New host record of Thelazia callipaeda (Nematoda: Spirurida) with a notably wide host range and shared zoonotic lineage in Japan.

Thelazia callipaeda (Nematoda: Spirurida: Thelaziidae) parasitizes the eyes of dogs, cats, humans, and various wild mammals, and is transmitted by drosophilid flies. In Japan, T. callipaeda is considered an emerging parasite that has expanded its endemic region northward. However, reports of its detection in mammals other than domestic animals and humans are scarce. This study reports the detection of T. callipaeda in Japanese red fox (Vulpes vulpes japonica), masked palm civet (Paguma larvata), Japanese badger (Meles anakuma), Japanese black bear (Ursus thibetanus japonicus), raccoon (Procyon lotor), Japanese raccoon dog (Nyctereutes viverrinus), domestic dog (Canis lupus familiaris), domestic cat (Felis silvestris catus), and human. Of these, the Japanese red fox, masked palm civet, Japanese badger, and Japanese black bear have been reported as novel host records. Sequence analysis of the cytochrome c oxidase subunit I gene of T. callipaeda revealed two unique lineages specific to Japan, with no regional or host species differences. These results suggest a wide host range for T. callipaeda, highlighting the significant role of wildlife as a reservoir for this parasite in Japan.

Subtotal esophagectomy and concurrent reconstruction with free jejunal flap for primary esophageal cancer after pancreatoduodenectomy.

BACKGROUND: Pancreatoduodenectomy and subtotal esophagectomy are widely considered the most invasive and difficult surgical procedures in gastrointestinal surgery. Subtotal esophagectomy after pancreatoduodenectomy is expected to be extremely difficult due to complicated anatomical changes, and selecting an appropriate intestinal reconstruction method will also be a difficult task. Therefore, perhaps because the method is considered impossible, there have been few reports of subtotal esophagectomy after pancreatoduodenectomy. CASE PRESENTATION: A 73-year-old man with a history of pancreatoduodenectomy was diagnosed with superficial thoracic esophageal squamous cell carcinoma. Definitive chemoradiation therapy was recommended at another hospital; however, he visited our department to undergo surgery. We performed the robot-assisted thoracoscopic subtotal esophagectomy. There were some difficulties with the reconstruction: the gastric tube could not be used, the reconstruction was long, and the organs reconstructed in the previous surgery had to be preserved. However, the concurrent reconstruction was achieved with the help of a free jejunal flap and vascular reconstruction. All reconstructions from the previous surgery, including the remnant stomach, were preserved via regional abdominal lymph node dissection. After reconstruction, intravenous indocyanine green showed that circulation in the reconstructed intestines was preserved. On postoperative day 1, no recurrent nerve paralysis was observed during laryngoscopy. The patient could start oral intake smoothly 2 weeks after surgery and did not exhibit any postoperative complications related to the reconstruction. The patient was transferred to another hospital on postoperative day 21. CONCLUSIONS: Owing to the free jejunal flap interposition method, we safely performed one stage subtotal esophagectomy and concurrent reconstruction, preservation of the remnant stomach, and pancreaticobiliary reconstruction in patients with a history of pancreatoduodenectomy. We believe that this method is acceptable and useful for patients undergoing complicated reconstruction.

Near-infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Patient-Derived Xenografts Using a Humanized Anti-Fibroblast Activation Protein Antibody.

Esophageal cancer remains a highly aggressive malignancy with a poor prognosis, despite ongoing advancements in treatments such as immunotherapy. The tumor microenvironment, particularly cancer-associated fibroblasts (CAF), plays a crucial role in driving the aggressiveness of esophageal cancer. In a previous study utilizing human-derived xenograft models, we successfully developed a novel cancer treatment that targeted CAFs with near-infrared photoimmunotherapy (NIR-PIT), as an adjuvant therapy. In this study, we sought to translate our findings toward clinical practice by employing patient-derived xenograft (PDX) models and utilizing humanized mAbs, specifically sibrotuzumab, which is an antihuman fibroblast activation protein (FAP) Ab and already being investigated in clinical trials as monotherapy. PDX models derived from patients with esophageal cancer were effectively established, preserving the expression of key biomarkers such as EGFR and FAP, as observed in primary tumors. The application of FAP-targeted NIR-PIT using sibrotuzumab, conjugated with the photosensitizer IR700DX, exhibited precise binding and selective elimination of FAP-expressing fibroblasts in vitro. Notably, in our in vivo investigations using both cell line-derived xenograft and PDX models, FAP-targeted NIR-PIT led to significant inhibition of tumor progression compared with control groups, all without inducing adverse events such as weight loss. Immunohistologic assessments revealed a substantial reduction in CAFs exclusively within the tumor microenvironment of both models, further supporting the efficacy of our approach. Thus, our study demonstrates the potential of CAF-targeted NIR-PIT employing sibrotuzumab as a promising therapeutic avenue for the clinical treatment of patients with esophageal cancer.

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.

Decline in the Conception Rate of Wild Japanese Monkeys after the Fukushima Daiichi Nuclear Power Plant Accident.

We examined the conception rate of wild Japanese monkeys (Macaca fuscata) in Fukushima City that were exposed to radiation as a result of the Fukushima Daiichi Nuclear Power Plant accident in March 2011. The conception rate in the year of delivery from 2009 to 2022 was estimated by dissecting individuals that were euthanized by the government for population control as a countermeasure against crop damage. To evaluate the effects of exposure, the cumulative exposure dose for each individual was calculated using the concentration of radiocesium deposited in the soil at the capture site and the concentration of radiocesium in muscle estimated from the aggregated transfer factor. There were no significant differences in conception rates across all age classes over time. In terms of conception rates by age class, there was a significant decrease post-exposure compared with pre-exposure in the age class ≥ 8 years, but no significant differences in the age class 5-7 years. The non-ovulation rate did not significantly differ between the pre- and post-exposure periods for any age class. Body fat index, which can affect fertility, was compared between the pre- and post-exposure periods, and no significant differences were found in either age class. In contrast, the median total cumulative exposure (cumulative internal exposure + cumulative external exposure) was significantly higher in the age class ≥ 8 years compared with the age class 5-7 years. These results suggest that the total cumulative exposure dose may be one of the reasons for the lower conception rate in the post-exposure period among the age class ≥ 8 years.

Laparoscopic Resection of Transverse Colon Cancer with an Anomaly of the Middle Colic Artery Originating from the Splenic Artery: A Case Report.

Introduction: We encountered a colon cancer case with a very rare anomaly of the middle colic artery (MCA) originating from the splenic artery (SA). Case Presentation: A woman was referred to our hospital for transverse colon cancer. Three-dimensional computed tomography (3D-CT) angiography showed an anomalous MCA originating from the SA rather than from the superior mesenteric artery (SMA) as is typical. Laparoscopic left hemicolectomy with D3 lymph node dissection was performed. The lymph nodes around the SMA were dissected from the caudal view, confirming the absence of a typical MCA. An anomalous SA-originating MCA was identified just below the pancreas, where it was clipped and ligated; subsequently, total mesenteric excision was achieved. Conclusion: As D3 lymph node dissection for transverse colon cancer is technically difficult, 3D-CT angiography is useful for identifying vascular anomalies preoperatively, thereby avoiding intraoperative injury. This is the first case report of laparoscopic colectomy associated with a SA-originating MCA anomaly.

Fibroblast activation protein-targeted near-infrared photoimmunotherapy depletes immunosuppressive cancer-associated fibroblasts and remodels local tumor immunity.

BACKGROUND: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a critical role in tumor immunosuppression. However, targeted depletion of CAFs is difficult due to their diverse cells of origin and the resulting lack of specific surface markers. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that leads to rapid cell membrane damage. METHODS: In this study, we used anti-mouse fibroblast activation protein (FAP) antibody to target FAP+ CAFs (FAP-targeted NIR-PIT) and investigated whether this therapy could suppress tumor progression and improve tumor immunity. RESULTS: FAP-targeted NIR-PIT induced specific cell death in CAFs without damaging adjacent normal cells. Furthermore, FAP-targeted NIR-PIT treated mice showed significant tumor regression in the CAF-rich tumor model accompanied by an increase in CD8+ tumor infiltrating lymphocytes (TILs). Moreover, treated tumors showed increased levels of IFN-γ, TNF-α, and IL-2 in CD8+ TILs compared with non-treated tumors, suggesting enhanced antitumor immunity. CONCLUSIONS: Cancers with FAP-positive CAFs in their TME grow rapidly and FAP-targeted NIR-PIT not only suppresses their growth but improves tumor immunosuppression. Thus, FAP-targeted NIR-PIT is a potential therapeutic strategy for selectively targeting the TME of CAF+ tumors.

Salvage reconstruction of the esophagus using the left colon with microscopic supercharge following failed ileocolic reconstruction: A case report.

INTRODUCTION: Ileocolic interposition is often used for the reconstruction of patients with esophageal cancer with a history of gastrectomy. However, graft failure due to conduit necrosis has been reported in 0-5 % of patients. Salvage reconstruction surgery for this situation is considered challenging, and only a few cases of successful salvage operations following failure of ileocolic interposition have been reported. PRESENTATION OF CASE: A 70s year-old male patient with a history of distal and total gastrectomy underwent subtotal esophagectomy for esophageal cancer. Reconstruction using a pedicled ileocolic interposition was performed; however, the ileocolic graft failed. After recovery of the nutritional status, salvage reconstruction was planned. Due to a history of Roux-en-Y reconstruction for gastric cancer, jejunal reconstruction was not considered feasible. Therefore, salvage reconstruction was performed using left colon interposition with microscopic supercharge and superdrainage anastomosis. The graft was pedicled by the left colic artery and the inferior mesenteric vein, and microscopic anastomosis was performed between the intrathoracic and middle colic vessels. The patient recovered without major complications and retained the ability to consume normal food. DISCUSSION: Microscopic supercharge and superdrainage vascular anastomosis have been reported to ensure augmented blood flow. This is the first case report of successful salvage reconstruction using the left colon interposition technique following failure of ileocolic interposition for esophageal cancer. CONCLUSION: We report a case of salvage reconstruction using left colon interposition with microscopic supercharge and superdrainage anastomosis following failure of ileocolic reconstruction for esophageal cancer.

Near-infrared photoimmunotherapy targeting Nectin-4 in a preclinical model of bladder cancer.

Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) that targets Nectin-4, has shown promising results in the treatment of bladder cancer. However, multiple resistance mechanisms that are unique to ADCs limit the therapeutic potential of EV in clinical practice. Here, we developed and tested a Nectin-4-targeted near-infrared photoimmunotherapy (NIR-PIT) that utilizes the same target as EV but utilizes a distinct cytotoxic and immunotherapeutic pathway in preclinical models of bladder cancer. NIR-PIT was effective in vitro against luminal subtype human bladder cancer cell lines (RT4, RT112, MGH-U3, SW780, and HT1376-luc), but not against other subtype cell lines (UMUC3 and T24). In vivo, the tumor site was clearly visible by Nectin-4-IR700 fluorescence 24 h after its administration, suggesting the potential as an intraoperative imaging modality. NIR-PIT significantly suppressed tumor growth and prolonged survival in SW780 and RT112 xenograft models. Weekly treatment with NIR-PIT further improved tumor control in RT112 xenograft models. The effectiveness of NIR-PIT was also confirmed in HT1376-luc orthotopic xenograft models. Histological analysis verified that NIR-PIT induced a significant pathologic response. Taken together, Nectin-4-targeted NIR-PIT shows promise as a treatment for luminal subtype bladder cancers.

Trends in long-term outcomes of patients with HCV-associated hepatocellular carcinoma after hepatectomy: A comparison before and after introduction of direct-acting antivirus therapy.

Backgrounds: The success of direct-acting antiviral (DAA) therapy provides a cure for patients chronically infected with hepatitis C virus (HCV); however, outcomes after hepatectomy for HCV-associated hepatocellular carcinoma (HCC) before and after DAA introduction remain poorly studied. Methods: Patients who underwent R0/R1 hepatectomy for HCV-associated HCC were retrospectively analyzed. Two time periods were defined: Pre-DAA (2007-2011, December 2013 was defined as the end of follow-up) and Post-DAA groups (2014-2018, December 2020 was defined as the end of follow-up). Propensity score matching (PSM) analyses were performed to highlight the effect of DAA therapy. Results: A total of 155 patients with HCV-associated HCC were included in this study (Pre-DAA group, n = 103 and post-DAA group, n = 52). In the Post-DAA group, DAA therapy was performed in 26 patients (50.0%), and all of these patients achieved sustained virologic response (SVR) (preoperative SVR, n = 7; postoperative SVR, n = 19). There was no significant difference between the two groups regarding surgical settings and tumor pathology. There was no significant difference in the 5-year overall survival (OS) rate (61.1% and 64.8%, pre- and post-DAA group, respectively, p = 0.441); meanwhile, the 5-year recurrence-free survival (RFS) rate in the post-DAA group was better than the pre-DAA group (21.1% and 40.2%, p = 0.073) with a trend toward significance. After PSM except for the postoperative SVR status, there were no significant differences in OS (p = 0.586) and RFS (p = 0.888). Conclusions: This study showed that survival outcomes were not changed in hepatectomized cases of HCV-associated HCC before and after the introduction of DAA therapy.

REV7 is involved in outcomes of platinum-based chemotherapy in pancreatic cancer by controlling the DNA damage response.

REV7 is a multifunctional protein implicated in various biological processes, including DNA damage response. REV7 expression in human cancer cells affects their sensitivity to DNA-damaging agents. In the present study, we investigated the significance of REV7 in pancreatic ductal adenocarcinoma (PDAC). REV7 expression was immunohistochemically examined in 92 resected PDAC specimens and 60 endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) specimens of unresectable PDAC treated with platinum-based chemotherapy, and its association with clinicopathologic features was analyzed. Although REV7 expression was not significantly associated with the progression of primary tumors (T-factor and Stage) in either resected or unresectable PDAC, decreased levels of REV7 expression in EUS-FNAB specimens of unresectable PDAC were significantly associated with better outcomes of platinum-based chemotherapy and a favorable prognosis. REV7-deficient PDAC cell lines showed suppressed cell growth and enhanced sensitivity to cisplatin in vitro. Tumor-bearing mice generated using REV7-deficient PDAC cell lines also showed enhanced sensitivity to cisplatin in vivo. RNA sequencing analysis using WT and REV7-deficient PDAC cell lines revealed that REV7 inactivation promoted the downregulation of genes involved in the DNA repair and the upregulation of genes involved in apoptosis. Our results indicate that decreased expression of REV7 is associated with better outcomes of platinum-based chemotherapy in PDAC by suppressing the DNA damage response. It is also suggested that REV7 is a useful biomarker for predicting the outcome of platinum-based chemotherapy and the prognosis of unresectable PDAC and is a potential target for PDAC treatment.

Near-infrared photoimmunotherapy in the models of hepatocellular carcinomas using cetuximab-IR700.

Epidermal growth factor receptor (EGFR) has emerged as an important therapeutic target in many cancers, and overexpression of EGFR is frequently observed in hepatocellular carcinomas (HCCs). Near-infrared photoimmunotherapy (NIR-PIT) is a new anticancer treatment that selectively damages the cell membrane of cancer cells after NIR light-induced photochemical reaction of IR700, which is bound to a targeting antibody on the cell membrane. NIR-PIT using cetuximab-IR700 has already been approved in Japan, is under review by the US Food and Drug Administration (FDA) for advanced head and neck cancers, and its safety has been established. However, EGFR has not been investigated as a target in NIR-PIT in HCCs. Here, we investigate the application of NIR-PIT using cetuximab-IR700 to HCCs using xenograft mouse models of EGFR-expressing HCC cell lines, Hep3B, HuH-7, and SNU-449. In vitro NIR-PIT using EGFR-targeted cetuximab-IR700 killed cells in a NIR light dose-dependent manner. In vivo NIR-PIT resulted in a delayed growth compared with untreated controls. In addition, in vivo NIR-PIT in both models showed histological signs of cancer cell damage, such as cytoplasmic vacuolation and nuclear dysmorphism. A significant decrease in Ki-67 positivity was also observed after NIR-PIT, indicating decreased cancer cell proliferation. This study suggests that NIR-PIT using cetuximab-IR700 has potential for the treatment of EGFR-expressing HCCs.

PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer.

The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity.

Adenocarcinoma arising from widespread heterotopic gastric mucosa in the cervicothoracic esophagus: a case report.

BACKGROUND: In Japan, about 6% of esophageal cancers are adenocarcinomas, although most of them arise from Barrett's epithelium. Adenocarcinoma arising from heterotopic gastric mucosa (HGM) is very rare. Due to its rarity, there is no unified view on its treatment strategy and prognosis. CASE PRESENTATION: A 57-year-old man presented with a protruding lesion in the cervicothoracic esophagus that was detected by an upper gastrointestinal series at a medical checkup. Esophagoscopy revealed a 30 mm Type 1 tumor circumferentially surrounded by widespread HGM. Computed tomography (CT) and fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed no metastasis or invasion of the surrounding organs. We diagnosed the lesion as cT2N0M0 cStageIIB [Union for International Cancer Control (UICC) 8th Ed] cancer and performed subtotal esophagectomy with three-field lymph node dissection. The tumor was determined to be a well-differentiated adenocarcinoma arising from HGM, with deep invasion of the submucosa. The patient underwent no adjuvant therapy and has currently survived without any evidence of recurrence for 15 months. CONCLUSIONS: Although the treatment for adenocarcinoma arising from HGM is basically the same as that for squamous cell carcinoma (SCC) of the esophagus, it is important to determine the treatment strategy based on the characteristics of the adenocarcinoma arising from HGM.

Evaluation of the Effect of Pb Pollution on Avian Influenza Virus-Specific Antibody Production in Black-Headed Gulls (Chroicocephalus ridibundus).

Lead (Pb), an environmental pollutant, has been widely reported to have contaminated mammals, including humans and birds. This study focuses on the effects of Pb pollution on avian influenza virus (AIV) antibody production. A total of 170 black-headed gulls (Chroicocephalus ridibundus) were captured in Tokyo Bay (TBP) from January 2019 to April 2020 and in Mikawa Bay (MBP) from November 2019 to April 2021. The gulls were weighed, subjected to blood sampling, and released with a ring band on their tarsus. The samples were used to measure blood Pb levels (BLL) and AIV-specific antibodies. The BLL were compared using the Wilcoxon two-sample test between the period when black-headed gulls arrived and the wintering period, defined by the number of gulls counted in each area. A significant increase was found in the TBP. A decrease in BLL significantly increased antibody titer during wintering in TBP and MBP. Pb pollution had a negative effect on the production of AIV antibodies. These findings suggest that wild birds that were contaminated by Pb in the environment may facilitate the spread of zoonotic diseases, further increasing the possibility that environmental pollutants may threaten human health.

Intratumoral IL15 Improves Efficacy of Near-Infrared Photoimmunotherapy.

IL15 is a potent inducer of differentiation and proliferation of CD8+ T and natural killer (NK) cells, making it a promising candidate for cancer immunotherapy. However, limited efficacy of systemic monotherapy utilizing intravenous IL15 suggests the needs for alternative routes of administration or combination treatment with other therapies. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective anticancer treatment that elicits a massive release of tumor antigens and immunogenic signals. Here, we investigated whether intratumoral IL15 can enhance the effectiveness of cancer cell-targeted NIR-PIT using syngeneic murine tumor models. Intratumoral injection of IL15 was more effective than intraperitoneal IL15 in vivo in suppressing tumor growth and inducing intratumoral immune responses. When the efficacy of CD44-targeted NIR-PIT was compared in vivo between IL15-secreting MC38 (hIL15-MC38) and parental MC38 tumors, the hIL15-MC38/NIR-PIT group showed the best tumor growth inhibition and survival. In addition, the hIL15-MC38/NIR-PIT group showed significant dendritic cell maturation and significant increases in the number and Granzyme B expression of tumor-infiltrating CD8+ T, NK, and natural killer T cells compared with the treated parental line. Furthermore, intratumoral IL15 injection combined with CD44-targeted NIR-PIT showed significant tumor control in MC38 and Pan02-luc tumor models. In bilateral tumor models, CD44-targeted NIR-PIT in hIL15-MC38 tumors significantly suppressed the growth of untreated MC38 tumors, suggesting abscopal effects. Mice that achieved complete response after the combination therapy completely rejected later tumor rechallenge. In conclusion, local IL15 administration synergistically improves the efficacy of cancer cell-targeted NIR-PIT probably by inducing stronger anticancer immunity, indicating its potential as an anticancer treatment strategy.

Quantifying the shear modulus of the adductor longus muscle during hip joint motion using shear wave elastography.

The present study aims to assess the effect of the hip flexion angle on the shear modulus of the adductor longus (AL) muscle associated with passive hip abduction and rotation. Sixteen men participated in the study. For the hip abduction task, the hip flexion angles used were - 20, 0, 20, 40, 60, and 80°, and the hip abduction angles were 0, 10, 20, 30, and 40°. For the hip rotation task, the hip flexion angles used were - 20, 0, 20, 40, 60, and 80°, hip abduction angles were 0 and 40°, and hip rotation angles were 20° internal rotation, 0° rotation, and 20° external rotation. The shear modulus at 20° extension was significantly higher than that at 80° flexion for the 10, 20, 30 and 40° hip abduction (i.e., P < 0.05). The shear modulus at 20° internal rotation and 20° extension was significantly higher than that at 0° rotation and 20° external rotation, regardless of the hip abduction angle (i.e., P < 0.05). The mechanical stress of the AL muscle associated with hip abduction was higher in the extended position. Furthermore, the mechanical stress could increase with internal rotation only at the hip-extended position.

Conventional Cancer Therapies Can Accelerate Malignant Potential of Cancer Cells by Activating Cancer-Associated Fibroblasts in Esophageal Cancer Models.

Esophageal cancer is one of the most aggressive tumors, and the outcome remains poor. One contributing factor is the presence of tumors that are less responsive or have increased malignancy when treated with conventional chemotherapy, radiotherapy, or a combination of these. Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Focusing on conventional cancer therapies, we investigated how CAFs acquire therapeutic resistance and how they affect tumor malignancy. In this study, low-dose chemotherapy or radiotherapy-induced normal fibroblasts showed enhanced activation of CAFs markers, fibroblast activation protein, and α-smooth muscle actin, indicating the acquisition of malignancy in fibroblasts. Furthermore, CAFs activated by radiotherapy induce phenotypic changes in cancer cells, increasing their proliferation, migration, and invasion abilities. In in vivo peritoneal dissemination models, the total number of tumor nodules in the abdominal cavity was significantly increased in the co-inoculation group of cancer cells and resistant fibroblasts compared to that in the co-inoculation group of cancer cells and normal fibroblasts. In conclusion, we demonstrated that conventional cancer therapy causes anti-therapeutic effects via the activation of fibroblasts, resulting in CAFs. It is important to select or combine modalities of esophageal cancer treatment, recognizing that inappropriate radiotherapy and chemotherapy can lead to resistance in CAF-rich tumors.

Safe and curative modified two-stage operation for T4 esophageal cancer after definitive chemoradiotherapy: a case report.

BACKGROUND: The prognosis of esophageal cancer (EC) with organ invasion is extremely poor. In these cases, definitive chemoradiotherapy (CRT) followed by salvage surgery can be planned; however, the issue of high morbidity and mortality rates persists. Herein, we report the long-term survival of a patient with EC and T4 invasion who underwent a modified two-stage operation after definitive CRT. CASE PRESENTATION: A 60-year-old male presented with type 2 upper thoracic EC with tracheal invasion. First, definitive CRT was performed, which resulted in tumor shrinkage and improvement in the tracheal invasion. However, an esophagotracheal fistula subsequently developed, and the patient was treated with fasting and antibiotics. Although the fistula recovered, severe esophageal stenoses made oral intake impossible. To improve quality of life and cure the EC, a modified two-stage operation was planned. In the first surgery, an esophageal bypass was performed using a gastric tube with cervical and abdominal lymph node dissections. After confirming improved nutritional status and absence of distant metastasis, the second surgery was performed with subtotal esophagectomy, mediastinal lymph node dissection, and tracheobronchial coverage of the fistula. The patient discharged without major complications after radical resection and has been recurrence-free for 5 years since the start of treatment. CONCLUSION: A standard curative strategy could be difficult for EC with T4 invasion due to differences in the invaded organs, presence of complications, and patient condition. Therefore, patient-tailored treatment plans are needed, including a modified two-stage operation.