Journal Of Gastrointestinal Oncology Research Articles

Current research status of transarterial therapies for hepatocellular carcinoma

With continuous advancements in interventional radiology, considerable progress has been made in transarterial therapies for hepatocellular carcinoma (HCC) in recent years, and an increasing number of research papers on transarterial therapies for HCC have been published. In this editorial, we comment on the article by Ma et al published in the recent issue of the World Journal of Gastro intestinal Oncology: “Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC”. We focus specifically on the current research status and future directions of transarterial therapies. In the future, more studies are needed to determine the optimal transarterial local treatment for HCC. With the emergence of checkpoint immunotherapy modalities, it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.

Application of the CARE guideline as reporting standard in the Journal of Gastrointestinal Oncology

Application of the CARE guideline as reporting standard in the Journal of Gastrointestinal Oncology

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancy.

Peritoneal surface malignancies have historically presented a treatment challenge for clinicians. Not infrequently, epithelial cancers can seed the peritoneal cavity. Neoplasms of the appendix can result in peritoneal dissemination of disease and pseudomyxoma peritonei; in colon cancer, up to 25% with recurrent disease will develop a peritoneal surface predominant pattern of recurrence (1), and among those resected advanced gastric cancer, the majority of patients who recur in the first five years following surgery will develop peritoneal disease (2). Among the approximately 21,290 cases of ovarian cancer cases estimated to be diagnosed in 2015 (3), most will present in an advanced disease state, many with evidence of peritoneal carcinomatosis. In addition to epithelial derived cancers, 10-15% of the approximately 2,500 cases of malignant mesothelioma diagnosed in the U.S. will develop in the peritoneal cavity (4). For all these tumor histologies, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered in the treatment algorithm for selected patients. Over time, CRS/HIPEC has seen an increased utilization in treating select patients with peritoneal disease patterns previously considered inoperable, and has been associated with favorable survival outcomes. In patients with colorectal peritoneal carcinomatosis, a recent retrospective study of 539 patients undergoing a complete cytoreduction reported a median overall survival of 32.6 months (5). No doubt these observed improved outcomes compared to historical cohorts are multifactorial, reflecting improvements in systemic therapies, refinements in surgical techniques and perioperative care, and a better understanding of tumor biology contributing to better patient selection for surgery. Nonetheless, the remarkably favorable data are compelling and speak for the importance of consideration of CRS/ HIPEC in the context of a multidisciplinary approach for patients with peritoneal surface malignancy. This issue of Journal of Gastrointestinal Oncology (JGO) focuses on CRS/HIPEC and its application for various cancers. A paper led by the editors highlight some of the important historical developments in the evolution of CRS and HIPEC. Dr. Paul Sugarbaker and colleagues share their extensive expertise discussing surgical techniques of CRS/ HIPEC and pharmacology of intraperitoneal chemotherapy, while Dr. Goodman provides an excellent review of the selection of chemotherapeutic agents used for this procedure. Dr. Low presents an interesting summary on the use of MRI in the pre-operative evaluation and surveillance of patients being considered for or treated with CRS/HIPEC. Finally, each of the five tumor histologies discussed above is considered in depth in a separate manuscript, including two original papers studying CRS/HIPEC for high grade appendiceal cancer and ovarian cancer. Also in this issue is an important section on quality issues pertaining to CRS/HIPEC, including a review paper discussing the morbidity and mortality associated with the procedure. These procedures can be extensive, and not without risk, and consideration of these factors in the clinical decision making is essential. Dr. Lambert provides a very thoughtful synopsis of the palliative role of CRS/HIPEC, and Dr. Turaga discusses the impact of surgical volume in centers of these procedures on surgical outcomes. Dr. Votanopoulos presents a review of the indications and outcomes following repeat HIPEC surgery, which can be sometimes considered in select patients. Finally, Dr. Nash discusses current

Applying tumor genotyping and new clinical approaches to the management of colorectal cancer.

The last two decades have seen a dramatic improvement in outcomes for patients with metastatic colorectal cancer (mCRC) with median survival now more than 30 months. This improvement in outcomes has come from a multidisciplinary approach to the care of patients with mCRC that combines systemic chemotherapy with improved surgical techniques, sophisticated radiologic interventions, and local therapy, and from the use of targeted drugs that have ushered in an era of genomic analysis in the standard care of mCRC. Treatment of mCRC is now individualized both based on pattern and extent of metastatic disease and tumor genetics, particularly mutations in oncogenes, such as KRAS, NRAS, and BRAF, and inactivation of the mismatch repair enzymes. In this special issue of the Journal of Gastrointestinal Oncology (JGO), applying tumor genotyping and new clinical approaches to the management of colorectal cancer, experts in the field review key advances in the management of CRC patients. The topics addressed in this issue encompass a variety of timely themes. Several articles address the use of genetic information in the management of CRC. Sylvester and Vakiani discuss genetic progression in mCRC and tumor heterogeneity between primary and metastatic CRC. Kawakami, Zaanan, and Sinicrope review implications of mismatch repair-deficient status on the management of early stage colorectal cancer. Clarke and Kopetz summarize the emerging understanding of BRAF mutant CRC as a distinct subset in CRC, and Corcoran discusses exciting early results in the targeting of these tumors. Finally, Lipsyc and Yaeger discuss recent data that oncogene mutations may affect the pattern of metastases of CRC. Several authors discuss advances in the treatment of patients with limited metastatic disease. McAuliffe, Qadan, and D’Angelica review advances in liver resection and hepatic arterial therapy for patients with colorectal cancer liver metastases. Ridge and Solomon review the use of radiofrequency ablation to treat colorectal lung metastases. Guend, Patel, and Nash discuss advances in the treatment of peritoneal-limited colorectal metastases and the use of intraperitoneal therapies. We believe this special issue of the JGO addresses many of the challenges and new approaches in the management of CRC. We hope you find it informative and enjoyable.

Pancreas cancer: why bother?

Pancreas cancer: why bother?

Ca19-9 and pancreatic cancer: Is it really that good?

In the current issue of Journal of Gastrointestinal Oncology, Ballehaninna and Chamberlain (1) provide a comprehensive appraisal of the utility of Ca19-9 in pancreatic cancer. The authors suggest a number of roles for Ca19-9 including: (I) As a diagnostic and screening tool in symptomatic patients; (II) In the assessment of tumour stage and respectability; (III) As a biomarker of prognosis following resection; (IV) In the assessment of response to chemotherapy; (V)As a predictor of post-operative recurrence. Indeed, the only area where Ca19-9 would not appear to be useful is in population screening. However, in analyzing each of these areas in turn, it is clear that there is a major limitation to the use of Ca19-9 as the universal biomarker in pancreatic cancer, namely what is the optimal cut off level for assessment? Each of the areas evaluated demonstrated marked variation in median levels of Ca19-9 for the variable assessed, and likewise the cut-off levels utilized for determining outcome measures. This leaves the clinician with the quandary as to what levels to use for basing their clinical decisions. Certainly a tumour marker whose diagnostic threshold varies would not be optimal, and would lead to a great deal of confusion. Indeed, as a result of the diagnostic overlap, the American Society of Clinical Oncology does not currently advocate its use for screening, evaluation of resectability or disease follow-up (2). There are a number of reasons to account for the variations in the Ca19-9 levels reported in the individual studies. The authors highlight the fact that between 1 in 10 and 1 in 20 patients with pancreatic cancer will not express Ca19-9 at all. There are also racial and gender variations in expression of Ca19-9 with highest levels observed in Caucasians (3). Ca19-9 is well known to be elevated in benign conditions (4), as acknowledged in the review, and these must be taken into consideration in relation to the diagnosis of malignancy. The confusion caused by obstructive jaundice in interpreting Ca19-9 levels is also well documented. It is well known that benign pancreato-biliary disease may cause a rise in Ca19-9, usually related to biliary obstruction. In interpreting Ca19-9 levels in an individual believed to have pancreatic cancer it is important for the clinician to be aware whether a stent was inserted and if so was the Ca19-9 level taken pre-or post-stenting. Marrelli and colleagues (5) reported that bilirubin levels fall in patients with benign disease following stenting but remain elevated in those with malignant disease. Furthermore it has been shown that for benign disease the Ca19-9 levels correlate with bilirubin but for malignant disease these to variables are independent of each other (6). A further factor in the confusion is the term that is often interchangeably used for pancreatic cancer. Traditionally, series of pancreatic resections have indicated a predominance of pancreatic carcinoma but with more accurate pathological evaluation (7) the prevalence of pancreatic adenocarcinoma is lower and that of distal common bile duct cholangiocarcinoma higher, with similar prevalence for ampullary lesions (8). The Ca19-9 levels of these tumours, when assessed separately are significantly different, and so failure to accurately characterize the nature of the periampullary lesion will certainly affect the assessment of Ca19-9 (6). Likewise, histopathological assessment of the lesions according to the format popularised by Verbeke (7) will radically alter assessment of tumour resection status and of stage that in turn may account for the variation in data in relation Ca19-9 and disease stage. Despite the questions raised regarding Ca19-9, it is certainly the most useful clinical biomarker we have for pancreatic cancer. However, it is clear that currently, at least, there is not one level that can be agreed upon to determine good and poor prognosis tumours. It is imperative therefore that biomarkers such as Ca19-9 are interpreted in a multi-disciplinary team setting where the patient's status, such as the relationship of the Ca19-9 to pre-operative stenting and concurrent disease processes, is clear when clinical decisions are being made. In such a setting it is likely to be a much more powerful tool. Finally, given the vogue for consensus statements, it would be appropriate timing for such a conference to evaluate Ca19-9 and its role in pancreatic cancer and to set cut of values for Ca19-9 against which future studies can be compared. Such a process for carcinoembryonic antigen levels in pancreatic cystic lesions lead to the Sendai guidelines (9) adopting a CEA level of ≥192 ng/mL as that for determining if a cyst deemed positive for CEA or not. Such a process for Ca19-9 would, within a short period of time, through audit processes, allow confirmation that such guideline values were correct and would aid all clinicians managing pancreatic cancer.