The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that posttranscriptionally regulate gene expression by targeting their corresponding messenger RNAs (mRNAs). Dysregulated miRNAs have been considered as a new type of ‘‘oncomiRs” or ‘‘tumor suppressors,” playing essential roles in cancer initiation and progression. Using genome-wide detection methods, ubiquitously aberrant expression profiles of miRNAs have been identified in a broad array of human cancers, showing great potential as novel diagnostic and prognostic biomarkers of cancer with high specificity and sensitivity. The detectable miRNAs in tissue, blood, and other body fluids with high stability provide an abundant source for miRNA-based biomarkers in human cancers. Despite the fact that an increasing number of potential miRNA biomarkers have been reported, the transition of miRNAs-based biomarkers from bench to bedside still necessitates addressing several challenges. In this review, we will summarize our current understanding of miRNAs as potential biomarkers in human cancers.

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MicroRNAs as potential biomarkers in cancer: opportunities and challenges.

Precision medicine and personalized medicine are based on the development of biomarkers, and liquid biopsy has been reported to be able to detect biomarkers that carry information on tumor development and progression. Compared with traditional 'solid biopsy', which cannot always be performed to determine tumor dynamics, liquid biopsy has notable advantages in that it is a noninvasive modality that can provide diagnostic and prognostic information prior to treatment, during treatment and during progression. In this review, we describe the source, characteristics, technology for detection and current situation of circulating tumor cells, circulating free DNA and exosomes used for diagnosis, recurrence monitoring, prognosis assessment and medication planning.

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Liquid Biopsy for Cancer: Circulating Tumor Cells, Circulating Free DNA or Exosomes?

Objectives Soft tissue infections are a common presenting complaint in the emergency department (ED). The authors sought to determine the utility of ED bedside ultrasonography (US) in detecting subcutaneous abscesses. Methods Between August 2003 and November 2004, a prospective, convenience sample of adult patients with a chief complaint suggestive of cellulitis and/or abscess was enrolled. US was performed by attending physicians or residents who had attended a 30-minute training session in soft tissue US. The treating physician recorded a yes/no assessment of whether he or she believed an abscess was present before and after the US examination. Incision and drainage (I + D) was the criterion standard when performed, while resolution on seven-day follow-up was the criterion standard when I + D was not performed. Results Sixty-four of 107 patients had I + D-proven abscess, 17 of 107 had negative I + D, and 26 of 107 improved with antibiotic therapy alone. The sensitivity of clinical examination for abscesses was 86% (95% confidence interval [CI] = 76% to 93%), and the specificity was 70% (95% CI = 55% to 82%). The positive predictive value was 81% (95% CI = 70% to 90%), and the negative predictive value was 77% (95% CI = 62% to 88%). The sensitivity of US for abscess was 98% (95% CI = 93% to 100%), and the specificity was 88% (95% CI = 76% to 96%). The positive predictive value was 93% (95% CI = 84% to 97%), and the negative predictive value was 97% (95% CI = 88% to 100%). Of 18 cases in which US disagreed with the clinical examination, US was correct in 17 (94% of cases with disagreement, chi(2) = 14.2, p = 0.0002). Conclusions ED bedside US improves accuracy in detection of superficial abscesses.

https://onlinelibrary.wiley.com/doi/pdf/10.1197/j.aem.2005.01.016

ABSCESS: applied bedside sonography for convenient evaluation of superficial soft tissue infections

Skin and soft tissue infections in injection drug users

AIM: To develop a panel of blood-based diagnostic biomarkers consisting of circulating microRNAs for the detection of pancreatic cancer at an early stage.

METHODS: Blood-based circulating microRNAs were profiled by high throughput screening using microarray analysis, comparing differential expression between early stage pancreatic cancer patients (n = 8) and healthy controls (n = 11). A panel of candidate microRNAs was generated based on the microarray signature profiling, including unsupervised clustering and statistical analysis of differential expression levels, and findings from the published literature. The selected candidate microRNAs were then confirmed using TaqMan real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) to further narrow down to a three-microRNA diagnostic panel. The three-microRNA diagnostic panel was validated with independent experimental procedures and instrumentation of RT-qPCR at an independent venue with a new cohort of cancer patients (n = 11), healthy controls (n = 11), and a group of high risk controls (n = 11). Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of the three-microRNA panel.

RESULTS: In the initial high throughput screening, 1220 known human microRNAs were screened for differential expression in pancreatic cancer patients versus controls. A subset of 42 microRNAs was then generated based on this data analysis and current published literature. Eight microRNAs were selected from the list of 42 targets for confirmation study, and three-microRNAs, miR-642b, miR-885-5p, and miR-22, were confirmed to show consistent expression between microarray and RT-qPCR. These three microRNAs were then validated and evaluated as a diagnostic panel with a new cohort of patients and controls and found to yield high sensitivity (91%) and specificity (91%) with an area under the curve of 0.97 (P < 0.001). Compared to the CA19-9 marker at 73%, the three-microRNA panel has higher sensitivity although CA19-9 has higher specificity of 100%.

CONCLUSION: The identified panel of three microRNA biomarkers can potentially be used as a diagnostic tool for early stage pancreatic cancer.

Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer

Laparoscopic distal pancreatectomy has steadily replaced open approach in recent years. However, because of long learning curve associated with the technique, it has not been widely adopted. The advent of the da Vinci Robotic System may help more open surgeons to join the minimally invasive pancreatic surgery. This paper describes the author’s technique along with tips and trick that he has developed and refined over the past 10 years. Outcome studies were also discussed.

Robotic Distal Pancreatectomy

Actinomyces is a normal commensal of the upper aerodigestive tract, colon and female reproductive tract. It can give rise to invasive disease in case of any breach in mucosal integrity, as well as, in patients with immunosuppression. Rarely, actinomycosis can involve the pancreas especially after episodes of pancreatitis or in post operative patients. We observed a case of actinomycosis affecting recurrent intraductal papillary mucinous neoplasm (IPMN) of pancreatic remnant, 5 years after a Whipple's procedure. Our patient, a 66 years old male with a history of Whipple's procedure for IPMN of pancreatic uncinate process, presented with repeated episodes of acute pancreatitis. Repeated radiological investigations (CT, MRI and EUS) revealed resolving pancreatitis with recurrent IPMN of the pancreatic tail. The patient underwent laparobotic assisted resection of the remnant pancreas and spleen 3 months later. Intraoperatively, in addition to the recurrent IPMN of pancreatic tail, we found a dense peripancreatic desmoplastic reaction with areas of thick yellow pus pockets in the remnant pancreatic body. Bacteriology and histopathology revealed it as a recurrent IPMN associated with actinomycosis of pancreas with chronic xanthogranulomatous changes. We conclude that actinomycosis of the pancreas is a rare entity with only 5 cases reported in English literature to the best of our knowledge. If diagnosed preoperatively, early institution of antibiotics can improve the surgical outcome. Fortunately, after diagnosis, we were able to start antibiotics in early postoperative period with successful outcome.

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Actinomycosis of the Pancreas: A Case Report and Review.

Our objective is to demonstrate the feasibility of robotic adrenalectomy by a traditional open surgeon using the da Vinci Robotic Surgical System and to analyze our outcomes. All patients who underwent robotic adrenalectomy by a single surgeon from July 2001 to April 2011 were included in the study. Vascular inflow control was obtained early on to facilitate dissection and handling of the adrenal gland. Forty adrenalectomies were performed during the study period in 39 patients (15 males; 25 left sided; 1 bilateral). Four patients underwent conversion to complete the procedure. The mean tumor size was 6.97 ± 2.4 cm. The mean operating room (OR) time was 117 ± 50.4 min. Comparing the OR time between da Vinci and da Vinci S robotic systems showed that the OR time was significantly less (169 ± 46 vs. 94.25 ± 32 min; P = 0.002) while blood loss, length of stay, size and weight were not different. The mean length of stay was 3 days. There were no mortalities in our study. Benign neoplasms formed a majority of the tumors removed. Robotic adrenalectomy is an option for surgeons without extensive training in advanced laparoscopic techniques provided they have adequate open experience.

Robotic adrenalectomy by an open surgeon: are outcomes different?

Background This pioneering study is aimed to design training models for robotic pancreaticojejunostomy (PJ) and to assess their usefulness using quality improvement exercise in the dry lab. Methods Three dry lab models were developed including the anastomosis model of a transected silicon pancreatic stent (model 1), a rough model (model 2) simulating PJ, and an advanced three-dimensional printed model (model 3) more vividly simulating PJ. Three surgeons (A, B, C) with same specialty and levels of expertise in surgery were enrolled in the training which was divided into three rounds of tasks. In the first round, all three surgeons (A, B, C) participated in the training on basic technical tasks before moved on to the next rounds. While surgeons A, B participated in the second round on model 1, only surgeon A worked on model 2 in the third round. Their proficiency of performance was evaluated on model 3. Results The results of the first and second rounds between surgeons are similar. Surgeon A practiced with model 2 for 6 h, completing 10 cases. In model 3, the times of attempts before achieving a consecutively three times of satisfactory anastomosis procedures were compared, for surgeon A, six cases, 20 for B and 25 for C. Conclusions The specifically designed series of dry lab training models may be a potential training tool for advancing the robotic PJ through quality improvement exercise in dry lab. Further larger and well-designed studies are warranted to validate this issue.

Anusak Yiengpruksawan

Papers

Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer

Robotic Distal Pancreatectomy

Actinomycosis of the Pancreas: A Case Report and Review.

Robotic adrenalectomy by an open surgeon: are outcomes different?

Three-dimensional printed dry lab training models to simulate robotic-assisted pancreaticojejunostomy