Developed Tumor Recurrence Research Articles

Prognostic factors in patients with occult ruptured hepatocellular carcinoma after hepatectomy

Objective To study the prognostic factors in patients with occult ruptured hepatocellular carcinoma (HCC) after hepatectomy. Methods The clinical data of 31 patients with occult ruptured HCC who underwent hepatectomy at the Heze Multiple Hospital from January 2001 to December 2014 were retrospectively analyzed. There were 27 males and 4 females, with ages ranging from 29 to 73 years. Kaplan-Meier survival analysis was carried out for survival analysis, and compared by the log-rank test. Multivariate analysis was conducted using the Cox proportional hazards regression model. Results Of 31 patients in this study, 27(87.1%) had died, and 25(80.6%) had developed tumor recurrence and metastasis. The median overall survival was 8 months and the median tumor-free survival was 4 months. On Cox regression analysis, non-R0 resection was an independent risk factor of overall survival (RR=2.816, 95%CI: 1.006-7.887) and disease-free survival (RR=3.295, 95%CI: 1.215-8.940). Poor tumor differentiation was an independent risk factor of overall survival (RR=3.120, 95%CI: 1.193-8.160). Conclusions The prognosis of patients with occult rupture HCC who underwent no R0 resection was poor. However, the prognosis of patients who underwent non-R0 resection was even poorer. Key words: Carcinoma, hepatocellular; Hepatectomy; Rupture; Prognosis; Influencing factor

Outcomes of Endoscopic Submucosal Dissection for Subepithelial Lesions Localized Within the Submucosa, Including Neuroendocrine Tumors: A Multicenter Prospective Study.

Endoscopic submucosal dissection (ESD) seems to be a reasonable option for gastrointestinal subepithelial lesions (SELs) localized within the submucosa. Indications for ESD include small neuroendocrine tumors (NETs) and indeterminate SELs. However, the prospective data regarding ESD and surveillance remain unclear. This study was performed to prospectively investigate the outcomes of ESD, including organ-specific outcomes and the mid-term prognosis. This prospective multicenter study included 57 patients who underwent ESD for SELs localized within the submucosa [definite NETs (n = 42) and indeterminate SELs (n = 15)]. The efficacy and safety of ESD were evaluated in the whole cohort and in subgroups (NETs and indeterminate SELs). All patients were followed up. The rates of en bloc resection, curative resection, and complications were 98.2%, 66.7%, and 7.7% for the overall population (n=57); 100%, 61.9%, and 2.4% for NETs (n=42); and 93.3%, 80.0%, and 20.0% for indeterminate SELs (n=15), respectively. The rates of curative resection for NETs were poorer in the stomach (20%, n=5) and duodenum (33%, n=3) than in the rectum (71%, n=34). Including 11 of 16 patients with NETs who underwent a conservative approach resulting in non-curative resection, no patients developed tumor recurrence during the follow-up period (median, 24.5 months; range, 1-60 months). ESD followed by surveillance demonstrated acceptable mid-term outcomes for non-curative NETs. ESD can be an efficient therapy for SELs localized within the submucosa. However, gastric and duodenal ESD for NETs may be limited in terms of its curative and technical aspects. Clinicians should be aware of the potential complications of ESD for indeterminate SELs.

Buschke-Lowenstein tumor of the penis

Buschke-Lowenstein (BLT) tumor or giant condyloma acuminatum (GCA) is a rare viral disease belonging to the group of verrucous carcinomas; the virus responsible is human papilloma virus (HPV) type 6 and 11 which is transmitted in humans by sexual contact. It is characterized by its extension within the surface layer and at depth, by its degenerative potential and by its recurrent nature after treatment. Therapy is based on surgery. We report the case of a 53-year old patient with a history of recurrent urethritis and a multiplicity of partners without homosexual encounters, presenting with a lesion at the level of the penis. The symptoms started three years before and were caused by a nonpainful budding tumor growing gradually at the level of the root of the penis resulting in tingling and bleeding. Clinical examination showed a dyschromic, infiltrating, cauliflower-like, papillomatous tumor measuring 13cm along its longer axis on the dorsal surface of the penis, with patchy ulcers and extending to the suprapubic region. The remainder of the clinical examination was normal and the assessment of sexually transmitted infection (STI) was negative. Treatment was based on complete surgical resection of the tumor. Soft tissue was covered by the surrounding skin. The anatomopathological study showed a giant genital wart without signs of malignancy. The postoperative course was uneventful. The patient didn't develop tumor recurrence during a 5-year follow-up period.

Extraneural metastatic gliosarcoma: A case report and review of the literature

Extraneural metastasis of gliosarcoma (GS) is a rare event. In this report, we describe a 15-year-old girl with a frontal GS who underwent complete resection, but developed tumor recurrence requiring a second operation after 3 years. Eight months after the second operation, she presented with a left postauricular mass. The clinical, neuroimaging, and histopathological findings were described. We also conducted a literature review and identified 26 cases of GS with extraneural metastasis, including the current report. The prognosis of GS with extracranial metastasis was poor, with a median survival of approximately 8.0 months. The common metastatic organs were the lungs (65.4%), liver (34.6%), and skeleton (23.1%). We also discuss the pathogenesis of GS with extraneural metastasis. We report an unusual case of a pediatric patient with GS with extraneural metastasis, with a long survival. GS with extraneural metastasis should be considered as a differential diagnosis in patients with soft-tissue masses. This work was approved by the Ethics Committee of the Faculty of Medicine, Prince of Songkla University, Thailand (REC 62-259-10-1) on September 9, 2019.

Prognosis and Recurrence sites after pancreatectomy for stage 1 pancreatic invasive ductal carcinoma

Background: Pancreatic invasive ductal carcinoma (PIDC) is one of the deadliest cancers and is associated with high mortality and recurrence rates after surgery. Early stage PIDC is difficult to detect; thus, the prognosis after stage 1 PIDC resection is still not well known. Here, we investigated the prognosis and recurrence sites after pancreatectomy for stage 1 PIDC. Material & Methods: Between 2007 and 2017, 265 patients underwent pancreatectomy for PIDC at Kobe University Hospital. Out of the 265 patients, 11 patients were histologically diagnosed with stage 1 PIDC. We reviewed the prognosis and recurrence sites of 11 patients with stage 1 PIDC. Results: Out of 11 patients (5 males, 6 females), 6 patients underwent pancreaticoduodenectomy and 5 patients underwent distal pancreatectomy. Ten patients received adjuvant therapy with gemcitabine or S-1. The five-year survival rate was 76.2% (median follow-up time, 1949 days; range, 608–3843). Recurrence was noted in 4 patients. Three patients developed tumor recurrence in the remnant pancreas, and 1 patient developed invasive carcinoma derived from intraductal papillary mucinous neoplasm in the remnant pancreas. All patients with recurrence underwent total remnant pancreatectomy, but had R1 resections due to infiltrations of cancer cells at the dissected pancreatic tissue margin. Three out of 4 patients after total remnant pancreatectomy died from re-recurrence. One patient was alive 1 year after total remnant pancreatectomy. Six out of 7 patients without recurrence are alive. One patient died of other causes two years after pancreatectomy. Conclusions: Prognosis after pancreatectomy for stage 1 PIDC was favorable. All patients with recurrence developed recurrence in the remnant pancreas. For patients after pancreatectomy for stage 1 PIDC, surveillance with intensive care for the remnant pancreas is mandatory.

Treatment of consistent BRAF/HRAS gene mutation and MYC amplification radiation-induced abdominal wall angiosarcoma with low-dose apatinib: a case report

BackgroundAn extremely rare condition, radiation-induced angiosarcoma is characterized by a poor prognosis, high recurrence rate and lack of effective treatment. Herein, we present a case report of a 48-year-old female patient with radiation-induced abdominal wall angiosarcoma who showed a dramatic response to low-dose apatinib.Case presentationThe patient, who was diagnosed with cervical squamous cell carcinoma 20 years ago, had received radiotherapy and chemotherapy after operation. Angiosarcomas of the abdominal wall appeared 9 years later. After repeated surgical operations and intravenous chemotherapy for the angiosarcomas, the patient developed tumor recurrence and pulmonary metastasis. The abdominal wall tumors showed repeated rupture and bleeding, with poor wound healing. On evaluation, laboratory findings detected the negative serum tumor markers CEA, CA 125, CA 15–3 and CA 19–9. Imaging showed multiple subcutaneous nodules and masses in the abdominal wall, accompanied by suspected small subpleural nodule at the lower lobe of the right lung. Immunohistochemistry of previous surgical pathology indicated that CD31, ERG and Vim were positive. The result of whole exome sequencing suggested the mutations of BRAF and HRAS, and the amplification of MYC. Based on the above results, the patient was clinically diagnosed with radiation-induced angiosarcoma of the abdominal wall with pulmonary metastasis. The patient was treated with low-dose apatinib and rejected reoperation or chemotherapy.ResultsAt the 6-month follow-up visit, the abdominal wall lesions that had previously ruptured stopped bleeding and showed significant shrinkage. Imaging showed that most of the abdominal wall lesions had partially regressed, and some of the lesions on the abdominal wall and the suspected lesion of subpleural nodule at the lower lobe of the right lung had disappeared.ConclusionsWe described this case and reviewed the literature on radiation-related angiosarcoma. Importantly, this case suggests that apatinib may be an effective and sensitive treatment for radiation-induced angiosarcoma even at the lowest dosage, without aggravating the bleeding of lesions.

Diffusion-weighted imaging for identifying patients at high risk of tumor recurrence following liver transplantation

BackgroundTumor recurrence is the major risk factor affecting post-transplant survival. In this retrospective study, we evaluate the prognostic values of magnetic resonance (MR) diffusion-weighted imaging (DWI) in liver transplantation for hepatocellular carcinoma (HCC).MethodsFrom April 2014 to September 2016, 106 HCC patients receiving living donor liver transplantation (LDLT) were enrolled. Nine patients were excluded due to postoperative death within 3 months and incomplete imaging data. The association between tumor recurrence, explant pathologic findings, and DWI parameters was analyzed (tumor-to-liver diffusion weighted imaging ratio, DWIT/L; apparent diffusion coefficients, ADC). The survival probability was calculated using the Kaplan–Meier method.ResultsSixteen of 97 patients (16%) developed tumor recurrence during the follow-up period (median of 40.9 months; range 5.2–56.5). In those with no viable tumor (n = 65) on pretransplant imaging, recurrence occurred only in 5 (7.6%) patients. Low minimum ADC values (p = 0.001), unfavorable tumor histopathology (p < 0.001) and the presence of microvascular invasion (p < 0.001) were risk factors for tumor recurrence, while ADCmean (p = 0.111) and DWIT/L (p = 0.093) showed no significant difference between the groups. An ADCmin ≤ 0.88 × 10− 3 mm2/s was an independent factor associated with worse three-year recurrence-free survival (94.4% vs. 23.8%) and overall survival rates (100% vs. 38.6%).ConclusionsQuantitative measurement of ADCmin is a promising prognostic indicator for predicting tumor recurrence after liver transplantation.

Failure patterns after curative resection for intrahepatic cholangiocarcinoma: possible implications for postoperative radiotherapy

BackgroundTo explore the patterns of failures and areas at highest risk of recurrence for postoperative intrahepatic cholangiocarcinoma (IHCC), with the aim to guide IHCC adjuvant radiotherapy.MethodsPatients with IHCC who had undergone radical surgery at our institution from July 2010 to August 2017 were retrospectively analyzed. The survival and prognostic factors were analyzed by univariate and multivariate analysis. All sites of recurrence were found out and classified as the surgical margin, regional lymph nodes, liver remnant and distant metastasis. According to the recurring area at highest risk, the target volume of adjuvant radiotherapy was proposed.ResultsThe median follow-up time was 23.5 months (2–85 months). The median recurrence free survival (RFS) and overall survival (OS) were 12.1 months and 24.8 months, respectively. Seventy-three (73/127, 57.5%) IHCC patients developed tumor recurrence. Initial recurrences occurred in the potential postoperative radiotherapy (PORT) volume, remnant liver and distant sits were 46 (46/73, 63.0%), 36 (36/73, 49.3%) and 22 (22/73, 30.1%) cases, respectively. Of the 46 patients whose initial recurrence inside the potential PORT volume, 29 (29/73, 39.7%) developed recurrence only inside the potential PORT volume, including 13 tumor bed recurrences, 7 lymph node metastases, and 9 with both tumor bed recurrences and lymph node metastases. The most common lymph node metastases sites were nodes around the abdominal aorta, followed by lymph nodes along the celiac artery, the common hepatic artery, and in the hepatoduodenal ligament.ConclusionsHigh proportion of the recurrences occurred only inside the potential PORT volume, implying adjuvant radiotherapy might improve the local-regional control. Surgical margins and lymph node stations No.16a2, 9, 8, 12, 13, and 14 are suggested to be included in the radiation volume.

SURG-34. CLINICAL PREDICTORS OF TUMOR RECURRENCE AFTER PITUITARY ADENOMA RESECTION

Abstract INTRODUCTION Repeat surgery after tumor recurrence after pituitary adenoma resection can be challenging due to formation of scar tissue and loss of surgical landmarks, which can lead to increased rates of postoperative complications. Identification of clinical predictors of tumor recurrence would allow for appropriate stratification of patients to optimize preoperative counseling and postoperative management. METHODS We conducted a retrospective review of 349 patients who underwent pituitary adenoma resection at Johns Hopkins Hospital between 2003 and 2017. We used unadjusted and adjusted logistic regression to identify predictors of tumor recurrence. Factors which were associated with tumor recurrence in univariable models (p&lt; 0.1), were included in our multivariable model. Factors that remained significantly associated with tumor recurrence (p&lt; 0.05) in our multivariable model were considered predictors of recurrence. RESULTS 59 (16.9%) patients developed tumor recurrence at the time of our study. Patients who had surgery through one nare, transcranial surgery, visual field deficit, larger tumor volume, bilateral cavernous sinus invasion, carotid artery invasion, and postoperative cerebral spinal fluid (CSF) leak were more likely to have tumor recurrence. Conversely, patients who are younger in age, had sphenoid packing, and gross total resection were less likely to have tumor recurrence. In our multivariable model, only age (adjusted odds ratio[aOR]: 0.96), surgery through one nare (aOR: 2.05), gross total resection(aOR: 0.21), and presence of CSF leak(aOR: 4.43) remained significantly associated with tumor recurrence. CONCLUSIONS We identified several predictors of tumor recurrence after pituitary adenoma resection. Notably, having gross total resection of the primary tumor had the most significant protective effect on tumor recurrence. Given the increased complication associated with repeat surgery, gross total resection should be attempted in all patients, if feasible. Patients with other predictors of tumor recurrence should be monitored more frequently to allow for early detection of recurrence to optimize treatment strategies.

Eosinophilic solid and cystic renal cell carcinoma: clinicopathological analysis and molecular characterization

Objective: To study the clinicopathological features, immunohistochemical phenotype, molecular changes, differential diagnosis and prognosis of eosinophilic solid and cystic renal cell carcinoma (ESC RCC). Methods: A total of 15 cases were selected from 2005 to 2019 at Nanjing Jinling Hospital,Nanjing University School of Medicine for clinicopathological and immunohistochemical analysis, 10 of which were subject to cancer-associated mutation analysis using targeted next-generation sequencing (NGS) panel. A literature review was also performed. Results: The patients' ages ranged from 15 to 68 years (mean, 33 years). The male-to-female ratio was 1.1∶1.0. During a mean follow-up of 22 months, none of the patients developed tumor recurrence, progression or metastasis. Histologically, the tumors typically demonstrated solid and cystic architectures and the neoplastic cells contained voluminous eosinophilic cytoplasm with prominent granular cytoplasmic stippling. Immunohistochemically, tumor cells in all cases were immunoreactive for CK20. Signal pathway related protein mTOR and S6 were positive in 14/15 and 6/15 cases, respectively. Cathepsin K, Melan A and HMB45 were at least focally positive in 12/15, 6/15 and 2/15 cases, respectively. CK7 and CD10 showed focal immunostain positivity in some cases, while TFE3, TFEB, CA9 and CD117 were negative in all cases. NGS demonstrated TSC1/TSC2 mutations in all tested cases (10/10). Conclusions: ESC RCC is a rare tumor that tends to occur in young patients with an indolent behavior. Diagnosis can be established by its distinct clinical and histopathologic findings, immunohistochemical phenotype and molecular genetics. The tumor may be considered as a new subtype of RCC.

Prognostic significance of anaplastic lymphoma kinase rearrangement in patients with completely resected lung adenocarcinoma.

Reports of the prognostic significance of anaplastic lymphoma kinase (ALK) rearrangement in early stage lung adenocarcinoma have been contradictory. This study aimed to identify the associations of ALK rearrangement with clinicopathologic features and prognosis in patients with surgically resected stage I-IIIA lung adenocarcinoma. Analysis of ALK status was performed by a fully-automated immunochemistry assay (with rabbit monoclonal Ventana D5F3 antibody) in tissue sections of 2,103 patients with surgically-resected stage I-IIIA lung adenocarcinoma. ALK positive patients were matched with negative patients in a 1:1 ratio using propensity score matching (PSM). Clinical outcomes were assessed by disease-free survival (DFS) and overall survival (OS) after surgery. Initial recurrence pattern was also investigated according to ALK status. Among 2,103 stage I-IIIA lung adenocarcinoma cases, 81 (3.9%) were ALK positive. ALK positivity was significantly associated with younger age (P<0.001), solid predominant adenocarcinoma (P<0.001), variants of invasive adenocarcinoma (P<0.001), higher frequency of pleura invasion (P=0.040), smaller tumor size (P=0.014), mediastinal lymph node involvement (N2; P<0.001) and later pathologic stage (IIIA; P=0.001). In the match cohort, ALK positivity was not associated with DFS [hazard ratio (HR), 0.58; 95% confidence interval (CI): 0.33-1.03, P=0.063] or OS (HR, 0.61; 95% CI: 0.22-1.67, P=0.334). Lymph node involvement (HR: 5.36, 95% CI, 3.01-9.65, P<0.001) and solid predominant adenocarcinoma subtype (HR, 2.02; 95% CI: 1.07-3.79; P=0.029) were the independent prognostic factors of inferior DFS, and lymph node involvement was the independent prognostic factors of worse OS (HR, 6.61; 95% CI: 2.43-17.94; P<0.001). ALK positive patients had a higher risk of developing tumor recurrence in liver (P=0.043). ALK rearrangement was not an independent prognostic factor in stage I-IIIA lung adenocarcinoma patients but leaded to a higher risk of developing recurrence in liver.

Clinicopathological study of BCOR rearrangement in high grade endometrial stromal sarcoma

Objective: To investigate clinicopathological, cytogenetic features and differential diagnoses of high grade endometrial stromal sarcoma (HGESS) with BCOR gene rearrangement. Methods: Five cases of HGESS with BCOR rearrangement were collected from consultant files (2016-2018) at Fudan University Shanghai Cancer Center. Interphase FISH was performed using a dual color break-apart probe. The clinical data, histologic features and immunohistochemical findings were reviewed. Results: All 5 cases occurred in adult women with a median age of 48 (range, 45-55) years. Abdominal pain and abnormal vaginal bleeding were the most common symptoms. Microscopically, the tumors showed mainly tongue-like and/or intersecting myometrial invasion. Stromal myxoid matrix and/or collagen plaques were prominent in all the cases. Most tumors consisted of uniform, haphazard fascicles of short spindle cells with mild to moderate nuclear atypia. Mitotic figures and necrosis were easily identified. Significant nuclear pleomorphism was not seen. Most tumors were rich in thick-walled small vessels. Prominent perivascular tumor cell whorling seen in conventional low-grade endometrial stromal sarcoma was not seen. All tumors expressed CD10 with only focal or absent desmin, SMA and/or h-caldesmon staining. ER or PR expression was seen in 4 tumors and 1 tumor showed both marker expression. Diffuse cyclin D1 was present in 2 tumors. BCOR immunoreactivity was present with strong staining in 3 cases and moderate staining in 1 case respectively. Ki-67 index ranged from 10% to 30%. Fluorescence in situ hybridization confirmed chromosomal aberration of BCOR gene in all tumors, that were previously diagnosed as myxoid leiomyosarcoma (2 cases), spindle cell uterine sarcoma (2 cases) and low-grade endometrial stromal sarcoma (1 case). Limited follow-up information revealed that 3/5 patients developed tumor recurrence, metastasis or death within one year. Conclusion: BCOR rearranged HGESS has distinct morphological features and aggressive clinical behavior. In the presence of significant overlapping morphologic features between BCOR rearranged HGESS and other myxoid uterine mesenchymal tumors, especially myxoid leiomyosarcoma, molecular analysis is essential for accurate diagnoses.

Outcome and prognosis after pancreatectomy in patients with solid pseudopapillary neoplasms

BackgroundSolid pseudopapillary neoplasms (SPN) are rare and represent approximately 4% of all cystic pancreatic tumors. The prognosis is excellent, although 10–15% of SPN patients show metastasis at the time of surgery or tumor recurrence during follow-up after pancreatectomy. Aim of the study was to analyze surgical management, risk factors for malignancy as well as long-term outcome and prognosis of this distinct tumor entity. MethodAll patients with pancreatic resection for SPN between 10/2001 and 07/2018 in the authors’ institution were identified from a prospective database. Clinicopathologic details, perioperative data and long-term follow-up results were retrospectively analyzed. ResultsFifty-two patients were identified, 44 (85%) of them were female and the median age was 29 years (IQR 9–71). Seven (13%) patients showed a malignant behaviour of SPN with N1 (n = 2) or M1 (n = 1) disease at resection; 5 patients developed tumor recurrence, after a median of 21 months. During follow-up time (median 54 months) all patients were alive, the 5- and 10-year rates for disease-free survival were 89.0% and 81.6%, respectively. Significant risk factors for recurrence were age <18 years (p = 0.0087) and parenchyma-preserving surgical approaches (p = 0.0006). The postoperative long-term outcome showed ECOG = 0–1 in all patients, with resection related exocrine insufficiency in 20 (41%) and diabetes mellitus in 2 (4%) patients. ConclusionsAge < 18 years is a significant risk factor for malignancy in SPN, and parenchyma preserving resections harbor a significant risk for tumor recurrence. As recurrence may occur late, a systematic life-long follow-up should be performed.

Does Putting Back Hyperostotic Bone Flap in Meningioma Surgery Cause Tumor Recurrence? An Observational Prospective Study

Replacing the skull defect with synthetic materials for hyperostotic bone secondary to meningioma is recommended owing to the possibility of tumor invasion. In our institution, neurosurgeons have been putting back the refashioned hyperostotic bone flap after meningioma excision because of budget constraints. The aim of this study was to review the long-term meningioma recurrence rate in these patients. This was a nonrandomized, prospective observational study conducted from September 2011 to January 2015 on patients with intracranial convexity and parasagittal meningiomas. Preoperative computed tomography brain scans were obtained in all patients to confirm bony hyperostosis. Intraoperatively, part of the hyperostotic bone was sent for histopathologic examination. The rest of the bone flap was refashioned by drilling off the hyperostotic part. The bone flap was put back over the craniotomy site after soaking in distilled water. All patients were followed up for tumor recurrence. The study included 34 patients with convexity or parasagittal meningioma World Health Organization grade I-II who underwent Simpson grade Ia and IIa excision. Median follow-up was 63.5 months (mean 64.9 ± 9.4 months). The hyperostotic bone flap showed presence of tumor in 35% of patients. There were 2 patients with parasagittal meningiomas after Simpson grade IIa resections who developed tumor recurrences. Our study found that meningioma recurrence was unlikely when autologous cranioplasty was done with refashioned hyperostotic bone. This could be done in the same setting with meningioma excision. There was no recurrence in convexity meningiomas at mean 5-year follow-up.

Improving the definition of high-risk patients for tumor recurrence from clear cell renal cell carcinoma: The U-CISS classification.

629 Background: Thirty percent of patients with localized clear cell renal cell carcinoma (ccRCC) will ultimately develop recurrence (local or metastatic) after nephrectomy. Current risk stratification systems still misclassify patients. A better stratification is needed to select high-risk patients who may benefit from adjuvant therapy. We sought to improve the existing UISS by the addition of genetic information in a new UCLA cytogenetic integrated staging system (U-CISS). Methods: A total of 240 patients from UCLA with localized ccRCC and cytogenetic analysis on tumor specimen were included in the study. In a continuation of our previous research, cytogenetic (combined loss 3p-14q) and a pathological high-risk feature, microvascular invasion (MVI) were implemented in the UISS. Association with recurrence free survival (RFS) was analyzed in a uni- and multivariable fashion; prognostic accuracy was tested with the c-index. All tumors that had either MVI, combined loss 3p/14q or both in the UISS low-risk group were placed into the U-CISS intermediate group. Tumors with one or both risk factors in the UISS intermediate group were placed into the new U-CISS high-risk group. Results: Fifty patients developed tumor recurrence. On multivariate analysis, combined loss 3p-14q, and MVI were independent prognostic factors. The U-CISS placed significantly better prognosticated RFS in the high-risk group (7/50 (14%) with UISS vs. 23/50 (46%) with U-CISS) and thus, was more accurate in prognosticating RFS. The c-index for recurrence prognostication was improved in the U-CISS (0.70 vs. 0.65 for the UISS). Furthermore, the U-CISS was a better prognostication tool when the intermediate and high-risk group were combined (prognostication of 74% with U-CISS vs. 68% UISS). Conclusions: The use of U-CISS, which integrates genomic alterations with clinical and pathologic features, allowed a re-allocation of patients to create a better stratification of recurrence risk. This new definition of high-risk of recurrence could significantly improve selection of patients who are in greatest need of closer surveillance and/or adjuvant treatment. C.L. and N.K. contributed equally to first authorship.

Cost-utility analysis of adjuvant imatinib treatment in patients with high risk of recurrence after gastrointestinal stromal tumour (GIST) resection in Thailand

BackgroundMany patients develop tumour recurrence within a few years after undergoing surgical resection of gastrointestinal stromal tumours (GIST). Adjuvant imatinib treatment is recommended for patients with high risk of GIST recurrence as it can improve recurrence-free survival and overall survival of patients. This study aims to assess the cost-utility of adjuvant imatinib in patients with high risk of GIST recurrence after surgery compared with no adjuvant therapy in Thailand.MethodsA Markov model was developed to estimate lifetime costs and outcomes of using adjuvant imatinib treatment and other treatment alternatives if recurrence occurred compared with the current situation of no adjuvant therapy in high-risk patients after surgery. A 1-month cycle length was deployed in the model. Transition probabilities were derived from literature review. Costs were collected and calculated for the year 2014 from a societal perspective. Future costs and outcomes were discounted at 3% per year. One-way and probabilistic sensitivity analyses were conducted to assess parameter uncertainties.ResultsThree years of adjuvant imatinib treatment followed by imatinib treatment and best supportive care if recurrence occurred after or during adjuvant therapy, respectively, was the best option as it produced more health outcomes (1.23 life years (LYs) and 1.16 quality-adjusted life years (QALYs)) compared to no adjuvant therapy while yielding the lowest incremental cost-effectiveness ratio (ICER) of 1,648,801 Thai Baht (THB) per QALY gained. Three years of adjuvant imatinib treatment followed by sunitinib treatment if recurrence occurred had an ICER of 2,608,264 THB per QALY gained compared to the best option, while other options were dominated. A one-way sensitivity analysis showed that the utility of patients receiving adjuvant imatinib had the greatest effect on the model, followed by the discount rate and probability of GIST recurrence.ConclusionsAdjuvant imatinib treatment improved the health benefits of patients with high risk of GIST recurrence. However, in the Thai context, it was not cost-effective at the current price.

Clinical management of endoscopically resected pT1 colorectal cancer.

Background Implementation of colorectal cancer (CRC) screening programs increases endoscopic resection of polyps with early invasive CRC (pT1). Risk of lymph node metastasis often leads to additional surgery, but despite guidelines, correct management remains unclear. Our aim was to assess the factors affecting the decision-making process in endoscopically resected pT1-CRCs in an academic center. Methods We retrospectively reviewed patients undergoing endoscopic resection of pT1 CRC from 2006 to 2016. Clinical, endoscopic, surgical treatment, and follow-up data were collected and analyzed. Lesions were categorized according to endoscopic/histological risk-factors into low and high risk groups. Comorbidities were classified according to the Charlson comorbidity index (CCI). Surgical referral for each group was computed, and dissociation from current European CRC screening guidelines recorded. Multivariate analysis for factors affecting the post-endoscopic surgery referral was performed. Results Seventy-two patients with endoscopically resected pT1-CRC were included. Overall, 20 (27.7 %) and 52 (72.3 %) were classified as low and high risk, respectively. In the low risk group, 11 (55 %) were referred to surgery, representing over-treatment compared with current guidelines. In the high risk group, nonsurgical endoscopic surveillance was performed in 20 (38.5 %) cases, representing potential under-treatment. After a median follow-up of 30 (6 – 130) months, no patients developed tumor recurrence. At multivariate analysis, age (OR 1.21, 95 %CI 1.02 – 1.42; P = 0.02) and CCI (OR 1.67, 95 %CI 1.12 – 3.14; P = 0.04) were independent predictors for subsequent surgery. Conclusions A substantial rate of inappropriate post-endoscopic treatment of pT1-CRC was observed when compared with current guidelines. This was apparently related to an overestimation of patient-related factors rather than endoscopically or histologically related factors.

Albumin-bilirubin (ALBI) grade-based nomogram to predict tumor recurrence in patients with hepatocellular carcinoma

BackgroundTumor recurrence after curative resection is common in hepatocellular carcinoma (HCC), but large-scale long-term prediction on an individual basis has seldom been reported. We aimed to construct an albumin-bilirubin (ALBI) grade-based nomogram to predict tumor recurrence in patients with HCC undergoing surgical resection. MethodsA total 1038 patients with newly diagnosed HCC undergoing curative resection between 2002 and 2016 were enrolled. Baseline characteristics, tumor status and severity of liver functional reserve were collected. The Cox proportional hazards model was used to predict tumor recurrence and construct the nomogram. The performance of the nomogram was evaluated by the discrimination and calibration tests. ResultsAfter a mean follow up time of 30 months, 510 (49%) patients developed tumor recurrence. The cumulative recurrence-free survival at 1, 3, 5, and 10 years were 79%, 51%, 38% and 26%, respectively. In the Cox multivariate model, ALBI grade 2–3, multiple tumors, tumor size equal or large than 2 cm, serum ɑ-fetoprotein level equal or greater than 20 ng/ml and total tumor volume equal or larger than 227 cm3 were independent risk factors associated with tumor recurrence. A nomogram was constructed based on these five variables. Internal validation with 10,380 bootstrapped sample sets had a good concordance of 0.607 (95% of confidence interval: 0.587–0.627). The calibration plots for 1-, 3- and 5-year recurrence-free survival well matched the idealized 45-degree line. ConclusionsALBI is a feasible marker for tumor recurrence. This easy-to-use ALBI grade-based nomogram may predict tumor recurrence for individual HCC patient undergoing surgical resection.

Predictors of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals

BackgroundDespite the dramatic improvement in viral eradication rates that has been reached with direct antiviral agents (DAAs), the real benefit of viral eradication after DAAs on hepatocellular carcinoma (HCC) development is still controversial. AimTo prospectively assess the risk of HCC occurrence and early recurrence in a large cohort of DAA-treated HCV-cirrhotic patients and to identify potential predictors of HCC development. MethodsWe analyzed data prospectively collected from 1927 consecutive HCV-infected cirrhotic patients treated with DAA from January to December 2015 in 10 tertiary liver centers in Italy and followed-up for one year after therapy. 161 patients had a previous HCC. Results38/161 subjects developed tumor recurrence during the follow-up (recurrence rate = 24.8 per 100-year), patients with SVR had a significantly lower rate of recurrence. Lack of SVR and alpha-fetoprotein (AFP) were independent predictors of HCC recurrence. 50/1766 patients without a previous HCC history developed HCC during follow-up (incidence rate = 2.4 per 100-year). Lack of SVR was the strongest predictor of HCC development. Furthermore, patients with SVR and no stigmata of portal hypertension have a lower incidence rate of HCC (1.0 per 100-year). ConclusionsSVR is associated with a significant decrease of recurrent or de novo HCC. Baseline AFP and signs of portal hypertension can help to stratify the risk of HCC.

Outcomes of surgery for functional cardiac paragangliomas: A single-center experience of 17 patients

ObjectiveCardiac paragangliomas are rare neuroendocrine tumors. Early surgical treatment improves clinical symptoms and prolongs survival. We review our experience in 17 patients who underwent surgical resection for functional cardiac paraganglioma. MethodsSeventeen patients underwent surgery for functional cardiac paraganglioma from 2004 to 2017 were identified. Clinical data and long-term outcomes were extracted and analyzed. ResultsAll 17 patients with cardiac paraganglioma (11 males) with a median age of 35 years (range, 11 to 51 years) were hormonally functional and underwent operations. A 24-hour urine catecholamine assay documented elevation of norepinephrine, epinephrine, and dopamine. Tumors were determined with octreotide scintiscan in all 17 patients and metaiodoben-zylguanidine scintigraphy in 10 of 15 patients. Tumor sites were right atrioventricular groove in 4 patients, between the main arteries in 10 patients, and interatrial groove in 4 patients. All patients underwent complete resection. Concomitant surgeries were: structural reconstruction in 16 patients (94%) and coronary artery bypass graft in 8 patients (47%). One patient had a history of incomplete resection of an intra-atrial tumor. One patient died postoperatively. Operative mortality is 5.8%. During follow-up (mean, 6.5 years; range, 1.5 to 14.2 years), 16 patients are alive in functional class I or II. Two patients developed tumor recurrence and 14 remained symptom-free with normal urinary catecholamines. ConclusionsWith a multidisciplinary treatment, early diagnosis, complete resection for the tumor along with complex reconstruction is achievable for most patients, and it offers promising long-term survival.