Focal coagulative necrosis of the liver in a patient with sustained virologic response to anti-hepatitis C virus therapy.

A 69-year-old woman with chronic hepatitis C virus (HCV) infection was referred to our hospital due to liver enzyme abnormalities. Four years after anti-HCV therapy, the patient with sustained virologic response and no clinical symptoms developed an oval hepatic mass with mixed high and low internal echoes near the portal vein on ultrasound. Magnetic resonance imaging (MRI) of the liver lesion showed a slightly hypo intense pattern on T1-weighted images, a hyper intense pattern both on T2- and diffusion-weighted images, a slight rim enhancement pattern with no intra-lesional enhancement up to the late phase, and a very low intense pattern on hepatobiliary phase images. Positron emission tomography/computed tomography (PET / CT) showed no areas of avid radiotracer uptake in the liver. No tumor markers showed abnormally high values. All these images and laboratory findings led us to the assessment of the liver lesion as a non-neoplastic disorder. However, due to the patient's strong preference to get both definitive diagnosis and cure of the lesion, the patient underwent laparoscopic partial hepatectomy. Pathological study showed 2 necrotic areas surrounded by multiple lymph follicles, epithelioid cells, lymphocytes, collagen fibers, and plasma cells, leading to the diagnosis of focal coagulative necrosis of the liver (FCNL). Physicians should note that FCNL can occur without any symptoms and can be diagnosed at least as a non-neoplastic disorder with combined MRI and PET/CT analysis.

UV laser-processed microstructure for building biohybrid actuators with anisotropic movement.

Fabrication of a biohybrid actuator requires muscle cells anisotropically aligned in a line, curve, or combination of lines and curves (similar to the microstructure of living muscle tissue) to replicate lifelike movements, in addition to considering the arrangement of skeletal structure or muscular structure with anisotropic straight patterns. Here, we report a UV laser-processed microstructure for freely directing cellular alignment to engineer a biohybrid actuator composed of poly(styrene-block-butadiene-block-styrene triblock copolymer) (SBS) thin film with tailor-made microgrooves (MGs) and skeletal myotubes aligned along these MGs. Specifically, straight, circular, or curved MGs were transferred to SBS thin films from a UV laser-processed template, allowing for the successful alignment of myotubes along MGs. The biohybrid actuator, composed of anisotropically aligned myotubes on a curved microgrooved SBS thin film, was contracted by electrical stimulation. Contraction of biohybrid actuators with curved aligned myotubes permits twisted-like behavior, unlike straight microgrooved films. Therefore, the UV laser-ablation system is a unique maskless and rapid microfabrication technique that provides intriguing opportunities for omni-directional microgrooved structures to achieve the complex motion of living organisms.

Epithelioid Hemangioendothelioma of the Liver Showing Spontaneous Complete Regression after the Cessation of Methotrexate Intake.

A 71-year-old man with slight fever and dull abdominal pain was referred to our hospital. He had been receiving methotrexate (MTX) to treat his rheumatoid arthritis for more than 6 years but stopped taking MTX after admission due to the rapid aggravation of his liver function. Computed tomography (CT) showed multiple liver lesions with late enhancement, highly suggesting them to be cholangiocarcinomas. Tumor marker levels were normal except for a slightly elevated PIVKA-II level, i.e., 45 mAU/mL (range 0-40 mAU/mL). We did a biopsy to the largest lesion and endoscopic biliary drainage to make a definitive diagnosis of the hepatic lesions and treat jaundice, respectively. Pathological study showed round, polygonal, and spindle-shaped epithelial atypical cells growing in a sarcomatoid fashion. Atypical cells were positive for CD31, CD34, vimentin, and TFE3, and some of them had intracellular vacuoles, leading to the diagnosis of epithelioid hemangioendothelioma (EHE) of the liver. The patient got well 4 weeks after the endoscopic biliary drainage. CTs showed marked regression of the EHE lesions 3 months after biliary drainage and complete regression in 12 months. The patient further developed Hodgkin lymphoma in the para-aortic lymph nodes 23 months after the biliary drainage and is now under chemotherapy for the malignant lymphoma. We, however, have not detected any EHE lesions in the liver or distant organs for at least 16 months after the confirmation of complete regression of the EHE lesions. Oncologists should note the spontaneous regression of the EHE and investigate the correlation between MTX cessation and EHE regression.

Immunological analysis of hybrid neoantigen peptide encompassing class I/II neoepitope-pulsed dendritic cell vaccine.

Neoantigens/ are tumor-specific antigens that evade central immune tolerance mechanisms in the thymus. Long-term tumor-specific cytotoxic T lymphocyte activity maintenance requires class II antigen-reactive CD4+ T cells. We had previously shown that intranodal vaccination with class I neoantigen peptide-pulsed dendritic cells (DCs) induced a robust immune response in a subset of patients with metastatic cancer. The present study aimed to perform a detailed ex vivo analysis of immune responses in four patients receiving an intranodal hybrid human leukocyte antigen class II neoantigen peptide encompassing a class I neoantigen epitope (hybrid neoantigen)-pulsed DC vaccine. After vaccination, strong T-cell reactions against the hybrid class II peptide and the class I-binding neoantigen peptide were observed in all four patients. We found that hybrid class II neoantigen peptide-pulsed DCs stimulated CD4+ T cells via direct antigen presentation and CD8+ T cells via cross-presentation. Further, we demonstrated that hybrid class II peptides encompassing multiple class I neoantigen epitope-pulsed DCs could present multiple class I peptides to CD8+ T cells via cross-presentation. Our findings provide insight into the mechanisms underlying hybrid neoantigen-pulsed DC vaccine therapy and suggest future neoantigen vaccine design.

Does Pathological T-Factor Affect Long-term Prognosis of Locally Advanced Colorectal Cancer Treated With Laparoscopic Multivisceral Resection?

BACKGROUND/AIM: Locally advanced colorectal cancer (LACC) has poor long-term outcomes. Our hypothesis was that the pathological tumor depth would affect postoperative outcomes in patients who underwent multivisceral resection with clear margins (R0). The aim of this study was to analyze short- and long-term outcomes in patients who underwent multivisceral resection for LACC, comparing between T3 and T4 stages. PATIENTS AND METHODS: This was a propensity score-matched, retrospective study. All 8,764 consecutive patients who underwent surgery for colorectal cancer between April 2007 and January 2021 at the Saitama Medical University International Medical Center were screened; 572 underwent multivisceral resection for LACC. We compared the T3 and T4 groups to evaluate outcomes. RESULTS: The 5-year disease-free survival (DFS) rates did not significantly differ between the two groups (hazard ratio=1.344, 95% confidence interval=0.638-2.907, p=0.33). The 5-year overall survival (OS) rates were significantly worse for the T4 group than for the T3 group (hazard ratio=3.162, 95% confidence interval=1.077-11.44), p=0.037). To determine the association between American Society of Anesthesiologists (ASA) score, transfusion, pathological T and OS, we performed univariate and multivariate analyses. ASA, transfusion, and pathological T-stage were associated with worse OS in univariate analysis (T4 vs. T3, respectively). CONCLUSION: Our study showed that postoperative complications and DFS of the T4 group were similar to those of the T3 group of locally advanced colorectal cancer treated with laparoscopic multivisceral resection. However, OS was worse in the T4 group compared with the T3 group. Multivariate risk factors for poor OS were ASA>2, transfusion, and T4 stage.

Experimental analysis of the sweepback angle effect on the thrust generation of a robotic penguin wing.

Penguins have evolved excellent swimming skills as diving birds, benefiting from their agile wings. This paper experimentally analyzes the effects of the wing sweepback angle on thrust generation using a robotic penguin wing. A developed wing mechanism that can realize penguin-like flapping and feathering motion was used for actuating five alternative wing models, with different sweepback angles ranging from 0° to 50°. Force measurements under a steady water flow were conducted for both fixed and flapping states for all wing models. The results showed that small sweepback angles of 30° or less in the fixed state caused a steep lift curve and a moderate sweepback angle of 30° produced the largest lift-to-drag ratio. In the flapping state, the smaller sweepback wings generated a larger net thrust for the same wing motion, whereas the larger-sweepback wings produced more thrust under the same Strouhal number. The findings also revealed that larger sweepback wings more easily achieve the maximum net thrust in terms of less angle-of-attack control. In contrast, the hydrodynamic efficiency was not greatly affected by the sweepback. Regardless of the sweepback, the trend of the efficiency increasing with increasing flow speed indicates that the penguin wings can be more suitable for high-speed locomotion for higher hydrodynamic efficiency.

Small bowel fistula with colorectal cancer and mesenteric lymph node metastasis: a report of two cases.

A 65-year-old man presented to our hospital with complaints of diarrhea. Computed tomography showed a fistula with the small intestine, and a single incision laparoscopic low anterior resection for rectum with D3 dissection and partial resection of the small intestine were performed. Lymph node dissection, including a part of the inflow vessel area, was also performed because lymph node swelling was observed in the mesentery of the small intestine around the fistula. Histopathological analysis revealed that the lymph nodes in the small intestine were positive for metastasis. The patient was a 61-year-old woman who presented to our hospital with a chief complaint of diarrhea. A partial resection of the small intestine, including resection of the left hemicolectomy and lymph node dissection around the fistula, was performed at laparotomy. Histopathological examination revealed numerous lymph node metastases in the small intestinal mesentery.

Kinematic and hydrodynamic analyses of turning manoeuvres in penguins: body banking and wing upstroke generate centripetal force.

Penguins perform lift-based swimming by flapping their wings. Previous kinematic and hydrodynamic studies have revealed the basics of wing motion and force generation in penguins. Although these studies have focused on steady forward swimming, the mechanism of turning manoeuvres is not well understood. In this study, we examined the horizontal turning of penguins via 3D motion analysis and quasi-steady hydrodynamic analysis. Free swimming of gentoo penguins (Pygoscelis papua) at an aquarium was recorded, and body and wing kinematics were analysed. In addition, quasi-steady calculations of the forces generated by the wings were performed. Among the selected horizontal swimming manoeuvres, turning was distinguished from straight swimming by the body trajectory for each wingbeat. During the turns, the penguins maintained outward banking through a wingbeat cycle and utilized a ventral force during the upstroke as a centripetal force to turn. Within a single wingbeat during the turns, changes in the body heading and bearing also mainly occurred during the upstroke, while the subsequent downstroke accelerated the body forward. We also found contralateral differences in the wing motion, i.e. the inside wing of the turn became more elevated and pronated. Quasi-steady calculations of the wing force confirmed that the asymmetry of the wing motion contributes to the generation of the centripetal force during the upstroke and the forward force during the downstroke. The results of this study demonstrate that the hydrodynamic force of flapping wings, in conjunction with body banking, is actively involved in the mechanism of turning manoeuvres in penguins.

Fluid drag reduction by penguin-mimetic laser-ablated riblets with yaw angles.

The bodies of penguins, which swim underwater to forage, are densely covered with feathers, in which the barbs are oriented in the longitudinal direction. We hypothesize that these barbs act as riblets and reduce friction drag during swimming. Considering various real-world swim conditions, the drag reduction effect is expected to be robust against changes in the flow speed and yaw angle relative to the flow. To test this hypothesis, we created trapezoidal riblets based on the morphology of these barbs and measured the drag of flat plates with these fabricated riblets in a water tunnel. The spacing, width, and height of the barbs were found to be approximately 100, 60, and 30 µm, respectively. This spacing resulted in a nondimensional spacings+of 5.5 for a typical penguin swimming speed of 1.4 m s-1. We fabricated four types of riblets on polyimide films by ultraviolet laser ablation. The first was a small-scale riblet for which the spacing was decreased to 41 µm to simulate the surface flow condition of the usual and slower swim behaviors in our water tunnel. The other three were manufactured to the actual scale of real barbs (spacing of 100 µm) with three different rib ridge widths: 10, 25, and 50 µm. Yaw angles of 0°, 15°, 30°, and 45° were also tested with the actual-scale riblets. The drag reduction rate of the small-scale riblet was maximized to 1.97% by the smallests+of 1.59. For all three actual-scale riblets, increasing the yaw angle from zero to 15° enhanced the drag reduction rate for the full range ofs+up to 13.5. The narrow-ridge riblet reduced drag at an even higher yaw angle of 45°, but the drag increased with zero yaw angle. Overall, the medium-ridge riblet, which was representative of the barbs, was well-balanced.

[A Case of Delayed Anastomotic Leakage after Ileocecal Resection in a Hemodialysis Patient].

A 66-year-old man was referred to our department with the diagnosis of ascending colon cancer. He was undergoing dialysis for chronic renal failure due to diabetic nephropathy. Laparoscopic ileocecal resection was planned for the ascending colon cancer, but the procedure was converted to laparotomy owing to intraoperative bleeding. The patient was discharged from the hospital after 7 days. On the 14th postoperative day, the patient presented with purulent drainage from the wound and fever and was diagnosed to have a minor anastomotic leak. The suture of the anterior sheath was exposed in part of the wound. The patient's general condition was stable, and conservative treatment was planned. However, when he coughed, the wound separated and the intestine prolapsed, and emergency surgery was performed. Intraoperative findings showed leakage of intestinal fluid from the anastomotic border, and we diagnosed delayed suture failure. We present a rare case of delayed anastomotic leakage in a hemodialysis patient.

Laparoscopic low anterior resection for rectal cancer associated with Leriche syndrome: a case report.

A 78-year-old male presented with a positive fecal occult blood test. Rectal cancer was detected during lower gastrointestinal endoscopy, and further investigations led to a diagnosis of cT1N0M0 cStage I (UICC classification, 8th edition). Preoperative contrast-enhanced computed tomography (CT) showed that the patient also had Leriche syndrome, which is associated with reduced blood flow to the rectum that may result in ischemic anastomosis during rectal cancer surgery with anastomotic reconstruction. The inferior epigastric arteries often function as collateral pathways to the lower limbs in patients with Leriche syndrome; therefore, care is needed to avoid vascular damage during trocar insertion when performing laparoscopic surgeries. We herein described a case of safe laparoscopic low anterior resection in a rectal cancer patient with Leriche syndrome using vascular architecture images obtained by preoperative CT angiography.

Bayesian-based decipherment of in-depth information in bacterial chemical sensing beyond pleasant/unpleasant responses.

Chemical sensing is vital to the survival of all organisms. Bacterial chemotaxis is conducted by multiple receptors that sense chemicals to regulate a single signalling system controlling the transition between the direction (clockwise vs. counterclockwise) of flagellar rotation. Such an integrated system seems better suited to judge chemicals as either favourable or unfavourable, but not for identification purposes though differences in their affinities to the receptors may cause difference in response strength. Here, an experimental setup was developed to monitor behaviours of multiple cells stimulated simultaneously as well as a statistical framework based on Bayesian inferences. Although responses of individual cells varied substantially, ensemble averaging of the time courses seemed characteristic to attractant species, indicating we can extract information of input chemical species from responses of the bacterium. Furthermore, two similar, but distinct, beverages elicited attractant responses of cells with profiles distinguishable with the Bayesian procedure. These results provide a basis for novel bio-inspired sensors that could be used with other cell types to sense wider ranges of chemicals.

Contribution of pre-existing neoantigen-specific T cells to a durable complete response after tumor-pulsed dendritic cell vaccine plus nivolumab therapy in a patient with metastatic salivary duct carcinoma.

Although immune checkpoint inhibitors (ICIs) have emerged as new therapeutic options for refractory cancer, they are only effective in select patients. Tumor antigen-pulsed dendritic cell (DC) vaccine therapy activates tumor-specific cytotoxic T lymphocytes, making it an important immunotherapeutic strategy. Salivary ductal carcinoma (SDC) carries a poor prognosis, including poor long-term survival after metastasis or recurrence. In this study, we reported a case of refractory metastatic SDC that was treated with a tumor lysate-pulsed DC vaccine followed by a single injection of low-dose nivolumab, and a durable complete response was achieved. We retrospectively analyzed the immunological factors that contributed to these long-lasting clinical effects. First, we performed neoantigen analysis using resected metastatic tumor specimens obtained before treatment. We found that the tumor had 256 non-synonymous mutations and 669 class I high-affinity binding neoantigen peptides. Using synthetic neoantigen peptides and ELISpot analysis, we found that peripheral blood mononuclear leukocytes cryopreserved before treatment contained pre-existing neoantigen-specific T cells, and the cells obtained after treatment exhibited greater reactivity to neoantigens than those obtained before treatment. Our results collectively suggest that the rapid and long-lasting effect of this combination therapy in our patient may have resulted from the presence of pre-existing neoantigen-specific T cells and stimulation and expansion of those cells following tumor lysate-pulsed DC vaccine and ICI therapy.

Dual scope method: A novel application of a simultaneous multi-image display system for a thoracoscopic robotic lobectomy.

The advantages of a multi-input display system platform in robotic thoracic surgery have not been well described. We report the novel application of a multi-display system for simultaneous visualization of an additional thoracoscopic image during a robotic lobectomy, which we have named the dual scope method. An additional thoracoscope is inserted from the bottom of the thoracic cavity. This thoracoscope visualizes the whole operative field, including the robot arms, from a bystander's viewpoint. By providing an integrated image from the robot scope and the thoracoscope, various problems, such as arm collision, inappropriate instrument direction, excessive traction, and injury, can be solved or avoided much more easily and safely than with the use of the robotic image alone. The dual scope method facilitates the safety and efficiency of robotic lobectomy.

Kinematics and hydrodynamics analyses of swimming penguins: wing bending improves propulsion performance.

Penguins are adapted to underwater life and have excellent swimming abilities. Although previous motion analyses revealed their basic swimming characteristics, the details of the 3D wing kinematics, wing deformation and thrust generation mechanism of penguins are still largely unknown. In this study, we recorded the forward and horizontal swimming of gentoo penguins (Pygoscelis papua) at an aquarium with multiple underwater action cameras and then performed a 3D motion analysis. We also conducted a series of water tunnel experiments with a 3D printed rigid wing to obtain lift and drag coefficients in the gliding configuration. Using these coefficients, the thrust force during flapping was calculated in a quasi-steady manner, where the following two wing models were considered: (1) an 'original' wing model reconstructed from 3D motion analysis including bending deformation and (2) a 'flat' wing model obtained by flattening the original wing model. The resultant body trajectory showed that the penguin accelerated forward during both upstroke and downstroke. The motion analysis of the two wing models revealed that considerable bending occurred in the original wing, which reduced its angle of attack during the upstroke in particular. Consequently, the calculated stroke-averaged thrust was larger for the original wing than for the flat wing during the upstroke. In addition, the propulsive efficiency for the original wing was estimated to be 1.8 times higher than that for the flat wing. Our results unveil a detailed mechanism of lift-based propulsion in penguins and underscore the importance of wing bending.

Stapling of an endobronchial suction tube with the bronchus during robot-assisted right lower lobectomy: a case report.

BACKGROUND: Troubleshooting intraoperative complications requires careful management, and the safest technique should be chosen. We recently experienced a unique intraoperative bronchial complication during pulmonary lobectomy in robot-assisted thoracic surgery (RATS). There is no consensus on whether to continue RATS or convert to a more familiar technique, such as video-assisted thoracic surgery (VATS) or thoracotomy, for intraoperative complications that occur during RATS, and the decision should be determined individually. CASE PRESENTATION: A 74-year-old woman with primary lung adenocarcinoma (clinical stage IA2) underwent robot-assisted right lower lobectomy under one-lung ventilation and CO2 insufflation. Intraoperatively, the anesthesiologist placed the endobronchial suction tube in the right bronchus with intention of maintaining the right lung collapse, which was simultaneously stapled with the right lower bronchus during the right lower lobe bronchial closure using a robotic stapler. During robot-assisted manipulation, we removed the staples involved with the suction tube, one by one, using robotic-arm forceps and sutured the partially opened stump. Subsequently, the bronchial stump was covered with a pedicled pericardial fat pad. The postoperative course was uneventful, and the patient developed no complications when followed up 8 months after discharge. Hence, we could rectify this intraoperative bronchial complication using a robot-assisted technique and avoid conversion to VATS or thoracotomy. CONCLUSION: The precise manipulation techniques in RATS contributed to facilitate the successful execution of surgical procedures, such as staple removal and re-suturing of the bronchial stump and may be a useful as a method for such troubleshooting such intraoperative complications.

Efficacy of Intranodal Neoantigen Peptide-pulsed Dendritic Cell Vaccine Monotherapy in Patients With Advanced Solid Tumors: A Retrospective Analysis.

BACKGROUND/AIM: Neoantigens are tumor-specific antigens that emerge due to gene mutations in tumor cells, and are highly antigenic epitopes that escape central immune tolerance in the thymus, making cancer vaccine therapy a desirable option. PATIENTS AND METHODS: Tumor neoantigens were predicted in 17 patients with advanced cancer. They were resistant to the standard treatment regime, and their synthetic peptides were pulsed to the patient's monocyte-derived dendritic cells (DCs), and administered to the patient's lymph nodes via ultrasound. RESULTS: Some patients showed sustained tumor shrinkage after this treatment, while some did not respond, showing no ELISpot reaction. Although the number of mutations and the predicted neoantigen epitopes differed between patients, the clinical effect depended more on the presence or absence of an immune response after vaccination rather than the number of neoantigens. CONCLUSION: Intranodal neoantigen peptide-pulsed DC vaccine administration therapy has clinical and immunological efficacy and safety.

[A Case of Anastomotic Recurrence 10 Years after Excision of Sigmoid Colon Cancer with Submucosal Invasion].

A 72-year-old woman underwent sigmoid colon resection plus D2 lymph node dissection in 2008, with additional resection after endoscopic mucosal resection(EMR). Histopathological examination revealed only atypical ducts in the EMR scar, with no invasion below the submucosa. No lymphatic, venous, or nerve invasions were confirmed, and oral and anal stumps and lymph node metastases were negative. She was followed up for 5 years after the surgery, and no recurrence was detected. In 2018, she visited our hospital with the chief complaint of diarrhea and constipation. Colonoscopy revealed a circumferential lesion around the anastomosis. She underwent laparoscopic low anterior resection for suspected anastomotic recurrence, which was confirmed by histopathological diagnosis. The anastomotic recurrence 10 years after surgery for SM cancer of the colon with negative lymph node metastasis and vascular factor was extremely rare. We recognized the importance of surveillance 5 years after surgery.

[A Case of Sarcoid‒Like Reaction with Multiple Lymphadenopathy by Rectal Cancer after an Operation].

We are reporting on a case of lymphadenopathy after surgery for rectal cancer. The case was a 66‒year‒old female. Laparoscopic high anterior resection(D3 dissection)was performed for rectal cancer(pT1bpN0M0, pStage Ⅰ)in April 2018, and she was followed up with on an outpatient basis. In July of the same year, a painless mass had formed in the right groin. An abdominal contrast‒enhanced CT showed lymph node swelling around the right groin and external iliac artery, but the tumor markers, CEA 2.3 ng/mL and CA19‒9 <2 U/mL, were within the standard values. An inguinal lymph node biopsy was performed during the same month. Pathological examination revealed no cancer cells and formation of epithelioid granuloma with giant cells. There was no suspicion of systemic sarcoidosis based on the test results and clinical findings. From the above, the patient was diagnosed with sarcoid reaction due to the tumor. Abdominal contrast‒enhanced CT scan 2 months after the biopsy showed lymph node shrinkage and there was no recurrence 2 years after the biopsy.