Hartwig Kørner

Incidence of acute nonperforated and perforated appendicitis: Age- specific and sex-specific analysis

Abstract. This prospective study was performed to investigate epidemiological characteristics in terms of the age- and sex-specific incidence in patients with perforated and nonperforated appendicitis. The study population comprised 1486 consecutive patients who underwent appendectomy for suspected acute appendicitis between 1989 and 1993. Two patient cohorts [n = 544 (37%)] were analyzed with regard to prehospitalization duration of symptoms and in-hospital observation time. The crude incidence of acute appendicitis was 86 per 100,000 per year. Although the incidence of nonperforated appendicitis was highest among adolescents and young adults (13–40 years of age), perforated appendicitis occurred at almost the same incidence in all sex and age groups. The diagnostic accuracy was 76%. Perforated appendicitis occurred in 19%, with higher rates in small children and the elderly, irrespective of gender. A high diagnostic accuracy was not associated with an increased rate of perforation. In small children and the elderly, the diagnostic accuracy was low and the perforation rate high. Patients with perforation had a significantly longer duration of symptoms as well as in-hospital observation time than did patients with nonperforated appendicitis. Perforated appendicitis showed a different incidence pattern than nonperforated appendicitis and was associated with a significantly longer duration of symptoms and in-hospital observation time, probably due to patient-related factors. We suggest this observation deserves attention regarding clinical diagnosis and treatment decision-making for patients with suspected acute appendicitis.

Microsatellite instability in colorectal cancer

Microsatellite instability (MSI) causes hereditary non‐polyposis colorectal cancer (HNPCC), and occurs in about 15 per cent of sporadic colorectal cancers. Although the basic mechanisms are not clear, there is increased understanding of the clinicopathological consequences of MSI.

Bile duct cysts in adults

Bile duct cysts are rare and of uncertain origin. Most have been reported in young females of Asian descent, but an increasing number have occurred in Western adults.

Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis: The SCANDIV Randomized Clinical Trial

IMPORTANCE Perforated colonic diverticulitis usually requires surgical resection, which is associated with significant morbidity. Cohort studies have suggested that laparoscopic lavage may treat perforated diverticulitis with less morbidity than resection procedures. OBJECTIVE To compare the outcomes from laparoscopic lavage with those for colon resection for perforated diverticulitis. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized clinical superiority trial recruiting participants from 21 centers in Sweden and Norway from February 2010 to June 2014. The last patient follow-up was in December 2014 and final review and verification of the medical records was assessed in March 2015. Patients with suspected perforated diverticulitis, a clinical indication for emergency surgery, and free air on an abdominal computed tomography scan were eligible. Of 509 patients screened, 415 were eligible and 199 were enrolled. INTERVENTIONS Patients were assigned to undergo laparoscopic peritoneal lavage (n = 101) or colon resection (n = 98) based on a computer-generated, center-stratified block randomization. All patients with fecal peritonitis (15 patients in the laparoscopic peritoneal lavage group vs 13 in the colon resection group) underwent colon resection. Patients with a pathology requiring treatment beyond that necessary for perforated diverticulitis (12 in the laparoscopic lavage group vs 13 in the colon resection group) were also excluded from the protocol operations and treated as required for the pathology encountered. MAIN OUTCOMES AND MEASURES The primary outcome was severe postoperative complications (Clavien-Dindo score >IIIa) within 90 days. Secondary outcomes included other postoperative complications, reoperations, length of operating time, length of postoperative hospital stay, and quality of life. RESULTS The primary outcome was observed in 31 of 101 patients (30.7%) in the laparoscopic lavage group and 25 of 96 patients (26.0%) in the colon resection group (difference, 4.7% [95% CI, -7.9% to 17.0%]; P = .53). Mortality at 90 days did not significantly differ between the laparoscopic lavage group (14 patients [13.9%]) and the colon resection group (11 patients [11.5%]; difference, 2.4% [95% CI, -7.2% to 11.9%]; P = .67). The reoperation rate was significantly higher in the laparoscopic lavage group (15 of 74 patients [20.3%]) than in the colon resection group (4 of 70 patients [5.7%]; difference, 14.6% [95% CI, 3.5% to 25.6%]; P = .01) for patients who did not have fecal peritonitis. The length of operating time was significantly shorter in the laparoscopic lavage group; whereas, length of postoperative hospital stay and quality of life did not differ significantly between groups. Four sigmoid carcinomas were missed with laparoscopic lavage. CONCLUSIONS AND RELEVANCE Among patients with likely perforated diverticulitis and undergoing emergency surgery, the use of laparoscopic lavage vs primary resection did not reduce severe postoperative complications and led to worse outcomes in secondary end points. These findings do not support laparoscopic lavage for treatment of perforated diverticulitis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01047462.

Trypsin in colorectal cancer: molecular biological mechanisms of proliferation, invasion, and metastasis.

Trypsin is involved in colorectal carcinogenesis and promotes proliferation, invasion, and metastasis. Although a well‐known pancreatic digestive enzyme, trypsin has also been found in other tissues and various cancers, most importantly of the colorectum. Moreover, colorectal cancers with trypsin expression have a poor prognosis and shorter disease‐free survival. Biological understanding of how trypsin causes cancer progression is emerging. It seems to act both directly and indirectly through a ‘proteinase–antiproteinase‐system’, and by activation of other proteinase cascades. Invasion of the basal membrane by cancer cells may be promoted directly by trypsin digestion of type I collagen. Trypsin activates, and is co‐expressed with matrix metalloproteinases (MMPs), which are known to facilitate invasion and metastasis. MMP‐2, MMP‐7, and MMP‐9 are co‐expressed together with trypsin and seem to be of particular importance in proliferation, progression, and invasion. MMPs may play a role in both conversion from adenoma to carcinoma, and in the initiation of invasion and metastasis. Co‐segregation of trypsin and MMPs within the tumour environment is important for the activation of MMPs, and may explain the deleterious effect of trypsin on prognosis in colorectal cancer. Trypsin and proteinase‐activated receptor 2 (PAR‐2) act together in an autocrine loop that promotes proliferation, invasion, and metastasis through various mechanisms, of which prostaglandin synthesis is important. Stimulated by trypsin, both MMP and PAR‐2 may activate the mitogenic MAPK–ERK pathway through activation of the epidermal growth factor receptor. Experimental trypsin inhibition is feasible but not very effective, and trypsin as a target for clinical therapy is unlikely to be successful owing to its universal distribution. However, as the pathways of trypsin and co‐activated protein cascades emerge, biological understanding of colorectal carcinogenesis will be further illuminated and may pave the way for prognosticators, predictors, and novel targets of therapy. Copyright

Evolving molecular classification by genomic and proteomic biomarkers in colorectal cancer: Potential implications for the surgical oncologist

Colorectal cancer (CRC) is one of the most frequent cancers in the Western world and represents a major health burden. CRC development is a multi-step process that spans 10-15years, thereby providing an opportunity for early detection and even prevention. As almost half of all patients undergoing surgery develop recurrent disease, surveillance is advocated, albeit with various means and intervals. Current screening and surveillance efforts have so far only had limited impact due to suboptimal compliance. Currently, CEA is the only biomarker in clinical use for CRC, but has suboptimal sensitivity and specificity. New and better biomarkers are therefore strongly needed. Non-invasive biomarkers may develop through the understanding of colorectal carcinogenesis. Three main pathways occur in CRC, including chromosomal instability (CIN), microsatellite instability (MSI) and epigenetic silencing through the CpG Island Methylator Phenotype (CIMP). These pathways have distinct clinical, pathological, and genetic characteristics, which can be used for molecular classification and comprehensive tumour profiling for improved diagnostics, prognosis and treatment in CRC. Molecular-biological research has advanced with the sequencing of the human genome and the availability of genomic and proteomic high-throughput technologies using different chip platforms, such as tissue microarrays, DNA microarrays, and mass spectrometry. This review aims to give an overview of the evolving biomarker concepts in CRC, with concerns on methods, and potential for clinical implications for the surgical oncologist.

Systematic follow-up after curative surgery for colorectal cancer in Norway: A population-based audit of effectiveness, costs, and compliance

In this study, we analyzed the Norwegian guidelines for systematic follow-up after curative colorectal cancer surgery in a large single institution. Three hundred fourteen consecutive unselected patients undergoing curative surgery for colorectal cancer between 1996 and 1999 were studied with regard to asymptomatic curable recurrence, compliance with the program, and cost. Follow-up included carcinoembryonic antigen (CEA) interval measurements, colonoscopy, ultrasonography of the liver, and radiography of the chest. In 194 (62%) of the patients, follow-up was conducted according to the Norwegian guidelines. Twenty-one patients (11%) were operated on for curable recurrence, and 18 patients (9%) were disease free after curative surgery for recurrence at evaluation. Four metachronous tumors (2%) were found. CEA interval measurement had to be made most frequently (534 tests needed) to detect one asymptomatic curable recurrence. Follow-up program did not influence cancer-specific survival. Overall compliance with the surveillance program was 66%, being lowest for colonoscopy (55%) and highest for ultrasonography of the liver (85%). The total program cost was € 228,117 (US

Survival effect of implementing national treatment strategies for curatively resected colonic and rectal cancer

280,994), translating into € 20,530 (US

Microsatellite instability and DNA ploidy in colorectal cancerx: Potential implications for patients undergoing systematic surveillance after resection

25,289) for one surviving patient after surgery for recurrence. The total diagnosis yield with regard to disease-free survival after surgery for recurrence was 9%. Compliance was moderate. Whether the continuing implementation of such program and cost are justified should be debated.

Quantitative RT-PCR detection of tumor cells in sentinel lymph nodes isolated from colon cancer patients with an ex vivo approach.

The surgical management of rectal cancer has changed substantially over the past decade. There are limited data on the long‐term outcome of implementing systematic management strategies.