Histopathological findings in colorectal liver metastases after electrochemotherapy.

Electrochemotherapy of colorectal liver metastases has been proven to be feasible, safe and effective in a phase I/II study. In that study, a specific group of patients underwent two-stage operation, and the detailed histopathological evaluation of the resected tumors is presented here. Regressive changes in electrochemotherapy-treated liver metastases were evaluated after the second operation (in 8-10 weeks) in 7 patients and 13 metastases when the treated metastases were resected. Macroscopic and microscopic changes were analyzed. Electrochemotherapy induced coagulation necrosis in the treated area encompassing both tumor and a narrow band of normal tissue. The area became necrotic, encapsulated in a fibrous envelope while preserving the functionality of most of the vessels larger than 5 mm in diameter and a large proportion of biliary structures, but the smaller blood vessels displayed various levels of damage. At the time of observation, 8-10 weeks after electrochemotherapy, regenerative changes were already seen in the peripheral parts of the treated area. This study demonstrates regressive changes in the whole electrochemotherapy-treated area of the liver. Further evidence of disruption of vessels less than 5 mm in diameter and preservation of the larger vessels by electrochemotherapy is provided. These findings are important because electrochemotherapy has been indicated for the therapy of metastases near major blood vessels in the liver to provide a safe approach with good antitumor efficacy.

Intraoperative electrochemotherapy of colorectal liver metastases.

BACKGROUND AND OBJECTIVES: Electrochemotherapy is effective in treatment of various cutaneous tumors and could be translated into treatment of deep-seated tumors. With this aim a prospective pilot study was conducted to evaluate feasibility, safety, and efficacy of intraoperative electrochemotherapy in the treatment of colorectal liver metastases. METHODS: Electrochemotherapy with bleomycin was performed during open surgery, by insertion of long needle electrodes into and around the tumor according to the individualized pretreatment plan. RESULTS: A 29 metastases in 16 patients were treated in 16 electrochemotherapy sessions. No immediate (intraoperative) and/or postoperative serious adverse events related to electrochemotherapy were observed. Radiological evaluation of all the treated metastases showed 85% complete responses and 15% partial responses. In a group of seven patients that underwent a second operation at 6-12 weeks after the first one, during which electrochemotherapy was performed, the histology of resected metastases treated by electrochemotherapy showed less viable tissue (P = 0.001) compared to non-treated ones. CONCLUSIONS: Electrochemotherapy of colorectal liver metastases proved to be feasible, safe, and efficient treatment modality, providing its specific place in difficult to treat metastases, located in the vicinity of major hepatic vessels, not amenable to surgery or radiofrequency ablation.

Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy.

BACKGROUND: Electrochemotherapy treats tumors by combining specific chemotherapeutic drugs with an intracellular target and electric pulses, which increases drug uptake into the tumor cells. Electrochemotherapy has been successfully used for treatment of easily accessible superficial tumor nodules. In this paper, we present the first case of deep-seated tumor electrochemotherapy based on numerical treatment planning. METHODS: The aim of our study was to treat a melanoma metastasis in the thigh of a patient. Treatment planning for electrode positioning and electrical pulse parameters was performed for two different electrode configurations: one with four and another with five long needle electrodes. During the procedure, the four electrode treatment plan was adopted and the patient was treated accordingly by electrochemotherapy with bleomycin. The response to treatment was clinically and radiographically evaluated. Due to a partial response of the treated tumor, the metastasis was surgically removed after 2 months and pathological analysis was performed. RESULTS: A partial response of the tumor to electrochemotherapy was obtained. Histologically, the metastasis showed partial necrosis due to electrochemotherapy, estimated to represent 40-50% of the tumor. Based on the data obtained, we re-evaluated the electrical treatment parameters in order to correlate the treatment plan with the clinical response. Electrode positions in the numerical model were updated according to the actual positions during treatment. We compared the maximum value of the measured electric current with the current predicted by the model and good agreement was obtained. Finally, tumor coverage with an electric field above the reversible threshold was recalculated and determined to be approximately 94%. Therefore, according to the calculations, a small volume of tumor cells remained viable after electrochemotherapy, and these were sufficient for tumor regrowth. CONCLUSIONS: In this, the first reported clinical case, deep-seated melanoma metastasis in the thigh of the patient was treated by electrochemotherapy, according to a treatment plan obtained by numerical modeling and optimization. Although only a partial response was obtained, the presented work demonstrates that treatment of deep-seated tumor nodules by electrochemotherapy is feasible and sets the ground for numerical treatment planning-based electrochemotherapy. TRIAL REGISTRATION: EudraCT:2008-008290-54.

The validity of clinical risk score for patients undergoing liver resection for colorectal metastases.

BACKGROUND/AIMS: The purpose of this study was to examine the validity of the clinical risk score (CRS) for a selection of patients for surgery. METHODOLOGY: In the period of January 1996 to June 2007, 169 patients underwent their first surgical and/or local ablative therapy for CRLM. This study assesses five preoperative prognostic criteria which define the CRS (nodal status of the primary tumor, the disease-free interval, the number of hepatic metastases, the preoperative CEA level, and the size of the largest metastasis). In the present study was analyzed the calculated CRS with respect to patient's postoperative survival. RESULTS: An individual CRS was found to be predictive of survival. CRS stratified into two groups (CRS scores 0-2 and 3-5) were also found to be predictive of survival, with 5-year survival rates of 41% and 13%, respectively. CRS stratified into three groups (CRS scores 0-1; 2-3 and 4-5) were found predictive of survival as well, with 5-year survival rates of 72.7%, 21% and 4.6%, respectively. CONCLUSIONS: Immediate hepatic resection is reasonable in patients with CRS 0 to 1. In patients with CRS 2 to 3, chemotherapy may be required in addition to hepatic resection. In patients with CRS 4 to 5, hepatic resection is probably reasonable only if there is a response to chemotherapy.

Prognostic value of additional pathological variables for long-term survival after curative resection of rectal cancer.

AIM: To evaluate the prognostic value of some pathological variables in rectal cancer survival. METHODS: 247 patients who underwent curative resection of rectal cancer were included in the study. The influence on survival of five pathological variables (histopathological tumor type, histopathological tumor grade differentiation, blood vessel invasion, perineural invasion and lymphatic invasion) was assessed using statistical analyses. RESULTS: Overall 5-year survival was 71.2%. Univariate analysis of all tested variables showed an effect on survival but only the effect of lymphatic invasion was statistically significant. At stages three and four it had a negative effect on survival (P = 0.0212). Lymphatic invasion also significantly affected cancer related survival in multivariate analysis at stages three and four. At lower stages (stage 0, stage 1 and stage 2) multivariate analysis showed a negative effect of perineural invasion on cancer related survival. CONCLUSION: Patients with lymphatic and perineural invasion have a higher risk for rectal cancer related death after curative resection. Examination of these variables should be an important step in detecting patients with a poorer prognosis.

An experimental model of reproducible liver trauma.

The aim of the study was to create an experimental model of reproducible and controllable liver trauma in pigs. The few reported experimental models of liver trauma use the "clamp and crush" mechanism of injury and do not cause reproducible liver injury. In the present study, force was applied through the thoracic wall to mimic a chest injury. Nine pigs were used as experimental animals. In anaesthetised animals, blunt liver trauma was caused with a crossbow using an arrow with a spherical aluminium head as a projectile. Liver injuries of stages II to III according to liver injury scale were inflicted on all the animals. The stage of liver trauma was proportional to the pressure impulse (ratio between the product of the arrow's mass (m) and the velocity (v) and the contact surface area of the arrow (S)). The presented model of controllable liver injury will enable the study of various aspects of liver trauma since the experiment can be designed in such a way to produce a spectrum of liver injuries.

Anatomical basis of the liver hanging maneuver.

BACKGROUND/AIMS: The anterior approach to right hepatectomy using the liver hanging maneuver without liver mobilization claims to be anatomically evaluated. During this procedure a 4 to 6-cm blind dissection between the inferior vena cava and the liver is performed. Short subhepatic veins, entering the inferior vena cava could be torn and a hemorrhage, difficult to control, could occur. METHODOLOGY: On 100 corrosive casts of livers the anterior surface of the inferior vena cava was studied to evaluate the position, diameter and draining area of short subhepatic veins and inferior right hepatic vein. The width of the narrowest point on the planned route of blind dissection was determined. RESULTS: The average value of the narrowest point on the planned route of blind dissection was 8.7+/-2.3mm (range 2-15mm). The ideal angle of dissection being 0 degrees was found in 93% of cases. In 7% we found the angle of 5 degrees toward the right border of inferior vena cava to be the better choice. CONCLUSIONS: Our results show that liver hanging maneuver is a safe procedure. With the dissection in the proposed route the risk of disrupting short subhepatic veins is low (7%).

Congruence between the courses of the biliary ductal and the hepatic arterial systems.

The development of diagnostic methods and new surgical techniques means it is increasingly important to have accurate knowledge of the anatomy of the hepatic arterial and biliary systems, including their variations, at extrahepatic and intrahepatic levels. The aim of this study was to determine how often the biliary and arterial systems run together and branch in the same pattern. Fifty corrosion casts of the liver were used to analyse the origin and branching patterns of arteries and the confluences of bile ducts. In addition, both systems were analysed to determine the frequency of normal arrangements and variations. The congruence of the course of both systems was analysed at the porta hepatis and in the left and right hemilivers down to the segmental level. A congruent course of the arterial and the biliary systems was identified in 38% of cases at the porta hepatis, in 32% of cases in the left hemiliver and in 30% of the right hemiliver. The congruence of both systems at the porta hepatis and in the left hemiliver was identified only if both systems were normal. In the right hemiliver, however, the congruence of both systems was identified even when both systems were variable, but only in 10% of cases. The results of the study show that, on the basis of knowledge of the course and branching of one system, the other system cannot be predicted.

What have we learned from surgical treatment of gastric adenocarcinoma? A comparison of two periods.

In January 1992, a standardized and more radical surgical approach in gastric cancer treatment and a standardized pathohistological workup of specimens was introduced at our institution. The aim of our retrospectively designed study was to compare the results of two consecutive groups of altogether 348 patients who underwent a total or subtotal gastrectomy for gastric cancer (period A: 162 patients operated between 1992 and 1996; period B: 186 patients operated between 1997 and 2000). The two groups of patients were comparable in age, sex, their general condition, and the proportion of potentially curable (R0) resections. There was a significant difference between the groups with regard to tumor site (fewer distal and more proximal stomach tumors in period B), type of operation (more total gastrectomies in period B), extent of lymphadenectomy (more D2 and D3 in period B), average number of affected lymph nodes (higher in period B), average number of examined nodes (higher in period B), and in UICC stage (less stage II in period B). UICC classification was impossible in 19 patients overall, but there were fewer non-classified patients in period B. The incidence of surgical complications (15.6% vs. 18.7%) and average hospital stay (14.72 days vs. 14.70 days) was not significantly different in the two groups. The drop in overall mortality rate (potentially curable and non-curable resections) in period B almost reached statistical significance (period A: 8%, period B: 6.5%; p = 0.57). The 5-year survival for all R0 resected patients (279) in 9 years was 31%. The median survival was significantly longer in period B (941 days) than in period A (570 days) for R0 and non-curable (R2) resections together (p=0.0132) as well as for R0 resections alone (period A: 844 days, period B: 1176 days; p = 0.0127). Comparison of the two consecutive groups of patients shows that after a defined period of systematic surgical work our results improved, reflected in the higher number of extracted lymph nodes, the higher number of total gastrectomies, and the longer median survival in the second period.

Acute presentation of a solid pseudopapillary tumor of the pancreas.

We report a case of acute presentation of a solid pseudopapillary tumor of the pancreas in a young boy who had suffered a blunt abdominal trauma. Urgently performed CT examination and repeated ultrasound revealed a subhepatic mass, which gradually increased in size, but the imaging features were not specific enough to permit a precise diagnosis. Because signs of peritoneal irritation and increased circulatory instability gradually developed within the hours of observation, the decision was made to perform an urgent exploratory laparotomy. The exploration revealed a hematoperitoneum and a large hematoma-like subhepatic bleeding mass. Further exploration showed that this mass was a tumor arising from the head of the pancreas, which had ruptured on the surface. A curative pancreatoduodenectomy was performed. Pathohistological examination of the resected specimen revealed a solid pseudopapillary tumor of the pancreas, an extremely rare tumor predominantly occurring in adolescent girls and in young adult women. It has a favorable prognosis if resected radically. The boy in our report is feeling well 36 months after the operation.

Urgent Whipple resection for solid pseudopapillary tumor of the pancreas.

We report a 14-year-old boy who was urgently transferred to our institution after a blunt abdominal trauma. CT scan and repeated ultrasound examinations revealed a subhepatic mass, which slowly increased in size. Imaging features were not specific enough to permit a precise diagnosis. Because of the positive peritoneal signs and increased signs of circulatory instability, the decision was made to perform an urgent explorative laparotomy. The exploration revealed that the large haematoma-like bleeding mass was a tumor arising from the head of the pancreas, which ruptured on the surface. We performed a curative R0 Whipple resection. Histology of the resected specimen revealed a solid pseudopapillary tumor of the pancreas, an extremely rare tumor predominantly occurring in young and middle-aged women. It has a favorable prognosis if resected radically. The boy is well 30 months after the operation. To our knowledge, there are only two other descriptions of pancreatic solid pseudopapillary tumor in boys treated urgently by Whipple resection because of acute presentation after blunt abdominal trauma.

Anatomical variations of the right hepatic veins and their relevance to surgery.

BACKGROUND/AIMS: In a morphological study of the right hepatic veins anatomical characteristics of surgical importance were looked for. METHODOLOGY: 110 cadaveric human livers were prepared by the corrosion casts method. The confluence patterns of the superior right hepatic vein, the hepatocaval confluence, the accessory right hepatic veins and the anastomoses between hepatic veins in the right hemiliver were examined. RESULTS: Four types of the superior right hepatic vein, based on the length of its trunk and the confluence pattern of its main tributaries were determined and their frequency was calculated. Type I was found in 20%, type II in 40%, type III in 25% and type IV in 15%. Accessory right hepatic veins with a minimal caliber of 0.4 cm, which were always present in type IV, were also found in other types, all together in 27% of the casts. The tributary-free part of the superior right hepatic vein at hepatocaval confluence was longer than 1 cm in 77%. In the right hemiliver 109 anastomoses were found in 29/110 liver casts. CONCLUSIONS: Knowing the characteristics of different superior right hepatic vein types and of the accessory right hepatic veins may be useful in segment-oriented liver resections and in right side living donor resections.

Follicular lymphoma of the gallbladder and extrahepatic bile ducts.

We report a case of a 63-year-old female, who presented with symptoms and signs of an acute biliary tract obstruction with jaundice and pain. Ultrasound together with intraoperative examination suggested a Klatskin tumour. Following radical resection, a tumour located predominantly in the wall of gallbladder, but infiltrating extensively also the walls of cystic, common hepatic and choledochus duct, was found. On the basis of cell morphology and the results of immunohistochemical analysis, the tumour was classified as an extranodal follicular lymphoma, grade II of the gallbladder, involving also hilar extrahepatic bile ducts. To the best of our knowledge, this is the first report of an extranodal follicular lymphoma in this location. A postoperative follow-up of more than 3 years has been completely uneventful without any symptoms or signs of disease recurrence.

Reconstruction of the main portal vein for a large saccular aneurysm.

BACKGROUND: A large aneurysm of the main portal vein is rare, and the appropriate surgical procedure is uncertain. Reconstruction of a main portal vein affected by a large saccular aneurysm is described. CASE OUTLINE: Abdominal pain led to the diagnosis of a large saccular aneurysm of the main portal vein in a 58-year-old woman who had undergone cholecystectomy 10 years earlier. At laparotomy a dorsolateral approach to the hepatoduodenal ligament was performed with no attempt at extensive separate exposure of the anatomical structures in the hepatoduodenal ligament, so as to avoid the devascularisation of the common hepatic duct and additional weakening of the portal vein wall. The aneurysm was longitudinally incised, and the portal vein was reconstructed from the walls of the aneurysm with a longitudinal running suture. The rest of the aneurysmal wall was wrapped around the portal vein, leaving it normal in size and contour. Recovery was uneventful. Follow-up CT scan showed a patent portal vein in the region of the former aneurysm. DISCUSSION: Large saccular aneurysms can rupture, bleed and cause death. The potential hazards of manipulation of large portal vein aneurysms are negligible in comparison with the possible complications of the aneurysm itself. In our opinion the ease with which the main portal vein was dissected and reconstructed make an elective operation in such cases a reasonable approach.

Anatomical variations of the cystic artery.

Thorough knowledge about the origin of the cystic artery is surgically important, especially when intraoperative or post-operative bleeding occurs in the gallbladder fossa. The arterial supply of the gallbladder was studied in 81 livers. The gallbladder was supplied by one cystic artery in 86% and by two arteries in 14% of cases. When a single artery was present, it originated from the right hepatic artery in 53% of livers. Other origins included the anterior or the posterior sectional hepatic artery, the replacing right hepatic artery, and in 5% of cases, segmental arteries for segments 4, 5, 6 and 8. When two cystic arteries supplied the gallbladder, both most commonly originated from the right hepatic artery (7% incidence). In 1% of cases, a subsegmental branch for segment 6 and a subsegmental branch for segment 5 respectively, originated from the cystic artery.

Anatomical variations of the arterial pattern in the right hemiliver.

The arterial supply to the right hemiliver was studied in 80 liver casts. The arteries were divided into 10 groups according to their origin and branching pattern. The right hemiliver was supplied by one artery in 96% of cases and by two arteries in 4%. When there was only one artery it originated from the proper hepatic artery in 73/77 cases and from the superior mesenteric artery in 4/77 cases. The replacing right hepatic artery which originated from the superior mesenteric vessel supplied the whole right hemiliver in 5% of cases. The incomplete replacing right hepatic artery which supplied only a part of the right hemiliver was found in 4% of cases. The anterior section (segments 5 and 8) was supplied by one artery in 61%, by two arteries in 30% and by three arteries in 9% of cases. The posterior section (segments 6 and 7) was supplied by one artery in 66%, by two arteries in 31% and by three arteries in 3% of cases. Segments 5 and 7 were predominantly supplied by one artery, whereas segments 6 and 8 by two arteries.

Anatomical variations of the arterial pattern in the left hemiliver.

The arterial supply to the left hemiliver was studied in 70 liver casts. The arteries were divided into 15 groups according to their origin and branching pattern. The left hemiliver was supplied by one artery in 53% of cases, by two arteries in 40% and by three arteries in 7%. The left hepatic artery, which originated from the proper hepatic artery, supplied all three left segments in 39% of specimens. The replacing left hepatic artery, which originated from the left gastric artery, supplied the whole left hemiliver in 3% of cases. The incomplete, replacing left hepatic artery supplied segments 2, 3 and a part of segment 4 in 6% of cases, and only segments 2 and 3 in 11%. There was one segmental artery for segment 2 in 86%, and two in 14%. Segment 3 was supplied by one artery in 87%, and by two in 13%. Segment 4 was supplied by one artery in 39% of cases, by two arteries in 43%, by three in 14% and by four arteries in 4%.

Surgical anatomy of hepatoduodenal ligament and hepatic hilus.

The anatomical situation and variations of structures in the hepatoduodenal ligament and hepatic hilus are a legacy of their embryological development. The vascular, biliary, and lymphatic structures contribute to the functioning of blood and bile flow as well as lymph drainage of the liver. Connective tissue, fatty tissue, and the peritoneal sheet are enveloping underlying structures. Their position, shape, and relation to neighboring structures influence the situation during operative procedures. The cystic artery origin is variable, as is the number; and its recognition is important for safe cholecystectomy. Venous drainage of the gallbladder goes into the portal system of adjacent segments 4 and 5 and influences the spread of gallbladder pathology. There are some surgically important variations in the course and distribution of bile ducts and arteries in the hepatoduodenal ligament. The biliary anatomical variations significantly influence the incidence of bile ducts injuries during laparoscopic cholecystectomy. The arterial supply of extrahepatic bile ducts is delicate and variable and should be considered when trying to prevent ischemic injuries to the bile ducts. Inflammation and the combination of inflammation and anatomical variation are thought to contribute to a dangerous situation in regard to eventual injury to the bile ducts and vascular structures during operative procedures. This paper explores these questions.