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

OBJECTIVE This study aimed to identify the computed tomographic colonography (CTC) findings of incomplete colonoscopy compared with those of complete colonoscopy. METHODS The clinical data and CTC imaging data from January 2004 to December 2012 were retrospectively obtained at 2 different institutions and reviewed by the central review system. A total of 71 patients who underwent both videocolonoscopy and CTC were included in this study. The CTC findings and clinical data were evaluated for the completeness of colonoscopy. RESULTS In the CTC analysis, differences in total colon length, abdominal circumference, and sigmoid colon diameter were statistically significant between both groups (P < 0.05). Body mass index (BMI) and height were identified as significant clinical factors influencing the completeness of colonoscopy. In multiple logistic regression tests, only BMI and sigmoid colon diameter were independent factors (P < 0.05). CONCLUSIONS High BMI larger diameter of sigmoid colon was associated with incomplete colonoscopy based on CTC.

Risk Factors Associated With Incomplete Colonoscopy Based on the Analysis of Computed Tomographic Colonography Findings.

Background Systemic treatments, namely, either monotherapy or combination therapy, are commonly administered to patients with advanced or metastatic colorectal cancer (CRC). This study aimed to provide the complete efficacy and safety profiles and ranking of systemic therapies for the treatment of unresectable advanced or metastatic CRC. Methods We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception until June 30, 2021, and also the bibliographies of relevant studies. Randomized controlled trials comparing two or more treatments, namely, at least capecitabine, 5-fluorouracil, leucovorin, irinotecan, bevacizumab, cetuximab, oxaliplatin, or panitumumab were investigated. A network meta-analysis using the Bayesian approach was performed to compare the efficacy and safety of treatments. The surface under the cumulative ranking curve (SUCRA) was calculated for the probability of each treatment as the most effective. The overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), adverse events (AEs) grade ≥3, and serious adverse events (SAEs) were evaluated. Results One hundred two publications with 36,147 participants were assigned to 39 different treatments. Among 11 treatments with full information on six outcomes, FOLFIRI/FOLFOX/FOLFOXIRI + bevacizumab significantly improved both the ORR and DCR, compared to FOLFIRI. Although FOLFOX and FOLFIRI/FOLFOX + cetuximab significantly prolonged both OS and PFS, treatments were comparable in terms of AEs grade ≥3 and SAEs. The top highest SUCRA values were observed in the FOLFOXIRI + panitumumab group for ORR (96%) and DCR (99%), FOLFIRI + bevacizumab + panitumumab group for OS (62%) and PFS (54%), and FOLFOXIRI + bevacizumab group for AEs grade ≥3 (59%) and SAEs (59%) outcomes. Conclusions These findings suggest an available range of systemic treatment therapies with different efficacy and safety profiles with patients. Further investigations of the side effects and mutation status are required to confirm our findings. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD42019127772

/pdf/efficacy-and-safety-of-systemic-treatments-among-colorectal-2we4r6g1.pdf

Efficacy and Safety of Systemic Treatments Among Colorectal Cancer Patients: A Network Meta-Analysis of Randomized Controlled Trials

Complete resection of submucosal invasive colorectal cancer (SICC) showing favorable histology is regarded as curative. We report on two cases of SICC showing recurrence within 5 years despite complete resection. The first patient was a 68-year-old woman with well differentiated rectal adenocarcinoma invading the superficial submucosa, which recurred after 4.7 years. The second patient was a 53-year-old man with pT1N0 moderately differentiated colonic adenocarcinoma. He developed widespread tumor recurrence after 3.9 years. Retrospective pathologic review of the original tumors showed multiple foci of tumor budding at the invasive front. Immunohistochemical staining for D2-40 of deeper levels of the paraffin blocks showed rare foci of small lymphatic invasion. Tumor budding at the invasive front may be an important indicator for SICC aggressiveness or may reflect early lymphatic invasion. More aggressive pathologic examination and follow-up is required for patients with SICC showing tumor budding, even in the absence of unfavorable histologic findings.

/pdf/tumor-budding-and-recurrence-in-submucosal-invasive-3u2xdlhyfg.pdf

Tumor Budding and Recurrence in Submucosal Invasive Colorectal Cancers of Favorable Histology: Case Reports of Two Early Colorectal Cancers with Advanced Recurrences

Acute pericarditis may be caused by a variety of disorders. Most cases of acute pericarditis without any initial apparent cause are idiopathic, although presumably viral in origin. While staphylococcus aureus, streptococcus pneumonias and streptococcus pyogens were the predominant organisms recovered prior to 1950, gram negative bacilli, anaerobic bacteria and fungus were recovered after 1950. These changes of the etiologic diversity of acute pericarditis were related to the development and advances of cardiac surgery, antibiotics, chemotherapy for cancer and immunosuppressive treatments. It is important for the therapy of acute bacterial pericarditis to establish the proper regimen of antibiotics and to drain pericardial effusion, if needed. We report a case of acute pericarditis, caused by Klebsiella pneumoniae, an uncommon pathogen that caused purulent pericarditis with cardiac tamponade. (Korean Circulation J 2002;32(1):80-84)

/pdf/a-case-of-acute-purulent-pericarditis-caused-by-klebsiella-y67z5f5qes.pdf

A Case of Acute Purulent Pericarditis, Caused by Klebsiella Pneumoniae, without Preceeding Diseases

Purpose Minute T1 colorectal cancer (CRC) lesions (≤5 mm) are rare; however, little is known about their characteristics and aggressiveness. In this study, we evaluated the characteristics of minute T1 CRC in relevance to pathology and treatment. Methods This retrospective study included 849 patients with T1 CRC endoscopically or surgically treated between January 2001 and December 2016. The patients were stratified into 4 groups according to tumor size; minute group (≤5 mm), small group (6-10 mm), medium group (11-20 mm), and large group (≥21 mm). Clinicopathological variables were evaluated with respect to tumor size. Results The incidence of the minute T1 CRC was 2.4% (20 of 849). Minute T1 CRC was significantly associated with flat type (minute, 25%; small, 12.6%; medium, 8.8%; large, 12.6%; P = 0.016), right-sided cancer (30%, 15.4%, 15.4%, 15.1%, P = 0.002) and the absence of background adenoma (BGA) (50%, 40.7%, 32.8%, 18.1%, P < 0.001). In patients who underwent surgery, lymph node metastasis (LNM) was significantly higher in the minute group (36.4%, 15.9%, 15.7%, 9.2%, P = 0.029). Conclusion Minute T1 CRC is significantly associated with flat type, right-sided cancers, as well as with the absence of BGA and LNM. These results suggested the minute T1 CRC lesions are often aggressive and are likely to be missed during colonoscopy.

/pdf/characteristics-of-minute-t1-colorectal-cancer-in-relevance-4lxrsuow81.pdf

Byung Chang Kim

Papers

Risk Factors Associated With Incomplete Colonoscopy Based on the Analysis of Computed Tomographic Colonography Findings.

Efficacy and Safety of Systemic Treatments Among Colorectal Cancer Patients: A Network Meta-Analysis of Randomized Controlled Trials

Tumor Budding and Recurrence in Submucosal Invasive Colorectal Cancers of Favorable Histology: Case Reports of Two Early Colorectal Cancers with Advanced Recurrences

A Case of Acute Purulent Pericarditis, Caused by Klebsiella Pneumoniae, without Preceeding Diseases

Characteristics of minute T1 colorectal cancer in relevance to pathology and treatment.