Research progress of spontaneous ruptured hepatocellular carcinoma: Systematic review and meta-analysis.

Background: Spontaneously ruptured hepatocellular carcinoma (rHCC) with hemorrhage is characterized by rapid onset and progression. The aim of this systematic review was to explore the current studies on rHCC with hemorrhage and determine the optimum treatment strategy. Method: The PubMed, Web of Science, Embase, and the Cochrane Library databases were searched for studies reporting survival outcomes with comparison between emergency resection (ER) and transarterial embolization following staged hepatectomy (SH) were included by inclusion and exclusion criteria, the perioperative and survival data were statistically summarized using Review Manager 5.3 software. Result: A total of 8 retrospective studies were included, with a total sample size of 556, including 285 (51.3%) in the ER group and 271 (48.7%) in the SH group. The perioperative blood loss and blood transfusion volume in the SH group were less than those in the ER group, and there were no significant differences in the operative time, incidence of complications, mortality and recurrence rate of tumors between the two groups. The 1-, 2-, 3-year overall survival and 1-, 2-, 3-, 5-year disease-free survival of the ER group were not significantly different from those of the SH group, and the 5-year overall survival rate of ER group was lower than that of the SH group (hazard ratios=1.52; 95% confidence intervals: 1.14-2.03, P=0.005). Conclusion: There was no significant difference in the short-term efficacy of ER or SH in the treatment of ruptured HCC, and SH was superior to ER in the long-term survival.

Survival of Patients Subjected to Hepatectomy After Spontaneous Rupture of Hepatocellular Carcinoma: A Meta-analysis of High-quality Propensity Score Matching Studies.

Background: The spontaneous rupture of hepatocellular carcinoma (HCC) is associated with high mortality rates, and liver resection can provide better outcomes than other available treatments. However, the survival length of patients subjected to hepatectomy after spontaneous rupture of hepatocellular carcinoma remains controversial. Method: Articles reporting the comparison of the survival outcome between patients with rupture HCC (rHCC) and non-rupture HCC (nrHCC) from the inception until December 31, 2021 by PubMed, Web of Science, OVID, and the Cochrane Library databases were included. The high-quality propensity score matching analysis was used to investigate the impact of rupture on disease-free survival (DFS) and overall survival (OS) between the rHCC and nrHCC group with no heterogeneity. Result: A total of 606 patients from six cohort studies were included. The major baseline characteristics of the eligible patients were well balanced between rHCC and nrHCC group. The 1-, 3-, and 5-year hazard ratios of DFS were 3.45 (95% confidence interval [CI] 2.54-4.68), 3.63 (95% CI 2.87-4.60), and 3.72 (95% CI 2.93-4.72), respectively. The 1-, 3-, and 5-year hazard ratios of OS were 5.01 (95% CI 3.26-7.69), 5.49 (95% CI 4.08-7.39), and 4.20 (95% CI 3.20-5.51), respectively. Conclusion: The present meta-analysis demonstrated that the DSF and OS were significantly shorter in the rHCC group than in the nrHCC group, thus revealing that spontaneous HCC rupture was a predictor of poor survival.

Treatment of Metastatic Primary Extramammary Paget Disease With Combination Anlotinib and Tislelizumab: A Case Report and Review of the Literature.

Extramammary Paget's disease (EMPD) is a rare cutaneous neoplasm with distant metastases and a poor prognosis. We report the case of a 63-year-old male patient exhibiting stage IV primary EMPD with neuroendocrine differentiation, and harboring a somatic mutation in AMER1. After four cycles of Anlotinib combined with Tislelizumab, the patient achieved partial response for the metastatic lesions according to mRECIST1.1 criteria. Total positron emission tomography and computed tomography (PET-CT) scans revealed a significant reduction in SUV from 18.9 to 5.3, and the serum CEA decreased to normal levels after the treatment regimen. However, the patient developed fractures of the fourth and fifth thoracic vertebrae during the treatment. Therefore, percutaneous vertebroplasty was performed, and the patient experienced severe postoperative pneumonia and died from pulmonary encephalopathy and respiratory failure in June 2021. The overall and progression-free survival of the patient after diagnosis were 9 and 8 months, respectively. During the systemic treatment, the patient suffered grade 1 rash in the back and thigh and grade 1 hypertension. Nevertheless, the combination treatment of anlotinib and tislelizumab had a favorable clinical outcome and provided a survival advantage, and should be considered a therapeutic option for patients with AMER1-mutant metastatic EMPD.

Lenvatinib Plus Immune Checkpoint Inhibitors Improve Survival in Advanced Hepatocellular Carcinoma: A Retrospective Study.

BACKGROUND: Nivolumab and pembrolizumab disrupt the programmed cell death-1 immune checkpoint and display promising efficacy and safety results in advanced hepatocellular carcinoma (HCC). However, the benefits remain limited. The preliminary results of lenvatinib (LEN) combined with immune checkpoint inhibitors (ICIs) reveal that the combinations were well-tolerated and encouraging. This study aimed to analyze the safety and efficacy of LEN plus ICIs in a real-world cohort of patients with advanced HCC. METHOD: Between June 4, 2017, and June 30, 2019, 16 patients received LEN plus nivolumab, and 13 patients were treated with LEN plus pembrolizumab, with the confirmed advanced HCC retrospectively analyzed. The clinical parameters, as well as the outcomes, were assessed. RESULTS: All the patients had Barcelona Clinical Liver Cancer Stage C. LEN with ICIs was used as systemic second-, third-, and fourth-line treatments in seven (24.1%), 14 (48.3%), and eight (27.6%) patients, respectively. At the time of data cutoff, six patients (37.5%) were still receiving LEN with nivolumab, while another six patients (46.2%) were still receiving LEN with pembrolizumab. An objective response was recorded in seven patients (25.9%), while the best overall responses were from one complete response and six partial responses. The 6- and 12-month over survival (OS) rates were 62.6% and 53.7%, respectively. Furthermore, the 6- and 12-month progression-free survival (PFS) rates were 43.5% and 31.8%, respectively. In the subgroup analyses, the 6- and 12-month OS and PFS rates for patients treated with LEN plus nivolumab were 62.5% and 52.1%, respectively, and 43.8% and 30.0%, respectively. The 6- and 12-month OS and PFS rates for patients treated with LEN plus pembrolizumab were 51.3% and 51.3%, respectively, and 49.2% and 49.2%, respectively. A total of 11 (31%) deaths were reported in this study, four of which were attributed to grade 5 adverse events presented as fatal treatment-related hepatitis. CONCLUSION: The combination of LEN and ICIs is a promising new strategy for the treatment of HCC patients. However, high-grade hepatic toxicity was observed and further evaluation of this combination is still required.

The Efficacy of Combined Cisplatin and Nanoparticle Albumin-Bound Paclitaxel in a Stage IV Pancreatic Squamous Cell Carcinoma Patient With a Somatic BRCA2 Mutation: A Case Report.

Pancreatic squamous cell carcinoma (SCC) is a rare primary pancreatic malignancy with a poor prognosis. The median overall survival (OS) for metastatic setting is only 4 months and the optimal management remains poorly defined. In the present study, we report a 52-year-old female patient with stage IV primary SCC of the pancreas harboring a deleteous BRCA2 somatic mutation. After 10 cycles of chemotherapy of cisplatin combined with nanoparticle albumin-bound paclitaxel, metastatic lesions in the liver and lymph nodes achieved radiographic complete responses and pancreatic lesion shrank from 5.7 to 1.5 cm in diameter. The patient subsequently underwent a posterior radical antegrade modular pancreatosplenectomy with R0 resection and residual liver lesions were also resected. After 3 months, a tumor relapsed in the liver. She was then treated with olaparib combined with pembrolizumab and achieved stable disease on the liver lesion. The patient eventually died from cerebral hemorrhage with a long OS of 21 months. Our case demonstrated a favorable clinical activity and survival advantage of the combined cisplatin and nanoparticle albumin-bound paclitaxel, which might serve as a therapeutic option for the patient with BRCA-mutant pancreatic SCC.

Meta-analysis of Percutaneous vs. Surgical Approaches Radiofrequency Ablation in Hepatocellular Carcinoma.

Background: Radiofrequency ablation (RFA) is a curative modality for hepatocellular carcinoma (HCC) patients who are not suitable for resection. It remains controversial whether a surgical or percutaneous approach is more appropriate for HCC. Method: A search was performed on the PubMed, Web of Science, Embase, and Cochrane Library databases from the date of database inception until April 17, 2021. Studies reporting outcomes of comparisons between surgical RFA (SRFA) and percutaneous RFA (PRFA) were included in this study. The meta-analysis was performed using the Review Manager 5.3 and Stata 12.0 software. Result: A total of 10 retrospective studies containing 12 cohorts, involving 740 patients in the PRFA group and 512 patients in the SRFA group, were selected. Although the tumor size in PRFA group was smaller than the SRFA group (p = 0.007), there was no significant difference in complete ablation rate between the SRFA and PRFA groups (95.63% and 97.33%, respectively; Odds ratio [OR], 0.56; 95% confidence intervals [CI], 0.26-1.24; p = 0.15). However, the SRFA group showed a significantly lower local tumor recurrence than the PRFA group in the sensitivity analysis (28.7% in the PRFA group and 21.79% in the SRFA group, respectively; OR, 1.84; 95% CI, 1.14-2.95; p = 0.01). Pooled analysis data showed that the rate of severe perioperative complications did not differ significantly between the PRFA and SRFA groups (14.28% and 12.11%, respectively; OR, 1.30; 95% CI, 0.67-2.53; p = 0.44). There was no significant difference in the 1-, 3-, and 5-year overall survival rates, as well as the 1- and 3-year disease-free survival (DFS) between the PRFA and SRFA groups. The 5-year DFS of the PRFA group was significantly lower than the SRFA group (hazard ratio 0.73; 95% CI 0.54-0.99). Conclusion: Based on our meta-analysis, the surgical route was superior to PRFA in terms of local control rate. Furthermore, the surgical approach did not increase the risk of major complications.

Is anatomical resection necessary for early hepatocellular carcinoma? A single institution retrospective experience.

Aim: The present study aimed to determine whether anatomical resection was necessary for early hepatocellular carcinoma. Methods: A log-rank test or two-stage test was used for univariate analysis. A Cox proportional hazards model was used for multivariable analysis. Results: For patients without microvascular invasion, a resection margin ≥1 cm provided the longest recurrence-free survival time regardless of whether they underwent anatomical resection (p = 0.005) or nonanatomical resection (p = 0.006). For patients with microvascular invasion, anatomical resection combined with a resection margin ≥1 cm provided the longest recurrence-free survival time compared with other treatments (p = 0.001). Conclusion: Anatomical resection was not necessary for patients without microvascular invasion. However, for patients with microvascular invasion, both anatomical resection and a resection margin ≥1 cm were necessary.

Surgical outcomes between patients with and without a cirrhotic liver undergoing laparoscopic liver resection: A meta-analysis.

BACKGROUND: Laparoscopic surgery in patients with liver cirrhosis (CL) is considered to be challenging. Recent studies have shown that laparoscopic liver resection (LLR) is more beneficial of reduced operative stress and postoperative complications in patients with CL. AIM: A meta-analysis was done to review the currently available published data comparing LLR for patients with CL versus those non-cirrhosis of the liver (NCL). METHODS: The electronic databases of PubMed, Wiley, Web of Science, Embase, and the Cochrane Library were searched from date of inception to January 29, 2018. Studies reporting a comparison of outcomes and methods of LLR in CL and NCL groups were included. The studies were evaluated using the modified Newcastle-Ottawa Scale. RESULTS: A total of 1573 patients from six cohort studies were included in final analysis. The CL group had a slightly shorter operative time compared with the NCL group (weighted mean difference [WMD], 18.78min shorter; 95% confidence interval [CI], -43.54-5.98; P=0.14) and delayed hospital stay (WMD, 1.26 days longer; 95% CI, -0.05-2.56; P=0.06). Blood loss, blood transfusion rate, mortality, and conversion rate did not differ significantly between the groups. CONCLUSIONS: LLR is safe and feasible in the CL compared with the NCL groups. Our present review indicates that LLR should be considered when selecting surgery for patients with CL.

Clinicopathologic characteristics, laboratory parameters, treatment protocols, and outcomes of pancreatic cancer: a retrospective cohort study of 1433 patients in China.

OBJECTIVES: The prognosis of people with pancreatic cancer is extremely unfavorable. However, the prognostic factors remain largely undefined. We aimed to perform comprehensive analyses of clinicopathologic characteristics, laboratory parameters, and treatment protocols for exploring their role as prognostic factors of pancreatic cancer. METHODS: Patients diagnosed with pancreatic cancer and hospitalized at the China National Cancer Center between April 2006 and May 2016 were enrolled in this retrospective cohort study. Clinicopathologic characteristics, laboratory parameters, and treatment protocols were compared among patients at different stages of the disease. The association between these factors and overall survival (OS) was analyzed using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: The present study included 1,433 consecutive patients with pancreatic cancer. Median OS was 10.6 months (95% confidence interval [CI] 9.8-11.3 months), with 1-, 3-, and 5-year survival rates of 43.7%, 14.8%, and 8.8%, respectively. Cox multivariate analysis findings identified the following factors as independent predictors of OS: gender (female vs male, hazard ratio 0.72, 95% CI [0.54-0.95]); elevated total bilirubin (TBil; 1.82, 1.34-2.47); elevated carbohydrate antigen 19-9 (CA19-9; 1.72, 1.17-2.54); tumor being located in pancreatic body and tail (1.52, 1.10-2.10); advanced T stage (T3-4 vs T1-2, 1.62, 1.15-2.27); lymph node metastasis (1.57, 1.20-2.07); distant metastasis (1.59, 1.12-2.27); the presence of surgical resection (0.53, 0.34-0.81); and the presence of systemic chemotherapy (0.62, 0.45-0.82). CONCLUSIONS: Being male, elevated TBil and carcinoembryonic antigen, tumor being located in pancreatic body and tail, advanced T stage, lymph node and distant metastasis, the absence of surgical resection, and the absence of systematic chemotherapy were associated with worse OS in patients with pancreatic cancer.

Clinicopathologic features, surgical treatments, and outcomes of small bowel tumors: A retrospective study in China.

BACKGROUND: Small bowel tumors are relatively rare. Accumulation of data regarding their clinical presentation, pathologic features, prognostic factors, treatment modalities, and outcome has been an issue. We summarize the clinicopathologic features and evaluate the long-term outcome of patients with small bowel tumors who underwent surgery. METHODS: This is a retrospective study of medical records of 456 patients with small bowel tumors treated surgically at a Cancer Hospital between 1999 and 2016. RESULTS: The study included 275 males (60.3%) and 181 females (39.7%). Small bowel tumors were difficult to diagnose because of non-specific symptoms. The most common symptoms were alimentary symptoms (56.8%) and abdominal pain (37.3%). Final histopathology revealed 241 adenocarcinomas (52.9%), 153 gastrointestinal stromal tumors (GISTs; 33.6%), 16 neuroendocrine tumors (NETs; 3.5%), and 46 other types of tumors (10.1%). The 456 surgeries performed included 153 pancreaticoduodenectomies, 241 limited duodenum resections, 60 palliative bypass surgeries, and 2 abdominal explorations. The 5-year overall survival and progression-free survival rates for patients with small bowel tumor were 57.2% and 44.6%, respectively. Adenocarcinomas resulted in the worst overall survival compared to GISTs or NETs, and tumors with duodenal location resulted in a worse survival compared to those with non-duodenal location. CONCLUSION: Surgery is the mainstay of treatment for small bowel tumors. Adenocarcinomas and duodenal involvement seem to contribute to poor outcomes.

Perivascular epithelial cell tumor (PEComa) of the pancreas: A case report and review of literature.

RATIONALE: Perivascular epithelial cell tumors (PEComas) of the pancreas are rare mesenchymal tumors and, to our knowledge, only 20 cases have been reported to date. PATIENT CONCERNS: We report a 43-year-old female who presented with upper abdominal pain for 1 year. She underwent an exploratory laparotomy at a local hospital, which failed to resect the tumor. Five months later, she came to the Chinese National Cancer Center for surgery. Preoperative imaging revealed an 11.5-cm-sized mass located in the head of the pancreas. At the microscopic level, the tumor was composed of epithelioid and spindle cells possessing clear to focally granular eosinophilic cytoplasm, which grew in a nested and alveolar pattern around blood vessels. The tumor cells showed immunoreactivity for human melanoma black 45 (HMB-45), but did not express epithelial or endocrine markers. DIAGNOSES: Pancreatic PEComa. INTERVENTIONS: Pancreaticoduodenectomy, partial hepatectomy, and vascular replacement were performed. After the surgery, the patient received 4 cycles of chemotherapy. OUTCOMES: The patient is free of recurrence and metastasis 1.5 years after surgical resection. LESSONS: PEComa should be recognized as a preoperative differential diagnosis of pancreatic tumors. For treatment, removal of the tumor should be attempted, and in the case of tumors with malignant tendencies, the addition of chemotherapy should be considered.

Duct-to-mucosa versus invagination pancreaticojejunostomy after pancreaticoduodenectomy: a meta-analysis.

OBJECTIVE: We aimed to compare the two most commonly used pancreatico-jejunostomy reconstruction techniques-duct-to-mucosa and invagination. METHODS: Databases, including MEDLINE, EMBASE, Cochrane Library, and several clinical trial registration centers were searched. Randomized controlled trials that compared duct-to-mucosa and invagination pancreaticojejunostomy techniques after pancreaticoduodenectomy were included and analyzed. RESULTS: In total, seven RCTs were included, involving 850 patients. The difference in postoperative pancreatic fistula rate between the duct-to-mucosa and invagination pancreaticojejunostomy was not significant (RR = 1.03, 95% CI = 0.76-1.39, P = 0.86). There was no significant difference in clinically relevant postoperative pancreatic fistula between the two groups (RR = 0.78, 95% CI = 0.15-3.96, P = 0.77). The overall morbidity, overall mortality, delayed gastric emptying, intra-abdominal collection, reoperation rate, and length of hospital stay between the two groups were not significantly different. Sensitivity analysis showed that the meta-analysis was stable. Further, no significant publication bias was seen. CONCLUSIONS: Duct-to-mucosa and invagination pancreaticojejunostomy techniques after pancreaticoduodenectomy were comparable in terms of postoperative pancreatic fistula incidence and other parameters.