A Case of a Metastatic Pancreatic Neuroendocrine Tumor: A Surgical Conundrum Wrapped in Functionality's Embrace.

This case study reports a rare case of a non-functioning metastatic pancreatic neuroendocrine tumor (pNET) transforming into a functioning pNET. A 59-year-old male, previously treated with distal pancreatectomy, splenectomy, lymph node dissection, liver metastasectomy, and pharmacotherapy, presented with weakness, hypoglycemia, and daily episodes of watery diarrhea. A functioning neuroendocrine liver metastasis expressing insulin and gastrin was identified. Surgical intervention, including left lateral hepatectomy and microwave ablation of multiple intrahepatic lesions, resulted in symptom resolution and uneventful recovery. However, metastatic liver disease re-emerged seven months post-surgery, necessitating chemotherapy. This case highlights the importance of vigilance for symptom development in non-functioning pNETs, signaling potential disease relapse and phenotype transformation, and suggests surgical treatment as a viable option in select cases.

Hepatic Small Vessel Neoplasm: A Case Report and Review of the Literature.

Hepatic small vessel neoplasm (HSVN) is a recently described vascular neoplasm of the liver. It demonstrates an infiltrative growth pattern and lacks cytologic atypia and mitotic activity. So far, no cases of metastasis or disease recurrence after excision have been reported in the literature. In this report, we present the case of a 31-year-old woman with a lesion in segments VII-VIII of the liver who was referred to our surgical department due to right lumbar pain. She underwent an atypical wedge hepatectomy (segments VII, VIII) and cholecystectomy. The histopathology of the resected specimen confirmed a 40mm HSVN. The patient did not receive any adjuvant therapy and is scheduled for follow-up with serial magnetic resonance imaging (MRI) scans over the next five years due to the unknown malignant potential of the tumor.

A Huge Asymptomatic Urachal Mucinous Cystic Carcinoma: A Case Report With Differential Diagnosis and Surgical Considerations.

Cystic mucinous neoplasms of urachal origin cover a wide spectrum of benign and malignant lesions arising from the remnants of the urachus. They display various degrees of tumor cell atypia and local invasion, with no reported cases of metastasis or recurrence after complete surgical resection. We present a 47-year-old man who referred to our Surgical Department due to an abdominal cystic mass incidentally found upon abdominal ultrasound. He underwent en block resection of the cystic mass along with partial bladder dome cystectomy. The histopathology of the resected specimen revealed a cystic mucinous epithelial tumor of low malignant potential with areas of intraepithelial carcinoma. The patient showed no evidence of disease recurrence or distant metastasis 6 months after resection and is scheduled for follow-up with serial MRI or CT scans and blood tumor markers over the next 5 years.

Individualized Approach in the Surgical Management of Hepatocellular Carcinoma: Results from a Greek Multicentre Study.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of death worldwide. The management of HCC is complex, with surgical treatment providing long-term survival in eligible patients. This study aims to present the experience of aggressive surgical management of HCC in Greece. Methods: This is a retrospective multicentre clinical study with 242 patients. Results: Most patients were male (79%) and had a median age of 71 yrs. According to the most recent BCLC criteria, 172 patients (71.1%) were classified as BCLC 0-A stage, 33 patients (13.6%) were classified as BCLC B, and 37 (15.3%) were classified as BCLC C. A total of 54% of the patients underwent major hepatectomy. Major postoperative morbidity was 15.6%, and the 90-day postoperative mortality rate was 4.5%. The median follow-up was 33.5 months. Three- and five-year overall survival was 65% and 48%, respectively. The median overall survival was 55 months. Significantly, five-year survival was 55% for BCLC A, and 34% and 21% for BCLC B and C, respectively. In univariate analysis, cirrhosis, type of resection (R status), and BCLC stage were associated with overall survival. Multivariate analysis indicated that R1 and R2 resections compared to R0, and BCLC C compared to BCLC 0-A, were independently associated with increased mortality. Conclusions: Aggressive surgical treatment of HCC offers satisfactory long-term survival prospects. A significant percentage (29%) of HCCs that underwent liver resection were of the intermediate and advanced BCLC stage. The management of patients with HCC should be discussed in multidisciplinary tumour board meetings on a case-by-case basis to be more effective.

Role and Efficacy of Robotic-assisted Radical Antegrade Modular Pancreatosplenectomy (RAMPS) in Left-sided Pancreatic Cancer.

Distal pancreatectomy with splenectomy is the gold-standard surgery for the treatment of left-sided pancreatic cancer. Margin negative resection accompanied by effective lymphadenectomy are the deciding factors affecting the outcome of tail-body pancreatic adenocarcinoma. Radical antegrade modular pancreatosplenectomy (RAMPS) is considered as a reasonable approach for margin-negative and systemic lymph node clearance. Herein, we aim to present all existing data regarding this novel approach including surgical technique and comparison with standardized procedures. RAMPS has shown oncological superiority comparing to distal pancreatectomy with splenectomy due to radical lymphadenectomy and improved dissection of the posterior pancreatic aspects. Robotic-assisted RAMPS has recently been described as a valuable alternative to open RAMPS. With this novel technique, anterior, posterior or modified approaches can be achieved; favorable clinical and oncological outcomes have been reported in the current literature, with reduced conversion rates compared to other minimally invasive approaches, as well as vastly improved maneuverability, accuracy and vision. Robotic-assisted RAMPS is not only technically feasible but also oncologically safe in cases of well-selected, left-sided pancreatic cancer.

Revision of Roux-en-Y Gastric Bypass for Inadequate Weight Loss or Weight Regain.

Inadequate weight loss or weight regain after Roux-en-Y gastric bypass (RYGBP) occurs in more than a quarter of patients for various reasons. Available remedying treatment options include endoscopic and surgical techniques for revision of the gastric pouch and the gastro-jejunal anastomosis, conversion of standard to distal gastric bypass (DRYGBP) or the conversion of RYGBP to biliopancreatic diversion (BPD) or duodenal switch (DS). There is quite a variability concerning the technical simplicity, safety, and effectiveness of these techniques and the small number of patients in the numerous single-center reports precludes any meaningful comparisons. This review aimed to describe all available methods and present the advantages and disadvantages of each of them, to facilitate, rather than guide, the decision of the average bariatric surgeon who encounters such a patient.

The Impact of Thromboprophylaxis on the Survival of Patients with Advanced Pancreatic Cancer. The Pancreatic Cancer and Tinzaparin (PaCT) Study.

Pancreatic cancer (PaC) induces a prothrombotic and hypercoagulable state. The aim of this study was to investigate the effect of tinzaparin in combination with chemotherapy. The PaCT (pancreatic cancer and tinzaparin) study was a retrospective observational study that collected data regarding progression free survival (PFS) in advanced or metastatic PaC patients who received thromboprophylaxis with tinzaparin during chemotherapy with nab-paclitaxel (N) and gemcitabine (G). The primary end point was to compare, from already published data, the PFS of patients receiving thromboprophylaxis with tinzaparin with the PFS of patients receiving chemotherapy with N-G but no thromboprophylaxis. Secondary end points were efficacy and safety of anticoagulation. In total, 110 PaC patients, 93% with advanced or metastatic disease, treated with N-G and tinzaparin (10,291 ± 1176 Anti-Xa IU, OD, median duration 8.7, IQR: 5.6-11.9 months) were enrolled. Of these, 52% were males and; the median age was 68 (40-86 years). The tumor was located to in the pancreatic head at in 45% of the patients. The median PFS was 7.9 months (IQR: 5.0-11.8 months). Out of 14 similar studies (involving 2994 patients) identified via systematic search, it was determined that the weighted PFS of patients receiving N-G but no anticoagulation was 5.6 months. Therefore, patients receiving tinzaparin had 39.54% higher PFS than patients without thromboprophylaxis (p < 0.05). During the follow-up period of 18.3 ± 11.7 months, three (2.7%) thrombotic events were recorded while two clinically relevant non-major bleeding events occurred (1.9%). In conclusion, PFS in advanced PaC patients undergoing chemotherapy is positively impacted by anticoagulation. Thromboprophylaxis with tinzaparin in treatment dose is efficient and safe.

Combinatorial Treatment of Tinzaparin and Chemotherapy Can Induce a Significant Antitumor Effect in Pancreatic Cancer.

Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) such as tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approaches to treat highly malignant and refractory cancers such as PC, we hypothesized that tinzaparin can augment the effectiveness of traditional chemotherapeutic drugs and induce efficient antitumor activity. PANC-1 and MIAPaCa-2 were incubated alone or in combination with tinzaparin, nab-paclitaxel and gemcitabine. In vivo evaluation of these compounds was performed in a NOD/SCID mouse using a model injected with PANC-1. Tinzaparin enhances the anti-tumor effects of nab-paclitaxel and gemcitabine in mtKRAS PC cell lines via apoptosis in in vitro experiments. The triple combination power acts through the induction of apoptosis, reduction of the proliferative potential and angiogenesis; hence, contributing to a decrease in tumor volume observed in vivo. The triple regimen provided an extra 24.3% tumor reduction compared to the double combination (gemcitabine plus nab-paclitaxel). Combinatorial strategies can create novel therapeutic approaches for the treatment of patients with PC, achieving a better clinical outcome and prolonged survival. Further prospective randomized research is needed and the investigation of various concentrations of tinzaparin above 150 UI/Kg, would potentially provide a valuable synergistic effect to the conventional therapeutic compounds.

The ancient Greek roots of the term Toxic.

In ancient Greek literature the adjective toxic (Greek: τoξικόν) derives from the noun τόξo, that is the arc. This noun according to the Liddell - Scott - Jones lexicon had several meanings. Apart from the meaning that someone is able to use a bow or the military department of the archers, the medical context of the term is that a substance has the characteristic of a poison. This concept of the term survived until today with little differentiation.

Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC).

OBJECTIVES: Locally advanced pancreatic cancer (LAPC) is found in about 40% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a nonthermal ablative technique that provides an alternative in patients with LAPC and can be safely combined with chemotherapy. MATERIALS AND METHODS: From 2015 until October of 2019, we performed laparotomic IRE in a total of 40 patients with stage III LAPC. The median age of these patients was 65.2 years (range: 46 to 81 y), and the median tumor size was 3.8 cm (range: 2 to 5.2 cm). 33 of 40 patients were treated preoperatively with FOLFIRINOX or nab-paclitaxel plus gemcitabine and in case of disease control, IRE was performed, whereas in 7 patients, IRE was performed without previous chemotherapy. RESULTS: All patients were treated successfully with IRE as the tumor evaluation showed no disease progression after the completion of induction chemotherapy. No IRE-related deaths occurred. Two major grade III complications were reported: pancreatic fistula grade A in 8 patients and 3 patients diagnosed with delayed gastric emptying. Up to October 31, 2019, the median overall survival (OS) of all patients was 24.2 months (range: 6 to 36 mo), and the median progression-free survival was 10.3 months (range: 3 to 24 mo). After the completion of IRE, 30 patients (75%) continued with adjuvant chemotherapy. Fifteen patients (37%) have >24 months OS and 3 patients (8%) have reached 36 months OS and are still alive. CONCLUSION: The combination of chemotherapy with IRE, which is a safe and effective procedure, may result in a survival benefit for patients with LAPC.

A novel tool for visualization and detection of pancreatic neuroendocrine tumours. A 'fluorescent' world is calling for exploration?

AIM OF THE STUDY: Pancreatic neuroendocrine tumours (pNETs) are rare tumours with a propensity to metastasize. Physicians frequently face a huge clinical challenge during the localization of these lesions. The aim of this study is to investigate whether fluorescence-guided localization techniques with indocyanine green (ICG) can be utilized as a detection tool in pNETs, along with any other clinical implications of this technique. MATERIAL AND METHODS: A thorough literature search in PubMed and Google Scholar, under the terms 'ICG OR Indocyanine OR Fluorescence AND Neuroendocrine' until 31 June 2021, regarding the utilization of indocyanine-fluorescence in localization of pancreatic neuroendocrine, was conducted by the authors, and the associated results are presented. RESULTS: Indocyanine fluorescence imaging may facilitate the efforts of surgeons to identify occult pancreatic neuroendocrine lesions, assisting them in the identification of resection margins and delineation of the surgical anatomy when it is difficult to clarify. CONCLUSIONS: Indocyanine-fluorescence imaging might play a pivotal role in pancreatic surgery in terms of localization for neuroendocrine tumours. However, further large-scale clinical studies are needed to assess the absolute indications and optimal use of this technique.

Insulinomas: from diagnosis to treatment. A review of the literature.

Insulinoma is the most common pancreatic neuroendocrine tumor (NET). Insulinomas are most commonly benign, well-differentiated NETs, whereas malignant neoplasms account for approximately 5-10% of all cases. Management includes conservative treatment with drugs targeting insulin-induced hypoglycemia, non-operative invasive procedures, as well as curative open or laparoscopic tumor resection. The current review aimed to summarize the current literature evidence on insulinoma and investigate the advantages and complications of available treatments.

Unique Spatial Immune Profiling in Pancreatic Ductal Adenocarcinoma with Enrichment of Exhausted and Senescent T Cells and Diffused CD47-SIRPα Expression.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is resistant to single-agent immunotherapies. To understand the mechanisms leading to the poor response to this treatment, a better understanding of the PDAC immune landscape is required. The present work aims to study the immune profile in PDAC in relationship to spatial heterogeneity of the tissue microenvironment (TME) in intact tissues. METHODS: Serial section and multiplex in situ analysis were performed in 42 PDAC samples to assess gene and protein expression at single-cell resolution in the: (a) tumor center (TC), (b) invasive front (IF), (c) normal parenchyma adjacent to the tumor, and (d) tumor positive and negative draining lymph nodes (LNs). RESULTS: We observed: (a) enrichment of T cell subpopulations with exhausted and senescent phenotype in the TC, IF and tumor positive LNs; (b) a dominant type 2 immune response in the TME, which is more pronounced in the TC; (c) an emerging role of CD47-SIRPα axis; and (d) a similar immune cell topography independently of the neoadjuvant chemotherapy. CONCLUSION: This study reveals the existence of dysfunctional T lymphocytes with specific spatial distribution, thus opening a new dimension both conceptually and mechanistically in tumor-stroma interaction in PDAC with potential impact on the efficacy of immune-regulatory therapeutic modalities.

The efficacy and safety of the open approach irreversible electroporation in the treatment of pancreatic cancer: A systematic review.

BACKGROUND: Irreversible Electroporation (IRE) is a novel non-thermal ablation technique used in patients with locally advanced pancreatic cancer (LAPC), in the proximity of sensitive structures such as vessels, intestinal wall and the bile duct. Currently, it is only used in the setting of clinical trials. This systematic review aimed to tackle the knowledge gap in the literature, in relation to the safety and efficacy of the open approach IRE. METHODS: MEDLINE, EMBASE and Cochrane libraries were searched for English language articles published from January 2000 to December 2019. Data related to safety and efficacy were extracted. RESULTS: Nine studies involving 460 patients with LAPC were included. Open approach IRE was associated with high morbidity (29.4%) but with a survival benefit compared to traditional treatment. Median overall survival (OS) was at 17.15 months. Major morbidity was at 10.2% and mortality at 3.4%. CONCLUSIONS: Despite the paucity of literature and the low quality of evidence, the results regarding safety and efficacy appear to be encouraging. The high morbidity seems to be mitigated by a demonstrated improvement in OS. The potential of this technique is more evident when mortality and major morbidity are considered, since they are at acceptable levels. The limitations of this review have made it difficult to extract definitive conclusions. Higher quality evidence is needed in the form of large-scale multicentre randomized controlled trials. It remains to be elucidated whether the rate of adverse events decreases as our experience with this technique increases.

Treatment of Fournier's Gangrene With Vacuum-assisted Closure Therapy as Enhanced Recovery Treatment Modality.

BACKGROUND/AIM: Fournier's gangrene is an uncommon, but extremely serious condition of necrotizing, soft tissue infection. There is a great debate regarding the management of larger defects and wound closure, with various techniques being described in the current literature. We aimed to present the surgical management of extensive Fournier's gangrene treated successfully with Vacuum-assisted closure (VAC) therapy, a novel approach to treatment algorithm that can lead to a paradigm shift. CASE: A 66-year-old male patient with Fournier's gangrene was treated with extensive surgical debridement, protective colostomy and VAC therapy. RESULTS: After initial extensive surgical debridement, VAC therapy significantly improved the clinical and aesthetic condition of the patient. CONCLUSION: VAC therapy in Fournier's gangrene patients may be a safe and effective technique with favorable clinical outcomes, by improving and enhancing wound healing and recovery.

Conditioning attenuates kidney and heart injury in rats following transient suprarenal occlusion of the abdominal aorta.

Suprarenal aortic clamping during abdominal aortic aneurysm (AAA) repair results in ischemia-reperfusion injury (IRI) in local (i.e. kidney) and distant (i.e. heart) tissue. To investigate perioperative approaches that mitigate IRI-induced tissue damage, Wistar rats underwent suprarenal aortic clamping either alone or in combination with short cycles of ischemic conditioning before and/or after clamping. Serum analysis revealed significant reduction in key biochemical parameters reflecting decreased tissue damage at systemic level and improved renal function in conditioned groups compared to controls (p < 0.05), which was corroborated by histolopathological evaluation. Importantly, the levels of DNA damage, as reflected by the biomarkers 8-oxo-G, γH2AX and pATM were reduced in conditioned versus non-conditioned cases. In this setting, NADPH oxidase, a source of free radicals, decreased in the myocardium of conditioned cases. Of note, administration of 5-HD and 8-SPT blocking key protective signaling routes abrogated the salutary effect of conditioning. To further understand the non-targeted effect of IRI on the heart, it was noted that serum TGF-ß1 levels decreased in conditioned groups, whereas this difference was eliminated after 5-HD and 8-SPT administration. Collectively, conditioning strategies reduced both renal and myocardial injury. Additionally, the present study highlights TGF-ß1 as an attractive target for manipulation in this context.

Lymphoepithelial pancreatic cyst: A rare entity among pancreatic cystic lesions. Report of two cases.

Lymphoepithelial pancreatic cysts are extremely rare benign pancreatic cystic lesions. High suspicion and an individual approach are imperative for the best management of those extremely rare entities.

The Role of E3, E4 Ubiquitin Ligase (UBE4B) in Human Pathologies.

The genome is exposed daily to many deleterious factors. Ubiquitination is a mechanism that regulates several crucial cellular functions, allowing cells to react upon various stimuli in order to preserve their homeostasis. Ubiquitin ligases act as specific regulators and actively participate among others in the DNA damage response (DDR) network. UBE4B is a newly identified member of E3 ubiquitin ligases that appears to be overexpressed in several human neoplasms. The aim of this review is to provide insights into the role of UBE4B ubiquitin ligase in DDR and its association with p53 expression, shedding light particularly on the molecular mechanisms of carcinogenesis.

Bronchobiliary fistula after hepatectomy: A case report and review of the literature.

Bronchobiliary fistula (BBF) is a rare complication following hepatectomy, and consists of an abnormal intercommunication between the biliary tract and bronchial tree. The management of this rare entity is challenging with limited current evidence to date on how to treat this condition. Herein, a case of BBF following a central hepatectomy and the successive steps of the management was presented. Fourteen months postoperatively, the patient presented to the Oncology Department complaining of new onset fever and expectoration. A computerized tomography scan revealed a BBF and the patient was subsequently referred to our department for further treatment. The surgical team decided that a further operation was required. Using the transabdominal approach, a communication between the initial intrahepatic collection and one inferior lobular bronchus was revealed. Transhiatal removal of fistula was performed with closure of the defect through the abdomen. There was no bile leak through the remaining liver parenchyma. Multidisciplinary management should be considered, taking into consideration the underlying pathology leading to this rare complication. Conservative treatment should be considered first, while surgical resection of the BBF remains an option when other therapies have failed. Surgeons should be aware of this rare complication bile duct injuries during hepatic operations can cause.

Associations between skeletal muscle mass index, nutritional and functional status of patients with oesophago-gastric cancer.

BACKGROUND AND AIMS: Cancer patients frequently suffer from disease-related malnutrition and functional decline. The aim of the current study is to investigate the association between traditional methods of nutritional assessment (unintentional weight loss, Patient Generated-Subjective Global Assessment, anthropometric measurements), functional assessment and muscle mass assessment in oesophago-gastric cancer patients prior to surgery. METHODS: A cross-sectional study was performed in 108 consecutive patients with oesophageal and gastric cancer who were admitted for surgery in the First Department of Surgery, Laikon General Hospital, Athens, Greece. The assessment of muscle mass was based on preoperative Skeletal Muscle Mass Index (SMI) values. The assessment of malnutrition was based on the Patient Generated Subjective Global Assessment, whereas laboratory markers and anthropometric measurements were also recorded. Muscle strength and physical performance were evaluated by measuring patients' handgrip strength and gait speed respectively. RESULTS: 76.8% of the study sample were severely malnourished and moderately or suspected of being malnourished, while the prevalence of low muscle mass was 49.1%. Age was significantly higher in low SMI patients compared to normal SMI individuals (67.2 ± 9.2 vs 60 ± 10.8, p < 0.001). Albumin was significantly lower in low SMI compared to normal SMI patients, as well as BMI, mid-upper arm circumference, calf circumference and corrected mid arm muscle area. Moreover, malnourished patients exhibited higher rates of low muscle mass (57.8% vs 42.2%, p = 0.022) than well-nourished patients. SMI was also significantly correlated with patients' handgrip strength and gait speed. CONCLUSIONS: Low muscle mass is strongly correlated with malnutrition and should be taken into consideration when evaluating the nutritional status of patients with oesophago-gastric cancer.