Unusual Presentation of an Uncommon Malignancy: A 74-Year-Old Woman with Aggressive Fibromatosis of the Large Intestine Presenting as a Liver Mass and the Therapeutic Management.

BACKGROUND Desmoid tumors are a fibroblastic proliferation of soft tissues, with an extreme inclination for local dissemination and recurrence. Surgical excision is the usual treatment choice, with data regarding pharmaceutical treatment being scarce. CASE REPORT A 74-year-old female patient was admitted to "Laikon" General Hospital of Athens, Greece presenting with acute kidney injury secondary to diarrhea. The ultrasound, CT, and abdominal MRI performed showed a 12×6×10 cm tumorous liver lesion. Biopsy of the lesion revealed loosely organized, mesenchymal tissue with spindle cells, and myxoid stroma. Immunochemistry was positive for SMA and b-catenin. Right hemicolectomy was performed with tumor-free surgical margins (R0 resection) and tamoxifen was initiated. Six months after the last MRI (3 months after the use of tamoxifen), a follow-up MRI was performed. The tumor had increased to 14.2×11×12.3 cm, and at the next follow-up it had grown to 20.3×19 cm maximal dimensions; no new metastases were found. The patient received sorafenib and pazopanib. Our patient had PFS with sorafenib for more than 2 years and remained in a good performance status (ECOG 1). For Pazopanid, the median PFS for this treatment option was 6.5 months. CONCLUSIONS The results were good and show a promising method for the treatment of this rare but severe malignancy.

The prognostic significance of Caspase-3 and survivin expression in colorectal cancer patients.

PURPOSE: To investigate the expressions of caspase-3 and survivin in colorectal cancer patients and their possible associations with clinicopathological parameters and the oncological outcome. METHODS: Between January 2008 and December 2011, 85 patients with sporadic colorectal cancer were submitted to colectomy with curative intent. Postoperatively, all patients were followed every three months up to the 36th month. Immunohistochemical detection of the apoptosis-related proteins was carried out on 4-µm-thick deparaffinized sections from all primary tumors. Univariate and multivariate analyses were performed by using the R software for Windows, version 3.3.2. RESULTS: Setting the cut-off point for caspase-3 positivity at 5%, 48% of the patients were characterized as caspase-3(+). Caspase-3 positivity was not found related either to any clinicopathological parameter or to the oncological outcome. Choosing simple survivin positivity as the cut-off point for its expression, 78% of the patients were considered as survivin(+). Survivin inexpression predisposed to poorly differentiated tumors of advanced T stage. However, neither a dismal nor a favorable prognostic role for survivin expression or inexpression was disclosed. By dividing all enrolled patients in four different groups, a trend for worse 3-year overall survival rate in the caspase-3(-)/survivin(-) subgroup of patients was noticed (p=0.067). CONCLUSION: Caspase-3 expression was unrelated to the oncological outcome in colorectal cancer patients. The proposed favorable prognostic role for survivin inexpression was not confirmed. On the contrary, survivin(-) tumors were mainly of poor differentiation and advanced T stage. An inverse relationship between caspase-3 and survivin expressions was also not confirmed. Future studies focusing on specific survivin isoforms expression or inexpression may give answers on apoptotic-antiapoptotic interactions on cancer cell death.

Replication Protein A (RPA1, RPA2 and RPA3) expression in gastric cancer: correlation with clinicopathologic parameters and patients' survival.

PURPOSE: Replication Protein A (RPA) consists of three subunits (RPA1, RPA2 and RPA3) essential for all major DNA metabolic pathways. Although RPA seems to be a promising therapeutic target, its role in human cancers has not been fully elucidated. This is the first study investigating the expression of all the three RPA subunits in a series of 74 resected gastric carcinomas and analyzing the possible correlations with clinicopathologic parameters (histological type, grade, lymphovascular invasion, lymph node status and disease stage), Ki-67 proliferative index, Topoisomerase IIa expression and patients' survival. METHODS: Immunohistochemistry using monoclonal antibodies. Univariate and multivariate statistical analysis. RESULTS: All the three subunits showed widespread nuclear expressions in gastric carcinomas with significant associations among their expressions. RPA2 demonstrated higher expression levels in low grade carcinomas and a gradual significant decrease from N0 to N3 and from stage I to stage IV carcinomas. All the three subunits were statistical significantly more abundant in lymph node negative and earlier stage (stage I & II) gastric carcinomas. No associations were established among RPAs and the proliferative marker Ki-67. In patients with positive lymph nodes and advanced tumor stage, RPA1 expression seemed to predict a better overall survival implying a probable predictive role. CONCLUSIONS: The widespread expression of RPA(1-3) suggests one or more roles in gastric cancer. Their presence in earlier stage tumors probably offers an opportunity for early targeted therapy. Their probable predictive value in node positive and advanced stage tumors needs further investigation with respect to specific chemotherapeutic treatments.

Capecitabine, Oxaliplatin, Irinotecan, and Bevacizumab Combination Followed by Pazopanib Plus Capecitabine Maintenance for High-Grade Gastrointestinal Neuroendocrine Carcinomas.

OBJECTIVES: Gastrointestinal neuroendocrine carcinoma (NEC) is a lethal, uncommon, and understudied neoplasm. We present the efficacy and safety of first-line capecitabine (CP), oxaliplatin, irinotecan, and bevacizumab (CAPOXIRI-BEV) combination followed by pazopanib plus CP maintenance therapy in patients with advanced high-grade poorly differentiated gastrointestinal NEC. METHODS: This was a two-stage phase II study conducted at multiple institutions. Patients were consecutively enrolled and had advanced NEC of the colon or small bowel. Patients received irinotecan 125 mg/m, oxaliplatin 80 mg/m on day 1, CP 1000 mg/m twice daily on days 1 to 14, plus bevacizumab 8 mg/kg on day 1 for six 21-day cycles. Maintenance therapy was given to those who responded (complete response/partial response) or had stable disease after 6 cycles with CAPOXIRI-BEV with pazopanib 800 mg daily plus CP 1600 mg/m daily on days 1 to 14 every 3 weeks until disease progression or unacceptable toxicity. Patients who progressed on CAPOXIRI-BEV received standard etoposide-carboplatin. The primary endpoint was overall response rate. RESULTS: Twenty-two patients were enrolled of whom 19 were evaluable. The median age was 60 years. The overall response rate (3 complete response/6 partial response) was 47.4% (95% confidence interval: 29.5-76.1), the overall disease control rate was 78.9% (95% confidence interval: 62.6-99.6), and, at median 30 (11 to 41 mo) months' follow-up, 5 patients (26.3%) were still alive. Median progression-free survival was 13 months, and the 1-year progression-free survival rate was 52.6%. The median overall survival was 29 months. The median overall survival of the 9 patients who responded versus those with stable disease/progressive disease was 30.5 versus 14 months, respectively. The median duration of response was 16 months. Predictable toxicity was observed. CONCLUSIONS: First-line CAPOXIRI-BEV followed by pazopanib plus CP maintenance therapy for advanced NEC demonstrates promising efficacy and predictable toxicity. Further investigation is warranted.

Harnessing the versatile role of OPG in bone oncology: counterbalancing RANKL and TRAIL signaling and beyond.

More than 2 decades ago, the discovery of osteoprotegerin (OPG) as inhibitor of the receptor of activator of nuclear factor Kb (RANK) ligand (RANKL) revolutionized our understanding of bone biology and oncology. Besides acting as decoy receptor for RANKL, OPG acts as decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). OPG, RANKL, and TRAIL are ubiquitously expressed, stimulating per se pivotal signaling cascades implicated in cancer. In the context of cancer cell-bone cell interactions, cancer cells skew the OPG/RANKL/RANK (RANKL cognate receptor) balance towards bone destruction and tumor growth through favoring the RANKL/RANK interface, circumventing OPG. Numerous preclinical and clinical studies demonstrate the dual role of OPG in cancer: antitumor and tumor-promoting. OPG potentially conveys an antitumor signal through inhibiting the tumor-promoting RANKL signaling-both the osteoclast-dependent and the osteoclast-independent-and the tumor-promoting TRAIL signaling. On the other hand, the presumed tumor-promoting functions of OPG are: (i) abrogation of TRAIL-induced apoptosis of cancer cells; (ii) abrogation of RANKL-induced antitumor immunity; and (iii) stimulation of oncogenic and prometastatic signaling cascades downstream of the interaction of OPG with diverse proteins. The present review dissects the role of OPG in bone oncology. It presents the available preclinical and clinical data sustaining the dual role of OPG in cancer and focuses on the imbalanced RANKL/RANK/OPG interplay in the landmark "vicious cycle" of skeletal metastatic disease, osteosarcoma, and multiple myeloma. Finally, current challenges and future perspectives in exploiting OPG signaling in bone oncology therapeutics are discussed.

Retroperitoneal perivascular epithelioid cell tumours: A case report and review of literature.

BACKGROUND: The perivascular epithelioid cell tumour (PEComa) family of tumours mainly includes renal and hepatic angiomyolipomas, pulmonary lymphangioleiomyomatosis and clear cell "sugar" tumour of the lung. Several uncommon tumours with similar morphological and immunophenotypical characteristics arising at a variety of sites (abdominal cavity, digestive tract, retroperitoneum, skin, soft tissue and bones) are also included in the PEComa family and are referred to as PEComas not otherwise specified. CASE SUMMARY: We present a 37-year-old female patient who underwent resection of an 8.5 cm × 8 cm × 4 cm retroperitoneal tumour, which eventually was diagnosed as PEComa of uncertain biological behaviour. Three years after the operation, the patient remains without any evidence of recurrence. A search was performed in the Medline and EMBASE databases for articles published between 1996 and 2018, and we identified 31 articles related to retroperitoneal and perinephric PEComas. We focused on sex, age, maximum dimension, histological and immunohistochemical characteristics of the tumour, follow-up and long-term outcome. Thirty-four retroperitoneal (including the present one) and ten perinephric PEComas were identified, carrying a malignant potential rate of 44% and 60%, respectively. Nearly half of the potentially malignant PEComas presented with or developed metastases during the course of the disease. CONCLUSION: Retroperitoneal PEComas are not as indolent as they are supposed to be. Radical surgical resection constitutes the treatment of choice for localized disease, while mammalian target of the rapamycin (mTOR) inhibitors constitute the most promising therapy for disseminated disease. The role of mTOR inhibitors as adjuvant or neoadjuvant therapies needs to be evaluated in the future.

Emergency inguinal hernioplasties in a tertiary public Hospital in Athens Greece, during the economic crisis.

BACKGROUND: Although the effect of the recent Greek economic crisis and austerity on the population's health and the health system effectiveness have been discussed a lot recently, data on common surgical conditions affecting large part of the population are missing. Using inguinal hernia as a model we investigated possible changes of citizens' attitude regarding the time of referral, the perioperative details and the intraoperative findings of the emergency hernioplasties. METHODS: The present retrospective study was conducted by a Department of Surgery in a tertiary public hospital of the Greek capital. We reviewed the records of all hernioplasties performed during two 5-year periods: 2005-2009 and 2012-2016, i.e. before and during the crisis focusing on the emergency ones (either incarcerated or strangulated). RESULTS: An equal number of hernioplasties was performed in both periods. During the crisis however, an emergency hernioplasty was significantly more probable (HR 1.269, 95% CI 1.108-1.1454, p = 0.001), at a younger age (p = 0.04), mainly in patients younger than 75 years old (p = 0.0013). More patients presented with intestinal ischemia (7 vs 18, p = 0.002), requiring longer hospitalization (5.2 vs 9.6 days, p = 0.04), with higher cost (560 ± 262.4€ vs 2125 ± 1180.8€ p < 0.001). In contrast the percentage of patients with intestinal resection, their hospitalization length and treatment-cost remained unchanged. During the crisis there was a non-significant increase of emergency patients requiring ICU postoperatively (0 vs 4, p = 0.07) and a non-significant 60% increase of emergency operations in migrants/refugees population (3.5% vs 5.8%, p = 0.28). Epidural anesthesia was significantly more frequent during the crisis. CONCLUSION: During the crisis: (i) the emergency hernioplasties increased significantly, (ii) more patients (exclusively Greek) presented with intestinal ischemia requiring longer hospitalization and higher treatment cost, (iii) the mean age of the urgently treated patients decreased significantly (iv) regional (epidural) anesthesia was more frequent. Although a direct causal relation could not be proven by the present study most observations can be explained by an increase of the patients who delayed the elective treatment of their hernia, and by a redistribution of the surgical workload towards big central hospitals. This can be prevented by adequately supporting the small district hospitals.

Right main bronchus rupture due to blunt chest trauma.

Bronchial rupture following major blunt chest trauma should be suspected in every case of massive and persistent air leak through the intercostal drain tube. Chest radiogram offers indirect signs, while chest CT scan demonstrates specific signs highly suggestive for this extremely rare tracheobronchial injury. Bedside bronchoscopy confirms the diagnosis.

Neutrophils to lymphocytes ratio as a useful prognosticator for stage II colorectal cancer patients.

BACKGROUND: The incidence of colorectal cancer (CRC) is expected to increase by 80% in year 2035. Even though advantages in treatment of CRC have being made over the last decades, the outcome remains poor. Recently, several inflammatory markers including pretreatment neutrophil to lymphocyte ratio (NLR), have being used as prognostic factors, since host inflammatory response to cancer is believed to determine disease progression. The aim of this study is to evaluate the prognostic significance of pretreatment NLR, in terms of overall survival (OS), 5-year survival, disease-free survival (DFS) and recurrence, in CRC patients who underwent curative resection. METHODS: We retrospectively reviewed 296 patients, who were submitted to elective surgery as first therapeutic option in curative intent, between January 2010 and December 2015. Pretreatment NLR, as well as demographics, clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS, 5-year survival, DFS and recurrence. RESULTS: The cutoff point of NLR was calculated with Kaplan-Meier curves and log-rank test to 4.7. Univariate and multivariate analyses disclosed elevated NLR as a significant dismal prognostic factor for DFS (HR 1.88; 95% CI 1.01-3.52; p = 0.048), 5-year survival (HR 2.14; 95% CI 1.12-4.10; p = 0.021) and OS (HR 2.11; 95% CI 1.11-4.03; p = 0.023). In a subgroup analysis, in patients with stage II CRC, NLR > 4.7 was a stronger poor predictor for DFS (HR 2.76; 95% CI 1.07-7.13; p = 0.036), 5-year survival (HR 3.84; 95% CI 1.39-10.63; p = 0.01) and OS (HR 3.62; 95% CI 1.33-4.82; p = 0.012). After adjusting stage for gender, age, location of the primary tumor, differentiation, as well as the presence of perineural, vascular, and lymphovascular invasion, the significance of NLR > 4.7 became more prominent for DFS (HR 2.85; 95% CI 1.21-6.73; p = 0.0176), 5-year survival (HR 4.06; 95% CI 1.66-9.93; p = 0.002) and OS (HR 4.07; 95% CI 1.69-9.91; p = 0.002) in stage II patients. CONCLUSION: Pretreatment NLR > 4.7 is a poor prognostic factor for DFS, 5-year survival and OS in CRC patients undergoing curative resection. The dismal prognostic effect of NRL is magnified in Stage II CRC patients.

High versus low ligation of inferior mesenteric vessels in rectal cancer surgery: A retrospective cohort study.

PURPOSE: To retrospectively evaluate the short-term and the long-term oncological outcome between two groups of patients who had undergone either high or low ligation of inferior mesenteric vessels (IMV) in rectal cancer surgery. METHODS: Between January 2009 and December 2014, 120 patients with rectosigmoid and rectal adenocarcinoma were operated with curative intent as first therapeutic option. Patients were divided in two groups depending on the level of the inferior mesenteric artery (IMA) ligation. High ligation was defined as the division of the IMA less than 2cm from the aorta followed by the ligation of the inferior mesenteric vein at its origin from the lower border of the pancreas (n=76), while low ligation was defined as the division of IMA immediately distal to the origin of the left colic artery (n=44). RESULTS: The median follow up was 51 months. Univariate analyses disclosed that low ligation was related to a higher postoperative complications rate, mainly related to the higher rate of urinary dysfunction but it was also related to a favorable 5-year overall survival (OS) rate. However, multivariate analyses among factors which might influence the short- and long-term outcomes did not disclose the level of ligation as a factor influencing the postoperative course, the recurrence, the disease free survival (DFS) and the 1-, 3- and 5-year OS rates. CONCLUSIONS: The present study disclosed no differences in surgical, histological, short-term and long-term oncological outcomes between patients treated with either high or low ligation of IMA.

Differences in gastric cancer surgery outcome between East and West: differences in surgery or different diseases?

The Dutch D1D2 Trial revealed a noncompliance rate of 51% in gastric cancer patients who should have undergone a D2 dissection, while it disclosed that the D2 lymph node dissection group of patients exhibited a higher 15-year overall survival (OS) rate, lower rates of local and regional recurrence, lower rates of liver metastases and lower cancer-related death rates compared to the D1 group, implying that the surgical technique per se may influence outcomes. On the other hand, the predominant up-regulation of invasive and metastatic genes in the Western tumor libraries, the differences in the criteria used for gastric cancer diagnosis in the East and the steady fnding that the Asian ethnicity is a favorable prognostic factor for patients with gastric cancer treated in the US, have been proposed as possible explanations for the differences observed in the gastric cancer outcome between the East and the West. Moreover, literature addresses that gastric cancers in the East are mainly diagnosed at younger ages, they are of intestinal type, located distally, diagnosed at an early stage of disease, while gastric cancers in the West are mainly affecting elderly patients with comorbidities, they are of diffuse type, located proximally, and diagnosed at an advanced stage of disease. Future discoveries in genetics and molecular biology may clarify the characteristics of each tumor, while future achievements in imaging modalities and biological or target therapies may establish "personalized" therapies. Until that time, all efforts for improving our surgical techniques and optimizing the perioperative care are mandatory.

Update on Surgical Management of Small Bowel Neuroendocrine Tumors.

The widespread use of endoscopy and imaging in combination with the continuous update of the staging systems for neuroendocrine tumors has led to an increase in the incidence of small intestinal neuroendocrine tumors (si-NENs) globally. Despite high survival rates, severe complications may occur even in early stages due to the anatomic location of the primary site and the desmoplastic reaction. Surgery plays a central role in the management of patients with si-NENs. Excision of locoregional disease along with extensive lymph node dissection should be performed in fit patients, even in the presence of metastases. Multimodality treatment of liver metastases includes hepatectomy, ablative techniques and liver transplantation. Hormone therapy with somatostatine analogs is of high importance for symptomatic control; special caution should be exercised both pre- and intra-operatively. A multidisciplinary approach is essential in order to provide personalized therapeutics for patients with si-NENs. Clinical research and specialization in this field should be further encouraged.

Cullin-1 and -2 Protein Expression in Colorectal Cancer: Correlation with Clinicopathological Variables.

BACKGROUND/AIM: The cullin (CUL) family of proteins is involved in the ubiquitin/mediated degradation of proteins, regulating cell proliferation, cell-cycle control, migration, invasion and metastasis in the process of tumor progression. The aim of the present study was to examine if there is any correlation between the immunohistochemical (IHC) expression of Cullin-1 and -2 proteins in colorectal cancer tissue specimens with several clinicopathological variables. MATERIALS AND METHODS: Between January 2012 and December 2014, 96 consecutive adenocarcinoma patients were submitted to oncological colectomy, as the first therapeutic option, with a curative intent. CUL-1 and -2 protein expression was examined with IHC on paraffin-embedded tissue sections. CUL-1 and -2 protein positivity, was correlated with patients' age, gender, stage, histological grade, proliferative capacity (Ki-67 labeling index) and mutant p53 protein expression. The positivity for CUL-1, CUL-2, mutant p53 protein and Ki-67 index, was determined by the percentage of their IHC expression in the total number of cancer cells. RESULTS: Choosing as a cut-off point for CUL-1 positivity the 10%, a statistically significant relationship of the expression of the mutant p53 protein (p=0.04) and the co-expression of CUL-2 (p=0.003) were noticed. By setting the cut-off limit for CUL-2 expression to 10%, no statistically significant differences were observed between its expression and the examined clinicopathological variables. However, by increasing the cut-off limit for CUL-2 expression to 30%, a statistically significant correlation of its expression to the mutated p53 protein was noticed (p=0.047). Co-expression of CUL-1 and -2 in more than 10%, significantly correlated to the coexistence of adenomatous polyps along the large bowel (p=0.0329). Multivariate analysis of CUL-1 and -2 co-expression in more than 10% disclosed their expression as an independent factor for adenomatous polyps development in the large bowel (p=0.035, RR=2.1). CONCLUSION: CUL-1 overexpression may happen early in the process of carcinogenesis mainly affecting the vulnerable p53(+) large bowel cells, arresting them in the G1 phase of cell-cycle, while it may also induce the expression of CUL-2. Co-expression of CUL-1 and CUL-2, in the arrested (in G1 phase) large bowel cells, promotes carcinogenesis up to adenomatous polyp formation. Since no relationship between cullins expression and development of cancer on adenoma was found, the results of the present study may be useful explaining the initiation but not the progression of carcinogenesis in colorectal cancer. Further molecular and clinical studies are needed in order to delineate the clinical importance of these proteins in the management of colorectal cancer patients.

Kallikrein-related peptidase 6 (KLK6) expression differentiates tumor subtypes and predicts clinical outcome in breast cancer patients.

Novel molecular markers that address the heterogeneity of breast cancer (BC) and provide meaningful prognostic information for BC patients are needed. Kallikrein-related peptidase 6 (KLK6) is aberrantly expressed and functionally implicated in BC and, like other members of the KLK family, may prove a useful molecular tool for clinical management. Our objective was to assess, for the first time, the clinical relevance of KLK6 mRNA expression in BC. Total RNA was isolated from 165 breast tumors, as well as 100 adjacent non-cancerous tumor specimens. After cDNA synthesis, and following quality control, quantitative real-time PCR for KLK6 expression analysis took place. Receiver operating characteristic curves were constructed in order to assess the ability of KLK6 mRNA expression levels to differentiate between molecular BC subtypes. Survival analyses, using DFS as endpoint, were performed at the univariate and multivariate levels. Publicly available BC databases and online survival analysis tools were used to validate our findings. A significant downregulation of KLK6 mRNA expression was observed in BC tissue sections compared to the non-cancerous component (P < 0.001). The expression of KLK6 is positively associated with tumor grade (P = 0.038) and is overexpressed in TNBC and HER2-positive tumors (P < 0.001). Aberrant KLK6 expression predicts the clinical outcome of BC patients in terms of DFS, independently of currently used prognostic markers (HR = 7.11, 95% CI = 1.19-42.45). The differential expression of KLK6 and its association with unfavorable outcome in BC patients was validated via in silico analyses. Although an independent external cohort is necessary to confirm our findings, we proved for the first time that KLK6 can provide independent prognostic information for BC patients.

Towards a tailored lymphadenectomy for gastric cancer based on the correlation between the primary tumor location and the first lymphatic drain basin: Preliminary data.

PURPOSE: The contradictory long-term results following D2 lymphadenectomy have revealed the necessity for a more tailored lymphadenectomy in cases of gastric cancer. Among the patients who had undergone a modified D2 lymphadenectomy for gastric cancer, we further analyzed the subgroup in which histologically and immunohistochemically solitary lymph node metastases were detected. Classifying the primary tumors as towards to the lesser and towards to the grater curvature, we propose possible routes of lymphatic spread and possible clinical implications. METHOD: Between January 2007 and December 2016, 212 patients suffering from gastric adenocarcinoma underwent a modified D2 lymphadenectomy. Solitary lymph node metastases were detected by histology in 14 patients (7 skip metastases) and by immunohistochemistry in an additional 10 patients (5 skip micrometastases). RESULTS: The incidence of the histologically detected solitary lymph node metastases was 6.6% for the whole cohort, increasing to 11.3% with the use of immunohistochemistry. The incidence of the histologically detected skip solitary lymph node metastases was 3.3% for the whole cohort, increasing to 5.7% with the use of immunohistochemistry. Tumors of the lower and middle third of the stomach were equally drained both to the level I and II lymph node stations. However, tumors towards the lesser curvature were mainly drained in the level II lymph node stations (12 out of 19; 63%), while tumors towards the greater curvature were all drained in the level I lymph node stations (5 out of 5; 100%). CONCLUSION: Primary gastric tumors towards the lesser curvature should be treated by a modified D2 lymphadenctomy. However, for tumors towards the greater curvature, a D1(+) lymphadenectomy always including the no. 7 & 9 lymph node stations complex, might be enough.

Updates and Critical Evaluation on Novel Biomarkers for the Malignant Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) are presumed to evolve from low-grade dysplasia to high-grade dysplasia to invasive carcinoma. Resection of lesions before the development of pancreatic cancer may prevent the development of an incurable process as, once IPMNs progress to invasive cancer, the prognosis may be as poor as resected conventional pancreatic ductal adenocarcinoma. Resection of IPMNs, particularly in the setting of high-grade dysplasia, is presumed to provide a survival benefit. IPMNs also present many challenges as the identification of high-grade dysplasia and early invasive carcinoma and the timing and frequency of malignant progression are not yet established. The limited predictive accuracy presents a challenge as pancreatic resection is associated with a risk of substantial morbidity and mortality; 20-30% and 2-4%, respectively. Diagnostic armamentarium contains pancreas-protocol computed tomography (CT) scan, gadolinium-enhanced magnetic resonance imaging (MRI) with or without magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS). The most promising method is endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as this technique allows analysis of cyst fluid using biomarkers. Until now, in clinical practice, we utilize two biomarkers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9); however, DNA analysis of pancreatic cystic fluid and genomic analysis could offer new tools to the diagnosis and administration of IPMNs. Novel genomic and serum biomarkers could play an important future role to identify those individuals who will benefit from an early operation and those who will benefit from watchful waiting approach. More prospective studies are needed.

Incidence and Risk Factors for Organ/Space Infection after Radiofrequency-Assisted Hepatectomy or Ablation of Liver Tumors in a Single Center: More than Meets the Eye.

INTRODUCTION: Surgical site infections (SSIs) and especially organ/space infection (O/SI) after resection or ablation of liver tumors are associated with increased morbidity and mortality. A secondary blood stream infection (BSI) is considered an O/SI but the exact prevalence is unknown. We aimed to investigate the incidence of O/SI and BSIs in a cohort of consecutive patients after liver resection or ablation, to seek for a possible connection between them and to search for potential risk factors. MATERIALS AND METHODS: We reviewed all patients who underwent hepatic resection or intraoperative liver ablation between January 2012 and December 2016 in our department. We focused on age, gender, Child-Pugh score, preoperative biliary drainage, indication for surgery, type of resection, resection or ablation of tumor, need for bilioenteric reconstruction, additional procedure to hepatectomy, blood transfusion, operative time, postoperative admission to ICU, and antibiotic chemoprophylaxis. All positive cultures from intra-abdominal fluids and blood were recorded. O/SI and BSIs were diagnosed by the criteria set by Centers for Disease Control. All variables were compared between the group with O/SI and the group without infection. BSIs were associated with these infections also. RESULTS: Eighty-one consecutive patients with a mean age of 64 years were enrolled. Fifteen patients presented a positive culture postoperatively: intra-abdominal fluid in eight, blood cultures in six, and both blood and intra-abdominal fluid in one patient. The directly estimated incidence of O/SI amounted to 11.1%. Four blood cultures were secondary to O/SI, and the remaining two secondary to central line catheter. O/SI was diagnosed indirectly, through the BSI in an additional 4.9% of the patients, raising the incidence of SSI to 16%. Among the factors studied, only admission to the ICU was found to be statistically significant as a risk factor for the development of O/SI (p = 0.026). CONCLUSION: O/SI should be actively seeked for after liver surgery including blood cultures. Patients with affected physical status, comorbidities are in greater risk of developing O/SI.

Laparoscopic Splenectomy for Benign Hematological Disorders in Adults: A Systematic Review.

BACKGROUND: Since its introduction in the early 1990s, laparoscopic splenectomy (LS) has gained worldwide acceptance for spleen removal, especially in hematological patients. AIM: The present review summarizes the current knowledge and results of LS for the treatment of benign hematological diseases in adults. MATERIALS AND METHODS: A MEDLINE/PubMed database research was performed using the terms: "laparoscopic splenectomy" OR "laparoscopy" OR "splenectomy" AND "hematological disorders" OR "hematological disease" OR "hematology" AND "adults" as key words. We set our analysis starting date as January 1st 2010 and the end date as December 31st 2016. We identified 247 relative articles. All the references from the identified articles were searched for relevant information. RESULTS: Twenty-seven articles were deemed appropriate for our analysis. LS was found to be feasible and safe in the majority of patients with benign hematological disorders, with a mortality rate ranging from 0% to less than 4% and the postoperative complications rate from 0% to 35.7%. The conversion rate was also very low (4%) and response (complete or partial) was achieved in more than 80% of patients. Lateral approach with four trocars was the most commonly used approach with concommitant cholecystectomy being correlated with increased operative time and morbidity. CONCLUSION: Current literature holds that whenever splenectomy is required for the treatment of hematological disorders in adults, a laparoscopic approach should be offered as the gold standard. However, to strengthen the clinical evidence in favor of LS, more high-quality clinical trials on several issues of the procedure are necessary.

The beneficial role of simultaneous splenectomy after extended hepatectomy: experimental study in pigs.

BACKGROUND: The role of hepatic hemodynamic modulation in the development of "small-for-size" syndrome (SFSS) after extended hepatectomy (EH) or living-donor liver transplantation is still controversial. We have designed an experimental study to investigate the effect of hemodynamic parameters of the liver circulation on the development of SFSS after EH in a porcine model. METHODS: Eighteen pigs were randomly divided into two groups: group A has received EH (75%-80%) without splenectomy, and group B with EH and simultaneous splenectomy was carried out. Portal hemodynamics, liver function tests, histologic findings, injury and survival rates were compared between groups A and B. RESULTS: The 7-d survival rate in the splenectomy group was significantly improved compared with group A (88.9% versus 44.4%, P < 0.05). Portal vein pressure, portal vein flow, and liver function tests in the splenectomy group were significantly lower than in group A immediately after splenectomy and postoperatively until the day of sacrifice. Histologic findings in group A clearly illustrate severe inflammation, bridging necrosis, ischemic cholangitis, and severe congestion, while in group B there were less serious histologic changes. CONCLUSIONS: Our experimental study indicates that perioperative portal modulation can successfully prevent the manifestation of SFSS after EH. Therefore, by focusing on "flow" rather than on "size," researchers may understand better the pathophysiology of this syndrome.

Radiofrequency Energy in Hepatic Bed during Partial Cystectomy for Hydatid Liver Disease: Standing Out from the Usual Conservative Surgical Management.

Background. Surgical treatment of hydatid liver disease (HLD) is divided into conservative and radical procedures. While conservative techniques are easier and faster to perform, there is an emerging need to reduce their morbidity and recurrence rates. Our aim was to present and evaluate the efficiency and safety of the application of radiofrequency energy (TissueLink® and Aquamantys® systems) in hepatic bed during partial cystectomy. Materials and Methods. Eighteen consecutive patients with hydatid liver cysts were referred to our department between April 2006 and June 2014. Data about demographics, mortality, morbidity, and recurrence rate were obtained and analyzed retrospectively. Results. The mean follow-up was 38 months (range: 4-84 months). The postoperative course of most patients was uneventful. One case of recurrence was found in our series in a patient with 4 cysts in the right lobe, 3 years after initial treatment. He was reoperated on with the same method. Conclusions. Saline-linked RF energy seems to be an effective means to be employed in conservative surgical procedures of HLD, with satisfactory postoperative morbidity. Recurrence rates appear to be low, but further follow-up is needed in order to draw safer conclusions.