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Ketamine was discovered in 1964 by merging a ketone with an amine. Patients described feeling disconnected like they were floating in outer. Thus, it was characterized as a dissociative anesthetic. It is a unique drug that expresses hypnotic, analgesic, and amnesic effects. No other drug used in clinical practice produces these three important effects at the same time. Its newly found neuroprotective, anti-inflammatory, antitumor effects and low dose applications have helped to widen the clinical profile of ketamine. Ketamine as an analgesic adjunct in chronic pain patients is currently being researched. Combined use of ketamine and an opiate analgesic has been found to provide good perioperative pain control with reduction in symptoms such as nausea and vomiting, sedation, and respiratory insufficiency.

Worldwide, cancer is one of the leading causes of mortality and cancer rates are set to increase at alarming rate globally. There are various types of cancer in which the leading type is the lung cancer. In recent years lipid-based carriers, such as liposomes, have successfully encapsulated chemotherapeutic agents ameliorating some toxicity issues, while enhancing the overall therapeutic activity in cancer patients. In addition to this, nanomaterials can help to improved half-life in the body, morphology, for increased drug loading and many other ways. The survey discussed in this review will lead the anticancer therapy and cancer management which will provide the platform to the next generation. Therefore, this critical review includes the therapeutic interventions, liposomes target delivery, active and passive drug loading. Finally, we attempt to summarize the current challenges in nanotherapeutics and provide an outlook on the future of this important field. Keywords: Drug Delivery, Liposomes target Delivery, Nanostructures, Drug loading

Colorectal cancer is the third most commonly diagnosed cancer in the world characterized by neoplasia in the colon, rectum, or vermiform appendix. Current treatment approaches include chemotherapy, radiotherapy and surgery however non-specific bio-distribution of anti-cancer drug, lack of effective and safe drug delivery career, drug resistance and relapse are major limiting factors of current therapy. Gene therapy is a technique for correcting defective genes responsible for disease development. The future of gene therapy depends on achieving successful delivery of wild type gene to replace a faulty gene. Recently, there has been an increasing interest in delivery of drugs and gene via the gastrointestinal tract. Gene therapy via this route has many advantages, including non-invasive access and the versatility to treat local diseases, such as inflammatory bowel disease, colorectal cancer, as well as systemic diseases, such as haemophilia. However, the intestine presents several distinct barriers and, therefore, the design of robust non-viral delivery systems is key to future success. The review covers obstacles in the path of successful gene therapy using oral route to treat colorectal cancer as well as strategies to overcome. Keywords: Colorectal cancer, Oral gene delivery, Targeted delivery

Clinical inertia is a widespread reason for suboptimal control of patients with diabetes (DM). One approach to addressing clinical inertia is to include non-physician providers in DM management. Evidence suggests that intervention by pharmacists improves glycemic control more than usual care. There is little data, however, on the effect of pharmacist care delivered by phone as an adjunct to DM care provided by an Endocrinologist. We conducted a retrospective analysis to assess the effect of phone-based DM management by a Doctor of Pharmacy (PharmD) on glycemic control among patients seen by an Endocrinologist. Between 02/2018-12/2018, 65 adult DM patients were referred by their Endocrinologists to a PharmD for phone intervention at an urban academic medical center. The intervention included medication reconciliation, education on medication self-administration, coordination with pharmacies to dispense medications, and adjustment of DM medications. A total of 41 patients (INT) received 1+ intervention phone call (median [iQR] 3 [2-5] calls), and 24 patients (NoINT) were referred but could not be contacted (n=20) or required no intervention (n=4). At baseline, all INT patients and 96% of NoINT patients were on insulin, 41% and 21% were on a GLP-1RA, and 56% and 46% were on oral medication(s). In the INT group, mean A1C decreased significantly 1.9 ± 2.2% from 10.2 ± 2.4% before the first call to 8.3 ± 1.7% (p Phone-based DM management of Endocrinology patients by a PharmD may lead to better glycemic control than management by an Endocrinologist alone. These data should encourage the conduct of an RCT to test this promising strategy for addressing clinical inertia in DM patients. Disclosure D.J. Rubin: Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. J. Wu: None. D. Patel: None. U. Hajari: None. M. Barros: None.

Hereditary diffuse gastric cancer (HDGC) syndrome results from a germline CDH1 mutation, and microscopic foci of signet-ring carcinoma cells (SRCC) are present in nearly all gastrectomy specimens.1 The lifetime risk of invasive gastric cancer (GC) has been thought to be 70%,2 but recent data have suggested a lower risk of 37%.3 Prophylactic total gastrectomy is considered the standard of care, but many patients choose surveillance endoscopy instead. We sought to define the outcomes in CDH1-positive individuals who pursued endoscopic surveillance.

The current practice of cancer genetic counseling is undergoing widespread change and scrutiny. While there are clinical resources for genetic counselors (GCs) regarding the delivery of cancer genetic services, there is limited literature regarding effective management of a genetic counseling clinical program. We have developed administrative tools to manage a large team of GCs at a single academic medical center over a period of increasing demand for genetics services, with the initial aim of decreasing wait time for urgent genetic counseling visits. Here, we describe the three main elements of the clinical operations: Balancing patient volume between GCs, scheduling tracks for both routine and urgent appointments, and a team of triaging GCs to ensure appropriate patient referrals. For each of these elements, we describe how they have been modified over time and present data to support the utility of these strategies. The preliminary evidence offered here suggests that these tools allow for an equitable distribution of patient volume between team members, as well as the timely and accurate scheduling of urgent patients. As a result of the experiences presented here, other genetic counseling programs grappling with similar issues should be aware that it is possible to shift clinical operations to serve certain patient populations in a more timely fashion while keeping both providers and GC staff satisfied.

The management of hereditary diffuse-type gastric cancer revolves around surveillance biopsies and the timing of prophylactic gastrectomy. In the absence of a validated surveillance biopsy protocol, we modeled bioptic diagnostic yield on the basis of the topographic distribution of cancer foci in a series of 10 gastrectomies in CDH1-mutation carriers. Complete histologic examination was performed in all cases, and 1817 slides were evaluated for the presence of in situ, intramucosal, or submucosal diffuse-type carcinoma. Detailed maps determined the density of cancer foci. On the basis of the number of sampled glands per biopsy in routine surveillance preoperative endoscopy, we estimated the theoretical number of biopsies necessary for a 90% rate of detection of neoplastic foci, and we evaluated this number, taking into account the regional distribution of these foci. A total of 96 m of gastric mucosa with ≈ 1,193,453 gastric glands yielded 302 cancer foci [in situ (n=89), intramucosal (n=209), and submucosal (n=4)] spanning the width of a total of 1820 glands (8 to 1205 per case; average 182 ± 115). On the basis of the number of glands per stomach and the average number of glands sampled during surveillance biopsy (28.7 ± 1.7; range, 0 to 79; n=112), the theoretical number of biopsies necessary to capture at least 1 cancer focus was estimated to be 1768 (range, 50 to 5832) to assure a 90% detection rate. Mapping of cancer foci showed the highest density in the anterior proximal fundus (37%) and cardia/proximal fundus (27%). Our results argue for the incorporation of cancer focus distribution into any biopsy protocol, although detection is likely to remain extremely low, and they call into question the validity of endoscopic surveillance.

Deleterious mutations in BRCA1 and BRCA2 include those identified by sequencing technology as well as large genomic rearrangements (LGR). The main testing laboratory in the United States, Myriad Genetics Laboratory (MGL), has defined criteria for inclusion of LGR testing (i.e., BRACAnalysis Rearrangement Test, or BART™) when BRCA1 and BRCA2 testing is ordered. We were interested in determining how many of our patients with LGR mutations in BRCA1 and BRCA2 fulfilled these MGL criteria. A retrospective chart review was performed on all individuals who underwent genetic testing at our institution since August 2006. Individuals who underwent LGR testing were classified as either having or not having a LGR in BRCA1 or BRCA2. Each individual's history was classified as meeting MGL defined LGR criteria, meeting criteria using third-degree relatives, or not meeting criteria. A total of 257 BART tests were ordered at our institution from August 2006 to August 2009. Five individuals (1.9%) had an LGR mutation. Two LGR were identified in patients who met MGL defined LGR criteria. One LGR was identified in a patient that met MGL defined LGR criteria only when using third-degree relatives. Two LGR were identified in individuals who did not meet MGL defined criteria. LGR are present in individuals who do not have a high pretest probability of carrying a mutation in BRCA1 or BRCA2. These data suggest that when BRCA1 and BRCA2 genetic testing is performed, testing should always include LGR testing so that the results are the most comprehensive and reliable.

Background Germline mutation of the CDH1 gene, which encodes for the E-cadherin adhesion protein, is rare but confers an estimated lifetime risk of hereditary diffuse gastric cancer of 87%. Fewer than 100 prophylactic total gastrectomies have been reported for this condition. Methods Patients with germline CDH1 mutation who underwent multidisciplinary counseling followed by prophylactic total gastrectomy were reviewed. Results Ten patients (6 male, 4 female) with a median age of 42 years (range, 26–51) underwent prophylactic total gastrectomy between 2006 and 2009. Of the 6 families represented, there were 4 missense, 1 frameshift, and 1 splice site mutation. Median time from genetic testing to surgery was 3 months (range, 1–7). All patients had an upper endoscopy before surgery, identifying only 1 patient with a focus of diffuse gastric cancer. After prophylactic total gastrectomy, extensive pathologic analysis demonstrated that 9 patients had up to 77 foci of noninvasive cancer, and 2 of these patients had 4–12 foci of T1 invasive cancer. Median operative time was 213 minutes; there were no anastomotic leaks, and the length of stay was 7–8 days. One patient had a complication within 30 days (pulmonary embolism), and 3 patients had late complications (2 small bowel obstructions and 1 anastomotic stricture). Median weight loss at 6 months was 19%. Conclusion The majority of patients with germline CDH1 mutation have foci of noninvasive or invasive gastric cancer by middle age. Serial upper endoscopies provide inadequate screening. Prophylactic total gastrectomy is the procedure of choice for definitive treatment.

In the genetic counseling setting, the health care provider can be challenged by opposing duties to members of the same family: protecting the privacy of the patient identified with a gene mutation and the ethical obligation to warn at-risk relatives. In a situation of nondisclosure between members of a family with a known disease-predisposing mutation, this type of dilemma can present in acute form for the provider who cares for different members of the family. This can hinder effective medical decision making. To minimize this effect, we recommend detailed pretest genetic counseling steps to empower the patient to communicate with their at-risk relatives their intent to pursue testing and willingness to share information. In addition, post-test counseling should reiterate the implications of a positive result for at-risk relatives and conclude with a written summary that patients can share with their family.

A 38-year-old woman came to the Gastrointestinal Cancer Genetics Clinic of this hospital because of a family history of breast and gastric cancer. Her mother had died of gastric cancer, and her maternal aunt had bilateral breast cancer and died of gastric cancer. Screening upper gastrointestinal endoscopy had been negative in the patient. A diagnostic procedure was performed.

Families that have several relatives with melanoma, multiple primary melanomas in one individual, younger than average ages of melanoma onset, and/or the presence of both pancreatic cancer and melanoma may be suggestive of a hereditary melanoma syndrome and are candidates for genetic counseling and risk assessment. Genetic counseling for hereditary melanoma presents many complexities. Only a minority of hereditary melanoma cases have been attributed to a single genetic factor, CDKN2A. Both the frequency and the penetrance of CDKN2A mutations has been shown to be dependent on multiple factors. The clinical utility of genetic testing for hereditary melanoma families is debatable because CDKN2A status may not impact medical management in patients with melanoma. No standard medical management guidelines exist for families with CDKN2A mutations; however, family history of melanoma and pancreatic cancer may warrant further discussion. Clinicians should discuss the clinical and psychological implications before genetic testing. Genetic counseling and pretest education regarding melanoma risk factors provides an opportunity to increase knowledge and understanding of melanoma risk, while addressing psychological risks and concerns.

Although only 5–10% of all cases of cancer are attributable to a highly penetrant cancer predisposition gene, the identification of individuals at inherited risk for cancer has become an integral part of the practice of predictive and preventative medicine. Identifying those individuals with a significantly higher risk of developing specific cancers allows health-care providers to intervene with appropriate counseling and education, increased cancer surveillance, and sometimes even cancer prevention. This chapter focuses on the identification of patients at high risk for cancer and the importance of referral to genetic counselors and other genetics professionals. The chapter also discusses the intricacies surrounding genetic testing, including the ethical, legal, and social implications of identifying those at increased risk for cancer.

Personalized cancer risk assessment remains an essential imperative in postgenomic cancer medicine. In hereditary melanoma, germline CDKN2A mutations have been reproducibly identified in melanoma-prone kindreds worldwide. However, genetic risk counseling for hereditary melanoma remains clinically challenging. To address this challenge, we developed and validated MelaPRO, an algorithm that provides germline CDKN2A mutation probabilities and melanoma risk to individuals from melanoma-prone families. MelaPRO builds on comprehensive genetic information, and uses Mendelian modeling to provide fine resolution and high accuracy. In an independent validation of 195 individuals from 167 families, MelaPRO exhibited good discrimination with a concordance index (C) of 0.86 [95% confidence intervals (95% CI), 0.75–0.97] and good calibration, with no significant difference between observed and predicted carriers (26; 95% CI, 20–35, as compared with 22 observed). In cross-validation, MelaPRO outperformed the existing predictive model MELPREDICT (C, 0.82; 95% CI, 0.61–0.93), with a difference of 0.05 (95% CI, 0.007–0.17). MelaPRO is a clinically accessible tool that can effectively provide personalized risk counseling for all members of hereditary melanoma families. Cancer Res; 70(2); 552–9