Clinical benefits of precision medicine in treating solid cancers: European Society of Medical Oncology-Magnitude of Clinical Benefit Scale score-based analysis.

BACKGROUND: Precision and matched cancer medicine has the potential to complement the existing biomarker approaches in cancer treatment. However, despite their promising potential, certain negative results have highlighted their limitations in molecular biology-driven treatment strategies. This study aimed to evaluate the clinical benefits of precision therapies. MATERIALS AND METHODS: Three reviewers independently identified and assessed precision and matched cancer treatment studies published between January 2015 and December 2020. Clinical benefits of the treatments included in our cohort were assessed using two established frameworks; the European Society of Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) and the American Society of Clinical Oncology Value Framework. RESULTS: Of the 290 eligible studies, 130 were for lung cancer, 51 for solid tumors, 24 for melanoma, and 24 for breast cancer. The common targets were: epidermal growth factor receptor (N = 66), serine/threonine-protein kinase B-Raf (N = 40), anaplastic lymphoma kinase (ALK) (N = 34), breast cancer protein (N = 26), phosphatidylinositol-3 kinase/protein kinase B/phosphatase and tensin homolog (PI3K/AKT/PTEN) pathway (N = 19), receptor tyrosine-protein kinase erbB-2 (HER2) (N = 19), mitogen-activated protein kinase (RAS/RAF/MAPK) pathway (N = 18), programmed death-ligand 1 (N = 12), fibroblast growth factor receptor (N = 8), and others (N = 43). The ESMO-MCBS scales ranged from 0 to 4. Based on the clinical benefit values, tumor mutational burden/mismatch repair-deficient/microsatellite instability-high for immunotherapy, anaplastic lymphoma kinase, and neurotrophic receptor tyrosine kinase therapeutic targets were considered high, whereas RAS/RAF/MAPK and PI3K/AKT/PTEN were considered low. Additionally, we found a significant difference between each average score (P < 0.001). CONCLUSIONS: This study showed that precision and matched cancer therapies require further improvement. This is consistent with the views of the tumor board and of clinicians that precision strategies need to be revised to improve their therapeutic effects.

Donor site selection and clinical outcomes of nipple-areola skin-sparing mastectomy with immediate autologous free flap reconstruction: A single-institution experience.

BACKGROUND: The objective of this study was to examine the clinical outcomes of immediate breast reconstruction using perforator flaps from different donor sites, and to characterize the trends among these flaps. METHODS: We retrospectively reviewed 136 consecutive patients who underwent immediate breast reconstruction using free flaps after skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM). The whole breast was pathologically analyzed in 5-mm sections. Breast reconstruction was performed using the deep inferior epigastric perforator (DIEP) flap, gluteal artery perforator (GAP) flap, and posterior medial thigh perforator (PMTP) flap. Patient characteristics were compared among donor sites. RESULTS: NSM was converted to SSM because of intraoperative subareolar tumor positivity in 7 of 107 patients. Eleven patients had positive margins in permanent sections. All but one patient had a positive horizontal margin in the peripheral direction. The 5-year recurrence-free survival rate was 91.9%. The locoregional recurrence rate was 5.1% with a mean follow-up observation period of 75 months. DEIP, GAP, and PMTP flaps were used in 64 (47.1%), 38 (27.9%), and 34 (25.0%) patients, retrospectively. DIEP flaps were used in older patients and those with a higher body mass index. GAP flaps were used in younger patients. DIEP and GAP flaps were used for larger breasts, and PMTP flaps for smaller breasts. CONCLUSION: NSM or SSM with immediate perforator flap breast reconstruction is an oncologically acceptable surgical option. We believe that age, desire to have children, body mass index, and excised breast volume are valuable factors for selecting the optimal donor site.

Outcomes of immediate perforator flap reconstruction after skin-sparing mastectomy following neoadjuvant chemotherapy.

BACKGROUND: The impact of neoadjuvant chemotherapy (NACT) on immediate free flap breast reconstruction remains controversial. Furthermore, the oncological outcomes of immediate free flap breast reconstruction after skin-sparing mastectomy (SSM) following NACT remain unclear. This study aimed to investigate the surgical complications and oncological outcomes of immediate perforator flap reconstruction after SSM following NACT. METHODS: A total of 201 consecutive patients with indications for immediate perforator flap reconstruction after SSM were included between 2004 and 2012. Surgical and oncological outcomes were compared between patients with and without NACT. RESULTS: There were 38 patients in the NACT group and 163 in the non-NACT control group. The median age of the NACT group was 39.5 years, which was significantly younger than the control group (43.0 years; P < 0.05). Patients in the NACT group also had more advanced and aggressive disease (P < 0.05). There was no significant difference in the frequency of surgical complications between the groups, no difference in the type of complications, and no significant difference in the frequencies of major and minor complications. No patients in the NACT group had delayed adjuvant therapy. Eight patients (4%) developed recurrences, with a median follow-up time of 3.0 years. Local recurrences occurred in three control patients but no patients in the NACT group. CONCLUSION: NACT does not affect short-term or interim outcomes after immediate perforator flap reconstruction and may thus represent a safe and practical treatment option for the multidisciplinary treatment of breast cancer.

Adolescent growth: genes, hormones and the peer group. Proceedings of the 20th Aschauer Soiree, held at Glücksburg castle, Germany, 15th to 17th November 2013.

The association between poverty, malnutrition, illness and poor socioeconomic conditions on the one side, and poor growth and short adult stature on the other side, is well recognized. Yet, the simple assumption by implication that poor growth and short stature result from poor living conditions, should be questioned. Recent evidence on the impact of the social network on adolescent growth and adult height further challenges the traditional concept of growth being a mirror of health. Twenty-nine scientists met at Glücksburg castle, Northern Germany, November 15th - 17th 2013, to discuss genetic, endocrine, mathematical and psychological aspects and related issues, of child and adolescent growth and final height.

Electronic excited states of a strongly correlated organic radical 1,3,5-trithia-2,4,6-triazapentalenyl (TTTA) adsorbed on a Si(001) surface.

Electronic excited states of a strongly correlated organic radical, 1,3,5-trithia-2,4,6-triazapentalenyl (TTTA), adsorbed on a Si(001) surface were investigated by means of two-photon photoemission spectroscopy (2PPE) to elucidate the functional organic thin-film formation on a typical semiconductor substrate. The spectra were interpreted with the aid of density functional theoretical calculations. The unpaired electron of TTTA forms a covalent bond with the dangling bond of the Si-dimer initially, and there are resonant states of TTTA to Si near the surface. The molecules adsorbed at room temperature form dimers having diamagnetic properties at thicknesses of a few monolayers, while the paramagnetic phase appears at multilayer thickness. From the change in the work function, the orientation of the adsorbed TTTA molecules was determined to change depending on the thickness of the adsorbed layer.

Diversity in auxology: between theory and practice. Proceedings of the 18th Aschauer Soiree, 13th November 2010.

Auxology has developed from mere describing child and adolescent growth into a vivid and interdisciplinary research area encompassing human biologists, physicians, social scientists, economists and biostatisticians. The meeting illustrated the diversity in auxology, with the various social, medical, biological and biostatistical aspects in studies on child growth and development.

Steady state characteristics of acclimated hydrogenotrophic methanogens on inorganic substrate in continuous chemostat reactors.

A Monod model has been used to describe the steady state characteristics of the acclimated mesophilic hydrogenotrophic methanogens in experimental chemostat reactors. The bacteria were fed with mineral salts and specific trace metals and a H(2)/CO(2) supply was used as a single limited substrate. Under steady state conditions, the growth yield (Y(CH4)) reached 11.66 g cells per mmol of H(2)/CO(2) consumed. The daily cells generation average was 5.67 x 10(11), 5.25 x 10(11), 4.2 x 10(11) and 2.1 x 10(11) cells/l-culture for the dilutions 0.071/d, 0.083/d, 0.1/d and 0.125/d, respectively. The maximum specific growth rate (mu(max)) and the Monod half-saturation coefficient (K(S)) were 0.15/d and 0.82 g/L, respectively. Using these results, the reactor performance was simulated. During the steady state, the simulation predicts the dependence of the H(2)/CO(2) concentration (S) and the cell concentration (X) on the dilution rate. The model fitted the experimental data well and was able to yield a maximum methanogenic activity of 0.24 L CH(4)/g VSS.d. The dilution rate was estimated to be 0.1/d. At the dilution rate of 0.14/d, the exponential cells washout was achieved.

Studies on the constituents of bark of Parameria laevigata Moldenke.

One new trimeric proanthocyanidin, epicatechin-(2beta-->O-->7, 4beta-->6)-epicatechin-(2beta-->O--->7, 4beta-->8)-epicatechin (5) and two new tetrameric proanthocyanidins, epicatechin-(2beta-->O-->7, 4beta-->8)-[epicatechin-(4beta-->6)]-epicatechin-(4beta-->8)-epicatechin, named as parameritannin A-1 (6), and epicatechin-(2beta-->O-->5, 4beta-->6)-[epicatechin-(2beta-->O-->7, 4beta-->8)]-epicatechin-(4beta-->8)-epicatechin, named as parameritannin A-2 (7), have been isolated from the bark of Parameria laevigata Moldenke (Apocynaceae) along with the two known dimers, proanthocyanidin A-2 (1) and proanthocyanidin A-6 (2), and two trimers, cinnamtannin B-1 (3) and aesculitannin B (4). These structures were elucidated by spectral and chemical evidence.

Flavonoid glucuronides from Helicteres isora.

Five flavonoid glucuronides were obtained from the fruit of Helicteres isora, three of which were previously unknown compounds: isoscutellarein 4'-methyl ether 8-O-beta-D-glucuronide 6"-n-butyl ester. isoscutellarein 4'-methyl ether 8-O-beta-D-glucuronide 2", 4"-disulfate and isoscutellarein 8-O-beta-D-glucuronide 2",4"-disulfate. The structures were determined on the basis of spectroscopy and hydrolysis experiments.

Gram stain index of a natural bacterial community at a nutrient gradient in the freshwater environment.

Species succession of a natural bacterial community was indicated by the Gram stain index (GSI) using an experimental nutrient gradient in an oligotrophic pond created with an in situ gradostat. Various trophic conditions, ranging from eutrophic to mesotrophic, were formed experimentally with continuous inflow of sterile peptone solution in the gradostat, while the water mass outside the gradostat was oligotrophic. The GSI spectra of the natural bacterial populations show different profiles in accordance with the trophic level of the ambient water and the time progression of adaptation to different levels of eutrophication. Therefore, GSI can be used as a potential indicator of organic pollution in aquatic environments.

Change of body composition over an eight year period among Japanese university students.

This study examined the change of body composition in Japanese university students. Subjects were university students divided into two groups by sex for two different time periods: 67 males and 46 females for 1986-1987 and 47 males and 64 females for 1994-1995. Body height, weight, and underwater weight were measured to estimate the percentage of body fat. The fat mass index (FMI) was applied after adjusting fat mass and the fat-free mass index (FFMI) applied after adjusting fat-free mass for body physique by dividing (body height)2. The mean body mass index (BMI) increased from 1986-1987 to 1994-1995 in males and decreased in females, although there were no statistical differences between two time periods in both sexes. The FMI indicates that in 1994-1995 males had significantly more fat adjusted for body height than in 1987. Females in 1994-1995 had significantly less FFMI than those in 1986 despite FMI similar to that of 1986. Our results thus warn against a trend toward excessive thinness in collegiate females and insufficiency of evaluating body composition using the BMI alone.

Light and scanning electron microscopic study of the digestive tract in the catfish Pseudoplatystoma Corruscans Agassiz, 1829 (Pisces, Pimelodidae)

O trato digestivo do surubin Pseudoplatystoma corruscans foi estudado morfologicamente utilizando a microscopia de luz e eletrônica de varredura (MEV), além de técnicas histoquímicas. O epitélio estratificado do palato e faringe está constituído de uma camada basal com células indiferenciadas de núcleos elípticos de posiçäo central; uma camada média constituída de células intermediárias indiferenciadas, células gigantes acidófilas e células mucosas; e uma camada superficial de células achatadas. O esôfago apresenta estrutura semelhante, com células gigantes acidóficas menos numerosas e células poilimorfonucleares entre as células da camada basal, ao MEV, o palato evidenciou vários sulcos, sendo que a porçäo superficial está constituída de células hexagonais ou poligonais, em cuja área apical está presente as microcristas. A parte superficial da faringe apresenta células com microcristas dispostas concentricamente. O esôfago mostrou pregas longitudinais complexas, um epitélio estratificado cujas células apresentam microcristas irregulares. Os carbohidratos presentes nas células do tracto digestivo foram identificados como sendo mucosubstâncias neutras e ácidas

[Intracranial dural malignant lymphoma: case report].

A case of intracranial dural malignant lymphoma was presented. A 35-year-old woman was admitted with generalized seizure. The neurological findings and laboratory data were normal. Computed tomography (CT) showed a nodular lesion in the left frontal convexity with marked enhancement by contrast medium. Angiography showed a slight tumor stain and the feeding artery from the ethmoid artery. On surgery, a soft pinkish tumor was found to be located in the dura and subdural space. It was resected subtotally. The histological diagnosis was malignant lymphoma of B cell origin. Postoperative Ga scintigraphy and abdominal CT disclosed no abnormalities in other organs, but bone marrow examination revealed lymphoma cells, which suggested that the patient might have systemic lymphoma. The patient and her family refused additional treatment. The patient is alive and well now over six years after the craniotomy. Primary central nervous system (CNS) lymphomas usually arise in the cerebral parenchyma, while secondary CNS lymphomas commonly involve leptomeninges and perivascular spaces. Mass lesions arising in the dura are very rare.

Effects of upper limb exercise on thermoregulatory responses in patients with spinal cord injury.

We evaluated changes in body temperature, heart rate, and oxygen uptake during arm cranking exercise (20 watts, 30 min) in an artificial climate room at a temperature of about 25 degrees C or 35 degrees C (relative humidity, about 50%) in 5 patients with paraplegics due to spinal cord injury (SCI). The tympanic temperature (Tty) was significantly higher from rest to recovery at 35 degrees C than at 25 degrees C. The mean Tty after 10 minutes of rest was 36.68 degrees C +/- 0.396 (mean +/- SD) at a room temperature of 25 degrees C and 37.25 degrees C +/- 0.253 at 35 degrees C, showing a difference of about 0.5 degrees C. This difference was maintained during exercise and recovery. The Tty at the end of exercise was higher than that at the start of exercise by 0.66 degrees C +/- 0.218 (mean +/- SD) at 25 degrees C and by 0.59 degrees C +/- 0.210 at 35 degrees C. The skin temperature (Tsk) in each measurement area (the head, arm, chest, thigh, shin, and calf) was significantly higher at 35 degrees C. Oxygen uptake did not differ between 25 degrees C and 35 degrees C. The heart rate was significantly higher at 35 degrees C than at 25 degrees C during rest and at the start of exercise but did not differ during exercise and recovery. Thus, mild-moderate exercise in this study did not cause marked changes such as increases in body temperature and heart rate that affect biological function in SCI.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of anaesthetic agents on the phagocytic function of human polymorphonuclear leukocytes through analysis with a phagocytic plaque method.

We examined the effects of the intravenous anaesthetic agents, thiamylal and ketamine, on the phagocytic function of polymorphonuclear leukocytes (PMN) in heparinized peripheral blood from healthy individuals using the phagocytic plaque method. Subclinical doses of thiamylal caused enhancement of the phagocytic activity of PMN and super-clinical doses of thiamylal inhibited phagocytic activity of PMN. Ketamine did not adversely affect phagocytic function at relevant therapeutic concentrations. The results presented in this manuscript indicate the phagocytic plaque method can provide a quantitative assessment of the phagocytic function of leukocytes. This method may prove useful in determining whether anaesthetic agents and other drugs adversely affect leukocyte function and hence help prevent the increased susceptibility to infection which can occur in anaesthetized patients. Conversely, the phagocytic plaque method may prove useful in the search for immune-enhancing drugs.

[A case of essential thrombocythemia with clonal evolution in the terminal phase].

This 50-year-old male was admitted to the hospital on April 1983 with complaints of severe chest pain attacks 2 weeks previously. Laboratory data: On admission the blood findings were Hb 14.3 Gm/dl of blood, RBC 4.70 million/mm3, WBC 11,600/mm3 and a platelet count of 1.1 million/mm3. ECG showed elevation of ST-T in V1 to V4. Serum LDH and CPK levels were high. He was diagnosed as acute myocardial infarction with thrombocythemia. Three days after admission he abruptly fell into a semicomatose state and left hemiplesia. Head computed tomography showed a large, low-density lesion in the right mid-cerebral artery area, and we also diagnosed cerebral infarction. He was given nimustine (ACNU) 100 mg/week three times as remission induction therapy. For maintenance chemotherapy, at first we administered mitobronitol (DBM) 150 mg/day then changed to intermittent administration of ACNU 100 mg. On September 1991, the patient was admitted to the hospital with progressive anemia and uncontrollable thrombocythemia. Bone marrow chromosome analysis revealed aneuploidy. The patient received interferon alpha 3 million unit/day. The thrombocythemia could be controlled but his general condition deteriorated. On April 1992, he died of interstitial pneumonia.