Could Flow Cytometry Provide New Prognostic Markers in Colorectal Cancer?

Background/Objectives: Colorectal cancer (CRC) is still accompanied by significant mortality, which poses the necessity of novel markers to predict treatment success and patient survival. This study aims to evaluate the prognostic and survival impact of flowytometry (FC) in CRC patients. Methods: In this prospective study, 106 surgically resectable CRC patients were included. Tissue specimens from tumor and normal mucosa were collected and analyzed by FC. DNA and tumor index were calculated. In a subgroup of 46 patients, the CD26 expression on tumor cells was estimated. These parameters were compared with patients' tumor characteristics as stage, histology data, responsiveness to treatment, metastasis/recurrence, and, finally, patients' survival to identify possible new biomarkers. Results: The overall survival and the disease-specific survival in our study group was 76% and 72%, respectively, during the 7-year follow up period. Diploid tumors had better median survival than the aneuploid ones. The DNA index had significant correlation to the tumor index and response to neoadjuvant treatment. Similarly, the tumor index was also significantly related to the response to neoadjuvant treatment. Patients with a higher tumor index had worst survival rates. Surprisingly, CD26 levels were not associated with any of the parameters examined and were negatively related to tumor stage and differentiation. Conclusions: FC is a rapid and reliable method of cell analysis. In CRC, it has been used for prognostic and diagnostic purposes. In this study, we have shown that DNA and tumor index could become predictive biomarkers of tumor response to neoadjuvant treatment and survival of resectable CRC patients.

Protocol for an independent patient data meta-analysis of prophylactic mesh placement for incisional hernia prevention after abdominal aortic aneurysm surgery: a collaborative European Hernia Society project (I-PREVENT-AAA).

INTRODUCTION: Incisional hernia (IH) is a prevalent and potentially dangerous complication of abdominal surgery, especially in high-risk groups. Mesh reinforcement of the abdominal wall has been studied as a potential intervention to prevent IHs. Randomised controlled trials (RCTs) have demonstrated that prophylactic mesh reinforcement after abdominal surgery, in general, is effective and safe. In patients with abdominal aortic aneurysm (AAA), prophylactic mesh reinforcement after open repair has not yet been recommended in official guidelines, because of relatively small sample sizes in individual trials. Furthermore, the identification of subgroups that benefit most from prophylactic mesh placement requires larger patient numbers. Our primary aim is to evaluate the efficacy and effectiveness of the use of a prophylactic mesh after open AAA surgery to prevent IH by performing an individual patient data meta-analysis (IPDMA). Secondary aims include the evaluation of postoperative complications, pain and quality of life, and the identification of potential subgroups that benefit most from prophylactic mesh reinforcement. METHODS AND ANALYSIS: We will conduct a systematic review to identify RCTs that study prophylactic mesh placement after open AAA surgery. Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase, Web of Science Core Collection and Google Scholar will be searched from the date of inception onwards. RCTs must directly compare primary sutured closure with mesh closure in adult patients who undergo open AAA surgery. Lead authors of eligible studies will be asked to share individual participant data (IPD). The risk of bias (ROB) for each included study will be assessed using the Cochrane ROB tool. An IPDMA will be performed to evaluate the efficacy, with the IH rate as the primary outcome. Any signs of heterogeneity will be evaluated by Forest plots. Time-to-event analyses are performed using Cox regression analysis to evaluate risk factors. ETHICS AND DISSEMINATION: No new data will be collected in this study. We will adhere to institutional, national and international regulations regarding the secure and confidential sharing of IPD, addressing ethics as indicated. We will disseminate findings via international conferences, open-source publications in peer-reviewed journals and summaries posted online. PROSPERO REGISTRATION NUMBER: CRD42022347881.

Treatment of Gastric Cancer Means Surgery, but Not Surgery Alone.

Despite numerous studies, gastric cancer (GC) still presents a high mortality rate in Eastern and Western countries, increasing attention for new therapeutic strategies [...].

Complete mesogastric excision for gastric cancer: is it the future of gastric cancer surgery?

Gastric cancer remains undoubtedly one of the most common and deadly cancers worldwide. The global incidence shows wide geographic variation with a high prevalence in Asia. Besides that, there are evident differences in epidemiology, histopathology, tumor location, diagnosis and treatment strategy between east and west countries. Gastric cancer represents an aggressive disease, with many factors influencing its development and also recurrence after surgical resection. New knowledge of disease spread and new routes of metastases are now emerging and the 'novel' concept of complete mesogastric excision for gastric cancer is under consideration and debate. This article aims to analyze and highlight this new concept after a careful literature review, offering also a view toward the future.

Surgical oncology during the post-COVID-19 era: What is next?

During first outburst of COVID-19, several strategies had been applied for surgical oncology patients to minimize COVID-19 transmission. COVID-19 infection seemed to compromise survival and major complication rates of surgical oncology patients. However, survival, tumor progression and recurrence rates of surgical oncology patients were associated to the consequences of COVID-19 pandemic on their management. In addition, the severity of COVID-19 infections has been downgraded. Therefore, management of surgical oncology patients should be reconsidered.

Detection of cancer cells and tumor margins during colorectal cancer surgery by intraoperative flow cytometry.

BACKGROUND: Flow Cytometry is an analytical technique for the precise quantification of cellular phenotype. Intraoperative Flow Cytometry (iFC) utilizes flow cytometry for DNA content/ploidy and cell cycle distribution analysis during surgery for cancer cell characterization and evaluation of tumor margins. Various types of cancers, including intracranial, head and neck, breast and liver malignancies have been evaluated with iFC. In the current study we present an intraoperative Flow Cytometry protocol for colorectal cancer cell detection and potential resection margin evaluation. MATERIALS AND METHODS: This study includes 106 colorectal cancer patients in which samples from cancer and normal colon epithelium were prospectively collected intraoperatively and comparatively assessed with iFC. Patients' demographics, tumor data and cytometry parameters were assessed. RESULTS: We have demonstrated that a cut-off value of 10.5% for tumor-index (fraction of cells in S and G2/M cell cycle phases) predicts with ∼91% accuracy (82.2% sensitivity and 99.9% specificity) the presence of cancer cells. Evaluation of tumor margins by iFC in the subpopulation of rectal cancer patients with or without neoadjuvant therapy, revealed an accuracy of 79% and 88%, respectively. CONCLUSION: Our data support that regarding colorectal cancer, iFC is a useful adjunct method for tumor cell identification and probably margin evaluation, which could be utilized in rectal cancer treatment in the era of organ sparing procedures.

Neoadjuvant chemotherapy for gastric cancer. Has the time to decelerate the enthusiasm passed us by?

Neoadjuvant therapy for locally advanced gastric cancer is a treatment option well recognized in international guidelines. However, neither completed randomized trials nor ongoing studies (will) offer definitive answers about the efficacy of neoadjuvant therapy. With extensive experience confirming the safety and some efficacy for this approach most current studies are focused on identifying the best preoperative treatment regimen. We try to clarify if is really the time to slow down the enthusiasm about neoadjuvant approach.

Sentinel Node Navigation in Gastric Cancer: Where Do We Stand?

BACKGROUND: Early gastric cancer (EGC) is more common nowadays and is related a to low percentage of lymph node metastasis. For this reason, there is enormous interest to implicate minimally invasive approaches. Recently, special efforts have been made towards a potential intraoperative (real-time) lymph node metastasis (LNM) assessment, as nodal disease status could not be identified with precision before or during surgery. In this direction, accurate prediction of the LNM status through sentinel LN mapping has been attempted, as an approach to the intraoperative detection of sentinel lymph nodes (SLNs). A careful literature search was conducted in order to clarify the potential clinical application of SN biopsy in the gastric cancer field. CONCLUSION: The real clinical application of SN biopsy in gastric cancer treatment has been more than challenging due to the "complicated" nature of gastric lymphatic drainage and the high possibility of "skip" metastasis phenomenon. Notably, sophisticated technical aspects, such as the preferred tracer used and the potential "ideal" method to verify the presence of metastases in the resected SLNs, made SN biopsy application in gastric cancer field extremely demanding. Assessing the potential role of SN navigation for gastric cancer treatment in the era of advanced technology, where the minimally invasive surgical approaches are in the top of the scientific interest, it has to be highlighted that SN navigation for gastric cancer is a topic that remains highly controversial, and the need for future clinical trials on this topic is obvious.

In Surgical Colon Cancer Patients Extended-Duration Thromboprophylaxis (30 days) with the Highest Dose of Tinzaparin (4,500 IU s.c./q.d.) Normalizes the Postoperative VEGF Levels.

Background/Purpose: In colon cancer (CC) patients preoperative (pre-op) levels of VEGF-A165 (VEGF) is a strong predictor for disease recurrence. Elevated postoperative (post-op) VEGF levels could have undesirable effects by enhancing tumor growth and metastasis formation. It has been suggested that thromboprophylaxis with a Low Molecular Weight Heparin (LMWH) in surgical cancer patients, further to thromboembolic protection, may exert some anti-neoplastic properties, as well. The aim of our study was to assess the potential impact of the LMWH Tinzaparin (Innohep® - Leo Pharma, Copenhagen, Denmark), given at different doses and for different perioperative (peri-op) periods, upon the post-op variability of serum VEGF levels in surgical CC patients. Methods: A total of 54 consecutive CC patients who underwent a curative resection were randomized in four groups according to their peri-op thromboprophylaxis scheme, which was based on administrating Tinzaparin in different doses and at different periods, as follows: group I: 3,500 IU for 10 days, group II: 3,500 IU for 30 days, group III: 4,500 IU for 10 days and group IV: 4,500 IU for 30 days. Serum VEGF concentrations were evaluated on the pre-op day (Day 0) and on the 10th and 30th post-op days (Day 10 and Day 30, respectively). For statistical analyses the mixed design ANOVA was used. P < 0.05 was considered significant. Results: On Day 0, VEGF didn't differ between groups I, II, III and IV (p>0.05, for every comparison). On Day 10, VEGF was increased in all groups. Between Day 10 and Day 30, VEGF remained stable in groups I (p=0.031) and II (p=1.000) and increased significantly in group III (p=0.005). On the contrary, VEGF decreased significantly in group IV (p<0.001). The most remarkable finding was observed when we compared VEGF between Day 0 and Day 30: while in groups I, II and III, VEGF remained significantly higher compared to Day 0 (p<0.001, p=0.041 and p<0.001, respectively), on the contrary, in group IV (extended-duration with the highest dose of 4,500 IU of tinzaparin) it was comparable to Day 0 (p=1.000). Conclusions: In surgical CC patients only the recommended thromboprophylaxis scheme with the highest prophylactic dose of Tinzaparin (4,500 IU) for extended-duration (30 days) normalizes VEGF levels at the end of the first post-op month by reducing them to the pre-op levels.

Identification of novel genes by whole-exome sequencing can improve gastric cancer precision oncology.

AIM: By identifying cancer driver genes involved in tumorigenesis, whole-exome sequencing (WES) analyses enable the development of robust biomarkers and novel therapeutic targets to reach precision oncology. PATIENTS & METHODS: WES analyses were performed in matched gastric cancer-normal gastric tissues from two patients. We compared genes highlighted with those of a database and recent WES/whole-genome sequencing studies. RESULTS: We identified 32 highlighted gastric cancer genes, two of these (DEFB118 and RNF43) may provide future potential clinical implications. CONCLUSION: Definitive evidence on extensive genetic heterogeneity suggests the need for large-scale next-generation sequencing studies to validate gastric cancer driver genes catalog. This list represents the foundation for developing genome-based biomarkers to guide precision gastric cancer treatment.

Management of concomitant abdominal aortic aneurysm and colorectal cancer.

OBJECTIVE: To conduct a systematic review of the literature and perform an analysis of outcomes of treatment of concomitant colorectal cancer (CRC) and abdominal aortic aneurysm (AAA) with a focus on the different treatment options and the related therapeutic outcomes. METHODS: A review of the English-language medical literature from 1980 to 2015 was undertaken using the PubMed and EMBASE databases to identify studies reporting surgical treatment of patients with concomitant CRC and AAA. The search identified 24 articles encompassing 254 patients (81% male; mean age 73.5 ± 6.1 years). RESULTS: In 96 patients (37.9%) cancer resection was performed first, followed by AAA repair at a later stage (open aortic repair [OAR], 79.2%; endovascular abdominal aortic repair [EVAR], 20.8%). Eighty-two patients (32.3%) underwent AAA repair (OAR, 47.5%; EVAR, 52.5%) before CRC resection. Seventy-one patients (27.9%) underwent combined OAR and CRC resection, and just five (1.9%) were treated with EVAR and cancer surgery in a single stage. There were eight of 96 interval AAA ruptures (8.3%), mostly in the early postoperative period concerning aneurysms >6 cm in diameter. The mean interval between the two procedures was much shorter in patients treated with EVAR than OAR (11.5 ± 1.8 days vs 103.9 ± 42.3 days). The overall 30-day mortality rate was 10.9%. Data from observational studies showed no significant differences in 30-day mortality between patients treated in one or two stages (P = .89). No mortality was recorded in any of the EVAR-treated patients. There was only one graft infection recorded (0.4%). CONCLUSIONS: Among different approaches, no significant differences in 30-day outcomes among patients treated in either two or one stage were evident. EVAR showed the lowest mortality and also diminished the delay between the two procedures in <2 weeks for a two-stage approach, although it has been associated with a significant risk for thrombotic events. The coexistence of AAA and CRC seems to favor the use of EVAR in treating those patients.

Management of an aorto-esophageal fistula, complicating a descending thoracic aortic aneurysm endovascularly repaired.

Aorto-esophageal fistula (AEF) is a rare but devastating complication of thoracic aorta endovascular repair (TEVAR). We report a case of a 64-year-old male who presented with chest pain and high CRP levels 10 months after TEVAR for a 9 cm diameter descending thoracic aortic aneurysm. The diagnosis of an AEF was confirmed and the patient was treated conservatively with broad spectrum antibiotics and total parental alimentation. After control of sepsis was achieved, esophagectomy with gastric tube reconstruction was performed and an omental pedicle was used to cover the aortic wall. No intervention to the aorta was made at that time due to the potentially infected mediastinum. The patient's recovery was uneventful and 2 years postoperatively he is in good condition and lives a normal life. Esophagectomy seems to be a mandatory stage of treatment in the setting of AEF. In cases where signs of graft infection are persistent, aortic surgery might be also necessary.

Sentinel node navigation in gastric cancer: new horizons for personalized minimally invasive surgical oncology?

Complete (R0) resection and regional lymph nodes (LNs) dissection represent undoubtedly the basic surgical tools for patients with gastric cancer. It is reported that the LN metastasis rate in patients with early gastric cancer (EGC) is approximately 15-20%. Therefore, the innovative clinical application of sentinel node navigation surgery (SNNS) for EGC might be able to prevent unnecessary LN dissection as well as to reduce significantly the volume of gastric resection. Recent evidence suggests that double tracer methods appear superior compared to single tracer techniques. However, the researchers' interest is now focused on the identification of new LN detection methods utilizing sophisticated technology such as infrared ray endoscopy, fluorescence imaging and near-infrared technology. Despite its notable limitations, hematoxylin-eosin is still considered the mainstay staining for assessing the metastatic status of LNs. In this review, we summarize the current evidences and we provide the latest scientific information assessing safety, efficacy and potential limitations of the innovative sentinel node (SN) navigation technique for gastric cancer. We try also to provide a "view" towards a future potential application of personalized minimally invasive surgery in gastric cancer field.

BMI and lymph node ratio may predict clinical outcomes of gastric cancer.

AIM: BMI and the lymph node (LN) ratio can affect short- and long-term outcomes of patients with gastric cancer. PATIENTS & METHODS: This study includes 104 consecutive patients with gastric adenocarcinoma who underwent curative gastrectomy divided in two groups: overweight group (group A) and normal weight group (group B). RESULTS: We found that 53.4% of our patients were overweight (group A). The overall rate of postoperative complications was 16.3%, while mortality was 1%. Statistical analyses revealed that postoperative morbidity was significantly higher in group A (p < 0.05). Long-term survival was significantly higher in group B. Cox regression showed a statistically significant correlation between higher BMI and poor long-term survival after curative gastrectomy. Multivariate analysis has identified age and the LN ratios as independent prognostic factors of survival. CONCLUSION: In this retrospective analysis, BMI and LN ratio were independently associated with survival in patients with gastric cancer. Further studies are needed to confirm our findings.

Use of the vascu-guard bovine pericardium patch for arteriotomy closure in carotid endarterectomy. Early and long-term results.

BACKGROUND: To report the early and long-term results of Vascu-Guard bovine pericardium (BP) for patch angioplasty in carotid endarterectomy (CEA). METHODS: We retrospectively analyzed the data of 256 CEAs with BP patch closure performed in 238 patients during the past 12 years in our department. Patch-related complications (restenosis, infection, and aneurysm formation) and early and late (12 to 144 months follow-up) clinical outcomes were recorded and statistically analyzed. RESULTS: Thirty-day postoperative stroke rate was 1.2% (3/256) with zero mortality. Major complications occurred in 3.5% (9 of 256) of the procedures and cranial nerve injury in 4.3% (11 of 256). At 12 years, cumulative estimates of freedom from any stroke, stroke-free survival, and freedom from restenosis were 88.4% (standard error [SE]: 3.3%), 60% (SE: 7.8%), and 98.3% (SE: 0.8%), respectively. No patient experienced patch infection or aneurysm formation. CONCLUSIONS: This series shows the efficacy, safety, and durability of CEA with BP patch closure, in both the short and long term. BP combines the advantages of vein and synthetic patches, representing a suitable option when performing CEA.

A patient presenting with acute abdomen due to metastatic small bowel melanoma: a case report.

INTRODUCTION: Malignant tumors of the small bowel are rare. Melanoma of the small intestine is in most cases metastatic from a primary skin lesion. Perforation of small bowel melanoma is an extremely rare entity. To the best of our knowledge this is the fifth case published to date. CASE PRESENTATION: We report a rare case of acute abdomen due to perforated metastatic small bowel melanoma in a 38-year-old Caucasian man. CONCLUSIONS: In the majority of cases small bowel melanoma represents metastasis from cutaneous sites. Although rare, the possibility of abdominal metastatic melanoma presenting with the clinical picture of acute abdomen must be always considered by the operating surgeon in patients with a history of primary cutaneous malignant lesion.