Unraveling the potential clinical utility of circulating tumor DNA detection in colorectal cancer-evaluation in a nationwide Danish cohort.

BACKGROUND: Increasingly, circulating tumor DNA (ctDNA) is proposed as a tool for minimal residual disease (MRD) assessment. Digital PCR (dPCR) offers low analysis costs and turnaround times of less than a day, making it ripe for clinical implementation. Here, we used tumor-informed dPCR for ctDNA detection in a large colorectal cancer (CRC) cohort to evaluate the potential for post-operative risk assessment and serial monitoring, and how the metastatic site may impact ctDNA detection. Additionally, we assessed how altering the ctDNA-calling algorithm could customize performance for different clinical settings. PATIENTS AND METHODS: Stage II-III CRC patients (N = 851) treated with a curative intent were recruited. Based on whole-exome sequencing on matched tumor and germline DNA, a mutational target was selected for dPCR analysis. Plasma samples (8 ml) were collected within 60 days after operation and-for a patient subset (n = 246)-every 3-4 months for up to 36 months. Single-target dPCR was used for ctDNA detection. RESULTS: Both post-operative and serial ctDNA detection were prognostic of recurrence [hazard ratio (HR) = 11.3, 95% confidence interval (CI) 7.8-16.4, P < 0.001; HR = 30.7, 95% CI 20.2-46.7, P < 0.001], with a cumulative ctDNA detection rate of 87% at the end of sample collection in recurrence patients. The ctDNA growth rate was prognostic of survival (HR = 2.6, 95% CI 1.5-4.4, P = 0.001). In recurrence patients, post-operative ctDNA detection was challenging for lung metastases (4/21 detected) and peritoneal metastases (2/10 detected). By modifying the cut-off for calling a sample ctDNA positive, we were able to adjust the sensitivity and specificity of our test for different clinical contexts. CONCLUSIONS: The presented results from 851 stage II-III CRC patients demonstrate that our personalized dPCR approach effectively detects MRD after operation and shows promise for serial ctDNA detection for recurrence surveillance. The ability to adjust sensitivity and specificity shows exciting potential to customize the ctDNA caller for specific clinical settings.

Acute endocarditis treated with radical debridement and implantation of mechanical or stented bioprosthetic devices.

BACKGROUND: Operation for active infective endocarditis carries high mortality and morbidity rates, especially when the annulus is involved. Overall the literature favors the use of autograft and homograft valves because of better resistance to infection. In our clinic during the last 5 years we used an aggressive surgical approach to infective endocarditis in combination with implantation of mechanical or stented bioprosthetic devices. METHODS: From 1994 to 1999, 50 adults with aortic and/or mitral valve endocarditis underwent valve replacement. The median age of the 36 men and 14 women was 58 years (range, 17 to 78 years). All patients had active endocarditis at the time of operation. Native valve endocarditis was present in 48 patients and prosthetic valve endocarditis was present in 2 patients. The aortic valve was affected in 24 patients, the mitral valve in 21 patients, and both the aortic and mitral valves in 5 patients. Two of the patients with mitral endocarditis also had infection of the tricuspid valve. Annular destruction was present in 24 patients (48%). The patients were treated with radical excision of all infected tissue. The annular defects were closed, if possible, with direct sutures. Otherwise, a reconstruction was performed. Follow-up was 100% complete with a median follow-up period of 45 months (range, 6 to 66 months). RESULTS: The procedures were performed without lethal bleeding complications. Early mortality was 12% and the actuarial survival at follow-up was 80%. In none of the patients who died was death related to the prosthetic valve or recurrence of the endocarditis. Only 1 patient (2%) developed recurrence of the infective endocarditis and was reoperated with a Ross procedure. Three and a half years later the patient developed severe valve insufficiency of the autograft and was operated again with implantation of a mechanical device. CONCLUSIONS: Native and prosthetic valve endocarditis can be treated successfully with aggressive surgical debridement and implantation of mechanical or stented bioprosthetic devices with a low risk of recurrent endocarditis.

Cholecystectomy in patients with normal gallbladder function did not alter characteristics in duodenal motility which was not correlated to size of bile acid pool.

Nine gallstone patients with normal gallbladder function as assessed by hepatobiliary scintigraphy were included. Fasting and postprandial duodenal motility were studied before and one month after an uncomplicated laparoscopic cholecystectomy. An ambulatory continuous pressure recording was obtained from 5 PM to 8 AM with a sampling frequency of 4 Hz. At 6 PM, the patients received a 1400-kJ standard meal. The size of the bile acid pool after cholecystectomy was measured according to the dilution principle using [C14]cholic acid as the marker. Preoperatively the migrating motor complex (MMC) cycle was 0.48/hr (quartiles 0.42-0.68) compared to 0.68/hr (0.43-0.77) postoperatively. This difference was not significant. An increase in the MMC cycle frequency was observed postoperatively in three patients, and a decrease was seen in four patients. The migration velocity was 5.61 cm/min (4.26-8.01) preoperatively and 7.16 cm/min (4.79-9.71) postoperatively, a difference that was not significant. The time period from meal ingestion to appearance of phase III was 297 min (218-431) at the preoperative examination and 443 min (192-494) at the postoperative examination. This difference was not significant. The size of the bile acid pool after cholecystectomy was 3.68 mmol (2.69-8.47) and was not significantly correlated to the frequency of the MMC cycle or the time period from food ingestion to phase III activity. It is concluded that in gallstone patients with a normally functioning gallbladder, cholecystectomy does not alter duodenal motility, which was not correlated to the size of the bile acid pool.

Late mesh rejection as a complication to transabdominal preperitoneal laparoscopic hernia repair.

BACKGROUND: The use of a mesh in transabdominal preperitoneal laparoscopic hernia repair (TAPP) caries the risk of late rejection or infectious complications related to the mesh. The aim of this study was to describe the extent of these complications. METHODS: We performed a retrospective study of 500 consecutive patients with TAPP for inguinal hernia. RESULTS: Late mesh rejection was observed in three patients at 5-19 months after surgery. The mesh was removed via a suprapubic midline incision. At 3-4 month's follow-up, none of the patients had recurrence of the hernia, even though no hernia repair had been done. CONCLUSION: Late mesh rejection is a potential complication of TAPP and has to be considered when choosing the surgical method of hernia repair.

[Incarceration of the ventricle through a right-sided Bochdalek hernia with symptoms of tension pneumothorax]. / Inkarceration af ventriklen gennem et højresidigt. Bochdalek-hernie med symptomer på overtrykspneumothorax.

Acute herniations through a posterolateral diaphragmatic defect (Bochdalek hernia) are rare in adults. Most of these hernias are on the left side causing gastrointestinal symptoms. We present af case of a Bochdalek hernia on the right side, where incarceration and distension of the stomach was followed by dyspnoea and haemoptysis. Aetiology, symptoms, diagnosis and treatment are discussed.

Long-term survival and complications in patients with mechanical aortic valves without anticoagulation. A follow-up study from 1 to 15 years.

In aortic valve replacement most centres prefer to use a mechanical valve for younger patients without special bleeding risks and treat the patient with lifelong anticoagulation. However, a few patients do not receive anticoagulation at all or have this withdrawn after some time. We examined the prognosis of 43 patients, 37 men and 6 women (mean age 52 years), who were treated with anticoagulation for approximately only 1 year (mean 13 months; range 4-35 months) after isolated aortic valve replacement with a mechanical valve. The mean follow-up period was 7 years and 3 months (1.5 months to 15 years and 10 months). After 5 and 10 years, 70% and 59%, respectively, were free of thromboembolic events, 65% and 55%, respectively, were free of valve-related events, and 87% and 83%, respectively, had survived. These figures correspond to linearized rates of thromboembolic events of 5.2%/pt-yr, valve-related events of 6.2%/pt-yr and death of 2.9%/pt-yr. We conclude that the best postoperative treatment in isolated aortic valve replacement with a mechanical valve is lifelong anticoagulation.