Abstract We have previously shown that a human soluble cell conditioned media (CCM) from hypoxia-induced, potentially multipotent cells, grown in a perfusion bioreactor system inhibits tumor cell growth in vitro and in two animal models. Here we present data that indicate that a low molecular weight sub-fraction from the CCM has an increased anti-oncogenic activity. This activity was demonstrated in orthotopic pancreatic models, nRAS melanoma assays and over 10 additional human cancer cell lines in vitro. In an orthotopic BxPC3 pancreatic cancer model, there was a statistically significant improvement in survival following weekly intravenous injections of 0.1ml of sub fractioned CCM, as well as a significant improvement with 0.5ml intraperitoneal injections post-resection, as measured by Kaplan Meier analysis (p<0.05) (figures below). Uveal and nRAS melanoma cancer cell growth was inhibited by greater than 90% in in-vitro proliferation assays. The mechanism of action of the CCM is the induction of apoptosis through the upregulation of Caspase 3 and 9, as demonstrated by immunostaining of Annexin V and immunoblot ayalysis. In a Miapaca nude mouse daily dose study, tumor mass and metastatic extent was substantially reduced in treated mouse versus the control. Further, in a BXPC3 nude mouse daily dose study, 60% (p<0.05) of treated mice were tumor free after four weeks of treatment, while only 10% were tumor free in the control group . Little or no apparent drug toxicity was observed. These results indicate that the CCM sub-fraction could be a useful raw material for a treatment for a large range of neoplastic diseases. Citation Format: Emmett Pinney, Mayra Montes-Camacho, Kayler Brintle, Christian Posch, Rhiana Menen, David Easter, Michael Bouvet, Robert Hoffman, Gail Naughton. Sub-fractions of conditioned medium, from hypoxia-induced cells with multipotent potential, exhibit a significant anti-oncogenic activity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2265. doi:10.1158/1538-7445.AM2014-2265

Abstract A human extracellular matrix (hECM) was extracted from deposits made by neonatal dermal fibroblasts that were seeded on dextran microspheres and cultivated in a stirred bioreactor. The resulting hECM is high in collagen content with reduced hydroxylation as well as proteins found primarily in fetal ECM. These include high concentrations of SPARC, fibulin-2, tenascin, decorin, lumican, and fibromodulin. This hECM was used to treat tumor lines that were introduced onto the CAM of the fertilized chicken egg or growing subcutaneously in the nude mouse. In the CAM model significant tumor inhibition by hECM was seen with the following tumor lines: B16 melanoma was reduced 67%, C6 glioma 58% and MDA-MB-435 breast cancer 78%. Histology indicated that where the cells are in contact with hECM the cells appeared apoptotic. In the nude mouse models similar inhibition by hECM was observed: B16 melanoma was reduced 61%, C6 glioma 60% and MDA-MB-435 breast cancer reduced 58%. Apoptotic pathway activation was confirmed with caspase 9 upregulation in a dose-dependent response to hECM. These data indicate that an ECM rich in fetal proteins is capable of retarding tumor growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 432. doi:10.1158/1538-7445.AM2011-432

BACKGROUND:Natural orifice translumenal endoscopic surgery (NOTES) has the potential to decrease the burden of an operation on a patient. Limitations of the endoscopic platform require innovative solutions to provide retraction and create an operation comparable with the gold standard, laparoscopic cholecystectomy.METHODS:Four patients underwent transvaginal cholecystectomy. All procedures were performed under laparoscopic vision to ensure safety. The endoscope and a long articulating RealHand instrument were placed via a 15-mm vaginal trocar. A magnetic retraction system was used to retract the gallbladder safely. Laparoscopic clips were used to ligate the cystic duct and artery. All four gallbladders were successfully removed. No complications occurred. The mean operating time was 102 min.RESULTS:All four procedures were completed without complications. The four patients all were discharged shortly after surgery and reported normal sexual activity without pain.CONCLUSIONS:Transvaginal cholecystectomy can be completed safely using current technology. Further studies are needed to determine the safety of the procedure and to determine whether it confers any benefits other than cosmesis.

Background During transgastric natural orifice transluminal endoscopic surgery (NOTES), there is an iatrogenic perforation of the gastric wall with leakage of gastric contents into the peritoneal cavity. The aim of this study is to determine the effect of proton-pump inhibitors (PPI) and alterations of gastric pH on infection during transgastric surgery.Methods Thirty 250-g male Sprague-Dawley rats were divided into a study group (SG, n = 15) and a control group (CG, n = 15). SG were given 5 mg/kg pantoprazole for 3 days before procedure and another dose 1 h before. CG received saline at similar time points. A mini-laparotomy with gastrotomy was performed. Aspiration of 2.0 cc gastric contents was removed from the stomach and injected into the peritoneal cavity of both groups. Gastric pH and peritoneal pH levels were obtained. Gastric aspirate was sent for culture. White blood cell counts (WBC) were obtained on postoperative days 1, 7, and 14, and C-reactive protein (CRP) levels were obtained on postoperative day 1. At day 14, a necropsy was performed and aerobic and anaerobic cultures of the peritoneal cavity were obtained.Results There were no deaths in either group. The average gastric pH in the SG was 5.13 versus 3.26 (p = 0.03) in the CG. The average peritoneal pH was similar in both groups. The WBC in the SG was 4.5 vs. 3.5 (1,000 cells/mm) in the CG. There was no elevation in CRP levels in either group. Bacterial cultures were positive in 3/15 (20%) rats in the CG and in 9/15 (60%) in the SG (p = 0.008). Intra-abdominal abscesses were found in 2/15 (13%) rats in the CG and in 5/15 (33%) in the SG (p = 0.08).Conclusions Pretreatment with a PPI resulted in a higher rate of peritoneal bacterial contamination and abscess formation. The acidic environment of the stomach appears to be protective against infection when intraperitoneal contamination occurs as a result of gastrotomy.

Risk of gastric spillage during transgastric surgery is a potential complication of NOTES procedures. The aim of this study was to determine risk outcomes from gastric spillage in a rat survival model by measuring local and systemic inflammatory markers, adhesive disease, and morbidity.We performed a minilaparotomy with needle aspiration of 2 ml of gastric contents mixed with 2 ml of sterile saline (study group, SG) or 4 ml of sterile saline (control group, CG) injected into the peritoneal cavity of 60 male rats. Inflammatory markers (TNFalpha, IL-6, and IL-10) were analyzed at 1, 3, 6, and 24 h postoperatively by obtaining plasma levels and peritoneal washings. At necropsy, the peritoneal cavity was examined grossly for adhesions.Adhesions were seen more frequently in the SG versus the CG (100% vs. 33.3%, p < 0.014). There was a significant difference in the peritoneal TNFalpha levels in the SG compared with the CG, which peaked 1 h after surgery (p < 0.02). Both peritoneal IL-6 and IL-10 levels were higher in the SG versus the CG, which peaked 3 h after surgery (p < 0.005 and p < 0.001, respectively). All peritoneal inflammatory markers returned to undetectable levels at 24 h for both groups. Plasma cytokines were undetectable at all time intervals.The inflammatory response was found to be a localized and not systemic event, with plasma cytokine levels remaining normal while peritoneal washings revealed a brisk, short-lived localized inflammatory response. There was a significantly higher rate of adhesive disease in the SG compared with the CG; this, however did not translate into a difference in apparent clinical outcome. We conclude that gastric leakage in this NOTES rodent model induces a localized inflammatory response, followed by mild to moderate adhesive disease. This may be important in human NOTES.

BACKGROUND:Transvaginal cholecystectomy has been performed at several institutions using hybrid natural orifice translumenal endoscopic surgery (NOTES) techniques.METHODS:A 42-year-old woman with symptomatic cholelithiasis was taken to the operating room for transvaginal cholecystectomy after giving informed consent. A single 5-mm laparoscope was placed at the umbilicus, followed by a 15-mm trocar through the vaginal conduit. The endoscope and a long flexible RealHand surgical instrument (Novare, Cupertino, CA) were placed via the vaginal trocar. The cystic duct and artery were identified and clipped using laparoscopic clips from the umbilical port. The long articulating laparoscopic instrument provided stable retraction. Hook cautery was used to dissect the gallbladder, which was removed via the vaginal trocar. The vaginal incision was closed using a single figure-of-eight absorbable suture under direct vision. The procedure lasted 96 min.RESULTS:The cholecystectomy was successfully performed without spillage of bile. The patient was kept overnight for observation only as a precaution. She reported no pain and did not require a discharge prescription for narcotics.CONCLUSIONS:The described technique for NOTES cholecystectomy results in a virtually scarless operation. The single 5-mm umbilical trocar allows for safe clipping of the cystic duct. Further work is needed to determine the efficacy of this approach.

BACKGROUND:Natural orifice translumenal endoscopic surgery (NOTES) has moved quickly from preclinical investigation to clinical implementation. However, several major technical problems limit clinical NOTES including safe access, retraction and dissection of the gallbladder, and clipping of key structures. This study aimed to identify challenges and develop solutions for NOTES during the initial clinical experience.METHODS:Under an Institutional Review Board (IRB)-approved protocol, patients consented to a natural orifice operation for removal of either the gallbladder or the appendix via either the vagina or the stomach using a single umbilical trocar for safety and assistance.RESULTS:Nine transvaginal cholecystectomies, one transgastric appendectomy, and one transvaginal appendectomy have been completed to date. All but one patient were discharged on postoperative day 1 as per protocol. No complications occurred.CONCLUSION:The limited initial evidence from this study demonstrates that NOTES is feasible and safe. The addition of an umbilical trocar is a bridge allowing safe performance of NOTES procedures until better instruments become available. The addition of a flexible long grasper through the vagina and a flexible operating platform through the stomach has enabled the performance of NOTES in a safe and easily reproducible manner. The use of a uterine manipulator has facilitated visualization of the cul de sac in women with a uterus to allow for safe transvaginal access.

Background and Aim: Ovine theileriosis caused by Theileria ovis and Theileria lestoquardi is an important infectious disease affecting small ruminants in regions of the tropic and subtropic zones. There is limited studies about ovine theileriosis in Egypt; so the present study aims to assess the occurrence of ovine theileriosis in Egypt at the molecular level. Materials and Methods: Blood samples were collected from 115 randomly selected sheep, which were apparently healthy; the ages of the sampled sheep ranged from 1 to 5 years old, from a local breed (barkae and balade), and showed no symptoms indicating infection with Theileria spp. The study was conducted in three governorates representing Lower Egypt (Menoufia and Beheira) and Upper Egypt (El-Wady El-Geded). All blood samples were subjected to polymerase chain reaction (PCR) and semi-nested PCR to target Theileria spp. 18S rRNA genes. Positive samples were sequenced, and these sequences were analyzed using nucleotide basic local alignment search tool (BLAST). Results: Six animals (5.22%) were PCR-positive carriers for ovine theileriosis. Nucleotide BLAST and phylogenetic analyses of the six obtained sequences showed that T. ovis was present in five animals (4.37%) in Menoufia (n=2) and El-Wady El-Geded (n=3), whereas T. lestoquardi was detected in 1 animal (0.87%) in El-Wady El-Geded. Conclusion: This study is the first to provide molecular evidence, genetic characterization, and phylogenetic analysis of ovine Theileria spp. in Egypt. Specifically, T. lestoquardi and T. ovis carrier statuses of sheep were confirmed. These results highlight the importance of developing an effective control strategy against ovine theileriosis carriers that might develop and/or spread theileriosis.

Background: Obesity is reaching epidemic proportions in the United States and worldwide. Roux-en-y gastric bypass is most common bariatric surgical procedure performed. We propose a minimally invasive technique which is easily duplicated to gain access to the gastric remnant and the biliary tree. Method: Report of two cases with suspicion of choledocholithiasis and history of roux-en-Y bypass. Under direct visualization and with two stay sutures at 3 and 9 o-clock a bladed 15 mm trocar inserted into the remnant. New sterile drape placed to include only the 15 mm trocar. Through the 15 mm trocar an ERCP scope easily passed and ampulla identified and cannulated. Successful stone retrieval and papillotomy performed. We then were able to close the gastrotomy with linear endo-GIA stapler. Case two required small incision and bringing the stomach through the fascia, gastrotomy performed with two layers of pursestrings and 15 mm trocar inserted. Gastrotomy was the closed in a two layer hand sewn fashion. Conclusion: The population of gastric bypass patients is increasing. This technique is easily duplicated and performed in private community hospitals where experienced laparoscopists and endoscopists are available.

Laparoscopic appendectomy was the second major laparoscopic operation adopted by many general surgeons. One obvious advantage was the exceptional ability to visualize the remainder of the abdomen, and thereby exclude other causes of right lower quadrant pain in patients with equivocal findings. Thus, laparoscopic appendectomy found early application to women of reproductive age with right lower quadrant pain. Although some advocate leaving the normal appendix in situ when another cause for the pain was found, most surgeons remove it, reasoning that occult pathology is often found and that the patient benefi ts more from removal. It has thus been diffi cult to demonstrate that laparoscopic appendectomy has reduced the negative appendectomy rate. As laparoscopic appendectomy found wider use, computed tomography (CT) scan improved in resolution and it became possible to use an appendiceal protocol scan to confi rm or rule out acute appendicitis. The question then arises, should a patient with equivocal symptoms have a CT scan or be taken straight to laparoscopic exploration and appendectomy. That is the issue discussed here.

INTRODUCTIONNatural orifice translumenal endoscopic surgery (NOTES) has gained much interest by minimal invasive surgeons and gastroenterologists. Performing abdominal operations without any abdominal wall incisions may offer all the advantages of minimally invasive surgery (MIS) and eliminate the complications associated with these wounds. The NOTES technique is rapidly being developed, but one of the major issues involved in the procedure that has to be addressed prior to implementation is in obtaining adequate spatial orientation.OBJECTIVEThe aim of this study was to combine the standard laparoscopic vision together with the endoscopic surgery procedure in order to acquire an independent satisfactory vision source.MATERIALS AND METHODSThe hybrid technique was performed in 6 porcine animal models. Among the procedures performed were tubal ligation, liver biopsies, oophorectomy, and cholecystectomy. All procedures were performed under general anesthesia, and all animals were euthanized at the termination of the procedure.RESULTSThe laparoscopic vision offers substantial advantages over the endoscopic vision. Spatial orientation is achieved in the same manner and quality as in MIS, and furthermore, the laparoscopic vision increases the safety of the NOTES procedure.CONCLUSIONSThe hybrid technique offers a superior vision source independent to the working endoscope. It may be an interim technique for developing NOTES until a novel imaging device will be available, or serve as the final solution for acquiring an adequate vision for this approach.

Traumatic rupture of the diaphragm is no longer uncommon. Because of the increasing frequency of motor vehicle accidents, the rate of blunt trauma to the chest and abdomen, which are the most common causes of diaphragmatic rupture, is increased as well. However, the diagnosis is frequently missed or delayed because of the lack of sensitivity and specificity of imaging modalities. Diagnostic laparoscopy is considered a standard tool for penetrating injuries to the left diaphragm and is widely practiced in selected cases. Right diaphragmatic tears, however, are more difficult to diagnose because of the sealing effect of the liver. Blunt abdominal trauma can cause large right diaphragmatic tears, causing liver incarcerations and respiratory compromise, therefore demanding the need for a comparable diagnostic tool. A high index of suspicion, together with knowledge of the mechanism of trauma, is the key factor for the correct diagnosis. Once the diagnosis has been considered, diagnostic laparoscopy and/or diagnostic thoracoscopy should be performed to confirm or rule out this injury. Factors suggestive of a right diaphragmatic tear include newly or progressive elevation of the right diaphragm and respiratory distress without underlining lung injury. The timing of the procedure should be in accordance with the hemodynamic and respiratory status of the patient. This procedure should be performed semielectively if there are no other indications for surgical intervention.

Quercetin, a bioflavonoid abundant in grapefruit, onion, berries, etc., has vast therapeutic potential, especially against Type 2 diabetes and its complications. Quercetin showed similar effects as that of metformin, (widely prescribed antidiabetic drug) in cell lines models (Sajan et al., 2010; Dhanya et al., 2017). In vivo findings also showcase it as a promising agent against diabetes and its pathophysiological complications.Quercetin can be produced on a large scale through a novel fermentation-based glycosylation strategy from cheap substrates and can be utilized as a dietary supplement. The review focuses on the mounting evidence pointing to Quercetin as a promising candidate for managing type 2 diabetes and its oxidative stress mediated pathophysiological complications.Quercetin acts on multiple targets of diabetes and regulates key signalling pathways which improve the symptoms as well as the complications of Type 2 diabetes. However further studies are needed to improve the bioavailability and to establish a dosing regimen for Quercetin.

Core competencies in surgical education and clinical care rely on effective patient-physician communication. We aim to develop quantitative and empirical tools for understanding critical communication tasks during patient interviews. Residents in surgical training and attending physicians were separately video recorded during stressful, first visit oncology patient interview sessions. Taped sessions (n = 16) were analyzed in detail to identify and label patient-initiated actions (PIAs), or “empathic opportunities,” that call for recognition or action from the caregiver. Doctor-responsive actions (DRAs) were labeled as matching to, or missing from, each empathic opportunity. Missed empathic opportunities occurred when a PIA did not have an associated DRA. Presession and postsession surveys queried the patient's perception of how well their health-care needs were met. Resident trainees and attending physicians missed 70% of 160 clearly identified empathic opportunities. There was no clear association with the level of physician training. This pilot study did not have enough power to discern differences in patient satisfaction. Physicians are often not very attentive to empathic opportunities offered by patients. Individual feedback and training regarding empathic opportunities in recorded patient communication encounters may improve resident and physician core competencies. These improvements may affect patient satisfaction related to these encounters.

CONTEXT:Serous cystadenoma of the pancreas and mucinous tumors of the vermiform appendix are rare. To our knowledge, the simultaneous occurrence of these two tumors has not been reported.CASE REPORT:Here, we report an adult female who presented with signs and symptoms of appendicitis. A preoperative CT scan confirmed the findings of appendicitis and also showed an incidental large mass in the head of the pancreas. The patient underwent uneventful appendectomy. Her pathology revealed an acutely inflamed appendix with a benign mucinous cystadenoma at the tip. Several months after her recovery, a Whipple procedure was performed. Pathologic examination showed a 5x5 cm serous cystadenoma of the head of the pancreas without evidence of malignancy. Two years later, the patient is alive and well without evidence of tumor recurrence.CONCLUSIONS:Cystadenomas of the pancreas and appendix are unusual and their simultaneous occurrence is a rare event.

Video-excerpts from routine oncology interviews are examined to reveal how patients demonstrate and doctors respond to "fears" about cancer. Vocally and visually, embodied impacts of dealing with dreaded consequences of cancer are apparent when addressing both good and potentially bad cancer news. Even a "brush" with cancer can promote negative and ongoing impacts provoking unresolved illness dilemmas. We reveal how, in the midst of extending answers and initiating concerns, patients exhibit trepidations when volunteering narrative information about their medical history and experience of symptoms. In response, doctors are shown to acknowledge yet exhibit minimal receptiveness to patients' lifeworld disclosures and demonstrations (e.g., redirecting attention away from patients' concerns by offering "textbook" symptoms and related pursuits of biomedical agendas). Discussion focuses on interactional criteria for identifying "fears", patients' lay orientations to medical visits, and implications for refining educational workshops for oncologists.