Optimizing Adjuvant Therapy after Surgery for Colorectal Cancer Liver Metastases: A Systematic Review.

The liver is the most common site of colorectal cancer metastatic spread. Although metastasectomy is the gold standard for fit patients with resectable colorectal cancer liver metastases (CRLMs), their management after surgical treatment remains controversial. The objective of this systematic review was to collate the currently available data of the agents used in the adjuvant setting in order to define the most optimal therapeutic strategy. A systematic review of the literature was conducted by searching PubMed/Medline and Cochrane library databases. We included studies that evaluated the efficacy, the tolerability and the safety profile of various chemotherapeutic agents that are used as adjuvant treatment after surgical resection of CRLMs. The outcomes of interest were regression-free survival (RFS), disease-free survival (DFS), overall survival (OS) and severe toxicities. From 543 initial articles, 29 publications with 7028 patients were finally included. In general, the results of the eligible studies indicated that adjuvant therapy after resection of CRLMs led to improved RFS/DFS rates, but this benefit did not contribute to a statistically significant prolongation of OS. Moreover, the choice of the therapeutic strategy, namely systematic or regional chemotherapy or the combination of both, did not seem to have a differential impact on patient outcomes. However, these results should be interpreted with caution since the majority of the chosen studies are of low or moderate quality. In this context, further high-quality clinical trials conducted on patient sub-populations with modern therapies are required in order to reduce in-study and between-study heterogeneity and determine which patients are expected to derive the maximum benefit from adjuvant therapy after surgery for CRLMs.

Iron Deficiency Anemia in Colorectal Cancer Patients: Is Preoperative Intravenous Iron Infusion Indicated? A Narrative Review of the Literature.

Iron deficiency anemia is the most common extraintestinal symptom in patients with colorectal cancer (CRC). Inflammation associated with malignancy leads to functional iron deficiency via the hepcidin pathway, whereas chronic blood loss causes absolute iron deficiency and depletion of iron stores. The assessment and treatment of preoperative anemia is of great importance in patients with CRC, since published data have consistently shown that preoperative anemia is associated with increased need for perioperative blood transfusions and more postoperative complications. Recent studies have documented mixed results regarding the preoperative intravenous iron administration in anemic CRC patients in terms of efficacy for anemia correction, cost-effectiveness, need for transfusions and risk for postoperative complications.

Indications, Safety, Efficacy and Survival Benefit of Intraperitoneal Chemotherapy in Patients With Advanced Gastric Cancer.

BACKGROUND/AIM: Advanced gastric cancer remains a significant concern for the medical community mostly due to the locoregional extension of the disease. Most commonly, stomach neoplasms are resectable, but not curable, due to the elevated percentage of peritoneal dissemination after gastrectomy and extensive lymph node dissection. Locoregional intraperitoneal chemotherapy plays a pivotal role in overall survival and prognosis of patients with advanced gastric cancer and shows a high probability of peritoneal dissemination after gastrectomy. In this review, we aimed to collect and present literature data concerning intraperitoneal chemotherapy in advanced stages of gastric cancer as well as evaluate the safety and survival benefit of the procedure. MATERIALS AND METHODS: We conducted a survey including all randomized controlled trials and clinical trials that were published in the last 30 years. The keywords used were: advanced gastric cancer, intraperitoneal chemotherapy and peritoneal carcinomatosis. We searched for clinical trials in Pubmed, Embase databases and the Cochrane library. Inclusion criteria were: patients with advanced gastric cancer with no macroscopical signs of peritoneal dissemination, who were treated with D2 gastrectomy and received one or more cycles of intraperitoneal chemotherapy. The final review included 20 articles. RESULTS: The safety of intraperitoneal chemotherapy, as well as the survival benefit of patients were evaluated. The majority of articles denoted that intraperitoneal chemotherapy is a safe procedure without severe or lethal complications. The majority of complications were hematological while non-hematologic complications were also noted. A survival benefit with statistically significant results (p<0.05) was observed in 6 out of 10 randomized controlled trials. CONCLUSION: Intraperitoneal chemotherapy for advanced gastric cancer is a safe procedure with promising results regarding survival benefit and prognosis. Further patient evaluation is required in order to standardize the type of chemotherapeutic agent and the sufficient dose and cycles for the most appropriate results.

Giant Ovarian Thecoma Associated with Meigs Syndrome: A Striking Case.

Introduction: Meigs syndrome consists of the presence of a benign ovarian tumor, ascites and pleural effusion, and the latter two subdued after surgical excision of the ovarian tumor. Elevated Ca-125 in this context is confusing and is reported only in a handful of cases. A rare but striking case with the above features is presented herein. Case Presentation: A 46-year-old woman with a giant pelvic/abdominal mass originating from her right adnexa, ascites and pleural effusion, with elevated Ca-125 (938 IU/mL) was treated with the presumptive diagnosis of stage IV ovarian cancer. Imaging modalities showed a 22 cm solid adnexal mass and the patient underwent total abdominal hysterectomy and bilateral salpigooophorectomy, omentectomy and drainage of 4L of ascetic fluid. Surprisingly, final histopathology was negative for malignancy, characterizing the primary tumor as ovarian thecoma. Ascites and pleural effusion resolved by the seventh postoperative day, setting the diagnosis of Meigs syndrome. Discussion: Meigs syndrome accounts for 1% of all ovarian tumors, however it should be considered in the differential diagnosis when clinicians come across the classic triad of the syndrome, even when Ca-125 is elevated. These patients have normal life expectancy with meticulous management, while pathophysiology of this condition remains uncertain in various points.

Single Dose of Sildenafil and Atorvastatin Increase Skin Survivability, but only Atorvastatin Increase Nitric Oxide in Rat Ischeamia Reperfusion Model.

Background: Ischeamia reperfusion injury is a frequent challenge during tissue reconstruction. Atorvastatin and Sildenafil, have been studied for their protective and/or therapeutic effects on various organ systems subjected to IRI. The aim of the present study was to compare a single dose of Atorvastatin and Sildenafil pretreatment on acute oxidative/nitrosative stress and the subsequent dermal flap necrosis. Materials and Methods: Forty-five Sprague-Dawley rats, were randomly allocated into three equal groups(n=15): Group A: Control rats treated with intraperitoneal saline, Group B: Sildenafil group, and Group C: atorvastatin group. All rats underwent flap elevation and inferior epigastric artery occlusion thirty minutes after drug administration. Myeloperoxidase activity, malondialdehyde levels and inducible nitric oxide synthase activity were evaluated 12 hours after reperfusion. Flap survivability was analysed 7 days after the procedure. Results: Statistically significant reduction was detected in sildenafil and atorvastation. Measurements of myelopyroxidase followed a similar pattern, interestingly malonadehyde levels measured to be significantly lower in the sildenafil group. Contrary, iNOS activity atorvastatin was significantly elevated in atorvastatin group. Conclusion: The single dose of atorvastatin or sildenafil increase flap survivability almost equally, however only atorvastatin enhances significantly iNOS expression.

Comparison of the laparoscopic versus open surgery in patients aged over 75 years old with colorectal cancer. Short- and Mid-term outcomes.

PURPOSE: The benefit of minimally invasive surgery in colorectal cancer patients has been established, however it is not clear whether these advantages apply to older patients as well. The aim of this study was to review short- and mid-term outcomes in elderly patients, over the age of 75 years, with colorectal cancer. METHODS: This was a retrospective study of selected patients over the age of 75 who underwent laparoscopic and open surgery for colorectal cancer between February 2013 and January 2018 in a tertiary referral center. All patients were categorized in two groups: Group 1 included patients who had open procedure (OP) and Group 2 those who underwent laparoscopic procedure (LP). Demographic, clinical, short- and midterm postoperative data were collected and analyzed between the two study groups. RESULTS: A total of 78 patients were included in our cohort; 39 (50%) were operated with LP. The LP was equally safe in comparison with the OP, considering the similar postoperative complications [9 patients (34.6%) in LP and 5 patients (18.5%) in OP (p=0.224)], including anastomotic leakage in 2 patients (7.7%) in LP and 1 patient (3.7%) in OP group (p=0.61). The median postoperative hospital stay favored the laparoscopic approach (6 days in LP group and 8 days in OP group; p=0.001). The number of harvested lymph nodes were without statistically significant differences [LP group retrieved 20.0 nodes in comparison with 20.5 nodes in OP group (p= 0.816)]. The overall survival analysis showed no difference between the two approaches in 12 and 24 postoperative months (p=0.098 and 0.387, respectively).

Receptor-Binding Cancer Antigen Expression in Thyroid Neoplasms: A Retrospective Study.

Background: Receptor-binding cancer antigen (RCAS1) is a membrane protein, regarded as a tumor-associated antigen. Cancer cells evade immune response with RCAS1 up-regulation, inducing apoptosis to tumor infiltrating lymphocytes. Thyroid cancer incidence is rising and its accurate diagnosis in early stage is targeted. The aim of this study is to access RCAS1 expression in benign and malignant thyroid pathology. Methods: This is a retrospective study of 110 patients, who had thyroidectomy in a single tertiary referral centre between January 2008 until December 2014. Immunohistochemistry study for RCAS1 expression was carried out and correlation with clinical and histopathological data is attempted. Results: RCAS1 immunostaining was found positive in 81 out of 110 cases. Notably it was deemed positive in all malignant thyroid tissue samples (p 0.001). In thyroid malignancy, tumor size, thyroid capsule invasion and positive lymph nodes status were positively correlated with moderate and strong expression of RCAS1. For papillary thyroid carcinoma, the vast majority (35/37 cases, 94.6%) were also classified as having moderate or strong RCAS1 expression. Conclusions: RCAS1 expression can aid in differential diagnosis between benign and malignant thyroid pathology, while its strong expression correlates with worse oncological features.

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.

Neoadjuvant chemoradiotherapy in rectal cancer and anorectal sphincter dysfunction: Review of the literature.

PURPOSE: The purpose of this article was to review the current medical literature regarding deterioration of anorectal function in patients receiving neoadjuvant chemoradiotherapy before surgery for locally advanced rectal cancer. METHODS: We reviewed the current literature including research studies, electronic database PUBMED-MEDLINE, published research results and metanalysis papers from high-volume institutes, collecting and comparing the different results. Pathophysiology as well as emerging solutions for treating anorectal sphincter dysfunction were researched in order to provide an insight of this complex issue. RESULTS: All available data suggest that neoadjuvant radiation therapy impairs internal anal sphincter function mostly through nerve damaging mechanisms, as nerves are more susceptible to damage than muscular fibers. CONCLUSION: Current radiotherapy recommendations are oriented in exclusion of anal canal from radiation field when oncologically safe or using new sphincter-sparing techniques for neoadjuvant radiotherapy aiming to improve the patient quality of life receiving radiation therapy prior to surgery. However, more well designed studies are required to assess the pathophysiology as well as treatment options for this complex matter, which strongly affects the quality of life of rectal cancer patients.

Primary adrenal leiomyosarcoma: A case report.

Adrenal leiomyosarcomas are rare mesenchymal tumors of the suprarenal region that are usually diagnosed after they have reached a large size. We report the case of a 62-year-old male with an incidentally found left adrenal mass. Magnetic resonance imaging of the retroperitoneal space showed a heterogeneously enhanced mass, measuring 10x8.2 cm, with characteristics suspicious of malignancy. The patient underwent left radical adrenalectomy after the hormonal evaluation of the tumor due to the high probability of adrenocortical carcinoma. However, microscopic examination of the tumor showed a spindle cell sarcoma. Immunohistochemically the neoplastic cells were found positive for desmin and smooth muscle actin and the diagnosis of a well differentiated adrenal leiomyosarcoma was established. During follow-up the patient presented an aggressive course as he developed bone, liver and pulmonary metastases early postoperatively, which were treated with radiation therapy and chemotherapy. The patient has progressive metastatic disease while on chemotherapy 31 months after surgery.

Survivin expression in hepatocellular carcinoma. Correlation with clinicopathological characteristics and overall survival.

PURPOSE: Survivin expression is a potential prognostic indicator in various carcinomas. The prognostic value of Survivin for survival in hepatocellular carcinoma, (HCC) however, remains controversial. The aim of the study is to examine the expression of the inhibitor of apoptosis Survivin in HCC and investigate the correlation with the clinic-pathologic characteristics and overall survival (OS) following surgical resection. METHODS: Specimens from patients with resected HCC were examined by Immunohistochemical staining for Survivin and BCL-2expression. Clinical and histopathological data were retrieved from medical and pathology records, while OS was determined by reviewing records from the department of Oncology and personal communication with survivors. Bivariate analysis was performed using the Chi-square and Mann-Whitney U tests, while survival was estimated by Kaplan Meier method and compared with log-rank test. RESULTS: Sixty patients were included in the study. Survivin was expressed in 26 patients (43.3%). Survivin expression was significantly correlated to OS (p=0.014). A statistically significant negative correlation between Survivin and BCL-2 was also noted (p<0.001). CONCLUSIONS: Survivin expression reflects aggressive histological and clinical behavior of HCC and correlates with poorer OS. Further studies are required to confirm if Survivin can be used as a predictive biomarker to evaluate prognosis and target treatments for HCC.

Long non-coding RNA polymorphisms and prediction of response to chemotherapy based on irinotecan in patients with metastatic colorectal cancer.

BACKGROUND: Colorectal cancer is the fourth cause of cancer related death. Drug resistance and toxicity remain major clinical issues. HOTAIR and MALAT1 are long non-coding RNAS that affect cellular proliferation, apoptosis and drug resistance; their up-regulation has been linked with a poor prognosis. OBJECTIVE: Investigation of the association between rs4759314 HOTAIR and rs3200401 MALAT1 polymorphisms and irinotecan-based chemotherapy in terms of drug efficacy and toxicity. METHODS: Samples from 98 patients receiving different regimens of irinotecan-based therapy were included. Efficacy and toxicity were evaluated. KRAS mutation, rs3200401 HOTAIR and rs4759314 MALAT1 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR. RESULTS: Neither rs3200401 MALAT1 nor rs4759314 HOTAIR polymorphism are associated with response to treatment regimens. Rs4759314 was also not associated with increased toxicity in patients receiving irinotecan-based regimens. CT genotype of rs3200401 was associated with significantly reduced overall survival. An association between KRAS mutation and AG/GG genotypes in the rs4759314 was detected. CONCLUSIONS: CT genotype of rs3200401 MALAT1 polymorphism could serve as a toxicity biomarker. Carriers of the G allele of the rs4759314 HOTAIR are more likely to be carriers of KRAS mutations too. However, further studies in larger patient populations are required.

The Role of TAMIS (Transanal Minimally Invasive Surgery) in the Management of Advanced Rectal Cancer - One Shared Story of Three Exceptional Cases.

Purpose of the study: The current gold standard for contemporary treatment of rectal cancer is total mesorectal excision (TME), achieving excellent local disease control and low recurrence rates. However, TME may be associated with postoperative mortality and quality of life deterioration. Therefore, the need to develop less radical treatment strategies has emerged. Transanal minimally invasive surgery (TAMIS) is currently indicated only for early rectal cancer. However, local excision following chemoradiation has yielded promising clinical outcomes in selected cases with more advanced disease. Materials and methods: We describe three cases of patients with advanced rectal cancer, who were managed with TAMIS, either due to patients' unwillingness to tolerate permanent colostomy or due to significant comorbidities. Results: Two of the three patients who also received adjuvant chemoradiation are still in remission for 18 and 15 months respectively. The third patient died early after hospital release due to unrelated causes. Conclusions: Local excision utilizing minimally invasive techniques, alongside with chemoradiotherapy and close follow up can be a viable alternative in carefully selected rectal cancer patients with advanced disease who deny permanent colostomy or are ineligible for major operations.

Left Gastroepiploic Artery True Aneurysm: Case Report and Review of the Literature.

Although the aneurysm of the splenic artery represents the third most common abdominal arterial aneurysm next to the aortic and iliac aneurysms, the aneurysm of the gastroepiploic artery is extremely rare occurring at a frequency of 3-4% of all visceral arteries' aneurysms; only 17 cases have been reported in the English literature. We present the case of a 65-year-old woman with an asymptomatic visceral artery aneurysm, which was an incidental ultrasonography finding. Magnetic resonance imaging showed an arterial aneurysm close to the peripheral splenic artery with intense tortuosity of the celiac and splenic artery. Abdominal computed tomography angiography confirmed the existence of an arterial aneurysm with a diameter of 2.3 cm near the splenic hilus without identifying the involved vessel. Endoluminal treatment was considered cumbersome due to anticipated anatomic obstacles; the patient underwent an elective open surgery in which the tortuosity of the celiac and splenic arteries and the aneurysm of the left gastroepiploic artery were revealed. The aneurysm was resected after proximal and distal ligation of the gastroepiploic artery; the flow of the splenic artery was intact. Histologically, it was a true aneurysm. The patient left the hospital on the fourth postoperative day without any complication. Historically, most aneurysms of the gastroepiploic arteries have been observed in men in the sixth decade of their life and after rupture; in modern times, their early incidental apocalypse is frequent due to the widespread use of imaging studies. Diagnostic approach and preoperative planning is of paramount importance to avoid complications. Current therapeutic modalities include catheter-based techniques or laparoscopic surgery.

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.

Reversal of Acute Mesenteric Ischemia by Salvation of the Meandering Mesenteric Artery with Stenting of the Left Internal Iliac Artery.

The presence of the meandering mesenteric artery, which is a nonconstant tortuous arterial component unifying the peripheral intestinal circulation, is evidence of chronic occlusive disease of the main intestinal arteries. This collateral intestinal arterial pathway, when present, must be preserved in any abdominal intervention, as it is often the only remaining arterial supply of the intestine; its ligation can be accompanied by intestinal ischemia. We present herein, the case of a 42-year-old man, heavy smoker, who had chronic mesenteric ischemia without particular clinical manifestations till the hospitalization for acute myocardial infarction for which he underwent balloon angioplasty and stenting of the left circumflex coronary artery. Three days later, he experienced acute-on-chronic intestinal ischemia with crescendo clinical manifestations; intra-arterial angiography revealed the presence of a meandering mesenteric artery in a milieu of celiac, superior and inferior mesenteric, and right internal iliac artery occlusion accompanied by a tight stenosis of the left internal iliac artery. Successful stenting of the orifice of the left internal iliac artery was followed by a well-defined dilatation of the meandering artery, revascularization of the peripheral branches of the inferior-through the superior hemorrhoidal artery-and superior mesenteric arteries and complete resolution of the acute mesenteric ischemia. Thus, time was gained for the patient in order to have, if needed, a future elective open revascularization of the mesenteric artery, when the perioperative risk of mortality from the recent myocardial infarction and the coronary angioplasty and stenting will be minimal.

Large Paraesophageal Hiatus Hernia: Is Surgery Mandatory?

Purpose/Aim: Paraesophageal hiatus hernias are seldom found, however the incidence is increasing accounting for 5-10% of all hiatal hernias. The aim of this review is to emphasize controversies in clinical presentation, essential workup investigations and highlight non-surgical and surgical management options. Materials and Methods: A PubMed literature search using the keywords "large or giant paraesophageal hernia", "hiatus or hiatal hernia", "laparoscopic surgery", "antireflux surgery", "mesh", "gastric volvulus" and "diaphragmatic hernia" published between 1998 until 2017 was conducted. Results: Presenting symptoms are non-specific and can be erroneously attributed to various more common medical conditions. Significant complications as gastric volvulus and stomach necrosis, may occur and the obscured clinical presentation can be confusing for the clinician. Management options in the elective setting are controversial, and surgical repair cannot be easily justified for a minimally symptomatic condition, especially in an elderly and perhaps frail patient. However, in the era of laparoscopic surgery around the hiatus, reduced operative stress makes surgical repair appealing in the elective setting. Surgical matters as the adjunct of an antireflux procedure or not, the use of prosthetic mesh to reinforce the hiatus, gastropexy and the clinical importance of radiological or endoscopic recurrence are still under debate. Conclusions: The laparoscopic treatment of paraesophageal hiatus hernias is effective with low morbidity rates, offered in symptomatic patients and good operative risk asymptomatic individuals. More studies are needed to assess improvement suggestions, as the use of prosthetic mesh or gastropexy, regarding complications and recurrence risks.

Novel Endoscopic Management of Eroding Laparoscopic Adjustable Gastric Band: A Case Series.

Complications of laparoscopic adjustable gastric bands include migration and slippage of the band, dilation of the proximal gastric pouch, troublesome gastroesophageal reflux symptoms, and erosion of the stomach. The latter occurs in 0.6-12.7% of cases and necessitates removal of the band. Several open and laparoscopic surgical techniques have been described for band extraction, while fully endoscopic techniques have emerged and proven safe. Three cases of eroding gastric bands treated in a single center with fully endoscopic removal of the band are analyzed in this study. Novel use of the duodenoscope and endoscopic retrograde cholangiopancreatography instruments and accessories is described, in order to perform endoscopic division of the plastic band and retraction through the mouth. All three cases were successfully treated utilizing this novel technique. Gastric wall erosion from the band has nonspecific symptoms and various predisposing factors. Removal of the foreign material is required. Endoscopic procedures are effective in 77-92% of cases, avoiding general anaesthesia with low surgical morbidity. As a result patients are discharged early resolving quicker to a normal diet.