Implementation of robotic pancreaticoduodenectomy at a community tertiary care hospital utilizing a comprehensive curriculum.

BACKGROUND: We evaluated the outcomes of a robotic pancreaticoduodenectomy (RPD) program implemented at a community tertiary care hospital. METHODS: A retrospective review of 65 RPD cases compared surgical outcomes and performance to benchmark data. RESULTS: Postoperative complications occurred in 31% (20) of patients vs. ≤73% (variance -42), with grade IV complications in 3% (2) vs. ≤5% (variance -2). Postoperative pancreatic fistula type B frequency was 12% (8) vs. ≤15% (variance -3). One 90-day mortality occurred (1.5% vs. 1.6%). Failure to rescue rate was 7% vs. ≤9% (variance -2), and R1 resection rate was 2% vs. ≤39% (variance -37). There was a downward trend of operative time (rho â€‹= â€‹-0.600, P â€‹< â€‹0.001), with a learning curve of 27 cases. Median hospital length of stay was 6 days vs. ≤15 days (variance -9). CONCLUSION: Our comprehensive RPD training program resulted in improved operative performance and outcomes commensurate with benchmark thresholds.

Alcohol intake can reduce gambling behavior.

Prolonged and risky gambling can have negative consequences financially and in health (e.g., developing an addiction). As gambling frequently occurs together with alcohol intake, we investigated whether we could reduce persistent and risky gambling under the influence of alcohol. Specifically, following alcohol myopia theory (Steele & Josephs, 1990), stating that intoxicated people's behavior is disproportionally guided by salient cues, we propose that making low chances of winning salient in a gambling situation should reduce persistent and risky gambling in alcohol intoxicated participants. In 3 laboratory studies, participants either consumed alcohol or a placebo. We made low chances of winning salient (vs. not) by explicitly displaying the low chances in large letters. Making low chances salient led intoxicated participants to gamble less persistently on a computerized slot machine (Study 1 and 2) and with less risk in a lottery game (Study 3) compared with sober participants and compared with sober and intoxicated participants in a control condition in which low chances were not salient. Moreover, using eye-tracking in Study 3, we found that the effect of alcohol on less risky gambling was mediated by intoxicated participants' greater attention to the salient low chances. Finally, we replicated the findings from our laboratory studies in the field: When low chances were made salient, the more alcohol bar patrons had consumed, the less persistently they gambled on a slot machine (Study 4). The findings have applied implications for reducing excessive gambling under the influence of alcohol by making low chances salient on games of chance. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Gr1-/low CD11b-/low MHCII+ myeloid cells boost T cell anti-tumor efficacy.

Conventional APCs that express MHC class II (MHCII) and co-stimulatory molecules include dendritic cells (DCs) and macrophages. Beyond these conventional APCs, immune stimulatory cells have been more recently shown to extend to a class of atypical APCs, composed of mast cells, basophils, and eosinophils. Here, we describe a unique type of APC, Gr1-/low CD11b-/low cells with a granularity and size characteristic of myeloid cells and with the ability to present Ag for crosspresentation. These cells constitutively express MHCII and the costimulatory molecules, CD80, CD86, and CD40. They do not express pan markers of myeloid DCs (CD11c), plasmacytoid DCs (Ly6C), or macrophages (F4/80), and their frequency is inversely correlated with myeloid-derived suppressor cells (MDSCs) in tumor-bearing mice. Among splenocytes, they are more abundant than DCs and macrophages, and they exhibit antitumor immune stimulatory function at a steady state without further activation, ex vivo. They are also found within the tumor bed where they retain their immune stimulatory function. Our findings suggest the use of these novel APCs in additional preclinical studies to further investigate their utility in APC-based cancer immunotherapies.

Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy.

Breast cancer patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu-overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy. We explored two strategies: 1) transient blockade of autophagy with chloroquine (CQ), which blocks fusion of autophagosomes and lysosomes during ADR treatment, and 2) permanent inhibition of autophagy by a stable knockdown of ATG5 (ATG5KD), which inhibits the formation of autophagosomes in MMC during and after ADR treatment. We found that while CQ prolonged tumor dormancy, but that stable knockdown of autophagy resulted in early escape from dormancy and recurrence. Interestingly, ATG5KD MMC contained an increased frequency of ADR-induced polyploid-like cells and rendered MMC resistant to immunotherapy. On the other hand, a transient blockade of autophagy did not affect the sensitivity of MMC to immunotherapy. Our observations suggest that while chemotherapy-induced autophagy may facilitate tumor relapse, cell-intrinsic autophagy delays tumor relapse, in part, by inhibiting the formation of polyploid-like tumor dormancy.

Medical students' communication skills in clinical education: Results from a cohort study.

OBJECTIVE: To assess students' communication skills during clinical medical education and at graduation. METHODS: We conducted an observational cohort study from 2007 to 2011 with 26 voluntary undergraduate medical students at Hamburg University based on video-taped consultations in year four and at graduation. 176 consultations were analyzed quantitatively with validated and non-validated context-independent communication observation instruments (interrater reliability ≥0.8). Based on observational protocols each consultation was also documented in free-text comments, salient topics were extracted afterwards. RESULTS: 26 students, seven males, were enrolled in the survey. On average, graduates scored higher in differential-diagnostic questioning and time management but showed deficiencies in taking systematic and complete symptom-oriented histories, in communication techniques, in structuring consultations and in gathering the patients' perspectives. Patient-centeredness and empathy were rather low at graduation. Individual deficiencies could barely be eliminated. CONCLUSION: Medical students were able to enhance their clinical reasoning skills and their time management. Still, various communication deficiencies in final year students became evident regarding appropriate history taking, communication skills, empathy and patient-centeredness. PRACTICE IMPLICATIONS: The necessity of developing a longitudinal communication curriculum with enhanced communication trainings and assessments became evident. A curriculum should ensure that students' communication competencies are firmly achieved at graduation.

Impaired immunological synapse in sperm associated antigen 6 (SPAG6) deficient mice.

Sperm associated antigen 6 (SPAG6), a component of the central apparatus of the "9 + 2" axoneme, plays a central role in ciliary and flagellar motility; but, its contribution to adaptive immunity and immune system development is completely unknown. While immune cells lack a cilium, the immunological synapse is a surrogate cilium as it utilizes the same machinery as ciliogenesis including the nucleation of microtubules at the centrosome. This prompted our hypothesis that SPAG6 critically regulates the formation and function of immunological synapses. Using bone marrow reconstitution studies of adult WT mice, we demonstrate that SPAG6 is expressed in primary and secondary lymphoid tissues, is associated with the centrosome in lymphocytes, and its deficiency results in synapse disruption due to loss of centrosome polarization and actin clearance at the synaptic cleft. Improper synapse formation in Spag6KO mice was associated with defective CTL functions and impaired humoral immunity as indicated by reduced germinal centers reactions, follicular CD4 T cells, and production of class-switched antibody, together with expansion of B1 B cells. This novel report demonstrates the requirement of SPAG6 for optimal synapse formation and function, its direct role in immune cell function, and provides a novel mechanism for infertility disorders related to SPAG6.

Tumor-reactive immune cells protect against metastatic tumor and induce immunoediting of indolent but not quiescent tumor cells.

Two major barriers to cancer immunotherapy include tumor-induced immune suppression mediated by myeloid-derived suppressor cells and poor immunogenicity of the tumor-expressing self-antigens. To overcome these barriers, we reprogrammed tumor-immune cell cross-talk by combined use of decitabine and adoptive immunotherapy, containing tumor-sensitized T cells and CD25(+) NKT cells. Decitabine functioned to induce the expression of highly immunogenic cancer testis antigens in the tumor, while also reducing the frequency of myeloid-derived suppressor cells and the presence of CD25(+) NKT cells rendered T cells, resistant to remaining myeloid-derived suppressor cells. This combinatorial therapy significantly prolonged survival of animals bearing metastatic tumor cells. Adoptive immunotherapy also induced tumor immunoediting, resulting in tumor escape and associated disease-related mortality. To identify a tumor target that is incapable of escape from the immune response, we used dormant tumor cells. We used Adriamycin chemotherapy or radiation therapy, which simultaneously induce tumor cell death and tumor dormancy. Resultant dormant cells became refractory to additional doses of Adriamycin or radiation therapy, but they remained sensitive to tumor-reactive immune cells. Importantly, we discovered that dormant tumor cells contained indolent cells that expressed low levels of Ki67 and quiescent cells that were Ki67 negative. Whereas the former were prone to tumor immunoediting and escape, the latter did not demonstrate immunoediting. Our results suggest that immunotherapy could be highly effective against quiescent dormant tumor cells. The challenge is to develop combinatorial therapies that could establish a quiescent type of tumor dormancy, which would be the best target for immunotherapy.

Peripheral blood mononuclear cells of patients with breast cancer can be reprogrammed to enhance anti-HER-2/neu reactivity and overcome myeloid-derived suppressor cells.

Two major barriers in the immunotherapy of breast cancer include tumor-induced immune suppression and the establishment of long-lasting immune responses against the tumor. Recently, we demonstrated in an animal model of breast carcinoma that expanding and reprogramming tumor-sensitized lymphocytes, ex vivo, yielded T memory (Tm) cells as well as activated CD25+ NKT cells and NK cells. The presence of activated CD25+ NKT and NK cells rendered reprogrammed T cells resistant to MDSC-mediated suppression, and adoptive cellular therapy (ACT) of reprogrammed lymphocytes protected the host from tumor development and relapse. Here, we performed a pilot study to determine the clinical applicability of our protocol using peripheral blood mononuclear cells (PBMCs) of breast cancer patients, ex vivo. We show that bryostatin 1 and ionomycin combined with IL-2, IL-7, and IL-15 can expand and reprogram tumor-sensitized PBMCs. Reprogrammed lymphocytes contained activated CD25+ NKT and NK cells as well as Tm cells and displayed enhanced reactivity against HER-2/neu in the presence of MDSCs. The presence of activated NKT cells was highly correlated with the rescue of anti-HER-2/neu immune responses from MDSC suppression. Ex vivo blockade experiments suggest that the NKG2D pathway may play an important role in overcoming MDSC suppression. Our results show the feasibility of reprogramming tumor-sensitized immune cells, ex vivo, and provide rationale for ACT of breast cancer patients.

The Frey procedure for chronic pancreatitis secondary to pancreas divisum.

IMPORTANCE: Pancreas divisum is an uncommon congenital anomaly that may result in chronic pancreatitis (chronic pancreatitis secondary to pancreas divisum [CPPD]) and intractable pain. We evaluated the role of the Frey procedure in the management of patients with pain related to CPPD as compared with patients with chronic pancreatitis secondary to alcohol (CPA) or idiopathic causes (ICP). OBJECTIVE: To review our experience with the Frey procedure for the management of chronic pancreatitis related to pancreas divisum. DESIGN: This was a 2-year institutional retrospective of patients undergoing the Frey procedure for chronic pancreatitis related-pain from April 2008 to June 2010. SETTING: Academic tertiary care referral center. PARTICIPANTS: A consecutive sample of 14 patients undergoing the Frey procedure for chronic pancreatitis and disease-related intractable pain. We sought to examine the utility of the Frey procedure in patients with CPPD as compared with CPA and ICP. INTERVENTION: The Frey procedure. MAIN OUTCOMES AND MEASURES: Perioperative outcomes and postoperative narcotic requirement were compared among patient groups. RESULTS: Fourteen patients underwent the Frey procedure. The etiology of the disease was pancreas divisum in 6 patients, alcohol in 5, and idiopathic in 3. The most common indication for surgery was intractable pain, and all patients had undergone endoscopic retrograde cholangiopancreatography for attempted relief in the past. There were no statistically significant differences in median operative time (263 minutes), intraoperative blood loss (425 mL), median length of stay (9.5 days), or rate of morbidity (21%) between the 3 etiologies. Two-thirds of patients required less or no opioid at follow-up, although follow-up was significantly longer for CPPD and ICP than CPA (median, 249, 259, and 42 days, respectively; P < .02). CONCLUSIONS AND RELEVANCE: In this series, outcomes for patients with CPPD treated with the Frey procedure were equivalent to those treated for CPA. Patients with pancreas divisum and a dilated pancreatic duct may be ideally suited for this surgical strategy. The potential advantage of this approach over minor duct sphincteroplasty and lateral pancreaticojejunostomy is the removal of the fibrotic tissue of the head of the pancreas, thought to be the epicenter of pain in this condition. The benefits over resection alone include a more extensive ductal drainage procedure.

Distal splenorenal and temporary mesocaval shunting at the time of pancreatectomy for cancer: initial experience from the Medical College of Wisconsin.

BACKGROUND: Vascular resection/reconstruction at the time of pancreatectomy is performed when limited vascular involvement is the only barrier to complete resection. Splenic vein (SV) ligation facilitates resection/reconstruction of the superior mesenteric vein (SMV)-portal vein (PV) confluence and widely exposes the superior mesenteric artery and celiac origin. If the inferior mesenteric vein does not provide for retrograde decompression, SV ligation may result in sinistral portal hypertension; creation of a distal splenorenal shunt (DSRS) can prevent this complication. Additional complexity occurs in the setting of cavernous transformation of the PV. A mesocaval shunt (MCS) can be utilized to temporarily divert portal flow allowing for a safe portal dissection. Herein we report our initial experience utilizing DSRS and MCS at the time of pancreatectomy for cancer. METHODS: We reviewed all patients who underwent pancreatic resection for cancer and had either a DSRS and/or MCS performed between January 1, 2009 and February 1, 2012. RESULTS: Of 11 patients identified, 10 had adenocarcinoma, 9 underwent standard or extended pancreaticoduodenectomy, and 2 underwent total pancreatectomy. Median operative time was 9.5 hours, median blood loss was 1,000 mL and median duration of stay was 10 days. There were no mortalities. There was 1 Clavien grade III complication during the index admission and 3 others were readmitted. No patient required reoperation. CONCLUSION: We provide proof of concept that extended pancreatic resection in the setting of limited vascular involvement can be safely performed. This is the first report utilizing MCS and DSRS to facilitate resection of the SMV-PV confluence in the setting of cavernous transformation of the PV.