Patients with cancer should appropriately receive antiemetic therapies against chemotherapy-induced nausea and vomiting (CINV). Antiemetic guidelines play an important role in managing CINV. ...Accordingly, the first Japanese antiemetic guideline published in 2010 by the Japan Society of Clinical Oncology (JSCO) has considerably aided Japanese medical staff in providing antiemetic therapies across chemotherapy clinics. With the yearly advancements in antiemetic therapies, the Japanese antiemetic guidelines require revisions according to published evidence regarding antiemetic management worldwide. A revised version of the first antiemetic guideline that considered several upcoming evidences had been published online in 2014 (version 1.2), in which several updated descriptions were included. The 2015 JSCO clinical practice guideline for antiemesis (version 2.0) (in Japanese) has addressed clinical antiemetic concerns and includes four major revisions regarding (1) changes in emetogenic risk categorization for anti-cancer agents, (2) olanzapine usage as an antiemetic drug, (3) the steroid-sparing method, and (4) adverse drug reactions of antiemetic agents. We herein present an English update summary for the 2015 JSCO clinical practice guideline for antiemesis (version 2.0).
Background
Accurate identification of tumor sites during laparoscopic colorectal surgery helps to optimize oncological clearance. We aimed to assess the timing of the local injection preoperatively ...and clarify the usefulness and limitation of tumor site marking using indocyanine green (ICG) fluorescence imaging.
Methods
Consecutive patients who underwent primary colorectal cancer surgery from September 2017 to January 2019 were included. Preoperatively, lower endoscopy was used to inject the ICG solution into the submucosal layer near the tumor. During laparoscopic surgery, ICG fluorescence marking as the tumor site marking was detected using a laparoscopic near-infrared camera system. The detection rate and factors associated with successful intraoperative ICG fluorescence visualization including the interval between local injection and surgery were evaluated.
Results
One hundred sixty-five patients were enrolled. Using the laparoscopic near-infrared system, the intraoperative detection rates of ICG marking were 100% for ICG injection within 6 days preoperatively, 60% for injection between 7 and 9 days preoperatively, and 0% for injection earlier than 10 days preoperatively. There were no complications associated with ICG marking. Additionally, this method did not disturb the progress of the surgical procedure because injected ICG in the submucosal layer did not cause any tissue inflammation, and if ICG spilled into the serosa, it was invisible by white light.
Conclusion
Advantages of ICG fluorescence tumor site marking were high visibility of infrared imaging during laparoscopic colorectal surgery and minimal adverse events of surgery. One of the most important findings regarding practical use was a rapid decrease in fluorescence marking visibility if one week passed from the time of ICG local injection.
Aquaporin 4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) is an autoimmune astrocytopathic disease pathologically characterized by the massive destruction and ...regeneration of astrocytes with diverse types of tissue injury with or without complement deposition. However, it is unknown whether this diversity is derived from differences in pathological processes or temporal changes. Furthermore, unlike for the demyelinating lesions in multiple sclerosis, there has been no staging of astrocytopathy in AQP4-IgG+NMOSD based on astrocyte morphology. Therefore, we classified astrocytopathy of the disease by comparing the characteristic features, such as AQP4 loss, inflammatory cell infiltration, complement deposition and demyelination activity, with the clinical phase. We performed histopathological analyses in eight autopsied cases of AQP4-IgG+NMOSD. Cases comprised six females and two males, with a median age of 56.5 years (range, 46-71 years) and a median disease duration of 62.5 months (range, 0.6-252 months). Astrocytopathy in AQP4-IgG+NMOSD was classified into the following four stages defined by the astrocyte morphology and immunoreactivity for GFAP: (i) astrocyte lysis: extensive loss of astrocytes with fragmented and/or dust-like particles; (ii) progenitor recruitment: loss of astrocytes except small nucleated cells with GFAP-positive fibre-forming foot processes; (iii) protoplasmic gliosis: presence of star-shaped astrocytes with abundant GFAP-reactive cytoplasm; and (iv) fibrous gliosis: lesions composed of densely packed mature astrocytes. The astrocyte lysis and progenitor recruitment stages dominated in clinically acute cases (within 2 months after the last recurrence). Findings common to both stages were the loss of AQP4, a decreased number of oligodendrocytes, the selective loss of myelin-associated glycoprotein and active demyelination with phagocytic macrophages. The infiltration of polymorphonuclear cells and T cells (CD4-dominant) and the deposition of activated complement (C9neo), which reflects the membrane attack complex, a hallmark of acute NMOSD lesions, were selectively observed in the astrocyte lysis stage (98.4% in astrocyte lysis, 1.6% in progenitor recruitment, and 0% in protoplasmic gliosis and fibrous gliosis). Although most of the protoplasmic gliosis and fibrous gliosis lesions were accompanied by inactive demyelinated lesions with a low amount of inflammatory cell infiltration, the deposition of complement degradation product (C3d) was observed in all four stages, even in fibrous gliosis lesions, suggesting the past or chronic occurrence of complement activation, which is a useful finding to distinguish chronic lesions in NMOSD from those in multiple sclerosis. Our staging of astrocytopathy is expected to be useful for understanding the unique temporal pathology of AQP4-IgG+NMOSD.
Tumor angiogenesis is an important therapeutic target in colorectal cancer (CRC). We aimed to identify novel genes associated with angiogenesis in CRC. Using RNA sequencing analysis in normal and ...tumor endothelial cells (TECs) isolated from primary CRC tissues, we detected frequent upregulation of adipocyte enhancer‐binding protein 1 (AEBP1) in TECs. Immunohistochemical analysis revealed that AEBP1 is upregulated in TECs and stromal cells in CRC tissues. Quantitative RT‐PCR analysis showed that there is little or no AEBP1 expression in CRC cell lines, but that AEBP1 is well expressed in vascular endothelial cells. Levels of AEBP1 expression in Human umbilical vein endothelial cells (HUVECs) were upregulated by tumor conditioned medium derived from CRC cells or by direct coculture with CRC cells. Knockdown of AEBP1 suppressed proliferation, migration, and in vitro tube formation by HUVECs. In xenograft experiments, AEBP1 knockdown suppressed tumorigenesis and microvessel formation. Depletion of AEBP1 in HUVECs downregulated a series of genes associated with angiogenesis or endothelial function, including aquaporin 1 (AQP1) and periostin (POSTN), suggesting that AEBP1 might promote angiogenesis through regulation of those genes. These results suggest that upregulation of AEBP1 contributes to tumor angiogenesis in CRC, which makes AEBP1 a potentially useful therapeutic target.
We identified that adipocyte enhancer‐binding protein 1 (AEBP1) is upregulated in tumor endothelial cells in primary colorectal cancers. Upregulation of AEBP1 in vascular endothelial cells promotes cell proliferation, migration, and angiogenesis. We also found that AEBP1 might mediate tumor angiogenesis through regulating expression of angiogenesis‐related genes, including aquaporin 1 (AQP1) and periostin (POSTN).
Purpose
The low anterior resection syndrome (LARS) score (LS) has been widely validated and has become an international tool for evaluating postoperative bowel dysfunction. However, many physicians ...still use the conventional incontinence scores in LARS treatment. Moreover, interpretation of LS and its relationship with conventional incontinence scores are not yet well understood. Here we compared the LS with the Cleveland Clinic Incontinence Score (CCIS) to clarify the clinical utility and characteristics of the LARS score.
Methods
We performed a multicentre observational study, recruiting 246 rectal cancer patients following sphincter-preserving surgery. Patients completed the LS, CCIS, and SF36 questionnaires.
Results
The response rate was 76.4%, and a total of 180 patients were analysed. The LS was strongly correlated with the CCIS (
P
< 0.001, rs = 0.727). However, among 116 patients determined to not have incontinence (CCIS 0–5), 51 (44%) were diagnosed with LARS (29 with minor LARS and 22 with major LARS). Among 68 patients without LARS, only 3 were diagnosed as having incontinence (CCIS > 6). In comparison with background factors, aging and elapsed time were associated with only LS. High LS and CCIS both showed significant quality-of-life impairment as assessed by the SF-36.
Conclusion
This is the first study to determine the difference in the numeric values between the CCIS and LS. The LS can be a convenient tool for LARS screening, identifying a wide range of patients with LARS, including those with incontinence evaluated by CCIS. Assessment using the CCIS may often underestimate LARS.
Purpose
Some recent studies have suggested that fluorescence angiography with indocyanine green (ICG) might be useful for preventing anastomotic leakage (AL) after laparoscopic colorectal surgery. ...However, its efficacy has not been proven. We evaluated whether intraoperative ICG fluorescence angiography could decrease the AL rate with laparoscopic colorectal cancer surgery.
Methods
This retrospective study included patients with colorectal cancer who underwent laparoscopic surgery at our institution between March 2014 and December 2018. Patients were divided into two groups: with or without ICG fluorescence angiography. The primary outcome was the rate of AL.
Results
A total of 488 patients were included: 223 patients in the ICG group and 265 patients in the no-ICG group. In the ICG group, the transection line was changed to a more proximal location in seven patients (3.1%), including one patient with transverse colon surgery and six with rectal surgery. None of these seven patients developed AL. There were 18 ALs (3.7%) overall. The AL rate was 1.8% in the ICG group and 5.3% in the no-ICG group. For colon cancer, there were no significant differences in the AL rate between the groups (
p
= 0.278). In rectal cancer, the AL rate was significantly lower in the ICG group than in the no-ICG group (3.5% vs. 10.5%,
p =
0.041). After propensity score matching, the AL rate was also significantly lower in the ICG group for rectal cancer (
p =
0.044).
Conclusion
ICG fluorescence angiography can potentially reduce the AL rate with laparoscopic rectal cancer surgery.
A 29-year-old man presented with a high-grade fever, headache, and urinary retention, in addition to meningeal irritation and myoclonus in his upper extremities. A cerebrospinal fluid (CSF) ...examination showed pleocytosis and high adenosine deaminase (ADA) levels with no evidence of bacterial infection, including Mycobacterium tuberculosis. T2-weighted brain magnetic resonance imaging showed transient hyper-intensity lesions at the splenium of the corpus callosum (SCC), bilateral putamen, and pons during the course of the disease. The CSF was positive for anti-glial fibrillary acidic protein (GFAP) antibodies. He was diagnosed with autoimmune GFAP astrocytopathy. The present case shows that the combination of an elevated ADA level in the CSF and reversible T2-weighted hyper-intensity on the SCC supports the diagnosis of autoimmune GFAP encephalopathy.
Aim Although MRI has a substantial role in directing treatment decisions for locally advanced rectal cancer, precise interpretation of the findings is not necessarily available at every institution. ...In this study, we aimed to develop artificial intelligence-based software for the segmentation of rectal cancer that can be used for staging to optimize treatment strategy and for preoperative surgical simulation. Method Images from a total of 201 patients who underwent preoperative MRI were analyzed for training data. The resected specimen was processed in a circular shape in 103 cases. Using these datasets, ground-truth labels were prepared by annotating MR images with ground-truth segmentation labels of tumor area based on pathologically confirmed lesions. In addition, the areas of rectum and mesorectum were also labeled. An automatic segmentation algorithm was developed using a U-net deep neural network. Results The developed algorithm could estimate the area of the tumor, rectum, and mesorectum. The Dice similarity coefficients between manual and automatic segmentation were 0.727, 0.930, and 0.917 for tumor, rectum, and mesorectum, respectively. The T2/T3 diagnostic sensitivity, specificity, and overall accuracy were 0.773, 0.768, and 0.771, respectively. Conclusion This algorithm can provide objective analysis of MR images at any institution, and aid risk stratification in rectal cancer and the tailoring of individual treatments. Moreover, it can be used for surgical simulations.
According to the current international guidelines, high‐risk patients diagnosed with pathological T1 (pT1) colorectal cancer (CRC) who underwent complete local resection but may have risk of ...developing lymph node metastasis (LNM) are recommended additional intestinal resection with lymph node dissection. However, around 90% of the patients without LNM are exposed to the risk of being overtreated due to the insufficient pathological criteria for risk stratification of LNM. Circulating tumor DNA (ctDNA) is a noninvasive biomarker for molecular residual disease and relapse detection after treatments including surgical and endoscopic resection of solid tumors. The CIRCULATE‐Japan project includes a large‐scale patient‐screening registry of the GALAXY study to track ctDNA status of patients with stage II to IV or recurrent CRC that can be completely resected. Based on the CIRCULATE‐Japan platform, we launched DENEB, a new prospective study, within the GALAXY study for patients with pT1 CRC who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk stratification criteria for LNM. The aim of this study is to explore the ability of predicting LNM using ctDNA analysis compared with the standard pathological criteria. The ctDNA assay will build new evidence to establish a noninvasive personalized diagnosis in patients, which will facilitate tailored/optimal treatment strategies for CRC patients.
Based on the CIRCULATE‐Japan platform, we launched DENEB, a new prospective study, within the GALAXY study for patients with pT1 colorectal cancer who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk stratification criteria for lymph node metastasis. The aim of this study is to explore the ability of predicting lymph node metastasis using circulating tumor DNA (ctDNA) analysis compared with the standard pathological criteria. The ctDNA assay will build new evidence to establish a noninvasive personalized diagnosis in patients, which will facilitate tailored/optimal treatment strategies for colorectal cancer patients.
Background
Although conventional one-step nucleic acid amplification (OSNA) is a useful molecular-staging method, its complexity hinders its use in clinical practice. A pooled approach for OSNA ...(pOSNA) has been evaluated for its feasibility in pathologically node-negative colon cancer (pNNCC) for molecular staging of lymph node metastasis in clinical practice.
Methods
Subjects were patients diagnosed with clinical stage II–IIIA colon cancer between January 2017 and September 2018. pOSNA involved harvesting pericolic lymph nodes from fresh surgical specimens, cutting them in half, placing 50% of the nodes in a single test tube, and performing the OSNA assay. The remaining halved pericolic, intermediate, and main lymph nodes were submitted for histopathologic examination, with metastasis determined by hematoxylin and eosin staining of a cut surface of each node.
Results
Of the 98 enrolled patients, 92 formed the analysis set. The mean number of harvested lymph nodes per case was 24.3 (range 5–66) and the mean number of lymph nodes used for pOSNA analysis was 6.9 (range 1–35). The concordance rate, sensitivity, and specificity between methods were 89.1%, 84.6% (95% confidence interval CI 0.80–0.91), and 90.9% (95% CI 0.88–0.94), respectively. The pOSNA upstaging rate for node-negative patients was 9.1% (6/66), and pOSNA returned false-negative results in 15.4% of node-positive cases (4/26).
Conclusions
pOSNA demonstrated an upstaging rate for pNNCC equivalent to that in previous studies, suggesting its feasibility for molecular staging of pNNCC in clinical practice.
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