Tissue injury of the remnant liver following radiofrequency-assisted partial hepatectomy.

PURPOSE: To evaluate remnant liver tissue damage in a pig model of radiofrequency (RF)-assisted liver resection employing either the sequential coagulate cut (SCC) Belgrade technique using a monopolar RF electrode or the one using the bipolar Habib-4x device. METHODS: Sixteen pigs underwent either a) resection of part of the left lateral and left median hepatic lobes employing the SCC (SCC group), the Habib-4X (H group) or the "crushclamp" technique (CC group) or b) sham operation (Sham group). Forty-eight hours later, tissue specimens were excised from the right lateral hepatic lobe for histopathological examination and immunohistochemical assessment of tissue injury, mitosis and inflammation. RESULTS: Histopathologic lesions, apoptotic activity, HSP 40 and TNFα expression were more intense, while mitotic activity was less prominent in the SCC group technique compared to H group. Comparison between CC and H groups suggested the pivotal role of partial hepatectomy (PH) per se in the changes noted in H group. CONCLUSION: The Habib-4X liver resection technique proved to be less injurious in the remnant liver tissue after PH compared to the SCC technique.

Is there any benefit from expanding the criteria for the resection of hepatocellular carcinoma in cirrhotic liver? Experience from a developing country.

BACKGROUND: Patients with large-size (>10 cm) hepatocellular carcinoma (HCC) in Child B cirrhosis are usually excluded from curative treatment, i.e., hepatic resection, because of marginal liver function and poor outcome. This study was designed to evaluate the feasibility of the radiofrequency (RF)-assisted sequential "coagulate-cut liver resection technique" in expanding the criteria for resection of large HCC in cirrhotic livers with impaired liver function. METHODS: Forty patients with Child-Pugh A or B cirrhosis underwent liver resection from December 1, 2001 to December 31, 2008. Of these, 20 patients (13 Child-Pugh A and 7 Child-Pugh B) with advanced stage HCC (stage B and C according to Barcelona-Clinic Liver Cancer Group) underwent major liver resection. The two groups were comparable in terms of patient age, liver cirrhosis etiology, tumor number, and size. RESULTS: All resections were performed without the Pringle maneuver. There was no significant difference found between the two groups regarding resection time, perioperative transfusion, postoperative complications, hospital stay, and day 7 values of hemoglobin and liver enzymes. Likewise, there was no significant difference found in the overall survival between Child A and Child B patients who underwent major liver resection CONCLUSIONS: RF-assisted sequentional "coagulate-cut liver resection technique" may be a viable alternative for management of patients with advanced HCC in cirrhotic liver with impaired function.

Impact of diseased liver parenchyma on perioperative outcome among patients with hepatocellular carcinoma undergoing hepatectomy: Experience from a developing country.

INTRODUCTION: Limited data can be found about surgical outcome of patients with hepatocellular carcinoma (HCC) arising in non-diseased liver. The study aim was to compare short- and long-term outcomes among HCC patients with normal and diseased liver parenchyma, undergoing potentially curative liver resection in a developing country. MATERIALS AND METHODS: From November 2001 until January 2017, 228 patients with HCC underwent curative-intent hepatectomy at the University Clinic for Digestive Surgery. From that number, 190 patients were eligible for analysis. Diseased liver (DL) was present in 112 patients while 78 patients had HCC in non-diseased liver (NDL). RESULTS: Median age, sex, ASA score, the presence of extrahepatic disease and lobar distribution of tumors were similar in both groups. The number of tumors was higher in DL group, while tumor diameter was higher in NDL group. Anatomic liver resection and major liver resections were performed more commonly in NDL than in DL group (66.7 vs 47.4%, p = 0.008; 33.3 vs. 15.2%, p = 0.003). Postoperative morbidity was significantly higher in DL group (p = 0.004). Overall survival was statistically longer in NDL group (p = 0.024). By univariate analysis potential prognostic factors for long-term survival were identified: presence of chronic HCV infection, presence of cirrhosis, Child-Pugh score B and operative time longer than 240 min. The last two were confirmed by multivariate analysis as independent negative prognostic factors for overall survival. CONCLUSION: Liver resection in patients with HCC arising in non-diseased livers, despite of need for extended hepatectomies, provides favorable long-term prognosis.

Weight-centric pharmacological management of type 2 diabetes mellitus - An essential component of cardiovascular disease prevention.

Obesity and overweight are contributing factors for diseases such as type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, and ultimately, cardiovascular (CV) disease. Obesity is imposing an increasing health burden in rich and poor nations, with almost 30% of people globally now either obese or overweight - a staggering 2.1 billion. The link between obesity and T2DM is widely held to involve two adverse effects: obesity-induced insulin resistance and ß-cell failure. This "unified field theory" raises questions about whether defects favoring progressive weight gain and metabolic impairment also contribute to ß-cell decompensation. The concept of weight-centric management of T2DM is considered justified because of the strong negative impact of obesity on the effects of treatment of diabetes. Two pharmacotherapy options are considered: drugs developed primarily for blood glucose control that also exert a favorable effect on body weight and drugs developed primarily to induce weight loss that also have a favorable effect on glycemia. Treating hunger counter-regulatory mechanisms will have an additional effect on glucose control in T2DM. This narrative review addresses advances in pharmacotherapy for the management of obesity and obesity-related co-morbidities, with a focus on T2DM. It is also important to identify the correct balance between weight-centric and glucose-centric management of T2DM.

Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative-intent surgery for hepatocellular carcinoma: experience from a developing country.

PURPOSE: The aim of the study was to evaluate a prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) on long-term survival of cirrhotic and noncirrhotic hepatocellular cancer (HCC) patients managed by a curative-intent liver surgery in a developing country. PATIENTS AND METHODS: During the study period between November 1, 2001, and December 31, 2012, 109 patients underwent potentially curative hepatectomy for HCC. Data were retrospectively reviewed from the prospectively collected database. The median follow-up was 25 months. NLR was estimated by dividing an absolute neutrophil count by an absolute lymphocyte count from the differential blood count. Receiver operating characteristic curve was constructed to assess the ability of NLR to predict long-term outcomes and to determine an optimal cutoff value for all patients group, the subgroup with cirrhosis, and the subgroup without cirrhosis. The optimal cutoff values were 1.28, 1.28, and 2.09, respectively. RESULTS: The overall 3- and 5-year survival rates were 49% and 45%, respectively, for low NLR group and 38% and 26%, respectively, for high NLR group. The difference was statistically significant (p=0.015). Overall survival was similar between low and high NLR groups in patients with cirrhosis; no difference was found between the groups (p=0.124). In patients without cirrhosis, low NLR group had longer overall survival compared with high NLR group (p=0.015). Univariate analysis identified four factors as significant predictors of long-term survival: cirrhosis, Child-Pugh score, platelet count, and NLR. On multivariate analysis, only platelet count and NLR were independent prognostic factors of long-term survival. CONCLUSION: Prognostic value of NLR was confirmed in noncirrhotic HCC patients who underwent curative-intent liver surgery. In HCC patients with cirrhosis, the prognostic role of NLR was not confirmed.

Microscopic assessment of the tissue-sparing potential of radiofrequency-assisted liver resection techniques in a porcine model.

BACKGROUND: The aim of the present study was to microscopically assess the tissue-sparing potential of contemporary radiofrequency-assisted liver resection (RF-LR) techniques. METHODS: Twenty-four pigs were subjected to either (1) partial hepatectomy (PH) using the sequential-coagulate-cut (SCC) technique (group SCC, n = 6) using a monopolar electrode, the technique using the bipolar electrode Habib-4X (group H, n = 6) or the "crush-clamp" technique (group CC, n = 6); or (2) sham operation (group Sham, n = 6). At 48 h post-operation, liver parenchyma proximal to the ablation rim was excised for histopathologic examination and immunohistochemical assessment of apoptosis (antibody M30) and inflammatory response (antibodies IL-6, TNFα and NFκB). RESULTS: Histopathologic index increased from the 1st to the 4th , the 1st to the 2nd or only the 1st cm from the inner margin of the ablation rim in group SCC, H or CC, respectively. The index was higher in group SCC compared to the other groups. Tissue expression of M30, IL-6, TNFα and NFκB increased in all PH groups, being higher and more expanded in group SCC, H, SCC and SCC, respectively. CONCLUSIONS: RF-LR techniques had variable microscopically assessed tissue-sparing effect. The Habib-4X proved to be less injurious compared to the SCC Belgrade technique regarding the severity and extent of tissue damage proximal to the ablation rim.

Hepatocellular carcinoma: From clinical practice to evidence-based treatment protocols.

Hepatocellular carcinoma (HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide, HCC is a leading cause of cancer-related deaths, as it is the fifth most common cancer and the third most important cause of cancer related death in men. Among various risk factors the two are prevailing: viral hepatitis, namely chronic hepatitis C virus is a well-established risk factor contributing to the rising incidence of HCC. The epidemic of obesity and the metabolic syndrome, not only in the United States but also in Asia, tend to become the leading cause of the long-term rise in the HCC incidence. Today, the diagnosis of HCC is established within the national surveillance programs in developed countries while the diagnosis of symptomatic, advanced stage disease still remains the characteristic of underdeveloped countries. Although many different staging systems have been developed and evaluated the Barcelona-Clinic Liver Cancer staging system has emerged as the most useful to guide HCC treatment. Treatment allocation should be decided by a multidisciplinary board involving hepatologists, pathologists, radiologists, liver surgeons and oncologists guided by personalized -based medicine. This approach is important not only to balance between different oncologic treatments strategies but also due to the complexity of the disease (chronic liver disease and the cancer) and due to the large number of potentially efficient therapies. Careful patient selection and a tailored treatment modality for every patient, either potentially curative (surgical treatment and tumor ablation) or palliative (transarterial therapy, radioembolization and medical treatment, i.e., sorafenib) is mandatory to achieve the best treatment outcome.

Jaundice after Billroth II resection. A case report.

Ultrasonography is the first line imaging investigation in patients with jaundice, right upper quadrant pain, or hepatomegaly. Most patients with jaundice have parenchymal or obstructive jaundice. A 56-year old man was admitted to the Institute of Digestive Diseases, Belgrade, with severe pains in the epigastrium, vomiting, icteric coloration of sclera, white stools and dark urine. The symptoms had developed 5 days after a Billroth II resection. The functional liver test indicated a pronounced cholestasis. Real-time ultrasonography showed in the projection of the pancreas head, a clear bordered unechogenic oval formation, with a size of 40 x 35 mm. This finding indicated a possibility of an afferent loop obstruction, accompanied by consecutive obstructive icterus due to compression on the common bile duct. Ultrasonographic examination was followed by surgical reintervention. With the development of noninvasive imaging, transcutaneous ultrasonography, computed tomography and magnetic resonance imaging, the diagnosis of pancreatic and other cysts in upper abdomen is usually straightforward. The important ultrasonographic characteristic of empty organs, compared to cysts and pseudocyts, is a change in the morphology and size of organs after a specific time interval. Air bubbles in the organs lumen are like mobile reflectors, and they are an important sign in identifying segments of the gastrointestinal tract.

Heparin-induced thrombocytopenia with iliacofemoropopliteal thrombosis in a patient operated for colorectal carcinoma liver metastases.

We report a case of heparin-induced thrombocytopenia thrombosis (HITT) syndrome in a patient prophylactically treated with low molecular weight heparin. A 66-year-old men underwent radiofrequency-assisted partial liver resection for colorectal carcinoma liver metastases a year-and-a-half after he had been operated for rectal cancer. In the postoperative period, patient was prophilactically treated with reviparin sodium. On the 8th postoperative day, the platelet count decreased by more than 50% without clinical signs of thrombosis. HITT syndrome was suspected on the 19th postoperative day, after iliacofemoropopliteal thrombosis had developed, and related diagnosis was supported by the strongly positive particle gel agglutination technique immunoassay. Heparin was withdrawn and alternative anticoagulant, danaparoid sodium, was introduced in therapeutic doses. Despite delayed recognition, favorable clinical outcome was achieved. HITT syndrome should be considered with priority among the possible causes of thrombocytopenia in a surgical patient on heparin.

Effects of n-3 Fatty Acids Supplementation on Plasma Phospholipids Fatty Acid Composition in Patients with Obstructive Jaundice- a Pilot Study.

Nutritional and immunological status of patients with obstructive jaundice is usually severely altered, with high mortality rates. The n-3 polyunsaturate fatty acids (PUFA), particularly eicosapentaenoic acid (EPA, 20:5 n-3), posess potent immunomodulatory activities. Thus, our aim was to compare the plasma phospholipid fatty acid (FA) composition of these patients with healthy subjects, as well as before and after 7 days preoperative supplementation with high doses of EPA (0.9 g per day) and docosahexaenoic acid (DHA, 22:6 n-3, 0.6 g per day). We found impaired FA status in obstructive jaundice patients, especially EPA, DHA and PUFA, but significantly increased content of total n-3 FA, 22:5 n-3 FA and particularly EPA, which increased more than 3 fold, after 7 days supplementation. In addition, the n6/n3 ratio significantly decreased from 14.24 to 10.24, demonstrating severely improved plasma phospholipid profile in these patients after the intervention.

A radiofrequency-assisted minimal blood loss liver parenchyma dissection technique.

BACKGROUND/AIMS: Intraoperative blood loss is still a major concern for surgeons operating on the liver since it is associated with a significantly higher rate of postoperative complications and shorter long-term survival. An original radiofrequency (RF)-assisted minimal blood loss technique for transecting liver parenchyma is presented. METHODS: In a prospective study, starting November 2001 and ending December 2005, a total of 90 RF-assisted liver resections were done. Pre-cut coagulative desiccation was produced by the Cool-tip (Valleylab, Tyco) water-cooled, single, RF tumor ablation electrode connected to a 480-kHz 200 W generator (Valleylab Cool-tip RF System). Vascular occlusion techniques and low central venous pressure anesthesia were not used. RESULTS: Only 14 (15.5%) patients received blood transfusion (mean transfused blood volume 397 ml; mode 310 ml) and 10 of 14 patients received <310 ml of blood. There was no statistical difference between the patients who underwent major and minor liver resection in frequency of blood transfusion. Blood loss was associated with dense adhesions and difficult liver mobilization and not with liver transection. CONCLUSION: The 'sequential coagulate-cut' RF-assisted liver resection technique is a safe liver transection technique associated with minimal blood loss and it has facilitated tissue-sparing liver resection.

Surgery for colorectal liver metastases: expanding the boundaries but where have all the patients gone.

AIM: To review and discuss the current strategies and controversies in the surgical management of colorectal cancer liver metastases. METHODS: An analysis of indications, contraindications and scoring systems and concepts for expanding the indications for resection are discussed. The findings and discussion are related to our own experience, especially with radiofrequency assisted liver resection for colorectal cancer liver metastases. RESULTS: Resection is the only management strategy that can potentially cure the patient. Certain controversies still exist, such as contraindications for surgery, timing of treatment of synchronous metastases, significance of extra-hepatic disease etc. Strategies that can improve respectability are discussed. Parenchyma oriented, tissue sparing surgery facilitates reresection should it become necessary. CONCLUSION: The management of colorectal cancer liver metastases is still a confusing issue for general oncologists and general surgeons. A multidisciplinary approach that tailors the management strategy to the individual patient is the only option that provides optimal results for patients with advanced disease.

[Surgical treatment of pain in chronic pancreatitis].

INTRODUCTION: The principal indication for surgical intervention in chronic pancreatitis is intractable pain. Depending upon the presence of dilated pancreatic ductal system, pancreatic duct drainage procedures and different kinds of pancreatic resections are applied. OBJECTIVE: The objective of the study was to show the most appropriate procedure to gain the most possible benefits in dependence of type of pathohistological process in chronic pancreatitis. METHOD: Our study included 58 patients with intractable pain caused by chronic pancreatitis of alcoholic genesis. The first group consisted of 30 patients with dilated pancreatic ductal system more than 10 mm. The second group involved 28 patients without dilated pancreatic ductal system. Pain relief, weight gain and glucose tolerance were monitored. RESULTS: All patients of Group I (30) underwent latero-lateral pancreaticojejunal--Puestow operation. 80% of patients had no pain after 6 month, 13.6% had rare pain and 2 patients, i.e. 6.4%, who continued to consume alcohol, had strong pain. Group II consisting of 28 patients was without dilated pancreatic ductal system. This group was subjected to various types of pancreatic resections. Whipple procedure (W) was done in 6 patients, pylorus preserving Whipple (PPW) in 7 cases, and duodenum preserving cephalic pancreatectomy (DPCP) was performed in 15 patients. Generally, 89.2% of patients had no pain 6 month after the operation. An average weight gain was 1.9 kg in W group, 2.8 kg in PPW group and 4.1 kg in DPCP group. Insulin-dependent diabetes was recorded in 66.6% in W group, 57.1% in PPW group and 0% in DPCP group. CONCLUSION: According to our opinion, DPCP may be considered the procedure of choice for surgical treatment of pain in chronic pancreatitis in patients without dilatation of pancreas ductal system because of no serious postoperative metabolic consequences.