Intraoperative ultrasound examination is useful for monitoring transplanted islets: A case report

A 39-y-old man, who had an episode of pancreatic bleeding due to chronic pancreatitis, received total pancreatectomy with islet autotransplantation (TP with IAT). Intraoperative ultrasound (US) examination was done to detect transplanted islets and evaluate the quality of US imaging. Islet isolation from the resected total pancreas was performed and approximately 230,000 islet equivalents (IEQ) (the tissue volume was 600 µL and the purity was 30%) were acquired. A double lumen catheter, used for transplantation and for monitoring the portal vein pressure, was inserted into the portal vein via the superior mesenteric vein, and the tip of the catheter was positioned at the bifurcation of the anterior and posterior branch of the portal vein to selectively infuse the islets into the right lobe of the liver in order to prevent total liver embolization. Intraoperative US examination (central frequency 7.5 MHz, Nemio™ XG, Toshiba Medical System Co.) was started at the same time as the transplantation. US examination revealed the transplanted islets as hyperechoic clusters that flowed from the tip of the catheter to the periphery of the portal vein. There were no findings of portal thrombosis or bleeding in the US image, and also no increase of the portal vein pressure during transplantation. In conclusion, we succeeded in visualizing human islets using US, which enabled us to perform islet transplantation safely. The hyperechoic images were considered to be viable islets. Intraoperative US examination can be useful for detecting islets at transplantation in a clinical setting.     

Institutional indications for islet transplantation after total pancreatectomy

Background/Purpose

This study was designed to establish institutional indications for pancreatic islet transplantation by examining patients with total pancreatectomy as candidates for islet allotransplantation.

Methods

In 12 patients who underwent total pancreatectomy, we compared pre-and postoperative plasma glucose level, body mass index, HbA1c, and daily insulin use; we examined candidacy for islet allotransplantation based on the guidelines of Japan’s islet transplantation registry.

Results

Eight of the 12 patients with total pancreatectomy were operated for intraductal papillary mucinous neoplasm. At our institution, the 5-year survival of patients with intraductal papillary mucinous neoplasm was far better (76.3%) than that of patients with pancreatic cancer. Postoperatively, plasma glucose level, HbA1c, and daily insulin use were increased in all patients with total pancreatectomy. Of the 12 patients treated with total pancreatectomy, 4 (intraductal papillary mucinous neoplasm, n = 2; islet cell tumor, n = 1; and acute pancreatitis due to arteriovenous malformation, n = 1) showed deteriorated diabetic control and therefore were considered to be candidates for islet allotransplantation according to the guidelines.

Conclusions

Islet allotransplantation could be indicated for patients with favorable postoperative survival who have had a total pancreatectomy for either benign or neoplastic disease.     

Continuous Glucose Monitoring Analysis as Predictor of Islet Yield and Insulin Requirements in Autologous Islet Transplantation After Complete Pancreatectomy

We analyzed the pretransplant continuous glucose monitoring (CGM) data of 45 patients that underwent total pancreatectomy followed by autologous islet transplantation (AIT) at the University of Arizona Medical Center. Traditional and novel metrics of CGM time series were correlated to the total islet count (TIC), islet equivalents (IEQs), and weight-normalized IEQs (IEQ/kg). In a subset cohort (n = 26) we analyzed the relationship among the infused number of islets, the CGM indicators, and the first recorded insulin requirement after the procedure. We conclude that receiving a high islet yield is sufficient yet not necessary to achieve low or null insulin requirements within the first 50 days after surgery. Furthermore, CGM inertia and CGM length of curve (2 novel CGM indicators) are shown to be correlated to islet yield, and the CGMs normalized area (Ao) and time ratio above hyperglycemic level (To) are strongly correlated to insulin requirement. A screening test based on To is shown to have 100% sensitivity and 88% specificity discriminating insulin independence upon discharge.     

Duodenum-Preserving total pancreatectomy for chronic pancreatitis

Preservation of the duodenum when performing total pancreatectomy lessens postoperative gastrointestinal disturbance. This paper describes the technique of duodenum-preserving total pancreatectomy where all pancreatic tissue within the C-loop is removed, and compares the out-come of patients who had a duodenum-preserving procedure with those who underwent a standard pancreatoduodenectomy. There was no operative mortality following duodenum-preserving total pancreatectomy, and all patients are alive at 46–125 months follow up. The major drawback of duodenum preservation has proven to be the development of a biliary stricture, in six patients. In carefully selected patients, duodenum-preserving total pancreatectomy has produced good long-term results.     

Induction of beta-cell resistance to hypoxia and technologies for oxygen delivery to transplanted pancreatic islets

Hypoxia is believed to be a crucial factor involved in cell adaptation to environmental stress. Islet transplantation, especially with immunoisolated islets, interrupts vascular connections, resulting in the substantially decreased delivery of oxygen and nutrients to islet cells. Insulin‐producing pancreatic beta cells are known to be highly susceptible to oxygen deficiency. Such susceptibility to hypoxia is believed to be one of the main causes of beta‐cell death in the post‐transplantation period. Different strategies have been developed for the protection of beta cells against hypoxic injury and for oxygen delivery to transplanted islets. The enhancement of beta‐cell defense properties against hypoxia has been achieved using various techniques such as gene transfection, drug supplementation, co‐culturing with stem cells and cell selection. Technologies for oxygen delivery to transplanted islets include local neovascularization of subcutaneous sites, electrochemical and photosynthetic oxygen generation, oxygen refuelling of bio‐artificial pancreas and whole body oxygenation by using hyperbaric therapy. Progress in the field of oxygen technologies for islet transplantation requires a multidisciplinary approach to explore and optimize the interaction between components of the biological system and different technological processes. This review article focuses mainly on the recently developed strategies for oxygenation and protection from hypoxic injury – to achieve stable and long‐term normoglycaemia in diabetic patients with transplanted pancreatic islets. Copyright © 2012 John Wiley & Sons, Ltd.     

Imaging of transplanted islets by positron emission tomography,magnetic resonance imaging,and ultrasonography

While islet transplantation is considered a useful therapeutic option for severe diabetes mellitus (DM), the outcome of this treatment remains unsatisfactory. This is largely due to the damage and loss of islets in the early transplant stage. Thus, it is important to monitor the condition of the transplanted islets, so that a treatment can be selected to rescue the islets from damage if needed. Recently, numerous trials have been performed to investigate the efficacy of different imaging modalities for visualizing transplanted islets. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are the most commonly used imaging modalities for this purpose. Some groups, including ours, have also tried to visualize transplanted islets by ultrasonography (US). In this review article, we discuss the recent progress in islet imaging.     

Magnetosome-like ferrimagnetic iron oxide nanocubes for highly sensitive MRI of single cells and transplanted pancreatic islets

For ultrasensitive magnetic resonance imaging (MRI), magnetic nanoparticles with extremely high r2 relaxivity are strongly desired. Magnetosome-like nanoparticles were prepared by coating polyethylene glycol-phospholipid (PEG-phospholipid) onto ferrimagnetic iron oxide nanocubes (FIONs). FIONs exhibited a very high relaxivity (r2) of 324 mM^-1 s^-1, allowing efficient labeling of various kinds of cells. The magnetic resonance (MR) imaging of single cells labeled with FIONs is demonstrated not only in vitro but also in vivo. Pancreatic islet grafts and their rejection could be imaged using FIONs on a 1.5 T clinical MRI scanner. The strong contrast effect of FIONs enabled MR imaging of transplanted islets in small rodents as well as in large animals. Therefore, we expect that MR imaging of pancreatic islet grafts using FIONs has the potentials for clinical applications. Furthermore, FIONs will enable highly sensitive noninvasive assessment after cell transplantation.     

Therapeutic ultrasound for chronic total coronary artery occlusions

This article focuses on the use of catheter-delivered ultrasound as a device for treatment of coronary arterial total occlusion (CTO). The standard treatment of CTO is reviewed and serves as the basis for the need for new treatment options, such as catheter-delivered ultrasound (SONICROSS). The results of FDA-approved Phase I and Phase II clinical trials using SONICROSS for refractory CTO are described. The Phase II trials indicate that the SONICROSS-facilitated guidewire passage in 71% of CTOs are otherwise refractory to guidewire passage. However, at present, the SONICROSS catheter system is limited in its ability to be delivered reliably to the CTO because of catheter size and trackability.     

Novel use of ultrasound guidance for recanalization of iliac,femoral, and popliteal arteries

Objectives : We attempted to demonstrate the safety and feasibility of intravascular ultrasound (IVUS)‐guided endluminal endovascular therapy for chronic total occlusion (CTO) of the iliac and/or femoropopliteal arteries using Treasure 12, a stiff guidewire for peripheral CTO of 0.018 in. in monodirectional approach setting. Background : Endovascular therapy for CTO of the iliac and femoropopliteal arteries is still technically challenging. Methods : Endovascular therapy was performed in 110 patients who were admitted to Hyogo College of Medicine Hospital with iliac and/or femoropopliteal artery disease from January 2006 to October 2007. We retrospectively analyzed the data of consecutive 47 patients who underwent the endovascular therapy by monodirectional approach for CTO lesions of the iliac and femoropopliteal arteries. From January 2006 to November 2006 (phase 1), standard technique was applied for the treatment of 21 lesions. From December 2006 to October 2007 (phase 2), IVUS‐guided endovascular therapy was applied for the treatment of 31 lesions. Results : Clinical and lesion characteristics in phase 1 were not significantly different from those in phase 2. The overall initial technical success rate improved from 81% in phase 1 to 97% in phase 2. There were no significant differences in radiation exposure time between phase 1 and phase 2. Total volume of contrast material was significantly smaller in phase 2 than in phase 1 (P < 0.01). Conclusions : The IVUS‐guided endovascular therapy for CTO using Treasure 12 guidewire is feasible and safe, minimizes contrast material, and has a high initial technical success rate. © 2008 Wiley‐Liss, Inc.     

自制新型血管内超声双腔微导管引导下行慢性完全闭塞病变介入治疗

处理入口不明的慢性完全闭塞病变(CTO)可借助血管内超声,但反复交换微导管和超声导管可能增加操作相关并发症。解放军白求恩国际和平医院自主研发的新型血管内超声双腔微导管,由血管内超声导管以及与其并联为一体的治疗微导管构成,超声导管和工作导丝同步进入病变部位,相当于在血管内超声实时探查下进行直接定位操作,有助于正确把握穿刺方向,为介入医师进行慢性闭塞病变的治疗增添了新工具。在此基础上,本文通过结合1例应用此新型血管内超声双腔微导管成功治疗入口闭塞的CTO病变经验,为读者提供更为直观的认识。     

Subintimal guidewire tracking during successful percutaneous therapy for chronic coronary total occlusions: Insights from an intravascular ultrasound analysis

Objectives : We sought to determine the frequency of subintimal guidewire tracking during successful percutaneous coronary intervention (PCI) for chronic coronary total occlusions (CTOs) and to better understand the procedural implications of this event. Background : Successful PCI for chronic CTO is associated with improved outcomes in patients with ischemia. While subintimal guidewire tracking resulting in failure to cross is recognized as the major mode of failure for CTO PCI, the implications of subintimal guidewire tracking during successful CTO PCI are unknown. Methods : Between March 2007 and October 2007, 26 consecutive patients, each with one de‐novo CTO lesion successfully crossed with a guidewire were included in the analysis. Intravascular ultrasound (IVUS) was performed in each CTO vessel after guidewire crossing. Cases were classified as having definite subintimal wire tracking or no clear evidence of subintimal wire tracking based on analysis of IVUS images. Results : Subintimal wire tracking occurred in 45% of cases. In cases where subintimal wire tracking was present, a previous attempt at CTO PCI was more common (42% vs. 7%, P ≤ 0.05). Subintimal wire tracking was also associated with significantly longer final mean stent length (71 vs. 50 mm), procedure time (122 vs. 69 min), fluoroscopy time (47 vs. 22 min), and contrast dose (300 vs. 199 mL, P ≤ 0.05 for all). There was one perforation in the subintimal group which was successfully treated with stent placement. Conclusions : Subintimal wire tracking occurs frequently during successful PCI for CTO and is associated with increased lesion and procedural complexity.© 2011 Wiley Periodicals, Inc     

Intravascular ultrasound guided wiring re‐entry technique for complex chronic total occlusions

Background

The successful recanalization rate of chronic total occlusion (CTO) lesions without retrograde collaterals available is always low. Intravascular ultrasound (IVUS) may be useful to guide the subintimal guidewire to re‐enter the true lumen. We evaluated the clinical feasibility and efficacy of the IVUS‐guided wiring re‐entry technique for these complex CTO lesions.

Methods

Twenty consecutive patients (19 male, mean age: 65.3 ± 12.8 years) with both failed antegrade and retrograde approaches were enrolled. The IVUS catheter was introduced into the subintimal space to identify the entry point into the subintimal space, and guide another stiff wire to re‐enter the true lumen with the adjacent side‐branch or first wire as markers, or using IVUS‐guided parallel wire technique.

Results

The entry point into the subintimal space was identified by IVUS in all cases, and the IVUS‐guided wiring re‐entry technique succeeded in 17 cases (85%). No procedure‐related complication was noted except one case of delayed cardiac tamponade due to the wire perforation. During the mean follow‐up period of 1.9 ± 1.3 years, there was no adverse cardiac event, except one patient died of the complication of cardiac transplantation.

Conclusion

The IVUS‐guided wiringre‐entry technique might be feasible and safe for the recanalization of complex CTO lesions.

     

Red blood cell phenotyping is a sensitive technique for monitoring chronic myeloid leukaemia patients after T-cell-depleted bone marrow transplantation and after donor leucocyte infusion

Fifteen consecutive patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukaemia (CML) who relapsed from T-cell-depleted bone marrow transplantation (BMT) were successfully treated with donor leucocyte infusions (DLIs). Chimaerism was analysed using red blood cell phenotyping (RCP), and the results were compared with cytogenetic analysis and outcome of qualitative and quantitative polymerase chain reaction (PCR) for breakpoint molecules. In all patients, an increase in autologous erythrocytes and/or a decrease in donor red cells indicated relapse. Donor erythrocytes started to increase from 4 to 20 (median 12) weeks after DLI. At 6 and 12 months after DLI, complete donor chimaerism was found in 11 and 15 patients, respectively, and all patients were in cytogenic remission. A high percentage of autologous red cells at the time of DLI predicted pancytopenia. During relapse and after DLI, the percentage of autologous red cells was strongly correlated with the reappearance and disappearance of Ph-positive metaphases (r = 0.90; P < 0.001 and r = 0.96; P < 0.001 respectively). The same was true for the correlation between the percentage of autologous red cells and positivity/negativity in PCR for Bcr-Abl breakpoint molecules (r = 0.94; P < 0.001). A normalized Bcr-Abl dose of greater than 10-3 in real-time quantitative PCR correlated well with relapse and the presence of autologous red blood cells (r = 0.77; P < 0.001). We conclude that RCP is a sensitive, easy to perform and fast technique for the prediction of pending relapse after BMT for CML. RCP also predicts the response to DLI and the occurrence of bone marrow aplasia after DLI.     

Colour Doppler ultrasonography of a segmental branch of the portal vein is useful for early diagnosis and monitoring of the therapeutic course of veno-occlusive disease after allogenic haematopoietic stem cell transplantation

We report two cases in which visualization of the segmental branch of the hepatic portal vein with the colour Doppler ultrasonography (US) technique was useful for the early diagnosis of veno-occlusive disease. The change in blood flow in the segmental branch of the portal vein occurred 5 and 6 d before the clinical criteria were fulfilled in the two cases. Reverse flow in the segmental branch began partially in the liver at first, and then spread to the whole liver several days later. All the US findings in both cases disappeared after thrombolytic therapy.     

ESWL for large pancreatic calculi: Report of over 5000 patients

IntroductionThe primary aim of this study was to evaluate efficacy, safety and short-term pain relief after ESWL for large pancreatic calculi in over 5000 patients at a single center.MethodsThis is a retrospective analysis of prospectively collected data. Patients with painful calculi >5 mm, located in the head, neck and body region in the MPD, who were not amenable for extraction by the standard procedure of endoscopic pancreatic sphincterotomy were subjected to ESWL using a third generation dual focus lithotripter. Patients were followed up at 6 months for outcome evaluation.ResultsA total of 5124 patients (66% males) were subjected to ESWL. Majority of stones (79.2%) were radiopaque. Single calculi were seen in 3851 (75.1%).The majority of stones were located in head region of MPD in 2824 (55.1%) patients. 4386 (85.5%) patients required 3 or less sessions for fragmentation and complete stone clearance was achieved in 3722 (72.6%). EPS was performed in 5022 (98%) while PD stenting was required in 3536 (69%) patients. Of the 4280 patients followed up for 6 months, 3529 (82.6%) patients were pain free. Another 512 (11.9%) patients had significant reduction in VAS score. In 229 (5.3%) there was no decrease in pain intensity. Minor and self-limiting complications were reported in 1153 (22.5%).DiscussionOur study confirms the safety and efficacy and short-term pain relief of ESWL for large calculi in the MPD. In properly selected patients, this should be offered as the first line of therapy for all large MPD calculi not amenable to the standard techniques of stone extraction.     

Surgical approach and short-term outcomes in adults and children undergoing total pancreatectomy with islet autotransplantation: A report from the Prospective Observational Study of TPIAT

BackgroundTotal pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation.MethodsWe evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n = 84) with adults (n = 195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP.ResultsChildren more commonly underwent splenectomy (100% versus 91%, p = 0.002), pylorus preservation (93% versus 67%; p < 0.0001), Roux-en-Y duodenojejunostomy reconstruction (92% versus 35%; p < 0.0001), and enteral feeding tube placement (93% versus 63%; p < 0.0001). Median islet equivalents/kg transplanted was higher in children (4577; IQR 2816-6517) than adults (2909; IQR 1555-4479; p < 0.0001), with COBE purification less common in children (4% versus 15%; p = 0.0068). Median length of hospital stay was higher in children (15 days; IQR 14–22 versus 11 days; IQR 8–14; p < 0.0001), but 30-day readmissions were lower in children (13% versus 26%, p = 0.018). Rate of portal vein thrombosis was significantly lower in children than in adults (2% versus 10%, p = 0.028). There were no mortalities in the first 90 days post-TPIAT.ConclusionsPancreatectomy techniques differ between children and adults, with islet yields higher in children. The rates of portal vein thrombosis and early readmission are lower in children.