A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen‐derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor‐specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1_140–162, which effectively activated TWIST1‐specific CD4⁺ T‐cells. In a short‐term culture system, we detected more TWIST1‐specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1‐reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.     

Treatment of secondary pneumothorax with interstitial lung disease: the surgical indications at the start of treatment is important

BackgroundSecondary pneumothorax with interstitial lung disease (ILD) is often difficult to treat in comparison to primary pneumothorax. The purpose of this study was to analyze the actual management and outcome, and to find the most effective treatment.MethodsAmong 180 patients with pneumothorax caused by ILD, who were managed between January 2000 and April 2021, 129 patients were included. Fifty-one patients with observation only were excluded. In the present study, a patient was considered to be cured if their chest tube could be removed.ResultsThe managements included chest tube drainage alone (n=41), pleurodesis (n=67), bronchoscopic treatment (n=14), and surgery (include overlapping cases) (n=25). The mean number of pleurodesis treatments was 2.4 (range, 1–9), and the most frequently used agent was blood-patch. All patients who received bronchoscopic treatment underwent bronchial occlusion with silicon spigots. The surgical procedures included bullectomy (n=20), lung cyst ligation (n=3), pleural covering with oxidized cellulose sheet (n=1), and spraying of fibrin glue alone (n=1). One hundred patients (77.5%) were curatively treated, 27 patients (20.9%) died, and 2 patients were transferred without chest tube removal. Among 25 patients who received surgery [including 6 patients with performance status (PS) ≥2], 24 patients (96.0%) were cured, and 1 patient died due to an acute exacerbation of ILD after surgery. The univariate analysis revealed that PS ≥2 and >3 pleurodesis treatments were significant non-curative factors, while steroid treatment before the development of pneumothorax was not.ConclusionsThe outcomes of surgery for pneumothorax in patients with ILD were good, and it is desirable to consider the surgical indications.     

Efficacy of sitting balance training with delayed visual feedback among patients with stroke: a randomized crossover clinical trial

[Purpose] This study aimed to determine the effect of delayed visual feedback on the center of pressure and sitting balance in patients with stroke. [Participants and Methods] This was a single-blinded, randomized crossover trial. The duration of each intervention in real-time visual feedback and delayed visual feedback conditions while sitting on the platform was five days. We measured the center of pressure, function in sitting test, and functional independence measure for physiotherapy assessment. [Results] Twenty patients with stroke were included in this study. The delayed visual feedback condition improved the center of pressure for lateral distance, function in sitting test, and functional independence measure. The lateral center of pressure deviation increased significantly after 500 ms of intervention. The function in sitting test evaluated the interaction between pre- and post-training, and these conditions revealed that timing and condition factors contributed to the improvement. Sitting balance training affected the functional independence measure. [Conclusion] Sensory-motor and cognitive learning was facilitated through balance training with delayed visual feedback, and the internal model was updated with the efference copy of error correction. Sensory-motor feedback to visual stimulation can improve postural control, balance, and activities of daily living.     

Time-lapse Microscopy and DNA Double-strand Breakage of Chinese Hamster Cells Under Conditions Promoting or Preventing PLD Repair after Irradiation with 60Co γ Rays

Summary

We have confirmed previous time-lapse microscopic observations (Suzuki 1985) using Chinese hamster hai and V79 cells. The proportion of non-dividing to dividing cells was the same under conditions of potentially lethal damage (PLD) repair and non-PLD repair after irradiation with ⁶⁰Co γ-rays. This finding suggested that the radiation-induced damage to cellular DNA was similarly repaired so that cells undergo a first division to the same extent under both sets of conditions. In fact, direct measurement of double-strand breaks (dsb) in DNA from the two cell lines by the neutral elution technique showed no differences either in the initial amount of damage or in the time-course under conditions promoting or preventing PLD repair. These results indicate that PLD repair (i.e. an increase in cell survival) cannot be simply explained by a difference in the repair of dsb, but it can perhaps be explained by assuming that DNA damage is repaired with either fewer or more errors in the presence or absence of PLD repair respectively.     

Leukotriene B4 12-hydroxydehydrogenase/15-ketoprostaglandinΔ13-reductase (LTB4 12-HD/PGR) responsible for the reduction of a double-bond of the α,β-unsaturated ketone of an aryl propionic acid non-steroidal anti-inflammatory agent CS-670

CS-670 is a non-steroidal anti-inflammatory agent with an α,β-unsaturated ketone structure. It exerts its pharmacological activity after being transformed to the active metabolite (2S,1′R,2′S)-trans-alcohol. Two consecutive reductions are needed for the formation of the active metabolite, reduction of the double-bond of the α,β-unsaturated ketone moiety, followed by reduction of the resulting saturated ketone. The objective of the current study was to identify the enzyme responsible for reduction of the double-bond. An enzyme purified from rat liver cytosol as a single band on sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was analysed by a Mascot database search of nano-LC tandem mass spectrometry (MS/MS) data and the enzyme was identified as 2-alkenal reductase (EC 1.3.1.74), which is known as an β-nicotinamide adenine dinucleotide phosphate (NADPH)-dependent alkenal/one oxidoreductase and has a role for leukotriene B₄ 12-hydroxydehydrogenase/15-ketoprostaglandinΔ13-reductase (LTB₄ 12-HD/PGR). The identification was confirmed by cloning LTB₄ 12-HD/PGR cDNA from rat liver, expressing it in Escherichia coli, and characterizing the properties of the enzyme. The identity was further supported by the subcellular localization in cytosol, a cofactor requirement for NADPH, substrate specificity, and substantial inhibition by 15-ketoPGF_2α, benzylideneacetophenone, indomethacin, and quercitrin. In addition to catalysing the biological reduction of eicosanoids, including prostaglandins, leukotrienes, and lipoxins, LTB₄ 12-HD/PGR was also determined to function as a xenobiotic-metabolizing enzyme.     

Clinicopathological prognostic factors and impact of surgical treatment of mass-forming intrahepatic cholangiocarcinoma

The clinicopathological characteristics relevant to prognosis after surgical treatment of intrahepatic cholangiocarcinoma (ICC) remain unclear. In this study, the clinicopathological features of 19 patients with mass-forming ICC, the most common form of the disease, were reviewed to analyze prognostic determinants. Two or more segmentectomies of the liver with systematic lymphadenectomy were performed in 18 patients. Resection of the extrahepatic bile duct was performed in 14 patients, and reconstruction of the portal vein was accomplished in 5 patients. Stage IVA or IVB tumors were seen in 13 patients, and lymph node (LN) metastasis was present in 14 patients. The estimated 5-year survival rate after surgery for mass-forming ICC was 28%, with median survival time of 18 months. In univariate analysis, five variables were determined to be significantly correlated with poor survival of patients with mass-forming ICC after surgery. These variables include mass-forming ICC with periductal infiltration, perineural invasion, portal vein invasion, presence of intrahepatic metastasis, and two or more LN metastases. Survival rates of 5 patients without LN metastasis and 6 patients with a single LN metastasis were 80% and 33% at 5 years, respectively, while 8 patients with two or more LN metastasis failed to survive beyond 2 years. Multivariate analysis revealed the presence of intrahepatic metastasis to be an independent prognostic factor of poor survival. Hepatectomy with resection of the extrahepatic bile duct and systematic lymphadenectomy yields a good chance for prolonged survival for patients with mass-forming ICC when the lesion is singular and LN metastasis is limited to a regional LN. Because the presence of intrahepatic metastasis was closely related to a poor prognosis in patients with mass-forming ICC, efficacious chemotherapy would be needed to control development of the lesion.     

Surgical outcomes of foramen magnum decompression for syringomyelia associated with Chiari I malformation: relation between the location of the syrinx and body pain

Background  

There have been few reports about the relation between the morphology of syrinxes and body pain in syringomyelia associated with Chiari I malformation. To investigate this phenomenon, the relation between the location of the syrinx and body pain before and after foramen magnum decompression (FMD) were evaluated.     

The giant schwannoma in the pelvic cavity: a case report

A 62-year-old man presented with a giant tumor in the pelvic cavity that was incidentally revealed by abdominal ultrasonography. Abdominal magnetic resonance imaging showed the heterogenous tumor in the pelvis with cystic components. The tumor was 10.8 × 10.5 × 11.7 cm in diameter and adhered to the sacral wall. The tumor was extirpated following diagnosis as a benign neurogenic tumor by needle biopsy. The pelvic cavity was occupied by the tumor rigidly adhered to the sacrum. The histopathological diagnosis of the specimen was benign schwannoma, type Antoni A.     

A case of paracecal hernia

A 63-year-old male patient suddenly suffered right lower abdominal pain. The patient had tenderness and rebound tenderness at the right lower abdomen. Marked small bowel dilatation and an intestinal obstruction were evident upon abdominal X-ray and abdominal computed tomography (CT) imaging. CT imaging also revealed a dilated small bowel cluster in a wrapped round shape in the right lower abdomen. The cecum and the ascending colon were displaced inward. Strangulation in the ileocecal region was suspected, and emergency surgery was performed. A part of the small bowel was incarcerated within the retrocecal recess, and the intestinal tract was strangulated in the hernia orifice, by which paracecal hernia was diagnosed. The strangulated intestinal tract was repositioned, and the orifice to the hernia was closed. Paracecal hernia is a rare disease; an internal hernia should always be considered in patients with ileus without a history of surgery.     

Laparoscopic Intragastric Full-thickness Excision (LIFE) of Posterior Gastric Lesions under Flexible Endoscopic Control—A Feasibility Study

Background We have developed a new technique for treatment of intramucosal carcinoma which exceeds the standard indication for endoscopic mucosal resection and carcinoma invading the submucosa without lymph node metastasis that are located in the posterior wall of the stomach, which we refer to as laparoscopic intragastric full-thickness excision (LIFE) under flexible endoscopic control. Surgical Technique Three pigs were used for the study. Three trocars were used. The first trocar (trocar # 1) was placed in the subumbilical region to introduce the videoscope, whereas the second and third trocars (trocar # 2 and trocar # 3) were punctured percutaneously into the abdominal cavity. A straight needle with 3-0 silk suture was attached to a T-bar on the wire side and inserted into the abdominal cavity. An area adjacent to the lesion in the posterior wall of the stomach was pierced by the straight needle, which was then pulled into the stomach using the forceps of the endoscope. The T-bar, after being passed through the abdominal wall, was fixed outside the gastric wall, and trocar # 3 was repositioned in the stomach by the percutaneous transgastric route. The posterior wall of the stomach was pulled inward by the T-bar, and the lesion was removed by several excisions with laparoscopic stapling devices inserted through trocar # 3; extraction of the specimen was achieved through trocar # 3. The gastrotomy site was suture-closed using instruments positioned through trocar # 2 and trocar # 3 under laparoscopy. Conclusions Based on a feasibility study in pigs, the LIFE procedure can be performed for lesions of the posterior wall of the stomach.