Multiple Primary Carcinomas Research Articles

794. RETROSPECTIVE ANALYSIS OF CLINICAL CHARACTERISTICS AND PROGNOSIS OF SYNCHRONOUS MULTIPLE PRIMARY ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Multiple primary esophageal squamous cell carcinoma (MPESCC) is a rare and complex type of esophageal cancer, categorized into synchronous multiple primary esophageal squamous cell carcinoma (S-MPESCC) and metachronous multiple primary esophageal squamous cell carcinoma (M-MPESCC). Compared to solitary esophageal squamous cell carcinoma (SESCC), multiple primary esophageal squamous cell carcinoma (MPESCC) generally has a poorer prognosis, with significant differences in treatment strategies and survival outcomes. This study aims to explore the clinical characteristics and prognosis of S-MPESCC through a retrospective analysis of a large patient cohort. Methods This study retrospectively analyzed clinical data from 758 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgical resection at two medical centers in China from January 2012 to December 2021. The S-MPESCC group included 68 patients, and the SESCC group included 690 patients. All patients underwent radical esophagectomy with systematic lymph node dissection. Preoperative and postoperative data were collected, including gender, age, family history, tumor staging, and lymph node metastasis. Results There were no significant differences in baseline characteristics, such as gender, age, and family history, between the S-MPESCC and SESCC groups. The lymph node metastasis rate was significantly higher in the S-MPESCC group compared to the SESCC group, especially in the upper mediastinal and abdominal regions (P<0.05). Survival status was monitored through outpatient visits and telephone calls until December 2022. The results showed that the 3-year and 5-year survival rates of the S-MPESCC group were significantly lower than those of the SESCC group (P< 0.05). Patients with a greater depth of primary tumor infiltration had poorer survival outcomes in the S-MPESCC group. Conclusion This study clarified the clinical characteristics and prognosis of S-MPESCC through a retrospective analysis of 758 ESCC patients. S-MPESCC patients had a significantly higher rate of lymph node metastasis and a poorer prognosis compared to SESCC patients. Future efforts should focus on optimizing treatment strategies to improve the prognosis and survival rates of patients with S-MPESCC.

795. REVIEW OF CLINICAL CHARACTERISTICS AND PROGNOSIS OF MULTIPLE PRIMARY ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Multiple Primary Esophageal Squamous Cell Carcinoma (MPESCC) is a rare and highly aggressive type of tumor, classified into Synchronous Multiple Primary Esophageal Squamous Cell Carcinoma (S-MPESCC) and Metachronous Multiple Primary Esophageal Squamous Cell Carcinoma (M-MPESCC). MPESCC has garnered increasing attention in recent years due to its complex pathogenesis, poor prognosis, and unclear treatment protocols. Compared to solitary esophageal squamous cell carcinoma (SESCC), patients with MPESCC typically show higher rates of lymph node and distant metastasis, leading to a poorer prognosis. This review aims to summarize the clinical characteristics, common treatment methods, and prognosis of MPESCC by analyzing existing literature, providing references for clinical practice. Methods The clinical characteristics of MPESCC patients differ significantly from those of SESCC patients, relevant literature was collected for meta-analysis of the following data of the patients: Gender and Age, Medical History, Pathological Features, Lymph Node and Distant Metastasis, Tumor Distribution. Treatment Methods include Surgical Treatment, Radiotherapy and Chemotherapy. Postoperative recurrence and metastasis are also included in the statistics. Results Tumors in MPESCC patients exhibit significant differences in pathological staging and grading, which makes treatment more challenging. Patients with MPESCC have significantly higher rates of lymph node and distant metastasis compared to those with SESCC. MPESCC tumors can appear in multiple locations within the esophagus, with pathological characteristics that may vary between sites. Surgery remains the primary treatment method for MPESCC. Due to the high risk of recurrence and metastasis in MPESCC patients, regular endoscopic and imaging examinations are necessary postoperatively to detect and address any recurrent or new tumors early. Conclusion MPESCC is a complex type of esophageal cancer with a poor prognosis. It’s clinical characteristics and treatment strategies differ significantly from those of SESCC. Multidisciplinary comprehensive treatment and close postoperative follow-up are crucial for improving the prognosis of patients with MPESCC. Further research is needed to optimize treatment protocols and enhance patient survival rates.

COEXISTENCE OF SYNCHRONOUS TRIPLE CARCINOMAS RESECTED IN A76YEAR OLD PATIENT- A RARE CASE REPORT

The coexistence of synchronous triple carcinomas in a single patient is a rare occurrence. Only a few cases and patient reviews of triple malignancy have been reported in literature. We report here a case of 76year old male that details the existence of squamous cell carcinoma of lip, basal cell carcinoma of left ala of nose and basaloid variant of squamous cell carcinoma of chest wall. Existence of multiple primary carcinomas can be considered as a rare occurrence but due to improved effectiveness in therapies and diagnostic tools, the situation has become more frequent in recent times.

Multiple primary carcinoma in post renal transplant immunocompromised patient-a case report

Introduction: Cancer is an important outcome after kidney transplantation because of immunosuppression and it is the second leading cause of death. The excess risk of cancer after transplantation is approximately two to three times higher than the age- and sex-matched general population, driven largely by viral- and immune-related cancers. Case presentation: 68 yr old male with single transplanted kidney and no tobacco habit presented with multiple primary malignancy over 8 yr period from carcinoma soft palate, carcinoma rectum and Hepatocellular carcinoma. Diagnosis: Patient underwent Radiation alone for softplate carcinoma, Surgery followed by chemo radiation for carcinoma rectum and Hepatocellular carcinoma. Patient on follow up PET CT and MRI have no active disease Conclusion: Carcinoma incidence is inevitable for renal transplant patient. With multimodality approach of surgery, Radiation and chemotherapy patient having a better quality of life

Synchronous and metachronous primary colorectal cancers with concordant and discordant mismatch repair status

Multiple primary colorectal carcinomas (CRCs) synchronous, when detected approximately at the same time, or metachronous, when a significant amount of time has elapsed between diagnoses can show both mismatch repair (MMR) status concordance and discordance between primary tumors. The aim was to evaluate the MMR status of a monoinstitutional, retrospective cohort of synchronous and metachronous CRCs, with a focus on the frequency of cases with discordant MMR status, and explore the MMR status of metastatic nodal deposits. All synchronous and metachronous CRCs diagnosed in our institution between 2011 and 2023 were collected. Clinicopathologic characteristics were evaluated, including MMR status of all CRCs, BRAF mutation, and MLH1 promoter methylation analyses. MMR status discordant cases were further analyzed, and MMR testing was performed on nodal metastases. Of 3671 patients, 107 (2.9%) had multiple CRCs (94 synchronous and 13 metachronous; total number of CRCs 220). Sixty CRCs were MMR deficient (dMMR) (27.3%), and most were right-sided and high-grade and showed special histologic features (P<.00001). Ninety-three patients showed intertumoral MMR concordance: 70 (65.4%) with MMR-proficient (pMMR) CRCs, and 23 (21.5%) were dMMR. Fourteen patients (13.1%) showed intertumoral MMR discordance (at least one dMMR and one pMMR), and in 5 patients, nodal metastases were present: 2 patients harbored metastases only from their pMMR cancer, 2 only from their dMMR cancer, and in 1 patient both pMMR and dMMR metastases were present. In conclusion, all multiple primary CRCs should be analyzed for MMR status as discordant MMR is possible as well as discordant metastatic nodal deposits, and this may be important for patient management.

Multifocal biliary carcinoma; whether synchronous or metastatic: A need to conquer

Multiple synchronous primary carcinoma involving gall bladder, liver and common bile duct are rare and difficult to differentiate with hepatic and extrahepatic bile duct metastasis from single primary. Radiological features, molecular landscape, and even integrated mutational profiling are not of much help. We describe a case of 48-year-old male who presented with jaundice and follow up CT scan raised the suspicion of gall bladder carcinoma with hepatic metastasis. Peroperative frozen section examination revealed adenocarcinoma with involvement of cystic duct margin; however revised common duct margin was free from tumor invasion. Final histopathology on resected gall bladder revealed multifocal adenocarcinoma, while histomorphology of hepatic nodule was consistent with cholangiocarcinoma. Common bile duct a one focus had also revealed adenocarcinoma while cut margins were negative form malignancy. In view of different morphology of gall bladder and hepatic tumor, no continuity of three tumors and single large, firm, non umblicated hepatic nodule, diagnosis of multiple synchronous carcinoma was suggested.

Efficacy of surgical comprehensive therapy for 456 cases of hypopharyngeal carcinoma

Objective: To retrospectively analyse the efficacy of surgerical comprehensive treatment for hypopharyngeal cancer. Methods: Four hundred and fifty-six cases of hypopharyngeal squamous cell carcinoma treated from Jan 2014 to Dec 2019 were analyzed retrospectively, including 432 males and 24 females, aged 37-82 years old. There were 328 cases of pyriform sinus carcinoma, 88 cases of posterior pharyngeal wall carcinoma, and 40 cases of postcricoid carcinoma. According to American Joint Committe on Cancer(AJCC) 2018 criteria, 420 cases were of stage Ⅲ or Ⅳ; 325 cases were of T3 or T4 stage. Treatment methods included surgery alone in 84 cases, preoperative planned radiotherapy plus surgery in 49 cases, surgery plus adjuvant radiotherapy or concurrent chemoradiotherapy in 314 cases, and inductive chemotherapy plus surgery and adjuvant radiotherapy in 9 cases. The primary tumor resection methods included transoral laser surgery in 5 cases, partial laryngopharyngectomy in 74 cases, of them 48 cases (64.9%) presented with supracricoid hemilaryngopharyngectomy, total laryngectomy with patial pharyngectomy in 90 cases, total laryngopharyngectomy or with cervical esophagectomy in 226 cases, and total laryngopharyngectomy with total esophagectomy in 61 cases. Among 456 cases, 226 cases received reconstruction surgery with free jejunum transplantation, 61 cases with gastric pull-up, and 32 cases with pectoralis myocutaneous flaps. All patients underwent retropharyngeal lymph node dissection, and high-definition gastroscopy was performed during admission and follow-up. SPSS 24.0 software was used to analyze the data. Results: The 3-year and 5-year overall survival rates were respectively 59.8%, and 49.5%. The 3-year and 5-year disease specific survival rates were respectively 69.0% and 58.8%. Total metastasis rate of retropharyngeal lymph nodes was 12.7%. A total of 132 patients (28.9%) suffered from simultaneous and metachronous multiple primary carcinoma of the hypopharynx. Multivariate Logistic regression analysis showed that T3-4 disease, cervical lymph node metastasis, retropharyngeal lymph node metastasis and postoperative adjuvant radiotherapy were independent factors affecting the prognosis of patients (all P<0.05). As of April 30, 2022, a total of 221 patients died during follow-up, of 109 (49.3%) with distant metastases, which were the main cause of death. Conclusions: The efficacy of comprehensive treatment for hypopharyngeal cancer can be improved by accurate preoperative evaluation, improved surgical resection, active retropharyngeal lymph node dissection and full process intervention of the second primary cancer.

Detection of Merkel cell polyomavirus in multiple primary oral squamous cell carcinomas

Oral microbiome studies have mainly focussed on bacteria, with the relationship between viruses and oral cancers remaining poorly understood. Oral cancers can develop even in the absence of any history of daily smoking or drinking. Oral cancer patients frequently have multiple primary cancers in the oral cavity and other organs, such as the upper gastrointestinal tract. Merkel cell polyomavirus (MCPyV) is a novel oncovirus identified from a subtype of skin cancer in 2008. In this study, we investigated the potential involvement of MCPyV in the pathogenesis of oral squamous cell carcinoma (OSCC). Participants comprised 115 Japanese patients with OSCC (single primary: 109 tumours in 109 patients; multiple primaries: 16 tumours in 6 patients) treated in our department between 2014 and 2017. DNA was extracted from formalin-fixed paraffin-embedded specimens of primary lesions. MCPyV DNA copy counts were analysed by quantitative real-time polymerase chain reaction. Twenty-four of the 115 patients (20.9%) were positive for MCPyV DNA. No association was found between presence or absence of MCPyV DNA and clinical characteristics other than number of primary lesions. The MCPyV DNA-positive rate was significantly higher for multiple primary OSCCs (62.5%, 10/16 tumours) than for single primary OSCCs (16.5%, 18/109 tumours; P < 0.001). Furthermore, MCPyV DNA load was significantly higher for patients with multiple primaries (P < 0.05). MCPyV was observed more frequently and DNA load was significantly higher with multiple primary OSCCs than with single primary OSCC. MCPyV may play some role as an oncovirus for multiple primary OSCCs.

Survival and prognostic factors in patients with synchronous multiple primary esophageal squamous cell carcinoma receiving definitive radiotherapy: A propensity score-matched analysis.

To compare the lesion characteristics and radiotherapy efficacy of patients with single and multiple esophageal squamous cell carcinoma (ESCC), to evaluate the effect of multiple lesions on ESCC, and establish a nomogram survival prediction model for patients with synchronous multiple primary esophageal squamous cell carcinoma (SMPESCC) who received definitive radiotherapy. The study enrolled 1,034 patients with ESCC who underwent definitive radiotherapy between 2010 and 2020. The efficacy of radiotherapy was compared between 101 patients with SMPESCC and 933 patients with single ESCC. Propensity score matching was used to control for potential confounders. For patients with SMPESCC, a nomogram prediction model was established based on the Cox regression model. The median OS was 30.00 (95% CI = 25.08-34.92) months for the single lesion group and 19.00 (95% CI = 15.51-22.48) months for the multiple cancer group respectively. Multivariate COX regression analysis showed that multiple cancer was an independent prognostic factor for ESCC patients (HR=1.89, 95%CI=1.49-2.38, P<0.001). Cox multivariate analysis of SMPESCC patients showed that T stage (P =0.002), chemotherapy (P =0.006), and lesion spacing (P =0.004) were independent prognostic factors associated with OS. The nomogram was established by combining T stage, chemotherapy, and lesion spacing, and Harrell's C index was 0.711 after internal cross-validation. The calibration curve and decision curve analysis confirmed that the nomogram survival prediction model had a good predictive value for individual survival. The survival rate of single esophageal cancer is significantly better than that of multiple lesions. Patients with SMPESCC exhibit worse survival than patients with single ESCC. Multiple lesions have a significant impact on the survival of patients with ESCC. The nomogram model established for SMPESCC patients can well predict the individual survival of patients.

Comparison of the Clinicopathological Characteristics and Prognosis of Esophageal Squamous Cell Carcinoma with Intramural Metastases and Multiple Primary Carcinomas.

It is difficult to distinguish esophageal squamous cell carcinoma with intramural metastases (IM) from multiple primary oesophageal carcinoma (MPEC). Nevertheless, there are significant differences in their prognoses and treatments. Therefore, our study aims to clarify the clinicopathological and prognostic characteristics of these two entities and to provide clues for differential diagnosis. We retrospectively analyzed 6304 patients who underwent esophagectomy without neoadjuvant therapy. The clinicopathological and prognostic features of patients with IM and MPEC were evaluated. P53 and Rb1 were detected by immunohistochemical (IHC) staining using a tissue microarray. Among the 6304 patients, 127 (2.0%) had IM, and 138 (2.2%) had MPEC. Patients with IM were more likely to have an advanced pT (p < 0.001), pN (p < 0.001), more lymphovascular invasion (p < 0.001) and neural invasion (p < 0.001). Additionally, patients with IM had an extremely poor prognosis compared to those with MPEC, with 5-year overall survival (OS) rates of 18.9% and 56.9%, respectively. Meanwhile, IM was found to be an independent poor prognostic indicator for OS and DFS. In the IM group, all patients showed consistent p53 expression in both primary and IM foci. Of note, Rb1 loss was found in 3 pairs of primary foci and metastases, along with p53 nonsense mutation. Patients with IM had more risk factors and extremely worse prognosis than those with MPEC. It is essential to discriminate IM from MPEC when managing multifocal carcinomas. IHC staining of p53 and Rb1 may aid in differential diagnosis.

Comparison of clinicopathological features and prognostic significance between synchronous multiple primary and solitary esophageal squamous cell carcinomas

BackgroundSynchronous multiple primary esophageal squamous cell carcinoma (S-MPESCC) refers to more than one primary esophageal carcinoma detected in a solitary patient at the time of initial presentation. The purpose of this study was to evaluate the clinicopathological features, appropriate surgical approaches and long-term survival in patients with S-MPESCC by comparing with those with solitary esophageal squamous cell carcinoma (SESCC).MethodsIn total, 567 patients with esophageal squamous cell carcinoma surgically resected in Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2018 were screened for retrospective analysis (50 in the S-MPESCC group and 516 in the SESCC group).ResultsNo significant difference was observed in terms of other characteristics except total alcohol consumption (P = 0.029). S-MPESCC had higher lymph node rate than SESCC (62.0% and 44.1%, respectively; P = 0.015) especially in upper mediastinal (32.0% and 18.6%, respectively; P = 0.023) and abdominal (38.0% and 22.8%, respectively; P = 0.017) regions. The survival was not different between the two groups, and the 5-year survival rates of S-MPESCC and SESCC were 46.2% and 50.8%, respectively (P = 0.507). But for patients with pT3-4 cancers, the survival in S-MPESCC was worse than that in SESCC (P = 0.033). In the multivariate analysis, pT stage of primary cancer was an important independent predictor of prognosis in patients with S-MPESCC (hazard ratio [HR], 3.968; 95% confidence interval [CI], 1.031 to 15.268; P = 0.045).ConclusionsS-MPESCC was significantly different from SESCC in terms of clinicopathological characteristics include alcohol intake and pattern of lymphatic metastasis. Furthermore, S-MPESCC showed worse long-term survival than SESCC with increasing depth of primary cancer infiltration.

Multiple primary squamous cell carcinomas of the oral cavity: A cross-sectional study in vietnam

BackgroundMultiple primary squamous cell carcinomas (MPSCs) of the oral cavity are very uncommon in clinical practice. This study describes the clinical features, imaging, and treatment characteristics of the oral cavity with MPSCs at the same time of diagnosis in our center. Besides, we review the literature and prior studies on MPSCs. Study designA retrospective, descriptive study from January 2019 to December 2021 was conducted on seven patients with MPSCs of the oral cavity at the time of their first diagnosis. Evaluation of the patient's characteristics, the treatment plan, the response to treatment, and the overall survival (OS). ResultsSeven male patients ranging in age from 43 to 70 years (Mean: 53.5). Positron Emission Tomography/Computed Tomography (PET/CT) revealed a significantly increased standardized uptake value (SUV) in the index tumor (SUVi = 15.76 ± 1.96). The index tumor is often staged T3, T4; whereas the synchronous tumor is typically staged T1, T2. All patients had concurrent chemoradiotherapy (CCRT) and achieved a partial response in all cases. Mean OS was 14.71 ± 11.85 months. ConclusionsMPSCs of the oral cavity at the time of diagnosis are uncommon and associated with a poor prognosis for patients. Comprehensive clinical examination, combined imaging diagnostics, with PET/CT being critical for detecting the second lesion, particularly in patients with an advanced index tumor.

A LASSO-based survival prediction model for patients with synchronous colorectal carcinomas based on SEER.

BackgroundThe nomogram for postoperative prediction of overall survival (OS) in patients’ synchronous colorectal carcinomas (SCC) was developed and validated by least absolute shrinkage and selection operator (LASSO)-based Cox regression.MethodsThe data was obtained from the SEER database of patients diagnosed with colorectal cancer (CRC) more than one time between 2004 and 2013. Patients who had CRC more than 3 times or multiple metachronous primary carcinomas were excluded. The cut-off points for the continuous variable were identified by the K-adaptive partitioning algorithm and x-tile software. Using LASSO-based Cox regression, a model for predicting the OS of SCC was built, internally and externally validated, and measured through a calibration curve, C-index, Akaike information criterion (AIC), Bayesian information criterion (BIC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), time-dependent receiver operating characteristic (timeROC), time-dependent area under curve (timeAUC), and decision curve analysis (DCA), and results compared to the model developed by the Cox regression.ResultsPatients with SCC were found to be older, more often men, and likely to have a depth of invasion by T3. In addition, there were no significant differences between the model developed by LASSO-based Cox regression and the Cox regression in the C-index (0.712 and 0.710), AIC (33,420 and 33,431), BIC (4.49), IDI (0.002), NRI (–0.009), timeROC, and DCA. Besides, the model developed by LASSO-based Cox regression was found to perform better than the Cox regression in the timeAUC. Moreover, the model developed by LASSO-based Cox regression showed good C-index (0.712, 0.637, and 0.651), AIC (33,420, 34,043, and 33,994), BIC (1,178.76 and 1,098.57), IDI (–0.072 and –0.064), NRI (0.525 and 0.466), timeROC, timeAUC and had a larger net benefit compared to both the first time TNM staging and the combination of two times TNM staging.ConclusionsThis present study indicates that a close follow-up of older patients, male, and T3 should be made. Compared with the traditional Cox regression model, LASSO-based Cox regression decreases the variables of the model, avoids overfitting and collinearity and has clinical significance.

Cross Analysis of Genomic-Pathologic Features on Multiple Primary Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignancy cancer worldwide with a poor prognosis. Hepatic resection is indicated as a potentially curative option for HCC patients in the early stage. However, due to multiple nodules, it leads to clinical challenges for surgical management. Approximately 41%–75% of HCC cases are multifocal at initial diagnosis, which may arise from multicentric occurrence (MO-HCC) or intrahepatic metastasis (IM-HCC) pattern with significantly different clinical outcomes. Effectively differentiating the two mechanisms is crucial to prioritize the allocation of surgery for multifocal HCC. In this study, we collected a multifocal hepatocellular carcinoma cohort of 17 patients with a total of 34 samples. We performed whole-exome sequencing and staining of pathological HE sections for each lesion. Reconstruction of the clonal evolutionary pattern using genome mutations showed that the intrahepatic metastogenesis pattern had a poorer survival performance than independent origins, with variants in the TP53, ARID1A, and higher CNV variants occurring more significantly in the metastatic pattern. Cross-modality analysis with pathology showed that molecular classification results were consistent with pathology results in 70.6% of patients, and we found that pathology results could further complement the classification for undefined patterns of occurrence. Based on these results, we propose a model to differentiate the pattern of multifocal hepatocellular carcinoma based on the pathological results and genome mutations information, which can provide guidelines for diagnosing and treating multifocal hepatocellular carcinoma.

Comparative Genomic Analysis Reveals Genetic Variations in Multiple Primary Esophageal Squamous Cell Carcinoma of Chinese Population.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and lethal malignant tumors. The incidence of malignant transformation of esophageal mucosa increases greatly due to long-term exposure to factors such as smoking, drinking, and poor eating habits. Furthermore, multiple primary tumors could occur synchronously or asynchronously in the upper aerodigestive tract, especially in the esophagus, adding difficulty to the treatment of ESCC. Genetic mutations are important during the malignant transformation from normal mucosa to esophageal cancer, but the underlying mechanism has not been fully elucidated. In this study, we used whole-exome sequencing (WES) to profile genetic variations in physiologically normal mucosa (PNM) and ESCC tumors, as well as PNM of non-ESCC subjects. We found significant differences in mutation frequencies of NOTCH1 and NOTCH2, copy number variations (CNVs) at both gene and chromosomal arm levels, and cancer-related HIPPO, WNT, and NRF2 signaling pathways between ESCC tumors and normal mucosa. Our analysis of both primary tumors and paired PNM in bifocal ESCC revealed three different primary tumor evolution modes, and the most common mode exhibited a complete genomic divergence in all the samples from the same patient. Furthermore, the mutation frequency of TP53 was significantly higher in ESCC cases than that in non-ESCC cases. Overall, our results provide important evidence for further elucidating the mechanisms of genetic mutations underlying the cause of ESCC.

Local random flaps for cervical circumferential defect or tracheoesophageal fistula reconstruction after failed gastric pull-up: Two case reports

BACKGROUNDTotal pharyngo-laryngo-esophagectomy with a reconstruction of gastric pull-up is the most common treatment method for patients with multiple primary upper digestive tract carcinomas, such as hypopharyngeal carcinoma with thoracic esophageal carcinoma. However, neck circumferential defect and tracheoesophageal fistula after gastric necrosis are still challenging problems for surgeons and patients.CASE SUMMARYThis case report presents 2 patients who underwent reconstructive surgeries using 4 local random flaps with a split thickness skin graft in the first case, and 6 local random flaps in the second case to close the circumferential defect and tracheoesophageal fistula after failed gastric pull-up. Both patients achieved good swallowing function and could take solid diet without dysphagia postoperatively.CONCLUSIONFor selected patients, local random flaps (with a split thickness skin graft) can be a simple and reliable solution for reconstructing tracheoesophageal fistula or cervical circumferential defect after gastric necrosis, especially when the necrosis extends below the thoracic inlet.

Identification of the Unique Clinical and Genetic Features of Chinese Lung Cancer Patients With EGFR Germline Mutations in a Large-Scale Retrospective Study.

BackgroundEpidemiological surveys have suggested that lung cancer has inherited susceptibility and shows familial aggregation. However, the distribution and prevalence of epidermal growth factor receptor (EGFR) germline variants and their roles in lung cancer genetic predisposition in Chinese population remain to be elucidated.MethodsIn this study, EGFR germline and somatic variants were retrospectively reviewed from the next-generation sequencing results of 31,906 patients with lung cancer. Clinical information was also collected for patients with confirmed EGFR germline mutations.ResultsA total of 22 germline EGFR variants were identified in 64 patients with lung cancer, accounting for 0.2% of the total cases studied. Five patients were diagnosed as multiple primary carcinomas. Family history was documented in 31.3% (20/64) of patients, 55% of which were diagnosed as lung cancer. G863D was the most frequent EGFR germline mutation, followed by P848L, D1014N, and K757R. Somatic EGFR-sensitive mutations were identified in 51.6% of patients with germline EGFR mutations. The proportion of L858R mutation, exon 19 deletion, and rare sensitive mutation was 50%, 17.6%, and 32.4%, respectively. D1014N and T790M mutations were common in young patients. The family members of patients with P848L, R776H, V769M, and V774M mutations were more commonly diagnosed with cancers. A total of 19 patients were confirmed to have received EGFR tyrosine kinase inhibitors (TKIs), but the response to EGFR-TKIs differed among patients with different EGFR mutations.ConclusionChinese patients with lung cancer harbored unique and dispersive EGFR germline mutations and showed unique clinical and genetic characteristics, with varied response patterns to EGFR-TKI treatment.

An unusual case of multiple head and neck carcinoma with cutaneous metastasis

&lt;p class="abstract"&gt;The clinical presentation of multiple head and neck primary carcinomas is rare and may lead to the wrong diagnosis and treatment. The present case was of a 62 year old male who developed infiltrating squamous cell carcinoma of larynx and got treated with radiotherapy and chemotherapy. Subsequently after 3 years, he developed carcinoma tip of the nose. During work up for the same, there was accidental discovery of tonsillar adenosquamous carcinoma. The patient was treated for laryngeal carcinoma with radiotherapy and chemotherapy. Nasal tip carcinoma was treated with wide local excision with local flap reconstruction. Based upon histopathological examination and positron emission tomography (PET) scan for tonsillar adenosquamous carcinoma, the patient was referred for intensity modulated radiation therapy (IMRT). Patients with head and neck carcinoma should be inspected thoroughly with any history or development of new lesions since prognosis in such patients is very poor. However treatment and management is always palliative and should be individualized to the patient.&lt;/p&gt;

Incidence, mortality, and patterns of care for patients with multiple primary lower genital tract squamous cell carcinoma

<h3>Objectives:</h3> To define the incidence, prognosis, and treatment patterns associated with multiple primary lower genital tract squamous cell carcinoma (LGTSCC). <h3>Methods:</h3> Surveillance, Epidemiology, and End Results (SEER) database patients diagnosed with synchronous cervical, vaginal, vulvar, and/or anal SCC from 2000-2016 were included. Incidence and mortality were evaluated using Kaplan-Meier curves. Multivariable Cox proportional hazards regression was used to identify treatment patterns, risk factors, and mortality associated with LGTSCC. <h3>Results:</h3> Among 15,424 women with any LGTSCC, 138 patients had multiple primary LGTSCC (0.89%). Vulvar and vaginal SCC was the most common combination (49.3%), and cervical with anal SCC was the least common (1.4%). Only one patient had 3 or more primary LGTSCC (vulvar, cervical, and anal). Multiple primary LGTSCC was independently associated with higher mortality compared to single site LGTSCC (adjusted hazards ratio [aHR]=1.67; p<0.001). Multiple primary LGTSCC was significantly associated with older age (63 vs. 58 years, p<0.001) and have lower stage (adjusted odds ratio [aOR]=0.38; p<0.001) and grade of disease (aOR=0.32; p<0.001). Patients with multiple primary LGTSCC were more likely to receive radiation overall (aOR=1.74, p=0.005) and were more likely to receive adjuvant radiation after primary surgical resection compared to single site LGTSCC (aOR=1.88, p=0.007). Receipt of any treatment including radiation (aHR=0.85; p<0.001), chemotherapy (aHR=0.50; p<0.001), and surgery (aHR=0.70; p<0.001) was independently associated with decreased mortality hazard. <h3>Conclusions:</h3> Multiple primary LGTSCC is rare but is associated with increased mortality, and higher rates of adjuvant radiation compared to single site LGTSCC despite lower stage and grade at diagnosis. More research is needed to define optimal therapy for patients with multiple primary LGTSCC.

Prognostic Characteristics of Operated Breast Cancer Patients with Second Primary Lung Cancer: A Retrospective Study.

Background and PurposeThe number of breast cancer patients with second primary lung cancer is increasing year by year. The aim of this study was to explore the prognostic characteristics of these multiple primary breast and lung cancer patients.MethodsOperated breast cancer patients with subsequent lung cancer who were admitted to our hospital from January, 2010 to August, 2020 were retrospectively analyzed. The univariate and multivariate Cox regression analyses were conducted to explore the prognostic risk factors of such patients. Meanwhile, the propensity score match (PSM) method was applied to compare the prognosis between lung cancer patients with and without the history of breast cancer.ResultsA total of 137 cases were included and most of them (94.9%) were asynchronous multiple primary carcinomas. The median interval between the diagnoses of breast cancer and lung cancer was 60 months (2–456 months), median age at the diagnosis of breast cancer was 49.5 (28–81) years old and median age at the diagnosis of lung cancer was 58 (31–84) years old. Univariate and multivariate Cox regression analysis indicated that poor differentiation [hazard ratio (HR)=6.372, 95% confidence interval (CI): 2.441–16.633, P<0.001] and pTNM stage III/IV (HR=5.830, 95% CI: 2.295–14.813, P<0.001) of lung cancer were independent prognostic risk factors for these patients. Before and after the PSM, the overall survival (OS) of lung cancer patients with breast cancer was significantly worse than that of single primary lung cancer patients (P<0.001, P=0.002).ConclusionDifferentiation status and pTNM stage were independent prognostic factors in operated breast cancer patients with second primary lung cancer. Meanwhile, the prognosis of this group of patients was worse than single primary lung cancer patients, which indicated that the medical history of breast cancer was also a prognostic risk factor of female lung cancer patients.