Tom Mala

Laparoscopic liver resection has shown classical advantages of minimally invasive surgery over the open counterpart. In spite of introduction in early 1990-s only few centres worldwide adapted laparoscopic liver resection to routine practice. It was due to considerable technical challenges and uncertainty about oncologic outcomes. Various ablative techniques have been developed last 2 decades in parallel with laparoscopy. High intensity focused ultrasound (HIFU) attracts special interests due to its fully non-invasive nature. The main goal of this thesis was to estimate and develop new minimally invasive techniques in the treatment of patients with lesions in the liver: laparoscopic surgery and HIFU. Two hundred and twenty patients, who underwent laparoscopic liver resection during 244 procedures from August 1998 to December 2010 at the Oslo University Hospital, Rikshospitalet, formed the research basis for the clinical section of this thesis. An experimental porcine model was applied to study HIFU. The study revealed lower complication rate and shorter postoperative hospital stay after laparoscopic procedures compared with rates typical for conventional open surgery. However, favourite oncologic outcomes after laparoscopic liver resection, 51% of 5-year overall survival and 42% of 5-ear disease-free survival, were most important outcome of this thesis. The dissertation also proved both feasibility and efficiency of repeat liver resection. Effective technical solutions in regard to so-called difficult posterosuperior segments represented another secondary point of this thesis. The experimental section of the dissertation defined challenging points of HIFU techniques in regard to liver lesions and suggested efficient solutions to overcome them. List of papers. Papers I, II, III and V are removed from the thesis due to publisher restrictions. Paper I: Kazaryan AM, Marangos IP, Rosseland AR, Røsok BI, Mala T, Villanger O, Mathisen Ø, Giercksky K.E, Edwin B. Laparoscopic liver resection for malignant and benign lesions: 10 year Norwegian single centre experience. Arch Surg. 2010; 145(1): 34-40 doi:10.1001/archsurg.2009.229 Paper II: Kazaryan AM, Marangos IP, Røsok BI, Rosseland AR, Villanger O, Fosse E, Mathisen Ø, Edwin B. Laparoscopic resection of colorectal liver metastases: surgical and long term oncologic outcome. Ann Surg. 2010; 252(6): 1005-1012 doi:10.1097/SLA.0b013e3181f66954 Paper III: Shafaee Z, Kazaryan AM, Marvin M, Cannon R, Buell JF, Edwin B, Gayet B. Is Laparoscopic Repeat Hepatectomy Feasible? A Tri-institutional Analysis. J Am Coll Surg 2011; 212(2):171-9 doi:10.1016/j.jamcollsurg.2010.10.012 Paper IV: Kazaryan AM, Røsok BI, Marangos IP, Rosseland AR, Edwin B. Comparative evaluation of laparoscopic liver resection for posterosuperior and anterolateral segments. Surg. Endosc. 2011; 25(12):3881-9 doi:10.1007/s00464-011-1815-x This article is published with open access at Springerlink.com Paper V: Courivaud F, Kazaryan AM, Lund A, Pavlik Marangos I, Jebsen P, Fosse E, Hol PK, Edwin B. Acute and survival studies of magnet resonance guided high intensity focused ultrasound ablation in the swine liver. Submitted

Background: Laparoscopic resection is not an established treatment for tumors of the pancreas. We report our preliminary experience with this innovative approach to pancreatic disease. Methods: Thirty two patients with pancreatic disease were included in the study on an intention-to-treat basis. The preoperative indications for surgery were as follows: neuroendocrine tumors (n=13), unspecified tumors (n=11), cysts (n=2), idiopathic thrombocytopenic purpura with ectopic spleen (n=2), annular pancreas (n=1), trauma (n=1), aneurysm of the splenic artery (n=1), and adenocarcinoma (n=1). Results: Enucleations (n=7) and distal pancreatectomy with (n=12) and without splenectomy (n=5) were performed. Three patients underwent laparoscopic exploration only. Four procedures (13%) were converted to an open technique. One resection was converted to a hand-assisted procedure. The mortality rate for patients undergoing laparoscopic resection was 8.3% (two of 24). Complications occurred after resection in nine of 24 procedures (38%). The median hospital stay was 5.5 days (range, 2–22). Postoperatively, opioid medication was given for a median of 2 days (range, 0–13). Conclusion: Resection of the pancreas can be performed safely via the laparoscopic approach with all the potential benefits to the patients of minimally invasive surgery.

Cryoablation is a method used for in situ destruction of liver tumors not eligible for surgical resection. Local recurrences following such treatment have been reported at rates of 5–44%. Insufficient procedural monitoring of the ablation is one plausible explanation for these recurrences. The cryoablative procedure is usually monitored by ultrasonography, but acoustic shadowing and loss of signals, compromise visualisation of the cryolesion circumference. Other monitoring modalities such as computer tomography and invasive methods like the use of thermocouples and impedance measurements have also been studied, but are not in common clinical use as single monitoring modalities. Thermodynamic conditions assumed adequate for tumor eradication are likely to occur only in parts of the cryolesion. This tumoricidal part of the cryolesion is not adequately depicted using any of these modalities. Magnetic resonance imaging (MRI) provides a clear delineation of the cryolesion circumference. Noninvasive temperature measurements assisted by MRI indicate which parts of the cryolesion that may be subject to complete necrosis. In this article MRI monitored cryoablation of liver tumors is discussed. Improved peroperative monitoring as offered by MRI may reduce the rates of local recurrences after treatment, but further technological improvements are required.

Background: Freezing is used for in situ destruction (ablation) of liver tumours not eligible for resection. The procedure is typically done during laparotomy. The objective of this report was to study tumour control at the site of freezing and a minimally invasive approach to cryoablation of colorectal liver metastases. Methods: A prospective study of 19 patients was conducted between 1999 and 2003. Twenty‐five tumours were ablated during 24 procedures (i.e. 5 reablations). Sixteen procedures were performed percutaneously, 5 during laparotomy and 3 laparoscopically. Magnetic resonance imaging (MRI) was used for intraprocedural monitoring during most procedures. Nine patients had concomitant liver resections performed (5 during laparoscopy, 4 during laparotomy). Results: Out of 25 ablations, 18 (72%) were assumed adequate. Total ice‐ball volume during percutaneous procedures was median 62 cm ³ (range 32–114). Excellent imaging of the extent of freezing was achieved using MRI. Hospital stay for patients treated percutaneously was median 4 days (range 3–30). No perioperative mortality occurred. Tumour recurrence at the site of ablation occurred in 8 of 18 (44%) tumours adequately ablated. Actuarial 2‐year tumour‐free survival at site of ablation was 48%. At the time of analyses 12 out of 13 (92%) patients assumed to be adequately ablated were alive. Of all patients, 14 out of 19 (74%) survived. Conclusions: Short‐term tumour control can be achieved following cryoablation of colorectal liver metastases. A minimally invasive approach is feasible but the diameter of metastases considered for percutaneous cryoablation should not exceed 3 cm.

Liver resection performed by open surgery is standard treatment in selected patients with liver tumours. Recently, laparoscopic resection of the liver has been reported to be safe, with possible advantages to the patients such as reduced discomfort and shorter hospital stay. In this report we describe our preliminary experience with laparoscopic liver resection. 32 liver resections were performed in 19 patients during 23 procedures; i.e., four patients had repeated resections. Indications were colorectal metastases (15 patients), focal nodular hyperplasia (two patients), liver cyst (one patient) and metastasis from malignant melanoma (one patient). Three left lobectomies were done, the other resections were partial resections. Median duration of surgery was 187 minutes. Perioperative bleeding was median 650 ml. Tumour tissue was found in the resection margin in one patient and in three patients the resection margin was shorter than 1 mm. No procedures were converted to open resection. Median postoperative hospital stay was 3.5 days. Need of opioids were median 1 day. There was no 30 day mortality. Laparoscopic liver resection is safe in selected patients, but randomized trials between open and laparoscopic resections are necessary.

Background: Laparoscopic resection of liver tumors is feasible, but few studies have compared short-term outcome of the laparoscopic approach to that of a conventional technique. Methods: Eighteen tumor resections performed during 14 procedures (14 patients) by conventional surgery were compared to 21 similar resections performed laparoscopically during 15 procedures (13 patients). All patients had colorectal liver metastases. Results: No perioperative mortality occurred. Surgical time, peroperative bleeding and blood transfusion requirement were similar in the two groups. The resection margin was involved by tumor tissue in one specimen laparoscopically resected and in two specimens conventionally resected (p = 0.58). Patients operated laparoscopically remained in hospital for median 4 days, while patients operated conventionally stayed median 8.5 days (p <0.001). Patients operated laparoscopically required less opioid medication than patients having conventional surgery (median 1 vs 5 days; p = 0.001). Conclusions: Short-term outcome of laparoscopic liver resection compares to that of conventional surgery, with the additional benefits derived from minimal invasive therapy.