Near-infrared photoimmunotherapy targeting PD-L1: Improved efficacy by preconditioning the tumor microenvironment.

Near-infrared photoimmunotherapy (NIR-PIT) is a new type of cancer therapy that employs antibody-IRDye700DX conjugates (AbPCs) and near-infrared (NIR) light at a wavelength of 689 nm, the excitation wavelength of IR700. Administered intravenously, injected AbPCs bind specifically to cells expressing the target antigen, whereupon NIR light exposure causes rapid, selective killing. This process induces an anticancer T cell response, leading to sustained anticancer host immune response. Programmed cell death ligand-1 (PD-L1) is a major inhibitory immune checkpoint molecule expressed in various cancers. In this study, we first assessed the efficacy of PD-L1-targeted NIR-PIT (αPD-L1-PIT) in immune-competent tumor mouse models. αPD-L1-PIT showed a significant therapeutic effect on the tumor models with high PD-L1 expression. Furthermore, αPD-L1-PIT induced an abscopal effect on distant tumors and long-term immunological memory. In contrast, αPD-L1-PIT was not as effective for tumor models with low PD-L1 expression. To improve the efficacy of PD-L1-targeted NIR-PIT, PEGylated interferon-gamma (IFNγ) was administered with αPD-L1-PIT. The combination therapy improved the treatment efficacy by increasing PD-L1 expression leading to more efficient cell killing by αPD-L1-PIT. Furthermore, the PEGylated IFNγ led to a CD8+ T cell-dominant tumor microenvironment (TME) with an enhanced anticancer T cell response after αPD-L1-PIT. As a result, even so-called cold tumors exhibited complete responses after αPD-L1-PIT. Thus, combination therapy of PEGylated IFNγ and PD-L1-targeted NIR-PIT has the potential to be an important future strategy for cancer immunotherapy.

Middle-segment preserving pancreatectomy: a literature review and case report.

PURPOSE: Middle segment-preserving pancreatectomy (MSPP) is a relatively new parenchymal-sparing surgery that has been introduced as an alternative to total pancreatectomy (TP) for multicentric benign and borderline pancreatic diseases. To date, only 36 cases have been reported in English. METHODS: We reviewed 22 published articles on MSPP and reported an additional case. RESULTS: Our patient was a 49-year-old Japanese man diagnosed with Zollinger-Elison syndrome (ZES) caused by duodenal and pancreatic gastrinoma associated with multiple endocrine neoplasia syndrome type 1. We avoided TP and chose MSPP as the operative technique due to his relatively young age. The patient developed a grade B postoperative pancreatic fistula (POPF), which improved with conservative treatment. He was discharged without further treatment. To date, no tumor has recurred, and pancreatic function seems to be maintained. According to a literature review, the morbidity rate of MSPP is as high as 54%, mainly due to the high incidence of POPF (32%). In contrast, there was no perioperative mortality, and postoperative pancreatic function was comparable to that after conventional pancreatectomy. CONCLUSIONS: Despite the high incidence of POPF, MSPP appears to be safe, with low perioperative mortality and good postoperative pancreatic sufficiency.

Laparoscopic minor liver resection for hepatocellular carcinoma.

BACKGROUND: Previous studies have suggested that laparoscopic liver resection for hepatocellular carcinoma is associated with lower postoperative complications compared with open liver resection. METHODS: We conducted a retrospective analysis of 109 hepatocellular carcinoma patients who underwent minor liver resection at a Japanese tertiary care hospital from November 2010 to December 2022. RESULTS: The laparoscopic liver resection group experienced significantly lower median intraoperative blood loss compared with the open liver resection group (P = 0.0001). Furthermore, the laparoscopic liver resection group had a significantly shorter median hospital stay compared with the open liver resection group (P = 0.0002). However, there was no significant difference in median postoperative survival between the laparoscopic liver resection group and the open liver resection group (P = 0.717). CONCLUSIONS: Laparoscopic minor liver resection for hepatocellular carcinoma resulted in reduced blood loss and hospital stay without compromising long-term survival outcomes.

Percutaneous Transhepatic Gallbladder Intervention as a Bridge to Cholecystectomy: Aspiration or Drainage?

BACKGROUND: Percutaneous transhepatic gallbladder aspiration (PTGBA) and percutaneous transhepatic gallbladder drainage (PTGBD) are often the first-line treatments for acute cholecystitis, instead of surgical cholecystectomy. This retrospective study aimed to compare the treatment outcomes of PTGBA and PTGBD and evaluate the risks of treatment failure among patients undergoing PTGBA before surgical cholecystectomy. METHODS: We retrospectively reviewed 99 patients who underwent PTGBA or PTGBD as the first-line treatment before surgical cholecystectomy, between January 2014 and December 2019. Patient characteristics, computed tomography (CT) findings, and post-treatment outcomes were compared between the PTGBA and PTGBD groups. Additionally, risk factors, including CT findings for PTGBA failure, were assessed using multivariate univariate analysis with a backward selection model. RESULTS: Acute cholecystitis was not controlled in 21 of 47 (44.7%) patients in the PTGBA group and one of 52 patients (1.9%) in the PTGBD group (P < .001). Subsequent multiple logistic regression analysis identified the contrast effect of the gallbladder bed in the arterial phase of contrast-enhanced CT (odds ratio [OR] 9.17, 95% confidence interval [CI] 2.08-40.4, P = 0.003) and onset within 3 days (odds ratio [OR] 6.29, 95% confidence interval [CI] 1.37-29.0, P = 0.018) as independent risk factors for PTGBA failure. CONCLUSIONS: PTGBA is more prone to failure than PTGBD; however, it is a simpler gallbladder drainage treatment method without the need for X-ray fluoroscopy and catheter management after the procedure. Evaluating the risk of PTGBA failure using CT findings and onset date would help us choose a drainage approach more effectively.

Surgical management of appendicitis in patients with human immunodeficiency virus (HIV) positivity: a propensity score-matched analysis in a base hospital for HIV treatment in Japan.

PURPOSE: To investigate the impact of human immunodeficiency virus (HIV) infection on surgical outcomes after appendectomy. METHODS: Data on patients who underwent appendectomy for acute appendicitis between 2010 and 2020 at our hospital were investigated retrospectively. The patients were classified into HIV-positive and HIV-negative groups using propensity score-matching (PSM) analysis, adjusting for the five reported risk factors for postoperative complications: age, sex, Blumberg's sign, C-reactive protein level, and white blood cell count. We compared the postoperative outcomes of the two groups. HIV infection parameters, including the number and proportion of CD4 + lymphocytes and the HIV-RNA levels were also compared before and after appendectomy in the HIV-positive patients. RESULTS: Among 636 patients enrolled, 42 were HIV-positive and 594 were HIV-negative. Postoperative complications occurred in five HIV-positive patients and eight HIV-negative patients, with no significant difference in the incidence (p = 0.405) or severity of any complication (p = 0.655) between the groups. HIV infection was well-controlled preoperatively using antiretroviral therapy (83.3%). There was no deterioration in parameters and no changes in the postoperative treatment in any of the HIV-positive patients. CONCLUSION: Advances in antiviral drugs have made appendectomy a safe and feasible procedure for HIV-positive patients, with similar postoperative complication risks to HIV-negative patients.

Opening up new VISTAs: V-domain immunoglobulin suppressor of T cell activation (VISTA) targeted near-infrared photoimmunotherapy (NIR-PIT) for enhancing host immunity against cancers.

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an inhibitory immune checkpoint molecule that is broadly expressed on lymphoid and myeloid cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Near-infrared photoimmunotherapy (NIR-PIT) is a cancer treatment that utilizes an antibody-photoabsorber (IRDye 700DX NHS ester) conjugate to selectively kill target cells after the local application of NIR light. Depletion of VISTA-expressing cells in the tumor microenvironment (TME) using NIR-PIT could enhance anti-tumor immune responses by removing immune suppressive cells. The purpose of this study was to evaluate the anti-tumor efficacy of VISTA-targeted NIR-PIT using two murine tumor models, MC38-luc and LL2-luc. VISTA was expressed on T cells including Tregs and MDSCs in the TME of these tumors. In contrast, CD45 - cells, including cancer cells, did not express VISTA. VISTA-targeted NIR-PIT depleted VISTA-expressing cells ex vivo. In vivo VISTA-targeted NIR-PIT inhibited tumor progression and prolonged survival in both models. After VISTA-targeted NIR-PIT, augmented CD8 + T cell and dendritic cell activation were observed in regional lymph nodes. In conclusion, VISTA-targeted NIR-PIT can effectively treat tumors by decreasing VISTA-expressing immune suppressor cells in the TME. Local depletion of VISTA-expressing cells in the tumor bed using NIR-PIT is a promising new cancer immunotherapy for treating various types of tumors.

Selection of antibody and light exposure regimens alters therapeutic effects of EGFR-targeted near-infrared photoimmunotherapy.

Near-infrared photoimmunotherapy (NIR-PIT) is a cell-specific cancer therapy that uses an antibody-photoabsorber (IRDye700DX, IR700) conjugate (APC) and NIR light. Intravenously injected APC binds the target cells, and subsequent NIR light exposure induces immunogenic cell death only in targeted cells. Panitumumab and cetuximab are antibodies that target human epidermal growth factor receptor (hEGFR) and are suitable for NIR-PIT. In athymic nude mouse models, panitumumab-based NIR-PIT showed superior therapeutic efficacy compared to cetuximab-based NIR-PIT because of the longer half-life of panitumumab-IR700 (pan-IR700) compared with cetuximab-IR700 (cet-IR700). Two light exposures on two consecutive days have also been shown to induce superior effects compared to a single light exposure in the athymic nude mouse model. However, the optimal regimen has not been assessed in immunocompetent mice. In this study, we compared panitumumab and cetuximab in APCs for NIR-PIT, and single and double light exposures using a newly established hEGFR-expressing cancer cell line derived from immunocompetent C57BL/6 mice (mEERL-hEGFR cell line). Fluorescence imaging showed that the decline of pan-IR700 was slower than cet-IR700 confirming a longer clearance time. Among all the combinations tested, mice receiving pan-IR700 and double light exposure showed the greatest tumor growth inhibition. This group was also shown to activate CD8+ T lymphocytes in lymph nodes and accumulate CD8+ T lymphocytes to a greater extent within the tumor compared with the control group. These results showed that APCs with longer half-life and double light exposure lead to superior outcomes in cancer cell-targeted NIR-PIT in an immunocompetent mouse model.

Estimation of Physiologic Ability and Surgical Stress (E-PASS) Predicts Postoperative Major Complications After Hepato-Pancreato Biliary Surgery in the Elderly.

BACKGROUND: As society ages, an increasing number of elderly patients require hepato-pancreato-biliary (HPB) surgery. We investigated the risk factors for complications in elderly patients undergoing HPB surgery using surgical risk scoring models. METHODS: We retrospectively investigated 184 elderly patients (≥ 65 years old) who underwent HPB surgery, including the liver, pancreas, bile duct, and/or gallbladder resection, with exemption to simple cholecystectomy between January 2017 and December 2019. The surgical risk scoring models used included the Estimation of Physiological Ability and Surgical Stress (E-PASS), Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM), and Geriatric 8 (G8). We evaluated the correlations between the scores and severe complications. Complications were classified as severe (Clavien-Dindo classification [C-D] ≥ III) or non-severe (C-D ≤ II). RESULTS: Complications occurred in 78 patients (24 C-D ≥ III, 54 C-D ≤ II). Preoperative risk score (PRS), surgical stress score (SSS), and comprehensive risk score (CRS) were significantly higher in patients with C-D ≥ IIIa than in those with C-D ≤ II. Multiple logistic regression analysis revealed that PRS (P = 0.01) and SSS (P = 0.04) were independent predictive factors for severe complications. However, the POSSUM and G8 models showed no significant correlations to severe complications. CONCLUSION: E-PASS is a useful model for predicting complications in elderly patients undergoing HPB surgery.

Added value of indocyanine green fluorescence imaging in liver surgery.

Recently, indocyanine green (ICG) fluorescence imaging has been widely used as a substitute for cholangiography in hepatobiliary surgery, to detect hepatic tumors, for accurate anatomical hepatectomy, and to increase the safety and accuracy of minimally invasive (laparoscopic and robotic) hepatectomy. The clinical relevance of this method has been increasing gradually, as new procedures develop in this field. Various important roles and the latest added value of ICG fluorescence imaging in liver surgery are discussed in this report.

Norcyanine-Carbamates Are Versatile Near-Infrared Fluorogenic Probes.

Fluorogenic probes in the near-infrared (NIR) region have the potential to provide stimuli-dependent information in living organisms. Here, we describe a new class of fluorogenic probes based on the heptamethine cyanine scaffold, the most broadly used NIR chromophore. These compounds result from modification of heptamethine norcyanines with stimuli-responsive carbamate linkers. The resulting cyanine carbamates (CyBams) exhibit exceptional turn-ON ratios (∼170×) due to dual requirements for NIR emission: carbamate cleavage through 1,6-elimination and chromophore protonation. Illustrating their utility in complex in vivo settings, a γ-glutamate substituted CyBam was applied to imaging γ-glutamyl transpeptidase (GGT) activity in a metastatic model of ovarian cancer. Overall, CyBams have significant potential to extend the reach of fluorogenic strategies to intact tissue and live animal imaging applications.

Endoscopic near-infrared photoimmunotherapy in an orthotopic head and neck cancer model.

Near-infrared photoimmunotherapy (NIR-PIT) is a cell selective cancer therapy that uses an antibody-photoabsorber (IRDye700DX, IR700) conjugate (APC) and NIR light. NIR-PIT targeting epidermal growth factor receptor (EGFR) in head and neck cancer (HNC) was conditionally approved in Japan in 2020. APC-bound tumors can be detected using endoscopic fluorescence imaging, whereas NIR light can be delivered using endoscopic fiber optics. The aims of this study were: (1) to assess the feasibility of endoscopic NIR-PIT in an orthotopic HNC model using a CD44-expressing MOC2-luc cell line; and (2) to evaluate quantitative fluorescence endoscopic imaging prior to and during NIR-PIT. The results were compared in 3 experimental groups: (1) untreated controls, (2) APC injection without light exposure (APC-IV), and (3) APC injection followed by NIR light exposure (NIR-PIT). APC injected groups showed significantly higher fluorescence signals for IR700 compared with the control group prior to therapeutic NIR light exposure, and the fluorescence signal significantly decreased in the NIR-PIT group after light exposure. After treatment, the NIR-PIT group showed significantly attenuated bioluminescence compared with the control and the APC-IV groups. Histology demonstrated diffuse necrotic death of the cancer cells in the NIR-PIT group alone. In conclusion, endoscopically delivered light combined with quantitative fluorescence imaging can be used to "see and treat" HNC. This method could also be applied to other types of cancer approachable with endoscopy.

Diagnostic imaging in near-infrared photoimmunotherapy using a commercially available camera for indocyanine green.

Near-infrared photoimmunotherapy (NIR-PIT) is a new type of cancer treatment, which was recently approved in Japan for patients with inoperable head and neck cancer. NIR-PIT utilizes antibody-IRDye700DX (IR700) conjugates and NIR light at a wavelength of 690 nm. NIR light exposure leads to physicochemical changes in the antibody-IR700 conjugate cell receptor complex, inducing rapid necrotic cell death. Just as fluorescence guided surgery is useful for surgeons to resect tumors completely, real-time information of tumor locations would help clinicians irradiate NIR light more precisely. IR700 is a fluorescence dye that emits at 702 nm; however, there is no clinically available device optimized for detecting this fluorescence. On the other hand, many indocyanine green (ICG) fluorescence imaging devices have been approved for clinical use. Therefore, we investigated whether LIGHTVISION, one of the clinically available ICG cameras, could be employed for tumor detection. We hypothesized that irradiation with even low-power 690-nm laser light, attenuated by 99% with a neutral-density filter, could be detected with LIGHTVISION without fluorescence decay or therapeutic effect because of the long emission tail of IR700 beyond 800 nm (within the detection range of LIGHTVISION). We demonstrated that the LIGHTVISION camera, originally designed for ICG detection, can detect the tail of IR700 fluorescence in real time, thus enabling the visualization of target tumors.

Fluorescence Imaging of Tumor-Accumulating Antibody-IR700 Conjugates Prior to Near-Infrared Photoimmunotherapy (NIR-PIT) Using a Commercially Available Camera Designed for Indocyanine Green.

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that uses antibody-IRDye700DX (IR700) conjugates and was recently approved in Japan for patients with inoperable head and neck cancer. Exposure of the tumor with NIR light at a wavelength of 690 nm leads to physicochemical changes in the antibody-IR700 conjugate-cell receptor complex, resulting in increased hydrophobicity and damage to the integrity of the cell membrane. However, it is important that the tumor be completely exposed to light during NIR-PIT, and thus, a method to provide real-time information on tumor location would help clinicians direct light more accurately. IR700 is a fluorophore that emits at 702 nm; however, there is no clinically available device optimized for detecting this fluorescence. On the other hand, many indocyanine green (ICG) fluorescence imaging devices have been approved for clinical use in operating rooms. Therefore, we investigated whether LIGHTVISION, one of the clinically available ICG cameras, could be employed for NIR-PIT target tumor detection. Due to the limited benefits of adding IR700 molecules, the additional conjugation of IRDye800CW (IR800) or ICG-EG4-Sulfo-OSu (ICG-EG4), which has an overlapping spectrum with ICG, to trastuzumab-IR700 conjugates was performed. Conjugation of second NIR dyes did not interfere the efficacy of NIR-PIT. The dual conjugation of IR800 and IR700 to trastuzumab clearly visualized target tumors with LIGHTVISION by detecting emission light of IR800. We demonstrated that the conjugation of second NIR dyes enables us to provide a real-time feedback of tumor locations prior to NIR-PIT.

Detailed anatomy and procedure of celiac artery decompression in median arcuate ligament syndrome.

PURPOSE: Median arcuate ligament (MAL) syndrome is a clinical syndrome caused by the compression of the celiac artery (CA) by the MAL. This study aimed to present the detailed anatomy and a step-by-step procedure of CA decompression for MAL syndrome. METHODS: The CA decompression procedure involves exposing the diaphragmatic crura and aorta, taping the left gastric artery, and dividing the compressive tissues. The MAL and ganglionic tissue, which form a broad band with multiple layers overlying the CA, comprise the compressive tissues. Therefore, the compressive tissues overlying the CA are encircled and divided one by one until the CA stenosis is released. CA decompression is confirmed with intraoperative duplex ultrasonography of the CA, with a return to normal peak systolic velocities without variation between deep inspiration and expiration. CONCLUSION: This report presents the detailed anatomy and procedural steps for CA decompression in MAL syndrome.

Diagnosis of celiac artery stenosis using multidetector computed tomography and evaluation of the collateral arteries within the mesopancreas of patients undergoing pancreaticoduodenectomy.

INTRODUCTION: Celiac artery (CA) stenosis (CAS), caused by various factors, is often asymptomatic because collateral blood flow from the superior mesenteric artery supplies the CA outflow region. The purpose of this study was to investigate the usefulness of multidetector computed tomography (MDCT) for diagnosing CAS and associated collateral artery formation, and elucidating the effect of CAS on the numbers and diameters of the arteries within the mesopancreas. MATERIALS AND METHODS: We investigated 106 patients who underwent contrast-enhanced MDCT, before pancreaticoduodenectomy, between January 2015 and September 2019. MDCT was used to determine the percentage stenosis of the CAs; patients were classified into CAS (-) (0-29% stenosis) and CAS (+) (30-100% stenosis) groups. The dissection lines of the mesopancreas were classed as Level I or II, and the numbers and diameters of the arteries along each dissection line were counted and measured. RESULTS: There were 27 CAS (+) patients and 79 CAS (-) patients. In the CAS (+) group there were more arteries and they had larger diameters than those in the CAS (-) group, at both Levels I and II. There were significantly more arteries when the CA stenosis was ≥30% and they had larger diameters when the stenosis was ≥50%. CONCLUSIONS: MDCT is useful for diagnosing CAS, and CAS is associated with larger numbers and diameters of the arteries within the mesopancreas.

Real-Time Fluorescence Imaging Using Indocyanine Green to Assess Therapeutic Effects of Near-Infrared Photoimmunotherapy in Tumor Model Mice.

BACKGROUND: Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that causes an increase in tumor perfusion, a phenomenon termed the super-enhanced permeability and retention effect. Currently, in vivo treatment efficacy of NIR-PIT is observable days after treatment, but monitoring would be improved by more acute detection of intratumor change. Fluorescence imaging may detect increased tumor perfusion immediately after treatment. METHODS: In the first experiment, athymic nude mouse models bearing unilateral subcutaneous flank tumors were treated with either NIR-PIT or laser therapy only. In the second experiment, mice bearing bilateral flank tumors were treated with NIR-PIT only on the left-sided tumor. In both groups, immediately after treatment, indocyanine green was injected at different doses intravenously, and mice were monitored with the Shimadzu LIGHTVISION fluorescence imaging system for 1 hour. RESULTS: Tumor-to-background ratio of fluorescence intensity increased over the 60 minutes of monitoring in treated mice but did not vary significantly in control mice. Tumor-to-background ratio was highest in the 1 mg kg-1 and 0.3 mg kg-1 doses. In mice with bilateral tumors, tumor-to-untreated tumor ratio increased similarly. CONCLUSIONS: Acute changes in tumor perfusion after NIR-PIT can be detected by real-time fluorescence imaging.

Immunohistochemical staining as supportive diagnostic tool for pseudomyxoma peritonei arising from intraductal papillary mucinous neoplasm: A report of two cases and literature review.

BACKGROUND/OBJECTIVES: Pseudomyxoma peritonei (PMP) arising from an intraductal papillary mucinous neoplasm of the pancreas (IPMN) is a rare condition. The diagnosis of IPMN as the origin of PMP is mainly inferred from the clinical course and the exclusion of PMP from other organs. The pathological diagnosis has not yet been established. To evaluate the usefulness of immunohistochemical staining for the diagnosis of the primary lesion of PMP as IPMN. METHODS: There are 2 cases of PMP arising from IPMN between March 2010 and December 2019 at National Center for Global Health and Medicine. A PubMed search that reported PMP arising from IPMN identified 16 additional cases. Diagnostic methods and clinicopathological features of 18 cases were compared. RESULTS: Four cases including our two cases used immunohistochemical staining for the diagnosis of PMP arising from IPMN. The correspondence of the immunohistochemical staining between PMP and IPMN was shown in the three cases including previously reported two cases and one of our two cases to identify the primary lesion of PMP as IPMN. In addition, we revealed that the comparison of the immunostaining pattern of PMP with the representative immunostaining pattern of the candidate primary lesions is helpful for the diagnosis of the primary lesion of PMP. CONCLUSIONS: Immunohistochemical staining is helpful to identify the primary lesion of PMP as IPMN.

The Effect of Antibody Fragments on CD25 Targeted Regulatory T Cell Near-Infrared Photoimmunotherapy.

Regulatory T (Treg) cells play a major role in immune suppression permitting tumors to evade immune surveillance. Depletion of intratumoral Treg cells can result in tumor regression. However, systemic depletion of Tregs may also induce autoimmune adverse events. Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cell-specific cancer therapy that locally kills specific cells in the tumor. Antibody-photoabsorber (IRDye700DX) conjugates (APC) are injected and bind to the tumor, and subsequent administration of NIR light to the tumor results in rapid cell death only in targeted cells. CD25-targeted NIR-PIT has been shown to induce spatially selective depletion of tumor-associated Treg cells. In this study, we compared the efficacy of an antibody fragment, anti-CD25-F(ab')2, and a full antibody, anti-CD25-IgG, as agents for NIR-PIT. Tumor-bearing mice were divided into four groups: (1) no treatment; (2) anti-CD25-IgG-IR700 i.v. only; (3) anti-CD25-F(ab')2-IR700 i.v. with NIR light exposure; and (4) anti-CD25-IgG-IR700 i.v. with NIR light exposure. Although both CD25-targeted NIR-PITs resulted in significant tumor growth inhibition, the anti-CD25-F(ab')2-IR700 based NIR-PIT was superior to the anti-CD25-IgG-IR700 NIR-PIT. The anti-CD25-F(ab')2-IR700 demonstrated faster clearance from the body than the anti-CD25-IgG-IR700. Sustained circulation of anti-CD25-IgG-IR700 may block IL-2 binding on the activated effector T-cells decreasing immune response. In conclusion, anti-CD25-F(ab')2 based NIR-PIT was more effective in reducing tumor growth than anti-CD25-IgG based NIR-PIT. Absence of the Fc portion of the APC leads to faster clearance and therefore promotes a superior activated T cell response in tumors.

Activatable Near-Infrared Fluorescence Imaging Using PEGylated Bacteriochlorin-Based Chlorin and BODIPY-Dyads as Probes for Detecting Cancer.

Near infrared (NIR) fluorescent probes are attractive tools for biomedical in vivo imaging due to the relatively deeper tissue penetration and lower background autofluorescence. Activatable probes are turned on only after binding to their target, further improving target to background ratios. However, the number of available activatable NIR probes is limited. In this study, we introduce two types of activatable NIR fluorophores derived from bacteriochlorin: chlorin-bacteriochlorin energy-transfer dyads and boron-dipyrromethene (BODIPY)-bacteriochlorin energy-transfer dyads. These fluorophores are characterized by multiple narrow excitation bands with relatively strong emission in the NIR. Targeted bacteriochlorin-based antibody or peptide probes have been previously limited by aggregation after conjugation. Polyethylene glycol (PEG) chains were added to improve the hydrophilicity without altering pharmacokinetics of the targeting moieties. These PEGylated bacteriochlorin-based activatable fluorophores have potential as targeted activatable, multicolor NIR fluorescent probes for in vivo applications.

Arterial blood supply to the pancreas from accessary middle colic artery.

BACKGROUND: An accessory middle colic artery (AMCA) is an aberrant artery feeding the splenic flexure of the colon. Little is known about the branching pattern of an AMCA. We aimed to evaluate the branching pattern of the AMCA from the superior mesenteric artery (SMA) with special reference to the pancreatic artery using multidetector-row computed tomography (MDCT) before surgery. METHODS: We investigated 112 patients who underwent contrast-enhancement MDCT before surgical resection of the pancreas between January 2015 and July 2018. The pancreatic branch from the AMCA was divided into the dorsal pancreatic artery (DPA) and the inferior pancreaticoduodenal artery (IPDA). The branching level and angle of the AMCA from the SMA were also evaluated. RESULTS: The AMCA was present in 27.7% of patients (n = 31/112). The AMCA branching pattern was classified into four types: type A, no branch from the AMCA (n = 20); type B, a common trunk with the DPA (n = 6); type C, a common trunk with the IPDA (n = 3); and type D, a common trunk with the DPA and IPDA (n = 2). The AMCA with the IPDA (types C and D) branched more proximally compared to the AMCA without the IPDA (P = 0.04). The AMCA branched vertically from the SMA in most cases (n = 24/31, 77.4%). CONCLUSIONS: The AMCA had a pancreatic branch in 8.9% (10/112) of cases. Special attention should be paid to its branching pattern in pancreatic and colon surgery.