Impact of neoadjuvant chemotherapy on the difficulty and outcomes of laparoscopic and robotic major liver resections for colorectal liver metastases: A propensity-score and coarsened exact-matched controlled study

BackgroundMinimal invasive liver resections are a safe alternative to open surgery. Different scoring systems considering different risks factors have been developed to predict the risks associated with these procedures, especially challenging major liver resections (MLR). However, the impact of neoadjuvant chemotherapy (NAT) on the difficulty of minimally invasive MLRs remains poorly investigated.MethodsPatients who underwent laparoscopic and robotic MLRs for colorectal liver metastases (CRLM) performed across 57 centers between January 2005 to December 2021 were included in this analysis. Patients who did or did not receive NAT were matched based on 1:1 coarsened exact and 1:2 propensity-score matching. Pre- and post-matching comparisons were performed.ResultsIn total, the data of 5189 patients were reviewed. Of these, 1411 procedures were performed for CRLM, and 1061 cases met the inclusion criteria. After excluding 27 cases with missing data on NAT, 1034 patients (NAT: n = 641; non-NAT: n = 393) were included. Before matching, baseline characteristics were vastly different. Before matching, the morbidity rate was significantly higher in the NAT-group (33.2% vs. 27.2%, p-value = 0.043). No significant differences were seen in perioperative outcomes after the coarsened exact matching. After the propensity-score matching, statistically significant higher blood loss (mean, 300 (SD 128–596) vs. 250 (SD 100–400) ml, p-value = 0.047) but shorter hospital stay (mean, 6 [4], [5], [6], [7], [8][4], [5], [6], [7], [8] vs. 6 [5], [6], [7], [8], [9][5], [6], [7], [8], [9] days, p-value = 0.043) were found in the NAT-group.ConclusionThe current study demonstrated that NAT had minimal impact on the difficulty and outcomes of minimally-invasive MLR for CRLM.     

Pancreatic resections for metastases: A twenty-year experience from a tertiary care center

BackgroundLiterature data about pancreatic resections for metastases are limited to small series, so that the role of surgery in this setting remains unclear. We herein report our experience from a tertiary care center, analyzing the outcomes of patients who underwent pancreatic resections for metastases and discussing the role of surgical resection in their management.Materials and methodsFrom January 1999 to January 2019, 26 patients underwent pancreatic resections for metastases from renal cell carcinoma (RCC-group) or other primitive tumors (non-RCC-group). Details regarding pre-, intra-, post-operative course, and follow-up, prospectively collected in a database of pancreatic resection, were retrospectively analyzed and compared.ResultsRCC-group was composed of 21 patients, non-RCC-group of 5 patients. RCC-group presented a longer disease-free interval: 96.4 vs. 5.4 months (p < 0.001). In 9/21 patients (42.9%) of RCC-group the surgical resection of other organs or vascular structures was performed, while in non-RCC-group pancreatic resection alone was performed in all cases, p = 0.070. No local recurrence was reported in all cases. The systemic recurrence rate was 42.9% (9/21 patients) in RCC-group and 80% (4/5 patients) in non-RCC-group, p = 0.135. RCC-group presented a longer DFS and OS: 107.5 vs. 25.2 months (p = 0.002), and 109.1 vs. 36.2 months (p = 0.016), respectively.ConclusionsRadical pancreatic resection may confer a survival benefit for RCC metastases, while for other primitive tumors it should be applied more selectively. For RCC pancreatic metastases, an aggressive surgical approach, even in patient with locally advanced tumors, or associated extra-pancreatic localizations, or recurrent metastases should be taken in consideration.     

International Study Group of Pancreatic Surgery type 3 and 4 venous resections in patients with pancreatic adenocarcinoma:the Paoli-Calmettes Institute experience

IntroductionA new neoadjuvant regimen, together with more aggressive surgeries, appears to have increased the resectability rate in patients with pancreatic ductal adenocarcinoma (PDAC). Our study aimed to evaluate the outcomes of patients who underwent venous resection (VR) during pancreatectomies for PDAC.Materials and methodsBetween 2005 and 2017, 130 patients underwent pancreatectomies with type 3 or 4 (i.e., segmental resection without or with graft interposition, respectively) VR for PDAC. Patients’ characteristics, surgical techniques, perioperative management, pathological findings, and outcomes were recorded and compared during 2 inclusion periods: the landmark year for the introduction of the FOLFIRINOX regimen and the hyperspecialization of our pancreatic-surgery team was 2010.ResultsPerformance of pancreatectomies with VR steadily increased through the 2 inclusion periods. In the overall series (n = 130), the median overall survival time and the 5-year survival proportion were 26.3 months and 21%, respectively. Upon multivariate analysis, ASA score 3 (P = 0.01) and R1 resection margins (P < 0.01) were found to be negative independent factors influencing survival. Patients who underwent upfront VR (n = 47) had survival rates similar to those of patients who received neoadjuvant treatment (n = 83). After 2010, more complex VR were performed; however, no difference was found between the 2 periods with respect to postoperative courses, pathologic findings, or survival after a matching process based on patients’ characteristics and tumor stages.ConclusionOver the last 2 decades, VR during pancreatectomy has been confirmed as a safe procedure despite the increase in technical complexity. Disappointingly, we did not observe any dramatic survival improvement.     

Flow cytometric DNA analysis of fresh prostatic resections: Correlation with conventional prognostic parameters in patients with prostate cancer

Background. DNA ploidy analysis has been investigated as a prognostic indicator in prostate cancer. Most of the data is derived from retrospective studies using paraffin-embedded tissue. This method has drawbacks related to the quality of DNA histograms and uncontrolled data collection. Methods. DNA ploidy analysis of freshly resected prostatic tissue was prospectively compared with conventional prognostic variables in 97 men treated with radical prostatectomy for localized prostate cancer. Results. Regarding the patients, 31.9% were African American and 66% had pathologic Stages C or D1 disease. Only 9.6% of patients with Stages A2 and B had a prostate-specific antigen (PSA) value greater than 10 ng/ml, whereas 97% of patients with PSA values greater than 20 ng/ml had pathologic Stages C and D1. PSA levels correlated with Gleason score (P = < 0.05); 51% and 100% of patients with Gleason score 5–7 and 8–10, respectively, had PSA values greater than 10 ng/ml. Twenty-two patients (23%) had DNA aneuploid tumors. Comparisons of mechanical to enzymatic cell suspensions indicated that DNA aneuploidy was better preserved in mechanical cell preparations. DNA ploidy correlated with pathologic stage (P = < 0.05) and Gleason score (P = < 0.05). Fifteen of 79 patients (18.9%) with Gleason score 5–7 had DNA aneuploid tumors versus 71.4% of patients with Gleason score 8–10. PSA groups correlated with ploidy status (P = 0.01). Although the majority of patients (19 of 22) with DNA aneuploid tumors had elevated preoperative PSA levels, none had a PSA value greater than 50 ng/ml. Conclusions. DNA ploidy analysis correlated with established prognostic indicators in prostate cancer; however, its independent correlation with natural history and treatment outcome must be established for it to have an effect on therapeutic decisions.     

Pancreatic intraductal papillary mucinous neoplasms: Current diagnosis and management

Intraductal papillary mucinous neoplasms (IPMNs) represent approximately 1% of all pancreatic neoplasms and 25% of cystic neoplasms. They are divided into three types: main duct-IPMN (MD-IPPMN), branch duct-IPMN (BD-IPMN), and mixed type-IPMN. In this review, diagnostics, including clinical presentation and radiological investigations, were described. Magnetic resonance imaging is the most useful for most IPMNs. Management depends on the type and radiological features of IPMNs. Surgery is recommended for MD-IPMN. For BD-IPMN, management involves surgery or surveillance depending on the tumor size, cyst growth rate, solid components, main duct dilatation, high-grade dysplasia in cytology, the presence of symptoms (jaundice, new-onset diabetes, pancreatitis), and CA 19.9 serum level. The patient’s age and comorbidities should also be taken into consideration. Currently, there are different guidelines regarding the diagnosis and management of IPMNs. In this review, the following guidelines were presented: Sendai International Association of Pancreatology guidelines (2006), American Gastroenterological Association guidelines, revised international consensus Fukuoka guidelines (2012), revised international consensus Fukuoka guidelines (2017), and European evidence-based guidelines according to the European Study Group on Cystic Tumours of the Pancreas (2018). The Verona Evidence-Based Meeting 2020 was also presented and discussed.     

胰十二指肠切除改良胰管空肠吻合预防胰瘘

目的: 分析胰十二指肠切除术(PD)胰管空肠端侧粘膜对粘膜及胰管空肠套入式吻合方式,以其预防术后胰瘘发生。 方法: 2003年1月～2007年1月回顾性分析25例PD的临床资料,残胰的重建方式分别按胰管空肠粘膜对粘膜套入式端侧吻合,胰管支撑管胰液体外引流。 结果: PD24例术后恢复顺利,未发生胰瘘;1例术后腹腔创面广泛渗血,多器官功能衰竭围手术期死亡,其余随访无远期并发症。 结论: PD胰管空肠端侧粘膜对粘膜套入式吻合有明显避免胰瘘及并发症的发生,真正临床应用价值有待更大量的对照随机前瞻性大样本研究才能作出正确可靠的评价。     

Predictors of 30- and 90-day readmission following craniotomy for malignant brain tumors: analysis of nationwide data

Hospital readmissions are a major contributor to increased health care costs and are associated with worse patient outcomes after neurosurgery. We used the newly released Nationwide Readmissions Database (NRD) to describe the association between patient, hospital and payer factors with 30- and 90-day readmission following craniotomy for malignant brain tumor. All adult inpatients undergoing craniotomy for primary and secondary malignant brain tumors in the NRD from 2013 to 2014 were included. We identified all cause readmissions within 30- and 90-days following craniotomy for tumor, excluding scheduled chemotherapeutic procedures. We used univariate and multivariate models to identify patient, hospital and administrative factors associated with readmission. We identified 27,717 admissions for brain tumor craniotomy in 2013–2014, with 3343 (13.2%) 30-day and 5271 (25.7%) 90-day readmissions. In multivariate analysis, patients with Medicaid and Medicare were more likely to be readmitted at 30- and 90-days compared to privately insured patients. Patients with two or more comorbidities were more likely to be readmitted at 30- and 90-days, and patients discharged to skilled nursing facilities or home health care were associated with increased 90-day readmission rates. Finally, hospital procedural volume above the 75th percentile was associated with decreased 90-day readmission rates. Patients treated at high volume hospitals are less likely to be readmitted at 90-days. Insurance type, non-routine discharge and patient comorbidities are predictors of postoperative non-scheduled readmission. Further studies may elucidate potentially modifiable risk factors when attempting to improve outcomes and reduce cost associated with brain tumor surgery.     

Chemoradiation in Pancreatic Adenocarcinoma: A Literature Review

Adenocarcinoma of the exocrine pancreas has an annual incidence of 7,400 cases in the U.K. In comparison with other common cancers of solid organs, namely, breast, colorectal, and prostate cancer, pancreatic cancer has a high morbidity and mortality. Radical resection is possible in only 15%–20% of patients, and only 3%–4% of all patients presenting with this condition achieve long‐term control and cure. Various strategies in the form of neoadjuvant and adjuvant treatment have been employed over the years to improve outcome, with limited success. Systemic chemotherapy remains the gold standard in the metastatic setting in good performance status patients, and adjuvant chemotherapy after resection of localized and locally advanced cancer has been found to improve outcome. The role of radiotherapy, however, remains controversial and is an area that merits further investigation in well‐conducted multicenter trials at various stages of the disease in combination with systemic agents and exploiting recent advances in the delivery of radiotherapy. In this article, we review the published literature on the use of chemoradiation as a modality in various stages of pancreatic adenocarcinoma and highlight areas that future trials in this field should target for a way forward in this malignancy.     

胰腺癌中OASL的表达及其对癌细胞增殖和迁移的影响

目的探讨OASL的表达对胰腺癌细胞增殖和迁移能力的影响。方法GEPIA数据库分析OASL在胰腺癌组织和正常胰腺组织中的表达差异。TIMER数据库分析OASL表达与患者生存期的关系。TCGA数据库分析OASL表达与胰腺癌临床病理参数的相关性。shRNA技术敲减胰腺癌panc-1细胞中OASL基因的表达。慢病毒用于过表达胰腺癌panc-1细胞中OASL基因。MTT实验检测胰腺癌panc-1细胞的增殖能力,划痕实验及Transwell实验检测panc-1细胞的迁移能力,Westernblot实验检测与肿瘤增殖、迁移、侵袭相关蛋白的表达。结果胰腺癌组中的OASL表达量显著高于正常胰腺组织(P<0.05),且胰腺癌患者中OASL高表达患者与低表达患者相比具有较差的总生存期(P<0.05)。敲减OASL基因后,panc-1细胞的增殖和迁移能力均被抑制,而过表达OASL基因促进了panc-1细胞的增殖和迁移能力。敲减OASL后,p-STAT3蛋白表达增高,STAT3和BAK蛋白表达降低;过表达OASL后,p-STAT3蛋白表达降低,STAT3和BAK蛋白表达增高。结论OASL可能通过STAT3信号通路影响胰腺癌细胞增殖和迁移能力以及BAK表达来诱导细胞凋亡。     

Identification of K-ras Oncogene Mutations in the Pure Pancreatic Juice of Patients with Ductal Pancreatic Cancers

Pancreatic cancer is detected on the basis of morphological changes delineated by means of various image-diagnostic methods. However, differentiation between chronic pancreatitis and pancreatic cancer, especially at the early stage, is not always simple when based upon the morphological changes alone. Therefore, we attempted to elucidate K- ras mutations in the sediment of pure pancreatic juice (PPJ) containing exfoliated ductal pancreatic cancer cells. PPJ was collected endoscopically from 20 patients with pancreatic cancer (PC) and 18 patients with chronic pancreatitis (CP). Polymerase chain reaction and allele specific oligonucleotide dot blot hybridization for K- ras mutations were performed with the DNA extracted from these samples. A K- ras mutation at codon 12 was identified in the PPJ of 11/20 (55%) of the patients with PC. On the other hand, the same mutation was not identified in the PPJ of any patient with CP. Moreover, K- ras mutations at codons 13 and 61 were not recognized in the PPJ of any patient with either PC or CP. These findings suggested that the presence of a K- ras mutation at codon 12 in PPJ would be useful in confirming the diagnosis of PC.     

The prevalence of micronutrient deficiency in patients with suspected pancreatico-biliary malignancy: Results from a specialist Hepato-Biliary and Pancreatic unit

IntroductionThere is a paucity of information on micronutrient status in patients with pancreatico-biliary malignancies referred for surgery. Deficiency states could impact recovery from surgery. The purpose of this study was to investigate the frequency of deficiency states in our specialist Hepato-Biliary and Pancreatic (HPB) unit.MethodsPatients with suspected pancreatico-biliary malignancies referred to our surgical team between October 2019 and July 2020, and seen by a dietitian were included in the study. Serum levels of vitamins A, D, E, B₁₂, and folate, and minerals zinc, selenium, copper and iron were obtained.ResultsForty-eight patients were eligible for inclusion, 28 males and 20 females with a median age of 68 years. Pancreatic cancer was suspected in 40 patients, bile duct cancer in four patients, and duodenal cancer in four patients. Zinc, vitamin D, selenium and iron were the most frequently occurring micronutrient deficiencies. Zinc deficiency was found in 83% patients and vitamin D insufficiency in 57%. Selenium deficiency was less frequent but found in 24% cases, while iron deficiency suggested by low transferrin saturation was found in 23% patients.ConclusionsMicronutrient deficiencies and borderline status may be more frequent in this patient group than generally acknowledged. Routine analysis of specific vitamins and minerals may be useful to identify deficiency/sub-clinical deficiency states. Further more extensive studies are needed to inform practice and enable guideline development.     

Pancreatic cancer: Current and future treatment strategies

Pancreatic cancer is a disease with a high mortality rate and short survival, as a result of the high incidence of metastatic disease at diagnosis, the fulminant clinical course and the lack of successful therapeutic strategies. The administration of chemotherapeutic agents for the treatment of advanced disease has failed and currently, research focuses on the understanding of molecular pathways in order to investigate the role of targeted therapy. Trials on adjuvant and neo-adjuvant therapy of pancreatic cancer are also ongoing. This review presents the recent developments with newer chemotherapeutic and molecular-targeted agents, identifying the efforts for individualized treatment strategies.     

Pancreatic metastases from ductal and lobular carcinomas of the breast

The pancreas is an uncommon target for metastases from other primary tumours. We discuss clinical, diagnostic and therapeutic aspects of pancreatic metastases through presentation of two surgically treated cases of metastases originating from breast cancer.     

健择联合奥沙利铂双周方案治疗胰腺癌作用探讨

目的:比较健择联合奥沙利铂双周化疗方案和健择单药每周方案治疗胰腺癌的疗效及不良反应。方法:选择我科2003年11月至2005年1月胰腺癌患者30例,采用健择联合奥沙利铂双周化疗方案(设为A组:健择1000mg/m²d₁,奥沙利铂100mg/m²d₂,每隔14天进行1个周期)进行治疗;随机选择同时期使用健择单药方案(设为B组:健择1000mg/m²单药,每周1次,连续3周,随后休息1周为1个周期)化疗的胰腺癌患者30例做对照,比较两方案治疗胰腺癌的疗效和不良反应的差异。结果:A组PR3例,SD21例,PD6例,1年生存率为16.7%(5/30)。B组PR1例,SD14例,PD15例,1年生存率为10.0%(3/30)。化疗的主要不良反应包括:恶心、呕吐,骨髓抑制和外周神经毒性。结论:健择加奥沙利铂双周化疗方案在抑制肿瘤发展、延长生存期方面略优于传统健择单药方案,而两者不良反应大体相当,推荐临床使用。