Squamous Cell Carcinoma Of The Esophagus Research Articles

An analysis of the risk factors of anastomotic stricture after esophagectomy.

Anastomotic stricture after esophagectomy is a major cause of long-term morbidity and a poor quality of life. The aim of this study was to identify the risk factors for the development of anastomotic stricture after esophagectomy. The study subjects were 213 patients who underwent esophagectomy for squamous cell carcinoma of the esophagus between 2012 and 2014. Anastomotic stricture was defined as stenosis at the site of anastomosis that required endoscopic dilation. Refractory stricture was defined as that requiring more than four sessions of dilations. Univariate and multivariate logistic regression analyses were used to identify the potential risk factors for the development of anastomotic stricture. In this retrospective study, 29 patients (13.6%) developed anastomotic stricture within a median period of 108 postoperative days and required a median of 2 dilations. Tumors located in the upper part of the esophagus (p = 0.004), the presence of cardiovascular disease (p = 0.024) and anastomotic leakage (p = 0.002) were identified as independent risk factors for the development of anastomotic stricture. The time to the diagnosis of refractory stricture (85 ± 33 days) was significantly shorter than that of non-refractory stricture (171 ± 22 days, p = 0.038). Patients with squamous cell carcinoma in the upper esophagus with cardiovascular disease who develop postoperative anastomotic leakage should be carefully monitored to prevent the development of benign anastomotic stricture.

Comparison of neoadjuvant chemoradiation with carboplatin/ paclitaxel or cisplatin/ 5-fluoruracil in patients with squamous cell carcinoma of the esophagus

PurposeNeoadjuvant chemoradiation (nCRT) is the treatment of choice for patients with locally advanced squamous cell carcinoma of the esophagus (SCC). Today radiation oncologists can choose between two different therapy regimes including chemoradiation with cisplatin and 5-fluoruracil (CDDP/5FU) and chemoradiation analogue to the CROSS-regime with carboplatin and paclitaxel (Carb/TAX). However, there is a lack of studies comparing these regimes, especially for the subgroup of patients with SCC. In this study, we want to compare nCRT with CDDP/5FU and nCRT with Carb/TAX for patients with locally advanced SCC.Patients and methodsWe retrospectively compared 20 patients who were scheduled for nCRT with a total radiation dose of 41.4 Gy (daily dose of 1.8 Gy) and weekly chemotherapy with carboplatin (Area under the curve 2) and Paclitaxel (50 mg per square meter of body-surface area) according to the CROSS-regime to 31 patients who were scheduled for nCRT with a total radiation dose of 45 Gy (daily dose of 1.8 Gy) and simultaneous chemotherapy with cisplatin (20 mg/m2/d) and 5-fluoruracil (500 mg/m2/d) on day 1–5 and day 29–33. For the per-protocol (PP) analysis, per protocol treatment was defined as either complete radiation with 41.4 Gy, at least three complete cycles of Carb/TAX and subsequent surgery or complete radiation with 45 Gy, at least one complete cycle of CDDP/5FU and subsequent surgery.ResultsFifty-one patients (31 patients treated with CDDP/5FU and 20 patients treated with Carb/TAX) were evaluated for the intention-to-treat (ITT) analysis and 44 patients (26 patients treated with CDDP/5FU and 18 patients treated with Carb/TAX) were evaluated for the PP analysis. No significant differences were seen for baseline and tumor characteristics like age, sex, TNM-stage, grading and tumor extension between patients treated with Carb/TAX and patients treated with CDDP/5FU. The most common tumor regression grade after nCRT was grade I as classified by Becker et al., which was observed in 84 and 79% of patients. No significant differences in tumor regression grades were seen between both regimes. Postoperative insufficiency of the anastomosis was seen in 6 patients (33%) who were treated with Carb/TAX and 4 patients (15%) who were treated with CDDP/5FU (p = 0.273). Patients treated with CDDP/5FU developed significantly more cumulative hematologic III° (CTCAE) toxicities (58% vs 20%; p = 0.010) than patients treated with Carb/TAX. In contrast to that, there was no significant difference for overall survival (OS) and freedom from relapse (FFR) between treatment groups.ConclusionIn this retrospective analysis, no significant difference was seen for OS and FFR between nCRT with CDDP/5FU and nCRT with Carb/TAX. However, the application of CDDP/5FU was associated with significantly more hematologic III°- toxicities compared to Carb/TAX. Future prospective trials should investigate if these results are reproducible in randomized patient cohorts.

Endoscopic submucosal dissection of a squamous cell carcinoma of the esophagus developing in the area of a previous Heller’s myotomy for achalasia

Endoscopic submucosal dissection of a squamous cell carcinoma of the esophagus developing in the area of a previous Heller’s myotomy for achalasia

Overall Survival of Patients with Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma Treated with Nimotuzumab in the Real World.

Despite improvements in surgical techniques and treatments introduced into clinical practice, the overall survival of patients with esophageal squamous cell carcinoma remains low. Several epidermal growth factor receptor inhibitors are being evaluated in the context of clinical trials, but there is little evidence of effectiveness in real-world conditions. This study aimed at assessing the effectiveness of nimotuzumab combined with onco-specific treatment in Cuban real-life patients with locally advanced or metastatic esophageal squamous cell carcinoma. A comparative and retrospective effectiveness study was performed. The 93 patients treated with nimotuzumab were matched, with use of propensity score matching, with patients who received a diagnosis of locally advanced or metastatic squamous cell carcinoma of the esophagus in three Cuban provinces reported between 2011 and 2015 to the National Cancer Registry. The Kaplan-Meier method was used to estimate event-time distributions. Log-rank statistics were used for comparisons of overall survival between groups. A two-component mixture model assuming a Weibull distribution was fitted to assess the effect of nimotuzumab on short-term and long-term survival populations. There was an increase in median overall survival in patients treated with nimotuzumab (11.9months versus 6.5months without treatment) and an increase in the 1-year survival rate (54.0% versus 21.9% without treatment). The 2-year survival rates were 21.1% for patients treated with nimotuzumab and 0% in the untreated cohort. There were statistically significant differences in survival between groups treated and not treated with nimotuzumab, both in the short-term survival population (6.0months vs 4.0months, p=0.009) and in the long-term survival population (18.0months vs 11.0months, p=0.001). Our study shows that nimotuzumab treatment concurrent with chemoradiotherapy increases the survival of real-world patients with locally advanced or metastatic esophageal squamous cell carcinoma. Further prospective studies are required to confirm the therapeutic effectiveness of nimotuzumab in esophageal cancer.

Comparative Analysis of Clinical, Treatment, and Survival Characteristics of Basaloid and Squamous Cell Carcinoma of the Esophagus

Basaloid squamous cell carcinoma (BSC) is a rare variant of squamous cell carcinoma (SqCC) of the esophagus. Even though pathologically thought to be more aggressive than SqCC, there is discrepancy in the literature regarding the outcomes of BSC compared with those of SqCC. We conducted a retrospective cohort study using the Surveillance Epidemiology and End Results (SEER) database. All patients with a histologic diagnosis of BSC and SqCC between 2004 and 2013 were included. We compared treatment and survival characteristics of patients with BSC and SqCC. There were 16,158 patients included in this study; 173 patients (1.1%) had BSC. There were no significant differences between the 2 groups based on age, sex, marital status, insurance, or geographic region of diagnosis, but patients with BSC were more likely to be Caucasian (73.4% vs 64.7%; p= 0.017). Among staged patients, baseline tumor stage was similar in both groups. However, BSC tumors were more likely to be of high pathologic grade (56.8% vs 38.2%; p < 0.001). Patients with SqCC were more likely to receive radiation therapy (36.9% vs 53.9%; p < 0.001), while patients with BSC were more likely to undergo resection (32.4% vs 17.0%; p < 0.001). Median overall survival was similar in both groups (14 vs 9 months; log rank= 0.144), and this relationship persisted after stratification by treatment. Even though more likely to be poorly differentiated at presentation, BSC of the esophagus seems to have similar clinical features and survival outcomes when compared with SqCC. Patients with BSC and SqCC should undergo stage-specific treatment to achieve optimal outcomes.

With or without consolidation chemotherapy using cisplatin/5-FU after concurrent chemoradiotherapy in stage II–III squamous cell carcinoma of the esophagus: A propensity score-matched analysis

Background and purposeThe benefit of consolidation chemotherapy for locally advanced squamous cell carcinoma of the esophagus is unknown. The aim of this study was to investigate the efficacy of consolidation chemotherapy with cisplatin and 5-fluorouracil (5-FU) after concurrent chemoradiotherapy (CCRT) with the same agents in patients with stage II–III disease. Material and methodsData for patients with stage II–III squamous cell carcinoma of the esophagus treated with CCRT were retroactively reviewed. Patients who received CCRT alone (observation group) were compared with those who underwent CCRT followed by consolidation chemotherapy (consolidation group) with regard to progression-free survival, overall survival, treatment failure and toxicity. Differences in baseline characteristics were adjusted using the propensity score matching method. ResultsFrom September 2006 to September 2012, 812 patients were recruited (n = 272 for observation; n = 540 for consolidation). Among them, 290 (35.7%) had clinical stage II disease and 522 (64.3%) had stage III disease. In the overall study cohort, the median progression-free survival (22.1 months vs. 22.0 months, P = 0.917) and median overall survival (33.8 months vs. 31.3 months, P = 0.591) were comparable between the observation group and consolidation group. Comparisons of the observation and consolidation group in the matched population (262 patients in each group) showed median progression-free survival of 23.0 months and 25.4 months (hazard ratio [HR], 0.93; 95% CI [confidence interval], 0.74–1.15; P = 0.491), and median overall survival of 34.6 months and 35.0 months (HR, 0.92; 95% CI, 0.80–1.27; P = 0.919), respectively. There were no significant differences in local/regional failure and persistence disease (50.4% vs. 48.5%) and distant failure (10.7% vs. 8.8%) between the two groups. ConclusionsCompared to CCRT alone, consolidation chemotherapy did not further prolong progression-free survival and overall survival for patients with stage II–III squamous cell carcinoma of the esophagus. The role of consolidation therapy needs to be studied further.

Stereotactic body radiotherapy for oligo-recurrence in the liver in a patient with esophageal carcinoma: A case report.

Stereotactic body radiation therapy (SBRT) is a safe and effective treatment for solitary cancerous lesions. The present study reported a rare case of sustained remission after SBRT for oligorecurrence in the liver in a patient with esophageal carcinoma. A 60-year-old Japanese man presented with a chief complaint of dysphagia. On medical examination, the patient was diagnosed as having squamous cell carcinoma of the esophagus that was clinically staged as T4bN1M0. The patient received definitive concurrent chemoradiotherapy, consisting of four 28-day cycles of chemotherapy comprising nedaplatin 80 mg/m2 on day 1 and S-1 120 mg/body orally on days 1-14, with radiotherapy comprising a total of 50 Gy in daily fractions of 2 Gy. After a 9-month disease-free interval following the primary treatment, a solitary liver metastasis was identified. The patient underwent SBRT using a radiation dose of 48 Gy in 4 fractions and two 28-day cycles of adjuvant chemotherapy comprising nedaplatin 80 mg/m2 on day 1, and S-1 100 mg/body orally on days 1-14. The patient exhibited no signs of recurrence for 3 years with sustained local control. SBRT may be considered a treatment option for patients with relapsed esophageal cancer with oligo-recurrence in the liver.

A Rare Case of Squamous Cell Carcinoma of the Esophagus in a Patient With Goltz Syndrome

Introduction: Squamous cell carcinoma of the esophagus (SCCE) commonly involves the proximal esophagus and its incidence in the U.S. has been decreasing compared to adenocarcinoma (AC). While AC is mostly associated with Barrett's esophagus in elderly Caucasian men, SCCEis common in elderly African American men who consume tobacco and alcohol. The incidence in younger women is low and independent of race.Recently, SCCE has been described in patients with esophageal papillomatosis. Focal dermal hypoplasia (Goltz syndrome) is a rare disorder associated with musculoskeletal deformities and rarely oroesophageal papillomas that can result in dysphagia. We present a case of Goltz syndrome (GS) diagnosed with esophageal papillomas and SCCE during evaluation for dysphagia. Case presentation: A 37 years old African American female with history of GS presented with progressive dysphagia and weight loss. She denied tobacco and alcohol use. She was cachectic on exam. Syndactyly was noted in her hands and feet. Cutaneous hypo- and hyperpigmented areas were seen on her chest and arms. Her hemoglobin was 9 g/dl. Abdominal CT scan showed a large gastric mass with distal esophageal thickening. EGD revealed distal esophageal papillomas and a large, pedunculated mass arising from the gastroesophageal junction (GEJ) and extending into the gastric fundus. Endoscopic ultrasound (EUS) showed a large mass starting at the GEJ, involving all esophageal layers and encasing the aorta. Fine needle aspiration biopsy revealed moderately differentiated squamous cell carcinoma. Irinotecan and cisplatin were started. Discussion: Goltz syndrome is an uncommon X-linked dominant disorder with only about 300 cases reported worldwide. Females are predominantly affected as males die in utero. It presents with cutaneous and skeletal defects in the form of dermal pigmentary changes and hypoplasia, syndactyly, and dysplastic changes of the teeth and bones. Occasionally gastrointestinal defects such as oroesophageal papillomatosis occur. Given the rarity of GS, the natural history of associated esophageal papillomatosis in this setting is unknown. To our knowledge, this is the first described case of GS associated with esophageal malignancy. Clinicians caring for patients with esophageal papillomatosis should have a low threshold for utilizing endoscopy and possibly EUS in investigating dysphagia, especially in patients with Goltz syndrome.Figure: Skeletal and dermal deformities.Figure: CT abdomen showing mass at GE junction.Figure: Endoscopic view.

C2 Balloon Cryotherapy for Symptom Relief in Esophageal Squamous Cell Carcinoma: A Novel Approach: 2017 Presidential Poster Award

Introduction: Focal cryoballoon ablation therapy is a relatively new modality that has been reported in treatment of Barrett's esophagus and esophageal squamous cell neoplasia. It is safe and well-tolerated by patients. Here we report a case that highlights the rare use of C2 cryoballoon cryotherapy for symptoms relief in a patient with malignant dysphagia. Case: A 70 year-old female with medical history of atrial fibrillation and hyperplastic colonic polyps presented with a 5-week history of odynophagia and subsequent dysphagia with solids and liquids associated with increasing lower substernal chest pain and 20-lb of weight loss. Patient was found to have a poorly differentiated squamous cell carcinoma in the distal third of the esophagus from 33 to 38 cm with narrowing of the lumen but not fully obstructed. A CT scan demonstrated extensive mediastinal and gastrohepatic lymph node involvement but no metastases to the lungs or liver. In light of worsening of esophageal symptoms, she was initially referred for possible esophageal stent placement. On EGD, a near circumferential fungating mass was found in the lower third of the esophagus, consistent with established locally advanced squamous cell carcinoma of esophagus. Balloon-based TTS (C2 focal catheter) cryotherapy was applied in 6 sessions to the entire lesion using 12 seconds applications. Patient tolerated the procedures well with no complications and was discharged on a soft diet. Esophageal symptoms were greatly alleviated and she was to continue to follow with Oncology and Radiation Oncology.Figure: Circumferential fungating mass in distal third of esophagusFigure: Balloon-based through-the-scope (C2 focal catheter)Discussion: Cryoballoon Focal Ablation System is a novel through-the-scope, balloon catheter, easy-to-use, obviating the need for sizing, with a handle and a small disposable cryogen cartridge. It has been developed for treatment of Barrett's esophagus, including refractory disease, and potentially of esophageal squamous cell carcinoma. We described a case revealing the rare and unique use of C2 balloon cryotherapy for symptoms relief in a patient with locally advanced squamous cell carcinoma of the esophagus. For palliation of malignant dysphagia, esophageal stents are widely used despite their myriad complications. As highlighted in this case, focal cryoballoon ablation is a novel and promising therapy that is relatively safe and effective in achieving resolution of symptoms.Figure: Ablation of esophageal fungating mass using a Balloon-based TTS (C2 focal catheter)

A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer

BackgroundHuman epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity.MethodsThis open-label, dose-finding study comprised dose escalation, followed by expansion in patients with squamous cell carcinoma of the head and neck or esophagus, and HER2-overexpressing metastatic breast cancer or gastric cancer. During dose escalation, patients received LJM716 intravenous once weekly (QW) or every two weeks (Q2W), in 28-day cycles. An adaptive Bayesian logistic regression model was used to guide dose escalation and establish the RDE. Exploratory pharmacodynamic tumor studies evaluated modulation of HER3 signaling.ResultsPatients received LJM716 3–40 mg/kg QW and 20 mg/kg Q2W (54 patients; 36 patients at 40 mg/kg QW). No dose-limiting toxicities (DLTs) were reported during dose-escalation. One patient experienced two DLTs (diarrhea, hypokalemia [both grade 3]) in the expansion phase. The RDE was 40 mg/kg QW, providing drug levels above the preclinical minimum effective concentration. One patient with gastric cancer had an unconfirmed partial response; 17/54 patients had stable disease, two lasting >30 weeks. Down-modulation of phospho-HER3 was observed in paired tumor samples.ConclusionsLJM716 was well tolerated; the MTD was not reached, and the RDE was 40 mg/kg QW. Further development of LJM716 is ongoing.Trial registrationClinicaltrials.gov registry number NCT01598077 (registered on 4 May, 2012).

The Significance of SCC and CEA mRNA in the Pleural Cavity After Lymphadenectomy in Esophageal Cancer Patients who Underwent Preoperative Treatment.

This report focuses on the surgical manipulation and spread of cancer cells. Our previous study suggested an association between a poor prognosis and positive pleural lavage cytology after resection of esophageal cancer without preoperative treatment. However, little is known regarding the clinical significance of the lavage procedure in esophageal cancer patients who undergo preoperative treatment. A cohort of 94 patients with squamous cell carcinoma of the esophagus who underwent esophagectomy with radical lymph node dissection was prospectively analyzed for free cancer cells in the pleural cavity after mediastinal lymphadenectomy. Reverse transcription-polymerase chain reaction was performed to detect free cancer cells in the pleural lavage fluid by measuring squamous cell carcinoma-related antigen (SCC) and carcinoembryonic antigen (CEA). Forty-two patients (44.7%) were positive for SCC after thoracic lymphadenectomy, and 15 patients (15.9%) were positive for CEA. SCC positivity was significantly associated with venous invasion (p=0.037) and with the clinical response to preoperative treatment (p=0.001). Furthermore, SCC positivity was associated with poor prognosis compared with negative SCC (p=0.026). Multivariate analysis revealed that SCC positivity was an independent prognostic factor. Regarding recurrence patterns, SCC positivity tended to be associated with hematogenous recurrence (p=0.063). Conversely, positive CEA was not associated with any clinicopathological finding, treatment response, prognosis, or recurrence pattern. Tumor spillage during the evaluated surgical manipulation was assessed in esophageal cancer patients who underwent preoperative treatment. Tumor spillage as evaluated by SCC mRNA was associated with a poor prognosis.

Clinicopahological features of superficial basaloid squamous cell carcinoma of the esophagus.

Basaloid squamous cell carcinoma (BSC) of the esophagus is classified as an epithelial malignant tumor and is a rare variant of squamous cell carcinoma (SCC). Most previous reports have suggested that advanced BSC has a poorer prognosis than typical SCC because of its high biological malignancy, but the biological activity of superficial BSC remains unclear. Twenty cases of superficial BSC, which underwent surgical resection in Tokai University Hospital between January 2004 and December 2013, were analyzed retrospectively. Among these cases, 19 cases with a T1 depth of invasion (BSC group) were compared with 180 cases of SCC that were resected during the same period and were pathologically diagnosed as T1 (SCC group). The frequency of lymph node metastasis in the T1 BSC group was significantly lower (2 patients, 11%) than that in the SCC group (84 patients, 47%) (P=0.005). The frequency of lymphatic invasion in the BSC group was also lower (9 patients, 47%) than that in the SCC group (131 patients, 73%) (P=0.021). The pathological type of the metastatic lymph node was BSC in all the superficial BSC cases with lymph node metastasis. This study demonstrated that lymph node metastasis was less likely to occur in cases with superficial BSC than in cases with superficial SCC.

Racial disparities in cancer-related survival in patients with squamous cell carcinoma of the esophagus in the US between 1973 and 2013.

BackgroundEsophageal cancer makes up approximately 1% of all diagnosed cancers in the US. There is a persistent disparity in incidence and cancer-related mortality rates among different races for esophageal squamous cell carcinoma (SCC). Most previous studies investigated racial disparities between black and white patients, occasionally examining disparities for Hispanic patients. Studies including Asians/Pacific Islanders (API) as a subgroup are rare. Our objective was to determine whether there is an association between race and cancer-related survival in patients with esophageal SCC.Methods and findingsThis was a retrospective cohort study using the National Cancer Institute’s Surveillance, Epidemiology, and End Result (SEER) database. The SEER registry is a national database that collects information on all incident cancer cases in 13 states of the United States and covers nearly 26% of the US population Patients aged 18 and over of White, Black, or Asian/Pacific Islander (API) race with diagnosed esophageal SCC from 1973 to 2013 were included (n = 13,857). To examine overall survival, Kaplan-Meier curves were estimated for each race and the log-rank test was used to compare survival distributions. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios with 95% confidence intervals. The final adjusted model controlled for sex, marital status, age at diagnosis, decade of diagnosis, ethnicity, stage at diagnosis, and form of treatment. Additional analyses stratified by decade of diagnosis were conducted to explore possible changes in survival disparities over time. After adjustment for potential confounders, black patients had a statistically significantly higher hazard ratio compared to white patients (HR 1.08; 95% confidence interval (CI) 1.03–1.13). However, API patients did not show a statistically significant difference in survival compared with white patients (HR 1.00; 95% CI 0.93–1.07). Patients diagnosed between 1973 and 1979 had twice the hazard of death compared to those diagnosed between 2000 and 2013 (HR 2.05, 95% CI 1.93–2.19). Patients diagnosed in 1980–1989 and 1990–1999 had had HRs of 1.59 (95% CI 1.51–1.68) and 1.33 (95% CI 1.26–1.41), respectively. After stratification according to decade of diagnosis, the HR for black patients compared with white patients was 1.14 (95% CI 1.02–1.29) in 1973–1979 and 1.12 (95% CI 1.03–1.23) in 1980–1989. These disparities were not observed after 1990; the HR for black patients compared with white patients was 1.03 (95% CI 0.93–1.13) in 1990–1999 and 1.05 (95% CI 0.96–1.15) in 2000–2013.ConclusionsBlack patients with esophageal SCC were found to have a higher hazard of death compared to white and API patients. Survival disparities between races appear to have decreased over time. Future research that takes insurance status and other social determinants of health into account should be conducted to further explore possible disparities by race.

Prevalence of Squamous Cell Carcinoma of the Esophagus in a Single Tertiary Center of South Africa: A Cross Sectional Analytic Study.

The incidence of esophageal cancer varies widely in the world. In the Middle East, Africa, and Asia and parts of Europe, squamous cell carcinoma of the esophagus dominates the esophageal cancer landscape. Worldwide the rates are highest in Northern China, South Africa, Turkey and Iran. In the United States, the black population has a five-fold higher incidence of esophageal squamous cell carcinoma than the white population. To determine the prevalence of squamous cell carcinoma of the esophagus in a single tertiary center in South Africa. Patients referred to Gastroenterology Division of Steve Biko Academic Hospital for upper gastrointestinal endoscopy were recruited. Those with a known diagnoses of squamous cell carcinoma of the esophagus were recorded and those with suspicious lesions had biopsies done. These were then evaluated by an experienced histopathologist. 6118 patients were recruited. Squamous cell carcinoma was found in 59 patients giving us a prevalence of 0.96% 95%CI. The cancer was found mainly in back elderly males. The prevalence of squamous cell carcinoma of the esophagus in this single center study is 0.96%, 95% confidence interval and is a disease of black elderly males as seen elsewhere. Bigger multicenter studies are needed to further clarify this findings.

DVH- and NTCP-based dosimetric comparison of different longitudinal margins for VMAT-IMRT of esophageal cancer

PurposeTo cover the microscopic tumor spread in squamous cell carcinoma of the esophagus (SCC), longitudinal margins of 3–4 cm are used for radiotherapy (RT) protocols. However, smaller margins of 2–3 cm might be reasonable when advanced diagnostic imaging is integrated into target volume delineation. Purpose of this study was to compare the dose distribution and deposition to the organs at risk (OAR) for different longitudinal margins using a DVH- and NTCP-based approach.MethodsTen patients with SCC of the middle or lower third were retrospectively selected. Three planning target volumes (PTV) with longitudinal margins of 4 cm, 3 cm and 2 cm and an axial margin of 1.5 cm to the gross target volume (GTV) were defined for each patient. For each PTV two treatment plans with total doses of 41.4 Gy (neoadjuvant treatment) and 50.4 Gy (definite treatment) were calculated. Dose to the lungs, heart, myelon and liver were then evaluated and compared between different PTVs.ResultsWhen using a longitudinal margin of 3 cm instead of 4 cm, all dose parameters (Dmin, Dmean, Dmedian and V5-V35), except Dmax could be significantly reduced for the lungs. Regarding the heart, a significant reduction was seen for Dmean and V5, but not for Dmin, Dmax, Dmedian and V10-V35. When comparing a longitudinal margin of 4 cm to a longitudinal margin of 2 cm, a significant difference was calculated for Dmin, Dmean, Dmedian and V5-V35 of the lungs and for Dmax, Dmean and V5-V35 of the heart. Nevertheless, no difference was seen for median heart dose. An additional dose reduction for V10 of the heart was achieved for definite treatment plans when using a longitudinal margin of 3 cm. The NTCP-based risk of pneumonitis was significantly reduced by a margin reduction to 2 cm for neoadjuvant and definite treatment plans.ConclusionReduction of longitudinal margins from 4 cm to 3 cm can significantly reduce the dose to lungs and Dmean of the heart. Despite clinical benefit and oncologic outcome remain unclear, reduction of the longitudinal margins might provide the opportunity to reduce side effects of chemoradiation (CRT) for SCC in upcoming studies.

Identification of NCCRP1 as an epigenetically regulated tumor suppressor and biomarker for malignant phenotypes of squamous cell carcinoma of the esophagus.

The poor prognosis and increasing incidence of esophageal squamous cell carcinoma (ESCC) highlight the need for identification of novel ESCC-associated molecular events to improve the diagnosis, and treatment of this disease. Non-specific cytotoxic cell receptor protein 1 (NCCRP1) was reported to be abundantly expressed in human squamous epithelium and to be involved in cell proliferation; however, the role of NCCRP1 in ESCC remains unclear. To elucidate the oncological roles of NCCRP1 in ESCC, NCCRP1 expression, DNA methylation, and copy numbers were analyzed in ESCC cell lines. Nine ESCC cell lines demonstrated different NCCRP1 mRNA expression levels and all exhibited hypermethylation of the NCCRP1 promoter, but no copy number loss. Additionally, NCCRP1 expression was determined in 213 surgically resected esophageal tissue samples. NCCRP1 mRNA expression levels were reduced in ESCC tissues compared with corresponding non-cancerous adjacent tissues in 204 (95.8%) patients. Patients in the low NCCRP1 expression group tended to have a higher recurrence rate and a shorter overall survival time compared with those in the high NCCRP1 expression group. Additionally, multivariate analysis revealed that low NCCRP1 expression was an independent prognostic factor (hazard ratio, 1.75; 95% confidence interval, 1.08-2.87; P=0.022). The findings of the current study indicate that NCCRP1 acts as a putative tumor suppressor that is inactivated through promoter hypermethylation, and serves as a promising biomarker to predict postoperative prognosis in ESCC.

Endoscopic Management of Early Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus: Screening, Diagnosis, and Therapy

Because the esophagus is easily accessible with endoscopy, early diagnosis and curative treatment of esophageal cancer is possible. However, diagnosis is often delayed because symptoms are not specific during early stages of tumor development. The onset of dysphagia is associated with advanced disease, which has a survival at 5 years lower than 15%. Population screening by endoscopy is not cost-effective, but a number of alternative imaging and cell analysis technologies are under investigation. The ideal screening test should be inexpensive, well tolerated, and applicable to primary care. Over the past 10 years, significant progress has been made in endoscopic diagnosis and treatment of dysplasia (squamous and Barrett's), and early esophageal cancer using resection and ablation technologies supported by evidence from randomized controlled trials. We review the state-of-the-art technologies for early diagnosis and minimally invasive treatment, which together could reduce the burden of disease.

A novel gene expression scoring system for accurate diagnosis of basaloid squamous cell carcinoma of the esophagus.

Basaloid squamous cell carcinoma of the esophagus (BSCE) is a rare variant of squamous cell carcinoma that is difficult to distinguish from other carcinomas by preoperative endoscopic biopsy because of its histological varieties. Accurate diagnosis is essential for adequate treatment, and the methods proposed so far (e.g., immunohistochemical staining) have limitations. In this study, we tried to identify the characteristic bundles of gene expression in BSCE using comprehensive gene expression analysis (CGEA). Subsequently, we constructed a gene expression scoring system for the proper diagnosis of BSCE. Fifty-seven surgical specimens, including seven BSCEs, obtained from 30patients who underwent esophagectomy were used for constructing the scoring system. Three hundred and twelve biopsy specimens, including eight BSCEs, obtained from 80patients and 20commercially available formalin-fixed paraffin-embedded (FFPE) specimens diagnosed as esophageal cancer, including 13 BSCEs, were used for validation. After our original mathematical extraction algorithm, 75genes were extracted to distinguish BSCE from non-BSCE. The cumulative converted values (gene expression score) of the respective 75genes from each specimen were obtained and lined up in ascending order to assess the optimal gene expression cut-off score for a definitive diagnosis of BSCE. The validation of this scoring system showed high prediction of the biopsy specimens [area under the curve (AUC)=0.981; 95% confidence interval (CI): 0.952‑1.000] and the commercially available FFPE specimens (AUC=0.901; 95% CI: 0.750-1.000). In conclusion, using CGEA in a gene expression scoring system helps in differentiating BSCE from non-BSCE with high accuracy and may contribute in improving BSCE treatment.

Endoscopic diagnosis and management of early squamous cell carcinoma of esophagus

In recent years, diagnosis of early squamous cell carcinoma (SCC) of the esophagus has been increasingly emphasized. Utilization of image enhanced technology such as narrow band imaging (NBI) and magnification endoscopy allowed detailed examination of the esophageal mucosa. Different patterns of intrapapillary capillary loops (IPCL) have been proven to accurately diagnose and predict the depth of invasion of the tumors. In addition, the application of endoscopic submucosal dissection (ESD) has enabled safe en bloc resection of esophageal lesions. Promising results of ESD have been published and ESD is now the standard of therapy in early SCC of esophagus.

Combination of c-reactive protein and squamous cell carcinoma antigen in predicting postoperative prognosis for patients with squamous cell carcinoma of the esophagus.

BackgroundWe initially proposed a useful and novel prognostic model, named CCS [Combination of c-reactive protein (CRP) and squamous cell carcinoma antigen (SCC)], for predicting the postoperative survival in patients with esophageal squamous cell carcinoma (ESCC).MethodsTwo hundred and fifty-two patients with resectable ESCC were included in this retrospective study. A logistic regression was performed and yielded a logistic equation. The CCS was calculated by the combined CRP and SCC. The optimal cut-off value for CCS was evaluated by X-tile program. Univariate and multivariate analyses were used to evaluate the predictive factors. In addition, a novel nomogram model was also performed to predict the prognosis for patients with ESCC.ResultsIn the current study, CCS was calculated as CRP+6.33 SCC according to the logistic equation. The optimal cut-off value was 15.8 for CCS according to the X-tile program. Kaplan-Meier analyses demonstrated that high CCS group had a significantly poor 5-year cancer-specific survival (CSS) than low CCS group (10.3% vs. 47.3%, P <0.001). According to multivariate analyses, CCS (P =0.004), but not CRP (P =0.466) or SCC (P =0.926), was an independent prognostic factor. A nomogram could be more accuracy for CSS (Harrell's c-index: 0.70).ConclusionThe CCS is a usefull and independent predictive factor in patients with ESCC.