Safety of mFOLFOX6/XELOX as adjuvant chemotherapy after curative resection of stage III colon cancer: phase II clinical study (The FACOS study).

PURPOSE: Adjuvant chemotherapy with oxaliplatin combined with a fluoropyrimidine derivative is widely accepted as standard therapy for patients with stage III colon cancer, since few clinical data are available for Japanese patients. The FACOS trial investigated the tolerability of modified FOLFOX6 (mFOLFOX6) and XELOX regimens in Japanese colon cancer patients. METHODS: Twelve cycles of mFOLFOX6 or 8 cycles of XELOX were given to patients with eligibility: stage III curatively resected colon cancer, performance status of 0-1, age from 20 to 75 years, and adequate organ function. The primary endpoint was 3-year disease-free survival. Secondary endpoints were the incidence of adverse events (AEs) and the completion rate of study therapy. RESULTS: From April 2010 to April 2014, a total of 132 patients were enrolled. Safety was analyzed in 130 patients, with finalized data from 73 patients receiving mFOLFOX6 and 57 patients receiving XELOX. A total of 130 patients (100%) experienced AEs (any grade), and 52 patients (40.0%) experienced AEs of grade ≥ 3. No significant difference in the frequency of grade ≥ 3 AEs was observed between mFOLFOX6 and XELOX groups. Continuation of the planned cycle rate of protocol treatment was 69.9% in the mFOLFOX6 group and 68.4% in the XELOX group. Treatment was discontinued because of AEs in 14 patients (19.2%) in the mFOLFOX6 group and 8 (14.0%) in the XELOX group. Mean relative dose intensity for oxaliplatin was 78.0% in the mFOLFOX6 group and 82.8% in the XELOX group. CONCLUSION: As adjuvant chemotherapy for stage III colon cancer, mFOLFOX6/XELOX regimens are acceptable.

Application of Vacuum-Assisted Closure Therapy and Hyperbaric Oxygen Therapy for an Exposed Titanium Plate After Mandible Reconstruction.

The authors report a case of an 84-year-old woman with an exposed mandibular plate after reconstruction, which finally healed with combination therapy using vacuum-assisted closure therapy and hyperbaric oxygen therapy. The woman was diagnosed with mucosal carcinoma of the right oral cavity. During reconstruction after segmental excision of the mandible, a titanium plate was selected based on several risk factors. After the operation, the plate became exposed at the center of the chin. A second surgery was deemed inappropriate because of her age, malnutrition, and recurrent aspiration pneumonia. Instead, combination therapy consisting of vacuum-assisted closure therapy and hyperbaric oxygen therapy was initiated, leading to epithelizaion of the wound. Adapt Barrier Rings was effectively used to generate a stable negative pressure at the complicated craniofacial wound. A surgical or conservative approach is chosen as salvage treatment of an exposed plate. In this patient, only conservative treatment involving combination therapy resulted in complete healing of the wound with plate exposure. This patient highlights 2 important clinical issues: combination therapy was effective for an exposed mandibular plate, and a dressing technique using Adapt Barrier Rings enabled stable negative pressure in the craniofacial wound.

A phase II study of bevacizumab with modified OPTIMOX1 as first-line therapy for metastatic colorectal cancer: the TCOG-GI 0802 study.

BACKGROUND: Although bevacizumab plus FOLFOX is a standard treatment for metastatic colorectal cancer, oxaliplatin must be withdrawn in many patients because of cumulative neurotoxicity. We postulated that a reduced dose of oxaliplatin and modified treatment schedule would prolong the time to treatment failure and evaluated bevacizumab combined with a modified OPTIMOX1 regimen (mOPTIMOX1, oxaliplatin dose: 85 mg/m(2)). METHODS: Eligible patients had a histologically confirmed diagnosis of metastatic colorectal cancer and a performance status of 0-1. Patients were excluded if they had grade 1 or higher peripheral sensory neuropathy or had previously received chemotherapy for metastatic colorectal cancer. Patients received bevacizumab plus mFOLFOX6 every 2 weeks for 6 cycles, followed by 12 cycles of a simplified biweekly regimen of leucovorin and fluorouracil (sLV5FU2) plus bevacizumab. Oxaliplatin was then reintroduced, and bevacizumab plus mFOLFOX6 was continued until progressive disease. RESULTS: The median duration of disease control was 11.7 months (95 % confidence interval [CI], 9.7-13.5 months). The median overall survival was 23.1 months (95 % CI, 18.8-27.9 months). The overall response rate according to both the RECIST and WHO criteria was 51.3 %. The most common grade 3 or 4 toxicities were neutropaenia (32.5 %), hypertension (17.5 %), leukocytopaenia, sensory neuropathy, and diarrhoea (10.0 %). There were no treatment-related deaths. CONCLUSIONS: Bevacizumab plus mFOLFOX6 was well tolerated, and patients could continue chemotherapy for longer than with conventional FOLFOX regimens. This regimen might be an effective treatment option for patients with metastatic colorectal cancer.

Venoarterial extracorporeal membrane oxygenation for cardiopulmonary resuscitation: A retrospective study comparing the outcomes of fluoroscopy.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) using venoarterial extracorporeal membrane oxygenation is performed for out-of-hospital cardiac arrest; however, it is associated with a risk of several complications. Objective: To investigate whether the fluoroscopy equipment was removed from the emergency department (ED) and whether it would be beneficial to transport the patient to the fluoroscopy room to reduce vascular complications without affecting the induction time. Methods: This single-center, retrospective, before-and-after analysis was conducted at a tertiary emergency medical center and included 59 patients who underwent ECPR for out-of-hospital cardiac arrest between May 2017 and March 2022. The patients were divided into two groups: those who underwent cannulation in the ED without fluoroscopy (ED-ECPR group) and those who were transferred directly from the ED to the cardiac angiography room (ECPR call group). Results: The rate of vascular complications associated with ECPR was significantly lower in the ECPR group than in the ED-ECPR group (40.6 % [14/32] vs. 10 % [2/20], respectively; p = 0.014). The duration from ED arrival to venoarterial extracorporeal membrane oxygenation initiation was similar in the two groups (median: 23.0 min in the ED-ECPR group vs. 25.5 min in the ECPR call group, p = 0.71). Results adjusted for confounding factors showed that performing ECPR under fluoroscopy was a consistent and independent element of vascular complication rates (adjusted odds ratio: 9.92, 95 % confidence interval: 2.04 to 81.2, p = 0.011). Conclusions: Fluoroscopy-guided ECPR can significantly reduce the incidence of vascular complications even if the ED and fluoroscopy room are far apart. However, no significant difference was observed in the time required to establish ECPR in the cardiac catheterization laboratories.

Cricothyrotomy for an Unexpected Cannot Intubate, Cannot Ventilate Situation for a Patient with Chronic Graft-Versus-Host Disease After Induction of General Anesthesia: A Case Report.

BACKGROUND Chronic graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantations. Due to fibrotic changes, patients with GVHD are at risk for difficult airway management. We encountered a case of chronic GVHD that went into a "cannot intubate, cannot ventilate" (CICV) condition after induction of general anesthesia and was managed using cricothyrotomy. CASE REPORT A 45-year-old man with uncontrolled chronic GVHD developed pneumothorax of the right lung. Thoracoscopic dissection of the adhesions, closure of the pneumostomy, and drainage under general anesthesia were planned. In the preoperative airway assessment, we concluded that using a video laryngoscope or endotracheal fiber would be sufficient to intubate the patient after sedation and that airway management after the loss of consciousness would not be difficult. Therefore, general anesthesia was induced by rapid induction; however, the patient developed difficult mask ventilation. Intubation was attempted via a video laryngoscope or bronchofiber but failed. Ventilating using a supraglottic instrument was difficult. The patient was evaluated to have a CICV condition. Thereafter, because of a rapid decrease in oxygen saturation (SpO2) and bradycardia, a cricothyrotomy was performed. Subsequently, ventilation became adequate, SpO2 increased immediately and drastically, and respiration and circulatory dynamics recovered. CONCLUSIONS We believe that anesthesiologists should practice, prepare, and simulate airway emergencies that can be experienced during surgery. In this case, we recognized that skin sclerosis in the neck and chest could lead to CICV. It may be suitable for airway management of scleroderma-like patients to select conscious intubation with a bronchoscope as a first choice.

[Potential use of parathyroid hormone (PTH) in the treatments for oral diseases].

Bone formation is the key for successful dental treatments including periodontal tissue regeneration osseointegration of implant placement in which new alveolar bone formation is mandatory. Parathyroid hormone (PTH) is a peptide hormone containing 84 amino acids. Accumulated results show that intermittent PTH administration increases bone mass. Accordingly, recombinant N-terminal fragment of human PTH (1-34) , Teriparatide, is used for the treatments of osteoporosis worldwide. It is, therefore, expected that PTH has the potential to be a new therapeutic intervention for oral diseases that require increased bone remodeling and new bone formation.

Primary Teeth-Derived Demineralized Dentin Matrix Autograft for Unilateral Maxillary Alveolar Cleft during Mixed Dentition.

This clinical report describes the immediate autograft of primary (milk) teeth-derived demineralized dentin matrix (DDM) granules for a 6-year-old boy with unilateral alveolar cleft. First, four primary teeth were extracted, crushed in an electric mill for 1 min, and the crushed granules were demineralized in 2% HNO3 solution for 20 min. Simultaneously, the nasal mucoperiosteum was pushed upwards above the apices of the permanent central incisor adjacent to the cleft. The nasal and palatal openings were closed by suturing the mucoperiosteum on both sides of the cleft with absorbable threads. The wet DDM granules were grafted into the managed cleft triangle space, and a labial flap was repositioned. The radiographic images at 6 months showed the continuous hard tissues in the cleft area and DDM granules onto lateral incisor (22) and impacted canine (23). The 3D-CT views at 2 years showed impacted tooth (22) blocked by primary canine and the replacement of DDM granules by bone near teeth (22,23). At 4 years, tooth crown (22) was situated just under the mucous membrane, and teeth (22,23) erupted spontaneously until 6 years without a maxillary expansion and a tow guidance of canine. The DDM granules contributed to bone formation without the inhibition of spontaneous tooth eruption. We concluded that autogenous primary teeth DDM graft should become a minimally invasive procedure without bone harvesting and morbidities for unilateral alveolar cleft.

Sensitivity of Botrytis cinerea to fenpyrazamine in Japan and its disease control efficacy against the low-sensitive isolate.

The baseline sensitivity of Botrytis cinerea to fenpyrazamine was evaluated using 323 isolates collected in Japan prior to its launch. In this study, the isolates were classified as "sensitive" and "low-sensitive" according to their mycelial growth on 10 mg/L fenpyrazamine. However, their EC50 values for the germ-tube elongations from conidia were not significantly different between these two classes. In both a pot test and a field trial, diseases caused by the sensitive and low-sensitive isolates were effectively controlled by fenpyrazamine.

Successful Anesthetic Management Using Dexmedetomidine Sequentially with Propofol in the Asleep-Awake-Asleep Technique for Elderly Patients Undergoing Awake Craniotomy.

Anesthesiologists should supply proper sedation and high-quality awakening in awake craniotomy anesthesia. At our institution, we perform an asleep-awake-asleep technique for awake craniotomy anesthesia by using short-acting anesthetic drugs, such as propofol and remifentanil. However, elderly patients do not wake adequately in our normal protocol and hence are unable to complete the required neurological tasks. In this case series, we present the anesthetic management of three elderly patients with sequent use of propofol and dexmedetomidine as sedative agents for awake craniotomy. We hypothesized that this anesthetic protocol is advantageous in awake craniotomy management. For the awake phase, all patients were adequately awake and performed neurological tasks without adverse events and agitation. The use of dexmedetomidine sequentially with propofol in an asleep-awake-asleep technique for awake craniotomy in elderly patients might shorten the time to awakening and provide clear awakening.

Preference and Experience of Colonic Examination for Participants Presenting to Hospitals with a Positive Fecal Immunochemical Test Result.

PURPOSE: Patients who test positive on the fecal immunochemical test (FIT) for colorectal cancer (CRC) are referred for colonoscopy for further diagnostic evaluation. Colonoscopy is not a perfect method and may be a challenge for some FIT-positive patients. Computed tomographic colonography (CTC) is an alternative method that is less invasive and allows examination of the whole colon. The study objective was to evaluate the preference of FIT-positive patients for either colonoscopy or CTC for CRC examination. PATIENTS AND METHODS: Individuals older than 40 years with a positive FIT test at eight Japanese hospitals between December 2012 and July 2015 were invited to participate. Participants were given detailed information regarding colonoscopy and CTC before deciding on either examination. They completed questionnaires before the procedure regarding their preference and after the procedure regarding their experience. RESULTS: The pre- and post-questionnaires of 846 and 834 participants, respectively, were analyzed. Participants preferred colonoscopy over CTC (colonoscopy, 72%; CTC, 28%). The possibility of obtaining biopsy samples and removing colorectal polyps during the procedure was the main reason for colonoscopy selection. Patients selected CTC to reduce discomfort but reported that CTC bowel preparation was more burdensome than colonoscopy bowel preparation. The overall experience of the examination did not differ between the groups. CONCLUSION: Colonoscopy is the standard examination for FIT-positive patients. However, when given a choice, almost one-third of participants chose CTC because they thought it would be a more "comfortable" examination. Clinicians should therefore be aware of patients' potential preference for noninvasive colorectal examinations.

The importance of rectal cancer MRI protocols on interpretation accuracy.

BACKGROUND: Magnetic resonance imaging (MRI) is used for preoperative local staging in patients with rectal cancer. Our aim was to retrospectively study the effects of the imaging protocol on the staging accuracy. PATIENTS AND METHODS: MR-examinations of 37 patients with locally advanced disease were divided into two groups; compliant and noncompliant, based on the imaging protocol, without knowledge of the histopathological results. A compliant rectal cancer imaging protocol was defined as including T2-weighted imaging in the sagittal and axial planes with supplementary coronal in low rectal tumors, alongside a high-resolution plane perpendicular to the rectum at the level of the primary tumor. Protocols not complying with these criteria were defined as noncompliant. Histopathological results were used as gold standard. RESULTS: Compliant rectal imaging protocols showed significantly better correlation with histopathological results regarding assessment of anterior organ involvement (sensitivity and specificity rates in compliant group were 86% and 94%, respectively vs. 50% and 33% in the noncompliant group). Compliant imaging protocols also used statistically significantly smaller voxel sizes and fewer number of MR sequences than the noncompliant protocols CONCLUSION: Appropriate MR imaging protocols enable more accurate local staging of locally advanced rectal tumors with less number of sequences and without intravenous gadolinium contrast agents.

[A case of recurrent colon cancer patient who gained a long-term survival by repeated and aggressive surgical resection].

A case is a woman of 55-years-old. We performed right hemicolectomy with liver S7 partial excision (a postoperative diagnosis of the hepatic lesion, adenoma) for ascending colon carcinoma of type 2 with hepatic metastasis. Postoperative diagnosis was ss, n2, ly2, v2, Stage IIIb, based on the Japanese classification of colon cancer. Twelve months after the first operation, she was developed intestinal atresia by an abdominal wall recurrence, and we performed the operation of abdominal wall mass resection with a partial resection of small bowel. Afterwards she developed a recurrence three times in the abdominal wall or intra-abdominal lymph nodes during the next 1 year and six months, and we performed a local excision each time. The pathological findings in reoperations were all metastasis from ascending colon carcinoma of primary operation. After the final operation, we did not perform chemotherapy because the patient wished not to have it. There has been no recurrence for 6 years since the first operation, or 3 years since the last operation. Recently, the therapy for recurrent colon cancer has been shifted to more effective chemotherapy such as FOLFOX or FOLFIRI regimen, and a surgical resection is becoming rare. However, we experienced a case of recurrent colon cancer treated with four aggressive surgical resections that was beneficial for a long-term survival.

A Novel Eco-Friendly Wood Adhesive Composed by Sucrose and Ammonium Dihydrogen Phosphate.

Development of a bio-based wood adhesive is a significant goal for several wood-based material industries. In this study, a novel adhesive based upon sucrose and ammonium dihydrogen phosphate (ADP) was formulated in hopes of furthering this industrial goal through realization of a sustainable adhesive with mechanical properties and water resistance comparable to the synthetic resins used today. Finished particleboards exhibited excellent mechanical properties and water resistance at the revealed optimal adhesive conditions. In fact, the board properties fulfilled in principle the requirements of JIS A 5908 18 type standard, however this occured at production conditions for the actual state of development as reported here, which are still different to usual industrial conditions. Thermal analysis revealed addition of ADP resulted in decreases to the thermal thresholds associated with degradation and curing of sucrose. Spectral results of FT-IR elucidated that furanic ring chemistry was involved during adhesive curing. A possible polycondensation reaction pathway was proposed from this data in an attempt to explain why the adhesive exhibited such favorable bonding properties.

Visualization of solute diffusion into cell walls in solution-impregnated wood under varying relative humidity using time-of-flight secondary ion mass spectrometry.

The purpose of the present study is to clarify the diffusion of non-volatile substances into cell walls during the conditioning procedure under varying relative humidities (RH). In this paper, wood blocks were impregnated using an aqueous solution of melamine formaldehyde (MF), and they were subsequently conditioned under RHs of 11, 43, and 75%. The solute that diffused into the cell walls was visualized using time-of-flight secondary ion mass spectrometry (TOF-SIMS). The volumetric relative swelling of the samples during the conditioning procedure was calculated. The results showed increased cell wall swelling at higher RH, which may have been caused by higher MF diffusion into the cell walls and/or higher moisture content. Cryo-TOF-SIMS measurements showed that more cell cavities were unfilled with MF at higher RH, indicating that most of the MF diffused from the cell cavities into the cell walls. The relative intensity of MF in the cell walls of the cured samples was evaluated from dry-TOF-SIMS images, which showed a higher relative intensity of MF in the cell walls at higher RH. With the ability to visualize and semi-quantitatively evaluate the solute in cell walls, TOF-SIMS will serve as a powerful tool for future studies of solute diffusion mechanisms in solution-impregnated wood.

Development of the novel fungicide fenpyrazamine.

Fenpyrazamine is a novel fungicide with an aminopyrazolinone structure developed by Sumitomo Chemical Co., Ltd. Fenpyrazamine has good fungicidal properties, such as high antifungal activity, preventive activity, translaminar activity, inhibition activity in lesion development, and long lasting activity. The target enzyme of fenpyrazamine is 3-keto reductase in the ergosterol biosynthetic pathway. Fenpyrazamine shows high efficacy against gray mold, stem rot, and brown rot in field trials. Formulated products, PROLECTUS® and PIXIO®DF, have been registered since 2012. PROLECTUS® was first launched in Italy in 2012, and PIXIO®DF was launched in Japan in 2014.

[A clinical study of therapy for local recurrent rectal cancer].

To evaluate the therapy for local recurrent rectal cancer, we examined clinicopathological characteristics and prognoses of 54 local recurrent rectal cancer patients. The cumulative 5 year survival rate was 20.3%, 3-year survival rate was 74% for a curative surgery group, 21.8% for a non-curative surgery group and 0% for a non surgery group. There were significant differences in the rates of three year survival between the curative surgery group and non surgery group, but there were no differences between the non curative surgery group and non-surgery group. A survival analysis showed that prognoses of patients ew (-) or CEA under 10 ng/ml group were statistically better than the other group. Thirty four patients underwent operation. The mean operation time and the mean blood loss were 334.2 minutes and 1977 ml, respectively. Eighteen patients had some complications associated with the operation. Radiotherapy and chemotherapy did not contribute to improve survival rate, but contribute to improved symptoms. In conclusion, curative surgery is the only therapy for local recurrent rectal cancer to improve survival rates, but there are many complications associated with non curative surgery. We therefore must evaluate the indication of operation carefully.

Age-dependent decrease in serum transforming growth factor (TGF)-beta 1 in healthy Japanese individuals; population study of serum TGF-beta 1 level in Japanese.

Transforming growth factor-beta1 (TGF-beta1), a multi-functional cytokine, is involved in regulating a variety of cellular activities and the serum/plasma TGF-beta1 level is altered with various diseases. However, most published reports have described adult patients, and so we investigated the clinical significance of serum TGF-beta1 level in pediatric patients. The diagnostic application of the measurement of serum TGF-beta1 level depends critically on the control value, however, there is no information on the control value of serum TGF-beta1 for children. In the present study, we determined the serum TGF-beta1 level of healthy Japanese children as a control value with enzyme-linked immunosorbent assay (ELISA). The serum TGF-beta1 level of children (0-14 years old) was significantly higher than that of adults (over 15 years old) (p < 0.01). Thus, it is recommended that when the serum TGF-beta1 levels of patients are evaluated, they should be compared with those of age-matched controls.

Complex vibration ultrasonic welding systems with large area welding tips.

Vibration and welding characteristics of complex vibration ultrasonic welding systems of 27 and 40 kHz were studied. Complex vibration systems, which have elliptical to circular or rectangular to square locus, are effective for ultrasonic welding of various specimens including the same and different metal specimens, and for direct welding of semiconductor tips and packaging of various electronic devices without solder. The complex vibration systems consist of a one-dimensional longitudinal-torsional vibration converter with slitted part, a stepped horn and a longitudinal vibration transducer as a driving source. The complex vibration welding tips of 27 and 40 kHz have enough area of 6-8 mm square for various welding specimens. Aluminum plate specimens of 0.3-1.0 mm thickness were successfully joined with weld strengths almost equal to aluminum specimen strength, and independent to the specimen direction. Required vibration amplitude of 40 kHz is smaller than that of 27 kHz.

[High concentration of E-cadherin in portal drainage vein of colorectal cancer patients may predict metachronous liver metastasis].

AIMS: Liver metastasis is the most common recurrence after curative surgery for colorectal cancer. Adjuvant chemotherapy such as hepatic arterial infusion or intensive systemic infusion may protect against metastatic tumor formation in the liver, but conversely have some adverse effects on patients. Therefore, the patients with a high risk of liver metastasis after curative resection should be selected for the chemotherapy. Portal blood samples of tumor drainage vein were obtained during operation from 148 colorectal cancer patients (Dukes' A: 41, B: 41, C: 33, D: 33) in our institutes from August 1998 to June 2001. Serum E-cadherin concentration (ng/ml) was estimated using an ELISA kit according to the manufacturer's instructions (Takara Shuzo Co.). After at least 6 months follow-up, each patient's status regarding recurrence was re-examined, as were the sites of any recurrences. Serum E-cadherin concentration in each Dukes' stage at the primary operation was as follows: A: 1,664.0, B: 1,974.6, C: 2,270.8, D: 3,123.1. In these follow-up periods, 21 patients developed metastatic tumor (liver: 13, extrahepatic: 8) and 95 did not. The average E-cadherin concentration in each group was as follows: liver: 3,585.6, extrahepatic: 2,261.8, no metastasis: 1,848.4 (p < 0.01 as shown in Figure 4). If the cut-off point is set at 3,000 ng/ml, liver metastasis can be predicted with sensitivity of 62.1%, specificity of 90.3%, and positive predictive value of 64.3%. High levels (> 3,000 ng/ml) of serum E-cadherin in portal blood may predict metachronous liver metastasis after curative surgery.

[A clinical scoring system may identify good candidates for hepatic arterial infusion chemotherapy after hepatic resection for colorectal cancer].

The significance of hepatic arterial infusion chemotherapy (HAI) for the prognosis of metastatic colorectal cancer is controversial. We applied a clinical scoring system to find good candidates for HAI after hepatic resection. Ninety-four consecutive cases of hepatic metastases resected at a single institute were analyzed retrospectively. The cases were divided into 4 subgroups: those with a low risk score (0-2 points) with and without HAI and those with a high risk score (3-5 points) with and without HAI. The number of cases and the cumulative 5 year survival rate of each case were as follows: low risk score with HAI (n = 17) 64.1%, low risk score without HAI (n = 25) 27.4%, high risk score with HAI (n = 28) 16.9%, and high risk score without HAI (n = 24) 14.7%, respectively. These results suggest that hepatic resection with HAI seemed to contribute to the outcome for selected cases. The clinical scoring system may identify good candidates for HAI as well as predict recurrence after hepatic resection for metastatic colorectal cancer.