burden of CMV disease to patients and health care providers.     

The EMPOWER Study: Randomized, Prospective, Double-Blind, Multicenter Trial of Vagal Blockade to Induce Weight Loss in Morbid Obesity

Background

Intermittent, reversible intraabdominal vagal blockade (VBLOC? Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia.

Methods

Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated (n?=?192) or control (n?=?102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12?months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM.

Results

Study subjects consisted of 90?% females, body mass index of 41?±?1?kg/m², and age of 46?±?1?years. Device-related complications occurred in 3?% of subjects. There was no mortality. 12-month percent EWL was 17?±?2?% for the treated and 16?±?2?% for the control group. Weight loss was related linearly to hours of device use; treated and controls with ??12?h/day use achieved 30?±?4 and 22?±?8?% EWL, respectively.

Conclusions

VBLOC? therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.     

Patient satisfaction and functional status after treatment of infection at the site of a total knee arthroplasty with use of the PROSTALAC articulating spacer

BACKGROUND: Two-stage exchange arthroplasty remains the standard treatment of infection at the site of a total knee arthroplasty. The clinical and functional outcomes associated with the use of an articulating antibiotic spacer for two-stage revision for infection are not well established. We conducted a retrospective study to evaluate the outcomes associated with the use of the PROSTALAC articulating spacer between the first and second stages. METHODS: Fifty-eight patients underwent two-stage revision total knee arthroplasty for infection between January 1997 and December 1999. Of these, fifty-four were alive at the time of follow-up and forty-seven were available for inclusion in the present retrospective study. In all patients, a prosthesis of antibiotic-loaded acrylic cement (the PROSTALAC system) was implanted during the first stage after débridement. The amount of osteolysis that occurred between the stages and the range of motion of the knee joint were measured. After two years of follow-up, outcomes were assessed with use of the WOMAC, Oxford-12, and SF-12 instruments as well as a satisfaction questionnaire. RESULTS: At a minimum of two years (average, forty-one months) after revision arthroplasty, two patients (4%) had had a recurrence of infection. The amount of bone loss was unchanged between stages, and the range of movement of the knee improved from 78.2 degrees before the first stage to 87.1 degrees at two years. The average normalized WOMAC function and pain scores were 68.9 and 77.1, respectively; the average Oxford-12 score was 67.3; the average SF-12 mental and physical scores were 53.7 and 41.2, respectively; and the average satisfaction score was 71.7. CONCLUSION: A revision operation for infection at the site of a total knee replacement with use of an articulating spacer was associated with reasonable function and satisfaction scores. These findings may be related to the articulating features of the PROSTALAC system, which permits full active movement of the knee in the early postoperative period.     

Characterization of biochemical recurrence after radical prostatectomy

BACKGROUND: This study sought to characterize the variables that predict postoperative prostate-specific antigen doubling time (PSADT) and biochemical recurrence time (RT) in patients who have failed radical prostatectomy (RP). METHODS: A total of 477 patients underwent RP at our institution for clinically localized prostate cancer. Of these patients, 64 (13.4%) demonstrated evidence of postoperative biochemical failure. PSADT and biochemical RT were calculated for all patients. PSADT and RT were correlated with clinical variables including preoperative PSA level, patient age, race, prostate weight and with pathologic characteristics of the operative specimen using uni- and multivariate analyses. In addition, PSADT and RT were also correlated with each other and with the time to postoperative adjuvant therapy. RESULTS: Median postoperative PSADT for patients who recurred after radical prostatectomy was 9.7 months. Postoperative PSADT was predicted by lymph node involvement (p < 0.001) and Gleason grade (p = 0.06). Rapid PSADT also correlated with institution of postoperative adjuvant therapy (p = 0.003). Median biochemical RT for all patients was 6.7 months. Gleason grade and pathologic stage were found to be predictors of RT (p < 0.002). Postoperative PSADT did not correlate with RT (r = 0.08; p = 0.53). PSADT and RT were not different between Caucasian- versus African-Americans. CONCLUSIONS: These results serve to better characterize our cohort of patients who have evidence of biochemical recurrence after radical prostatectomy. Aggressiveness of recurrent disease (i.e. PSADT) seems to be predicted by lymph node involvement and higher pathologic grade. Furthermore, the lack of correlation of RT and PSADT suggests that early recurrences are not necessarily aggressive tumors: conversely, aggressive recurrences may occur at any point in the postoperative period. This information may aid in the postoperative treatment of recurrent disease and help to better define those patients who are at higher risk for developing clinical recurrence and who would benefit from greater vigilance during the postoperative period.     

Effects of JAK3 inhibition with CP-690,550 on immune cell populations and their functions in nonhuman primate recipients of kidney allografts

BACKGROUND: Janus Kinase (JAK) 3 is a tyrosine kinase essential for proper signal transduction downstream of selected cytokine receptors and for robust T-cell and natural killer cells activation and function. JAK3 inhibition with CP-690,550 prevents acute allograft rejection. To provide further insight into the mechanisms of efficacy, we investigated the immunomodulatory effects of CP-690,550 in vitro and in vivo in nonhuman primates. METHODS: Pharmacodynamic assessments of lymphocyte activation, function, proliferation and phenotype were performed in three settings: in vitro in whole blood isolated from untransplanted cynomolgus monkeys (cynos), in vivo in blood from untransplanted cynos dosed with CP-690,550 for 8 days, and in vivo in blood from transplanted cynos immunosuppressed with CP-690,550. Cell surface activation markers expression, IL-2- enhanced IFN-gamma production, lymphocyte proliferation and immune cell phenotype analyzes were performed with multiparametric flow cytometry. RESULTS: In vitro exposure to CP-690,550 resulted in significant reduction of IL-2-enhanced IFN-gamma production by T-cells (maximum inhibition of 55-63%), T-cell surface expression of CD25 (50% inhibitory concentration (IC50); 0.18 microM) and CD71 (IC50; 1.6 microM), and T-cell proliferative capacities measured by proliferating cell nuclear antigen expression (IC50; 0.87 microM). Similar results were observed in animals dosed with CP-690,550. In addition, transplanted animals displayed significant reduction of NK cell (90% from baseline) and T-cell numbers whereas CD8 effector memory T-cell populations were unaffected. CONCLUSIONS: Potent in vitro and in vivo immunomodulatory effects of the JAK3 inhibitor CP-690,550 likely contribute to its efficacy in the prevention of organ allograft rejection.     

Incidence and Characteristics of Atypical Femoral Fractures: Clinical and Geometrical Data

Despite the multitude of studies published on atypical femoral fractures (AFFs), a profile for patients at risk does not exist. This study aimed first at estimating AFF incidence over a 19‐month‐period in Quebec City using the ASBMR Task force criteria to define AFF. The medical records of patients hospitalized for hip or femoral fracture between June 1, 2009, and December 31, 2010, were reviewed. Thirty‐six cases of atypical fractures were identified during the 19‐month period, representing an AFF incidence of 7.0 (range, 4.7 to 9.3) cases per 100,000 person‐years. In the second part of the study, data regarding the characteristics suspected of increasing the risks of AFF were collected from medical and pharmacological records, proximal femur radiographs, and patient interviews. The data regarding each patient with an AFF during years 2008‐2011 were compared to two controls with a hip or femoral fragility fracture or a traumatic fracture, paired for age and sex. Twenty patients with AFF were added to the 36 patients with AFF selected in the first part, thereby 56 patients with AFF were investigated. The association between the occurrence of AFF and bisphosphonates (BPs) use was proven statistically significant in multivariate analysis, odds ratio (OR) = 10.39 (95% CI, 2.22 to 48.58; p = 0.0029). Compared to controls, patients with AFF had excessive femoral offset (43.1 mm versus 38.3 mm, p = 0.0007), proximal femoral neck angle in varus (128.9 degrees versus 134.0 degrees, p < 0.0001), and had greater proximal cortical thickness. This retrospective study confirms the low incidence of AFF, confirms its significant association with exposure to BPs, and reveals the possible contribution of proximal femoral geometry in AFF occurrence. © 2016 American Society for Bone and Mineral Research.