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

Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer

Excess body weight, as defined by the body mass index (BMI), has been associated with several diseases and includes subjects who are overweight (BMI≥25–29.9 kg/m2) or obese (BMI≥30 kg/m2). Overweight and obesity constitute the fifth leading risk for overall mortality, accounting for at least 2.8 million adult deaths each year. In addition around 11% of colorectal cancer (CRC) cases have been attributed to overweight and obesity in Europe. Epidemiological data suggest that obesity is associated with a 30–70% increased risk of colon cancer in men, whereas the association is less consistent in women. Similar trends exist for colorectal adenoma, although the risk appears lower. Visceral fat, or abdominal obesity, seems to be of greater concern than subcutaneous fat obesity, and any 1 kg/m2 increase in BMI confers additional risk (HR 1.03). Obesity might be associated with worse cancer outcomes, such as recurrence of the primary cancer or mortality. Several factors, including reduced sensitivity to antiangiogenic-therapeutic regimens, might explain these differences. Except for wound infection, obesity has no significant impact on surgical procedures. The underlying mechanisms linking obesity to CRC are still a matter of debate, but metabolic syndrome, insulin resistance and modifications in levels of adipocytokines seem to be of great importance. Other biological factors such as the gut microbita or bile acids are emerging. Many questions still remain unanswered: should preventive strategies specifically target obese patients? Is the risk of cancer great enough to propose prophylactic bariatric surgery in certain patients with obesity?

https://gut.bmj.com/content/gutjnl/62/6/933.full.pdf

Obesity and colorectal cancer

BACKGROUND & AIMS
A cascade of precursor lesions (eg, atrophic gastritis, intestinal metaplasia, and dysplasia) precedes most gastric adenocarcinomas. Quantification of gastric cancer risk in patients with premalignant gastric lesions is unclear, however. Consequently, endoscopic surveillance is controversial, especially in Western populations.


METHODS
To analyze current surveillance practice and gastric cancer risk in patients with premalignant gastric lesions, all patients with a first diagnosis between 1991 and 2004 were identified in the Dutch nationwide histopathology registry (PALGA); follow-up data were evaluated until December 2005.


RESULTS
In total, 22,365 (24%) patients were diagnosed with atrophic gastritis, 61,707 (67%) with intestinal metaplasia, 7616 (8%) with mild-to-moderate dysplasia, and 562 (0.6%) with severe dysplasia. Patients with a diagnosis of atrophic gastritis, intestinal metaplasia, or mild-to-moderate dysplasia received re-evaluation in 26%, 28%, and 38% of cases, respectively, compared with 61% after a diagnosis of severe dysplasia (P < .001). The annual incidence of gastric cancer was 0.1% for patients with atrophic gastritis, 0.25% for intestinal metaplasia, 0.6% for mild-to-moderate dysplasia, and 6% for severe dysplasia within 5 years after diagnosis. Risk factors for gastric cancer development were increasing severity of premalignant gastric lesions at initial diagnosis (eg, severe dysplasia, hazard ratio 40.14, 95% confidence interval 32.2-50.1), increased age (eg, 75-84 years, hazard ratio 3.75, 95% confidence interval 2.8-5.1), and male gender (hazard ratio 1.50, 95% CI 1.3-1.7).


CONCLUSIONS
Patients with premalignant gastric lesions are at considerable risk of gastric cancer. As current surveillance of these patients is inconsistent with their cancer risk, development of guidelines is indicated.

Gastric cancer risk in patients with premalignant gastric lesions

This review summarizes studies on the epidemiology and public health implications of Helicobacter pylori published in peer-reviewed journals from April 2010 through March 2011. Prevalence rates vary widely between different geographical regions and ethnic groups. An interesting study from the USA identified the degree of African ancestry as an independent predictor of H. pylori infection. Two studies have demonstrated early childhood as the period of transmission of infection and identified an infected sibling as an important risk factor. An oral–oral route of spread has been substantiated with several studies showing the presence of H. pylori in the oral cavity. Studies have shown the presence of H. pylori in drinking water and the role of poor living conditions and sanitation in H. pylori infection, supporting an oral–fecal route of spread. Screening for H. pylori as a gastric cancer pre-screening strategy has been described in Japan, and the importance of H. pylori eradication as a gastric cancer–prevention strategy has now been further emphasized in Japanese guidelines. Two studies have shown a decrease in the burden of dyspepsia and peptic ulcer disease with H. pylori eradication.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1523-5378.2011.00874.x

Epidemiology of Helicobacter Pylori Infection and Public Health Implications

Purpose: The dipeptidyl peptidase IV (DPPIV) gene family exhibits multiple functions and is involved in the pathogenesis of various diseases. It has attracted pharmaceutical interest in the areas of metabolic disorders as well as cancer. However, clinicopathologic significance of DPPIV family in colorectal cancer is not fully understood. Materials and Methods: The clinical relevance of DPPIV and DPP10 expression was determined by immunohistochemical staining, and by assessing its clinicopathologic correlation in 383 colorectal cancer patients with known clinical outcomes. Results: DPPIV was not expressed in normal colon mucosa, but it showed luminal expression in 52 of the 383 colorectal cancers (13.5%). DPPIV expression in tumors was associated with right-sided location of the colon (p=0.010) and more advanced tumor stage (p=0.045). DPP10 was expressed in normal colonic mucosa, but its expression varied in primary colorectal cancer tissues. Loss of DPP10 expression was found in 11 colorectal cancers (CRCs) (2.9%), and multivariate analysis showed that loss of DPP10 expression was an independent factor for poor patient prognosis (p=0.008). Conclusion: DPP10 may play a role in disease progression of colorectal cancer and loss of DPP10 expression in primary CRC is significantly associated with poor survival outcomes.

/pdf/dipeptidyl-peptidase-10-a-novel-prognostic-marker-in-35b4mtraqk.pdf

Dipeptidyl Peptidase 10, a Novel Prognostic Marker in Colorectal Cancer

BACKGROUND/AIMS We designed this study to determine the clinical characteristics of critically ill patients with lower gastrointestinal hemorrhage (LGIH) and to evaluate the effectiveness of bedside colonoscopy in diagnosing and managing LGIH in the intensive care unit (ICU) setting. METHODOLOGY We retrospectively reviewed the medical records of patients who underwent bedside colonoscopy for LGIH that developed while in the ICU at Severance Hospital from January 1999 to June 2006. The control group was a random sampling of patients hospitalized in the ICU without GIH. RESULTS A total of 28,101 patients were hospitalized in ICU during the study period. Of these, 43 patients were included in each group. There were no significant differences in age, sex, and primary and underlying diseases between the two groups. Hypoalbuminemia and high BUN levels were found to be risk factors for LGIH in ICU patients. Bleeding focus was recognized in 28 patients (65.1%) through bedside colonoscopy. Major endoscopic diagnoses were ischemic colitis (13, 30.2%), rectal ulcer (7, 20.9%), and hemorrhoids (6, 13.9%). Primary endoscopic hemostasis was achieved in 11 of 28 diagnosed patients (39.3%). CONCLUSIONS Our data suggest that patients' underlying conditions may affect LGIH in the ICU setting. Moreover, urgent bedside colonoscopy may be effective in diagnosing and guiding appropriate treatments for LGIH in critically ill patients.

Risk factors and the role of bedside colonoscopy for lower gastrointestinal hemorrhage in critically ill patients.

Objective

We aimed to investigate the association between a family history (FH) of colorectal cancer (CRC) and cancer recurrence and survival in patients with stage III CRC.



Methods

From April 2001 to December 2007, 1102 patients with stage III CRC were enrolled and their data including FH, clinicopathological characteristics of the tumor were retrospectively analyzed.



Results

Of 971 patients that were finally enrolled, 63 (6.5%) reported CRC in at least one first-degree relative. Death occurred in 12.7% of the CRC patients with an FH and 21.8% in those without an FH. A multivariate analysis showed that patients with an FH of CRC, compared with those without FH, had an adjusted hazard ratios (HR) of 0.674 (P = 0.281) for overall survival (OS) and 0.672 (P = 0.220) for disease-free survival (DFS). However, the location of tumor, preoperative carcinoembryonic antigen (CEA) level, tumor invasion (T) stage and lymph node (N) metastasis significantly affected OS and DFS. Furthermore, whereas the FH of CRC patients was associated with a favorable prognosis in stage III colon cancer (HR 0.224, P = 0.040) but not in rectal cancer (HR 1.225, P = 0.640).



Conclusions

In patients with stage III CRC, tumor location (especially in the rectum), a high preoperative CEA level and advanced T and N stages indicate a poor prognosis. However, in stage III colon cancer FH is associated with improved survival.

Influence of family history on survival in patients with colon and rectal cancer

Purpose This study aimed to validate an automated calculating system developed for determining the adenoma detection rate (ADR). Methods To calculate the automated ADR, the data linking processes were as follows: (1) matching the selected colonoscopy results with the pathological results, (2) matching the polyp number from colonoscopy with that from pathology and confirming the histopathological results of each colonic polyp, and (3) confirming the histopathological results, especially the adenoma status of each colonic polyp. To verify the accuracy of the automated ADR calculating system, we manually calculated the ADR for 3 months through medical record review. Accuracy was calculated by measuring the error rate for each value. The cause of error was analyzed by additional order and chart review. Results After excluding 318 cases, 2,543 patients (1,351 men and 1,192 women; median age, 57.9 years) who underwent colonoscopy were included in this study. When the automated calculating system was used, polyps were found in 1,336 cases (52.6%) and adenomas were found in 1,003 cases (39.4%). When the manual calculating system was used, polyps were found in 1,327 cases (52.2%) and adenomas were found in 1,003 cases (39.4%). The accuracies of the polyp detection rate and ADR according to the automated calculating system were 99.3% and 100%, respectively. Conclusion We developed a system to automatically calculate the ADR by extracting hospital electronic medical record results and verified that it provided satisfactory results. It may help to improve colonoscopy quality.

https://thesurgery.or.kr/Synapse/Data/PDFData/6037ASTR/astr-97-319.pdf

Validation of an automated adenoma detection rate calculating system for quality improvement of colonoscopy

Purpose This study aimed to analyze the learning curves for colorectal surgery fellows in a colonoscopy training program. Methods Between May 2003 and February 2017, 60 surgical fellows joined our 1-year colonoscopy training program as trainees and performed 43,784 cases of colonoscopy. All trainees recorded their colonoscopy experiences prospectively into the database. After excluding 6 trainees, who had experience with performing more than 50 colonoscopies before participating in our training program or who discontinued our training program with experience performing less than 300 colonoscopies, this study included 54 trainees who had performed 39,539 colonoscopy cases. We analyzed the cecal intubation rate (CIR) and cecal intubation time (CIT) using the cumulative sum (Cusum) technique and moving average method to assess the technical colonoscopy competence. Results Overall, the CIR by the trainees was 80.7%. The median number of cases of colonoscopy performed during the training period for each trainee was 696 (range, 322-1,669). The trainees were able to achieve a 90% CIR with 412 and 493 procedures when analyzed using the moving average and the Cusum, respectively. Using the moving average method, CIRs after 150, 300, and 400 procedures were 67.0%, 84.1%, and 89.2%, respectively. The CIT of trainees continuously decreased until 400 successful cases. Median CITs were 9.4, 8.3, and 7.4 minutes at 150, 300, and 400 successful cases, respectively. Conclusion We found that more than 400 cases of experience were needed for technical competence in colonoscopy. Continuous teaching and monitoring is required until trainees become sufficiently competent.

/pdf/colonoscopy-learning-curves-for-colorectal-surgery-fellow-47vtutwzk8.pdf

Byung Chang Kim

Papers

Dipeptidyl Peptidase 10, a Novel Prognostic Marker in Colorectal Cancer

Risk factors and the role of bedside colonoscopy for lower gastrointestinal hemorrhage in critically ill patients.

Influence of family history on survival in patients with colon and rectal cancer

Validation of an automated adenoma detection rate calculating system for quality improvement of colonoscopy

Colonoscopy learning curves for colorectal surgery fellow trainees: experiences with the 15-year colonoscopy training program