Development and validation of a nomogram for preoperative prediction of lymph node metastasis in pathological T1 esophageal squamous cell carcinoma

Endoscopic resection is increasingly used to treat patients with pathological T1 (pT1) esophageal squamous cell carcinoma (ESCC) because of its small surgical trauma. However, reports of the risk factors for lymph node metastasis (LNM) have been controversial. Therefore, we aim to build a nomogram to individually predict the risk of LNM in pT1 ESCC patients, to make an optimal balance between surgical trauma and surgical income.One hundred seventy patients with pT1 esophageal cancer in our hospital were analyzed retrospectively. Logistic proportional hazards models were conducted to find out the risk factor associated with LNM independently, and those were imported into R library “RMS” for analysis. A nomogram is generated based on the contribution weights of variables. Finally, decision analysis and clinical impact curve were used to determine the optimal decision point.Twenty-five (14.7%) of the 170 patients with pT1 ESCC exhibited LNM. Multivariable logistic regression analysis showed that smoking, carcinoembryonic antigen, vascular tumor thromboembolus, and tumor differentiation degree were independent risk factors for LNM. The nomogram had relatively high accuracy (C index of 0.869, 95% confidence interval: 0.794–0.914, P < .0001). The decision curve analysis provided the most significant clinical benefit for the entire included population, with scores falling just above the total score of 85 in the nomogram.Smoking, carcinoembryonic antigen, vascular tumor thromboembolus, and tumor differentiation degree may predict the risk of LNM in tumor 1 ESCC. The risk of LNM can be predicted by the nomogram.     

Clinicopathologic factors predicting lymph node metastasis in superficial esophageal squamous cell carcinoma

Abstract

Objective. Surgical resection is the treatment of choice for superficial esophageal squamous cell carcinoma (SESCC), but it is associated with high mortality and morbidity rates. Recently, endoscopic resection for SESCC has been indicated for patients with a low risk of lymph node metastasis (LNM). Therefore, to successfully treat SESCC with endoscopic resection, it is very important to identify patients with a low risk for LNM. The objective of this study was to investigate clinicopathologic factors that predict LNM in patients who underwent esophagectomy for SESCC. Methods. The study included 104 patients with SESCC from three university hospitals in Pusan, Korea. Clinicopathologic factors were evaluated to identify independent factors predicting LNM by univariate and multivariate analyses. Results. In univariate analysis, the depth of tumor invasion and lymphovascular invasion had significant influences on LNM (p = 0.001 and p < 0.001, respectively). Gross type, tumor size, and tumor differentiation were not predictive for LNM. In multivariate analysis, the depth of tumor invasion and lymphovascular invasion were signi?cantly associated with LNM in patients with SESCC (OR 9.04, p = 0.049; OR 11.61, p = 0.002, respectively). Conclusions. The depth of tumor invasion and lymphovascular invasion were independent predictors of LNM in patients with SESCC. Therefore, endoscopic resection could be performed in patients with SESCC that is limited to the mucosa, without lymphovascular invasion.     

Hypercalcaemia and elevated levels of parathyroid hormone-related protein in cutaneous squamous/basal cell carcinoma

Abstract. A patient with mixed squamous/basal cell carcinoma of the skin presented with hypercalcaemia and elevated serum levels of parathyroid hormone-related protein (PTH-rP). The tumour was resected, PTH-rP levels declined and the patient became normocalcaemic. This is the first case to associate squamous cell carcinoma of the skin with hypercalcaemia and significant levels of PTH-rP.     

Clinicopathological features and prognostic nomogram of giant cell carcinoma of the lung: A population-based study

Background

Due to its rarity, the features and prognosis of giant cell carcinoma of the lung (GCCL) are not well defined. The present study aimed to describe the clinicopathological features and prognostic analysis of this rare disease, compare it with lung adenocarcinoma (LAC), further determine the prognostic factors and establish a nomogram.

Methods

Patients diagnosed with GCCL and LAC were identified from the SEER database between 2004 and 2016. The features and survival between GCCL and LAC were compared in the unmatched and matched cohorts after propensity score matching (PSM) analysis. Univariate and multivariate Cox analyses were used to identify the prognostic factors, and a nomogram was constructed. Area under the curve (AUC), C-index, calibration curve and decision curve analysis (DCA) were used to confirm the established nomogram.

Results

A total of 295 patient diagnosed with GCCL and 149 082 patients with LAC were identified. Compared with LAC, patients with GCCL tend to be younger, male, black and have pathological Grade III/IV GCCL, more proportion of AJCC-TNM-IV, T3/T4 and distant metastases. The 1-, 2- and 5-year OS rates of the patients with GCCL were 21.7%, 13.4% and 7.9%, respectively. The median OS and CSS were 3 and 4 months, respectively. Patients with GCCL had significantly shorter OS and CSS than those with LAC in the unmatched and matched cohorts after PSM. Multivariate Cox analysis demonstrated that T, N and M stages and use of chemotherapy and surgery were independent of survival. Furthermore, we constructed a prognostic nomogram for OS and CSS by using independent prognostic factors. The C-index of OS-specific nomogram is 0.78 (0.74–0.81), and the C-index of CSS-specific nomogram is 0.77 (0.73–0.80). The calibration curve and ROC analysis showed good predictive capability of these nomograms. DCA showed that the nomogram had greater clinical practical value in predicting the OS and CSS of GCCL than TNM staging.

Conclusion

GCCL have distinct clinicopathological characteristics and significantly worse clinical outcomes. Prognostic nomograms for overall survival (OS) and CSS were constructed.     

Risk factors associated with the mortality rate of oral squamous cell carcinoma patients: A 10-year retrospective study

In Malaysia, oral cancer is very common and the reported 5-year survival of such patients is nearly 50% after treatment with surgery and radiotherapy, much lower than most of the developed countries. This study aimed to investigate the socio-demographic and clinicopathological parameters that influence the mortality rate of the patients suffering from oral squamous cell carcinoma (OSCC) in the Kelantanse population.In this retrospective study, data regarding socio-demographic, clinicopathological factors, and treatment outcome associated with OSCC were gathered from the archives of the medical records office of Hospital Universiti Sains Malaysia. For statistical analysis, simple and multiple logistic regression were performed. The significance level was set to P < .25.A total of 211 OSCC cases were registered in Hospital Universiti Sains Malaysia from January 1, 2000 to December 31, 2018. Majority of them were male (57.82%), non-smoker (54.97%), non-alcohol consumer (91.94%), and non-betel quid chewer (93.83%) Malay (60.66%) patients. The tongue was the most commonly involved part of the oral cavity (41.52%). Histologically, the majority of the cases had moderately-differentiated OSCC (52.82%). Most of the patients were diagnosed at stage IV at the time of diagnosis (61.61%). When this study was performed, the survival status of the majority of the patients was alive (68.24%).Within the analyzed socio-demographic and clinicopathological parameters, gender, alcohol consumption, T-classification, histological grading, and treatment status have been demonstrated as an independent risk factors for mortality rate in multivariate analysis. Hence, these parameters need to be taken into account for the individualized therapy management of OSCC patients.     

A visualized dynamic prediction model for overall survival in patients diagnosed with brain metastases from lung squamous cell carcinoma

Introduction

Patients presenting with brain metastases (BMs) from lung squamous cell carcinoma (LUSC) often encounter an extremely poor prognosis. A well-developed prognostic model would assist physicians in patient counseling and therapeutic decision-making.

Methods

Patients with LUSC who were diagnosed with BMs between 2000 and 2018 were reviewed in the Surveillance, Epidemiology, and End Results (SEER) database. Using the multivariate Cox regression approach, significant prognostic factors were identified and integrated. Bootstrap resampling was used to internally validate the model. An evaluation of the performance of the model was conducted by analyzing the area under the curve (AUC) and calibration curve.

Results

A total of 1812 eligible patients' clinical data was retrieved from the database. Patients' overall survival (OS) was significantly prognosticated by five clinical parameters. The nomogram achieved satisfactory discrimination capacity, with 3-, 6-, and 9-month AUC values of 0.803, 0.779, and 0.760 in the training cohort and 0.796, 0.769, and 0.743 in the validation cohort. As measured by survival rate probabilities, the calibration curve agreed well with actual observations. There was also a substantial difference in survival curves between the different prognostic groups stratified by prognostic scores. For ease of access, the model was deployed on a web-based server.

Conclusions

In this study, a nomogram and a web-based predictor were developed to assist physicians with personalized clinical decisions and treatment of patients who presented with BMs from LUSC.     

Squamous cutaneous epithelial cell carcinoma in two CML patients with progressive disease under imatinib treatment

Imatinib (glivec), formerly known as STI571) effectively blocks the ATP-binding site of the bcr/abl fusion protein thereby inactivating selectively the tyrosine kinase activity of bcr/abl. Therefore, it is a promising drug in Philadelphia chromosome positive chronic myeloid leukemia showing high hematologic and cytogenetic response rates combined with a mild toxicity profile. Here we report two cases of squamous cell carcinoma of the skin, which appeared in the photo-exposed areas in two elderly patients treated for advanced chronic myeloid leukemia with imatinib. The role of chemotherapy, chronic sun exposure and of possible additional risk factors such as human papillomavirus infection is discussed.     

Clinicopathological features and prognostic nomogram of giant cell carcinoma of the lung: A population‐based study

BackgroundDue to its rarity, the features and prognosis of giant cell carcinoma of the lung (GCCL) are not well defined. The present study aimed to describe the clinicopathological features and prognostic analysis of this rare disease, compare it with lung adenocarcinoma (LAC), further determine the prognostic factors and establish a nomogram.MethodsPatients diagnosed with GCCL and LAC were identified from the SEER database between 2004 and 2016. The features and survival between GCCL and LAC were compared in the unmatched and matched cohorts after propensity score matching (PSM) analysis. Univariate and multivariate Cox analyses were used to identify the prognostic factors, and a nomogram was constructed. Area under the curve (AUC), C‐index, calibration curve and decision curve analysis (DCA) were used to confirm the established nomogram.ResultsA total of 295 patient diagnosed with GCCL and 149 082 patients with LAC were identified. Compared with LAC, patients with GCCL tend to be younger, male, black and have pathological Grade III/IV GCCL, more proportion of AJCC‐TNM‐IV, T3/T4 and distant metastases. The 1‐, 2‐ and 5‐year OS rates of the patients with GCCL were 21.7%, 13.4% and 7.9%, respectively. The median OS and CSS were 3 and 4 months, respectively. Patients with GCCL had significantly shorter OS and CSS than those with LAC in the unmatched and matched cohorts after PSM. Multivariate Cox analysis demonstrated that T, N and M stages and use of chemotherapy and surgery were independent of survival. Furthermore, we constructed a prognostic nomogram for OS and CSS by using independent prognostic factors. The C‐index of OS‐specific nomogram is 0.78 (0.74–0.81), and the C‐index of CSS‐specific nomogram is 0.77 (0.73–0.80). The calibration curve and ROC analysis showed good predictive capability of these nomograms. DCA showed that the nomogram had greater clinical practical value in predicting the OS and CSS of GCCL than TNM staging.ConclusionGCCL have distinct clinicopathological characteristics and significantly worse clinical outcomes. Prognostic nomograms for overall survival (OS) and CSS were constructed.     

Esophageal papillomatosis complicated by squamous cell carcinoma in situ

We present a case of esophageal papillomatosis with underlying squamous cell carcinoma in situ. An esophageal lesion resected from a 74-year-old woman demonstrated histological findings characteristic of squamous cell papilloma (fibrovascular core and numerous finger-like projections covered with hyperplastic squamous epithelium) and severe dysplasia characteristic of squamous cell carcinoma. The relation of squamous papilloma and squamous cell carcinoma is discussed. It is suggested that esophageal squamous cell papilloma is a premalignant lesion.     

Primary radiotherapy with or without chemotherapy in non-metastatic esophageal squamous cell carcinoma: a retrospective study

The purpose of this study was to report the outcome of radio(chemo)therapy in the curative management of esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed 163 patients with T1‐T4, N0‐1, M0 ESCC who were treated between January 1988 and December 2006 at the Technische Universität München. One hundred sixty patients were inoperable due to a poor performance status, comorbidities or locally advanced unresectable disease. External beam radiation therapy (EBRT) was performed with (n= 146) or without (n= 17) systemic chemotherapy. Fifty‐four patients received an additional boost with intraluminal brachytherapy (IBT). Surviving patients were followed for a median of 72 months (range 10–173 months). The estimated overall survival (OS) at 2 and 5 years was 27 ± 4% and 11 ± 3%, respectively. Loco‐regional recurrence at the primary site was observed in 29% of patients (n= 47). The recurrence‐free survival (RFS) at 2 and 5 years was 24 ± 3% and 9 ± 2%, respectively. In multivariate analyses, the ECOG performance status (P= 0.004), 3D conformal (vs conventional) radiotherapy (P= 0.031) and continuous standard fractionation (vs split‐course radiotherapy, P= 0.048) were associated with a better OS. Simultaneous chemotherapy (P= 0.49) or IBT (P= 0.31) had no significant impact on survival. Outcome for patients with ESCC is poor. Despite the very unfavorable patient selection (poor performance status, high rate of comorbidities, and advanced disease), long‐term survival with radio(chemo)therapy was achieved in about 10% of patients. The introduction of modern treatment techniques/modalities (3D conformal planning/ continuous standard fractionation) might be associated with better outcomes.     

Cardiac metastasis from squamous cell carcinoma of gallbladder

A 65-year-old woman was admitted to our hospital with the diagnosis of gallbladder tumor. Right extended hepatic lobectomy plus lymph node dissection of the hepatoduodenal ligament and left hepaticojejunostomy with Roux-en-Y reconstruction was performed in July, 1993. The gallbladder tumor was histologically proven to be squamous cell carcinoma. Seventeen months later, the patient experienced dyspnea and pitting edema of the lower legs and was admitted, in December 1994, with a diagnosis of heart failure. Despite intensive cardiac support, she died 12 days after the second admission. Autopsy revealed multiple cardiac tumors in the left and right ventricles, left atrium, left coronary artery, and left diaphragm. Histologically, these tumors were shown to be squamous cell carcinoma, considered to have metastasized from the primary gallbladder carcinoma. As neither local recurrence of the gallbladder carcinoma. As neither local recurrence of the gallbladder carcinoma nor any lymph node metastasis was found, the cardiac metastasis of the gallbladder carcinoma may have occurred via the hematogenous route. Although rare, this route of cardiac metastasis of gallbladder carcinoma may be an important aspect of distant metastasis, which should be monitored for during follow-up after resection of the primary tumor.     

Survival and clinicopathological characteristics of cT4b oral squamous cell carcinoma based on different treatment modalities: A single-center retrospective study

Introduction:Primary surgical treatment for oral squamous cell carcinoma (OSCC) is reserved for T1 to T4a tumors, but not for T4b tumors, according to the present National Comprehensive Cancer Network clinical practice guidelines. In this retrospective study, we aimed to determine the association between the clinicopathological characteristics and different treatment modalities for T4b OSCC based on whether patients received primary surgical treatment. Therefore, we conducted a survival analysis based on different treatment modalities.Methods:This retrospective cohort study enrolled 125 patients with clinical stage T4b OSCC who received treatment and were followed up at Changhua Christian Hospital between January 1, 2008 and December 31, 2018.Results:Overall, 81 patients received primary surgical treatment and 44 received primary nonsurgical treatment. Comparison of the clinicopathological characteristics between those who did and did not undergo surgery revealed no significant differences in age at tumor diagnosis, tumor location, clinical N stage, and involved tumor area based on computed tomography or magnetic resonance imaging, or stratified Charlson Comorbidity Index scores. In the survival analysis, Kaplan–Meier curves revealed that patients who received treatment modalities including surgery exhibited better survival than those who received treatment modalities that did not include surgery.Conclusions:In the present study, patients with T4b OSCC treated with primary surgery had a better overall survival rate than those who received nonsurgical treatment. In the future, it will be necessary for clinicians worldwide to report the treatment outcomes of patients with T4b OSCC based on the common criteria.     

Nutrient patterns and risk of esophageal squamous cell carcinoma: a case-control study

Although Iran is a high-risk country for esophageal squamous cell carcinoma (ESCC), the contribution of overall nutrient intakes to this high incidence rate is not yet clear. The aim of this study was to examine the association between nutrient patterns and risk of ESCC in Iran. Forty-seven patients with ESCC and 96 frequency-matched hospital controls underwent private interviews, and dietary habits were collected using a validated food-frequency questionnaire. Factor analysis was conducted and two major nutrient patterns were retained; factor 1 (high in pantothenic acid, vitamin C, potassium, vitamin B(6), magnesium, folate, thiamin, copper, carbohydrate, vitamin K, niacin, α-tocopherol, zinc, total fiber, fluoride, and polyunsaturated fatty acids) and factor 2 (high in saturated fatty acid, biotin, selenium, monounsaturated fatty acids, riboflavin, sodium, fat, cholesterol, calcium, phosphorus, protein, iron, vitamin E, manganese, vitamin D, and vitamin B(12)). Factor 2 was inversely associated with ESCC (OR = 0.06, 95% CI: 0.01-0.28; P = 0.008), whereas no significant association was found for factor 1 (OR = 0.45, 95% CI: 0.11-1.82). The results of the present study suggested a possible role for a nutrient pattern similar to factor 2 in reducing the risk of ESCC.     

Predictive value of preoperative serum squamous cell carcinoma antigen level for lymph node metastasis in early-stage cervical squamous cell carcinoma

To explore the predictive value of preoperative serum squamous cell carcinoma antigen (SCC-Ag) level for lymph node metastasis (LNM), particularly, in patients surgically treated for early-stage cervical squamous cell carcinoma.We enrolled 162 patients with cervical squamous cell carcinoma stages IB to IIA following the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification. The patients had previously undergone radical surgery. Correlation of the SCC-Ag level with clinicopathological features and the predictive value of SCC-Ag for LNM were analyzed.High preoperative SCC-Ag level was correlated with FIGO stage (P = .001), tumor diameter >4 cm (P < .001), stromal infiltration (P < .001), LNM (P < .001) and lymphovascular space invasion (LVSI), (P = .045). However, it was not correlated with age, histological differentiation, parametrial involvement, and positive vaginal margin (P > .05). Univariate analysis revealed that FIGO stage (P = .015), tumor diameter (P = .044), stromal infiltration (χ² = 10.436, P = .005), SCC-Ag ≧ 2.75 ng/mL (χ² = 14.339, P < .001), LVSI (χ² = 12.866, P < .001), parametrial involvement (χ² = 13.784, P < .001) were correlated with LNM, but not with age, histological differentiation, and positive vaginal margin. Moreover, multivariate analysis demonstrated that SCC-Ag ≧2.75 ng/mL (P = .011, OR = 3.287) and LVSI (P = .009, OR = 7.559) were independent factors affecting LNM. The area under the receiver operator characteristic curve of SCC-Ag was 0.703 (P < .001), while 2.75 ng/mL was the best cutoff value for predicting LNM. The sensitivity and specificity of diagnosis were 69.4% and 65.9%, respectively.High SCC-Ag level was revealed to be an independent risk factor for the prognosis of squamous carcinoma of the cervix before an operation. Besides, SCC-Ag (2.75 ng/mL) can be utilized as a potential marker to predict LNM in early stage cervical cancer before an operation.