First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report 3-year efficacy and safety results from the phase III CheckMate 649 trial. Patients with previously untreated advanced or metastatic gastroesophageal adenocarcinoma were randomly assigned to nivolumab plus chemotherapy or chemotherapy. Primary end points were overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in patients whose tumors expressed PD-L1 combined positive score (CPS) ≥5. With 36.2-month minimum follow-up, for patients with PD-L1 CPS ≥5, the OS hazard ratio (HR) for nivolumab plus chemotherapy versus chemotherapy was 0.70 (95% CI, 0.61 to 0.81); 21% versus 10% of patients were alive at 36 months, respectively; the PFS HR was 0.70 (95% CI, 0.60 to 0.81); 36-month PFS rates were 13% versus 8%, respectively. The objective response rate (ORR) per BICR was 60% (95% CI, 55 to 65) with nivolumab plus chemotherapy versus 45% (95% CI, 40 to 50) with chemotherapy; median duration of response was 9.6 months (95% CI, 8.2 to 12.4) versus 7.0 months (95% CI, 5.6 to 7.9), respectively. Nivolumab plus chemotherapy also continued to show improvement in OS, PFS, and ORR versus chemotherapy in the overall population. Adding nivolumab to chemotherapy maintained clinically meaningful long-term survival benefit versus chemotherapy alone, with an acceptable safety profile, supporting the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastroesophageal adenocarcinoma.

Influence of Clinical Factors on miR-3613-3p Expression in Colorectal Cancer.

Colorectal cancer (CRC) is the second most common cause of cancer-related death globally. Because of a tendency to be an asymptomatic primary tumor and therefore resulting in late detection, most CRC patients are diagnosed in the advanced stage. Several miRNAs have the potential to become novel noninvasive biomarkers measured as diagnostic and prognostic indicators of CRC to guide surgical therapies and promote the understanding of the carcinogenesis of CRC. Since the change of miR-3613-3p was associated with several types of cancer other than colorectal cancer, there is a lack of functional evidence and the results are inconsistent. We conducted a pilot microarray study in which we noted a decreased expression of miR-3613-3p in colorectal cancer cells, then we confirmed the expression of miR-3613-3p by qPCR on a group of 83 patients, including 65 patients with colorectal cancer, 5 with a benign tumor and 13 from the control group. We noted that in both malignant and benign tumors, miR-3613-3p is downgraded relative to the surrounding tissue. As a result of the study, we also observed colorectal tumor tissue and surrounding tissue in patients with colorectal cancer who received radiotherapy before surgery, which showed a significantly higher expression of miR-3613-3p compared to patients who did not receive radiotherapy. In addition, we noted that the tissue surrounding the tumor in patients with distant metastases showed a significantly higher expression of miR-3613-3p compared to patients without distant metastases. The increased expression of miR-3613-3p in patients after radiotherapy suggests the possibility of using this miR as a therapeutic target for CRC, but this requires confirmation in further studies.

A plain language summary of the CheckMate 649 study: nivolumab in combination with chemotherapy compared to chemotherapy alone for untreated advanced or metastatic cancer of the stomach or esophagus.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of the 1-year results of a clinical research study known as CheckMate 649 published in The Lancet in June 2021. The 2-year results on the participants' health and overall quality of life from the same study are in a second publication in Nature in March 2022. Until recently, chemotherapy was the only first treatment option for people with advanced or metastatic gastroesophageal adenocarcinoma who had not been treated before. Patients receiving chemotherapy lived on average for less than 1 year. Nivolumab is an immunotherapy that works by activating a person's immune system to fight back against cancer cells. The goal of CheckMate 649 was to find out if the combination of nivolumab and chemotherapy would help patients with advanced or metastatic gastroesophageal adenocarcinoma live longer and without their cancer getting worse. WHAT WERE THE RESULTS?: Results from the final analysis are reported here. Of 1581 people who took part in the study, 789 received nivolumab and chemotherapy and 792 received chemotherapy. Researchers found that, on average, participants who received nivolumab and chemotherapy lived longer overall than those who received chemotherapy alone. The length of time participants lived without their cancer getting worse was also longer on average with nivolumab and chemotherapy than chemotherapy treatment alone. However, more participants in the nivolumab and chemotherapy group had side effects than those in the chemotherapy group. The three most common side effects in both types of treatment were nausea (urge to vomit), diarrhea and peripheral neuropathy. Participants who received nivolumab and chemotherapy had a lower risk of their cancer symptoms worsening and reported that they were 'less bothered' from side effects of treatment than those receiving chemotherapy alone. WHAT DO THE RESULTS MEAN?: The nivolumab and chemotherapy combination is considered a new standard treatment option and is approved in several countries as a treatment for adults who have not been treated before for their advanced or metastatic gastroesophageal cancer based on results from CheckMate 649. Clinical Trial Registration: NCT02872116 (ClinicalTrials.gov).

Pre-therapeutic molecular biomarkers of pathological response to neoadjuvant chemotherapy in gastric and esophago-gastric junction adenocarcinoma: A systematic review and meta-analysis.

PURPOSE: Multimodal treatment is the standard of care in patients with locally advanced gastric cancer. Unfortunately, the response rate after neoadjuvant treatment remains limited. The ability to predict the response has a potential to improve patient outcomes by promoting a more individualized approach. We sought to describe the current state of research in pre-treatment molecular biomarkers of response to neoadjuvant therapy in gastric adenocarcinoma available for testing before the initiation of treatment and to perform a systematic review and meta-analysis in order to summarize and evaluate the potential methods. METHODS: A systematic MEDLINE, EMBASE and CENTRAL literature search was conducted to extract articles on potentially predictive molecular biomarkers of pathological response to neoadjuvant therapy in patients with gastric- and esophago-gastric junction adenocarcinoma. Fixed and random effects models were used to undertake the meta-analysis when appropriate. RESULTS: Data on predictive biomarkers was reported in 38 studies. These articles described 47 biomarkers showing statistical significance. After evaluation of all reported biomarkers, 3 of them met the inclusion criteria for meta-analysis. The meta-analysis results indicate that >5 â€‹ng/mL pre-therapeutic serum concentration of carcinoembryonic antigen (CEA; norm <5 â€‹ng/mL) is significantly associated with tumor response (RR â€‹= â€‹5.13, 95% CI 2.53-10.43, P â€‹= â€‹0.026). CONCLUSION: Previous studies describe a large number of candidate biomarkers. Our meta-analysis indicated pre-therapeutic serum concentration of CEA >5 â€‹ng/mL as a potential and easy-accessible biomarker available for use before initiation of treatment. However, it could be only an additional tool for complex qualification for neoadjuvant therapy.

ApoA-I and ApoB levels, and ApoB-to-ApoA-I ratio as candidate pre-treatment biomarkers of pathomorphological response to neoadjuvant therapy in gastric and esophago-gastric junction adenocarcinoma.

<b><br>Introduction:</b> Neoadjuvant chemotherapy (NAC) is a part of the current standard of care in a locally advanced gastric adenocarcinoma (GA) and esophagogastric junction adenocarcinoma (EGJA), but only patients with good pathomorphological response (pR) to NAC benefit from prolonged overall survival.</br> <b><br>Aim:</b> The study aims to evaluate ApoA-I and ApoB as candidate pre-treatment biomarkers of pR to NAC in patients with GA and EGJA.</br> <b><br>Materials and methods:</b> Serum samples were collected from 18 patients with GA and 9 with EGJA before the initiation of NAC to determine the ApoA-I and ApoB levels. After NAC tumor regression grade (TRG) was evaluated in resected specimens according to the Mandard's tumor regression grading system and correlated with pre-treatment ApoA-I and ApoB serum concentration, and ApoB-to-ApoA-I serum concentration ratio.</br> <b><br>Results:</b> We found a positive correlation of ApoA-I level and pR (95% CI: -0.863 to -0.467; P < 0.0001), a negative correlation of ApoB level and pR (95% CI: 0.445 to 0.857; P < 0.0001), a negative correlation of ApoB-to-ApoA-I ratio and pR (95% CI: 0.835 to 0.964; P < 0.0001).</br> <b><br>Conclusions:</b> ApoA-I and ApoB levels, and ApoB-to-ApoA-I ratio are candidate pre-treatment predictors of pR to NAC in GA and may help to guide personalized therapy.</br>Our work fits into the dynamically developing trend of personalized treatment. It describes a potentially important rationale for further evaluation of apolipoprotein A-I and apolipoprotein B as predictors of cancer response to neoadjuvant therapy.

Polish Consensus on Gastric Cancer Diagnosis and Treatment - Update 2022.

This document - "Polish Consensus on Gastric Cancer Diagnosis and Treatment - Update 2022" - represents an expert consensus following a year's worth of dedicated effort by a team of specialists throughout 2021, put forward in a conference in December 2021 in Krakow, and finalized below for publication in 2022. The effective date of this document is June 14th 2022. The work that went into updating this consensus was made under auspices of the Polish Society of Surgical Oncology and the Association of Polish Surgeons.

Follow-up after bariatric surgery: are we effective enough?

Over the years, the rise in the obesity epidemic has led to an increasing demand for bariatric surgery. Considering the rapidly growing number of bariatric surgery procedures performed, intensive development of postoperative care and surveillance programs should be expected. However, the effectiveness of follow-up after bariatric surgery appears to be surprisingly low. The purpose of this review is to draw attention to the quality of follow-up programs and to encourage health care providers to make efforts to ensure adequate post-operative data collection. Awareness should be raised about inadequate data collection to strengthen the credibility and authenticity of treatment results, thus providing a clearer picture of treatment efficacy.

Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer.

Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma1-4. Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial5 (programmed death ligand-1 (PD-L1) combined positive score ≥5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries6. Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively7-11. Treatment combining 1 mg kg-1 nivolumab with 3 mg kg-1 ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer12. Here we report both long-term follow-up results comparing nivolumab plus chemotherapy versus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive score ≥5 (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score ≥ 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.

Successful Late Endoscopic Stent-Grafting in a Patient with Boerhaave Syndrome.

BACKGROUND Boerhaave syndrome is a rare esophageal injury associated with a high mortality rate of 14.8%. Immediate diagnosis and treatment have been associated with a better outcome. Surgery remains the mainstay of treatment for those who present early with widespread septic contamination. One of the most difficult dilemmas in the treatment of Boerhaave syndrome is selection of the most appropriate management for late perforations with severe septic complications. In this situation, aggressive surgical approach with esophagectomy and immediate or postponed reconstruction is usually recommended. CASE REPORT We report a patient with spontaneous esophageal rupture successfully treated by late endoscopic stent-grafting. The patient was transferred from a rural hospital after initial non-effective conservative treatment. Endoscopic stent-grafting was performed 7 days from the onset of symptoms. A self-expanding plastic stent-graft (Polyflex) used initially very early migrated to the stomach. The plastic stent-graft was then replaced by a fully covered self-expandable metal stent-graft (EndoMAXX), which was wider and equipped with anti-migration struts. Implantation of the EndoMAXX stent-graft resulted in clinical success, with the closure of esophageal rupture confirmed 8 weeks after stent-grafting. CONCLUSIONS Our case indicates that even late after spontaneous esophageal perforation, less invasive treatment by endoscopic stent-grafting with adequate drainage of septic contamination may be an attractive option for preserving the esophagus in selected patients in stable hemodynamic condition. Our case also supports implantation of wider metallic stent-grafts to seal benign esophageal perforation above the esophago-gastric junction to prevent early migration to the stomach.

First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.

BACKGROUND: First-line chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction adenocarcinoma has a median overall survival (OS) of less than 1 year. We aimed to evaluate first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma. We report the first results for nivolumab plus chemotherapy versus chemotherapy alone. METHODS: In this multicentre, randomised, open-label, phase 3 trial (CheckMate 649), we enrolled adults (≥18 years) with previously untreated, unresectable, non-HER2-positive gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma, regardless of PD-ligand 1 (PD-L1) expression from 175 hospitals and cancer centres in 29 countries. Patients were randomly assigned (1:1:1 while all three groups were open) via interactive web response technology (block sizes of six) to nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks) plus chemotherapy (capecitabine and oxaliplatin every 3 weeks or leucovorin, fluorouracil, and oxaliplatin every 2 weeks), nivolumab plus ipilimumab, or chemotherapy alone. Primary endpoints for nivolumab plus chemotherapy versus chemotherapy alone were OS or progression-free survival (PFS) by blinded independent central review, in patients whose tumours had a PD-L1 combined positive score (CPS) of five or more. Safety was assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT02872116. FINDINGS: From March 27, 2017, to April 24, 2019, of 2687 patients assessed for eligibility, we concurrently randomly assigned 1581 patients to treatment (nivolumab plus chemotherapy [n=789, 50%] or chemotherapy alone [n=792, 50%]). The median follow-up for OS was 13·1 months (IQR 6·7-19·1) for nivolumab plus chemotherapy and 11·1 months (5·8-16·1) for chemotherapy alone. Nivolumab plus chemotherapy resulted in significant improvements in OS (hazard ratio [HR] 0·71 [98·4% CI 0·59-0·86]; p<0·0001) and PFS (HR 0·68 [98 % CI 0·56-0·81]; p<0·0001) versus chemotherapy alone in patients with a PD-L1 CPS of five or more (minimum follow-up 12·1 months). Additional results showed significant improvement in OS, along with PFS benefit, in patients with a PD-L1 CPS of one or more and all randomly assigned patients. Among all treated patients, 462 (59%) of 782 patients in the nivolumab plus chemotherapy group and 341 (44%) of 767 patients in the chemotherapy alone group had grade 3-4 treatment-related adverse events. The most common any-grade treatment-related adverse events (≥25%) were nausea, diarrhoea, and peripheral neuropathy across both groups. 16 (2%) deaths in the nivolumab plus chemotherapy group and four (1%) deaths in the chemotherapy alone group were considered to be treatment-related. No new safety signals were identified. INTERPRETATION: Nivolumab is the first PD-1 inhibitor to show superior OS, along with PFS benefit and an acceptable safety profile, in combination with chemotherapy versus chemotherapy alone in previously untreated patients with advanced gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma. Nivolumab plus chemotherapy represents a new standard first-line treatment for these patients. FUNDING: Bristol Myers Squibb, in collaboration with Ono Pharmaceutical.

COVID-19 Pneumonia on Post-Operative Day 2 after Esophagectomy: Performing Esophago-Gastric Junction Cancer Surgery during the SARS-Cov-2 Second Wave.

The coronavirus disease 2019 (COVID-19) pandemic has had a substantial impact on the provision of medical healthcare. Due to an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) transmission, elective surgical treatment has been suspended in many centers. The effects of COVID-19 in the early post-operative period after esophagectomy remains unknown. In this report, we present three cases of patients diagnosed with esophago-gastric junction cancer who were scheduled for elective esophagectomy with a curative intention during second wave of COVID-19 pandemic in a single high-volume tertiary center. Despite all available safety measures, one of the patients developed COVID-19 pneumonia on post-operative day two, leading to an impaired respiratory function and increased pleural fluid collection from the chest tube, resulting in a prolonged time of hospital stay. Finding a good balance between the COVID-19-related perioperative risks and consequences of delaying surgical treatment in patients diagnosed with esophago-gastric cancer is a challenge. In order to achieve the best possible outcome, care must be taken to ensure availability of necessary treatment options and to reduce the risk of SARS-Cov-2 transmission perioperatively.

HER2 gene assessment in liquid biopsy of gastric and esophagogastric junction cancer patients qualified for surgery.

BACKGROUND: Amplification of HER2 gene (ERBB2) and overexpression of HER2 protein on cancer cells are found in 10-26% of gastric cancer (GC) and esophagogastric junction cancer (EGJC). Gene copy number variation (CNV) could be detected in these patients in liquid biopsy and in cancer cells. METHODS: We analysed HER2 gene CNV used qPCR method in 87 sera collected from GC and EGJC patients before surgical treatment and in 40 sera obtained from healthy donors. HER2 gene CNV was also assessed in formalin-fixed paraffin-embedded (FFPE) tumor tissue. Furthermore, we assessed the number of HER2 gene copies and HER2 expression in cancer cells using the fluorescent in situ hybridization method (FISH) and immunohistochemistry (IHC). RESULTS: We found that the HER2 gene copy number in liquid biopsy was higher in GC and EGJC patients compared to healthy people (p = 0.01). Moreover, EGJC patients had higher number of HER2 gene copies than healthy donors (p = 0.0016). HER2 CNV examination could distinguish healthy individuals and patients with gastric or esophagogastric junction cancers with sensitivity and specificity of 58% and 98% (AUC = 0.707, 95% CI 0.593-0.821, p = 0.004). We found that patients with a high copy number of the HER2 gene in the tumor tissue assessed by qPCR (but not by FISH) have significantly more often a high number of HER2 gene copies in liquid biopsy (p = 0.04). CONCLUSIONS: We suggested that HER2 testing in liquid biopsy could be used as an auxiliary method to analysis of HER2 status in tumor tissue in gastric or esophagogastric junction cancers.

Yield of staging laparoscopy in gastric cancer is influenced by Laurén histologic subtype.

BACKGROUND: Staging laparoscopy (SL) with cytologic lavage is a useful staging procedure that allows tailoring the treatment of advanced gastric cancer (GC). The current study aimed to evaluate the total yield of SL in patients with various Laurén histo-types of GC, before planned neoadjuvant chemotherapy and gastrectomy. METHODS: After exclusion of distant metastatic disease on imaging modalities, 173 patients with primary advanced gastric adenocarcinoma who underwent SL between August 2016 and September 2018, were eligible for the analysis. Patients sex, age, Lauren histo-type, tumor location, grade, cT, and cN were assessed in bivariate analysis. Multivariable logistic regression analysis was used to identify independent factors associated with peritoneal metastases. RESULTS: Peritoneal metastases, ascites, and positive cytology were found in 39 (22.5%), 17 (9.8%) and 38 (22%) patients, respectively. The total yield of the SL in the current study was 36.4%. Multivariable logistic regression analysis revealed that serosal involvement (cT4) and diffuse histo-type were independent predictors of peritoneal metastases (OR, 15; 95% CI, 1.9-119, P = .02 and OR, 2.4; 95% CI, 1.2-4.6, P = .01, respectively). CONCLUSIONS: Although cT4 and diffuse tumors show the highest association with peritoneal metastases, SL is a valuable diagnostic procedure in all advanced GC patients.

Blast from the past: Perioperative use of the Maruyama computer program for prediction of lymph node involvement in the surgical treatment of gastric cancer following neoadjuvant chemotherapy.

BACKGROUND: Surgical quality assurance is a key element of gastric cancer treatment. The Maruyama Computer Program (MCP) allows to predict lymph node involvement in stations no. 1-16. The aim of the current study was to evaluate the accuracy of the MCP predictions in GC patients treated with neoadjuvant chemotherapy (nCTH) followed by gastrectomy with adequate lymphadenectomy. METHODS: 101 patients who underwent preoperative nCTH followed by D2 gastrectomy with curative intent were analysed. The response to nCTH was measured using the tumour regression grade system. RESULTS: Test sensitivity, specificity, PPV, NPV and accuracy of the MCP were 92%, 33%, 41%, 89%, and 53%, respectively. In patients with response to nCTH, number of false positive (FP) results was significantly higher than in patients who did not respond to nCTH both in the N1 (56.3% vs 28.9%, p < 0.0001) and in the N2 (59% vs 41%, p < 0.0001) trier. The risk for FP results was 6 times higher in N1 (OR = 6.50, 95%CI: 3.91-10.82,; p < 0.0001) and N2 (OR = 5.84, 95%CI: 2.85-11.96; p < 0.0001) triers. In patients with intestinal type GC, the risk for FP results was 4 times higher than in other histologic types of GC in both N1 (OR = 4.23, 95%CI: 2.58-6.95; p < 0.0001) and N2 (OR = 4.23, 95%CI: 2.02-9.62; p = 0.0002) triers. CONCLUSIONS: MCP predictions in the GC patients treated with nCTH have low specificity due to significantly high number of FP results. Noticeably low accuracy level of predictions indicate a need for new prediction models, based on Laurén classification, since it may provide some information on expected regression grade.

Perfusion CT - A novel quantitative and qualitative imaging biomarker in gastric cancer.

OBJECTIVES: The aim of this research was to examine whether Perfusion Computed Tomography (P-CT) can qualitatively and quantitatively help detect gastric cancer neoangiogenesis in vivo as well as treatment response evaluation. We attempted to explore which P-CT parameters are best used in neoangiogenesis and neoadjuvant therapy for most effective evaluation. We also tried to recognize a positive prediction value of P-CT in early responders and non-responders patients identification. MATERIALS AND METHODS: Twenty-four patients with positive biopsy results and/or clinically proven gastric cancer were enrolled in the P-CT exam. Patients were qualified for systemic treatment (16 patients received chemotherapy and 8 patients received radiochemotherapy). The baseline Perfusion-CT exam and after neoadjuvant treatment Perfusion-CT exam were conducted using a 64-row GE tomograph based on a deconvolution model in first-pass protocol perfusion. The P-CT examined the following parameters: Blood Flow (BF), Blood Volume (BV), Mean Transit Time (MTT) and Permeability Surface (PS). Positive clinical response to neoadjuvant treatment (CHT and RCT) was defined as tumor size reduction 25% or more. RESULTS: Tumor dimension reduction after neoadjuvant therapy was significantly correlated with the BF and the PS. Neoadjuvant therapy was more effective for patients with higher output BF and PS values. We did not register a significant relationship between BV and MTT parameters and tumor dimension reduction. Patients with a positive treatment response showed a decrease in BF, BV and PS perfusion parameters with an increase in MTT. CONCLUSIONS: P-CT examination allows a noninvasive neoangiogenesis assessment in vivo, leading to early identification of responding and non-responding patients. As a standard procedure, a full evaluation of treatment response should include a P-CT exam assessing neoangiogenesis.

The Influence of Patient-related Constutional and Environmental Factors on Early Results of a Combined Modality Therapy of Esophageal Cancer.

Among many various factors affecting the outcome of cancer treatment one can distinguish patient, tumor- and treatment-related factors. The association of patient-related factors and results of a combined modality therapy of esophageal cancer has not been extensively explored. The aim of the study was to analyze the impact of patient-related constitutional and environmental factors on early results of combined modality therapy of esophageal squamous cell carcinoma. MATERIAL AND METHODS: We retrospectively analyzed prospectively collected data of 84 patients with esophageal cancer randomly assigned to a combined modality treatment. We evaluated the relationship between early outcome of neoadjuvant therapy (overall toxic events, serious toxic events, treatment-related mortality, clinical and pathological response to the treatment) or surgical treatment (postoperative morbidity, mortality and curative resections - R0) and constitutional (age, gender, height, body mass index, Karnofski Performance Status - KPS, blood type) or environmental (inhabitation, smoking duration and intensity, frequency and amount of alcohol consumption and occupational exposure) patient-related factors. RESULTS: Significantly more neoadjuvant therapy related deaths were found in patients with KPS 70-80 (p=0.0016). Interestingly, significantly more toxic events (p=0.0034) after neoadjuvant therapy and a higher postoperative morbidity rate (p=0.0293) were observed in nonsmokers. Similarly, significantly more toxic events (p=0.0029) after neoadjuvant therapy and a higher postoperative mortality rate (p=0.0405) were found in light drinkers. CONCLUSIONS: Smoking and consumption of excessive amount of alcohol may attenuate toxic effect of neoadiuvant and surgical therapy in patients treated due to esophageal cancer. The information regarding the mentioned above addictions should not result in giving up an attempt to provide a curative treatment.

Salivary bicarbonate as a major factor in the prevention of upper esophageal mucosal injury in gastroesophageal reflux disease.

BACKGROUND: It has been previously demonstrated that the exposure of the lower esophageal mucosa to acid and pepsin results in significant increase in salivary protective factors secretion, mediated by the esophago-salivary reflex. The impact of the upper esophageal mucosal exposure to acid and pepsin on salivary secretory response remains unknown. AIMS: To investigate the rate of salivary protective factors secretion during the upper esophageal mucosal exposure to acid and pepsin and to compare with the corresponding results recorded during the lower esophageal mucosal exposure, in the same group of asymptomatic volunteers. METHODS: The study was conducted in 10 asymptomatic volunteers. Salivary samples were collected during the esophageal mucosal exposure to saline, followed by acid/pepsin and the final saline, using the esophageal perfusion catheter. Salivary bicarbonate and non-bicarbonate buffers were analyzed using TitraLab. Salivary mucin and protein were quantified through PAS and Lowry methodologies, respectively, whereas PE2 using radioimmunoassay. Statistical analysis was performed using Σ-Stat software. RESULTS: The rate of salivary bicarbonate secretion was significantly higher (3.1-fold) during the upper versus the lower esophageal mucosal exposure to acid and pepsin (87.5 ± 14.4 vs. 28.0 ± 7.70 µEq/min, p < 0.05). The volumes of saliva, pH, salivary protein, mucin and PE2 were similar in both esophageal perfusions. CONCLUSIONS: Threefold stronger secretion of salivary bicarbonate could be a major factor protecting the upper esophageal mucosa. This phenomenon may represent an ultimate defense mechanism potentially preventing further complications within the upper esophageal mucosa; however, it needs to be confirmed in patients of gastroesophageal reflux disease.

Minimally invasive surgery for esophageal cancer - benefits and controversies.

Open esophagectomy (OE) requires extensive surgery and is associated with significant morbidity and mortality. Furthermore, the long-term results of esophageal cancer surgery are not satisfactory; hence, the best surgical approach is constantly under debate. During the last twenty years, minimally invasive esophagectomy (MIE) employing laparoscopy and/or thoracoscopy has been introduced in a growing number of centers worldwide. To date, several studies have demonstrated that MIE has better outcomes than OE, as it results in shorter hospital stay and decreased overall morbidity. However, the length of operating time in MIE is increased in comparison to OE. The survival benefit has been demonstrated to be similar in OE and MIE. Highly advanced laparo-thoracoscopic skills are required to perform MIE; along with the relatively long learning curve, this makes MIE feasible only in high-volume, experienced university surgical centers. There is a need for further large-scale comparative studies to prove the superiority of MIE over open surgery.

The value of percutaneous ultrasound in predicting conversion from laparoscopic to open cholecystectomy due to acute cholecystitis.

BACKGROUND: Laparoscopic cholecystectomy has become the treatment of choice for gallstone disease. Advantages of the laparoscopic approach include lower morbidity and mortality rates, reduced length of hospital stay, and earlier return to work. In acute cholecystitis, severe inflammation makes laparoscopic dissection technically more demanding, with a higher risk of related complications that require conversion to open cholecystectomy. METHODS: We reviewed the records of 5,596 patients who underwent cholecystectomy between 1993 and 2011 in a single institution. A laparoscopic approach was undertaken in 4,105 patients (73.4 %). The ultrasound signs of acute cholecystitis were found in 542 patients (13.2 %) who underwent laparoscopic cholecystectomy. We analyzed the ultrasound presentations of acute cholecystitis in patients who required conversion to open cholecystectomy and compared them with the ultrasound signs of acute cholecystitis in patients who had a completed laparoscopic cholecystectomy. RESULTS: A conversion to open cholecystectomy in patients with acute cholecystitis was necessary in 24 % (n = 130) of the patients compared to 3.4 % of the patients with uncomplicated gallstone disease. The most frequent ultrasound findings in patients requiring conversion were a pericholecystic exudate in 42 %, a difficult identification of anatomical structures due to local severe inflammation in 34 %, and gallbladder wall thickening of >5 mm in 31 %. Additionally, when the duration of symptoms exceeded 3 days, more than half of the patients required conversion to open cholecystectomy and the conversion rate was fivefold higher than for those with a shorter duration of acute cholecystitis. CONCLUSIONS: In patients with severe acute cholecystitis found on ultrasound, combined with gallbladder wall thickening to >5 mm, pericholecystic exudates or abscess adjacent to the gallbladder, difficulty identifying anatomical structures within Calot's triangle, specifically when the duration of symptoms exceeds 3 days, cholecystectomy should be done as an open approach because of the high risk of conversion.