Miroslav Milicevic

Borderline resectable pancreatic cancer: A consensus statement by the International Study Group of Pancreatic Surgery (ISGPS)

BACKGROUND This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability. METHODS An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer. RESULTS The International Study Group of Pancreatic Surgery (ISGPS) supports the National Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within 1 mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include: (1) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers. CONCLUSION Current evidence justifies portomesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given.

Autologous Infusion of Expanded Mobilized Adult Bone Marrow-Derived CD34+ Cells Into Patients With Alcoholic Liver Cirrhosis

OBJECTIVES: Recent advances in regenerative medicine, including hematopoietic stem cell (HSC) transplantation, have brought hope for patients with severe alcoholic liver cirrhosis (ALC). The aim of this study was to assess the safety and efficacy of administering autologous expanded mobilized adult progenitor CD34+ cells into the hepatic artery of ALC patients and the potential improvement in the liver function.METHODS: Nine patients with biopsy-proven ALC, who had abstained from alcohol for at least 6 months, were recruited into the study. Following granulocyte colony-stimulating factor (G-CSF) mobilization and leukapheresis, the autologous CD34+ cells were expanded in vitro and injected into the hepatic artery. All patients were monitored for side effects, toxicities, and changes in the clinical, hematological, and biochemical parameters.RESULTS: On average, a five-fold expansion in cell number was achieved in vitro, with a mean total nucleated cell count (TNCC) of 2.3 × 108 pre infusion. All patients tolerated the procedure well, and there were no treatment-related side effects or toxicities observed. There were significant decreases in serum bilirubin (P < 0.05) 4, 8, and 12 wk post infusion. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) showed improvement through the study period and were significant (P < 0.05) 1 wk post infusion. The Child-Pugh score improved in 7 out of 9 patients, while 5 patients had improvement in ascites on imaging.CONCLUSION: It is safe to mobilize, expand, and reinfuse autologous CD34+ cells in patients with ALC. The clinical and biochemical improvement in the study group is encouraging and warrants further clinical trials.

Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: A consensus statement by the International Study Group on Pancreatic Surgery (ISGPS)

BACKGROUND The lymph node (Ln) status of patients with resectable pancreatic ductal adenocarcinoma is an important predictor of survival. The survival benefit of extended lymphadenectomy during pancreatectomy is, however, disputed, and there is no true definition of the optimal extent of the lymphadenectomy. The aim of this study was to formulate a definition for standard lymphadenectomy during pancreatectomy. METHODS During a consensus meeting of the International Study Group on Pancreatic Surgery, pancreatic surgeons formulated a consensus statement based on available literature and their experience. RESULTS The nomenclature of the Japanese Pancreas Society was accepted by all participants. Extended lymphadenectomy during pancreatoduodenectomy with resection of Lns along the left side of the superior mesenteric artery (SMA) and around the celiac trunk, splenic artery, or left gastric artery showed no survival benefit compared with a standard lymphadenectomy. No level I evidence was available on prognostic impact of positive para-aortic Lns. Consensus was reached on selectively removing suspected Lns outside the resection area for frozen section. No consensus was reached on continuing or terminating resection in cases where these nodes were positive. CONCLUSION Extended lymphadenectomy cannot be recommended. Standard lymphadenectomy for pancreatoduodenectomy should strive to resect Ln stations no. 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b. For cancers of the body and tail of the pancreas, removal of stations 10, 11, and 18 is standard. Furthermore, lymphadenectomy is important for adequate nodal staging. Both pancreatic resection in relatively fit patients or nonresectional palliative treatment were accepted as acceptable treatment in cases of positive Lns outside the resection plane. This consensus statement could serve as a guide for surgeons and researchers in future directives and new clinical studies.

Changing concepts in the management of liver hydatid disease.

Hydatid disease is a rare entity primarily affecting the population of developing countries. The parasite shuttles between the liver and lungs. but almost any organ can be invaded, forming cysts. Septation and calcification of the cysts with a high antibody titre in the patient’s serum confirm the diagnosis, although more sophisticated tests have been applied recently. Surgery constitutes the primary treatment, with a variety of techniques based on the principles of eradication and elimination of recurrence by means of spillage avoidance. Minimally invasive techniques and percutaneous drainage of the cysts are now feasible because of progress in the field. The aim of this review is to collect the experience from three different institutions and to provide practical guidelines for diagnostic and therapeutic strategies.

When to perform a pancreatoduodenectomy in the absence of positive histology? A consensus statement by the International Study Group of Pancreatic Surgery

BACKGROUND Pancreatoduodenectomy (PD) provides the best chance for cure in the treatment of patients with localized pancreatic head cancer. In patients with a suspected, clinically resectable pancreatic head malignancy, the need for histologic confirmation before proceeding with PD has not historically been required, but remains controversial. METHODS An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature and worked together to establish a consensus on when to perform a PD in the absence of positive histology. RESULTS The incidence of benign disease after PD for a presumed malignancy is 5-13%. Diagnosis by endoscopic cholangiopancreatography brushings and percutaneous fine-needle aspiration are highly specific, but poorly sensitive. Aspiration biopsy guided by endoscopic ultrasonography (EUS) has greater sensitivity, but it is highly operator dependent and increases expense. The incidence of autoimmune pancreatitis (AIP) in the benign resected specimens is 30-43%. EUS-guided Trucut biopsy, serum levels of immunoglobulin G4, and HISORt (Histology, Imaging, Serology, Other organ involvement, and Response to therapy) are used for diagnosis. If AIP is suspected but not confirmed, the response to a short course of steroids is helpful for diagnosis. CONCLUSION In the presence of a solid mass suspicious for malignancy, consensus was reached that biopsy proof is not required before proceeding with resection. Confirmation of malignancy, however, is mandatory for patients with borderline resectable disease to be treated with neoadjuvant therapy before exploration for resection. When a diagnosis of AIP is highly suspected, a biopsy is recommended, and a short course of steroid treatment should be considered if the biopsy does not reveal features suspicious for malignancy.

Prevalence and clinicopathologic features of multiple squamous cell carcinoma of the esophagus

Background. The occurrence of independent synchronous esophageal carcinoma in patients with grossly invasive esophageal cancer (GEC) is well known. Although multiple primary carcinoma of the esophagus is not uncommon, the exact prevalence is controversial, and its clinicopathologic features remain relatively unknown.

Liver Resection With a New Multiprobe Bipolar Radiofrequency Device

HYPOTHESIS Liver resection can be associated with marked blood loss. A novel multiprobe bipolar radiofrequency device (Habib 4X; RITA Medical Systems Inc, Fremont, California) has been developed to assist in liver resection and to reduce intraoperative blood loss. DESIGN Prospective study. SETTING Tertiary referral unit. PATIENTS Sixty-two patients requiring liver resection between November 1, 2004, and February 28, 2006, primarily for metastatic cancer. INTERVENTION Liver resection with the radiofrequency device. MAIN OUTCOME MEASURES Intraoperative blood loss, liver parenchyma transection time, and complications. RESULTS There were 51 minor and 11 major hepatectomies. Mean (SD) transection time was 39 (27) seconds per square centimeter. Mean (SD) blood loss was 4.8 (5.6) mL per square centimeter. No patient required hepatic inflow occlusion. One patient required blood transfusion. There were no deaths, and the morbidity rate was 18%. Mean (SD) hospital stay was 8 (3) days. CONCLUSIONS This new bipolar radiofrequency device allows minor and major hepatectomies to be performed with minimal blood loss, low blood transfusion requirement, and reduced mortality and morbidity rates.

Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial.

BACKGROUND The treatment of cancer patients with mistletoe extract is said to prolong their survival and, above all, improve their quality of life. We studied whether the quality of life of patients with advanced pancreatic cancer could be improved by mistletoe extract. METHOD An open, single-center, group-sequential, randomized phase III trial (ISRCTN70760582) was conducted. From January 2009 to December 2010, 220 patients with locally advanced or metastatic pancreatic cancer who were receiving no further treatment for pancreatic cancer other than best supportive care were included in this trial. They were stratified by prognosis and randomly allocated either to a group that received mistletoe treatment or to one that did not. Mistletoe extract was given in escalating doses by subcutaneous injection three times a week. The planned interim evaluation of data from 220 patients indicated that mistletoe treatment was associated with longer overall survival, and the trial was terminated prematurely. After termination of the study, the results with respect to quality of life (assessed with the QLO-C30 scales of the European Organisation for Research and Treatment of Cancer) and trends in body weight were evaluated. RESULTS Data on quality of life and body weight were obtained from 96 patients treated with mistletoe and 72 control patients. Those treated with mistletoe did better on all 6 functional scales and on 7 of 9 symptom scales, including pain (95% confidence interval [CI] -29 to -17), fatigue (95% CI -36.1 to -25.0), appetite loss (95% CI -51 to -36.7), and insomnia (95% CI -45.8 to -28.6). This is reflected by the trend in body weight during the trial. CONCLUSION In patients with locally advanced or metastatic pancreatic carcinoma, mistletoe treatment significantly improves the quality of life in comparison to best supportive care alone. Mistletoe is an effective second-line treatment for this disease.The recent advances in oncology are plainly evident: more than half of all persons with cancer in Germany now survive their illness and are considered cured (1). Many types of cancer can be kept under control for a long period and converted into a disease with a chronic course and an acceptable quality of life (2). Unfortunately, some cancers still regularly lead to the death of the patient within a short time. Superficially considered, these diseases may seem to be a matter of fate that cannot be influenced by any type of treatment. In fact, however, physicians have many options at hand when treating patients nearing their lifes end, and there are many medical decisions to be taken. Pancreatic carcinoma is nearly always fatal; yet, even for this disease, further treatments have recently become available. New therapeutic approaches prolong survival and improve the manifestations of the disease and the patients? overall quality of life (3).

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.