English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) issued by the Japan Society of Clinical Oncology.

The Japan Society of Clinical Oncology Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) have been published in accordance with the Minds Manual for Guideline Development 2014 and 2017. A specialized team independent of the working group for the revision performed a systematic review. Since GIST is a rare type of tumor, clinical evidence is not sufficient to answer several clinical and background questions. Thus, in these guidelines, we considered that consensus among the experts who manage GIST, the balance between benefits and harms, patients' wishes, medical economic perspective, etc. are important considerations in addition to the evidence. Although guidelines for the treatment of GIST have also been published by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), there are some differences between the treatments proposed in those guidelines and the treatments in the present guidelines because of the differences in health insurance systems among countries.

Biomechanics of increased spin velocity of flying discs during forehand throws by skilled and unskilled throwers.

We aimed to assess the relationship between throwing distance and kinematic release parameters of the flying disc in unskilled throwers, and to assess the relationship between kinetic variables acting on flying discs and the change in spin velocity during long forehand throws by skilled and unskilled throwers. Ten skilled and eleven unskilled throwers performed throws at maximum effort. Reflective marker positions on the disc and body were recorded with a 3D motion capture system during the throws to derive kinematic variables of a disc and kinetic variables acting on the disc. The analysis interval was from maximum external shoulder rotation to disc release. Significant correlations were observed between the throwing distance and spin velocity in skilled (r = 0.722, P < 0.05) and unskilled throwers (r = 0.794, P < 0.01), between the change in spin velocity and the angular impulse of moments of force, in unskilled throwers (r = 0.703, P < 0.05), and between the change in spin velocity and the angular impulse of torque among skilled throwers (r = 0.680, P < 0.01). Therefore, a strategy for increasing spin velocity in unskilled throwers could be used to generate a larger torque, similar to that observed in skilled throwers.

First case report of bacteremia caused by Dysgonomonas mossii.

We here report a case of Dysgonomonas mossii bacteremia with cholangitis. An 85-year-old male patient with recurrent hepatitis B surface antigen-negative/anti-hepatitis C virus-negative hepatocellular carcinoma came to our hospital in poor physical condition. Two sets of blood cultures revealed a positive result for D. mossii. As matrix-assisted laser desorption/ionization time-of-flight mass spectrometry failed to identify D. mossii, analysis of 16S rRNA gene sequencing was performed; however, this gene is not specific enough to distinguish between D. mossii and D. oryzarvi. Finally, D. mossii infection was confirmed by gyrB and recA sequencing. To our knowledge, this is the first report of D. mossii causing human infection, which was identified in culture and confirmed using a combination of 16S rRNA, gyrB, and recA sequencing.

Asymmetry in Determinants of Running Speed During Curved Sprinting.

This study investigates the potential asymmetries between inside and outside legs in determinants of curved running speed. To test these asymmetries, a deterministic model of curved running speed was constructed based on components of step length and frequency, including the distances and times of different step phases, takeoff speed and angle, velocities in different directions, and relative height of the runner's center of gravity. Eighteen athletes sprinted 60 m on the curved path of a 400-m track; trials were recorded using a motion-capture system. The variables were calculated following the deterministic model. The average speeds were identical between the 2 sides; however, the step length and frequency were asymmetric. In straight sprinting, there is a trade-off relationship between the step length and frequency; however, such a trade-off relationship was not observed in each step of curved sprinting in this study. Asymmetric vertical velocity at takeoff resulted in an asymmetric flight distance and time. The runners changed the running direction significantly during the outside foot stance because of the asymmetric centripetal force. Moreover, the outside leg had a larger tangential force and shorter stance time. These asymmetries between legs indicated the outside leg plays an important role in curved sprinting.

Myocarditis, hepatitis, and pancreatitis in a patient with coxsackievirus A4 infection: a case report.

Viral myocarditis presents with various symptoms, including fatal arrhythmia and cardiogenic shock, and may develop chronic myocarditis and dilated cardiomyopathy in some patients. We report here a case of viral myocarditis with liver dysfunction and pancreatitis. A 63-year-old man was admitted to our hospital with dyspnea. The initial investigation showed pulmonary congestion, complete atrioventricular block, left ventricular dysfunction, elevated serum troponin I, and elevated liver enzyme levels. He developed pancreatitis five days after admission. Further investigation revealed a high antibody titer against coxsackievirus A4. The patient's left ventricular dysfunction, pancreatitis, and liver dysfunction had resolved by day 14, but his troponin I levels remained high, and an endomyocardial biopsy showed T-lymphocyte infiltration of the myocardium, confirming acute myocarditis. The patient underwent radical low anterior resection five weeks after admission for advanced rectal cancer found incidentally. His serum troponin I and plasma brain natriuretic peptide levels normalized six months after admission. He has now been followed-up for two years, and his left ventricular ejection fraction is stable.This is the first report of an adult with myocarditis and pancreatitis attributed to coxsackievirus A4. Combined myocarditis and pancreatitis arising from coxsackievirus infection is rare. This patient's clinical course suggests that changes in his immune response associated with his rectal cancer contributed to the amelioration of his viral myocarditis.

Cytologic features of low-grade cribriform cystadenocarcinoma of the submandibular gland: a case report.

BACKGROUND: Low-grade cribriform cystadenocarcinomas (LGCCC) are rare salivary gland tumors, classified into a variant of cystadenocarcinoma by the 2005 WHO classification. All previously reported cases arose from parotid glands, except for a case from a minor salivary gland. We report here for the first time a case of LGCCC arising from the submandibular gland. CASE: A 65-year-old man presented with a 4-cm multicystic mass in the left submandibular gland. Smears from fine-needle aspiration cytology showed tumor cells, appearing solitarily or partly in clusters, with thick cytoplasm and central nuclei. Some clustering tumor cells showed large cytoplasmic vacuoles and peripherally dislocated nuclei. Although these findings indicated a possible mucoepidermoid carcinoma in the submandibular gland, the final diagnosis of the resected specimen was LGCCC. CONCLUSION: LGCCC can arise not only from the parotid glands, but also in the submandibular glands. LGCCC is thought to be of low-grade malignancy; no reported cases have shown tumor metastasis and there are no patients who are known to have died of this disease. Thus, differential diagnosis of this tumor from other malignant salivary gland tumors is quite important; however, this might be difficult when based solely on cytological findings.

Ball spin in the tennis serve: spin rate and axis of rotation.

The purpose of this study was to describe three-dimensional ball kinematics including spin axis and spin rate for the flat, slice, and kick serves executed by elite male tennis players. Trajectories of three retro-reflective markers attached to the surface of the ball were measured using a Vicon MX motion analysis system. The local coordinate system of the ball enabled the ball's angular velocity vector to be determined. Mean (+/- SD) spin rates recorded were 127.4 (+/- 56.3), 232.1 (+/- 34.8), and 336.5 (+/- 51.5) rad/s for the flat, slice, and kick serves, respectively. The resultant horizontal velocities of the ball were 52.0 (+/- 2.9), 46.4 (+/- 3.4), and 40.8 (+/- 2.8) m/s, respectively, and a clear tradeoff existed between the development of ball spin rate and horizontal ball velocity. [corrected]. The spin axis and ball velocity vector were close to perpendicular regardless of serve type. Mean angles between the spin axis and the horizontal plane (elevation angles) were 65.68 (+/- 10.28), 68.48 (+/- 6.98), and 54.58 (+/- 8.48) for the flat, slice, and kick serves, respectively. [corrected].

Estimating flight trajectories of breaking balls from four-seam fastballs.

It is widely acknowledged that understanding the physical mechanics of the flight trajectories of four-seam fastballs and breaking balls is crucial for players and coaches to enhance pitching performance. The characteristics of the flight trajectories of four-seam fastballs and breaking balls have been revealed; however, the relationship between them has not been examined. Here, we show the characteristics of the flight trajectory of breaking balls from the four-seam fastballs. We found that the direction of the deviation of the curveballs could be generally predicted from that of the four-seam fastballs. We also found that the limits of the deviation of the sliders can be determined from the direction of the deviation of the four-seam fastball. This study revealed the deviation of the breaking ball from the four-seam fastballs, which clearly showed the differences in the characteristics between curveballs and sliders. This study moved forward with the description of the physical properties of each pitch type and allowed us to obtain valuable insights and practical implications.

Gastric schwannomas show an obviously increased fluorodeoxyglucose uptake in positron emission tomography: report of two cases.

Schwannomas are tumors originating from any nerve that has a Schwann cell sheath. Gastrointestinal (GI) schwannomas represent only 3% of all GI mesenchymal tumors. The stomach is the most common site of GI schwannomas, and schwannomas account for 0.2% of all gastric neoplasms. This report presents two cases of gastric schwannomas showing increased [18F]fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET; maximum standardized uptake value 7.10 and 6.05). Additional immunohistochemical staining of glucose transporter type 1 (GLUT1) and the autocrine motility factor (AMF) was conducted after the tumors were resected, to identify the mechanism that increased FDG uptake on PET. Immunohistochemical expression of AMF was positive in both cases, whereas GLUT1 was negative. Autocrine motility factor is also known as phosphoglucose isomerase. However, the mechanism by which FDG is accumulated in schwannoma cells is uncertain, and may be related to intracellular glycolytic activity.

Factors determining the spin axis of a pitched fastball in baseball.

In this study, we wished to investigate the factors that determine the direction of the spin axis of a pitched baseball. Nineteen male baseball pitchers were recruited to pitch fastballs. The pitching motion was recorded with a three-dimensional motion analysis system (1000 Hz), and the orientations of the hand segment in a global coordinate system were calculated using Euler rotation angles. Reflective markers were attached to the ball, and the direction of the spin axis was calculated on the basis of their positional changes. The spin axis directions were significantly correlated with the orientations of the hand just before ball release. The ball is released from the fingertip and rotates on a plane that is formed by the palm and fingers; the spin axis of the ball is parallel to this plane. The lift force of the pitched baseball is largest when the angular and translational velocity vectors are mutually perpendicular. Furthermore, to increase the lift forces for the fastballs, the palm must face home plate.

Mechanical energy flow in torso during baseball toss batting.

The purpose of this study was to clarify the relationship between the efficiency of mechanical energy flow in the torso and bat head speed at impact. Ninety-eight amateur baseball players batted a light ball tossed from the pitcher direction 3.2 m away. The batting motion and ground reaction forces acting on each foot were recorded using a motion capture system and two force plates, respectively. The mechanical powers of the joint forces and joint torques were calculated to measure the generation, absorption, and transfer of mechanical energy in the torso. The transfer efficiency of mechanical energy in the torso was defined as the ratio of the mechanical energy inflow into the thorax from the torso joint to the mechanical energy outflow from the pelvis to the torso joint. The correlation coefficient between the bat head speed and transfer efficiency of mechanical energy in the torso was very low. Conversely, the mechanical energy flow in the torso was significantly correlated to the bat head speed. Therefore, the results suggest that the torso in baseball batting is not utilised for the generation of mechanical energy but acts as a pathway for the transfer of mechanical energy.

A case of 18 years disease-free survival after combined pancreatoduodenectomy and hemicolectomy for carcinosarcoma of the transverse colon.

BACKGROUND: Ascertaining the origin of large tumors located in the region of the pancreas head and adjacent mesocolon can pose a challenge preoperatively. En bloc pancreatoduodenectomy with hemicolectomy is often required towards curative tumor resection (R0) of malignant tumors in this region. CASE PRESENTATION: Herein we report a case of a 48-year-old man with two contiguous masses each 5 cm in size, located in the pancreatic head. The masses were detected incidentally by abdominal ultrasonography at an annual health check. Endoscopic biopsies revealed inflammation with no malignancy. Cross-sectional imaging showed the tumor direct invasion of the uncinate process of the pancreas, and the third portion of the duodenum. Based on imaging, a malignant submucosal tumor originating from mesenchymal cells in the mesentery of the transverse colon was made preoperatively. The mass required en bloc pancreatoduodenectomy, right hemicolectomy, and resection of the superior mesenteric vein. The final pathology was carcinosarcoma of the transverse colon. The patient survived 18 years after surgery without recurrence. CONCLUSIONS: Malignant tumors located in the region of the pancreas head should be considered for an en bloc curative tumor resection and adjuvant chemotherapy treatments offered that might be beneficial for carcinosarcoma.

Pleomorphic phenotypes of gastrointestinal stromal tumors at metastatic sites with or without imatinib treatment.

Secondary resistance of gastrointestinal stromal tumors (GISTs) to tyrosine kinase inhibitors occurs after several years' administration. However, the mechanism of resistance has not been fully clarified. In this study, we analyzed the genotypes and the histologic and immunohistochemical phenotypes of metastatic GISTs with and without imatinib treatment, and clarified the pleomorphic nature of metastatic GISTs. We examined 31 autopsy cases in which the patients died of multiple metastases of GISTs, and two surgically resected specimens with and without imatinib treatment. A total of 152 primary and metastatic lesions in 33 cases of GISTs were examined for histologic and immunohistochemical expression of KIT and CD34. We analyzed the expression of other receptor tyrosine kinases (RTKs) in KIT-negative lesions, including human EGFR-related 2 (HER2), epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (MET), platelet-derived growth factor receptor-alpha (PDGFRA), and platelet-derived growth factor receptor-beta (PDGFRB). Fifteen lesions in seven cases (9.9%) lacked KIT expression, and 74 (49%) in 22 cases lacked CD34 expression. Eight KIT-negative lesions in five cases expressed PDGFRB, one of which also expressed EGFR, and three lesions in one case expressed MET. Results for the other RTKs were negative. Missense point mutations at PDGFRB gene exon 12 were detected in one PDGFRB-positive case. Our results indicate that histomorphology, immunohistochemical phenotypes, and genotypes of metastatic GISTs vary among lesions, even in cases without imatinib treatment. A KIT-independent mechanism, such as activation of other RTKs, might participate in the proliferation of late-stage GISTs and might be a cause of secondary imatinib resistance.

Use of tissue microarrays and immunohistochemistry to standardize the diagnosis of gastrointestinal stromal tumors.

We assessed the concordance among seven general pathologists with respect to histologic diagnosis and interpretation of c-kit proto-oncogene (KIT) and platelet-derived growth factor receptor alpha (PDGFRA) immunostaining of 36 cases of primary spindle-cell tumor, predominantly of the gastrointestinal tract, mesentery, and retroperitoneum, based on review of a tissue microarray (TMA) subjected to immunohistochemistry with antibodies to KIT/CD117, PDGFRA, vimentin, desmin, smooth muscle action, CD34, and S-100 protein. Tumors included 20 molecularly analyzed gastrointestinal stromal tumors (GISTs), 4 leiomyosarcomas, 4 schwannomas, 4 desmoid-type fibromatoses, and 4 solitary fibrous tumors. The mean overall concordance with original diagnosis for each histologic type was 91.1%, with a mean kappa value of 0.91. With respect to PDGFRA immunostaining, the four GISTs with PDGFRA mutation were interpreted as cytoplasm positive, but the 16 GISTs with c-kit mutation were interpreted as weak or positive. These results indicate that the overall concordance with original diagnosis in mesenchymal tumors with the use of immunohistochemical panels is high, despite the use of TMAs. To some extent, PDGFRA immunophenotyping may be useful in GISTs with PDGFRA mutation, but it was not highly reproducible or specific. Therefore, in KIT-negative or weakly positive GISTs, mutation analysis will be required.

CD24 expression is a novel prognostic factor in esophageal squamous cell carcinoma.

Esophageal cancer is one of the most difficult malignancies to cure, and identification of novel prognostic markers for patients with this disease is important. CD24 is a small highly glycosylated mucin-like protein. Several studies have shown that higher CD24 expression is significantly associated with shorter patient survival in various malignant tumors. However, the expression of CD24 and its clinicopathological significance in esophageal cancer remain largely unknown. Immunohistochemical analyses of CD24 and Ki-67 overexpression in 151 cases of esophageal squamous cell carcinoma were performed to examine the relationships of CD24 expression with clinicopathological parameters and patient survival. Five cell lines derived from esophageal cancer were subjected to Western blot analyses to evaluate CD24 expression. Immunohistochemically, CD24 expression was judged to be positive in 61 (40.4%) cases. CD24 expression was associated with lymph node metastasis (p = 0.005), pathologic stage (p = 0.018), number of nodal metastases (p = 0.003), lymphatic invasion (p = 0.002), venous invasion (p < 0.001), and Ki-67 labeling index (p < 0.001). The Pearson's correlation coefficient between the CD24 expression score and the Ki-67 labeling index was 0.404 (p < 0.001). CD24 expression was associated with disease-free survival (p < 0.001). A Cox multivariate regression analysis revealed that CD24 expression was an independent prognostic factor (p = 0.033). On Western blot analysis, CD24 was detected in all five cell lines. We conclude that overexpression of CD24, which was correlated with Ki-67 expression, is a novel independent prognostic marker for identifying patients with poor prognosis after curative resection of esophageal squamous cell carcinoma.

Gastrointestinal stromal tumor in the duodenum exhibiting hemangiopericytoma-like histological pattern.

Reported herein is a gastrointestinal stromal tumor (GIST) that exhibited a hemangiopericytoma (HPC)-like histological pattern. Such a morphological variant of GIST has not been described previously. A 57-year-old woman presented with bloody stools. On upper digestive tract endoscopy a submucosal tumor of diameter 2 cm was detected at the duodenal bulb, and enucleated. Grossly, the tumor was well-circumscribed, grayish to whitish, and solid, and its central portion was ulcerated. Histology indicated round to fusiform tumor cells that had proliferated around branching vessels that had a staghorn configuration. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin and KIT; partially positive for CD34 and muscle actin; and negative for alpha-smooth muscle actin. On mutation analysis a 42 bp deletion was found from codons 560 to 573 of exon 11 of the KIT gene, which is a mutational hot spot of GIST. In diagnosis of gastrointestinal tract tumors with an HPC-like histological pattern, pathologists should consider the possibility of GIST.

High-grade neuroendocrine carcinoma of the lung: comparative clinicopathological study of large cell neuroendocrine carcinoma and small cell lung carcinoma.

Large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) are high-grade neuroendocrine carcinomas. In order to clarify the similarities and differences between these cancers, 22 cases each of LCNEC and SCLC were collected and a comparative pathological study was carried out. First, their clinicopathological characteristics were confirmed, which were very similar to those previously reported. The 5 year survival rate of LCNEC and SCLC patients was 38.3% and 29.7%, respectively. The morphological characteristics of LCNEC and SCLC were then reviewed with regard to the morphology previously used to differentiate these cancers. As a result, many morphological indicators, such as tumor cell size, nuclear/cytoplasmic ratio, nuclear molding, rosette formation, prominent nucleoli and karyolysis were confirmed to be significant indicators for distinguishing LCNEC from SCLC. On comparative immunohistochemistry, LCNEC had significantly high staining scores for the expression of keratin 7 and 18, E- and P-cadherins, beta-catenin, villin 1, retinoblastoma protein (pRB), c-met and alpha-enolase. These results might reflect the differentiation or deviation of LCNEC toward an epithelial nature irrespective of neuroendocrine tumor lineage. In conclusion, the present comparative study of LCNEC and SCLC defined the similarities and differences between these cancers, and showed the biologically and clinicopathologically overlapping spectrum of the tumor lineage.

Gastrointestinal stromal tumor of the lesser omentum in a young adult patient with a history of hepatoblastoma: report of a case.

A gastrointestinal stromal tumor (GIST) of the lesser omentum is extremely rare. This report presents a case of GIST of the lesser omentum in a 22-year-old man with a history of hepatoblastoma. Computed tomography showed an abdominal mass about 30 mm in diameter adjacent to the lesser wall of the stomach. A laparotomy showed a mass of about 27 x 24 x 20 mm in diameter originating from the lesser omentum but isolated from the stomach and the liver. Histopathology showed that the tumor was composed of spindle-shaped tumor cells with high cellularity. Immunohistochemically, the tumor was positive for KIT and CD34. An in-frame deletion was observed in the c-kit gene exon 11. Therefore, the tumor was diagnosed as a GIST originating from the lesser omentum.

The effects of soil and Trifolium repens (white clover) on the fate of estrogen.

In this study, we investigated the behavior of estrogens in the rhizosphere of white clover (Trifolium repens, clover hereafter) with two different pot tests, using soil and agar as growth media. In a pot test using agar spiked with estrogen, the estrogen concentration in the agar with clover decreased to non-detectable levels within one month, while in the agar without clover, 60% of initially added estrogen remained after one month. The half-lives of estrone (E1) and 17beta -estradiol (E2) in the agar with clover were 2.4-3.8 and 13.2 d, respectively. The dissipation of E1 followed first-order rate law, while that of E2 fitted a zero-order reaction, indicating that they had different mechanisms of dissipation from agar. In the soil pot test, the behavior of E1 and E2 was not influenced by clover. An initial rapid decrease in the amount of estrogen extracted by methanol/acetic acid was followed by persistence for 1-3 months, regardless of presence of clover. Moreover, in three weeks E1 and E2 were only partly degraded by microbes extracted from the soil used in the pot test. In this study, abiotic degradation of estrogens and sorption of estrogen to soil, rather than the effects of soil microbes and clover, contributed to the initial rapid dissipation of estrogens in the soil. However, the results of the agar pot test suggested that vegetation such as clover may significantly contribute to removal of estrogens when estrogens in aqueous phase are discharged with surface runoff and preferential flow after heavy rain in agricultural fields, or when present in soils with low estrogen sorptivity.

Retroperitoneal Liposarcoma with Multilocular Cysts.

In this study, we describe a 60-year-old man with a giant retroperitoneal liposarcoma with multilocular cysts. He was admitted to our hospital because of a 5-month history of abdominal distention. Abdominal computed tomography revealed a giant lobulated cystic mass occupying the retroperitoneal space that contained partially solid fat components. Magnetic resonance imaging indicated that this complex mass exhibited a low signal intensity on a T1-weighted image, whereas it exhibited a high and focally intermediate signal intensity on a T2-weighted image. This patient was diagnosed with a mucinous type of retroperitoneal sarcoma, which was then resected. During surgery, the tumor was isolated from the retroperitoneum and other organs, but the detachment was required only because of fixation around the left external iliac artery. The histological diagnosis was a well-differentiated liposarcoma with multilocular cysts that contained old bloody, serous, and mucinous fluids, which are a rare phenomenon in liposarcoma. This case indicates that retroperitoneal liposarcoma should also be considered as a differential diagnosis of retroperitoneal cystic mass.