Preoperative Alpha-fetoprotein Research Articles

Colorectal adenocarcinoma with enteroblastic differentiation: a clinicopathological analysis of eight cases

Objective: To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED). Methods: Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed. Results: Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 μg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases. Conclusions: CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

Impact of MAFLD criteria on postoperative recurrence of non-B, non-C HCC.

This study aimed to clarify the population in whom the presence of metabolic dysfunction-associated fatty liver disease (MAFLD) especially contributes to recurrence after liver resection for non-B, non-C hepatocellular carcinoma (NBNC-HCC). Of the 199 patients who underwent liver resection for NBNC-HCC, those who exceeded Milan criteria and with pathologically proven vascular invasion, intrahepatic metastasis, and positive resection margins were excluded, and the remaining 94 were eligible for this study. We explored factors contributing to postoperative recurrence in populations with and without advanced liver fibrosis. Independent factors contributing to postoperative recurrence in the study population were male sex ( P = 0.023) and presence of type 2 diabetes (DM) ( P = 0.006) and advanced liver fibrosis ( P < 0.001). Factors in cases with advanced liver fibrosis (n = 43) were non-overweight ( P = 0.02), type 2 DM ( P = 0.006), and preoperative alpha-fetoprotein level of 8.2 ng/ml or higher ( P = 0.021). In cases without advanced liver fibrosis (n = 51), only presence of all three MAFLD criteria was related to recurrence. Liver fibrosis is a strong factor contributing to postoperative recurrence of NBNC-HCC, as previously reported. In patients with advanced liver fibrosis, presence of type 2 DM was the only factor associated with recurrence among MAFLD criteria. On the other hand, in patients without advanced liver fibrosis, the combination of all MAFLD criteria, rather than a specific criterion alone, contributed to recurrence. MAFLD criteria were found to have utility as predictors of postoperative recurrence in NBNC-HCC.

Analysis of Survival Rate and Influencing Factors in Surgical Treatment of Primary Hepatocellular Carcinoma

Objective: To study the survival rate of patients with primary hepatocellular carcinoma (HCC) undergoing clinical surgical treatment and various influencing factors, with the aim of further improving the survival rate of primary HCC patients. Methods: Sixty patients with primary hepatocellular carcinoma who underwent liver cancer resection surgery between January 2020 and December 2022 in our hospital were selected. A retrospective analysis was conducted on the patients' clinical characteristics (family medical history, alpha-fetoprotein levels, degree of liver cirrhosis, vascular invasion), treatment methods (surgical techniques, adjunctive therapies), and prognosis. The survival rate of patients and the influencing factors on the postoperative survival rate were analyzed. Results: There was a statistically significant difference in the five-year survival rate comparisons between different liver cirrhosis statuses, tumor sizes, preoperative alpha-fetoprotein levels, vascular invasion statuses, adjunctive treatment methods, and family medical histories (P &lt; 0.05). Comparisons between different genders, ages, tumor locations, tumor pathological types, hepatitis B surface antigens, Child-Pugh classifications of liver function, tumor numbers, and methods of liver cancer resection showed no statistically significant differences (P &gt; 0.05). Liver cirrhosis, tumor size ≥ 5cm, preoperative alpha-fetoprotein level &gt; 400ng/ml, change in alpha-fetoprotein levels pre-and post-surgery, vascular invasion, adjunctive treatment methods, and PLC family medical history are independent factors influencing the survival rate of surgical treatment in primary HCC patients. Conclusion: There are several factors affecting the postoperative survival rate of primary HCC patients. Clinicians need to take a comprehensive approach. For high-risk patients, regular follow-ups are necessary, coupled with early diagnosis and treatment, to improve the prognosis. This approach is worth promoting.

High serum alpha-fetoprotein and positive immunohistochemistry of alpha-fetoprotein are related to poor prognosis of gastric cancer with liver metastasis

Liver metastasis in gastric cancer is incurable. Alpha-fetoprotein-producing gastric cancer has a poor prognosis and is prone to liver metastasis. We investigated the association between preoperative serum alpha-fetoprotein levels, liver metastasis, and expression of primitive enterocyte phenotype markers. We reviewed the medical records of 401 patients with gastric cancer who underwent curative surgical resection and immunohistochemically evaluated the primitive phenotype markers. The preoperative serum alpha-fetoprotein levels were elevated and normal in 8 and 393 patients, respectively. Liver metastasis was more frequent in patients with higher preoperative alpha-fetoprotein levels. The 5-year postoperative recurrence-free survival and overall survival rates were significantly worse in patients with higher preoperative serum alpha-fetoprotein levels. Although alpha-fetoprotein and Glypican3 and Spalt-like transcription factor 4 tended to be stained with high preoperative serum alpha-fetoprotein levels, these markers were also positive in some patients with normal alpha-fetoprotein levels. In summary, patients with gastric cancer and high preoperative serum alpha-fetoprotein levels have a poor prognosis and high incidence of liver metastasis. Alpha-fetoprotein can help detect liver metastasis relating to the primitive enterocyte phenotype.

Comparison of clinical outcome between laparoscopic and open hepatectomy of high difficulty score for hepatocellular carcinoma: a propensity score analysis.

Laparoscopic liver resection (LLR) of high difficulty score is technically challenging. There is a lack of clinical evidence to support its applicability in terms of the long-term survival benefits. This study aims to compare clinical outcomes between LLR and the open liver resection of high difficulty score for hepatocellular carcinoma (HCC). From 2010 to 2020, using Iwate criteria, 424 patients underwent liver resection of high difficulty score by the laparoscopic (n = 65) or open (n = 359) approach. Propensity score (PS) matching was performed between the two groups. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival. The laparoscopic group had significantly fewer severe complications (3% vs. 10.8%), and shorter median hospital stays (6days vs. 8days) than the open group. Meanwhile, the long-term oncological outcomes were comparable between the two groups, in terms of the tumor recurrence rate (40% vs. 46.1%), the 5-year overall survival rate (75.4% vs. 76.2%), and the 5-year recurrence-free survival rate (50.3% vs. 53.5%). The high preoperative serum alpha-fetoprotein level, multiple tumors, and severe postoperative complications were the independent poor prognostic factors associated with worse overall survival. The surgical approach (Laparoscopic vs. Open) did not influence the survival. LLR of high difficulty score for selected patients with HCC has better short-term outcomes than the open approach. More importantly, it can achieve similar long-term survival outcomes as the open approach.

Prognostic implications of alpha-fetoprotein and C-reactive protein elevation in hepatocellular carcinoma following resection (PACE): a large cohort study of 2770 patients

BackgroundRoutine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP).MethodsData from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP’s prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging.ResultsPreoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P < 0.001). Increased PACE risk scores correlated significantly with early recurrence and extrahepatic metastases frequency (all P < 0.001). The multivariable analysis identified intermediate and high-risk PACE scores as independently correlating with poor postoperative OS and RFS. Furthermore, the PACE risk score proficiently stratified the prognosis of BCLC stages A and B patients, with multivariable analyses demonstrating it as an independent prognostic determinant for both stages.ConclusionThe PACE risk score serves as an effective tool for postoperative risk stratification, potentially supplementing the BCLC staging system.

Prognostic comparison of active surveillance and adjuvant chemotherapy in the treatment of patients with stage Ⅰ ovarian immature teratoma after fertility-sparing surgery

Objective: To compare the survival outcomes between surveillance and adjuvant chemotherapy in patients with stage Ⅰ ovarian immature teratoma (IMT) underwent fertility-sparing surgery. Methods: Clinical and pathological records of patients with stage Ⅰ ovarian IMT between Jan. 2011 to Feb. 2023 were collected from Peking Union Medical College Hospital, except stage Ⅰa grade 1. The consultation of risks and benefits regarding adjuvant chemotherapy was conducted by gynecologic oncologists. A shared decision about surveillance or chemotherapy was made by physician and patients or their guardians. Patients who finally decided to undergo surveillance were included in the surveillance group (n=40), the others were included in the adjuvant chemotherapy group (n=63). Clinical characteristics, treatment and survival outcomes were analyzed and compared between two groups. Results: A total of 103 patients were included. The median age of initial diagnosis was 20 years old (range: 3-39 years old), and the median follow-up time was 31 months (range: 1-254 months). The age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grade, surgical method, and preoperative and postoperative alpha-fetoprotein levels in the surveillance group and the adjuvant chemotherapy group were similar (all P>0.05). The surgical approach and maximum tumor diameter between two groups were significantly different (all P<0.05). Forty patients of the surveillance group were identified, only one patient with stage Ⅰa grade 2 IMT who underwent cystectomy had malignant recurrence on the same ovary. Another 63 patients received adjuvant chemotherapy after surgery, five patients had malignant recurrence, and two of them died of disease progression after relapsed. There were no significant differences in disease-free survival (DFS;20 vs 36 months) and overall survival (OS; 23 vs 39 months) between the surveillance group and the adjuvant chemotherapy group (follow-up time censored at 72 months; DFS: P=0.325, OS: P=0.278). Conclusions: There are no differences in survival outcomes between patients with stage Ⅰ ovarian IMT underwent adjuvant chemotherapy or not. Active surveillance might be safe and preferable in stage Ⅰ IMT patients underwent complete resection of tumor.

Combined hepatocellular-cholangiocarcinoma compared to hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Different survival, similar recurrence: Report of a large study on repurposed databases with propensity score matching

BackgroundCombined hepatocholangiocarcinoma is a rare cancer with a grim prognosis composed of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma morphologic patterns in the same tumor. The aim of this multicenter, international cohort study was to compare the oncologic outcomes after surgery of combined hepatocholangiocarcinoma to hepatocellular carcinoma and intrahepatic cholangiocarcinoma. MethodsPatients treated by surgery for combined hepatocholangiocarcinoma, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma from 2000 to 2021 from multicenter international databases were analyzed retrospectively. Patients with combined hepatocholangiocarcinoma (cases) were compared with 2 control groups of hepatocellular carcinoma or intrahepatic cholangiocarcinoma, sequentially matched using a propensity score based on 8 preoperative characteristics. Overall and disease-free survival were compared, and predictors of mortality and recurrence were analyzed with Cox regression after propensity score matching. ResultsDuring the study period, 3,196 patients were included. Propensity score adjustment and 2 sequential matching processes produced a new cohort (n = 244) comprising 3 balanced groups was obtained (combined hepatocholangiocarcinoma = 56, intrahepatic cholangiocarcinoma = 66, and hepatocellular carcinoma = 122). Kaplan–Meier overall survival estimations at 1, 3, and 5 years were 67%, 45%, and 28% for combined hepatocholangiocarcinoma, 92%, 75%, and 55% for hepatocellular carcinoma, and 86%, 53%, and 42% for the intrahepatic cholangiocarcinoma group, respectively (P = .0014). Estimations of disease-free survival at 1, 3, and 5 years were 51%, 25%, and 17% for combined hepatocholangiocarcinoma, 63%, 35%, and 26% for the hepatocellular carcinoma group, and 51%, 31%, and 28% for the intrahepatic cholangiocarcinoma group, respectively (P = .19). Predictors of mortality were combined hepatocholangiocarcinoma subtype, metabolic syndrome, preoperative tumor markers alpha-fetoprotein and carbohydrate antigen 19-9, and satellite nodules, and recurrence was associated with satellite nodules rather than cancer subtype. ConclusionDespite data limitations, overall survival among patients with combined hepatocholangiocarcinoma was worse than both groups and closer intrahepatic cholangiocarcinoma, whereas disease-free survival was similar among the 3 groups. Future research on immunophenotypic profiling may hold more promise than traditional nonmodifiable clinical characteristics (as found in this study) in predicting recurrence or response to salvage treatments.

Extracellular contrast agent-enhanced MRI is as effective as gadoxetate disodium-enhanced MRI for predicting microvascular invasion in HCC

PurposeTo compare the performances of gadoxetate disodium-enhanced MRI (EOB-MRI) and extracellular contrast agent-enhanced MRI (ECA-MRI) for predicting microvascular invasion (MVI) in HCC. Materials and MethodsFrom November 2009 to December 2021, consecutive HCC patients who underwent preoperative contrast-enhanced MRI were retrospectively enrolled into either an ECA-MRI or EOB-MRI cohort. In the ECA-MRI cohort, a preoperative MVI score was constructed in the training dataset using a logistic regression model that evaluated pathological type. In a propensity score-matched testing dataset of the ECA-MRI cohort, the MVI score was validated and compared with a previously proposed EOB-MRI-based MVI score calculated in the EOB-MRI cohort. Time-to-early recurrence survival was evaluated by the Kaplan–Meier method with the log-rank test. ResultsA total of 536 patients were included (478 men; 53 years, interquartile range, 46–62 years), 322 (60.1 %) with pathologically confirmed MVI. Based on the training dataset, independent variables associated with MVI included serum alpha-fetoprotein > 400 ng/ml (odds ratio [OR] = 2.3), infiltrative appearance (OR = 4.9), internal artery (OR = 2.5) and nodule-in-nodule architecture (OR = 2.4), which were incorporated into the ECA-MRI-based MVI score. The testing dataset AUC of the ECA-MRI score was 0.720, which was comparable to that of the EOB-MRI-based MVI score (AUC = 0.721; P =.99). Patients from either the ECA-MRI or the EOB-MRI cohort with model-predicted MVI had significantly shorter time-to-early recurrence than those without MVI (P <.001). ConclusionBased on the preoperative serum alpha-fetoprotein and three MRI features, ECA-MRI demonstrated comparable performance to EOB-MRI for predicting MVI in HCC.

Oncological prognosis and morbidity of hepatectomy in elderly patients with hepatocellular carcinoma: a propensity score matching and multicentre study

PurposeWith increasing life expectancy, the number of elderly patients (≥ 65 years) with hepatocellular carcinoma (HCC) has steadily increased. Hepatectomy remains the first-line treatment for HCC patients. However, the prognosis of hepatectomy for elderly patients with HCC remains unclear.MethodsClinical and follow-up data from 1331 HCC patients who underwent surgery between 2008 and 2020 were retrospectively retrieved from a multicentre database. Patients were divided into elderly (≥ 65 years) and non-elderly (< 65 years) groups, and PSM was used to balance differences in the baseline characteristics. The postoperative major morbidity and cancer-specific survival (CSS) of the two groups were compared and the independent factors that were associated with the two study endpoints were identified by multivariable regression analysis.ResultsOf the 1331 HCC patients enrolled in this study, 363 (27.27%) were elderly, while 968 (72.73%) were not. After PSM, 334 matched samples were obtained. In the propensity score matching (PSM) cohort, a higher rate of major morbidity was found in elderly patients (P = 0.040) but the CSS was similar in the two groups (P = 0.087). Multivariate analysis revealed that elderly age was not an independent risk factor associated with high rates of major morbidity (P = 0.117) or poor CSS (P = 0.873). The 1-, 3- and 5-year CSS rates in the elderly and non-elderly groups were 91.0% versus 86.2%, 71.3% versus 68.8% and 55.9% versus 58.0%, respectively. Preoperative alpha fetoprotein (AFP) level, Child‒Pugh grade, intraoperative blood transfusion, extended hemi hepatectomy, and tumour diameter could affect the postoperative major morbidity and preoperative AFP level, cirrhosis, Child‒Pugh grade, macrovascular invasion, microvascular invasion (MVI), satellite nodules, and tumor diameter were independently and significantly associated with CSS.ConclusionAge itself had no significant effect on the prognosis of elderly patients with HCC after hepatectomy. Hepatectomy can be safely performed in elderly patients after cautious perioperative management.

Nomogram based on clinical characteristics for predicting overall survival in gastric cancer patients with preoperative anemia.

Preoperative anemia is associated with increased postoperative morbidity and mortality and increased perioperative transfusion risk. For surgical patients, this affects physical and cognitive ability and quality of life, but it is an important and modifiable risk factor. To determine the effect of preoperative anemia on the prognosis of gastric cancer (GC) patients and generate a prognostic nomogram to predict the postoperative overall survival (OS) of GC patients with preoperative anemia. Clinicopathological and follow-up data of GC patients treated at Zhejiang Provincial People's Hospital (China) from 2010 to 2015 were collected. Independent prognostic factors were screened by univariate and multivariate Cox regression analyses. Then, these factors were used to construct a nomogram to predict 1-, 3-, and 5-year postoperative OS in preoperative anemic GC patients. The nomogram was assessed by calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Nine hundred and sixty GC patients were divided into two groups (preoperatively anemic and nonanemic), and postoperative survival analysis was performed on both groups, yielding a shorter postoperative survival for preoperatively anemic patients than for nonanemic patients. A total of 347 GC patients with preoperative anemia were included. Age, preoperative alpha-fetoprotein level, monocyte count, lymphocyte count, clinicopathological stage, liver metastasis, and GC type were identified as independent prognostic factors for OS. The area under the ROC curve (AUC) of the nomogram for predicting 1-, 3-, and 5-year OS was 0.831, 0.845, and 0.840, respectively, for the training cohort, and the corresponding AUC values in the validation cohort were 0.827, 0.829, and 0.812, respectively. Calibration curves and DCA indicated good performance of the nomogram. In all, we have successfully produced and verified a useful nomogram for predicting OS in GC patients with preoperative anemia. This nomogram based on a variety of clinicopathological indices can provide an effective prognostic assessment and help clinicians choose an appropriate treatment strategy for GC patients with preoperative anemia.

ASO Author Reflections: Impact of Surgical Margin Width on Prognosis After Resection of Hepatocellular Carcinoma Varies Based on Preoperative Alpha-Feto Protein and Tumor Burden Score.

ASO Author Reflections: Impact of Surgical Margin Width on Prognosis After Resection of Hepatocellular Carcinoma Varies Based on Preoperative Alpha-Feto Protein and Tumor Burden Score.

Impact of Surgical Margin Width on Prognosis Following Resection of Hepatocellular Carcinoma Varies on the Basis of Preoperative Alpha-Feto Protein and Tumor Burden Score.

We sought to examine the prognosticimpact of margin width at time of hepatocellular carcinoma (HCC) resection relative to the alpha-feto protein tumor burden score (ATS). Patients who underwent curative-intent hepatectomy for HCC between 2000 and 2020 were identified from a multi-institutional database. The impact of margin width on overall survival and recurrence-free survival was examined relative to ATS using univariable and multivariable analyses. Among 782 patients with HCC who underwent resection, median ATS was 6.5 [interquartile range (IQR) 4.3-10.2]. Most patients underwent R0 resection (n = 613, 78.4%); among patients who had an R0 resection, 325 (41.6%) had a margin width > 5mm while 288 (36.8%) had a 0-5 mm margin width. Among patients with high ATS, an increasing margin width was associated with incrementally better overall and recurrence-free survival. In contrast, among patients with low ATS, margin width was not associated with long-term outcomes. On multivariable Cox regression analysis, each unit increase in ATS was independently associated with a 7% higher risk of death [hazard ratio (HR) 1.07; 95% confidence interval (CI) 1.03-1.11, p < 0.001]. While the incidence of early recurrence was not associated with margin width among patients with low ATS, wider margin width was associated with an incrementally lower incidence of early recurrence among patients with high ATS. ATS, an easy-to-use composite tumor-related metric, was able to risk stratify patients following resection of HCC relative to overall survival and recurrence-free survival. The therapeutic impact of resection margin width had a variable impact on long-term outcomes relative to ATS.

Surgical treatment of hepatocellular carcinoma after Fontan operation: three case reports and review of the literature.

We herein describe three patients with Fontan-associated liver disease who developed hepatocellular carcinoma (HCC). The first patient was a 28-year-old woman who had undergone the Fontan operation (FO) at the age of 4years. She was diagnosed with HCC (cT4aN0M0, Stage IVA, UICC 8th edition), for which she underwent extended posterior right sectionectomy and partial hepatectomy of S2. She developed recurrence of peritoneal dissemination after 12months, and she was alive 18months after surgery. The second patient was a 43-year-old man who had undergone the FO at the age of 3years. He was diagnosed with HCC (cT2N0M0, Stage II), for which he underwent laparoscopic-assisted partial hepatectomy of S3. He remained free from recurrent HCC for 17months. The third patient was a 21-year-old woman who had undergone the FO at the age of 3years. She was diagnosed with HCC (cT3N0M0, Stage III), for which she underwent laparoscopic-assisted partial hepatectomy of S2 and S4. She remained free from recurrent HCC for 30months. We reviewed 18 surgical cases of HCC arising from Fontan-associated liver disease, including our 3 cases, and found that a high preoperative alpha-fetoprotein concentration might be a predictor of HCC recurrence.

Burned-out testicular germ cell tumors: a clinicopathological analysis of three cases

Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 μg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.

SP70 is a novel biomarker of hepatocellular carcinoma.

Tumor-specific protein 70 (SP70) was identified as a new biomarker associated with the proliferation and invasion of cancer cells. This study aimed to investigate the expression of SP70 in hepatocellular carcinoma (HCC) and assess its clinical value in the diagnosis and prediction of early HCC recurrence. A total of 1049 subjects from the First Affiliated Hospital of Nanjing Medical University were recruited in this study. Serum SP70, alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence II (PIVKA-II) were measured. The diagnostic performance for HCC was obtained using the receiver operating characteristic (ROC) curve, and recurrence-free survival (RFS) was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictive factors of RFS. SP70 was highly expressed in HCC cells and HCC tissue. Serum SP70 levels in the HCC group were significantly higher than in the benign liver diseases group and healthy control group (P<0.001). SP70 combined with AFP showed the best diagnostic performance (AUC=0.909, 95%CI [confidence interval]=0.890-0.929). Kaplan-Meier analysis revealed that patients with high SP70 levels had shorter median RFS than those with low SP70 levels (P=0.003). In addition, high SP70 levels were significantly associated with shorter RFS (P=0.037) in the AFP-negative subgroup. Univariate and multivariate analyses confirmed that preoperative serum SP70 level, serum AFP, tumor diameter and microvascular invasion were independent prognostic factors of RFS. SP70 is a promising biomarker in diagnosing HCC. High preoperative serum SP70 level is associated with an increased risk of early relapse and could be used as a valuable marker to predict early recurrence of HCC after resection.

Predictors and long-term prognosis of early and late recurrence for patients undergoing hepatic resection of hepatocellular carcinoma: a large-scale multicenter study.

Recurrence is common among patients undergoing hepatic resection for hepatocellular carcinoma (HCC), which greatly limits long-term survival. We aimed to identify predictors and long-term prognosis of early and late recurrence after HCC resection. Multicenter data of patients who underwent HCC resection between 2002 and 2016 were analyzed. Recurrence was divided into early (≤2 years) and late recurrence (>2 years after surgery). Predictors of early and late recurrence, and prognostic factors of post-recurrence survival (PRS) were identified by univariate and multivariate analyses. Among 1,426 patients, 554 (38.8%) and 348 (24.4%) developed early and late recurrence, respectively. Independent predictors associated with early recurrence included preoperative alpha-fetoprotein level >400 µg/L, resection margin <1 cm, and tumor size >5.0 cm, multiplicity, macrovascular and microvascular invasion, and satellites of the initial tumor at the first diagnosis of HCC; independent predictors associated with late recurrence included male, cirrhosis, and tumor size >5.0 cm, multiplicity, macrovascular and microvascular invasion, and satellites of the initial tumor. Patients with early recurrence had a lower likelihood of undergoing potentially curative treatments for recurrence (37.2% vs. 48.0%, P<0.001) and a worse median PRS (13.5 vs. 36.6 months, P<0.001) vs. patients who had late recurrence. Multivariate analysis revealed that early recurrence and irregular postoperative surveillance were independently associated with worse PRS [hazard ratio (HR) =1.250, 95% CI: 1.016-1.538, P=0.035; and HR =1.983, 95% CI: 1.677-2.345, P<0.001]. Predictors associated with early and late recurrence after curative resection for patients with HCC were generally same, although several did differ. Patients with late recurrence had better long-term survival than patients with early recurrence.

A Long-Term Outcome of the Patients with Sacrococcygeal Teratoma: A Bosnian Cohort.

Sacrococcygeal teratoma is an extragonadal germ cell tumor that develops during fetal and neonatal periods and is associated with significant perinatal morbidity and even mortality. This study aimed to determine the clinicopathologic characteristics, the clinical outcomes, and postoperative complications of sacrococcygeal teratoma cases in the low-volume pediatric surgery service in a developing country. The study included data from all sacrococcygeal teratoma cases diagnosed from 2011 to 2020. All the relevant clinicopathologic data were recorded and analyzed. A total of 7 pediatric (5 females and 2 males) patients with sacrococcygeal teratoma were identified, ranging in age from 3 to 222 days. A prenatal diagnosis was made in 57.1% of cases. The mean gestational age for all cases was 37.1 weeks (34-38 weeks), and the mean birth weight was 3285 g (range, 2300-4700 g). Preoperative alpha-fetoprotein levels had a mean value of 24.327 ng/mL (range, 649.7-110.600 ng/mL). The surgery involved resection of the primary tumor and coccygectomy in all cases. Three (42.9%) tumors were classified as Altman type II lesions, 2 (28.6%) tumors were type IV, and 2 remaining cases were types I and III, respectively. Histology was benign in 4 (57.1%) and immature in 3 patients (42.9%). The mean follow-up time was 101.4 months (30-146 months), with 2 recurrences of high-grade immature teratomas at 11 and 30 months following the surgery. Three patients had postoperative bladder and rectal dysfunctions. Sacrococcygeal teratomas are rare tumors associated with frequent postoperative dysfunctions. Recurrences may also be seen, particularly in immature, high-grade forms of sacrococcygeal teratomas.

Macrotrabecular-massive subtype-based nomogram to predict early recurrence of hepatocellular carcinoma after surgery.

To analyze the predictive factors on early postoperative recurrence of hepatocellular carcinoma (HCC) and to establish a new nomogram to predict early postoperative recurrence of HCC. A retrospective analysis of 383 patients who had undergone curative resection between February 2012 and September 2020 in our center was performed. The Kaplan-Meier method was used for survival curve analysis. Univariate and multivariate Cox regression were performed to identify independent risk factors associated with early recurrence, and a nomogram for predicting early recurrence of HCC was established. A total of 152/383 patients developed recurrence after surgery, of which 83 had recurrence within 1 year. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein level ≥400 ng/ml (P = 0.001), tumor diameter ≥5 cm (P = 0.009) and MVI (P = 0.007 and macrotrabecular-massive HCC (P = 0.003) were independent risk factors for early postoperative recurrence of HCC. The macrotrabecular-massive-based nomogram obtained a good C-index (0.74) for predicting early recurrence of HCC, and the area under the curve for predicting early recurrence was 0.767, which was better than the single American Joint Committee on Cancer T stage and Barcelona Clinic Liver Cancer stage. The nomogram based on macrotrabecular-massive HCC can effectively predict early postoperative recurrence of HCC.

Re-evaluation of the prognosis of alpha-fetoprotein-producing gastric cancer from a single center: a case series study.

Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is reported to have biologically aggressive features and poor prognosis. A relatively large number of patients with AFPGC have achieved a long-term prognosis after surgery in our institution. This study aimed to clarify the clinical features of and re-evaluate the long-term outcomes of AFPGC. This analysis involved 465 patients who underwent surgery for gastric cancer (GC) at our institute between 1996 and 2020. The clinical features and long-term outcomes of the 24 patients with AFPGC were assessed. The differences in clinicopathological characteristics between AFPGC and non-AFPGC patients were statistically analyzed. In patients with AFPGC, the median preoperative serum AFP level was 232 ng/mL. Tumor invasion of AFPGC was classified and clinical characteristics of AFPGC patients were as follows: nodal metastasis, simultaneous liver metastasis, with malignant cells in ascites, lymphatic, and venous involvement. Postoperative surveillance revealed adjuvant therapy in fourteen, recurrence in eight, and four patients died of GC. The 3- and 5-year overall survival (OS) rates were 85.2% and 75.7% in AFPGC patients and 79.6% and 77.7% in non-AFPGC patients, respectively. The log-rank test identified no significant difference in OS between AFPGC and non-AFPGC patients. Tumor depth, nodal, and venous involvement showed significant differences between AFPGC and non-AFPGC patients. AFPGC has aggressive biological features, but long-term prognosis after surgery does not seem to be as poor as claimed in previous studies. Therefore, it may be important to detect and start treatment early when surgery is feasible.