Very Late Recurrence in Germ Cell Tumor of the Testis: Lessons and Implications.

Background. Very late recurrence (LR), i.e., >5 years after initial presentation, occurs in about 1% of patients with germ cell tumors of the testis (TGCT) and is associated with poor prognosis. Methods. We retrospectively reviewed the records of patients at the M. D. Anderson Cancer Center who developed LR > 5 years after their initial diagnosis of TGCT. Results. We identified 25 patients who developed LR between July 2007 and August 2020. The median age at the time of LR was 46 years (range, 29−61). Pathology of LR: somatic transformation to carcinoma or sarcoma­11, nonseminoma with yolk sac tumor or teratoma­11, nonseminoma without yolk sac tumor or teratoma­2, not available­1. With a median follow-up of 3.5 years, 68% of patients are alive 3 years after LR. Patients with prior post-chemotherapy consolidation surgery do not have statistically significant longer survival compared to patients who did not receive post-chemotherapy consolidation surgery, 83.3% vs. 60.8% at 3 years, respectively, p = 0.50. Conclusions. Patients with LR > 5 years tend to harbor nonseminoma (with yolk sac tumor and or teratoma). Among these patients, a majority who did not undergo surgery to remove residual disease after chemotherapy developed somatic transformation and succumbed to their LR.

Assessment of arsenic species in human hair, toenail and urine and their association with water and staple food.

Arsenic intake from household drinking/cooking water and food may represent a significant exposure pathway to induce cancer and non-cancer health effects. This study is based on the human biomonitoring of 395 volunteers from 223 households with private water sources located in rural Punjab, Pakistan. This work has shown the relative contribution of water and staple food to arsenic intake and accumulation by multiple biological matrix measurements of inorganic and organic arsenic species, while accounting for potential confounders such as age, gender, occupation, and exposure duration of the study population. Multi-variable linear regression showed a strong significant relationship between total arsenic (tAs) intake from water and concentrations of tAs, inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) in urine and toenail samples. tAs intake from staple food (rice and wheat) also showed a strong significant relationship with hair tAs and iAs. The sole impact of staple food intake on biomarkers was assessed and a significant correlation was found with all of the urinary arsenic metabolites. Toenail was found to be the most valuable biomarker of past exposure to inorganic and organic arsenic species of dietary and metabolic origin.

Pilot study of dovitinib in patients with von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disease occurring in 1 in 35,000 births and leads to an increased risk of a phenotypically diverse array of tumor types including, but not limited to, clear cell renal cell carcinoma (ccRCC) and hemangioblastomas (HBs). Previous studies of patients with VHL disease treated with the tyrosine kinase inhibitor (TKI) sunitinib did not show clinical response in HBs. Interestingly, VHL-related HBs displayed increased fibroblast growth factor receptor 3 (FGFR3) protein expression when compared to VHL-related ccRCCs. Therefore, in this pilot study, we assessed the safety and efficacy profile of TKI 258 (dovitinib), a multi-tyrosine kinase inhibitor of VEGF receptor and fibroblast growth factor (FGF), in patients with VHL disease who had measureable HBs. The trial was stopped after six patients enrolled after the toxicity stopping rule was triggered. With regards to safety, 6/6 subjects had at least one adverse event (AE). Best response in 6/6 subjects was stable disease (SD) in HBs. While the negative safety and efficacy results of this pilot study do not favor the use of dovitinib for the treatment of asymptomatic HBs in VHL disease patients, further investigation into alternative scheduling and other FGFR inhibitors for the treatment of HBs in VHL disease patients is warranted given the promising pre-clinical and molecular data.

Arsenic species in wheat, raw and cooked rice: Exposure and associated health implications.

Arsenic concentrations above 10µgL-1 were previously found in 89% of ground water sources in six villages of Pakistan. The present study has ascertained the health risks associated with exposure to total arsenic (tAs) and its species in most frequently consumed foods. Inorganic arsenic (iAs) concentrations were found to be 92.5±41.88µgkg-1, 79.21±76.42µgkg-1, and 116.38±51.38µgkg-1 for raw rice, cooked rice and wheat respectively. The mean tAs concentrations were 47.47±30.72µgkg-1, 71.65±74.7µgkg-1, 105±61.47µgkg-1. Wheat is therefore demonstrated to be a significant source of arsenic exposure. Dimethylarsinic acid was the main organic species detected in rice, whilst monomethylarsonic acid was only found at trace levels. Total daily intake of iAs exceeded the provisional tolerable daily intake of 2.1µgkg-1day-1 body weight in 74% of study participants due to concurrent intake from water (94%), wheat (5%) and raw rice (1%). A significant association between tAs in cooked rice and cooking water resulted in tAs intake 43% higher in cooked rice compared to raw rice. The study suggests that arsenic intake from food, particularly from wheat consumption, holds particular significance where iAs is relatively low in water. Chronic health risks were found to be significantly higher from wheat intake than rice, whilst the risk in terms of acute effects was below the USEPA's limit of 1.0. Children were at significantly higher health risk than adults due to iAs exposure from rice and/or wheat. The dietary exposure of participants to tAs was attributable to staple food intake with ground water iAs <10µgL-1, however the preliminary advisory level (200µgkg-1) was achievable with rice consumption of ≤200gday-1 and compliance with ≤10µgL-1 iAs in drinking water. Although the daily iAs intake from food was lower than total water intake, the potential health risk from exposure to arsenic and its species still exists and requires exposure control measures.

Phase II Study of Two Weeks on, One Week off Sunitinib Scheduling in Patients With Metastatic Renal Cell Carcinoma.

Purpose Standard frontline treatment of patients with metastatic renal cell carcinoma currently includes sunitinib. A barrier to long-term treatment with sunitinib includes the development of significant adverse effects, including diarrhea, hand-foot syndrome (HFS), and fatigue. This trial assessed the effect of an alternate 2 weeks on, 1 week off (2/1) schedule of sunitinib on toxicity and efficacy in previously untreated patients with metastatic renal cell carcinoma. Methods Patients started with oral administration of 50 mg sunitinib on a 2/1 schedule and underwent schedule and dose alterations if toxicity developed. The primary end point was < 15% grade ≥ 3 fatigue, diarrhea, or HFS. With 60 patients, the upper bound of the CI would fall below the published 4/2 schedule grade ≥ 3 toxicity rate of 25% to 30%. Results Fifty-nine patients were treated between August 2014 and March 2016. Seventy-seven percent were intermediate or poor risk per Memorial Sloan Kettering Cancer Center criteria. With a median follow-up of 17 months, 25% of patients experienced grade 3 fatigue, HFS, or diarrhea; 37% required a dose reduction, and 10% discontinued because of toxicity. The overall response rate was 57%, median progression-free survival was 13.7 months, and median overall survival was not reached. At 12 weeks, Functional Assessment of Cancer Therapy-General scores dropped between 0% and 10% from baseline, with less reduction in patients who continued treatment longer. Conclusion The primary end point of decreased grade 3 toxicity was not met; however, treatment with a 2/1 sunitinib schedule is associated with a lack of grade 4 toxicity, a low patient discontinuation rate, and high efficacy.

A phase 2 study of the PARP inhibitor veliparib plus temozolomide in patients with heavily pretreated metastatic colorectal cancer.

BACKGROUND: Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors such as veliparib are potent sensitizing agents and have been safely combined with DNA-damaging agents such as temozolomide. The sensitizing effects of PARP inhibitors are magnified when cells harbor DNA repair defects. METHODS: A single-arm, open-label, phase 2 study was performed to investigate the disease control rate (DCR) after 2 cycles of veliparib plus temozolomide in patients with metastatic colorectal cancer (mCRC) refractory to all standard therapies. Fifty patients received temozolomide (150 mg/m2 /d) on days 1 to 5 and veliparib (40 mg twice daily) on days 1 to 7 of each 28-day cycle. Another 5 patients with mismatch repair-deficient (dMMR) tumors were also enrolled. Twenty additional patients were then treated with temozolomide at 200 mg/m2 /d. Archived tumor specimens were used for immunohistochemistry to assess mismatch repair, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and O(6)-methylguanine-DNA methyltransferase (MGMT) protein expression levels. RESULTS: The combination was well tolerated, although some patients required dose reductions for myelosuppression. The primary endpoint was successfully met with a DCR of 24% and 2 confirmed partial responses. The median progression-free survival was 1.8 months, and the median overall survival was 6.6 months. PTEN protein expression and MGMT protein expression were not predictors of DCR. There was also a suggestion of worse outcomes for patients with dMMR tumors. CONCLUSIONS: In this heavily pretreated mCRC population, a combination of veliparib and temozolomide was well tolerated with temozolomide doses up to 200 mg/m2 /d, and it was clinically active. PARP inhibitor-based therapy merits further exploration in patients with mCRC. Cancer 2018;124:2337-46. © 2018 American Cancer Society.

Evaluating water quality and ecotoxicology assessment techniques using data from a lead and zinc effected upland limestone catchment.

Point and diffuse sources associated with historical metal ore mining are major causes of metal pollution. The understanding of metal behaviour and fate has been improved by the integration of water chemistry, metal availability and toxicity. Efforts have been devoted to the development of efficient methods of assessing and managing the risk posed by metals to aquatic life and meeting national water quality standards. This study focuses on the evaluation of current water quality and ecotoxicology techniques for the metal assessment of an upland limestone catchment located within a historical metal (lead ore) mining area in northern England. Within this catchment, metal toxicity occurs at circumneutral pH (6.2-7.5). Environmental Quality Standards (EQSs) based on a simple single concentration approach like hardness based EQS (EQS-H) are more overprotective, and from sixteen sites monitored in this study more than twelve sites (>75%) failed the EQSs for Zn and Pb. By increasing the complexity of assessment tools (e.g. bioavailability-based (EQS-B) and WHAM-FTOX), less conservative limits were provided, decreasing the number of sites with predicted ecological risk to seven (44%). Thus, this research supports the use of bioavailability-based approaches and their applicability for future metal risk assessments.

Influence of induction chemotherapy in trimodality therapy-eligible oesophageal cancer patients: secondary analysis of a randomised trial.

BACKGROUND: A randomised phase 2 trial of trimodality with or without induction chemotherapy (IC) in oesophageal cancer (EC) patients showed no advantage in overall survival (OS) or pathologic complete response rate. To identify subsets that might benefit from IC, a secondary analysis was done. METHODS: The trial had accrued 126 patients (NCT 00525915). Recursive partitioning and proportional hazards regression with interactions were performed. RESULTS: The median follow-up of surviving patients was 6.7 years and the median OS duration was 3.8 years (95% confidence interval (CI), 2.6-5.8 years). OS was associated with tumour length (P=0.03), cT (P=0.02), cN (P=0.04), clinical stage (P=0.01), and tumour grade (P<0.001). The effect of IC differed according to tumour grade. Among patients with well or moderately differentiated (WMD) ECs (n=59), the 5-year survival rate was 74% with IC and 50% without IC, P=0.001. IC had no effect on OS of patients with poorly differentiated (PD) ECs (31% and 28%, respectively; interaction, P=0.04; IC, P=0.03). In the multivariate reduced model, WMD with IC was an independent prognosticator for better OS (HR=0.41, 95% CI, 0.25-0.67; P=<0.001). The following four EC phenotypes emerged for OS: (1) very high risk (PD, cN2/N3), (2) high risk (PD, cN0/N1, stage cIII), (3) moderate risk (PD, cN0/N1, stage cI/II or WMD without IC), and (4) low risk (WMD with IC). The 5-year survival rates were 11%, 27%, 48%, and 74%, respectively (P<0.001). CONCLUSIONS: Our data show that IC significantly prolonged OS of WMD EC patients who undergo trimodality; prospective evaluation is needed.

Assessment of Ileostomy Output Using Telemedicine: A Feasibility Trial.

BACKGROUND: Ileostomies are a routine part of the care of patients with rectal cancer, but are associated with significant risk for dehydration, readmission, and acute kidney injury. Telemedicine has proven beneficial in decreasing readmission in chronic medical illnesses, but its utility in patients with an ileostomy is not well studied. OBJECTIVE: The purpose of this study was to evaluate the feasibility of televideoconferencing in the assessment of ileostomy output. DESIGN: An institutional review board-approved, prospective clinical trial was conducted at a single institution from November 2014 through December 2015. SETTINGS: The study was conducted in a single, large academic medical center. PATIENTS: Patients >18 years of age undergoing surgery with plans for ileostomy were eligible. INTERVENTIONS: Televideoconference assessments of ileostomy output and the need for medical intervention were conducted during the postoperative stay and compared with in-person assessment. MAIN OUTCOME MEASURES: The primary end point of the trial was the feasibility of using teleconferencing to assess the need for medical intervention, defined as 90% agreement between telemedicine and in-person assessments. Secondary end points included patient/provider satisfaction, and correlative studies examined dehydration events and readmission. RESULTS: Twenty-seven patients underwent 44 teleconferencing assessments of ileostomy output. Compared with in-person treatment decisions, there was a 95% match (95% CI, 85%-99%). The readmission rate for the study participants was 31%, and 18% experienced dehydration events. Both patients and faculty responded favorably to surveys regarding the use of telemedicine in the perioperative period. LIMITATIONS: The study is limited by its in-hospital use of technology and small sample size. CONCLUSIONS: Televideoconference evaluation is a feasible, reliable means of assessing ileostomy output with high patient and physician acceptance. Our pilot study provides rationale for further study in the postdischarge setting for patients with ileostomies. The incorporation of televideoconference assessment within a teledischarge program may enable early intervention to improve patient outcomes. See Video Abstract at http://links.lww.com/DCR/A455.

The effect of association between inefficient arsenic methylation capacity and demographic characteristics on the risk of skin lesions.

This study was conducted in rural Pakistan to assess the dose-response relationship between skin lesions and arsenic exposure and their variation by demographic characteristics. The study included 398 participants (66 participants with skin lesions and 332 without) residing in six previously unstudied villages exposed to ground water arsenic in the range of <1 to 3090µgL-1. The skin lesions identification process involved interview and physical examinations of participants followed by confirmation by a physician according to UNICEF criteria. Urinary inorganic arsenic (iAs), total arsenic (tAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analysed to determine methylation capacity, methylation efficiency and the dose-response relationship with skin lesions. Study participants with skin lesions were found to be exposed to arsenic >10µgL-1 with a daily arsenic intake of 3.23±3.75mgday-1 from household ground water sources for an exposure duration of 10-20years. The participants with skin lesions compared to those without skin lesions showed higher levels of urinary iAs (133.40±242.48 vs. 44.24±86.48µgg-1Cr), MMA (106.38±135.04 vs. 35.43±39.97µgg-1Cr), MMA% (15.26±6.31 vs.12.11±4.68) and lower levels of DMA% (66.99±13.59 vs. 73.39±10.44) and secondary methylation index (SMI) (0.81±0.11 vs. 0.86±0.07). Study participants carrying a lower methylation capacity characterized by higher MMA% (OR 5.06, 95% CI: 2.09-12.27), lower DMA% (OR 0.64, 95% CI: 0.33-1.26), primary methylation index (PMI) (OR 0.56, 95% CI: 0.28-1.12) and SMI (OR 0.43, 95% CI: 0.21-0.88) had a significantly higher risk of skin lesions compared to their corresponding references after adjusting for occupation categories. The findings confirmed that inefficient arsenic methylation capacity was significantly associated with increased skin lesion risks and the effect might be modified by labour intensive occupations.

Patterns of relapse in patients with localized gastric adenocarcinoma who had surgery with or without adjunctive therapy: costs and effectiveness of surveillance.

PURPOSE: After therapy of localized gastric adenocarcinoma (GAC) patients, the costs of surveillance, relapse patterns, and possibility of salvage are unknown. MATERIALS AND METHODS: We identified 246 patients, who after having a negative peritoneal staging, received therapy (any therapy which included surgery) and were surveyed (every 3-6 months in the first 3 years, then yearly; ∼10 CTs and ∼7 endoscopies per patient). We used the 2016 Medicare dollars reimbursed as the "costs" for surveillance. RESULTS: Common features were: Caucasians (57%), men (60%), poorly differentiated histology (76%), preoperative chemotherapy (74%), preoperative chemoradiation (59%), and had surgery (100%). At a median follow-up of 3.7 years (range, 0.1 to 18.3), the median overall survival (OS) was 9.2 years (95% CI, 6.0 to 11.2). Tumor grade (p = 0.02), p/yp stage (p < 0.001), % residual GAC (p = 0.05), the R status (p = 0.01), total gastrectomy (p = 0.001), and relapse type (p = 0.02) were associated with OS. Relapse occurred in 79 (32%) patients (only 8% were local-regional) and 90% occurred within 36 months of surgery. P/yp stage (p < 0.001) and total gastrectomy (p = 0.01) were independent prognosticators for OS in the multivariate analysis. Only 1 relapsed patient had successful salvage therapy. The estimated reimbursement for imaging studies and endoscopies was $1,761,221.91 (marked underestimation of actual costs). CONCLUSIONS: The median OS of localized GAC patients was excellent with infrequent local-regional relapses. Rigorous surveillance had a low yield and high "costs". Our data suggest that less frequent surveillance intervals and limiting expensive investigations to symptomatic patients may be warranted.

Utility of endoscopic ultrasound-guided fine-needle aspiration of regional lymph nodes that are proximal to and far from the primary distal esophageal carcinoma.

Implications of assessing the proximal and far para-tracheal or sub-carinal nodes (para-tracheal [PTN] or sub-carinal [SCN]) associated with lower primary esophageal carcinomas (ECs) are unclear. To evaluate the value of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) for PTN and SCN, we analyzed results by positron emission tomography (PET) avidity, 4 EUS node malignancy features, and EUS-FNA results in all patients with Siewert's I or II EC. Of 133 patients (PTN, n=102; SCN, n=31) with EUS-FNA, 47 (35%) patients had malignant node, leading to treatment modifications. EUS-FNA diagnosed significantly more patients with malignant nodes (p=0.02) even when PET and EUS features were combined. Among 94 PET-negative and EUS-negative patients, 9 (10%) had malignant EUS-FNA. At a minimum follow-up of 1 year, only 3 (5%) of 62 patients with benign EUS-FNA had evidence of malignancy in the nodal area of prior EUS-FNA. Patients with malignant EUS-FNA independently had a much shorter overall survival (OS) than those with benign EUS-FNA (p<0.001). Our data suggest that a benign EUS-FNA is highly accurate and need not be pursued further. However, malignant EUS-FNA of PTN/SCN was independently prognostic, conferred a shorter OS, and altered the management of 35% of patients.

Understanding the mobilisation of metal pollution associated with historical mining in a carboniferous upland catchment.

Point and diffuse pollution from metal mining has led to severe environmental damage worldwide. Mine drainage is a significant problem for riverine ecosystems, it is commonly acidic (AMD), but neutral mine drainage (NMD) can also occur. A representative environment for studying metal pollution from NMD is provided by carboniferous catchments characterised by a circumneutral pH and high concentrations of carbonates, supporting the formation of secondary metal-minerals as potential sinks of metals. The present study focuses on understanding the mobility of metal pollution associated with historical mining in a carboniferous upland catchment. In the uplands of the UK, river water, sediments and spoil wastes were collected over a period of fourteen months, samples were chemically analysed to identify the main metal sources and their relationships with geological and hydrological factors. Correlation tests and principal component analysis suggest that the underlying limestone bedrock controls pH and weathering reactions. Significant metal concentrations from mining activities were measured for zinc (4.3 mg l-1), and lead (0.3 mg l-1), attributed to processes such as oxidation of mined ores (e.g. sphalerite, galena) or dissolution of precipitated secondary metal-minerals (e.g. cerussite, smithsonite). Zinc and lead mobility indicated strong dependence on biogeochemistry and hydrological conditions (e.g. pH and flow) at specific locations in the catchment. Annual loads of zinc and lead (2.9 and 0.2 tonnes per year) demonstrate a significant source of both metals to downstream river reaches. Metal pollution results in a large area of catchment having a depleted chemical status with likely effects on the aquatic ecology. This study provides an improved understanding of geological and hydrological processes controlling water chemistry, which is critical to assessing metal sources and mobilization, especially in neutral mine drainage areas.

Surgical Feeding Tubes in Pediatric and Adolescent Cancer Patients: A Single-institution Retrospective Review.

The purpose of our study was to evaluate surgical enteric access in pediatric cancer patients to determine factors associated with postoperative complications. We performed a single-institution retrospective review of all patients below 21 years old with a primary cancer diagnosis who underwent surgical procedures for enteral access between 2004 and 2014. Multivariate logistic regression was performed to determine independent predictors of postoperative complications. During the study period, 122 patients had surgically placed feeding tubes, of whom 58% developed ≥1 complication(s) and 16% experienced a major complication. No single factor was significantly associated with developing any complication or major complication. Several trends were noted including increased complications associated with jejunostomy tubes, percutaneous endoscopic gastrostomy tubes, and abdominal radiation. Surgically placed enteric access in pediatric and adolescent cancer patients is associated with an extremely high complication rate emphasizing the importance of careful evaluation of these patients before embarking on surgical feeding access. Future work should evaluate mechanisms to decrease complications and/or explore alternative methods to provide supplemental nutrition in children and adolescents with cancer.

A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter Infections in Cancer Patients.

For long-term central lines (CL), the lumen is the major source of central line-associated bloodstream infections (CLABSI). The current standard of care for maintaining catheter patency includes flushing the CL with saline or heparin. Neither agent has any antimicrobial activity. Furthermore, heparin may enhance staphylococcal biofilm formation. We evaluated the safety and efficacy of a novel nonantibiotic catheter lock solution for the prevention of CLABSI. Between November 2015 and February 2016, we enrolled 60 patients with hematologic malignancies who had peripherally inserted central catheters (PICC) to receive the study lock solution. The study lock consisted of 15 or 30 µg/ml of nitroglycerin in combination with 4% sodium citrate and 22% ethanol. Each lumen was locked for at least 2 h once daily prior to being flushed. After enrollment of 10 patients at the lower nitroglycerin dose without evidence of toxicity, the dose was escalated to the higher dose (30 µg/ml). There were no serious related adverse events or episodes of hypotension with lock administration. Two patients experienced mild transient adverse events (one headache and one rash) possibly related to the lock and that resolved without residual effect. The CLABSI rate was 0 on lock days versus 1.6/1,000 catheter days (CD) off lock prophylaxis, compared with a rate of 1.9/1,000 CD at the institution in the same patient population. In conclusion, the nitroglycerin-based lock prophylaxis is safe and well tolerated. It may prevent CLABSI when given daily to cancer patients. Large, prospective, randomized clinical trials are needed to validate these findings. (This study has been registered at ClinicalTrials.gov under identifier NCT02577718.).

Selective Perioperative Administration of Pasireotide is More Cost-Effective Than Routine Administration for Pancreatic Fistula Prophylaxis.

BACKGROUND: In a randomized trial, pasireotide significantly decreased the incidence and severity of postoperative pancreatic fistula (POPF). Subsequent analyses concluded that its routine use is cost-effective. We hypothesized that selective administration of the drug to patients at high risk for POPF would be more cost-effective. STUDY DESIGN: Consecutive patients who did not receive pasireotide and underwent pancreatoduodenectomy (PD) or distal pancreatectomy (DP) between July 2011 and January 2014 were distributed into groups based on their risk of POPF using a multivariate recursive partitioning regression tree analysis (RPA) of preoperative clinical factors. The costs of treating hypothetical patients in each risk group were then computed based upon actual institutional hospital costs and previously published relative risk values associated with pasireotide. RESULTS: Among 315 patients who underwent pancreatectomy, grade B/C POPF occurred in 64 (20%). RPA allocated patients who underwent PD into four groups with a risk for grade B/C POPF of 0, 10, 29, or 60% (P < 0.001) on the basis of diagnosis, pancreatic duct diameter, and body mass index. Patients who underwent DP were allocated to three groups with a grade B/C POPF risk of 14, 26, or 44% (P = 0.05) on the basis of pancreatic duct diameter alone. Although the routine administration of pasireotide to all 315 patients would have theoretically saved $30,892 over standard care, restriction of pasireotide to only patients at high risk for POPF would have led to a cost savings of $831,916. CONCLUSION: Preoperative clinical characteristics can be used to characterize patients' risk for POPF following pancreatectomy. Selective administration of pasireotide only to patients at high risk for grade B/C POPF may maximize the cost-efficacy of prophylactic pasireotide.

Refinement of arsenic attributable health risks in rural Pakistan using population specific dietary intake values.

BACKGROUND: Previous risk assessment studies have often utilised generic consumption or intake values when evaluating ingestion exposure pathways. If these values do not accurately reflect the country or scenario in question, the resulting risk assessment will not provide a meaningful representation of cancer risks in that particular country/scenario. OBJECTIVES: This study sought to determine water and food intake parameters for one region in South Asia, rural Pakistan, and assess the role population specific intake parameters play in cancer risk assessment. METHODS: A questionnaire was developed to collect data on sociodemographic features and 24-h water and food consumption patterns from a rural community. The impact of dietary differences on cancer susceptibility linked to arsenic exposure was evaluated by calculating cancer risks using the data collected in the current study against standard water and food intake levels for the USA, Europe and Asia. A probabilistic cancer risk was performed for each set of intake values of this study. RESULTS: Average daily total water intake based on drinking direct plain water and indirect water from food and beverages was found to be 3.5Lday-1 (95% CI: 3.38, 3.57) exceeding the US Environmental Protection Agency's default (2.5Lday-1) and World Health Organization's recommended intake value (2Lday-1). Average daily rice intake (469gday-1) was found to be lower than in India and Bangladesh whereas wheat intake (402gday-1) was higher than intake reported for USA, Europe and Asian sub-regions. Consequently, arsenic-associated cumulative cancer risks determined for daily water intake was found to be 17 chances in children of 3-6years (95% CI: 0.0014, 0.0017), 14 in children of age 6-16years (95% CI: 0.001, 0.0011) and 6 in adults of 16-67years (95% CI: 0.0006, 0.0006) in a population size of 10,000. This is higher than the risks estimated using the US Environmental Protection Agency and World Health Organization's default recommended water intake levels. Rice intake data showed early life cumulative cancer risks of 15 chances in 10,000 for children of 3-6years (95% CI: 0.0012, 0.0015), 14 in children of 6-16years (95% CI: 0.0011, 0.0014) and later life risk of 8 adults (95% CI: 0.0008, 0.0008) in a population of 10,000. This is lower than the cancer risks in countries with higher rice intake and elevated arsenic levels (Bangladesh and India). Cumulative cancer risk from arsenic exposure showed the relative risk contribution from total water to be 51%, from rice to be 44% and 5% from wheat intake. CONCLUSIONS: The study demonstrates the need to use population specific dietary information for risk assessment and risk management studies. Probabilistic risk assessment concluded the importance of dietary intake in estimating cancer risk, along with arsenic concentrations in water or food and age of exposed rural population.

Human exposure assessment of different arsenic species in household water sources in a high risk arsenic area.

Understanding arsenic speciation in water is important for managing the potential health risks associated with chronic arsenic exposure. Most arsenic monitoring studies to date have only measured total arsenic, with few looking at arsenic species. This study assessed 228 ground water sources in six unstudied villages in Pakistan for total, inorganic and organic arsenic species using ion chromatography inductively coupled plasma collision reaction cell mass spectrometry. The concentration levels approached 3090µgL-1 (95% CI, 130.31, 253.06) for total arsenic with a median of 57.55µgL-1, 3430µgL-1 (median=52) for arsenate (As+5) and 100µgL-1 (median=0.37) for arsenite (As+3). Exceedance of the WHO provisional guideline value for arsenic in drinking water (10µgL-1) occurred in 89% of water sources. Arsenic was present mainly as arsenate (As+5). Average daily intake of total arsenic for 398 residents living in the sampled houses was found up to 236.51µgkg-1day-1. This exposure estimate has indicated that 63% of rural residents exceeded the World Health Organization's provisional tolerable daily intake (PTDI) of 2.1µgkg-1day-1 body weight. Average daily intake of As+5 was found to be 15.63µgkg-1day-1 (95% CI, 5.53, 25.73) for children ≤16 and 15.07µgkg-1day-1 (95% CI, 10.33, 18.02) for adults. A mean daily intake of 0.09µgkg-1day-1 was determined for As+3 for children and 0.26µgkg-1day-1 for adults. Organic arsenic species such as monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and Arsenobetaine (AsB) were found to be below their method detection limits (MDLs).

Clinical risk stratification in patients with surgically resectable micropapillary bladder cancer.

OBJECTIVE: To analyse survival in patients with clinically localised, surgically resectable micropapillary bladder cancer (MPBC) undergoing radical cystectomy (RC) with and without neoadjuvant chemotherapy (NAC) and develop risk strata based on outcome data. PATIENTS AND METHODS: A review of our database identified 103 patients with surgically resectable (≤cT4acN0 cM0) MPBC who underwent RC. Survival estimates were calculated using Kaplan-Meier method and compared using log-rank tests. Classification and regression tree (CART) analysis was performed to identify risk groups for survival. RESULTS: For the entire cohort, estimated 5-year overall survival and disease-specific survival (DSS) rates were 52% and 58%, respectively. CART analysis identified three risk subgroups: low-risk: cT1, no hydronephrosis; high-risk: ≥cT2, no hydronephrosis; and highest-risk: cTany with tumour-associated hydronephrosis. The 5-year DSS for the low-, high-, and highest-risk groups were 92%, 51%, and 17%, respectively (P < 0.001). Patients down-staged at RC