Frequencies and prognostic role of KRAS and BRAF mutations in patients with localized pancreatic and ampullary adenocarcinomas.

OBJECTIVES: The frequencies and prognostic role of KRAS and BRAF mutations in patients operated on for pancreatic ductal adenocarcinomas (PDACs) and ampullary adenocarcinomas (A-ACs) are scantily studied. METHODS: KRAS and BRAF mutations were analyzed in formalin-fixed, paraffin-embedded tumor samples from primarily chemotherapy-naive patients operated on with radical intentions for PDAC (n = 170) and A-AC (n = 107). RESULTS: Eighty percent of PDAC patients had KRAS mutations (codon 12 mutations: 74%) and 67% with A-AC (codon 12 mutations: 54%). BRAF mutations were less common, 16% in PDAC and 12% in A-AC, and no V600E mutations were found. Fourteen percent with PDAC and 7% with A-AC had mutations in both KRAS and BRAF. Multivariate analysis, including KRAS status, stage, and American Society of Anesthesiologists physical status classification system score, demonstrated that KRAS mutations in patients with A-AC were associated with short recurrence-free survival (RFS) (hazard ratio, 2.45; 95% confidence interval, 1.19-5.06; P = 0.015) and overall survival (OS) (1.93, 95% 1.12-3.31; P = 0.018). KRAS mutations in patients with PDAC were not associated with RFS and OS. BRAF mutations were not associated with RFS and OS. CONCLUSIONS: KRAS mutations frequencies were high in PDAC and A-AC. KRAS mutations were associated with poor prognosis in patients with A-AC, but not in patients with PDAC.

[Diaphragmatic hernia presenting with colonic strangulation]. / Colonileus som komplikation til spontant diafragmahernie.

Diaphragmatic hernia may be asymptomatic and may have a delayed clinical manifestation. We describe a 78-year-old man who developed colonic obstruction as a complication to a diaphragmatic hernia. Unlike most diaphragmatic hernias, this case was not associated with a trauma. Normally, the diagnosis is made clinically by means of thoracic X-ray, computer tomography or magnetic resonance imagining of the abdomen. In this patient, barium enema showed a tumor-like stenosis of the left colonic flexure, but intraoperative findings demonstrated a defect in the left diaphragm with herniation of the left colonic flexure and the greater omentum.

[Traumatic diaphragmatic rupture with displacement of the liver to the right hemithorax]. / Traumatisk diafragmaruptur med displacering af leveren til thorax.

We report a case of a traumatic diaphragmatic rupture with the liver displaced to the right hemithorax. MR diagnosed the rupture and the displacement of the liver. The patient was operated on and the total right diaphragmatic rupture was reconstructed by suturing. Traumatic diaphragmatic rupture may occur after high velocity accidents, especially after lateral collisions in traffic. Diagnosis may be delayed as a result of variable clinical and radiological signs. It is important to discover the rupture in the acute phase. Treatment is operative.

[New liver surgery techniques. Few complications and more advantages?]. / Nye leverkirurgiske teknikker. Få komplikationer og flere fordele?

INTRODUCTION: Most blood loss in hepatic resections occurs during transection of the liver. To reduce this blood loss and avoid blood transfusions, initial experience with radiofrequency based dissecting devices are presented. Curative liver surgery requires combinations of classical resections and tumorablations. MATERIALS AND METHODS: Retrospective analysis of 22 patients who underwent various hepatic resections for colorectal liver metastases. Two commercially available devices were used for transection, either the TissueLink or the Habib Sealer. RESULTS: Mortality was zero and morbidity low. No blood transfusions were needed following the use of the Habib Sealer, whereas four patients received blood after TissueLink. 27% of the patients needed a combination of resection and tumorablation. CONCLUSION: Liver surgery and transection of the liver can be performed safely with radiofrequency based dissecting devices. Theoretical advantage could be more candidates to curative surgery.

[Surgical treatment of liver metastases and liver cancer]. / Kirurgisk behandling af levermetastaser og levercancer.

Hepatic resection is the golden standard in treatment of tumours from primary liver cancer and colorectal liver metastases, but is appropriate for a variety of other benign and malignant tumours in the liver. The selection of patients and criteria are discussed. Curative liver surgery is a prerequisite for treatment, whereas the size, number and localization of the tumours do not affect operability per se, but the prognosis is influenced by these factors. Surgical strategies, techniques and adjuvant chemotherapy are discussed. Recurrence or newly-evolved tumours can be treated.

Initial clinical experience with oral manganese (CMC-001) for liver MR imaging.

Recently, a new oral liver-specific manganese-based MR agent (CMC-001) has been introduced. This contrast medium is delivered to the liver in high concentrations in the portal vein and very low doses in the hepatic artery, as only small amounts of manganese enter the general circulation. It is taken up by the hepatocytes and excreted in the bile. Our initial experience with the new MR contrast medium in a variety of patients is reported. A total of 20 patients (11 males and 9 females) were studied with MR imaging 2 h after oral ingestion of the contrast agent. Sixteen patients were referred for evaluation of focal liver lesion(s), whereas in the remaining four patients, evaluation of the biliary tract was requested. In the 17 patients without biliary obstruction, there was an increased signal intensity of the liver parenchyma, whereas in the three patients with biliary obstruction, the uptake was delayed. There was excellent visualization of the biliary system on the T1-weighted images in the 16 patients without biliary obstruction referred for evaluation of a focal liver lesion. In seven patients, the uptake was patchy. In patients with focal liver lesions or biliary tract diseases, it is possible to increase the signal intensity of the liver parenchyma after the oral intake of CMC-001. In patients without biliary tract obstruction, the biliary system is easily visualized. Oral manganese seems to be useful in hepatobiliary MRI. Further research is strongly warranted.

Curative resection for left-sided pancreatic malignancy.

BACKGROUND: Surgical technique in pancreatic cancer has seen significant developments, but much of the knowledge refers to pancreatic head carcinoma. Reports on the management of tumours of the body and tail have been less frequent. Current knowledge teaches that adenocarcinomas of the body and tail of the pancreas have a worse prognosis. The aim of this study is to report the short- and long-term outcome in 20 patients with left-sided pancreatic malignancy, where 'resection for cure' was done. PATIENTS AND METHODS: Retrospective study of demographic data, symptomatology, diagnostic methods, operative management, pathology report, postoperative morbidity and mortality. RESULTS: Postoperative complications were seen in 40% of patients. One patient died on day 5 from sepsis with multiple organ failure. Other complications were intra-abdominal bleeding, bleeding from the gastroentero-anastomosis, postoperative jaundice, pleural exudate, wound dehiscence and intra-abdominal abscess. The patients with ductal adenocarcinoma had a median survival of 14 months and a 5-year survival of 17%. The median survival for the whole group of patients was 17 months and the 5-year survival was 23%. One patient with malignant insulinoma and two patients with adenocarcinoma had a survival exceeding 5 years (98, 174 and 183 months, respectively). DISCUSSION: Selected patients with left-sided pancreatic adenocarcinoma may be operated on with results similar to pancreaticoduodenectomy (Whipple procedure) for cancer of the pancreatic head regarding postoperative morbidity and mortality as well as long-term survival. Thus, although left-sided pancreatic cancer generally appears at a more advanced stage, it seems true that treatment results are similar if radical excision can be achieved.

[Treatment of liver and lung metastases from colorectal cancer]. / Behandling af lever- og lungemetastaser fra kolorektal cancer.

Metastases from colorectal cancer are most often confined to the liver or lungs, in which 20-25% may be resected with curative intent. Without treatment, no patients are alive after four years, whereas 30% are alive four years after radical resection. Early use of chemotherapy increases survival, and about 20% of patients may thus become suited for local therapy. After the primary operation, surveillance is recommended, with measurement of carcinoembryonal antigene every 3-6 months for 3 years, then every 6-12 months from years 3 to 5, plus ultrasound or CT scan every 6 months for 3 years, then yearly for up to 5 years.

[Diagnosis and treatment of complications during cholecystectomy]. / Diagnostik og behandling af komplikationer ved kolecystektomi.

The incidence of bile duct injury after laparoscopic cholecystectomy has been reduced to 0.6%. One factor contributing to such injuries is misidentification of the bile duct anatomy. During laparoscopic cholecystectomy the surgeon should follow the criteria for dissection of the triangle of Calot and dealing with bleeding. Immediate reconstruction over a T-tube may be possible, or a baby-feeding tube should be inserted into the proximal part of the bile duct and the patient should be transferred to a center with experience in bile duct reconstruction.

Resection of cancer of the body and tail of the pancreas.

BACKGROUND/AIMS: To report our results of resection of cancer in the body and tail of the pancreas and review the literature. METHODOLOGY: Thirteen patients with a median age of 62 years with cancer of the body and/or tail of the pancreas. The diagnosis was made by ultrasonography, computed tomography, endoscopic retrograde cholangiopancreatography and angiography. Eleven patients had distal or subtotal pancreatectomy and two patients total pancreatectomy. The surgical procedure included extensive dissection of lymph nodes and the connective tissue in the peripancreatic region. Main outcome measures were postoperative morbidity and mortality, median and 5-year survival rates. RESULTS: Ten of the resections were considered to be curative. Postoperative complications occurred in seven patients and one patient died in the postoperative period. The median survival time of operative survivors was 392 days. Two patients survived five years, and one was alive ten years after surgery. Eight patients died of recurrence. CONCLUSIONS: Long-term survival may be achieved in a quarter of the resectable patients.

[Ultrasound-guided radiofrequency ablation of malignant liver tumors]. / UL-vejledt radiofrekvensbehandling af maligne levertumorer.

INTRODUCTION: Radio frequency ablation (RFA) of malignant tumours is a new and promising treatment modality. The aim of this study was to evaluate the method in patients with non-resectable liver tumours. MATERIAL AND METHODS: RFA was performed under the guidance of ultrasonography and general anaesthesia in 37 patients from December 1998 to November 2001. Six patients had primary liver cancers, and 31 metastases from other cancer, often colorectal cancer. RESULTS: Eight patients could not be evaluated because of the short follow-up time. Twenty-four of 29 patients (83%) achieved a complete tumour response. Twelve patients (41%) are alive after 3-28 (median 16) months, without recurrence. Twelve patients (41%) are alive after 1-34 (median 14) months, with recurrence. Five patients (14%) died after 4-26 (median 11) months, because of recurrence in the liver and/or other organs. Four patients had minor complications and one a major complication. There was no postoperative mortality. DISCUSSION: RFA can be offered to patients with non-resectable liver tumours when it is technically possible. The treatment can be performed with few complications, requires only a short hospital stay, and is cheaper than other treatments. Prolonged survival is attained in 40-50% cent of the patients.

Improved detection and biopsy of solid liver lesions using pulse-inversion ultrasound scanning and contrast agent infusion.

The purpose of this study was to assess the ability of pulse-inversion ultrasound (US) scanning (PIUS), combined with an IV contrast agent, to detect malignant liver lesions and its impact on patient management (resectability). Additionally, to determine the feasibility of US-guided biopsy of new PIUS-findings at the same session. A total of 30 patients with known or clinically suspected cancer underwent conventional B-mode scanning and PIUS with IV-administered contrast agent. The number of liver metastases in the right and the left liver lobe, respectively, was recorded. All patients with additional findings by PIUS underwent US-guided biopsy. PIUS provided additional information in 18 patients (60%); of these, 13 (43%) had additional metastases. Of 19 patients found resectable by conventional US, 9 (47%) were considered inoperable using PIUS supported by biopsies. Biopsies of additional findings were performed in 17 of 18 patients. All biopsies of additional findings confirmed malignancy. PIUS with an IV contrast agent increased the ability to detect liver metastases compared to conventional US scanning. The technique had a high impact on patient management. The results showed that PIUS-guided biopsy was possible. PIUS with IV contrast will undoubtedly become an important diagnostic tool in the evaluation of patients with metastatic liver disease.