[A Case Report of Metastatic Breast Cancer with Peritoneal Metastasis and Massive Ascites Responding to CDK4/6 Inhibitor(Palbociclib)].

A 52-year-old woman was presented with abdominal distension. Chest-abdominal CT showed some tumors in the left breast, enlarged axillary lymph nodes, ovary metastasis peritoneal thickening, a large amount of ascites. The diagnosis of needle biopsy in the breast mass was invasive ductal carcinoma, Luminal A type. The large amount of ascites decreased after the start of administration of fulvestrant and CDK4/6 inhibitor(PAL). Also chest and abdominal CT showed reduction of all lesions. We found the high expression of cyclin D1 protein and the negative of p16 protein in tissues of the needle biopsy. Fifty months later, she continues to do good ADL and PR status. We experienced a case of metastatic breast cancer with massive ascites and peritoneal metastasis that was successfully treated with a CDK4/6 inhibitor(PAL)and achieved long- term survival.

18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging-Defined Extramural Venous Invasion Predicts Distant Metastasis and Reflects Strong Tumor Invasiveness in Rectal Cancer.

INTRODUCTION: Extramural vascular invasion in patients with rectal cancer is a poor prognostic factor associated with distant metastasis; thus, accurate preoperative diagnosis is important. However, the accurate detection of extramural vascular invasion using magnetic resonance imaging (MRI) is difficult, and an improved diagnostic modality is required. In addition, the factors involved in the formation of extramural venous invasion (EMVI) remain unclear. In this study, we aimed to examine the ability of 18F-fluorodeoxyglucose positron emission tomography/MRI ([18F] FDG PET/MRI) to detect EMVI and elucidate the factors involved in EMVI. METHODS: Thirty-one patients with rectal cancer were enrolled in this study between 2017 and 2021. We preoperatively evaluated the pelvic [18F] FDG PET/MRI to detect extramural vascular invasion ([18F] FDG PET/MRI-defined EMVI: pmrEMVI). To investigate the factors related to pmrEMVI, we confirmed the desmoplastic reaction (DR) and TWIST expression in the primary lesions of rectal cancer and examined its relationship with pmrEMVI. RESULTS: Six of the 31 patients were pmrEMVI positive. Four pmrEMVI-positive patients had distant metastases. The levels of immature DR and TWIST1 expression were significantly higher in cases with pmrEMVI positivity. CONCLUSION: pmrEMVI is a useful biomarker for predicting distant metastasis. In addition, pmrEMVI was significantly correlated with factors related to tumor invasiveness.

Monitoring Metastatic Colorectal Cancer Progression According to Reactive Oxygen Metabolite Derivative Levels.

Oxidative stress has been implicated in the development, proliferation, and metastasis of colorectal cancer, but few studies have considered how oxidative stress changes in relation to treatment response. In this study, we investigated whether the rate of change in reactive oxygen metabolite derivatives (d-ROM)-serum markers of oxidative stress-could predict treatment response in metastatic colorectal cancer. We enrolled 53 patients with metastatic colorectal cancer who were treated with 3 months of chemotherapy. We measured d-ROM levels and performed computed tomography before and after chemotherapy, and we examined the change in d-ROM levels for each anticancer treatment. Factors influencing the d-ROM ratio (post-treatment: pre-treatment levels) were examined using linear regression analysis. d-ROM levels decreased in patients showing a partial response (p < 0.001) and increased in those showing disease progression (p = 0.042). An increasing d-ROM ratio was associated with disease progression (regression coefficient: 0.416, 95% confidence interval: 0.279-0.555, p < 0.001). Our study indicates that d-ROM levels are useful markers of tumor progression and that the d-ROM ratio is useful for predicting treatment response in patients with metastatic colorectal cancer.

A proposed new Japanese classification of synchronous peritoneal metastases from colorectal cancer: A multi-institutional, prospective, observational study conducted by the Japanese Society for Cancer of the Colon and Rectum.

Aim: To establish a new Japanese classification of synchronous peritoneal metastases from colorectal cancer. Methods: This multi-institutional, prospective, observational study enrolled patients who underwent surgery for colorectal cancer with synchronous peritoneal metastases. Overall survival rates were compared according to the various models using objective indicators. Each model was evaluated by Akaike's information criterion (AIC). The region of peritoneal metastases was evaluated by the peritoneal cancer index (PCI). Results: Between October 2012 and December 2016, 150 patients were enrolled. The AIC of the present Japanese classification was 1020.7. P1 metastasis was defined as confined to two regions. The minimum AIC was obtained with the cutoff number of 10 or less for P2 metastasis and 11 or more for P3 metastasis. As for size, the best discrimination ability between P2 and P3 metastasis was obtained with a cutoff value of 3 cm. The AIC of the proposed classification was 1014.7. The classification was as follows: P0, no peritoneal metastases; P1, metastases localized to adjacent peritoneum (within two regions of PCI); P2, metastases to distant peritoneum, number ≤10 and size ≤3 cm; P3, metastases to distant peritoneum, number ≥11 or size >3 cm; P3a, metastases to distant peritoneum, number ≥11 and size ≤3 cm, or number ≤10 and size >3 cm; P3b, metastases to distant peritoneum, number ≥11 and size >3 cm. Conclusion: This objective classification could improve the ability to discriminate prognosis in patients with synchronous peritoneal metastases from colorectal cancer.

Follicular cholangitis mimicking a common bile duct cancer: a case report.

BACKGROUND: Follicular cholangitis (FC) is a benign bile duct disease that was first reported 2003. Pathologically, it is characterized by lymphoplasmacytic infiltration with multiple lymphoid follicle formations under the mucosal layer of the biliary tract. However, as this disease is extremely rare, little is known about its etiology and pathogenesis. CASE PRESENTATION: A 77-year-old woman was diagnosed with middle bile duct stenosis and potential increases in alkaline phosphatase (ALP) and γ-glutamyl transpeptidase levels (γ-GTP). Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and IgG4 levels were all within the normal limits. Contrast-enhanced computed tomography (CE-CT) and magnetic resonance imaging (MRI) revealed bile duct dilation from intrahepatic to upper common bile duct and an irregular mass lesion in distal bile duct. Additionally, multiple overlapping leaf-like folds were detected. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) did not demonstrate fluorodeoxyglucose uptake. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed because common bile duct cancer could not be ruled out. The resected specimen showed diffuse homogeneous middle bile duct wall thickening. Microscopically, the lesion exhibited thick fibrosis with several invaded lymphoplasmacytic cells, and lymphoid follicle formations were detected under the mucosal layer. Immunohistochemical staining (IHC) revealed positive for CD3, CD4, CD20 and CD79a, and these findings led to a final diagnosis of FC. The patient has not experienced recurrence to date (42 months postoperatively). CONCLUSIONS: Currently, accurate preoperative diagnosis of FC is difficult. More cases must be accumulated to generate additional knowledge on its precise diagnosis and proper treatment.

[18F]FES PET Resolves the Diagnostic Dilemma of COVID-19-Vaccine-Associated Hypermetabolic Lymphadenopathy in ER-Positive Breast Cancer.

Coronavirus disease (COVID-19) vaccination is known to cause a diagnostic dilemma due to false-positive findings on [18F]FDG PET in vaccine-associated hypermetabolic lymphadenopathy. We present two case reports of women with estrogen-receptor (ER)-positive cancer of the breast who were vaccinated for COVID-19 in the deltoid muscle. [18F]FDG positron emission tomography (PET) demonstrated primary breast cancer and multiple axillary lymph nodes with increased [18F]FDG uptake, diagnosed as vaccine-associated [18F]FDG-avid lymph nodes. Subsequent [18F]FES PET revealed single axillary lymph node metastasis in the vaccine-associated [18F]FDG-avid lymph nodes. To the best of our knowledge, this is the first study showing the usefulness of [18F]FES PET in diagnosing axillary lymph node metastasis in COVID-19-vaccinated patients harboring ER-positive breast cancer. Thus, [18F]FES PET has potential applications in the detection of true-positive metastatic lymph nodes in patients with ER-positive breast cancer regardless of the ipsilateral or contralateral side, who have received COVID-19 vaccination.

Annual report on National Clinical Database 2020 for gastroenterological surgery in Japan.

Aim: The National Clinical Database (NCD) of Japan is a nationwide data entry system for surgery, and it marked its 10th anniversary in 2020. The aim was to present the 2020 annual report of gastroenterological surgery of the NCD. Methods: The data of the surgical procedures stipulated by the training curriculum for board-certified surgeons of the Japanese Society of Gastroenterological Surgery in the NCD from 2011 to 2020 were summarized. Results: In total, 5 622 845 cases, including 593 088 cases in 2020, were extracted from the NCD. The total number of gastroenterological surgeries increased gradually in these 10 years, except for the year 2020 due to the COVID-19 pandemic. The annual number of surgeries of each organ, except the pancreas and liver, decreased by 0.4%-13.1% in 2020 compared to 2019. The surgical patients were consistently aging, with more than 20% of all gastroenterological surgeries in 2020 involving patients aged 80 years or older. The participation of board-certified surgeons increased for each organ (75.9%-95.7% in 2020). The rates of endoscopic surgery also increased constantly. Although the incidences of postoperative complications of each organ increased by 0.7%-7.9% in these 10 years, postoperative mortality rates decreased by 0.2%-1.5%. Conclusions: We present here the short-term outcomes of each gastroenterological operative procedure in 2020. This review of the 10-years of NCD data of gastroenterological surgery revealed a consistent increase of the number of surgeries (except for in 2020), especially endoscopic procedures, and aging of the Japanese population. The good safety of Japanese gastroenterological surgeries was also indicated.

Hepatocellular carcinoma progression promoted by 5-lipoxygenase activity in CD163(+) tumor-associated macrophages.

Arachidonic acid 5-lipoxygenase (5-LOX), an enzyme that synthesizes leukotrienes (LTs), is involved in cancer development including proliferation, invasion, metastasis and drug resistance. However, the functional role of 5-LOX in hepatocellular carcinoma (HCC) remains to be elucidated. In this study, we analyzed the contribution of 5-LOX in HCC progression and investigated the potential of targeted therapy. Analysis of 86 resected HCC specimens and the clinical data of 362 cases of liver cancer from The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset, showed that 5-LOX expression was associated with postoperative survival. The cancer proliferative and stem cell potential were correlated with the levels of 5-LOX in CD163(+) tumor-associated macrophages (TAMs). In an HCC mouse model, CD163(+) TAMs expressed 5-LOX and produced LTB4 and LTC/D/E4; the 5-LOX inhibitor, zileuton, suppressed HCC progression. LTB4 and LTC/D/E4 promoted cancer proliferation and stem cell capacity via phosphorylation of extracellular signal-regulated kinase 1/2 and stem cell-associated genes. Taken together, we identified a novel mechanism of HCC progression in which CD163(+) TAMs express 5-LOX and produce LTB4 and LTC/D/E4, thereby enhancing the proliferative and stem cell potential of HCC cells. Furthermore, inhibition of 5-LOX activity regulates HCC progression, suggesting it has potential as a new therapeutic target.

Anti-Prokineticin1 Suppresses Liver Metastatic Tumors in a Mouse Model of Colorectal Cancer with Liver Metastasis.

Multidisciplinary treatment for colorectal cancer (CRC) has undergone significant advances, and molecularly targeted drugs have substantially improved patient prognosis. However, one problem with current molecularly targeted therapeutics is that they must be used in combination with anticancer agents. New molecular targeted therapies that can be used alone are needed. We have previously identified prokineticin1 (PROK1) factor as a therapeutic potential target for CRC. PROK1 factor is involved in the angiogenesis of tissues surrounding CRC tumors. Additionally, PROK1 receptors 1 and 2 are expressed in CRC cell lines, playing roles in cell proliferation via an autocrine mechanism and in the signaling system. In this study, a liver metastasis mouse model was developed using human colorectal cancer cell lines, and mice were divided into anti-PROK1 antibody administration and control groups. Mice were treated intraperitoneally with antibodies or phosphate-buffered saline (control) every three days. The number, size, and cell proliferation ability of metastatic lesions were analyzed. Our results suggested that the number, size, and cancer cell proliferation ability of metastatic lesions decreased, and the survival time significantly increased in the antibody-treated group compared to those in the control group. Thus, the anti-PROK1 antibody therapy suppressed the cell proliferation ability of liver metastatic lesions in a CRC mouse model, suggesting its potential as a novel treatment strategy.

[Short-Term Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer].

In recent years, an increasing number of reports have demonstrated the usefulness of neoadjuvant chemoradiotherapy (NACRT). In our department, we consider cT3-4 and/or cN-positive locally advanced rectal cancer as an indication for NACRT. We have retrospectively evaluated the efficacy and safety of NACRT in 11 patients who underwent NACRT from November 2018 to July 2022. All patients were male, with a median age of 69 years, and cStage was Ⅱa: 1, Ⅱc: 1, Ⅲb: 5, Ⅲc: 3, and Ⅳa: 1. All patients completed NACRT, and there were no cases of CTCAE Grade 3 or higher adverse events or treatment interruptions. The response rate was 72.7%, and histological response grade were Grade 3: 1(9.1%), 2: 4 (36.4%), 1b: 6(54.5%), and surgical margin was negative in all cases. Pathological down stage was obtained in 45.5% of cases, and pCR was obtained in 1 case(9.1%). The median observation period was 17 months, and during the period, 2 cases(18.2%)developed recurrence, both of which were pulmonary metastases, and no local recurrence including pelvic lymph node recurrence was observed. NACRT for locally advanced rectal cancer is considered a relatively safe and highly locally controllable preoperative treatment.

[A Case of BRAF V600E-Mutant Colorectal Cancer Treated Effectively by Encorafenib, Binimetinib, and Cetuximab Triple Therapy].

A 76-year-old woman was diagnosed with left-sided transverse colon cancer invading the pancreatic tail with multiple liver metastases and peritoneal dissemination. Preoperative diagnosis was cT4b(SI)N2aM1c(H3, P1), cStage Ⅳc, harboring BRAF V600E mutation. Transverse colostomy was performed, and FOLFOXIRI plus bevacizumab(BEV)was administered. After 12 chemotherapy cycles, the primary tumor and metastatic lesions showed partial response. Because of CEA elevating after 5-FU plus LV plus BEV as maintenance therapy was changed, the regimen was switched to encorafenib plus binimetinib plus cetuximab as the second-line chemotherapy. The patient developed dermatitis around the colostomy after the start of the second-line chemotherapy, resulting in temporally cetuximab monotherapy. After improvement of dermatitis, the patient resumed encorafenib plus binimetinib, improving liver metastases. Eight months after the start of the second- line, the patient has been administered with triple therapy and had stable disease status.

Oxidative Stress as a Biomarker for Predicting the Prognosis of Patients with Colorectal Cancer.

INTRODUCTION: Excess oxidative stress is generated by inflammation and cancer, and it is involved in the development and metastasis of colorectal cancer. However, there are few reports on the relationship between blood oxidative stress and prognosis. This study examined the usefulness of derivatives of reactive oxygen metabolites (d-ROMs), a measure of oxidative stress, and the neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, as prognostic markers in colorectal cancer. METHODS: The study enrolled 163 patients who underwent colorectal cancer resection at our institution between 2013 and 2018. Blood samples were taken preoperatively to measure d-ROMs and NLR. Spearman's correlation analysis was used to examine the relationships between d-ROMs and NLR, and Cox regression analysis was performed to identify factors associated with d-ROMs and NLR. The Kaplan-Meier method was used to calculate disease-specific survival (DSS). RESULTS: There was no correlation between d-ROMs and NLR. Tumor size was significantly associated with d-ROMs and NLR. DSS was significantly worse among patients with high d-ROMs or high NLR, although patients with high d-ROMs and high NLR had the worst DSS. In the multivariate analysis, distant metastasis and the high d-ROM/NLR combination were significant factors associated with DSS (p < 0.001, hazard ratio [HR] = 22.880 and p = 0.049, HR = 2.391, respectively). CONCLUSION: Preoperative d-ROMs and NLR reflect the tumor size among patients with colorectal cancer. The combination of d-ROMs and NLR may effectively predict prognosis in patients with colorectal cancer.

Stage IV anal canal squamous cell carcinoma with long-term survival: a case report.

BACKGROUND: Currently, no established standard treatment exists for metastatic anal squamous cell carcinoma. We report a case of complete response in a patient with stage IV anal squamous cell carcinoma after undergoing multidisciplinary treatment. CASE PRESENTATION: A 62-year-old woman visited a nearby doctor with a chief concern of severe pain associated with a firm mass in the anus. The patient was diagnosed with anal canal squamous cell carcinoma and liver metastases and referred to First Department of Surgery Faculty of Medicine University of Fukui for treatment. The patient received a TNM classification of T4N0M1 and stage IV. Rectal amputation was performed; however, postoperative complications hindered immediate anticancer therapy and the liver metastases exacerbated. Radiofrequency hyperthermia and systemic chemotherapy were performed 3 months postoperatively. A prominent reduction in the liver metastasis was observed. Lung metastases appeared during the course of systemic chemotherapy. Radiotherapy was performed to treat the lung lesion and resolved. Radiotherapy was also performed for liver metastasis. The lesion in the liver showed resolution after 54 months postoperatively, and treatment with the anticancer drug was discontinued. Ten-year follow-up findings suggested complete resolution of the lesion in response to the treatment protocol followed in this case. This long-term survival was achieved through a multidisciplinary treatment. CONCLUSIONS: The present case suggests that multidisciplinary treatment approach is effective for resolving stage IV anal squamous cell carcinoma, and addition of new anticancer drug therapy may improve the overall prognosis of squamous cell carcinoma.

A case of diverticulum of the appendiceal base resembling a submucosal tumor of the cecum under colonoscopy: a hitherto undescribed lesion.

BACKGROUND: Diverticulosis of the appendix is an uncommon clinical entity, and a preoperative diagnosis is often difficult. Herein we report an unusual case of appendiceal diverticulosis. CASE PRESENTATION: A 72-year-old male was referred to our hospital to examine the cause of hematochezia. A colonoscopy study showed a protruding lesion resembling a submucosal tumor (SMT), approximately 20 mm in diameter, at the site around the appendiceal orifice of the cecum. An abdominal computed tomography and magnetic resonance imaging showed a cystic lesion at the appendiceal base. The lesion was clinically diagnosed as a cystic tumor of the appendix, but the possibility of a malignant tumor could not be excluded. Therefore, a laparoscopic ileocecal resection with lymph node dissection was performed. The pathological examination of the resected specimen revealed that the lesion was a diverticulum (pseudodiverticulum) occurring solitarily at the appendiceal base, in which the mucosal layer of the appendix was invaginated into the submucosa of the adjacent cecum, thus forming an SMT-like lesion. CONCLUSION: To our knowledge, this is the first case report in the English literature showing that an appendiceal diverticulum can manifest as an SMT-like lesion in the cecum. This condition should be recognized as a differential diagnosis for such lesions.

Vascular E-selectin Expression Detected in Formalin-fixed, Paraffin-embedded Sections With an E-selectin Monoclonal Antibody Correlates With Ulcerative Colitis Activity.

It is widely accepted that E-selectin, an inducible endothelial cell adhesion molecule, plays a critical role in the initial step of neutrophil recruitment to sites of acute inflammation. However, immunohistological analysis of E-selectin has been hampered by lack of E-selectin-specific monoclonal antibodies that can stain formalin-fixed, paraffin-embedded (FFPE) tissue sections. Here, we employed E-selectin•IgM (a soluble form of E-selectin) as immunogen, and then, after negative selection with L-selectin•IgM and P-selectin•IgM and screening of FFPE sections of both COS-1 cells overexpressing E-selectin and acute appendicitis tissues, we successfully generated an E-selectin-specific monoclonal antibody capable of staining FFPE tissue sections. We used this antibody, designated U12-12, to perform quantitative immunohistological analysis of 390 colonic mucosal biopsy specimens representing ulcerative colitis. We found that the higher the histological disease activity, the greater the number of vessels expressing E-selectin, an observation consistent with previous analyses of frozen tissue sections. Furthermore, in active ulcerative colitis, E-selectin-expressing vessels contained neutrophils attached to endothelial cells, presumably in the process of extravasation, which eventually could cause epithelial damage. These results overall indicate that U12-12 is effective for E-selectin immunohistochemistry in archived FFPE samples representing various human diseases.

Feasibility of [18F]FDG PET/MRI with Early-Delayed and Extended PET as One-Stop Imaging for Staging and Predicting Metastasis in Rectal Cancer.

BACKGROUND: We aimed to evaluate the diagnostic accuracy of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/magnetic resonance imaging ([18F]FDG PET/MRI) for preoperative staging and usefulness of the detection of extramural vascular invasion (EMVI) for predicting metastasis in rectal cancer. METHODS: Twenty-three patients underwent pretreatment [18F]FDG PET/MRI, including early-delayed and extended PET and dedicated pelvic MRI without using anticonvulsant or contrast agents. Seven patients received preoperative treatment and all subsequently underwent surgery. Clinical cancer stages were evaluated using postoperative histopathology as a reference. PET/MR-defined EMVI (pmrEMVI) and pathological (p) TN stages were correlated with disease progression for a maximum of 2 years. RESULTS: Of 16 patients without preoperative treatment, 10 had pT3, 4 tumors, 7 had pN1-3 lymph nodes, and 5 had synchronous metastases (SM; liver, lung, inguinal node). The sensitivity, specificity, and accuracy of PET/MRI were 90%, 67%, and 81% for T staging (T1, 2 vs. T3, 4), and 89%, 100%, and 94% for N staging (N0 vs. N1-3), respectively. Patient-based accuracy for SM staging was 100% (4/4). Of 23 patients, 6 were positive for pmrEMVI and 4 had metachronous metastases or local recurrence (MM; pelvic node, brain, lung, skin) during the follow-up periods. Five of the 6 pmrEMVI-positive patients had SM and/or MM (odds ratio = 37.5). Among pT, pN, and pmrEMVI, pmrEMVI-positivity was the only significant predictor for poorer progression-free survival (p < 0.05). CONCLUSIONS: [18F]FDG PET/MRI according to our suggested protocol is a one-stop, non-contrast, and valid diagnostic method for rectal cancer staging, and pmr-EMVI can be used as an imaging biomarker for predicting metastases.

Metastatic invasive lobular breast cancer presenting as linitis plastica of the colon: Tumour characterization using [18 F]FES PET/MRI.

Metastatic invasive lobular breast cancer (ILC) to the colon is rare and usually ER-positive. We present an ER-negative case of metastatic ILC presenting as linitis plastica of the colon where [18 F]FES PET/MRI allowed the evaluation of the ER phenotypic transformation in the colonic metastasis from the ER-positive breast ILC in vivo.

Has the COVID-19 pandemic influenced the oral health and nutritional status of elderly patients with digestive cancer?: A retrospective study in Fukui, Japan.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic has affected various aspects, including socioeconomic status and health. This retrospective study aimed to investigate the influence of the COVID-19 pandemic on oral health based on the number of teeth that contribute to mastication, and the nutritional status of elderly patients with digestive cancers.The authors defined the before and during COVID-19 periods in this study as January 2019 to December 2019 and January 2020 to December 2020, respectively. Patients with digestive cancer who underwent general, laboratory, and orthopantomograph examinations for preoperative oral health assessment before general anesthesia participated in this study. The authors investigated the following general characteristics: (1) sex, (2) age, and (3) the organ affected by disease and scheduled for surgery under general anesthesia. The authors collected information about (4) the number of teeth that could contribute to mastication as a clinical oral health parameter. The parameters: (5) body mass index, (6) serum total protein levels, and (7) serum albumin levels were used to indicate the nutritional status.A total of 233 elderly patients with digestive cancer participated in this study. There was no significant difference between the age of the patients with digestive cancer. There was also no significant difference in the number of teeth that could contribute to mastication. Additionally, there was no significant difference in nutritional status as indicated by the body mass index, serum total protein levels, and serum albumin levels.This study showed that the COVID-19 pandemic during 2020 did not have a significant influence on the oral health and nutritional status of elderly patients with digestive cancer. However, the influence of COVID-19 on community oral health may become apparent in the future. Thus, dental professionals should continue further research regarding the effects of COVID-19 on oral health.

Plasma Prokineticin 1, a prognostic biomarker in colorectal cancer patients with curative resection: a retrospective cohort study.

BACKGROUND: Prokineticin 1 (PROK1) was reported as an angiogenic factor, which is associated with tumor progression, cell invasion, and metastasis in colorectal cancer. Although the association between PROK1 expression in primary cancer lesion and patient prognosis was reported, it is unclear whether plasma PROK1 concentration may be a predictive factor in colorectal cancer patients. This study investigated the association between PROK1 concentration in plasma and prognosis in colorectal cancer patients. METHODS: We measured preoperative PROK1 plasma levels using ELISA method, while PROK1 expression in primary cancer lesion was evaluated using immunohistochemistry (IHC). The association between plasma PROK1 levels and cancer-related survival rate (CRS) was evaluated. Additionally, we examined whether simultaneous PROK1 expression in both primary cancer lesions and plasma was correlated with CRS. The cancer-related survival rate was calculated using the Kaplan-Meier method, and survival estimates were compared using the log-rank test. RESULTS: We have gathered eligible 130 CRC patients retrospectively. Out of 130 patients, 61 (46.9%) were positive on IHC in primary cancer, and 69 (53.1%) were negative, while 43 (33.1%) had high-value PROK1 in plasma. Out of these 43, 30 (25.4%) also had concomitant higher IHC expression in primary cancer. The plasma PROK1 levels tended to increase with advancing stages. The plasma PROK1-positive group had a lower 5-year CRS than the negative group (63.6% vs. 88.2%; P = 0.006). Additionally, simultaneous PROK1 expression was associated with a more significant decrease of 5-year CRS than both negative groups in all stages (76.2% vs. 92.5%; P = 0.003) and stage III (59.3% vs. 84.5%; P = 0.047). Multivariate analysis showed simultaneous PROK1 expression was independently associated with worse CRS (HR, 1.97; 95% CI 1.20­3.24, P < 0.01). CONCLUSION: PROK1 expression in preoperative plasma reflects poor prognosis in patients undergoing curative resection for colorectal cancer. The plasma PROK1 level may be a potential predictive marker, especially in stage III colorectal cancer patients.