[Indications and Outcomes of Laparoscopic Endoscopic Cooperative Surgery(LECS)for Gastric Gastrointestinal Stromal Tumor].

Laparoscopic and endoscopic cooperative surgery(LECS)for gastric gastrointestinal stromal tumor(GIST)has become a popular surgery with both curability and functional preservation. In this study, we examined the outcomes of 14 patients who underwent classical LECS or CLEAN-NET in our hospital. Until March 2022, classical LECS was performed in patients with intraluminal growth tumors or tumors close to the gastroesophageal junction. After April 2022, classical LECS was performed in patients with intraluminal growth tumors without ulceration, and CLEAN-NET was performed in patients with ulceration or intramural growth tumors. There were 10 males and 4 females with a median age of 80.5 years. Intraluminal growth tumor were 8 patients, close to the gastroesophageal junction tumor were 3, and intramural growth tumor were 4, respectively. Five of these patients had tumors with ulceration. Classical LECS was performed in 10 patients and CLEAN-NET in 4 patients, and the median operative time was 165.5 minutes. All patients underwent R0 resection, and no postoperative complications or recurrences were observed. LECS was performed safely, and it is important to select the surgical procedure according to the tumor site and growth type.

[A Case of Local Recurrence of Esophageal Cancer after Chemoradiation Therapy Successfully Treated with Nivolumab].

We report a case of a patient with locally recurrent esophageal cancer after chemoradiation therapy(CRT)who responded to nivolumab. The patient was an 86-year-old man with advanced esophageal cancer. Upper gastrointestinal endoscopy (EGD)revealed a type 2 lesion in the middle thoracic esophagus, and biopsy revealed squamous cell carcinoma(SCC). Contrast- enhanced CT showed invasion of the left main bronchi. The patient was diagnosed as Stage Ⅳa advanced esophageal cancer, and was treated with 5-FU plus cisplatin chemotherapy, and 60 Gy of radiation therapy. The tumor disappeared by CT and EGD, and the patient was followed up for observation. The patient experienced a feeling of tightness again, and EGD revealed an ulcerative lesion in the middle thoracic esophagus, and a biopsy detected SCC. Because of the early recurrence after CRT, the patient was judged to be resistant to 5-FU plus cisplatin chemotherapy, and 8 courses of nivolumab were administered as second-line treatment. Follow-up EGD confirmed disappearance of ulcerative lesions, and no tumors have been observed to date.

The Screening Test for Aphasia and Dysarthria (STAD) for Patients with Neurological Communicative Disorders: A Large-Scale, Multicenter Validation Study in Japan.

INTRODUCTION: Evaluation of multiple domains, such as language, articulation, and cognitive function, is frequently required in neurological communicative disorders. The purpose of this study was to investigate the performance of a 10-min screening scale for estimating aphasia, dysarthria, and cognitive dysfunction using a multicenter, large-sized consecutive series. METHODS: We conducted a multicenter validation study that included 314 patients with brain injury between February 1 and June 31, 2018, from 20 medical centers across Japan. The Screening Test for Aphasia and Dysarthria (STAD) was developed in Japan in 2009, and a previous smaller-scale retrospective study established its high to moderate validity. All patients had undergone the STAD, and 212 of them underwent the Western Aphasia Battery or Assessment of Motor Speech for Dysarthria. The effect size on all 29 items and receiver operating curves of 3 sections of the STAD were analyzed based on external criteria, which were decided considering the clinical diagnosis of aphasia, dysarthria, and cognitive dysfunction. Correlations between the STAD and reference tests were calculated. RESULTS: The phi coefficients of 23 out of 29 items exceeded the moderate effect size of 0.3 toward the targeted disorder. Overall, there was a good balance between sensitivity (82-92%) and specificity (77-78%), with moderate to large positive and negative likelihood ratios (3.7-4.19 and 0.1-0.23). The Pearson's r between the verbal section and Western Aphasia Battery Aphasia Quotient, the articulation section and Assessment of Motor Speech for Dysarthria, and the nonverbal section and Western Aphasia Battery Nonlinguistic Skills were 0.89, 0.70, and 0.79, respectively. CONCLUSION: We demonstrated that the STAD has acceptable content and concurrent validity for the assessment of communicative function in patients with brain injury. This short screening tool can be useful in specific contexts, such as in early bedside investigations, to obtain a quick summary of communicative function prior to the administration of other tests, and in cases where more in-depth testing is not feasible.

[Surgical ulcerative colitis complicated by multiple lung abscesses secondary to septic pulmonary embolism after multidrug immunosuppressive therapies].

This is a case implying a serious infectious complication risk during intensive severe ulcerative colitis treatment. A 26-year-old man developed diarrhea and bloody stool who was diagnosed with ulcerative colitis in 2018. He was managed with 5-aminosalicylic acid, but intolerance reaction resulted in discontinuation of treatment. He relapsed with severe abdominal pain and bloody stools in February 2019. He was referred to our department for intensive therapy. He had been treated with steroids, tacrolimus, granulocyte and monocyte apheresis, infliximab or tofacitinib, which temporarily improved his clinical symptoms. However, his medical condition could not be controlled. Hand-assisted laparoscopic subtotal colectomy was then performed in October 2019. He developed intermittent fever on postoperative day 3. Enhanced computed tomography (CT) revealed multiple deep vein thromboses and pulmonary embolism. Antibiotics and anticoagulation therapy were initiated, but postoperative day 13 CT showed multiple pulmonary cavities containing fluids and air, which were diagnosed as pulmonary abscess. His intermittent fever was over 38.0°C. Severe cough and hemoptysis lasted 3 weeks, the clinical symptoms and laboratory data then gradually improved after the fourth week.

Progression of ulcerative colitis following diversion colitis.

Diversion colitis and ulcerative colitis (UC) can be caused by different mechanisms; however, several case reports have described the development of typical UC following diversion colitis. A 63-year-old man underwent Hartmann's operation following a diagnosis of perforation of a sigmoid colon diverticulum and peritonitis. Stoma closure was performed 4 months later, and the portion of the sigmoid colon with the diverticulum was unintentionally left as a blind end. Following stoma closure, hematochezia worsened, and he was diagnosed as having developed diversion colitis only in the blind sigmoid colon. Intermittent use of topical mesalazine enemas controlled the bowel symptoms; however, 4 years after the stoma closure, bloody stools were observed again. Colonoscopy revealed coarse and friable granular mucosa with adherent mucopurulent exudate in the rectum, and mucosal erythematous edema with adherent mucopurulent exudate in the blind sigmoid colon. The histological findings indicated basal plasmacytosis, and goblet cell depletion and cryptitis in the lamina propria, which is characteristic of UC. To the best of our knowledge, this is the fourth description of a patient who developed UC following diversion colitis. Local inflammation may have triggered the development of UC through hematogenous or lymphogenous circulation of lymphocytes or autoantibodies.

Capsaicin and Proton Differently Modulate Activation Kinetics of Mouse Transient Receptor Potential Vanilloid-1 Channel Induced by Depolarization.

The transient receptor potential vanilloid type 1 (TRPV1) channel is a non-selective cation channel expressed with transient receptor potential ankyrin type 1 (TRPA1) in small and medial size neurons of the dorsal root ganglions and trigeminal ganglions. TRPV1 is activated by capsaicin, thermal stimuli higher than 43°C, mechanical stress, and protons (H+). Although the TRPV1 channel does not have positively charged residues at regular intervals on its transmembrane segments, alterations in membrane potential also affect the state of TRPV1 channel. In the presence of capsaicin, voltage-dependent probability of opening of the TRPV1 channel and its kinetics have been examined, but the characteristics in the low pH remain unclear. To understand the voltage-dependency of the TRPV1 channel activation, we recorded capsaicin- and proton-induced mouse TRPV1 channel currents in a heterologous expression system. Outward current evoked by depolarizing square pulses in the presence of capsaicin or protons was fitted to a two-exponential function with a time-independent component. The voltage-dependent changes in amplitude of the three components displayed shallow curves and the changes in their ratio to the total current display similar tendencies in the presence of capsaicin and under the low pH. However, the fast and slow time constants in the presence of capsaicin were respectively 5- and 8-fold lower than those obtained under low pH conditions. These results suggest that the TRPV1 channel slowly drives the feed-forward cycle of pain sensation, and capsaicin and protons differently modulate the voltage-dependent TRPV1 channel gating.

Trajectory and profile of quality of life in patients undergoing lung resection for lung cancer during hospitalization according to the EQ-5D.

OBJECTIVE: To clarify the trajectory and profile of quality of life (QOL) in lung cancer patients undergoing surgery during hospitalization. METHODS: Among prospectively enrolled 279 patients between 2015 and 2018, we used the EQ-5D-5 levels (EQ-5D-5L), which consist of a descriptive system of five dimensions and a visual analog scale (VAS) (from 0 to 100). The five dimensions are mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, which are rated according to a 5-grade evaluation. QOL assessments were performed preoperatively (Pre) and on postoperative day 1/3/5/7 (D1/D3/D5/D7). To observe the trajectory of QOL, the EQ-5D VAS was used. To define the profile of QOL, we applied univariate linear regression analysis to predict EQ-5D VAS based on the five dimensions of EQ-5D as explanatory variables and to determine the rank of absolute values of the standardized coefficient of each dimension that represented strength of the effect on the EQ-5D VAS. RESULTS: The means of VAS scores were as follows: Pre/D1/D3/D5/D7 = 79/45/58/64/71. Younger age, fewer comorbidities, and surgical indications decreased the VAS at D1. More comorbidities, advanced cancer stage, postoperative adverse events, and chest tube placements hampered restoration of the VAS. Regarding QOL profiles, anxiety/depression was the highest rank preoperatively while usual activity, but not pain/discomfort, was the highest postoperatively. CONCLUSIONS: This is the first study to visualize the trajectory of QOL in surgical patients with lung cancer during hospitalization. This information may help improve perioperative patient care.

Treatment of hepatocellular carcinoma with hepatic vein tumor thrombosis protruding into the inferior vena cava by conversion surgery following chemotherapy with regorafenib: a case report.

Regorafenib is an oral multikinase inhibitor affecting angiogenesis, oncogenesis, metastasis, and tumor immunity. As a systemic treatment, it has been shown to provide survival benefits in hepatocellular carcinoma (HCC) patients progressing on sorafenib treatment. We report herein a case of HCC with hepatic vein tumor thrombosis protruding into the inferior vena cava (IVC-HVTT) which was successfully treated by surgery following second-line chemotherapy with regorafenib. A 79-year-old man with chronic hepatitis was diagnosed with HCC. Computed tomography revealed a solitary tumor in segments 7 and 8 and an IVC-HVTT from the right hepatic vein. Since IVC-HVTT removal is a difficult procedure, the tumor was diagnosed as unresectable, and administration of sorafenib was started. Five weeks later, the lesion had increased in size by 15.3%; subsequently, regorafenib was given as second-line therapy for 12 months. After shrinkage of the IVC-HVTT, the patient was referred to our hospital for surgery. One month after the cessation of regorafenib, an extended resection of segment 8 and total removal of the IVC-HVTT was successfully performed without using total hepatic vascular exclusion. There were no serious postoperative complications. Additionally, there has been no recurrence for about 2 years since the initial therapy.

Decorin suppresses bone metastasis in a breast cancer cell line.

Decorin, the prototype of an expanding family of small leucine-rich proteoglycans, is involved in a number of cellular processes including matrix assembly, fibrillogenesis and the control of cell proliferation. In this study, we investigated the role of decorin in suppressing tumor aggressiveness and bone metastases. We used a metastatic breast cancer cell line, MDA-MB-231, to show that decorin causes marked growth suppression bothin vitro and in vivo. A cytomegaloviral vector containing the decorin transgene caused greatly reduced cell growth, motility and observed metastases. Bone metastases were decreased by >90% upon decorin transfection. These results demonstrate a novel role for decorin in the reduction or prevention of tumor metastases in this breast cancer model and could eventually lead to improved therapies for metastatic breast cancer.

Devastating ochronotic arthropathy with successful bilateral hip and knee arthroplasties.

Ochronotic arthropathy is a manifestation of long-standing alkaptonuria, a rare hereditary metabolic disorder characterized by the absence of the enzyme homogentisic acid oxidase. We describe a patient who developed rapidly progressive destructive ochronotic arthropathy in his knee and hip joints and underwent successful bilateral total knee and hip arthroplasties.

Decorin suppresses lung metastases of murine osteosarcoma.

Lung metastasis is the most crucial event affecting the therapeutic outcome of osteosarcoma. The prevention of lung metastasis is therefore important in improving the prognosis of patients with osteosarcoma. Decorin is a major extracellular matrix protein which has become the focus of various cancer studies. The biological role of decorin in osteosarcoma has yet to be clarified. The aim of this study was to examine the potential of decorin as a novel biological target for the treatment of osteosarcoma. In this study, the LM8 murine osteosarcoma cell line (LM8) with high metastatic potential to the lung was used. The two cell lines established were LM8-DCN which stably expressed human decorin (hDCN) and LM8-mock, established as a control. The LM8-DCN cell line was subcutaneously injected into the backs of mice. Significantly fewer pulmonary metastases were observed in mice with LM8-DCN compared to mice inoculated with LM8 and LM8-mock (P<0.001). In addition, the mice in the LM8-DCN inoculated group survived significantly longer than those in the LM8 and LM8-mock inoculated group, based on the Kaplan-Meier survival analysis and log-rank tests (P<0.005). The effect of decorin on the growth rates, motility and invasion ability of LM8 was investigated in vitro. There was no difference in the morphology and growth rates, but the motility and invasion of LM8 were inhibited by decorin. These results suggest that decorin has the therapeutic potential to prevent lung metastasis in osteosarcoma.

Pisa syndrome.

STUDY DESIGN: Case report. OBJECTIVE: We report a patient who developed Pisa syndrome (drug-induced pleurothotonus) after treatment with tricyclic antidepressant. SUMMARY OF BACKGROUND DATA: Pisa syndrome is familiar to neuropsychiatrists, but not to orthopedic surgeons and spinal surgery specialists, both of whom have reported few cases of this syndrome. METHODS: A 56-year-old woman had experienced feelings of depression and saw a local doctor, where the tricyclic antidepressant clomipramine hydrochloride (9x25 mg tablets daily) was prescribed. From about 2 months after starting medication, she developed flexion of the trunk to the left. RESULTS: Pisa syndrome was suspected, and then, the daily dose of clomipramine hydrochloride was decreased from 9x to 3x25 mg tablets. Approximately 2 weeks after reducing the dose, abnormal postures gradually improved, and after 1 month, flexion of the trunk resolved. CONCLUSIONS: We reported a case of Pisa syndrome in which pleurothotonus occurred after treatment with a tricyclic antidepressant and improved after dose reduction. When middle-aged or elderly patients who see orthopedic surgeons display abnormal postures of the trunk, physicians need to ask the patient whether they have received a drug that can cause Pisa syndrome, such as an antipsychotic or antiemetic.