An Adult Case of Pharyngeal Injury Caused by Toothbrush.

Most toothbrush-induced oral injuries occur in children and are relatively shallow, involving the oral mucous membranes and musculature, but rarely deeper layers. Here, the management of an adult case of pharyngeal injury caused by a toothbrush is discussed. A man fell while brushing his teeth, and his toothbrush stuck in his throat. Contrast-enhanced computed tomography showed a toothbrush stuck in the left parapharyngeal space, reaching the subcutaneous tissue of the posterior neck. The toothbrush was surgically removed because blind removal could damage major cervical arterioles and nerves. In intraoral injuries caused by deep penetrating toothbrushes, there is a risk that the injury extends to the major arterioles and nerves of the neck. The need for imaging studies, methods of removal, and possible complications should all be considered before taking an appropriate removal action.

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.

Proper use of appendiceal stump closure methods for surgical site infection in laparoscopic appendectomy.

INTRODUCTION: Although some studies have reported on the relationship between appendiceal stump closure methods and postoperative complications, there is no fixed method for this procedure. This study aimed to compare treatment outcomes of the existing procedures. METHODS: We retrospectively analyzed the records of 200 patients who underwent urgent laparoscopic surgeries and investigated whether the difference in the appendiceal stump closure method was a risk factor for surgical site infection. The patients were divided into the Endoloop and endostapler groups, and 45 propensity score-matched patients were included. The treatment outcomes of the two groups were compared. RESULTS: The patients with high body temperature showed significantly developed surgical site infection in multivariate analysis (P = .036). There was no significant difference in the appendix stump methods (Endoloop vs endostapler). Regarding postoperative complications, superficial and deep incisional surgical site infection, organ/space surgical site infection, ileus, and complications of Clavien-Dindo grade IIIa or higher; there was no significant difference between the endoloop and endostapler groups after propensity score matching (P = .725, 1.000, .645 and .557, respectively). CONCLUSION: By properly using the Endoloop and endostapler according to the severity of inflammation, the Endoloop can be safely performed in many cases. Inexpensive Endoloop as an option for stump closure methods should positively impact medical costs.

Dual-targeted near-infrared photoimmunotherapy for esophageal cancer and cancer-associated fibroblasts in the tumor microenvironment.

Cancer-associated fibroblasts (CAFs) play a significant role in tumor progression within the tumor microenvironment. Previously, we used near-infrared photoimmunotherapy (NIR-PIT), a next-generation cancer cell-targeted phototherapy, to establish CAF-targeted NIR-PIT. In this study, we investigated whether dual-targeted NIR-PIT, targeting cancer cells and CAFs, could be a therapeutic strategy. A total of 132 cases of esophageal cancer were analyzed for epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and fibroblast activation protein (FAP) expression using immunohistochemistry. Human esophageal cancer cells and CAFs were co-cultured and treated with single- or dual-targeted NIR-PIT in vitro. These cells were co-inoculated into BALB/c-nu/nu mice and the tumors were treated with single-targeted NIR-PIT or dual-targeted NIR-PIT in vivo. Survival analysis showed FAP- or EGFR-high patients had worse survival than patients with low expression of FAP or EGFR (log-rank, P < 0.001 and P = 0.074, respectively), while no difference was observed in HER2 status. In vitro, dual (EGFR/FAP)-targeted NIR-PIT induced specific therapeutic effects in cancer cells and CAFs along with suppressing tumor growth in vivo, whereas single-targeted NIR-PIT did not show any significance. Moreover, these experiments demonstrated that dual-targeted NIR-PIT could treat cancer cells and CAFs simultaneously with a single NIR light irradiation. We demonstrated the relationship between EGFR/FAP expression and prognosis of patients with esophageal cancer and the stronger therapeutic effect of dual-targeted NIR-PIT than single-targeted NIR-PIT in experimental models. Thus, dual-targeted NIR-PIT might be a promising therapeutic strategy for cancer treatment.

Giant esophageal liposarcoma with squamous cell carcinoma resected via the cervical approach: a case report.

BACKGROUND: Liposarcoma is one of the most common soft tissue sarcomas, but is extremely rarely found in the esophagus. There have been no reports of esophageal liposarcoma together with superficial carcinoma of the esophagus. Here, we report a patient who underwent complete resection of esophageal liposarcoma with carcinoma via a cervical approach. CASE PRESENTATION: A 66-year-old man was diagnosed with an esophageal tumor 11 years ago, but he left it untreated. He presented to our hospital with progressive dysphagia and appetite loss since the previous year. Esophagogastroduodenoscopy (EGD) showed a large pedunculated submucosal tumor (SMT) originating at the esophageal entrance, extending to the gastroesophageal junction. Additionally, there was a superficial carcinoma on the surface of the SMT, 30 cm from the incisor teeth. Three-dimensional computed tomography (3D-CT) showed a giant elongated intraluminal tumor extending downwards from the cervical esophagus. We diagnosed a giant esophageal polyp accompanied by a superficial carcinoma and performed tumor resection via a cervical approach. The excised specimen consisted of a 23.0 × 8.5 cm polypoid mass. The final diagnosis by histopathological and immunohistochemical examination was well-differentiated liposarcoma and esophageal squamous cell carcinoma. He was discharged on postoperative day 14 with drastic improvement in his swallowing ability. CONCLUSION: We reported an extremely rare case of esophageal liposarcoma together with esophageal squamous cell carcinoma that was successfully resected through a small cervical incision.

[Clinical Outcome of Robot-Assisted Distal Pancreatectomy in Our Institutional Introduction].

We evaluated the clinical outcome and assessed the safety of robot-assisted distal pancreatectomy(RADP)of early 5 cases in our institutional introduction. We followed the guidelines for introduction of robot-assisted pancreatectomy proposed by Japanese Society of Endoscopic Surgery. Patients' characteristics were 2 men and 3 women, 45-79(median 52) years old, and 3 patients with neuroendocrine neoplasm, 1 with intraductal papillary neoplasm and 1 with mucinous cystic neoplasm. Spleen-preserving RADP was performed in 2 cases. Clinical outcomes of 5 cases underwent RADP were, operation time was 308-437(median 330)minutes, blood loss was 5-270(median 100)mL and none received transfusion. Postoperative pancreatic fistula and postoperative complication more than Grade Ⅲa(Clavien-Dindo classification)were none. Postoperative hospital stay was 7-11(median 8)days. RADP in our institution was safely introduced by following the proposal of guidelines.

A case of Epstein Barr virus-associated primary squamous cell carcinoma of stomach.

BACKGROUND: Primary squamous cell carcinoma (SCC) of stomach is extremely rare. The pathogenesis of SCC of stomach remains unclear. There is only one report that Epstein Barr virus (EBV) infection may be involved in the pathogenesis of SCC arising in the stomach ever before. Here, we report a case of Epstein Barr virus infection-associated primary SCC of stomach in a 70-year-old woman. She was presented to the referring hospital with hematemesis. Initial endoscopy revealed a bleeding gastric ulcer in the upper part of gastric corpus and the coagulation therapy was followed. After a 3-month follow-up, endoscopy revealed a submucosal tumor-like protrusion instead of an ulcer. Computed tomography revealed a mass in the upper part of stomach and swollen lymph nodes along with the lesser curvature and para-aortic lymph node. Biopsy could not confirm the definitive diagnosis. We performed total gastrectomy with para-aortic lymph node sampling. Histological analysis revealed squamous cell carcinoma with EBV infection with lymph node metastases. Tumor cells were positive for EBV-encoded small RNA (EBER) by in situ hybridization. The postoperative course was uneventful and the patient was discharged on day 11 after the operation. CapeOX was started as adjuvant chemotherapy, and the patient remains alive without recurrence 7 months after surgery. CONCLUSION: This is the first case report of EBV infection-associated primary SCC of the stomach diagnosed by in situ hybridization of EBER. EBV infection may be related to the pathogenesis of primary SCC. Further evidence and studies are required to establish optimal strategy for this rare disease.

Laparoscopic Synchronous Resection for Descending Colon Cancer and Tailgut Cyst.

A 67-year-old woman underwent polypectomy for a tumor at the descending colon. Pathologically, the tumor was diagnosed as adenocarcinoma with an invasion of 2000 µm. Computed tomography showed a swollen paracolic lymph node and a mass lesion in the presacral space. Magnetic resonance imaging revealed a multio-cular cystic lesion. On diagnosis of descending colon cancer and tailgut cyst, she underwent synchronous lapa-roscopic resection. Histopathologically, the colon cancer was diagnosed as pT1bN1M0, pStage IIIa. The pre-sacral cystic lesion was diagnosed as a nonmalignant tailgut cyst with negative surgical margin. The patient is currently doing well without recurrence at 28 months.

[Successful Resection Using a Posterior Approach of a Tailgut Cyst in the Retrorectal Space].

We present the case of a Tailgut cyst occurring in the retrorectal space that was curatively resected using a posterior approach. A 40-year-old man presented to the Kochi Health Sciences Center with the chief complaint of perineal incongruity. Pelvic magnetic resonance imaging revealed a multilocular cystic lesion in the retrorectal space, with high signal intensity on T2-weighted imaging. After diagnosing a Tailgut cyst, we performed resection of the tumor using a posterior approach. The lesion was removed en bloc with the coccyx. Histopathologically, the lesion was diagnosed as a non-malignant Tailgut cyst, and the surgical margin was negative. The patient is currently doing well without recurrence at 20 months.

Nanog is a promising chemoresistant stemness marker and therapeutic target by iron chelators for esophageal cancer.

Esophageal cancer is a disease showing poor prognosis. Although combination chemotherapy using cisplatin (CDDP) and 5-fluorouracil is standard for unresectable esophageal cancer, the response rate is 35%. Cancer stem cells (CSCs) and inflammation are reportedly responsible for the poor prognosis of esophageal cancer. However, comprehensive analyses have not been conducted and proposals for progress remain lacking. Iron is known to be a key factor in the stemness of CSCs. Our study focused on the therapeutic potential of iron control using iron chelators for CSCs in esophageal cancer. Among 134 immunohistochemically analyzed cases, Nanog expression was high in 98 cases and low in 36 cases. High Nanog expression correlated with low overall and disease-free survivals. The iron chelators deferasirox (DFX) and SP10 suppressed the proliferation and expression of stemness markers in TE8 and OE33 cells. DFX and SP10 did not induce compensatory interleukin (IL)-6 secretion, although CDDP did result in high induction. Moreover, BBI608 and SSZ, as other CSC-targeting drugs, could not suppress the expression of stemness markers. Overall, Nanog expression appears related to poor prognosis in esophageal cancer patients, and inhibition of stemness and compensatory IL-6 secretion by iron chelators may offer a novel therapeutic strategy for esophageal cancer.

18F-Labeled dihydromethidine: positron emission tomography radiotracer for imaging of reactive oxygen species in intact brain.

Dihydromethidine (DHM) labeled with 18F at the para position of the peripheral benzene ring was designed as a positron emission tomography (PET) radiotracer for non-invasive imaging of reactive oxygen species (ROS). This compound readily crosses the blood-brain barrier and is oxidized by ROS, and the oxidation product is retained intracellularly. PET imaging of ROS-producing rat brain microinfused with sodium nitroprusside identified specific brain regions with high ROS concentrations. This tracer should be useful for studies of the pathophysiological roles of ROS, and in the diagnosis of neurodegenerative diseases.

A case of stage IV gastric cancer with para-aortic lymph node metastasis showing pathological complete response after neoadjuvant chemotherapy.

BACKGROUND: Stage IV advanced gastric cancer with para-aortic lymph node metastasis (PALM) is considered unresectable. Systemic chemotherapy is the treatment of choice for such tumors, while conversion surgery may be a treatment option in the case chemotherapy is effective but R0 resection is possible. We report a case of stage IV gastric cancer with PALM that showed pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) using S-1, oxaliplatin, and trastuzumab (SOX+HER). CASE PRESENTATION: A 69-year-old woman who was diagnosed with type 4 stage IV gastric cancer with PALM underwent five courses of NAC with the SOX+HER regimen. The primary tumor and the PALM shrank after treatment, suggesting that the NAC induced a partial response. We performed a total gastrectomy plus distal pancreaticosplenectomy with para-aortic lymph node dissection. Histological analysis revealed no remnant cancer cells in the primary tumor or the lymph nodes, confirming a pCR. The postoperative course was uneventful, and the patient was discharged on day 14 after the operation. S-1 was started as adjuvant chemotherapy, and the patient remains alive without recurrence 2 months after surgery. CONCLUSION: This case shows the possibility of conversion surgery after SOX+HER therapy for stage IV advanced gastric cancer with PALM.

Surgical Treatment of a Patient with a Solitary Thyroid Metastasis from Primary Sigmoid Adenocarcinoma: A Case Report and Literature Review.

Malignant metastases to the thyroid are rare and even rarer from colorectal cancer (CRC). Most cases of CRC metastasis to the thyroid involve metastases to other organs as well, particularly the liver and/or lung. There are only three reports of CRC metastasizing to the thyroid without involvement of another site. Patients with solitary thyroid metastasis from CRC have a poor prognosis after surgery, whereas resection is beneficial in their counterparts with a solitary liver or lung metastasis. This difference could be the result of delayed diagnosis of thyroid metastasis in patients with CRC, given that postoperative follow-up examination of the thyroid is not routinely performed. Here we describe a patient who was found to have a solitary metastasis of sigmoid cancer to the thyroid on postoperative imaging and has had prolonged disease-free survival after thyroidectomy. Our experience suggests that a low threshold of suspicion is crucial for timely diagnosis of thyroid metastasis from CRC and that resection can improve disease-free survival.

A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness.

Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy.

Cancer-associated fibroblasts (CAFs) promote the lymph node metastasis of esophageal squamous cell carcinoma.

Lymph node metastasis is a pathognomonic feature of spreading tumors, and overcoming metastasis is a challenge in attaining more favorable clinical outcomes. Esophageal cancer is an aggressive tumor for which lymph node metastasis is a strong poor prognostic factor, and the tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in particular, has been implicated in esophageal cancer progression. CAFs play a central role in the TME and have been reported to provide suitable conditions for the progression of esophageal cancer, similar to their role in other malignancies. However, little is known concerning the relevance of CAFs to the lymph node metastasis of esophageal cancer. Here, we used clinical samples of esophageal cancer to reveal that CAFs promote lymph node metastasis and subsequently verified the intercellular relationships in vitro and in vivo using an orthotopic metastatic mouse model. In the analysis of clinical samples, FAP+ CAFs were strongly associated with lymph node metastasis rather than with other prognostic factors. Furthermore, CAFs affected the ability of esophageal cancer cells to acquire metastatic phenotypes in vitro; this finding was confirmed by data from an in vivo orthotopic metastatic mouse model showing that the number of lymph node metastases increased upon injection of cocultured cancer cells and CAFs. In summary, we verified in vitro and in vivo that the accumulation of CAFs enhances the lymph node metastasis of ESCC. Our data suggest that CAF targeted therapy can reduce lymph node metastasis and improve the prognosis of patients with esophageal cancer in the future.

[The Elucidation of Tumor Immunosuppression Affected by Cancer-Associated Fibroblasts].

Development of immunotherapy, especially checkpoint inhibitors, dramatically improved the prognosis of some malignancies. However, problems on the occurrence of severe adverse effects and limited responses to these checkpoint inhibitors remain. Recently, tumor infiltrating lymphocytes(TILs)are the predictive markers of immunotherapies based on clinical evidence. The proportion of cytotoxic T cells in the tumor has been reported to affect the antitumor effect. TILs in the tumor are thought to be controlled by the interaction between cancer and tumor microenvironment. As a cause of tumor immunosuppression, cancer-associated fibroblasts(CAFs)play the main role in the tumor microenvironment. We considered the strong involvement of tumor microenvironment, particularly the role of CAFs, and reported the interaction between CAFs and proliferation, invasion, angiogenesis, and resistance in the conventional therapy. The correlation between CAFs and tumor immunity and the immunosuppression promoted by CAFs were also evaluated. Their effects will be reported in our future studies.

Cancer-Associated Fibroblasts Affect Intratumoral CD8+ and FoxP3+ T Cells Via IL6 in the Tumor Microenvironment.

Purpose: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a central role in tumor progression. We investigated whether CAFs can regulate tumor-infiltrating lymphocytes (TILs) and their role in tumor immunosuppression.Experimental Design: A total of 140 cases of esophageal cancer were analyzed for CAFs and CD8+ or forkhead box protein 3 (FoxP3+) TILs by IHC. We analyzed cytokines using murine or human fibroblasts and cancer cells. Murine-derived fibroblasts and cancer cells were also inoculated into BALB/c or BALB/c-nu/nu mice and the tumors treated with recombinant IL6 or anti-IL6 antibody.Results: CD8+ TILs and CAFs were negatively correlated in intratumoral tissues (P < 0.001), whereas FoxP3+ TILs were positively correlated (P < 0.001) in esophageal cancers. Cocultured Colon26 cancer cells and fibroblasts resulted in accelerated tumor growth in BALB/c mice, along with decreased CD8+ and increased FoxP3+ TILs, compared with cancer cells alone. In vitro, IL6 was highly secreted in both murine and human cancer cell/fibroblast cocultures. IL6 significantly increased Colon26 tumor growth in immune-competent BALB/c (P < 0.001) with fewer CD8+ TILs than untreated tumors (P < 0.001), whereas no difference in BALB/c-nu/nu mice. In contrast, FoxP3+ TILs increased in IL6-treated tumors (P < 0.001). IL6 antibody blockade of tumors cocultured with fibroblasts resulted not only in regression of tumor growth but also in the accumulation of CD8+ TILs in intratumoral tissues.Conclusions: CAFs regulate immunosuppressive TIL populations in the TME via IL6. IL6 blockade, or targeting CAFs, may improve preexisting tumor immunity and enhance the efficacy of conventional immunotherapies. Clin Cancer Res; 24(19); 4820-33. ©2018 AACR.

Two Cases of Cartilaginous Choristoma-Not Chondroma of the Bony External Auditory Canal.

The presence of a cartilaginous mass on the bony external auditory canal is an unusual finding. Currently, two different diagnoses have been used to describe this type of mass: chondroma and cartilaginous choristoma. There is currently no consensus on which diagnosis is appropriate for this type of lesion. Choristoma is defined as a tumor-like growth of normal tissue occurring in an abnormal location. Histological examination alone cannot be used to distinguish between cartilaginous choristoma and chondroma, as both lesions comprise normal mature hyaline cartilage. To diagnose a mass as cartilaginous choristoma on the bony external auditory canal, it is necessary to confirm that it does not originate from the underlying periosteum. Here, we present the cases of two patients with typical cartilaginous masses on the bony external auditory canal, in which the surgical findings showed that the masses were not in contact with the underlying periosteum, indicating that cartilaginous choristoma-not chondroma-is an appropriate diagnosis for these mass lesions. The clinical findings (characteristic appearance and location) reported here may aid clinicians in the diagnostic and surgical management of these cartilaginous masses.

Preoperative ultrasound for runoff-venous decompression of peripheral nerves for arteriovenous access-related pain in the upper limb.

INTRODUCTION: Arteriovenous access (AVA)-related pain treated successfully with runoff-venous decompression of the causative nerve, following ultrasound (US)-assisted preoperative evaluation, has never been reported. CASE PRESENTATION: A 57-year-old man suffering from constant exhausting pains along the outflow cephalic vein of the radiocephalic arteriovenous fistula at the wrist and the antecubital fossa, was treated surgically after the diagnosis of AVA-related pain derived from cephalic vein compression on two peripheral cutaneous nerves, the superficial radial nerve (SRN) and the lateral antebrachial cutaneous nerve (LACN). TECHNIQUE: The SRN and LACN, which ran along and/or provided sensory innervation to the painful regions in the upper limb, were traced using ultrasonography in the short axis and proved to be compressed by and in contact with veins where the pain existed, at the wrist and the antecubital fossa. Once diagnostic US-guided blocks of both were performed and pain disappeared, they were identified as the causative nerves. The cephalic venous decompression surgeries that separated and transposed the veins away from the SRN and the LACN were performed sequentially under pneumatic tourniquet inflation to improve nerve visualization. RESULTS: The pains disappeared after the operations. An adequate length of the runoff cephalic vein was maintained for needle cannulations during hemodialysis. CONCLUSIONS: Outflow venous compression to the peripheral nerves may be a cause of AVA-related pain. US-guided assessments of the nerves may improve the safety and efficiency of venous decompression surgeries to treat AVA-related pains.

Iron depletion is a novel therapeutic strategy to target cancer stem cells.

Adequate iron levels are essential for human health. However, iron overload can act as catalyst for the formation of free radicals, which may cause cancer. Cancer stem cells (CSCs), which maintain the hallmark stem cell characteristics of self-renewal and differentiation capacity, have been proposed as a driving force of tumorigenesis and metastases. In the present study, we investigated the role of iron in the proliferation and stemness of CSCs, using the miPS-LLCcm cell model. Although the anti-cancer agents fluorouracil and cisplatin suppressed the proliferation of miPS-LLCcm cells, these drugs did not alter the expression of stemness markers, including Nanog, SOX2, c-Myc, Oct3/4 and Klf4. In contrast, iron depletion by the iron chelators deferasirox and deferoxamine suppressed the proliferation of miPS-LLCcm cells and the expression of stemness markers. In an allograft model, deferasirox inhibited the growth of miPS-LLCcm implants, which was associated with decreased expression of Nanog and Sox2. Altogether, iron appears to be crucial for the proliferation and maintenance of stemness of CSCs, and iron depletion may be a novel therapeutic strategy to target CSCs.