The Role of Hyperthermic Intraperitoneal Chemotherapy in Uterine Cancer Therapy.

Endometrial cancer and uterine sarcoma represent the two major types of uterine cancer. In advanced stages, both cancer entities are challenging to treat and correlate with a meagre survival and prognosis. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a form of localized chemotherapy that is heated to improve the chemotherapeutic effect on peritoneal metastases. The aim of the current review is to study the role of HIPEC in the treatment of uterine cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms "hyperthermic intraperitoneal chemotherapy", "uterine cancer", "endometrial cancer", and/or "uterine sarcoma", we managed to identify 26 studies published between 2004 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HIPEC as treatment modality for peritoneally metastasized uterine cancer. Patients treated with cytoreductive surgery, alongside HIPEC, seem to profit from not only higher survival but also lower recurrence rates. Factors such as the completeness of cytoreductive surgery, the peritoneal cancer index, the histologic subtype, or the applied chemotherapeutic agent, all influence HIPEC therapy effectiveness. In summary, HIPEC seems to represent a promising treatment alternative for aggressive uterine cancer.

FDA-Approved Monoclonal Antibodies for Unresectable Hepatocellular Carcinoma: What Do We Know So Far?

Unresectable hepatocellular carcinoma (HCC) is an advanced primary liver malignancy with a poor prognosis. The Food and Drug Administration (FDA) has, to date, approved nivolumab, pembrolizumab, ramucirumab, nivolumab/ipilimumab, atezolizumab/bevacizumab, as well as tremelimumab/durvalumab, as first- or second-line monoclonal antibodies (mAbs) for unresectable HCC. The present review examines the current state of knowledge, and provides a useful update on the safety and efficacy of these therapeutic agents, thus attempting to define the suitability of each mAb for different patient subgroups.

Targeted Therapies for Hepatocellular Carcinoma Treatment: A New Era Ahead-A Systematic Review.

Hepatocellular carcinoma (HCC) remains one of the most common malignancies and the third cause of cancer-related death worldwide, with surgery being the best prognostic tool. Among the well-known causative factors of HCC are chronic liver virus infections, chronic virus hepatitis B (HBV) and chronic hepatitis virus C (HCV), aflatoxins, tobacco consumption, and non-alcoholic liver disease (NAFLD). There is a need for the development of efficient molecular markers and alternative therapeutic targets of great significance. In this review, we describe the general characteristics of HCC and present a variety of targeted therapies that resulted in progress in HCC therapy.

Operating on Jehovah's Witnesses: A Challenging Surgical Issue.

Blood transfusion is often utilized in surgery. Greece is the second-highest consumer of blood components in Europe. It has been shown that at least half of all transfusions are unnecessary and could be avoided. Jehovah's Witnesses (JWs) are a Christian religion that do not accept transfusion of whole blood or the four primary components of blood-namely, red blood cells, white blood cells, platelets, and plasma. This a retrospective study from September of 2015 to January of 2018, analyzing all JWs who underwent an elective operation at the Second Department of Propaedeutic Surgery in Laiko University Hospital. Twenty-nine (Rogers et al. in NCCN Guidelines Version 2.2014 Cancer- and Chemotherapy-Induced Anemia. NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network, Fort Washington, 2013) JW patients, 23 females (74.1%) and eight males, were operated on during the aforementioned period. The median ASA score was 1 (range 1-3), and only two of the patients needed postoperative monitoring in the ICU. Almost half of the patients (45.1%) needed iron infusion and EPO injection preoperatively. Two patients presented with postoperative complications, with no postoperative deaths. In conclusion, we found that surgery, in our small group of JW patients, was safe and successful despite the lack of blood transfusion. Techniques developed to treat JW patients should be more widely used to improve clinical outcomes and reduce costs to the healthcare system.

MAP17 Expression in Colorectal Cancer Is a Prognostic Factor for Disease Recurrence and Dismal Prognosis Already in Early Stage Disease.

BACKGROUND: Disease recurrence in colorectal cancer constitutes a major cause of significant cancer-associated morbidity and mortality. MAP17 is a small protein, and its overexpression in malignant tumors has been correlated with aggressive tumor phenotypes. The aim of the present study was to investigate the expression patterns of MAP17 in colorectal cancer specimens and to assess its clinical significance. PATIENTS AND METHODS: Surgical specimens of 111 patients with primary resectable colorectal cancer constituted the study population. Expression of MAP17 was assessed by immunohistochemistry, and the results were correlated with clinical and survival data. RESULTS: MAP17 was expressed in cancer cells and endothelial cells of tumor blood vessels. Expression of MAP17 more than 10% was correlated with advanced disease stage (p < 0.001), higher T classification (p = 0.007), the presence of lymph node metastasis (p < 0.001), vascular (p = 0.013) and perineural invasion (p = 0.012). Patients exhibiting MAP17 expression of more than 30% in cancer cells compared to those expressing MAP17 less than 10% demonstrated a significantly worse 3-year progression-free survival (35.2 vs. 91%, p < 0.001) and 5-year overall survival (40.8 vs. 91%, p < 0.001). Cox regression analysis confirmed MAP17 expression of more than 30% as a prognostic marker of progression free survival (HR 0.136, 95% CI = 0.056-0.329, p < 0.001) and overall survival (HR 0.144 [95% CI) = 0.049-0.419, p < 0.001) independent of other clinicopathological characteristics. Statistically significantly worse 3-year progression-free survival and 5-year overall survival was demonstrated in the subgroup analysis of patients with early stage cancer only and high expression of MAP17. CONCLUSIONS: High MAP17 expression in patients with colorectal cancer is a significant risk factor for cancer-associated morbidity and mortality already in early stage disease.

High fascin-1 expression in colorectal cancer identifies patients at high risk for early disease recurrence and associated mortality.

BACKGROUND: Fascin is the main actin cross-linker protein that regulates adhesion dynamics and stabilizes cell protrusion, such as filopodia. In human cancer, fascin expression correlates with aggressive clinical features. This study aimed to determine the expression patterns of fascin-1 and assessed its prognostic significance in colorectal cancer. METHODS: One hundred eleven specimens of patients with primary resectable colorectal cancer were examined via immunohistochemistry for the expression of fascin-1, and the results were correlated with clinicopathological characteristics and survival data. RESULTS: Fascin-1 staining displayed strong intensity in the cytoplasm of the colorectal cancer cells and endothelial cells of tumor blood vessels. Moderate to high fascin-1 expression was associated with progressive anatomic disease extent (p < 0.001), higher T classification (p = 0.007), the presence of lymph node (p < 0.001) and distant metastasis (p = 0.002), high grade tumors (p = 0.002) and vascular invasion (p < 0.001). Patients displaying moderate and high fascin-1 expression demonstrated a significantly worse 5-year overall survival [HR; 3.906, (95%CI) = 1.250-12.195] and significantly worse 3-year progression-free survival [HR; 3.448, (95%CI) = 1.401-8.475] independent of other clinicopathological characteristics. Besides, high fascin-1 expression in early-stage cancer only was associated with a dismal prognosis. CONCLUSIONS: High fascin-1 expression in colorectal cancer is an independent negative prognostic factor for survival, increasing the risk for disease recurrence or death almost by sevenfold. Fascin-1 expression could be potentially utilized to identify high-risk patients prone to metastasis already in early-stage disease.

L1CAM expression in colorectal cancer identifies a high-risk group of patients with dismal prognosis already in early-stage disease.

Background: Metastatic disease in colorectal cancer represents a major cause of significant cancer-associated morbidity and mortality. L1CAM is a stem cell marker, cell adhesion molecule, belongs to the immunoglobulin superfamily of cell adhesion molecules (IgCAM) and it is aberrantly expressed in several different types of human solid tumors. The aim of the present study was to assess the expression patterns of L1CAM and its clinical significance in colorectal cancer.Patients and methods: Surgical specimens of 109 patients with primary resectable colorectal cancer were examined for L1CAM expression via immunohistochemistry and the results were correlated with clinical and survival data.Results: L1CAM expression was significantly correlated with advanced stage of disease (p < .001), higher T classification (p = .040), the presence of lymph node (p < .001) and distant metastasis (p = .011). Patients displaying high L1CAM expression demonstrated a dismal three-year progression free survival (29.7% vs 87.1%, p < .001) and five-year overall survival (39.9% vs 87.7%, p < .001). Multivariate analysis using Cox proportional hazard models revealed high L1CAM expression as a prognostic marker of dismal progression free (HR 0.187, 95%CI = 0.075-0.467, p < .0001) and overall survival (HR 0.154, 95%CI = 0.049-0.483, p = .001) independent of other clinicopathological characteristics. Subgroup analysis comprised of patients with early stage disease only presented as well significantly worse progression free and overall survival when L1CAM exhibited high expression.Conclusions: Colorectal cancer patients displaying high expression of L1CAM harbor high risk for metastasis already in early stage disease identifying therefore a group of patients prone to dismal prognosis.

Nectin-1 Expression in Colorectal Cancer: Is There a Group of Patients with High Risk for Early Disease Recurrence?

BACKGROUND: Despite improvements in therapy of colorectal cancer, some patients will present occurrence of recurrence either locally or distantly. Tumor metastasis constitutes the major cause of cancer-associated morbidity and mortality. Nectin-1 belongs to the family of immunoglobulin-like cell adhesion molecules that contribute to the formation of cell-cell adhesions and regulate a series of cellular activities including cell polarization, differentiation, movement, proliferation, and survival. Expression of Nectin-1 in malignant tumors has been associated with aggressive tumor phenotypes. OBJECTIVES: The aim of the present study was to assess Nectin-1 expression patterns in colorectal cancer and to investigate its clinical significance. METHODS: Nectin-1 expression was assessed via immunohistochemistry in surgical specimens of a cohort comprised of 111 patients with primary resectable colorectal cancer. Results were correlated with clinicopathological characteristics and survival data. Progression-free survival was defined as the primary outcome of the present study. RESULTS: Nectin-1 was strongly expressed in the cytoplasm of colorectal cancer cells. High Nectin-1 expression was associated with advanced stage of disease (p = 0.012) and lymph node metastasis (p = 0.007). Progression-free survival of patients exhibiting high expression of Nectin-1 in the first 36 months after surgery was significantly worse compared to patients with low expression of Nectin-1 (55.7%, 95% CI = 47-70, vs. 82.1%, 95% CI = 69-93, p = 0.014) and independent of other clinicopathological characteristics (HR = 0.389, 95% CI = 0.156-0.972, p = 0.043). CONCLUSION: Nectin-1 expression in colorectal cancer is associated with a significantly worse 3-year progression-free survival identifying therefore a group of patients with high risk for early disease recurrence.

Primary Hepatic Leiomyosarcoma: a Case Report and Review of the Literature.

BACKGROUND/AIM: Primary hepatic leiomyosarcoma is an extremely rare type of liver sarcoma with relatively poor prognosis, with about 50 cases having been reported in the literature. Potential origins of this tumor in the liver are the smooth muscle cells in the round ligament, intrahepatic blood vessels and intrahepatic bile ducts. There is no apparent sex predilection and there is a wide age range. The clinical presentation is not specific and the diagnosis depends on the expression of markers such as smooth muscle actin, desmin and vimentin by tumor cells. PATIENTS AND METHODS: Herein, we present a case of a bulky primary hepatic leiomyosarcoma in a 68-year-old female patient. The patient underwent resection of the exophytic mass en block with the hepatic segments III and IVB. CONCLUSION: Surgical resection is the most effective among the treatment options.

KISS1 and KISS1R expression in gastric cancer.

PURPOSE: Kisspeptins, which are derived from the gene KISS1, supress tumor progression. We intended to investigate the production of KISS1 and its receptor (KISSR) in gastric cancer. METHODS: The expression of KISS1 and KISS1R in both normal and cancer tissue was examined with immunohistochemistry in tissue specimens of 40 cases of gastric adenocarcinoma. RESULTS: KISS1 expression in normal gastric mucosa was much higher than in malignant mucosa. KISS1 expression was higher in early stages (stage I or II) than in advanced stages (stage III or IV), in tumors with intestinal histological type than in those with diffuse histological type, in tumors without lymphovascular invasion than in those with and in cancers of older patients (≥70 years) than in younger patients. No significant differences were found regarding other clinicopathological parameters. There was no KISS1R expression in cancer tissues, while only low levels of KISS1R were detected in normal gastric epithelium. CONCLUSIONS: KISS1 expression is decreased during carcinogenesis in gastric mucosa. More advanced tumors and more aggressive histological types produce lower KISS1 levels. In addition, no KISS1R is produced in malignant gastric epithelium, while KISS1R is only weakly expressed in normal gastric epithelium.

Short-term outcomes in patients with colon cancer treated with robotic right colectomy.

PURPOSE: To report a single surgeon series of consecutive robotic right colectomies (RRC) performed for non-metastatic right colon cancer. METHODS: A retrospective review of a prospectively maintained database of patients who underwent elective robotic right colectomy for right colon adenocarcinoma was conducted. Patients with stage 0-III disease were included in the study. Outcomes evaluated included operative time, number of lymph nodes harvested, estimated blood loss, time to return of bowel function, length of hospital stay, complications and a minimum of 6-month follow up. RESULTS: Forty-five consecutive patients were included in this study. The mean operative time was 175 min, the mean lymph nodes harvested were 22 and the mean length of hospital stay was 5 days. The mean time to normal bowel function restoration and to discontinuation of patient-controlled analgesia was 2 days. The hospital post-operative courses were complicated in two patients by ileus and fever due to pulmonary atelectasia, respectively. No conversions to laparotomy, reoperations or 90-day deaths were recorded. CONCLUSIONS: Robotic colorectal surgery has gained a lot of supporters through the years although a debate still exists concerning the outcomes. The present study is one of the largest evaluating short-term results of RRCs performed by a single surgeon. We believe we demonstrated the safety and efficacy of RRC in the treatment of right colon nonmetastatic adenocarcinoma.

What can preoperative blood tests tell us about colorectal cancer?

PURPOSE: To study the diagnostic and/or prognostic role of preoperative blood tests in colorectal cancer. METHODS: Preoperative complete blood count tests and lactate dehydrogenase (LDH) serum levels of 167 patients with colorectal adenocarcinoma were examined for associations with clinicopathological parameters, disease-specific survival (DSS) and relapse-free survival (RFS). RESULTS: The following parameters showed high sensitivity (≥85%) in detecting these features: platelet to lymphocyte ratio (PLR) for T4 tumors, white blood cell count (WBC) and neutrophil count (NC) for distant metastases and lymphocyte count (LC) for high-grade tumors. The following parameters showed high specificity (≥85%) in excluding these features: lymphocyte percentage (LP) for tumors larger than 5 cm, LP, neutrophil to lymphocyte ratio (NLR), neutrophil to monocyte ratio (NMR), lymphocyte to monocyte ratio (LMR) and LDH for T4 tumors, platelet to monocyte ratio (PMR) for T2-T4 tumors, LDH for more than three infiltrated regional lymph nodes and distant metastases, LMR for high-grade tumors and neutrophil percentage (NP) for lymphovascular invasion. WBC and NLR were independent prognostic factors for DSS, whereas WBC, NP, LP and NLR were independent prognostic factors for RFS. CONCLUSIONS: Preoperative complete blood count and LDH serum levels can provide valuable information about diagnosis and prognosis in colorectal cancer.

Nestin and cluster of differentiation 146 expression in breast cancer: Predicting early recurrence by targeting metastasis?

The purpose of this study was to investigate the relationship between the expression of stem-cell markers nestin and cluster of differentiation 146 with clinicopathological characteristics in breast cancer and to determine whether a prognostic impact of nestin and CD146 expression exists regarding occurrence of disease relapse in breast cancer. A total of 141 patients who were histologically diagnosed with breast cancer and underwent radical operations from November 2006 to October 2013 in Laiko General Hospital, National and Kapodistrian University of Athens, were enrolled in the study. CD146 and nestin protein expression were evaluated using immunohistochemistry. Nestin expression was observed in 18.4% (26/141) of the cases, while CD146 expression was observed in 35.5% (50/141) of the cases. Nestin expression is significantly higher in younger patients with breast cancer. Nestin and CD146 expression were not correlated with the tumor size and the presence of lymph node metastasis. On the contrary, a significantly higher expression of nestin and CD146 was observed with triple-negative cancers (p < 0.0001 for both markers), low differentiated tumors (p = 0.021 for nestin and p = 0.008 for CD146), and increased Ki-67 expression (p = 0.007 for nestin and p < 0.0001 for CD146). The nestin-positive group of patients and the CD146-positive group of patients presented significantly higher rates of disease recurrence (log-rank test, p = 0.022 for nestin and p = 0.003 for CD146) with a distant metastasis, 30 months after the primary treatment. CD146 but not nestin, however, predicted independently (p = 0.047) disease recurrence. Nestin and CD146 are expressed in breast cancer cells with highly aggressive potency. They might contribute to disease relapse in breast cancer by activating the epithelial-mesenchymal transition pathway and assist tumor neovascularization.

Orchitis reveals an extragonadal primary mediastinal thymic seminoma: a coincidence or not?

BACKGROUND: Mediastinal thymic seminomas are rare male germ cell tumors with extragonadal origin that appear predominately with a cystic appearance. CASE PRESENTATION: A 22-year-old male was referred to our department for further investigation of a mediastinal mass discovered incidentally during routine chest X-ray. The patient has denied any symptoms including dyspnea, chest pain, cough, fever, dysphagia, hemoptysis, weight loss, and weakness. His past medical history was remarkable for orchitis, for which he had undergone a bilateral testicular biopsy, without the latter however, indicating the presence of a germ cell tumor or a premalignant lesion. Contrast-enhanced chest computed tomography revealed a lobulated and well-marginated cystic lesion in the anterior mediastinum. Differential diagnosis included mostly a multilocular thymic cyst, a lymphoma, a seminoma, or a soft tissue tumor. Resection of the mass revealed a primary thymic seminoma. CONCLUSIONS: A surgical approach for the management of these tumors might be reasonable considering that an extensive sampling is mandatory to gain an appropriate biopsy preoperatively in order to securely confirm or refute the presence of a mediastinal extragonadal tumor. Orchitis might be a sign of a general disorder of the germ cells which might transform in time.

Trends in white blood cell and platelet indices in a comparison of patients with papillary thyroid carcinoma and multinodular goiter do not permit differentiation between the conditions.

AIM: Carcinogenesis has been related to systematic inflammatory response. Our aim was to study white blood cell and platelet indices as markers of this inflammatory response in thyroid cancer and to associate them with various clinicopathological parameters. METHODS: We included 228 patients who underwent thyroidectomy within a period of 54 months, 89 with papillary thyroid carcinoma and 139 with multinodular hyperplasia. We examined potential links between white blood cell and platelet indices on the one hand and the type thyroid pathology and various clinicopathological parameters on the other. RESULTS: No significant differences were detected between thyroid cancer and multinodular hyperplasia and no significant associations were detected with regard to lymphovascular invasion and tumor size. However, the mean platelet volume was higher in multifocal tumors, while the platelet count, plateletcrit, and platelet-to-lymphocyte ratio were increased in cases with extrathyroidal extension and in T3 tumors. Additionally, T3 tumors had lower platelet distribution width. These associations demonstrated low accuracy in predicting these pathological features, but they were found to provide a satisfying negative predictive value, with the exception of the mean platelet volume. CONCLUSIONS: White blood cell and platelet indices cannot assist in distinguishing benign goiter from thyroid cancer. However, they can provide information about tumor multifocality, extrathyroidal extension, and presence of a T3 tumor, and they may be used as a means to exclude these pathological characteristics, especially the last two, in papillary thyroid carcinoma.

Safety and efficacy of liver resections in elderly patients.

PURPOSE: Elderly patients constitute a special group of surgical candidates due to the frequent coexistence of major comorbidities. We report our experience in performing liver resections in patients aged 75 years or older. METHODS: During a period of 62 months, 154 patients underwent liver resections, out of which 20 were 75 years old or older. Our prospectively maintained database was reviewed regarding patient and tumor characteristics, intraoperative and postoperative data. RESULTS: Out of the 20 patients aged 75 years or older, 15 were men and 5 women, with a mean age of 79.3 years. Sixteen patients (80%) had at least one major comorbidity. Indications for surgery was hepatocellular carcinoma (n=5), intrahepatic cholangiocarcinoma (n=7), liver metastases (n=5), liver abscess (n=2) and liver cyst with hemorrhage (n=1). Liver resections included 3 left hepatectomies, 1 left lateral hepatectomy combined with segmentectomy and wedge resection, 2 right hepatectomies, 1 central hepatectomy, 4 bisegmentectomies, 3 segmentectomies, 4 wedge resections and 2 unroofings of giant liver cysts. In 10 out of the 20 operations, patients underwent further procedures apart from the liver resection. Six patients were postoperatively admitted to intensive care unit for 1 or 2 days. Postoperative bile leak was documented in 2 patients and postoperative hemorrhage in 1 patient, for which no reoperation was needed. No postoperative death was recorded during the hospitalization of the patients. The mean length of hospital stay was 12.9 days. CONCLUSIONS: Liver resections, even major ones, can be tolerated by elderly patients with good postoperative outcomes under the presupposition of careful patient selection.

Laparoscopic liver resection for malignancy in high-risk surgical patients according to ASA classification.

Laparoscopic liver resection (LLR) represents one of the most recent evolutions in the field of surgical oncology. While offering to the patients all the short-term advantages of the laparoscopic approach, the ongoing experience underlines that the long-term outcomes are not negatively influenced through this minimally invasive method. We explored the surgical results in a case series of 5 high-risk patients with American Society of Anesthesiologists' (ASA) Class 3 or more, who underwent LLR in our department. Three bisegmentectomies, one segmentectomy and one wedge resection were performed. All patients could be discharged within the first postoperative week. LLR was safe and efficient in this high-risk patient group. Careful patient selection and individualized preparation for surgery remain the keys for the success of LLR in high ASA class patients.

Surgery for liver metastases from breast cancer.

INTRODUCTION: Liver metastases from breast cancer (BCLM) confer poor survival. Liver resection in BCLM patients has been increasingly employed. AIM: We undertook a systematic review to evaluate the role of hepatic resection in patients with breast cancer metastatic to the liver. MATERIALS & METHODS: In total, 36 studies were overviewed. Patient populations, characteristics, morbidity, mortality and survival were documented. RESULTS: Median overall survival was 41 months. Major morbidity was rare while 30-day postoperative mortality was near nil. CONCLUSION: Liver surgery for BCLM can be performed with low mortality, acceptable morbidity and promising survival benefit in carefully selected patients.