ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

BACKGROUND: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). METHODS: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. RESULTS: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. CONCLUSION: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

Irreversible electroporation in a case of pancreatic leiomyosarcoma: a novel weapon versus a rare malignancy?

BACKGROUND: Primary pancreatic leiomyosarcoma is an extremely rare entity that needs high clinical suspicion in order to diagnose it at an early stage. Clinical characteristics, diagnosis, and management still remain challenging and controversial, especially in advanced stages, when tumor invades adjacent vessels and organs or gives distant metastases. CASE PRESENTATION: Herein, we describe a case of a 57-year-old woman suffering from advanced pancreatic leiomyosarcoma with thrombosis of the superior mesenteric vein, as well as liver lesions which were suspicious for metastasis. Multidisciplinary team decided for upfront chemotherapy to assess tumor response. Follow-up imaging after the completion of chemotherapy led tumor board to decide for subsequent surgical exploration. The patient underwent exploratory laparotomy and irreversible electroporation ablation of the pancreatic tumor. Postoperative course was uneventful, and she was discharged 10 days later with a plan to receive adjuvant therapy. To the best of our knowledge, this is the first case of pancreatic leiomyosarcoma ever reported, treated with this novel technique of irreversible electroporation that could be an alternative and feasible way for the management of these rare malignancies. CONCLUSIONS: In conclusion, primary pancreatic leiomyosarcoma is a rare and highly malignant tumor associated with poor prognosis. Nowadays, R0 surgical resection remains the cornerstone treatment, combined with adjuvant and/or neoadjuvant chemotherapy prior to resection. In the advanced setting, when major vessel invasion and distant metastases occur, chemotherapy along with irreversible electroporation ablation could be a helpful and possibly effective modality for the management of this highly aggressive tumor.

Total robotic pancreaticoduodenectomy: a systematic review of the literature.

BACKGROUND: Pancreaticoduodenectomy (PD) is a complex operation with high perioperative morbidity and mortality, even in the highest volume centers. Since the development of the robotic platform, the number of reports on robotic-assisted pancreatic surgery has been on the rise. This article reviews the current state of completely robotic PD. MATERIALS AND METHODS: A systematic literature search was performed including studies published between January 2000 and July 2016 reporting PDs in which all procedural steps (dissection, resection and reconstruction) were performed robotically. RESULTS: Thirteen studies met the inclusion criteria, including a total of 738 patients. Data regarding perioperative outcomes such as operative time, blood loss, mortality, morbidity, conversion and oncologic outcomes were analyzed. No major differences were observed in mortality, morbidity and oncologic parameters, between robotic and non-robotic approaches. However, operative time was longer in robotic PD, whereas the estimated blood loss was lower. The conversion rate to laparotomy was 6.5-7.8%. CONCLUSIONS: Robotic PD is feasible and safe in high-volume institutions, where surgeons are experienced and medical staff are appropriately trained. Randomized controlled trials are required to further investigate outcomes of robotic PD. Additionally, cost analysis and data on long-term oncologic outcomes are needed to evaluate cost-effectiveness of the robotic approach in comparison with the open technique.

Irreversible electroporation (Nanoknife® treatment) in the field of hepatobiliary surgery: Current status and future perspectives.

PURPOSE: We aimed to provide an overview of current understanding on the potential use of irreversible electroporation (IRE) in the field of hepatobiliary surgery with a focus on current results in hepatic and pancreatic cancers, its limitations, and its current directions. METHODS: Through a review of the literature we have gathered the key articles and trials that are shaping our understanding of the current status of IRE and its prospective uses, and organized them in an easily understandable format showcasing the most up to date results. RESULTS: IRE appears to be comparable in effectiveness and postoperative pain to the more established thermal ablation methods, while having the benefit of avoiding their detrimental thermal effects. In liver cancer, IRE was shown to be efficacious with low levels of local recurrences and only minimal complications. In pancreatic cancer it proved to have significant survival benefits but more significant (although rare) complications compared to the ones seen when IRE is used in liver cancer. Current evidence suggests a promising future for IRE, but clinical randomized control trials, and further developments of treatment protocols are required to come to more stable conclusions on the effectiveness and safety of IRE. CONCLUSIONS: IRE is proving to be an adequate method for the treatment of tumors of the pancreas and liver in cases where traditional methods are unavailable. It has been proven particularly efficacious in patients with masses in close proximity to vital structures such as vessels, as well as major biliary and hepatic structures where thermal methods of ablation would cause significant complications.

The ALPPS procedure as a novel "liver-first" approach in treating liver metastases of colon cancer: the first experience in Greek Cypriot area.

BACKGROUND: Despite recent advances in multimodality and multidisciplinary treatment of colorectal liver metastases, many patients suffer from extensive bilobar disease, which prevents the performance of a single procedure due to an insufficient future liver remnant (FLR). We present a novel indication for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as a "liver-first" approach when inadequate FLR was faced preoperatively, in a patient with extensive bilobar liver metastatic disease of colon cancer origin. CASE PRESENTATION: A 51-year-old lady was referred to our center due to a stage IV colon cancer with extensive bilobar liver disease and synchronous colon obstruction. During the multidisciplinary tumor board, it was recommended to proceed first in a palliative loop colostomy (at the level of transverse colon) operation and afterwards to offer her palliative chemotherapy. After seven cycles of chemotherapy, the patient was re-evaluated by CT scans that revealed an excellent response (>30%), but the metastatic liver disease was still considered inoperable. Moreover, with the completion of 12 cycles, the indicated restaging process showed further response. Subsequent to a thorough review by the multidisciplinary team, it was decided to proceed to the ALPPS procedure as a feasible means to perform extensive or bilobar liver resections, combined with a decreased risk of tumor progression in the interim. CONCLUSIONS: All in all, ALPPS can offer a feasible but surgically demanding liver-first approach with satisfactory short-term results in selected patients. Larger studies are mandatory to evaluate short- and long-term results of the procedure on survival, morbidity, and mortality.

Ablation of the locally advanced pancreatic cancer: An introduction and brief summary of techniques.

Pancreatic ductal adenocarcinoma is a lethal and late presenting malignancy with dismal survival rates. An estimated total of 330,000 people died from this malignancy in 2012. Although there have been improvements in diagnostic and treatment methods, the survival of late stage pancreatic cancer has not shown significant improvement in the past 4 decades. Multiple treatment approaches are available including chemotherapy, radiotherapy, and immunotherapy, but to this day surgical resection remains the only curative treatment option. Ablative techniques use various forms of energy to cause local tissue destruction through necrosis or apoptosis. They are relevant in pancreatic ductal adenocarcinoma as they are a treatment option in non-resectable tumors where their use ranges from symptom control to reducing tumor size for resection. In this narrative review we have grouped and outlined the various ablative methods, classifying them into thermal (Radiofrequency ablation, Microwave ablation, High Intensity Focused Ultrasound ablation, Cryoablation), and non-thermal ablative methods (Irreversible Electroporation (NanoKnife®), Photodynamic Therapy). This is followed by a description and review of the available evidence on survival and complications for each of these ablative methods. According to the literature, thermal ablative methods appear to be more accessible but are implicated with more complications than non thermal ablative methods which show the most promise.

The effect of Guidelines in surgical decision making: The paradigm of hepatocellular carcinoma.

It is not inconceivable to envision surgeons, offering extended liver resection in patients beyond the Barcelona Clinic Liver Cancer (BCLC) staging system criteria with intermediate/advanced hepatocellular carcinoma (HCC), to be found negligent since extensive liver resection is correlated with increased morbidity compared to conservative or palliative treatment. Given that no other classification system than BCLC has been adopted widely for HCC staging and treatment, a revision of the BCLC algorithm and clinical guidelines should be tailored using new molecular and clinical treatment algorithms, as well as including patient's preferences.

Prognostic indicators following curative pancreatoduodenectomy for pancreatic carcinoma: A retrospective multivariate analysis of a single centre experience.

PURPOSE: Survival after curative resection of pancreatic, ampullary and lower common bile duct cancer remains very poor. The aim of this study was to assess important prognostic factors in patients with resectable pancreatic cancer. METHODS: From 2006 to 2010, 156 patients underwent pancreatoduodenectomy (PD) for malignancies of pancreatic, ampullary or lower common bile duct in our institution. Based on the inclusion criteria 101 patients were selected in our retrospective statistical analysis. Of these 101 cases of malignancies, 65.4% were located in the pancreatic head, 18.8% in the ampulla and 15.8% in the lower bile duct. 48.5% of patients underwent classical PD, and 51.5% pylorus-preserving pancreatoduodenectomy (PPPD). Clinical and pathological data were collected, Kaplan-Meier method and Cox proportional hazard models were used to evaluate prognostic factors. RESULTS: Multivariate analysis revealed that blood transfusion, vascular invasion, T4 vs T1 stage, and R0 resection margins were significant negative predictors of survival. Conversely, ampullary (vs pancreatic ductal) and adjuvant chemotherapy were significantly associated with longer survival. Lymph node ratio (LNR), in all its forms, was not found to have a significant effect on survival. For all patients, tumor grading (p=0.042), resection margins (p=0.004), T stage (p=0.001), perineural invasion (p=0.029), vascular invasion (p=0.007) and age >65 years (p=0.009) were factors that impacted survival. CONCLUSION: Surgical resection margins, tumor grade, T stage, perineural invasion, vascular invasion, age >65 and adjuvant chemotherapy are the strongest predictors of survival after surgical resection of pancreatic, ampullary and lower common bile duct cancer. In this series, lymph node ratio did not impact survival.

Microwave versus saline-linked radiofrequency (Aquamantys) assisted liver resection in a porcine liver resection model. A safety and feasibility pilot study.

PURPOSE: The aim of this study was to compare the feasibility, efficacy and safety of microwave ablation and saline-linked radiofrequency (Aquamantys) in liver resection. METHODS: Sixteen domestic pigs (8 per group) underwent thermoablations. Group A consisted of 8 pigs in which microwave left lateral liver resection was performed. Group B consisted of 8 pigs which underwent left lateral liver resection by the Aquamantys system. After 28 days of close follow-up, the animals were sacrificed in order to study the macroscopic and microscopic findings of each intervention on the liver edge. RESULTS: An average of 47.13 min was enough for the entire operation to take place using Aquamantys, whereas an average of 59.13 min was needed in the microwave liver resection group. Mean blood loss was 40 ml (range 5-85) with Aquamantys whereas mean blood loss was 72.37 ml (range 42-100) using microwave. Postoperative complications rates were extremely low in both groups. There was no intra- or postoperative mortality. CONCLUSIONS: Our study demonstrated that left lateral liver resection using Aquamantys system is technically feasible in the porcine model and proved to be highly effective and a safer hemostatic method compared to microwave ablation.

The value of calprotectin S100A8/A9 complex as a biomarker in colorectal cancer: A systematic review.

PURPOSE: Associations between inflammation and carcinogenesis have been reported for many years, as originally postulated by Virchow in his studies, but the results from prospective cohort studies remain controversial. We evaluated the role of calprotectin as a biomarker for colorectal cancer (CRC). METHODS: The MEDLINE/PubMed database was thoroughly searched using the keywords: "inflammation", "colorectal cancer, "calprotectin", "carcinogenesis" and/or "biomarkers". We focused on human and animal (rodent) studies of CRC and the role of calprotectin as a new biomarker and its potential value to the diagnosis, follow-up and CRC prognosis. RESULTS: According to the literature, calprotectin seems to be a reliable sensitive marker in the diagnosis and postoperative evaluation of CRC patients at the cost of low specificity and no correlation with the progress and stage of disease. CONCLUSIONS: Calprotectin stands for a novel but well-evaluated biomarker in CRC. The experimental studies focus on the CRC microenvironment and suggest that malignant cells and tissues overexpress S100A8 and S100A9 and the heterodimer S100A8/A9.

Optimization of a green extraction method for the recovery of polyphenols from olive leaf using cyclodextrins and glycerin as co-solvents.

Olive leaf, an agricultural by-product, was studied for the valorization of its biophenols using green extraction techniques; i.e. non-toxic and eco-friendly extraction solvents were used, involving water and glycerol. 2-hydroxypropyl-ß-cyclodextrin (CD), was also employed as an enhancer of the extraction, since cyclodextrins (CD's) are known to improve the extractability of olive leaf polyphenols by forming water soluble inclusion complexes. The process was optimized by implementing a central composite (Box-Behnken) experimental design and response surface methodology, taking into consideration the following independent variables: glycerol concentration (Cgl), CD concentration (CCD) and temperature (T). The evaluation of the extraction model was based on two responses: the total polyphenol yield (YTP) and the antiradical activity (AAR). Optimum values for the extraction process were obtained at 60% (w/v) glycerol content, T = 60 °C and 7% (w/v) CD content. LC-MS analysis was also applied in order to characterize the polyphenolic composition of extracts containing cyclodextrins. The main polyphenols present were oleuropein and oleuropein derivatives. Olive leaf aqueous extracts containing glycerol and cyclodextrins may be used as raw materials/ingredients for several end-users in the food, cosmetic and pharmaceutical industries.

Radiofrequency ablation-assisted liver resection: a step toward bloodless liver resection.

BACKGROUND: Liver resection is currently the most efficient curative approach for a wide variety of liver tumors. The application of modern techniques and new surgical devices has improved operative outcomes. Radiofrequency ablation is used more often for liver parenchymal transection. This study aimed to assess the efficacy and safety of radiofrequency ablation-assisted liver resection. METHODS: A retrospective study of 145 consecutive patients who underwent radiofrequency ablation-assisted liver resection was performed. Intraoperative blood loss, need for transfusion or intraoperative Pringle maneuver, the duration of liver parenchymal transection, perioperative complications, and postoperative morbidity and mortality were all evaluated. RESULTS: Fifty minor and ninety-five major liver resections were performed. The mean intraoperative blood loss was 251 mL, with a transfusion rate of 11.7%. The Pringle maneuver was necessary in 12 patients (8.3%). The mean duration for parenchymal transection was 51.75 minutes. There were 47 patients (32.4%) with postoperative complications. There is no mortality within 30 days after surgery. CONCLUSIONS: Radiofrequency ablation-assisted liver resection permits both major and minor liver resections with minimal blood loss and without occlusion of hepatic inflow. Furthermore it decreases the need for blood transfusion and reduces morbidity and mortality.

Combined ultrasonic aspiration and saline-linked radiofrequency precoagulation: a step toward bloodless liver resection without the need of liver inflow occlusion: analysis of 313 consecutive patients.

BACKGROUND: Hemorrhage is undoubtedly one of the main factors contributing to morbidity and mortality in liver resections. Vascular occlusion techniques are effective in controlling intraoperative bleeding, but they cause liver damage due to ischemia. We evaluated the effectiveness and safety of using a combined technique for hepatic parenchymal transection without liver inflow occlusion. METHODS: Three hundred and thirteen consecutive patients who underwent liver resection in four hepato-pancreato-biliary units. Hepatic parenchymal transection was carried out using a combined technique of saline-linked radiofrequency precoagulation and ultrasonic aspiration without liver inflow occlusion. RESULTS: During the study period 114 minor and 199 major hepatic resections were performed. The mean amount of intraoperative blood loss was 377 ml (SD 335 ml, range 50 to 2,400 ml) and the blood transfusion rate was 10.5%. The median amount of blood loss during parenchymal transection and parenchymal transection time was 222 ml (SD 224 ml, range 40 to 2,100 ml) and 61 minutes (range 12 to 150 minutes) respectively. There were two postoperative deaths (0.6%). Complications occurred in 84 patients (26.8%) and most complications were minor. CONCLUSIONS: Combined technique of saline-linked radiofrequency ablation and ultrasonic aspiration for liver resection is a safe method for both major and minor liver resections. The method is associated with decreased blood loss, reduced postoperative morbidity, and minimal mortality rates. We believe that this combined technique is comparable to other techniques and should be considered as an alternative.

Radiofrequency ablation assisted resection for hepatocellular carcinoma: morbidity, mortality and long term survival.

PURPOSE: Hepatic resection is the mainstay of the curative treatment of primary hepatic tumors, with constantly improving short and long term results. Radiofrequency ablation (RFA)-assisted liver resection is a relatively new method of transection of the liver parenchyma with favorable intra- and perioperative results. The aim of this study was to investigate the oncological efficacy (long term overall survival/OS and disease free survival/DFS) and to confirm the favorable short term morbidity and mortality. METHODS: Between May 2004 and January 2007, 28 patients underwent 32 resections with removal of 50 hepatocellular carcinoma (HCC) lesions. The technique of parenchymal transection has been described previously as RFA-assisted liver resection. RESULTS: Thirty-day morbidity and mortality were 42.8 and 0%, respectively. Blood transfusion was necessary for 28.5% of the patients. The median hospital stay was 16.5 days (range 5-34). The 1- and 3-year OS were 92.9 and 65.7%, respectively. The 1- and 3-year DFS were 62.3 and 54.6- respectively. No patient developed metastatic disease or local recurrence at the margin site. Twelve patients (42.9%) developed in-the-liver recurrence away from the resection area. CONCLUSION: RFA-assisted liver resection is a safe and oncologically efficacious method for the surgical treatment of HCC with results comparable to other surgical techniques.

History of biliary surgery.

Since ancient times biliary surgery has been one of the major interests of doctors and other scientists around the world. From the ancient Greeks and Egyptians to the greatest scientists of modern times biliary surgery has advanced remarkably. Especially during the last century huge progress has been made in this field. Minimally invasive surgical techniques have been developed and combined with general anesthesia and antisepsis that have made biliary surgery particularly safe for every patient and have made cholecystectomy one of the most common operations in the world today.

A pathological fracture and a solitary mass in the right clavicle: an unusual first presentation of HCC and the role of immunohistochemistry.

Hepatocellular carcinoma (HCC) is an aggressive malignant tumor that occurs throughout the world. Μetastases from hepatocellular carcinoma (HCC) were generally considered to be rare in the past, because the carcinoma had an aggressive clinical course. In our era, has been reported that extra-hepatic metastases occur in 13.5%-41.7% of HCC patients and this is considered as terminal-stage cancer. The prognosis for patients at this stage continues to be poor due to limited effective treatment. The common sites of extrahepatic metastases in patients with HCC are the lungs, regional lymph nodes, kidney, bone marrow and adrenals. We present here an extremely infrequent case of a patient, without known liver disease, in which the presenting symptom was a pathological-in retrospect-fracture of his right clavicle which wasn't properly evaluated, until he presented a bulky mass in the region 6 months later. For our patient, the added diagnostic difficulty alongside the unknown liver disease, has been that the clavicular metastases was the first presentation of any metastatic disease, rather than the more common sites of HCC spread to adjacent lung or lymph nodes.

Use of intraoperative endoscopy to localize bleeding in the small intestine.

INTRODUCTION: Bleeding within the small intestine is difficult to diagnose and localize because it typically occurs at a slow rate. These patients may undergo multiple transfusions and repeated endoscopy, contrast studies, bleeding scans, and angiography before the bleeding source is identified. CASE REPORT: We report a case of 64-year-old woman, where both endoscopic and angiographic techniques were used to localize protracted bleeding. During endoscopic treatment, the arteriovenous malformations continued bleeding. However, highly selective angiography and intraoperative endoscopy outlined the segments of small intestine for resection. This case reviews the evaluation, localization and treatment of small intestine bleeding. DISCUSSION: Localizing the site of protracted bleeding in the small intestine beyond the duodenum bulb can be problematic. For some patients, the course of examinations and transfusions can take years. The small intestine is an uncommon site for gastrointestinal hemorrhage, and only 3%-5% of gastrointestinal bleeding occurs between the ligament of Treitz and the ileocecal valve. The length and location of the small intestine, along with other anatomical factors, make this area difficult to assess with endoscopy or radiology. In this case of protracted bleeding, highly selective angiography and intraoperative endoscopy were used to locate the source of the bleeding.

Acute recurrent pancreatitis: a possible clinical manifestation of ampullary cancer.

CONTEXT: Acute recurrent pancreatitis still poses diagnostic difficulties. The coexistence or moreover the causative relationship of carcinoma of the ampulla of Vater and acute recurrent pancreatitis is fairly rare. CASE REPORT: We present a case of carcinoma of the ampulla of Vater that presented with acute recurrent necrotizing pancreatitis complicated with pseudocysts. A diagnosis of malignancy in the ampulla was only made after several ERCP attempts due to residual inflammation at the periampullary area. CONCLUSION: Malignancy at the ampulla of Vater causing recurrent episodes of pancreatitis represents a realistic risk and attempts to diagnose the underlying cause should always take into account the possibility of cancer.

Groove pancreatitis. A mini-series report and review of the literature.

CONTEXT: Groove pancreatitis is a rare condition characterized by fibrotic inflammation affecting the groove anatomical area between the head of the pancreas, the duodenum and the common bile duct. OBJECTIVES: We report a miniseries of five cases treated surgically in our centre over a period of four years. A review of the literature is also discussed. METHODS: Patients undergoing pancreaticoduodenectomy over a four-year period were retrospectively reviewed. Patients with a confirmed histological diagnosis of groove pancreatitis were assessed under the headings; patient demographics, presenting symptoms, radiological and histological findings. RESULTS: One-hundred and 60 pancreaticoduodenectomies were performed. Thirty-nine cases demonstrated benign disease and within this, five cases (3.1% of total series; 12.8% of benign cases) were groove pancreatitis. All patients presented with abdominal pain and weight loss, and the majority consumed excess alcohol and were smokers. Radiological findings (CT/MRCP/EUS) revealed duodenal wall thickening in all cases, abnormalities at the head of pancreas and bile duct dilation in four, and cystic changes in the duodenal wall and pancreatic duct dilation in three cases. Groove fibrosis, Brunner's gland hyperplasia and cystic changes in duodenal wall were present in all cases on histological review. All patients reported significant improvement in quality of life at 12 months after surgery. CONCLUSION: Groove pancreatitis can present in a similar fashion to head of pancreas cancer and chronic pancreatitis. For this reason it is paramount for clinicians to be aware of groove pancreatitis, as this can lead to the correct diagnosis and management of this unique disease.