Evaluation of diagnostic algorithm and therapeutic interventions for intra-abdominal desmoid tumors.

Desmoid-type fibromatosis (DF) is a distinctly rare condition, mostly of younger adults, characterized by the development of locally aggressive tumors of mesenchymal origin. Desmoid tumors (DT) arise either sporadically or in association with FAP (familial adenomatous polyposis), although certain risk factors have also been identified, including pregnancy and antecedent surgical trauma. They can emerge from any connective tissue including muscle, fascia and aponeurosis and are therefore classified, according to location, as intra-abdominal, of the abdominal wall and extra-abdominal. Despite the lack of metastasizing potential, the course can be unpredictable. Various mutations of APC and ß-catenin genes, among others, play a catalytic role in the pathogenesis of this neoplastic entity. Surgery has lost its traditional role as first line treatment of the disease and several other treatment methods are being considered. Cytotoxic chemotherapy, non-cytotoxic systemic therapy and targeted therapy have been revealed as part of different treatment regimens. Recent progress regarding DT biology and molecular pathways has led to the development of promising novel biological agents. In any case, a multidisciplinary approach is required and is gradually employed, espe-cially in intra-abdominal DTs. In this review, we aim to present current knowledge on DF and summarize current treatment regimens as well as their effectiveness, with emphasis on the intraperitoneal type of DT.

Primary Angiosarcoma of the Gastrointestinal Tract: A Systematic Review of the Literature.

Primary Gastrointestinal Angiosarcoma (PGAS) constitutes a rare malignant tumor arising from vascular or lymphatic endothelial cells. The aim of this study was to review the available literature on PGAS and to elucidate its biological behavior and optimal therapeutic approach. PubMed and Embase bibliographical databases were systematically searched (last search April 8th, 2020) for studies concerning PGAS. Ninety-eight studies met our inclusion criteria, involving 110 patients (male/female = 1.5) with an age of 62.40 ± 17.84 (mean, SD) years. They were most frequently located at small (44.5%) and large intestine (35.5%), while 12.7% were multifocal. Surgical resection of the tumor was conducted at 84.0% of the cases combined with adjuvant therapy at 12.3%. One-year cumulative survival was 55.18% (95% CI: 34.33%-71.84%) for large intestine, 30.2% (95% CI: 17.1%-44.5%) for small intestine, whereas multifocal PGAS had a 6-months cumulative survival of 23.08% (95% CI: 5.58%-47.46%). Therefore, PGAS is an extremely rare entity with atypical clinical presentation, challenging diagnosis and aggressive behavior. High clinical suspicion is crucial for its prompt management. Further studies and the development of novel therapeutic agents are required in order to improve survival.

The "misfortune" of being a COVID-19 negative patient during the coronavirus pandemic.

COVID-19 pandemic has obviously affected patients' behavior towards seeking medical help as well as physicians' decision in the management of emergencies. Our recent experience as surgeons at a COVID-19 referral hospital revealed cases which share an alerting characteristic: the delay in appropriate management. Unfortunately for COVID-19 negative patients a "coronacentric" health system has been adopted. In view of measures applied to avoid spread of the disease, a significant delay in patients' presentation as well as in their in-hospital management is observed. We present cases where delay in appropriate management affected the patients' outcome and underline the fact that balancing between COVID-19 safety measures and a patient who needs urgent treatment can be very challenging and stressful.

Evaluation of molecular and genetic predisposing parameters at diverticular disease of the colon.

BACKGROUND: Diverticular disease (DD) refers to the presence of diverticula throughout the gastrointestinal (GI) tract, mainly along colon. DD might evolve into diverticulitis that is accompanied by severe clinical presentation, which includes abscess formation, perforation, stricture, obstruction and/or fistula. AIM: The aim of the present review is to summarize the role of molecular and genetic factors in DD development, as well as their possible contribution towards new prognostic indicators, diagnostic algorithms and new therapeutic approaches. METHODS AND RESULTS: Except from common predisposing parameters, several genetic mutations, immune factors, neurotransmitters, hormones and protein dysfunctions have been associated to the early onset of DD symptoms, pathogenesis and prognosis of the disease. Specific structural changes in the colonic wall, altered matrix composition and compromised motility have been verified as possible pathogenic factors for the development of DD. Dysregulation in peristaltic activity and reduced ability of the longitudinal muscle to relax following contraction has been also associated with DD evolution. In addition, it has been suspected that genetic defects combined with alterations in intestinal microbiota might play an important role in diverticulitis presentation.

Clinical evidence, diagnostic approach and challenging therapeutic modalities for malignant melanoma of the anorectum.

Primary anorectal malignant melanoma (ARMM) is a rare, aggressive tumour that accounts for approximately 1.2% of all melanomas. This rare entity represents less than 5% of anorectal malignant tumours and 0.05-1% of all malignant colorectal neoplasms. The incidence increases with age while there is a higher prevalence in Caucasians. ARMM is often asymptomatic or presents with no disease-specific evidence so that it can mimic other rectal disorders, malignant or benign. Colonoscopy is obligatory as a diagnosing mean for ARMM. Furthermore, endoscopic ultrasonography, computed tomography and magnetic resonance imaging can be utilized for the evaluation of tumour infiltration and lymph node metastases. Moreover, diagnostic establishment of ARMM requires an undeniable demonstration of essential melanocytic features in histology and immunohistochemistry. Even though the standard of treatment remains surgical resection, the choice between wide local excision and abdomino-perineal resection is still controversial. Recently, there have been recommendations regarding new techniques which could be utilized for the surgical treatment of ARMM. Newer treatments that have been proposed such as immune-checkpoint inhibitors and targeted therapies need further validation. A multicenter study would allow clarification of the most appropriate therapeutic strategy for this uncommon nosological entity.

Combined hepatocellular-cholangiocarcinoma: An update on epidemiology, classification, diagnosis and management.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (CHC) is a rare subtype of primary hepatic malignancies, with variably reported incidence between 0.4%-14.2% of primary liver cancer cases. This study aimed to systematically review the epidemiological, clinicopathological, diagnostic and therapeutic data for this rare entity. DATA SOURCES: We reviewed the literature of diagnostic approach of CHC with special reference to its clinical, molecular and histopathological characteristics. Additional analysis of the recent literature in order to evaluate the results of surgical and systemic treatment of this entity has been accomplished. RESULTS: The median age at CHC's diagnosis appears to be between 50 and 75 years. Evaluation of tumor markers [alpha fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)] along with imaging patterns provides better opportunities for CHC's preoperative diagnosis. Reported clinicopathologic prognostic parameters possibly correlated with increased tumor recurrence and grimmer survival odds include advanced age, tumor size, nodal and distal metastases, vascular and regional organ invasion, multifocality, decreased capsule formation, stem-cell features verification and increased GGT as well as CA19-9 and CEA levels. In case of inoperable or recurrent disease, combinations of cholangiocarcinoma-directed systemic agents display superior results over sorafenib. Liver-directed methods, such as transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), hepatic arterial infusion chemotherapy (HAIC), radioembolization and ablative therapies, demonstrate inferior efficacy than in cases of hepatocellular carcinoma (HCC) due to CHC's common hypovascularity. CONCLUSIONS: CHC demonstrates an overlapping clinical and biological pattern between its malignant ingredients. Natural history of the disease seems to be determined by the predominant tumor element. Gold standard for diagnosis is histology of surgical specimens. Regarding therapeutic interventions, major hepatectomy is acknowledged as the cornerstone of treatment whereas minor hepatectomy and liver transplantation may be applied in patients with advanced cirrhosis. Despite all therapeutic attempts, prognosis of CHC remains dismal.

Does vascular occlusion in liver resections predispose to recurrence of malignancy in the liver remnant due to ischemia/reperfusion injury? A comparative retrospective cohort study.

BACKGROUND: Severe ischemic changes of the liver remnant after hepatectomy could expedite tumor recurrence on the residual liver. Our study aimed at assessing the effect of warm ischemic/reperfusion (I/R) injuries on surgery-to-local recurrence interval and patient overall survival, during major hepatectomies under inflow and outflow vascular control. METHODS: One hundred and eighteen patients were subjected to liver resection under total inflow and outflow vascular clamping and were assigned as study group. These individuals were retrospectively matched to 112 counterparts, who underwent liver surgery applying inflow and outflow vascular clamping only of the segment harboring the tumor, sparing the liver remnant from any I/R injury (control group). The two cohorts were compared regarding recurrence-free survival and overall survival. RESULTS: Reversible I/R injuries of the liver remnant subjected to vascular clamping were manifested, with increase of AST values at postoperative day 2 in the study group, as compared to the control group (603 ± 270 U/L vs. 450 ± 290 U/L, p < 0.001), reversing to normal by day 7. Recurrence-free survival and overall survival were no significantly different between the two groups (log rank statistic p = 0.298 and 0.639, respectively). CONCLUSION: Reversible I/R injuries of the liver remnant do not seem to be implicated in the precipitation of local malignant recurrence or in shorter long-term survival, in comparison to a technique sparing the residual liver of I/R injury. This retrospective cohort study was registered at clinicaltrials.gov under unique identifying number: NCT04257240.

Assessment of Synergistic Contribution of Histone Deacetylases in Prognosis and Therapeutic Management of Sarcoma.

Sarcomas are a rare group of neoplasms with a mesenchymal origin that are mainly characterized by the abnormal growth of connective tissue cells. The standard treatment for local control of sarcomas includes surgery and radiation, while for adjuvant and palliative therapy, chemotherapy has been strongly recommended. Despite the availability of multimodal therapies, the survival rate for patients with sarcoma is still not satisfactory. In recent decades, there has been a considerable effort to overcome chemotherapy resistance in sarcoma cells. This has led to the investigation of more cellular compounds implicated in gene expression and transcription processes. Furthermore, it has been discovered that histone acetylation/deacetylation equilibrium is affected in carcinogenesis, leading to a modified chromatin structure and therefore changes in gene expression. In addition, histone deacetylase inhibition is found to play a key role in limiting the tumor burden in sarcomas, as histone deacetylase inhibitors act on well-described oncogenic signaling pathways. Histone deacetylase inhibitors disrupt the increased cell motility and invasiveness of sarcoma cells, undermining their metastatic potential. Moreover, their activity on evoking cell arrest has been extensively described, with histone deacetylase inhibitors regulating the reactivation of tumor suppressor genes and induction of apoptosis. Promoting autophagy and increasing cellular reactive oxygen species are also included in the antitumor activity of histone deacetylase inhibitors. It should be noted that many studies revealed the synergy between histone deacetylase inhibitors and other drugs, leading to the enhancement of an antitumor effect in sarcomas. Therefore, there is an urgent need for therapeutic interventions modulated according to the distinct clinical and molecular characteristics of each sarcoma subtype. It is concluded that a better understanding of histone deacetylase and histone deacetylase inhibitors could provide patients with sarcoma with more targeted and efficient therapies, which may contribute to significant improvement of their survival potential.

Contribution of Histone Deacetylases in Prognosis and Therapeutic Management of Cholangiocarcinoma.

Cholangiocarcinoma (CCA), a malignant tumor that occurs in the epithelium of the biliary tract, has a very poor prognosis because affected patients are frequently diagnosed at an advanced stage and recurrence after resection is common. Over the last two decades, our understanding of the molecular biology of this malignancy has expanded, and various studies have explored targeted therapy for CCA in order to improve patient survival. The histone acetylation/deacetylation equilibrium is affected in carcinogenesis, leading to altered chromatin structure and therefore changes in gene expression. Understanding the molecular identity of histone deacetylases (HDACs), their cellular interactions and potential role as anticancer agents will help us develop new therapeutic strategies for CCA-affected patients. Furthermore, HDAC inhibitors act on cellular stress response pathways and decrease cancer angiogenesis. Downregulation of pro-angiogenic genes such as vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1), and endothelial nitric oxide synthase (eNOS) inhibit formation of new vessels and can negatively affect the metastatic process. Finally, recent clinical trials prove that administration of both HDAC inhibitors and DNA-targeting chemotherapeutic agents, such as topoisomerase inhibitors, DNA intercalating agents, inhibitors of DNA synthesis, covalently modifying DNA agents, and ionizing radiation, maximizes the anticancer effect by increasing the cytotoxic efficiency of a variety of DNA-damaging anticancer drugs. Therefore, combination therapy of classic chemotherapeutic drugs with HDAC inhibitors can act synergistically for the patients' benefit.

Malignant melanoma of the breast: controversies in the diagnosis and therapeutic management of a rare nosologic entity.

Melanoma of the breast is an infrequent entity, presenting as either primary or metastatic from extramammary solid neoplasms. Depending on the involvement of the skin, primary malignant melanoma of the breast (PMMB) can be classified as cutaneous or noncutaneous. Cutaneous PMMB accounts for <5% of all melanomas and only 0.5% of all breast cancers. Furthermore, despite the rarity of metastatic breast neoplasms, melanoma comprises a frequent source of metastases. Metastatic potential of melanoma is associated with poor prognosis, and the majority of patients present more than one metastatic foci at the time of diagnosis. Diagnostic approach for both primary and metastatic melanomas of the breast is substantiated by fine needle aspiration (FNA) cytology along with immunohistochemistry. Nevertheless, verification of a metastatic mammary melanoma requires the discovery of a primary lesion. The mainstay of treatment for primary tumors is surgery, with radical local excision and axillary lymph node dissection or, on occasion, axillary sentinel node resection, while for metastatic tumors it depends on the specificities of the melanoma. Adjuvant therapy is always implemented. The aim of this survey is to meticulously review the literature of primary and metastatic malignant melanomas of the breast and report epidemiologic and clinicopathologic data for this rare entity. Clinical features, histogenesis, morphological, and immunochemical findings are discussed, while the role of current diagnostic and therapeutic management of this uncommon entity is emphasized.

Primary Angiosarcoma of the Kidney: Literature Review of a Rare Nosologic Entity.

Primary angiosarcoma of the kidney is a rare tumor, hence little is known concerning its diagnostic features and therapeutic management. We conducted this survey to present a complete literature review with emphasis on clinicopathological features, diagnosis and therapy. A thorough search was conducted in MEDLINE/PubMed. All relevant studies concerning primary renal angiosarcomas in adults were thoroughly reviewed. Primary renal angiosarcoma is characterized by an overall poor prognosis, is of unknown etiology and occurs most commonly in males between 60 and 70 years old. Presence of distant metastasis at the time of diagnosis is prevalent. Histopathological examination and immunohistochemical studies are the most important diagnostic tools. Treatment options include surgery, chemotherapy, radiotherapy and immunotherapy. Conclusion: Primary renal angiosarcoma is a rare but aggressive malignancy with low response to available therapeutic regimens and dismal survival rates.

Successful management of adhesion related small bowel ischemia without intestinal resection: A case report and review of literature.

BACKGROUND: Intraabdominal adhesions develop spontaneously or after an inflammatory process or surgical procedure in the abdomen. They are the most common cause of small bowel obstruction (SBO). SBO occasionally leads to intestinal ischemia (InIs) which can be a life-threatening condition that requires management as soon as possible. We herein report a case of SBO with InIs presented in our institution and treated without intestinal resection. CASE SUMMARY: A 34-year-old man presented at the emergency department after a 12-h-onset diffuse abdominal pain, bloating and nausea. He had a history of traumatic right hepatectomy 11 years ago as well as adhesiolysis and resection of a long part of small bowel 2 years ago. An abdominal computed tomography (CT) showed dilated loops that led to the diagnosis of SBO. Due to deteriorating lactic acidosis, the patient was operated. Torsion of the small bowel around an adhesion led to 2.30 m of ischemic ileum. After the application of N/S 40 °C for 20 min, the intestine showed signs of improvement and it was decided to avoid resection and instead temporary close the abdomen with vacuum-pack technique. At the second-look laparotomy 48 h later, the intestine appeared normal. The patient was discharged on the 8th post-op day in excellent condition. CONCLUSION: In case of SBO caused by adhesions, extreme caution is needed if InIs is present, as the clinical signs are mild and you should rely for diagnosis in CT findings and lactate levels. Conservative surgical approach could reverse the effects of InIs, if performed quickly, so that intestinal resection is avoided and should be used even when minimum signs of viability are present.

Resection of abdominal inferior vena cava without graft interposition: Considerations in preserving renal function.

The management of tumors involving or infiltrating the inferior vena cava (IVC) constitutes a great surgical challenge, since radical resection affords patients the only possibility for long-term survival. These tumors can be resected without graft interposition, provided that there is adequate collateral circulation and that the renal function can be secured. Meanwhile, ligation of the left renal vein may be possible due to the existence of collateral circulation through the adrenal and gonadal veins. We briefly present our experience on renal outflow preservation through implantation of the right renal vein into the IVC stump or through diversion of the left renal vein into the inferior mesenteric vein.

Trauma system in Greece: Quo Vadis?

INTRODUCTION: Implementation of trauma systems has markedly assisted in improving outcomes of the injured patient. However, differences exist internationally as diverse social factors, economic conditions and national particularities are placing obstacles. The purpose of this paper is to critically evaluate the current Greek trauma system, provide a comprehensive review and suggest key actions. METHODS: An exhaustive search of the - scarce on this subject - English and Greek literature was carried out to analyze all the main components of the Greek trauma system, according to American College of Surgeons' criteria, as well as the WHO Trauma Systems Maturity Index. RESULTS: Regarding prevention, efforts are in the right direction lowering the road traffic incidents-related death rate, however rural and insular regions remain behind. Hellenic Emergency Medical Service (EKAB) has well-defined communications and emergency phone line but faces problems with educating people on how to use it properly. In addition, equal and systematic training of ambulance personnel is a challenge, with the lack of pre-hospital registry and EMS quality assessment posing a question on where the related services are currently standing. Redistribution of facilities' roles with the establishment of the first formal trauma centre in the existing infrastructure would facilitate the development of a national registry and introduction of the trauma surgeon subspecialty with proper training potential. Definite rehabilitation institutional protocols that include both inpatient and outpatient care are needed. Disaster preparedness entails an extensive national plan and regular drills, mainly at the pre-hospital level. The lack, however, of any accompanying quality assurance programs hampers the effort to yield the desirable results. CONCLUSION: Despite recent economic crisis in Greece, actions solving logistics and organising issues may offer a well-defined, integrated trauma system without uncontrollably raising the costs. Political will is needed for reforms that use pre-existing infrastructure and working power in a more efficient way, with a first line priority being the establishment of the first major trauma centre that could function as the cornerstone for the building of the Greek trauma system.

Penetrating Thoracic Trauma Patients with Gross Physiological Derangement: A Responsibility for the General Surgeon in the Absence of Trauma or Cardiothoracic Surgeon?

BACKGROUND: Penetrating trauma is becoming increasingly common in parts of the world where previously it was rare. At the same time, general surgeons and surgical trainees are becoming more specialized, and less comfortable operating within areas beyond their zone of specialization. OBJECTIVE: The purpose of this manuscript is to assess the technical difficulties encountered in operating on patients who have sustained penetrating trauma, and to prove to general surgeons that the technical skills and techniques required are no different to those required for abdominal surgery, and do not require additional dexterity. METHODS: This prospective study was conducted in an Academic Trauma unit over a 3-year period. All patients who were operated upon for penetrating thoracic trauma were included in the study. The pre-operative management, techniques of surgical repair and the outcome were assessed. RESULTS: One hundred and forty-five patients were included in the study over a 3-year period. There were 97 patients with stab wounds, 47 with gunshot wounds and 1 patient with an injury from an angle grinder. Mortality was six times greater in those patients with gunshot wounds, than those with stab wounds. Several patients had multiple thoracic organ injuries. There were 57 patients who were operated upon for thoracic vessel injury. There was a 3.5 % mortality overall. Eighty-eight patients sustained pulmonary injury with a 7 % mortality, and they were managed mainly by simply repair, tractotomy or stapled partial non-anatomical lobectomy. Of the 39 patients with cardiac trauma, there was 17 % mortality, and all cases were managed by simple repair. There were 5 patients with an oesophageal injury of whom 3 died (mortality of 60 %). Twenty-four patients had thoraco-abdominal injuries with 30 % mortality. CONCLUSION: Most of the injuries in the chest can be managed by simple procedures to control life-threatening bleeding. The techniques required are similar to those taught to and are practiced comfortably by general surgeons used to work in the abdominal cavity. We encourage the general surgeon who receives a grossly unstable patient with penetrating thoracic trauma to operate, instead of adding risk to the patient's physiology by a transfer to cardio-thoracic or dedicated trauma units.

Mucocele of the Appendix: Dilemmas in Differential Diagnosis and Therapeutic Management.

Mucocele of the appendix (AM) is a descriptive term for mucinous distension of the appendiceal lumen. It refers to the progressive retrograde dilatation of the vermiform appendix. Because of a lack of specific signs or due to its sometime quiet presentation, this condition is frequently diagnosed only at an advanced stage. We present three isolated cases of AM complicated by the development of acute inflammation of the appendix. Currently, the assessment of appendiceal lesions relies heavily on Ultra Sonography (US) as the primary diagnostic tool. This however may not always identify the origin of such a tumour. Therefore, additional investigative modalities are implemented. Despite recent research on the therapeutic strategies against appendiceal neoplastic disorders, surgical resection appears the only potentially curative approach. Accepted management includes appendectomy, right hemicolectomy, partial colectomy with debulking or palliative resection combined with additional chemotherapy. Even if laparoscopy has been successfully used to perform appendectomy, some concerns exist regarding its use in dealing with mucinous secreting lesions because of possible spillage of mucin intra-operatively. The aim of this investigation was to analyze all cases of AM complicated by the development of acute inflammation of the appendix presented in our institution. The relevant literature is briefly reviewed. Clinical features, diagnostic approach and management algorithm for appendiceal lesions are also discussed.