Combination of three miRNA (miR-141, miR-21, and miR-375) as potential diagnostic tool for prostate cancer recognition

Purpose

Prostate cancer (PCa) is a common tumor disease in western countries and a leading cause of cancer-driven mortality in men. Current methods for prostate cancer detection, like prostate-specific antigen screening, lead to significant overtreatment. The purpose of the study was to analyze circulating microRNAs in serum as non-invasive biomarkers in patients with diagnosis of prostate cancer and healthy individuals.

Methods

This preliminary study included a population of 20 patients with mean age of 68.6 years and mean PSA of 21.3 ng/ml. Eight healthy patients were used as control. MiRNAs were quantified in the total RNA fraction extracted from serum and levels of five microRNAs (miR-106b, miR-141, miR-21, mir-34a, and miR-375) were quantified by RT-qPCR. Statistical analyses evaluated correlation between clinicopathological data and miRNAs expression levels.

Results

Relative expression ratios of miR-106b, miR-141-3p, miR-21, and miR-375 were significantly increased (1.8-, ?1.9-, 2.4-, and 2.6-fold, respectively) in the PCa group compared to healthy control. Using receiver operating characteristics, the highest area under the curve equal to 0.906 was obtained for miR-357 and indicates a very good diagnostic properties of this biomarker. We found expression level of mir-34a not related with PCa.

Conclusions

Our results support previous findings on the possibility of discriminating prostate cancer patients from healthy controls by detecting miRNA (miR-141-3p, miR-21, and miR-375). Further insights into miRNA abundance and characteristics are necessary to validate the panel of miRNA as surrogate markers in diagnosis of prostate cancer.

     

MiRNA-199a-3p in Plasma as a Potential Diagnostic Biomarker for Gastric Cancer

Background

MicroRNA (miRNA) has been shown the potential of cancer diagnosis. We investigated whether plasma miRNA expression could discriminate between patients with and without gastric cancer.

Methods

This study was divided into three steps: (1) miRNA microarray profiling on plasma samples from 20 gastric cancer patients and 20 healthy controls; (2) miRNA selection by real-time qRT-PCR on 30 pairs of plasma from patients and controls; and (3) qRT-PCR validation on an independent set of plasma from 180 gastric cancer patients, 80 healthy controls, and 20 patients with gastric precancerous diseases.

Results

Of the 959 human miRNAs analyzed by microarray, 37 up-regulated miRNAs and seven down-regulated miRNAs were found in gastric cancer plasma. Of the seven discrepant miRNAs validated on the plasma from 30 gastric cancer patients and 30 healthy controls, both miRNA-199a-3p and miRNA-151-5p were significantly elevated (p < 0.05) and were significantly reduced after surgery (p < 0.05) in gastric cancer patients. Further large-scale validation showed that these two miRNAs expressions in plasma were significantly higher in gastric cancer patients than healthy controls and patients with gastric precancerous diseases, respectively. However, only the expression of miRNA-199a-3p in plasma was significantly associated with tumor invasion and with lymph node metastasis and tumor, node, metastasis stage. This marker yielded an area under the receiver operating characteristic curve area of 0.837 with 80 % sensitivity and 74 % specificity in discriminating gastric cancer patients from healthy controls. In gastric cancer tissue, miRNA-199a-3p was expressed in the cytoplasm of tumor cells.

Conclusions

miRNA-199a-3p in plasma could be a novel potential diagnostic biomarker for gastric cancer detection.

     

The Oncological Value of Omentectomy in Gastrectomy for Cancer

Aim

The aim of this study was to determine the oncologic value of omentectomy in patients undergoing gastrectomy for gastric cancer.

Methods

All consecutive patients with gastric cancer that underwent gastrectomy with curative intent between April 2012 and August 2015 were prospectively analyzed. The greater omentum was separately marked during operation and pathologically evaluated for the presence of omental lymph nodes and tumor deposits.

Results

In total, 50 patients were included. The greater omentum harbored lymph nodes in nine (18 %) patients. The omental lymph nodes contained metastases in one (2 %) patient, still free of disease after 20 months. Omental tumor deposits were found in four (8 %) patients; one died <30 days postoperative and three developed peritoneal carcinomatosa after 4, 4, and 8 months. Patients with omental tumor deposits had a significantly reduced 1-year disease-free survival compared to patients without tumor deposits (0 vs. 58.7 %, p?=?0.003). No predictive factors for omental tumor involvement could be identified.

Conclusion

Omental lymph node metastases or tumor deposits are present in 10 % of Western European patients undergoing gastrectomy for gastric cancer. Omentectomy has a prognostic and oncologic value in the curative treatment of patients with gastric cancer. As no predictive factors for omental tumor involvement could be identified, omentectomy should be the standard in gastrectomy for gastric cancer patients.

     

Outcomes,safety, and feasibility of video-assisted thoracic surgery in lung cancer patients on hemodialysis: a case series

Objective

The rate of surgical resection of lung cancer in patients on hemodialysis is expected to increase due to the development of hemodialysis, improved diagnosis of lung cancer, and increases in the number and age of patients. However, studies assessing outcomes of lung resection in these patients are limited. In this retrospective case series, we investigated the safety and efficacy of video-assisted thoracic surgery (VATS) for lobectomy or segmentectomy for lung cancer in patients on hemodialysis.

Methods

Between January 2010 and January 2017, lobectomy or segmentectomy using VATS was performed for seven lung cancer cases in six patients receiving hemodialysis at our institution. There were two female and five male patients, with a median age of 61 years (range 53–76 years). Six patients underwent lobectomy, and segmentectomy and wedge resection were performed in each one case, respectively; systematic mediastinal lymph node dissection (ND2a-2) was performed in six patients.

Results

There were no perioperative deaths in this case series. Median recurrence-free and overall survival rates were 20 months (range 3–82 months) and 31 months (range 3–82 months), respectively.

Conclusions

Video-assisted thoracic surgery (VATS) is a safe and effective procedure for resection of lung cancer in hemodialysis patients and should be considered after accurate determination of surgical indications and careful perioperative management.

     

Underutilization of Treatment for Regional Gastric Cancer Among the Elderly in the USA

Background

In the USA, a quarter of elderly patients do not receive any treatment for regional gastric cancer, which results in poorer outcomes. We sought to identify factors associated with undertreatment of regional gastric cancer in this population, as well as to assess overall survival in the undertreated population.

Methods

Elderly patients (aged ≥?65 years) diagnosed with regional gastric cancer between 2001 and 2009 were identified from the Surveillance Epidemiology and End Results (SEER)-Medicare linked databases. Treatment was defined as receiving any medical or surgical therapy for gastric cancer. Logistic regression analysis was used to identify factors associated with failure to receive treatment. Overall survival was analyzed using the Kaplan-Meier method and Cox proportional hazard model.

Results

Of 5972 patients with regional gastric cancer, 1586 (26.5%) received no treatment. Median age was 78 years; 56.1% of patients were men. On multivariable analysis, the factors strongly associated with lack of therapy were age?≥?80 years, black race, lower education level, and diagnosis before 2007. As expected, patients who received therapy had better overall survival (log-rank test, p?<?0.001). Specifically, median survival and 5-year survival were 16.5 months and 20.5% for treated patients, compared with 9.1 months and 19.0% for untreated patients.

Conclusions

Elderly patients with gastric cancer have better overall 5-year survival after receiving treatment for their cancer. Disparities in the use of treatment for curable cancers are associated with older age, black race, lower educational level, and diagnosis before 2007.

     

Expression of micro-RNAs and genes related to angiogenesis in ccRCC and associations with tumor characteristics

Background

Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer in adults. Our aim is to evaluate genes and miRNAs expression profiles involved with angiogenesis and tumor characteristics in ccRCC.

Methods

The expression levels of miRNAs miR-99a, 99b, 100; 199a; 106a; 106b; 29a; 29b; 29c; 126; 200a, 200b and their respective target genes: mTOR, HIF1-α, VHL, PDGF, VEGF, VEGFR1 and VEGFR2 were analyzed using qRT-PCR in tumor tissue samples from 56 patients with ccRCC. Five samples of benign renal tissue were utilized as control. The expression levels of miRNAs and genes were related to tumor size, Fuhrman nuclear grade and microvascular invasion.

Results

miR99a was overexpressed in most samples and its target gene mTOR was underexpressed, this also occurs for miRNAs 106a, 106b, and their target gene VHL. An increase in miR-200b was correlated with high-risk tumors (p?=?0.01) while miR-126 overexpression was associated with Fuhrman’s low grade (p?=?0.03).

Conclusions

Our results show that in ccRCC there are changes in miRNAs expression affecting gene expression that could be important in determining the aggressiveness of this lethal neoplasia.

     

Positive Lymph Node Ratio as an Indicator of Prognosis and Local Tumor Clearance in N3 Gastric Cancer

Background

Nodal metastasis is an important clinical issue in gastric cancer patients. This study was designed to investigate the clinical usefulness of the positive lymph node ratio (PLNR), which reflects both metastatic and retrieved lymph node numbers, in patients with pN3 gastric cancer.

Methods

We retrospectively analyzed the records of 138 consecutive pN3 patients who underwent curative gastrectomy with lymphadenectomy from 2000 to 2012.

Results

A PLNR of 0.4 was proved to be the best cutoff value to stratify the prognosis of patients with pN3 gastric cancer (P?<?0.001). Univariate and multivariate analyses revealed that older age, larger tumor size (≥10 cm), and PLNR?≥?0.4 [P?<?0.001, HR 3.1 (95 % CI 1.7–5.4)] were independent prognostic factors in pN3 gastric cancer. Regarding the recurrence, patients with PLNR <0.4 had a significantly lower rate of lymph node recurrence than those with PLNR ≥0.4 (P?=?0.020). There was no significant difference in the lymph node recurrence rate between N3a and N3b patients in the PLNR <0.4 group [P?=?0.546, 11.6 % (7/60) vs. 12.5 (1/8)], indicating a better local control regardless of pN3 subgroups.

Conclusions

PLNR is useful to stratify the prognosis and evaluate the extent of local tumor clearance in pN3 gastric cancer.

     

Evaluation of the Safety and Feasibility of Laparoscopic Total Gastrectomy in Clinical Stage I Gastric Cancer Patients

Background

This retrospective study was designed to assess the feasibility of laparoscopic total gastrectomy (LTG) in clinical stage I gastric cancer patients, and validate the appropriateness of the widespread adoption of LTG for experienced open surgeons.

Methods

Eighty-eight patients with clinical stage I gastric cancer underwent LTG in our hospitals (n = 55) and affiliated hospitals (n = 33). Esophagojejunostomy was performed intracoporeally using a circular stapler with an incision in the left upper abdomen. We investigated the patients’ clinicopathologic factor, and evaluated the effect of hospital volume on short-term outcomes.

Results

Fixed insertion of the anvil head was successfully achieved in all patients (lift-up method in 58 patients and transoral method in 28 patients), although 2 patients were converted to open surgery. The approach using a circular stapler through a small incision from the upper left quadrant of the abdomen facilitated a good laparoscopic visual field for the plane of the esophagojejunostomy. Fourteen patients developed Clavien–Dindo classification grade II or more postoperative complications, and the overall operative morbidity rate was 15.9 %. No anastomotic leakage was encountered in this series. No significant difference was observed in clinical outcomes between patients in the high- and low-volume hospital groups.

Conclusions

Laparoscopic total gastrectomy can be performed safely on clinical stage I gastric cancer patients by surgeons with sufficient experience in open gastrectomy and therefore represents a feasible procedure that is not clinically impacted by hospital volume.

     

Results of a nationwide questionnaire-based survey on nutrition management following gastric cancer resection in Japan

Purpose

A study was conducted to clarify the actual status of nutrition management after gastric cancer surgery in Japan and obtain basic data for optimizing perioperative nutrition management.

Methods

A questionnaire was sent to 354 hospitals with at least 50 cases of gastric cancer surgery per year. Questions included the perioperative nutrition management and length of hospital stay for patients who underwent gastric cancer surgery within three months of the survey.

Results

Responses were obtained from 242 hospitals (68%; 20,858 patients). Nutrition management was consistent between laparotomy and laparoscopic surgery for 84% of respondents. The number of postoperative days was the most commonly chosen index for starting oral feeding. The most commonly chosen index for hospital dischargeability was diet composition/amount consumed in 182 hospitals (44%), followed by laboratory data stabilization in 106 hospitals (26%), and the number of postoperative days in 87 hospitals (21%). A positive correlation was found between the mean length of postoperative hospital stay and starting oral feeding (r = 0.23 for distal gastrectomy; r = 0.34 for total gastrectomy). The length of hospital stay tended to be shorter with an earlier start of oral feeding (p < 0.01).

Conclusion

Early postoperative oral feeding may be a factor in reducing the length of hospital stay after gastric cancer surgery.

     

Converting a Sleeve Gastrectomy to a Gastric Bypass for Weight Loss Failure—Is It Worth It?

Background

Sleeve gastrectomy (SG) is gaining popularity and has become the procedure of choice for many bariatric surgeons. Long-term weight loss failure is not uncommon. The preferred revisional procedure for these patients is still under debate.

Objective

The objective of this study was to assess the safety and efficacy of laparoscopic gastric bypass as a revisional surgery for sleeve gastrectomy patients with weight loss failure.

Setting

The study was done at a bariatric surgery center in a university hospital.

Methods

We reviewed our prospectively collected database and identified all patients who underwent conversion of a sleeve gastrectomy to a gastric bypass for weight loss failure. Data on patient demographics, baseline characteristics, and outcomes of bariatric surgery were retrieved.

Results

Twenty-three patients with a mean body mass index (BMI) of 41.6 kg/m2 (range 34.1–50.1 kg/m2) underwent conversion to a gastric bypass. Four patients underwent a gastric band prior to the sleeve gastrectomy, and two patients underwent a re-sleeve gastrectomy prior to conversion to a gastric bypass.At a mean follow-up of 24 months (range 9–46 months), the average body mass index (BMI) decreased to 33.8 kg/m2 and the excess body mass index loss (EBMIL) was 42.6%. Diabetes, hypertension, dyslipidemia, and obstructive sleep apnea resolved or improved in 44.4, 45.5, 50, and 50% of the patients, respectively. Three patients developed early postop complications (13%), while late complications occurred in four patients (17%).

Conclusion

Converting a sleeve gastrectomy to a gastric bypass for weight loss failure is safe, yet weight loss benefit is limited.

     

Immuntherapie beim Prostatakarzinom – aus Alt macht Neu?

Background

Prostate cancer (PCA) seems to be more of an immunologic desert than other tumor entities. It is striking that only rarely does prostate cancer show abundant immune cells and a proimmunogenic microenvironment.

Objectives

Is immunotherapy in PCA effective and which patients can benefit.

Materials and methods

A review of the literature and recent congress data are presented.

Results

Preliminary results with sipuleucel-T for PCA cancer were very promising showing a significant overall survival benefit in randomised phase III studies and the US Federal Drug Administration (FDA) approval for this individualised vaccine. Contrary to other tumor entities this was not the immediate breakthrough to a new therapeutic era of immunotherapy but remained an isolated case and restricted to the USA. More recently, several trials evaluated immunotherapeutic agents but missed their preliminary endpoints. Interestingly, individual patients did benefit and showed long-term remission.

Conclusions

Genome sequencing and new biomarkers are also paving a novel pathway towards individualised immunotherapy for PCA. On-going research and clinical trials are exploring the question of which patients will benefit.

     

Laparoscopy,computerised tomography and fluorodeoxyglucose positron emission tomography in the management of gastric and gastro-oesophageal junction cancers

Background

The staging laparoscopy has been used in the management of gastrointestinal cancers. The aim of this study was to evaluate the role of staging laparoscopy, in comparison with computed tomography (CT) and fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in staging patients with gastro-oesophageal junction (GOJ) and gastric cancers.

Methods

The data were collected for patients between 1996 and 2013 undergoing investigation and treatment for GOJ and gastric cancers at a single institute. The pre-operative data (staging data), intraoperative details, post-operative course and follow-up were analysed for individual cases.

Results

Staging laparoscopy altered management plan in 64 (17 %) of 387 patients with negative staging CT and FDG-PET scan. Twenty-seven (7 %) patients with GOJ cancer (types I, II and III) were identified with pathological intraperitoneal nodes, 15 (4 %) gastric cancer with metastatic intraperitoneal deposits and liver metastases and 3 % gastric cancers with positive ascitic fluid for cancer cells. Ten (3 %) of patients were downstaged and were offered curative resection. Patients with metastatic disease were referred for palliative chemotherapy. The overall sensitivity of staging laparoscopy in diagnosing intraabdominal pathology was 86 % in comparison with CT (81 %) and FDG-PET (78 %).

Conclusions

The diagnostic laparoscopy is useful for detecting and confirming nodal involvement and distant metastatic disease not evident on the staging CT scan and FDG-PET. This could potentially alter treatment and prognosis in patients with upper gastrointestinal cancer. The diagnostic laparoscopy should be performed as part of investigation and treatment planning for patients suffering from GOJ and gastric cancers. This can help to avoid surgery in patients with advanced disease.

     

Comparison of the long-term results of patients who underwent laparoscopy versus open distal gastrectomy

Background

Survival data of patients who underwent laparoscopy assisted distal gastrectomy (LADG) compared with those of patients who underwent open distal gastrectomy (ODG) for gastric cancer are rarely presented. We compared long-term outcomes of LADG with those of ODG in patients with EGC who met the current indication for LADG.

Methods

A total of 2410 patients with early gastric cancer who underwent curative-intent gastric cancer surgery in three Korean tertiary hospitals between January 2003 and June 2009 were included in this multicenter, retrospective, propensity-score-matched cohort study. Cox proportional hazard regression models were used to evaluate the association between operation methods and survival.

Results

In the matched cohort, there were no significant differences in overall survival [hazard ratio (HR) for the LADG group 0.990; 95 % confidence interval (CI) 0.675–1.453] or recurrence-free survival (HR 0.989; 95 % CI 0.480–2.038). The patterns of recurrence were not different between the two groups. The most common pattern of recurrence was liver metastasis followed by metastasis to distant lymph nodes. The rate of complications in the LADG group was higher than that of the ODG group (6.7 vs. 4.6 %, P = 0.045). Grade III or worse complications that required surgical intervention or were life-threatening showed a marginal difference between the two groups (1.7 vs. 2.2 %, P = 0.052). There were no postoperative mortalities in either group.

Conclusion

Laparoscopy assisted distal gastrectomy for patients with early gastric cancer is feasible in terms of the long-term results including survival and recurrence.

     

Krukenberg Tumors of Gastric Origin: The Rationale of Surgical Resection and Perioperative Treatments in a Multicenter Western Experience

Background

In case of Krukenberg tumor (KT) of gastric origin it is controversial and debated whether radical surgery in case of synchronous KT or metastasectomy in case of metachronous ones is associated with additional benefits. Role of perioperative treatments is unclear.

Methods

Among 2515 female patients who were diagnosed with gastric cancer between January 1990 and December 2012 from 9 Italian centers, 63 presented simultaneously or developed KT as recurrence.

Results

Thirty patients presented with synchronous KT, while 33 developed metachronous ovarian metastases during follow-up. The differences between the two groups were analyzed and compared. The median age of 63 patients was 48.0 years (range 31–71). Resection was possible in 53 patients (20 synchronous and 33 metachronous). Twelve patients in the synchronous group and 15 patients of the metachronous group underwent hyperthermic intraperitoneal chemotherapy after resection of KT. All of them underwent adjuvant chemotherapy after KT resection. The median survival for all population was 23 months (95 % confidence interval, 7–39 months). The median survival time in the metachronous group was 36 months, which was significantly longer than that in the synchronous group, 17 months, p < 0.0001.

Conclusions

KT remains a clinical challenge for gastric cancer therapy. The extent of disease and feasibility of removal of the metastatic lesion must be carefully evaluated prior to surgery to define the patients group who could benefit most from a resection associated with perioperative treatments.

     

Impact of Carbohydrate Content and Glycemic Load on Postprandial Glucose After Roux-en-Y Gastric Bypass

Background

Abnormal glucose profiles have been described after Roux-en-Y gastric bypass (RYGB) with intense postprandial hyperglycemic peaks in some but not all the patients. The underlying mechanisms of these anomalies are not totally understood.

Objective

The aim of this study is to determine whether or not the composition of the meal impacts the existence and maximum interstitial glucose (IG) concentration, measured under real-life conditions.

Design

Retrospective cohort.

Setting

Referral bariatric surgery left.

Methods

Continuous glucose monitoring (CGM) and meal composition were recorded for at least 3 days on an outpatient basis in 56 patients after RYGB. The presence of postprandial peaks defined by IG above 140 mg/dl, the maximum postprandial IG, the carbohydrate content, and the glycemic load of the meals were analyzed.

Results

Thirty-two patients had a hyperglycemic peak (PEAK), and 24 did not (NO PEAK). The average max IG was 159.6?±?33.0 mg/dl in PEAK individuals and 111.8?±?13.0 mg/dl in NO PEAK. Age was significantly higher in PEAK, but no other parameter was different between the two groups, including meal composition. In the PEAK patients, in multivariate analyses, carbohydrate content in model one and glucose load in model two explained respectively 50 and 26 % of maximum IG variance. For each gram of ingested carbohydrates, interstitial glucose increased by 1.68 mg/dl.

Conclusions

Following a gastric bypass, under real-life conditions, irrespective of the carbohydrate content of the meal, some patients develop postprandial hyperglycemic peaks, whereas others do not. In patients with postprandial hyperglycemic peaks, the maximum IG depends on the carbohydrate content of the meal.

     

Metastasiertes kastrationsresistentes Prostatakarzinom

Background

At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented.

Objectives

The focus is on the clinical impact of these data.

Materials and methods

A group of German experts in the field of urogenital–oncologic expertise discussed the clinical impact with respect to the current data.

Results

The study results support the current clinical data. They confirm the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel for patients with mCRPC.

Conclusions

Cabazitaxel is an important treatment option after docetaxel progression. With respect to the performance status of a patient, it is adequate to reduce the dosage to 20?mg/m² cabazitaxel.

     

Right-Side Approach-Duet Totally Laparoscopic Distal Gastrectomy (R-Duet TLDG) Using a Three-Port to Treat Gastric Cancer

Background

Gastric cancer is commonly treated via minimally invasive surgery. The present study explored the feasibility of right-side approach-duet (R-duet) totally laparoscopic distal gastrectomy using a three-port compared with a four- or five-port.

Methods

A total of 251 patients who underwent curative totally laparoscopic distal gastrectomy for gastric cancer (72 R-duet, 74 four-port, and 105 five-port) at the Catholic Medical Center were enrolled. All operations were performed using conventional laparoscopic instruments. The clinicopathological characteristics, operative details, and postoperative short-term outcomes were analyzed retrospectively.

Results

The clinicopathological characteristics did not differ significantly among the groups, except that the N stage was higher in the five-port group. The operating time was significantly longer in the four-port than the R-duet group (R-duet, four-port, and five-port 148.2 ± 30.7, 162.4 ± 30.6, and 159.9 ± 31.5 min, respectively; p = 0.024). The estimated blood loss did not differ significantly. Postoperatively, the times to flatus and to soft diet consumption and the hospital stay were significantly longer in the five-port group. The extent of postoperative complications did not differ among the groups.

Conclusions

R-duet totally laparoscopic distal gastrectomy is a reliable form of reduced-port surgery when used to treat gastric cancer; no special instruments are required.