Efficacy of Switching From Oral to Intravenous Administration for Dexamethasone-Induced Hiccups in CyberKnife Radiotherapy: A Case Report.

Steroids are commonly used for medical purposes. While hiccups are a recognized side effect of steroid therapy, we have not found any reports of hiccups interfering with the progress of radiotherapy. A case of dexamethasone (DEX)-induced hiccups (DIH) during CyberKnife radiotherapy (CKR) is presented. A 42-year-old man with neurofibromatosis type I had a history of malignant peripheral schwannomas originating in the right femur. We started to perform CKR with oral DEX at an increased dose of 4 mg/day for the recurrence of cranial metastasis and primary lesions. Severe hiccups developed four days after the increased DEX dose. DEX was stopped six days after CKR initiation, and the hiccups subsided over the next four days. However, the CKR procedure was not possible due to the patient's worsening swelling of the head and thigh lesions, which prevented the proper fit of the mesh face mask and body fixation device. Intravenous (IV) DEX 6.6 mg/day was initiated, which allowed the resumption of CKR due to reduced swelling of the lesions. The CKR was completed due to the absence of hiccups following the transition to IV DEX. DIH could occur even at a dosage of 4 mg/day when taken orally. Our case suggests the significance of recognizing DIH during radiotherapy. Switching the administration from oral to IV DEX may be an option for dealing with DIH.

[365 Days in Newly Opened Cancer Treatment Center in Core Hospital of Mountainous Area].

The declining birthrate and aging population is one of the social issues in mountainous area in Japan. One regional core hospital at Aizu area in Fukushima prefecture opened cancer treatment center in these area in July, 2022. A high-performance radiation therapy system was newly installed and operated with the staff of Fukushima Medical University, and several supportive therapy for cancer chemotherapy including appearance care became possible in the center. The patients living in Aizu area can receive advanced treatments including radiation therapy without moving to long-distant bigger cities now. We report multiple preparations and several trials that we have made during one year since the opening of the center.

[An Abscopal Effect after Palliative Radiotherapy in a Patient with a Locally and Lymph Node Recurrent Gastric Cancer].

Radiotherapy is known to have a high local effect for cancer treatment. However, several reports that radiotherapy could stimulate the anti-tumor effect by releasing endogenous signals and cytokines, increasing the presentation of tumor associated antigens on dendritic cells, and proliferating tumor antigen-specific cytotoxic T lymphocytes have been shown. A tumor regression in both non-irradiated and irradiated fields have observed, which is called"abscopal effect". We report a case of the abscopal effect in adenocarcinoma of the stomach with locally and lymph node recurrence after surgery. A 59-year-old Japanese male was diagnosed with residual stomach cancer and underwent total gastrectomy and distal pancreatectomy. Three months after the surgery, a local recurrence and the involvement of para-aortic lymph node were diagnosed using computed tomography. The chemotherapy treatment(S-1, cisplatin, trastuzumab)was prescribed. However, the disease has progressed. Paclitaxel and ramucirumab were given for second-line, nivolumab for third-line and irinotecan for fourth-line. During that, tumor at local recurrent site invaded to the portal vein. The patients received 50 Gy in 25 fractions of radiotherapy. A remarkable reduction of the mass was shown. In addition to this, we observed that spontaneous shrinking of the para-aortic lymph node metastasis, which was located out of the radiation field. We observed a rare radiation-induced abscopal effect. Radiotherapy might represent a potential candidate for a combination with immunotherapy. A combination of immunotherapy as well as chemotherapy with radiotherapy represents a promising therapeutic strategy.

Myeloid-derived suppressor cells: Cancer, autoimmune diseases, and more.

Although cancer immunotherapy using immune checkpoint inhibitors (ICIs) has been recognized as one of the major treatment modalities for malignant diseases, the clinical outcome is not uniform in all cancer patients. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells that possess various strong immunosuppressive activities involving multiple immunocompetent cells that are significantly accumulated in patients who did not respond well to cancer immunotherapies. We reviewed the perspective of MDSCs with emerging evidence in this review. Many studies on MDSCs were performed in malignant diseases. Substantial studies on the participation of MDSCs on non-malignant diseases such as chronic infection and autoimmune diseases, and physiological roles in obesity, aging, pregnancy and neonates have yet to be reported. With the growing understanding of the roles of MDSCs, variable therapeutic strategies and agents targeting MDSCs are being investigated, some of which have been used in clinical trials. More studies are required in order to develop more effective strategies against MDSCs.

Treating Low-Grade Myxofibrosarcoma With Stereotactic Body Radiation Therapy Using CyberKnife®.

Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas. Low-grade MFS has a high local recurrence rate, similar to that of high-grade MFS. Hence, appropriate adjuvant therapy is required to control low-grade MFS. In this report, we present a case in which recurrent low-grade MFS was successfully treated with stereotactic body radiation therapy (SBRT) using CyberKnife® (CK) (Accuray Incorporated, Sunnyvale, CA). A 76-year-old man underwent SBRT using CK for recurrent low-grade MFS in the right posterior chest wall after undergoing resection and skin grafting four and three times, respectively. We planned CK treatment separately for each in two parts. For the lesion on the scapula side, the target volume was 109 cm3 and the total prescribed dose was 34.6 Gy, while the lesion on the spinal side had a target volume of 72 cm3 and a total prescribed dose of 36 Gy, both in five fractions. Each SBRT was performed on alternate days in a span of 14 days. The tumors gradually reduced in size with tolerable levels of toxicity. SBRT using CK could be a safe and effective adjuvant therapy for low-grade MFS.

Formation of Proton Motive Force Under Low-Aeration Alkaline Conditions in Alkaliphilic Bacteria.

In Mitchell's chemiosmotic theory, a proton (H+) motive force across the membrane (Δp), generated by the respiratory chain, drives F1Fo-ATPase for ATP production in various organisms. The bulk-base chemiosmotic theory cannot account for ATP production in alkaliphilic bacteria. However, alkaliphiles thrive in environments with a H+ concentrations that are one-thousandth (ca. pH 10) the concentration required by neutralophiles. This situation is similar to the production of electricity by hydroelectric turbines under conditions of very limited water. Alkaliphiles manage their metabolism via various strategies involving the cell wall structure, solute transport systems and molecular mechanisms on the outer surface membrane. Our experimental results indicate that efficient ATP production in alkaliphilic Bacillus spp. is attributable to a high membrane electrical potential (ΔΨ) generated for an attractive force for H+ on the outer surface membrane. In addition, the enhanced F1Fo-ATPase driving force per H+ is derived from the high ΔΨ. However, it is difficult to explain the reasons for high ΔΨ formation based on the respiratory rate. The Donnan effect (which is observed when charged particles that are unable to pass through a semipermeable membrane create an uneven electrical charge) likely contributes to the formation of the high ΔΨ because the intracellular negative ion capacities of alkaliphiles are much higher than those of neutralophiles. There are several variations in the adaptation to alkaline environments by bacteria. However, it could be difficult to utilize high ΔΨ in the low aeration condition due to the low activity of respiration. To explain the efficient ATP production occurring in H+-less and air-limited environments in alkaliphilic bacteria, we propose a cytochrome c-associated "H+ capacitor mechanism" as an alkaline adaptation strategy. As an outer surface protein, cytochrome c-550 from Bacillus clarkii possesses an extra Asn-rich segment between the region anchored to the membrane and the main body of the cytochrome c. This structure may contribute to the formation of the proton-binding network to transfer H+ at the outer surface membrane in obligate alkaliphiles. The H+ capacitor mechanism is further enhanced under low-aeration conditions in both alkaliphilic Bacillus spp. and the Gram-negative alkaliphile Pseudomonas alcaliphila.

[A Case of Recurrent Colon Cancer with Long-Term Complete Response Treated with FOLFOX Therapy].

A 69-year-old female was admitted to our hospital due to general malaise and appetite loss. On physical examination, a tumor was palpable in the upper left abdomen. A complete blood count revealed anemia. An abdominal computed tomography suggested ileus secondary to transverse colon cancer. Transverse colectomy with D3 lymph node dissection was performed. The final diagnosis was moderately differentiated tubular adenocarcinoma, StageⅡ, T4aN0M0. The tumor marker level was re-elevated at 9 months after surgery; computed tomography and lower gastrointestinal endoscopy indicated local recurrence. The patient underwent a second laparotomy; however, it became an exploratory surgery due to aggressive local invasion. FOLFOX therapy was initiated from postoperative day 55 for tumor control. Tumor markers decreased markedly after 5 courses of therapy, and a complete response was achieved at 6 months after the second surgery. Subsequently, 29 courses of FOLFOX therapy were administered for 2 years and 1 month. At this time, the patient discontinued chemotherapy at her desire. No signs of recurrence have been observed at 6 years after withdrawal.

Contribution of intracellular negative ion capacity to Donnan effect across the membrane in alkaliphilic Bacillus spp.

To elucidate the energy production mechanism of alkaliphiles, the relationship between the H(+) extrusion rate by the respiratory chain and the corresponding ATP synthesis rate was determined in the facultative alkaliphile Bacillus cohnii YN-2000 and compared with those in the obligate alkaliphile Bacillus clarkii DSM 8720(T) and the neutralophile Bacillus subtilis IAM 1026. Under high aeration condition, much higher ATP synthesis rates and larger Δψ in the alkaliphilic Bacillus spp. grown at pH 10 than those in the neutralophilic B. subtilis grown at pH 7 were observed. This high ATP productivity could be attributed to the larger Δψ in alkaliphiles than in B. subtilis because the H(+) extrusion rate in alkaliphiles cannot account for the high ATP productivity. However, the large Δψ in the alkaliphiles could not be explained only by the H(+) translocation rate in the respiratory chain in alkaliphiles. There is a possibility that the Donnan effect across the membrane has the potential to contribute to the large Δψ. To estimate the contribution of the Donnan effect to the large Δψ in alkaliphilic Bacillus spp. grown at pH 10, intracellular negative ion capacity was examined. The intracellular negative ion capacities in alkaliphiles grown at pH 10 under high aeration condition corresponding to their intracellular pH (pH 8.1) were much higher than those in alkaliphiles grown under low aeration condition. A proportional relationship is revealed between the negative ion capacity and Δψ in alkaliphiles grown under different aeration conditions. This relationship strongly suggests that the intracellular negative ion capacity contributes to the formation of Δψ through the Donnan effect in alkaliphilic Bacillus spp. grown at pH 10.

[A Case of Gastrointestinal Perforation in a Patient with Colon Cancer and Stent Placement during Bevacizumab Treatment, Alleviated with Conservative Therapy].

The case involved a 52-year-old man. He was diagnosed with sigmoid colon cancer and multiple liver and lung metastases. After placement of a metallic stent for circumferential stricture, 5-fluorouracil/Leucovorin/oxaliplatin (FOLFOX4) plus bevacizumab therapy was introduced. After 17 courses, gastrointestinal perforation was noted at the site of stent placement, but this was alleviated with conservative therapy. Although gastrointestinal perforation is known to be a serious complication that occurs during chemotherapy combined with bevacizumab, further studies are needed to investigate the incidence of gastrointestinal perforation after stent placement more fully.

Comparison between surgical outcomes of colorectal cancer in younger and elderly patients.

AIM: To compare the outcome of surgical treatment of colorectal adenocarcinoma in elderly and younger patients. METHODS: The outcomes of 122 patients with colorectal adenocarcinoma who underwent surgical treatment between January 2004 and June 2009 were analyzed. The clinicopathological and blood biochemistry data of the younger group (< 75 years) and the elderly group (≥ 75 years) were compared. RESULTS: There were no significant differences between the two groups in operation time, intraoperative blood loss, hospital stay, time to resumption of oral intake, or morbidity. The elderly group had a significantly higher rate of hypertension and cardiovascular disease. The perioperative serum total protein and albumin levels were significantly lower in the elderly than in the younger group. The serum carcinoembryonic antigen level was lower in the elderly than in the younger group, and there was a significant decreasing trend after the operation in the elderly group. CONCLUSION: The short-term outcomes of surgical treatment in elderly patients with colorectal adenocarcinoma were acceptable. Surgical treatment in elderly patients was considered a selectively effective approach.

A novel membrane-anchored cytochrome c-550 of alkaliphilic Bacillus clarkii K24-1U: expression, molecular features and properties of redox potential.

A membrane-anchored cytochrome c-550, which is highly expressed in obligately alkaliphilic Bacillus clarkii K24-1U, was purified and characterized. The protein contained a conspicuous sequence of Gly(22)-Asn(34), in comparison with the other Bacillus small cytochromes c. Analytical data indicated that the original and lipase-treated intermediate forms of cytochrome c-550 bind to fatty acids of C(15), C(16) and C(17) chain lengths and C(15) chain length, respectively, and it was considered that these fatty acids are bound to glycerol-Cys(18). Since there was a possibility that the presence of a diacylglycerol anchor contributed to the formation of dimeric states of this protein (20 and 17 kDa in SDS-PAGE), a C18M (Cys(18) --> Met)-cytochrome c-550 was constructed. The molecular mass of the C18M-cytochrome c-550 was determined as 15 and 10 kDa in SDS-PAGE and 23 kDa in blue native PAGE. The C18M-cytochrome c-550 bound with or without Triton X-100 formed a tetramer as the original cytochrome c-550 bound with Triton X-100, as determined by gel filtration. The midpoint redox potential of cytochrome c-550 as determined by redox titration was +83 mV, while that determined by cyclic voltammetric measurement was +7 mV. The above results indicate that cytochrome c-550 is a novel cytochrome c.

Feasibility of video-assisted thoracoscopic surgery segmentectomy for selected peripheral lung carcinomas.

OBJECTIVE: Segmentectomy for non-small cell lung cancer (NSCLC) is believed to increase the rates of recurrence and postoperative air leak. We sought to present our clinical data and outcome of VATS (video-assisted thoracoscopic surgery) segmentectomies with systematic node dissection for selected NSCLC patients. METHODS: Inclusion criteria were clinical T1N0M0 peripheral NSCLC measuring 7 days), which required no surgical intervention, occurred in two patients. The chest tube drainage duration was 3 days. There were no in-hospital deaths. The numbers of resected subsegments and reserved subsegments in comparison with lobectomy were 5 (2-13) and 5 (3-13), respectively. The FEV1.0 after VS was higher than the predictive FEV1.0 after lobectomy, if the latter was performed as standard procedure. We experienced four cases of distant metastasis after segmentectomy, but there was no case of local recurrence. The 5-year survival and recurrence-free survival rates in pathological stage IA NSCLC were 89.9% and 93.3%, respectively. CONCLUSIONS: VATS segmentectomy with systematic node dissection is a reasonable treatment option for selected peripheral NSCLC.

Dural arteriovenous fistula in the anterior cranial fossa: four case reports.

Three of 4 cases of dural arteriovenous fistulas (DAVFs) in the anterior cranial fossa were detected incidentally by magnetic resonance (MR) imaging, and one case manifested as intracerebral hemorrhage. Cerebral angiography revealed fistulas located in the anterior cranial fossa. Three patients underwent surgery, and the fistulas were successfully obliterated. One patient with nonruptured DAVF requested conservative medical management. Incidental detection of asymptomatic or nonruptured DAVFs in the anterior cranial fossa has increased with the wider use of MR imaging. Increase in the size of a venous varix is the indicator for aggressive therapeutic intervention in a patient receiving conservative medical management for asymptomatic or nonruptured DAVFs in the anterior cranial fossa.

Cytochrome c-552 from gram-negative alkaliphilic Pseudomonas alcaliphila AL15-21T alters the redox properties at high pH.

A soluble class I cytochrome c of an alkaliphile was purified and characterized, and its primary structure was determined. This is the first example of a soluble class I cytochrome c in alkaliphiles. Cells the alkaliphilic gram-negative bacterium Pseudomonas alcaliphila AL15-21(T) grown at pH 10 had a soluble cytochrome c content that was more than twofold that of strain AL15-21(T) cells grown at pH 7 under air-limited conditions. Cytochrome c-552, a soluble cytochrome c with a low molecular weight, was purified from strain AL15-21(T) cells grown at pH 10 under air-limited conditions. Cytochrome c-552 had a molecular mass of 7.5 kDa and exhibited an almost fully reduced state in the resting form, which exhibited absorption maxima at wavelengths of 552, 523 and 417 nm. In the oxidized state, it exhibited an absorption maximum at 412 nm when it was oxidized by ferricyanide, its isoelectric point (pI) was 4.3 and it contained one heme c as a prosthetic group. Cytochrome c-552 was autoreduced at pH 10, and the autoreduction was reproducible. On the other hand, the autoreduction of cytochrome c-552 was not observed at pH 7.0. When pH was increased from 7.0 to 8.3, its midpoint redox potentials (E(m) values) increased from +228 mV to +276 mV as determined by redox titrations, and from +217 mV to +275 mV as determined by cyclic voltammetric measurements. The amino acid sequence deduced by cytochrome c-552 gene analysis revealed that the sequence consists of 96 residues, including 19 residues as an amino-terminal signal peptide. A phylogenetic tree based on amino acid sequence indicated that the protein belongs to group 4, cytochrome c(5) in class I cytochrome c.

Batch foam separation of a soluble protein.

Removal of protein dissolved in water by batch foam separation was conducted with using ovalbumin (OA) as a model protein in the light of wastewater treatment reducing organic loading. The removal efficiency had a maximum value near the i.e.p. of OA (pH 4.6); thus, most experiments were conducted at pH 4.6. Typical experimental conditions; superficial gas velocity, U(g): 1.97 x 10(-2)-5.37 x 10(-2)cm/s; initial bulk concentration of OA, C(i): ca. 0.05-0.25 g/L; liquid volume, V: 600 cm(3). A model estimating bulk concentration profile was proposed by taking into account a mass balance of the present system. The model predicted that OA could be removed perfectly, however, was not all removed experimentally. The residual OA concentration of the bulk liquid within the column reached plateau value, which correspond to ca. 18% of the initial OA concentration. The plateau value of the bulk concentration was attained for ca. 100-500 min with U(g)=1.97 x 10(-2)-5.37 x 10(-2)cm/s. Foaming ability test revealed that the foaming limit concentration of OA at pH 4.6 was 9.72 x 10(-3)g/L. These results suggested that OA molecules could be damaged by interaction of bubble surface in the dispersed phase, since there were the residual OA concentrations over the limit concentration. To take account of this phenomena and correct the model, average surface density, X(d), which should convert protein molecule into the denatured protein molecule, was introduced. The corrected model could explain well the time profile of OA bulk concentration.

Colloid (enterogenous) cyst in the frontal lobe.

A 60-year-old man presented with a left frontal mass lesion incidentally detected at a health check without apparent symptoms. Computed tomography revealed the lesion as homogeneous high density and magnetic resonance (MR) imaging showed the lesion as hyperintense on T(1)-weighted images, isointense on T(2)-weighted images, and hypointense on diffusion-weighted images. T(1)-weighted MR images with gadolinium showed no enhancement of the mass lesion. Cerebral angiography revealed an avascular area around the left frontal lesion. Total removal of the lesion was achieved through a craniotomy without complications. Histological, immunohistochemical, and electron microscopy examinations established the definite diagnosis of colloid cyst.

Adenoendocrine cell carcinoma of the gallbladder: report of a case.

Adenoendocrine cell carcinoma of the gallbladder is an uncommon form of cancer. We treated a 36-year-old woman who came to us with a chief complaint of abdominal pain. The abnormality was diagnosed to be a tumor-like mass in the gallbladder, and adenomyomatosis of the gallbladder was strongly suspected. A laparoscopic cholecystectomy was successfully performed, and the histopathological finding was adenoendocrine cell carcinoma of the gallbladder. The tumor cells of the small round cell carcinoma partly stained positively for synaptophysin, neuron-specific enolase, and CD 56, while adenocarcinoma cells showed positive reactions to keratin, which was thus suggestive of adenoendocrine cell carcinoma. The patient is alive and doing well at 12 months after the treatment.

Variation of saturated surface density of ovalbumin on bubble surface in continuous foam separation.

The adsorption of ovalbumin (OA) onto the bubble surfaces was studied with various pHs (3.5, 4.6, 6.0 and 8.0) by a continuous foam separation technique. From the value of the saturated surface density of adsorbed OA, the variation of effective diameter (D) of an OA molecule on the bubble surface was estimated for various pHs (3.5, 4.6, 6.0 and 8.0) of the OA solutions, assuming that the cross section of the OA molecules be circular and that the OA molecules adsorb on the bubble surface in a closest packing structure. The estimated variation of D with pH was attempted to explain based on a model modified from that proposed by Pujar and Zydney. The modified model could well reproduce the variation of the effective diameter with pH; the values of D calculated on the basis of the modified model almost agreed with that estimated from the saturated surface density in the present experimental pH range. From these, conclusion was drawn that the modified model presented in this study can express the variation in the effective diameter with pH.

Cytochrome c and bioenergetic hypothetical model for alkaliphilic Bacillus spp.

Although a bioenergetic parameter is unfavorable for production of ATP (DeltapH<0), the growth rate and yield of alkaliphilic Bacillus strains are higher than those of neutralophilic Bacillus subtilis. This finding suggests that alkaliphiles possess a unique energy-producing machinery taking advantage of the alkaline environment. Expected bioenergetic parameters for the production of ATP (DeltapH and DeltaPsi) do not reflect the actual parameters for energy production. Certain strains of alkaliphilic Bacillus spp. possess large amounts of cytochrome c when grown at a high pH. The growth rate and yield are higher at pH 10 than at pH 7 in facultative alkaliphiles. These findings suggest that a large amount of cytochrome c at high pHs (e.g., pH 10) may be advantageous for sustaining growth. To date, isolated cytochromes c of alkaliphiles have a very low midpoint redox potential (less than +100 mV) compared with those of neutralophiles (approximately +220 mV). On the other hand, the redox potential of the electron acceptor from cytochrome c, that is, cytochrome c oxidase, seems to be normal (redox potential of cytochrome a=+250 mV). This large difference in midpoint redox potential between cytochrome c and cytochrome a concomitant with the configuration (e.g., a larger negative ion capacity at the inner surface membrane than at the outer surface for the attraction of H+ to the intracellular membrane and a large amount of cyrochrome c) supporting H+-coupled electron transfer of cytochrome c may have an important meaning in the adaptation of alkaliphiles at high pHs. This respiratory system includes a more rapid and efficient H+ and e- flow across the membrane in alkaliphiles than in neutralophiles.

Purification and characterization of Warnericin RB4, anti-Alicyclobacillus bacteriocin, produced by Staphylococcus warneri RB4.

In this study we characterized a bacteriocin, warnericin RB4, produced by Staphylococcus warneri RB4. Warnericin RB4 activity was completely inactivated by trypsin and actinase E. The activity was stable at 100 degrees C for 15 min, and had a pH range of 2 to 6. S. warneri RB4 showed antibacterial activity against only Alicyclobacillus acidoterrestris, A. acidocaldarius, and Micrococcus luteus, among 34 bacterial species tested. The amino acid sequence of the purified bacteriocin contained 27 amino acid residues (K-K-K-S-G-V-I-P-X-V-X-H-D-X-H-M-N-X-F-Q-F-V-F-X-X-X-S). The molecular mass of the bacteriocin was estimated to be 2,958.2 Da by ESI-MS. These results show that the Warnericin RB4 exhibiting specific antibacterial activity against thermo-acidophiles, Alicyclobacillus spp., is a Nukacin ISK-1 or closely related bacteriocin, classified with class IA (Lacticin 481 types). This is the first report that Warnericin RB-4 is effective to inhibit the growth of causative microorganisms of spoilage in various acidic drinks. Warnericin RB4 might prove useful in fruit juices and fruit juice-containing drinks.