Opium poppy husk traders in Rajasthan: The lives and work of businessman in the contemporary Indian opium industry.

This thesis is about the men who participate in the state-licensed opium poppy husk business in the North Indian state of Rajasthan. By depicting the interactions amongst poppy husk traders, as well as the interactions between traders and regulatory officials, this thesis describes the composition of the poppy husk trading community, explains their distinctive methods of managing the risk of their work's extra-legal and illegal aspects, identifies characteristics that differentiate this commercial community from others, and delineates traders' position amongst the middle classes of Rajasthan and India. Poppy husk traders resemble other upwardly mobile middle class Indian businessmen in their business organization and in their lives. Traders are, however, generally thought of and treated as something different and dangerous by Rajasthanis, State officials and legislators. This differentiation is rooted in powerful popular views of opium as a beneficial tradition, as a legendary source of wealth, and as a cause of corruption and violence. These views of opiate wealth and corruption are tied to expectations that the State should be accountable to the public, which are related to popular prescriptive beliefs about the legitimate use of violence and the acquisition of status and wealth. Such beliefs also explain traders' shared perceptions, justifications, and leadership strategies in the face of the high risks and opportunities associated with their various legal, illegal and extra-legal business structures and practices. In analysing State regulation and popular perceptions of corruption, this study contributes to scholarly debates on how Indians view and interact with "the State", and to debates about the relationship between society, the State, informal economic activities, and social mobility. Through these contributions, this thesis strengthens the understanding of collaboration in high-risk commercial environments by providing a robust alternative to common but fallacious explanations based on generalized notions of trust and kinship

Reproduction of Crassula helmsii by seed in western Europe

The amphibious plant species Crassula helmsii is a widely established and still-spreading alien in various parts of Europe, where it is considered invasive as its dense swards stress the viability of local biota. The species was considered to exclusively reproduce through vegetative means, until ex situ germination was recorded from a single locality in Belgium. We assessed whether this seed viability holds on a wider scale, by testing 16 populations from The Netherlands, Belgium, northern France, eastern England and northern Germany in a greenhouse germination experiment. Seedlings were observed from all populations but two, and from each of the five countries. Although most fruits were lacking seeds and the inferred germination percentages were overall low, germinable seed numbers are considerable given the high density of flowering stems. An in situ test revealed seeds to make it through normal winter conditions without signs of physical damage and with retention of germinability. Our results suggest that reproduction by seed is a relatively cryptic but widespread phenomenon throughout western Europe. The persistency of seed banks requires further investigation. Nonetheless, these findings already challenge the efficacy of techniques currently applied in C. helmsii control

An international multicentre evaluation of treatment strategies for combined hepatocellular-cholangiocarcinoma

BACKGROUND & AIMS: Management of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is not well-defined. Therefore, we evaluated the management of cHCC-CCA using an online hospital-wide multicentre survey sent to expert centres. METHODS: A survey was sent to members of the European Network for the Study of Cholangiocarcinoma (ENS-CCA) and the International Cholangiocarcinoma Research Network (ICRN), in July 2021. To capture the respondents\u27 contemporary decision-making process, a hypothetical case study with different tumour size and number combinations was embedded. RESULTS: Of 155 surveys obtained, 87 (56%) were completed in full and included for analysis. Respondents represented Europe (68%), North America (20%), Asia (11%), and South America (1%) and included surgeons (46%), oncologists (29%), and hepatologists/gastroenterologists (25%). Two-thirds of the respondents included at least one new patient with cHCC-CCA per year. Liver resection was reported as the most likely treatment for a single cHCC-CCA lesion of 2.0-6.0 cm (range: 73-93%) and for two lesions, one up to 6 cm and a second well-defined lesion of 2.0 cm (range: 60-66%). Nonetheless, marked interdisciplinary differences were noted. Surgeons mainly adhered to resection if technically feasible, whereas up to half of the hepatologists/gastroenterologists and oncologists switched to alternative treatment options with increasing tumour burden. Fifty-one (59%) clinicians considered liver transplantation as an option for patients with cHCC-CCA, with the Milan criteria defining the upper limit of inclusion. Overall, well-defined cHCC-CCA treatment policies were lacking and management was most often dependent on local expertise. CONCLUSIONS: Liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Marked interdisciplinary differences were reported, depending on local expertise. These findings stress the need for a well-defined multicentre prospective trial comparing treatments, including liver transplantation, to optimise the therapeutic management of cHCC-CCA. IMPACT AND IMPLICATIONS: Because the treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), a rare form of liver cancer, is currently not well-defined, we evaluated the contemporary treatment of this rare tumour type through an online survey sent to expert centres around the world. Based on the responses from 87 clinicians (46% surgeons, 29% oncologists, 25% hepatologists/gastroenterologists), representing four continents and 25 different countries, we found that liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Nonetheless, marked differences in treatment decisions were reported among the different specialties (surgeo

Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated

Robotic Versus Open Hepatic Arterial Infusion Pump Placement for Unresectable Intrahepatic Cholangiocarcinoma

Background: Hepatic arterial infusion pump (HAIP) chemotherapy is an effective treatment for patients with unresectable intrahepatic cholangiocarcinoma (iCCA). HAIP chemotherapy requires a catheter inserted in the gastroduodenal artery and a subcutaneous pump. The catheter can be placed using an open or robotic approach. Objective: This study aimed to compare perioperative outcomes of robotic versus open HAIP placement in patients with unresectable iCCA. Methods: We analyzed patients with unresectable iCCA included in the PUMP-II trial from January 2020 to September 2022 undergoing robotic or open HAIP placement at Amsterdam UMC, Erasmus MC, and UMC Utrecht. The primary outcome was time to functional recovery (TTFR). Results: In total, 22 robotic and 28 open HAIP placements were performed. The median TTFR was 2 days after robotic placement versus 5 days after open HAIP placement (p &lt; 0.001). One patient (4.5%) in the robotic group underwent a conversion to open because of a large bulky tumor leaning on the hilum immobilizing the liver. Postoperative complications were similar—36% (8/22) after robotic placement versus 39% (11/28) after open placement (p = 1.000). The median length of hospital stay was shorter in the robotic group—3 versus 5 days (p &lt; 0.001). All 22 robotic patients initiated HAIP chemotherapy post-surgery, i.e. 93% (26/28) in the open group (p = 0.497). The median time to start HAIP chemotherapy was 14 versus 18 days (p = 0.153). Conclusion: Robotic HAIP placement in patients with unresectable iCCA is a safe and effective procedure and is associated with a significantly shorter TTFR and hospital stay than open HAIP placement.</p

Robotic Versus Open Hepatic Arterial Infusion Pump Placement for Unresectable Intrahepatic Cholangiocarcinoma

Background: Hepatic arterial infusion pump (HAIP) chemotherapy is an effective treatment for patients with unresectable intrahepatic cholangiocarcinoma (iCCA). HAIP chemotherapy requires a catheter inserted in the gastroduodenal artery and a subcutaneous pump. The catheter can be placed using an open or robotic approach. Objective: This study aimed to compare perioperative outcomes of robotic versus open HAIP placement in patients with unresectable iCCA. Methods: We analyzed patients with unresectable iCCA included in the PUMP-II trial from January 2020 to September 2022 undergoing robotic or open HAIP placement at Amsterdam UMC, Erasmus MC, and UMC Utrecht. The primary outcome was time to functional recovery (TTFR). Results: In total, 22 robotic and 28 open HAIP placements were performed. The median TTFR was 2 days after robotic placement versus 5 days after open HAIP placement (p &lt; 0.001). One patient (4.5%) in the robotic group underwent a conversion to open because of a large bulky tumor leaning on the hilum immobilizing the liver. Postoperative complications were similar—36% (8/22) after robotic placement versus 39% (11/28) after open placement (p = 1.000). The median length of hospital stay was shorter in the robotic group—3 versus 5 days (p &lt; 0.001). All 22 robotic patients initiated HAIP chemotherapy post-surgery, i.e. 93% (26/28) in the open group (p = 0.497). The median time to start HAIP chemotherapy was 14 versus 18 days (p = 0.153). Conclusion: Robotic HAIP placement in patients with unresectable iCCA is a safe and effective procedure and is associated with a significantly shorter TTFR and hospital stay than open HAIP placement.</p

Comprehensive Geriatric Assessment, Treatment Decisions, and Outcomes in Older Patients Eligible for Pancreatic Surgery

Introduction: Periampullary cancer has a poor prognosis. Surgical resection is a potentially curative but high-risk treatment. Comprehensive geriatric assessment (CGA) can inform treatment decisions, but has not yet been evaluated in older patients eligible for pancreatic surgery. Methods: This prospective observational study included patients &gt;= 70 years of age eligible for pancreatic surgery. Frailty was defined as impairment in at least two of five domains: somatic, psychological, functional, nutritional, and social. Outcomes included postoperative complications, functional decline, and mortality. Results: Of the 88 patients included, 87 had a complete CGA. Sixty-five patients (75%) were frail and 22 (25%) were non-frail. Frail patients were more likely to receive nonsurgical treatment (43.1% vs. 9.1% p = 0.004). Fifty-seven patients underwent surgery, of which 52 (59%) underwent pancreaticoduodenectomy. The incidence of postoperative delirium was three times higher in frail patients (29.7% vs. 0%, p = 0.005). The risk of mortality was three times higher in frail patients (HR: 3.36, 95% CI: 1.43-7.89, p = 0.006). Conclusion: Frailty is common in older patients eligible for pancreatic surgery and is associated with treatment decision, a higher incidence of delirium and a three times higher risk of all-cause mortality. CGA can contribute to shared decision-making and optimize perioperative care in older patients

Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma

Background: The Hedgehog (Hh) signalling pathway is overexpressed in pancreatic ductal adenocarcinoma (PDA). Preclinical studies have shown that Hh inhibitors reduce pancreatic cancer stem cells (pCSC), stroma and Hh signalling. Methods: Patients with previously untreated metastatic PDA were treated with gemcitabine and nab-paclitaxel. Vismodegib was added starting on the second cycle. The primary endpoint was progression-free survival (PFS) as compared with historical controls. Tumour biopsies to assess pCSC, stroma and Hh signalling were obtained before treatment and after cycle 1 (gemcitabine and nab-paclitaxel) or after cycle 2 (gemcitabine and nab-paclitaxel plus vismodegib). Results: Seventy-one patients were enrolled. Median PFS and overall survival (OS) were 5.42 months (95% confidence interval [CI]: 4.37–6.97) and 9.79 months (95% CI: 7.85–10.97), respectively. Of the 67 patients evaluable for response, 27 (40%) had a response: 26 (38.8%) partial responses and 1 complete response. In the tumour samples, there were no significant changes in ALDH + pCSC following treatment. Conclusions: Adding vismodegib to chemotherapy did not improve efficacy as compared with historical rates observed with chemotherapy alone in patients with newly diagnosed metastatic pancreatic cancer. This study does not support the further evaluation of Hh inhibitors in this patient population. Trial registration: ClinicalTrials.gov Identifier: NCT01088815

Early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy:nationwide propensity-score-matched analysis

Background: Although robotic pancreatoduodenectomy has shown promising outcomes in experienced high-volume centres, it is unclear whether implementation on a nationwide scale is safe and beneficial. The aim of this study was to compare the outcomes of the early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy in the Netherlands. Methods: This was a nationwide retrospective cohort study of all consecutive patients who underwent robotic pancreatoduodenectomy or open pancreatoduodenectomy who were registered in the mandatory Dutch Pancreatic Cancer Audit (18 centres, 2014-2021), starting from the first robotic pancreatoduodenectomy procedure per centre. The main endpoints were major complications (Clavien-Dindo grade greater than or equal to III) and in-hospital/30-day mortality. Propensity-score matching (1 : 1) was used to minimize selection bias. Results: Overall, 701 patients who underwent robotic pancreatoduodenectomy and 4447 patients who underwent open pancreatoduodenectomy were included. Among the eight centres that performed robotic pancreatoduodenectomy, the median robotic pancreatoduodenectomy experience was 86 (range 48-149), with a 7.3% conversion rate. After matching (698 robotic pancreatoduodenectomy patients versus 698 open pancreatoduodenectomy control patients), no significant differences were found in major complications (40.3% versus 36.2% respectively; P = 0.186), in-hospital/30-day mortality (4.0% versus 3.1% respectively; P = 0.326), and postoperative pancreatic fistula grade B/C (24.9% versus 23.5% respectively; P = 0.578). Robotic pancreatoduodenectomy was associated with a longer operating time (359 min versus 301 min; P &lt; 0.001), less intraoperative blood loss (200 ml versus 500 ml; P &lt; 0.001), fewer wound infections (7.4% versus 12.2%; P = 0.008), and a shorter hospital stay (11 days versus 12 days; P &lt; 0.001). Centres performing greater than or equal to 20 robotic pancreatoduodenectomies annually had a lower mortality rate (2.9% versus 7.3%; P = 0.009) and a lower conversion rate (6.3% versus 11.2%; P = 0.032). Conclusion: This study indicates that robotic pancreatoduodenectomy was safely implemented nationwide, without significant differences in major morbidity and mortality compared with matched open pancreatoduodenectomy patients. Randomized trials should be carried out to verify these findings and confirm the observed benefits of robotic pancreatoduodenectomy versus open pancreatoduodenectomy.</p

Early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy:nationwide propensity-score-matched analysis

Background: Although robotic pancreatoduodenectomy has shown promising outcomes in experienced high-volume centres, it is unclear whether implementation on a nationwide scale is safe and beneficial. The aim of this study was to compare the outcomes of the early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy in the Netherlands. Methods: This was a nationwide retrospective cohort study of all consecutive patients who underwent robotic pancreatoduodenectomy or open pancreatoduodenectomy who were registered in the mandatory Dutch Pancreatic Cancer Audit (18 centres, 2014-2021), starting from the first robotic pancreatoduodenectomy procedure per centre. The main endpoints were major complications (Clavien-Dindo grade greater than or equal to III) and in-hospital/30-day mortality. Propensity-score matching (1 : 1) was used to minimize selection bias. Results: Overall, 701 patients who underwent robotic pancreatoduodenectomy and 4447 patients who underwent open pancreatoduodenectomy were included. Among the eight centres that performed robotic pancreatoduodenectomy, the median robotic pancreatoduodenectomy experience was 86 (range 48-149), with a 7.3% conversion rate. After matching (698 robotic pancreatoduodenectomy patients versus 698 open pancreatoduodenectomy control patients), no significant differences were found in major complications (40.3% versus 36.2% respectively; P = 0.186), in-hospital/30-day mortality (4.0% versus 3.1% respectively; P = 0.326), and postoperative pancreatic fistula grade B/C (24.9% versus 23.5% respectively; P = 0.578). Robotic pancreatoduodenectomy was associated with a longer operating time (359 min versus 301 min; P &lt; 0.001), less intraoperative blood loss (200 ml versus 500 ml; P &lt; 0.001), fewer wound infections (7.4% versus 12.2%; P = 0.008), and a shorter hospital stay (11 days versus 12 days; P &lt; 0.001). Centres performing greater than or equal to 20 robotic pancreatoduodenectomies annually had a lower mortality rate (2.9% versus 7.3%; P = 0.009) and a lower conversion rate (6.3% versus 11.2%; P = 0.032). Conclusion: This study indicates that robotic pancreatoduodenectomy was safely implemented nationwide, without significant differences in major morbidity and mortality compared with matched open pancreatoduodenectomy patients. Randomized trials should be carried out to verify these findings and confirm the observed benefits of robotic pancreatoduodenectomy versus open pancreatoduodenectomy.</p