Adolescent and Young Adults with Gastric Cancer (AYA-GC)-The Dilemma of an Under-Represented Group: A Multi-Institutional Analysis from the Indian Subcontinent.

Soumya Surath PandaGastric cancer (GC) is often ignored at a young age, which frequently leads to tragic consequences. The worldwide incidence of GC is increasing at a young age. In view of the limited Indian publication, we sought to characterize clinicopathological parameters and risk factors in the adolescents and young adults (AYA) population. Retrospective data from six centers (which are part of the Network of Oncology Clinical Trials in India) from 2015 to 2020 were collected from patient (18-39 years of age) records. This study was approved by the institutional ethical committee of individual centers. All statistical analyses were performed using Microsoft Excel and SPSS (Version 20). Data interpretation along with the analysis of obtained results was carried out using the following tests: Qualitative data was expressed in terms of frequency/percentage. One-hundred fifty-two AYA GC patients were enrolled. The 31 to 39 years age group was most affected in which 76.3% were females. The majority of patients were nonalcoholic (93.4%), nonsmokers (98.0%), and without a family history (98.0%). The most common (MC) presenting symptom was abdominal pain (67.1%). MC site was antrum (48%). Among esophagogastric junction cancers, the majority were type I and II Siewert classifications (77% [20/26] patients in cardia), MC histology-signet ring cell (67.1%) followed by diffuse-type (65.1%). Most were poorly differentiated (65.1%) and were diagnosed at an advanced stage (III & IV= 54.6%). This is one of our country's first large multicenter studies on GC in the AYA population. There was a higher female prevalence, aggressive tumor behavior and the majority of patients were diagnosed at a more advanced stage. The majority were nonsmokers with a negative family history. Awareness among general people, researchers, clinicians, and policymakers must be improved to better the loss of life years in the younger population.

Clinicopathologic Profile and Treatment Outcomes of Colorectal Cancer in Young Adults: A Multicenter Study From India.

PURPOSE: Colorectal cancer (CRC) in young adults is a rising concern in developing countries such as India. This study investigates clinicopathologic profiles, treatment patterns, and outcomes of CRC in young adults, focusing on adolescent and young adult (AYA) CRC in a low- and middle-income country (LMIC). METHODS: A retrospective registry study from January 2018 to December 2020 involved 126 young adults (age 40 years and younger) with CRC. Patient demographics, clinical features, tumor characteristics, treatment modalities, and survival outcomes were analyzed after obtaining institutional ethics committees' approval. RESULTS: Among 126 AYA patients, 62.70% had colon cancer and 37.30% had rectal cancer. Most patients (67%) were age 30-39 years, with no significant gender predisposition. Females had higher metastatic burden. Abdominal pain with obstruction features was common. Adenocarcinoma (65%) with signet ring differentiation (26%) suggested aggressive behavior. Limited access to molecular testing hindered mutation identification. Capecitabine-based chemotherapy was favored because of logistical constraints. Adjuvant therapy showed comparable recurrence-free survival in young adults and older patients. For localized colon cancer, the 2-year median progression-free survival was 74%, and for localized rectal cancer, it was 18 months. Palliative therapy resulted in a median overall survival of 33 months (95% CI, 18 to 47). Limited access to targeted agents affected treatment options, with only 27.5% of patients with metastatic disease receiving them. Chemotherapy was generally well tolerated, with hematologic side effect being most common. CONCLUSION: This collaborative study in an LMIC offers crucial insights into CRC in AYA patients in India. Differences in disease characteristics, treatment patterns, and limited access to targeted agents highlight the need for further research and resource allocation to improve outcomes in this population.

Two-photon microscopy for microrobotics: Visualization of micro-agents below fixed tissue.

Optical microscopy is frequently used to visualize microrobotic agents (i.e., micro-agents) and physical surroundings with a relatively high spatio-temporal resolution. However, the limited penetration depth of optical microscopy techniques used in microrobotics (in the order of 100 µm) reduces the capability of visualizing micro-agents below biological tissue. Two-photon microscopy is a technique that exploits the principle of two-photon absorption, permitting live tissue imaging with sub-micron resolution and optical penetration depths (over 500 µm). The two-photon absorption principle has been widely applied to fabricate sub-millimeter scale components via direct laser writing (DLW). Yet, its use as an imaging tool for microrobotics remains unexplored in the state-of-the-art. This study introduces and reports on two-photon microscopy as an alternative technique for visualizing micro-agents below biological tissue. In order to validate two-photon image acquisition for microrobotics, two-type micro-agents are fabricated and employed: (1) electrospun fibers stained with an exogenous fluorophore and (2) bio-inspired structure printed with autofluorescent resin via DLW. The experiments are devised and conducted to obtain three-dimensional reconstructions of both micro-agents, perform a qualitative study of laser-tissue interaction, and visualize micro-agents along with tissue using second-harmonic generation. We experimentally demonstrate two-photon microscopy of micro-agents below formalin-fixed tissue with a maximum penetration depth of 800 µm and continuous imaging of magnetic electrospun fibers with one frame per second acquisition rate (in a field of view of 135 × 135 µm2). Our results show that two-photon microscopy can be an alternative imaging technique for microrobotics by enabling visualization of micro-agents under in vitro and ex ovo conditions. Furthermore, bridging the gap between two-photon microscopy and the microrobotics field has the potential to facilitate in vivo visualization of micro-agents.

Intravascular Tracking of Micro-Agents Using Medical Ultrasound: Towards Clinical Applications.

OBJECTIVE: This study demonstrates intravascular micro-agent visualization by utilizing robotic ultrasound-based tracking and visual servoing in clinically-relevant scenarios. METHODS: Visual servoing path is planned intraoperatively using a body surface point cloud acquired with a 3D camera and the vessel reconstructed from ultrasound (US) images, where both the camera and the US probe are attached to the robot end-effector. Developed machine vision algorithms are used for detection of micro-agents from minimal size of 250 µm inside the vessel contour and tracking with error recovery. Finally, real-time positions of the micro-agents are used for servoing of the robot with the attached US probe. Constant contact between the US probe and the surface of the body is accomplished by means of impedance control. RESULTS: Breathing motion is compensated to keep constant contact between the US probe and the body surface, with minimal measured force of 2.02 N. Anthropomorphic phantom vessels are segmented with an Intersection-Over-Union (IOU) score of 0.93 ± 0.05, while micro-agent tracking is performed with up to 99.8% success rate at 28-36 frames per second. Path planning, tracking and visual servoing are realized over 80 mm and 120 mm long surface paths. CONCLUSION: Experiments performed using anthropomorphic surfaces, biological tissue, simulation of physiological movement and simulation of fluid flow through the vessels indicate that robust visualization and tracking of micro-agents involving human patients is an achievable goal.

SonoTweezer: An Acoustically Powered End-Effector for Underwater Micromanipulation.

Recent advances in contactless micromanipulation strategies have revolutionized prospects of robotic manipulators as next-generation tools for minimally invasive surgeries. In particular, acoustically powered phased arrays offer dexterous means of manipulation both in air and water. Inspired by these phased arrays, we present SonoTweezer: a compact, low-power, and lightweight array of immersible ultrasonic transducers capable of trapping and manipulation of sub-mm sized agents underwater. Based on a parametric investigation with numerical pressure field simulations, we design and create a six-transducer configuration, which is small compared to other reported multi-transducer arrays (16-256 elements). Despite the small size of array, SonoTweezer can reach pressure magnitudes of 300 kPa at a low supply voltage of 25 V to the transducers, which is in the same order of absolute pressure as multi-transducer arrays. Subsequently, we exploit the compactness of our array as an end-effector tool for a robotic manipulator to demonstrate long-range actuation of sub-millimeter agents over a hundred times the agent's body length. Furthermore, a phase-modulation over its individual transducers allows our array to locally maneuver its target agents at sub-mm steps. The ability to manipulate agents underwater makes SonoTweezer suitable for clinical applications considering water's similarity to biological media, e.g., vitreous humor and blood plasma. Finally, we show trapping and manipulation of micro-agents under medical ultrasound (US) imaging modality. This application of our actuation strategy combines the usage of US waves for both imaging and micromanipulation.

CeFlowBot: A Biomimetic Flow-Driven Microrobot that Navigates under Magneto-Acoustic Fields.

Aquatic organisms within the Cephalopoda family (e.g., octopuses, squids, cuttlefish) exist that draw the surrounding fluid inside their bodies and expel it in a single jet thrust to swim forward. Like cephalopods, several acoustically powered microsystems share a similar process of fluid expulsion which makes them useful as microfluidic pumps in lab-on-a-chip devices. Herein, an array of acoustically resonant bubbles are employed to mimic this pumping phenomenon inside an untethered microrobot called CeFlowBot. CeFlowBot contains an array of vibrating bubbles that pump fluid through its inner body thereby boosting its propulsion. CeFlowBots are later functionalized with magnetic layers and steered under combined influence of magnetic and acoustic fields. Moreover, acoustic power modulation of CeFlowBots is used to grasp nearby objects and release it in the surrounding workspace. The ability of CeFlowBots to navigate remote environments under magneto-acoustic fields and perform targeted manipulation makes such microrobots useful for clinical applications such as targeted drug delivery. Lastly, an ultrasound imaging system is employed to visualize the motion of CeFlowBots which provides means to deploy such microrobots in hard-to-reach environments inaccessible to optical cameras.

Impact of Segmented Magnetization on the Flagellar Propulsion of Sperm-Templated Microrobots.

Technical design features for improving the way a passive elastic filament produces propulsive thrust can be understood by analyzing the deformation of sperm-templated microrobots with segmented magnetization. Magnetic nanoparticles are electrostatically self-assembled on bovine sperm cells with nonuniform surface charge, producing different categories of sperm-templated microrobots. Depending on the amount and location of the nanoparticles on each cellular segment, magnetoelastic and viscous forces determine the wave pattern of each category during flagellar motion. Passively propagating waves are induced along the length of these microrobots using external rotating magnetic fields and the resultant wave patterns are measured. The response of the microrobots to the external field reveals distinct flow fields, propulsive thrust, and frequency responses during flagellar propulsion. This work allows predictions for optimizing the design and propulsion of flexible magnetic microrobots with segmented magnetization.

Spontaneous Rupture of Gallbladder Hemangioma Presenting as Hemoperitoneum.

Hemangioma of the gallbladder is rare, with less than 10 cases reported in the literature. It may represent a hamartomatous proliferation of connective tissue in the gallbladder or may be congenital in origin. Although liver hemangiomas rarely present with spontaneous rupture, it has not been documented in gallbladder hemangiomas. This report presents a case of gallbladder hemangioma that ruptured spontaneously and presented with hemoperitoneum.

Contactless acoustic micro/nano manipulation: a paradigm for next generation applications in life sciences.

Acoustic actuation techniques offer a promising tool for contactless manipulation of both synthetic and biological micro/nano agents that encompass different length scales. The traditional usage of sound waves has steadily progressed from mid-air manipulation of salt grains to sophisticated techniques that employ nanoparticle flow in microfluidic networks. State-of-the-art in microfabrication and instrumentation have further expanded the outreach of these actuation techniques to autonomous propulsion of micro-agents. In this review article, we provide a universal perspective of the known acoustic micromanipulation technologies in terms of their applications and governing physics. Hereby, we survey these technologies and classify them with regards to passive and active manipulation of agents. These manipulation methods account for both intelligent devices adept at dexterous non-contact handling of micro-agents, and acoustically induced mechanisms for self-propulsion of micro-robots. Moreover, owing to the clinical compliance of ultrasound, we provide future considerations of acoustic manipulation techniques to be fruitfully employed in biological applications that range from label-free drug testing to minimally invasive clinical interventions.

An Atypical Presentation of Pancreatic Pseudocyst Masquerading as Solid Pseudopapillary Neoplasm of Pancreas.

Pancreatic pseudocysts are the most common cystic lesions of the pancreas, and often present as a consequence of acute or chronic pancreatitis. On the other hand, cystic neoplasms of the pancreas are rare, but pose a significant diagnostic challenge. The differentiation between these entities often relies on the clinical features and characteristic radiological evidence. However, the diagnostic dilemma persists, leading to misdiagnosis and inappropriate treatment. We present a case of pancreatic pseudocyst in a 49-year-old male, which clinically and radiologically mimicked solid pseudopapillary neoplasm, a rare type of cystic neoplasm of the pancreas.

IRONSperm: Sperm-templated soft magnetic microrobots.

We develop biohybrid magnetic microrobots by electrostatic self-assembly of nonmotile sperm cells and magnetic nanoparticles. Incorporating a biological entity into microrobots entails many functional advantages beyond shape templating, such as the facile uptake of chemotherapeutic agents to achieve targeted drug delivery. We present a single-step electrostatic self-assembly technique to fabricate IRONSperms, soft magnetic microswimmers that emulate the motion of motile sperm cells. Our experiments and theoretical predictions show that the swimming speed of IRONSperms exceeds 0.2 body length/s (6.8 ± 4.1 µm/s) at an actuation frequency of 8 Hz and precision angle of 45°. We demonstrate that the nanoparticle coating increases the acoustic impedance of the sperm cells and enables localization of clusters of IRONSperm using ultrasound feedback. We also confirm the biocompatibility and drug loading ability of these microrobots, and their promise as biocompatible, controllable, and detectable biohybrid tools for in vivo targeted therapy.

A Contactless and Biocompatible Approach for 3D Active Microrobotic Targeted Drug Delivery.

As robotic tools are becoming a fundamental part of present day surgical interventions, microrobotic surgery is steadily approaching clinically-relevant scenarios. In particular, minimally invasive microrobotic targeted drug deliveries are reaching the grasp of the current state-of-the-art technology. However, clinically-relevant issues, such as lack of biocompatibility and dexterity, complicate the clinical application of the results obtained in controlled environments. Consequently, in this work we present a proof-of-concept fully contactless and biocompatible approach for active targeted delivery of a drug-model. In order to achieve full biocompatiblity and contacless actuation, magnetic fields are used for motion control, ultrasound is used for imaging, and induction heating is used for active drug-model release. The presented system is validated in a three-dimensional phantom of human vessels, performing ten trials that mimic targeted drug delivery using a drug-coated microrobot. The system is capable of closed-loop motion control with average velocity and positioning error of 0.3 mm/s and 0.4 mm, respectively. Overall, our findings suggest that the presented approach could augment the current capabilities of microrobotic tools, helping the development of clinically-relevant approaches for active in-vivo targeted drug delivery.