A case of Sjögren’s syndrome presenting as hypokalemic myopathy due to distal renal tubular acidosis

We report a case of hypokalemic myopathy with distal renal tubular acidosis which leads to the diagnosis of Sjögren’s syndrome (SS). A 67-year-old man was admitted to our department for progressive muscle weakness and myalgia. Laboratory data demonstrated hypokalemia with hyperchloremic acidosis, elevated muscle enzyme and inability to acidify urine. Findings of interstitial nephritis, which is consistent with renal tubular acidosis in SS, were found on renal biopsy. Remarkable changes of the renal tubule, including tubular atrophy, dilatation and intratubular casts, were observed. Potassium replacement therapy normalized the marked elevated urinaryβ ₂-microglobulin excretion as well as the improvement of muscle symptoms. Taken together with our findings, it it suggested that sustained hypokalemia may partly contribute to the exacerbation of the pre-existing renal tubular disorder in SS.     

Usefulness of V3-Radial Artery Graft-V4 Bypass in Bilateral Fusiform Aneurysms of Vertebral Artery: Case Report

A 55-year-old woman with bilateral vertebral artery (VA) aneurysms was transferred to our hospital. She suffered from a minor stroke. Magnetic resonance imaging (MRI) for the stroke incidentally revealed bilateral VA aneurysms. Due to its size, more observation was recommended, and the patient was found eager to be treated. Both side surgeries were found inappropriate because of severe lower cranial nerve disturbances. The right aneurysm involved the posterior inferior cerebellar artery (PICA) and the V4 segment was deviated to the right side. Therefore, the smaller right aneurysm was treated first with an occipital artery (OA)-PICA bypass and a V3-radial artery graft (RAG)-V4 bypass followed by proximal clipping of the PICA and the right VA. The right VA was successfully remade by RAG and the right aneurysm was not revealed on postoperative examination. By doing so, the opposite aneurysm was able to be eliminated by the parent artery occlusion even by using an interventional radiology (IVR). The V3-RAG-V4 bypass is a useful method for treating bilateral VA aneurysms. This is a new bypass which has not been reported so far to the best of our knowledge.     

Phase I study of primary treatment with 5-FU,oxaliplatin, irinotecan,levofolinate, and panitumumab combination chemotherapy in patients with advanced/recurrent colorectal cancer involving the wild-type <Emphasis Type="Italic">RAS</Emphasis> gene: the JACCRO CC-14 study

Background

FOLFOXIRI is now regarded as the chemotherapy regimen that offers the best platform for the treatment of colorectal cancer. However, the safety and efficacy of FOLFOXIRI + panitumumab has not been demonstrated. We conducted a phase I study to determine the recommended dose of FOLFOXIRI + panitumumab as first-line treatment for RAS wild-type metastatic colorectal cancer (mCRC).

Methods

Patients received combination therapy consisting of panitumumab (6 mg/kg on day 1) + FOLFOXIRI [irinotecan (CPT-11), oxaliplatin (L-OHP) 85 mg/m², and folinate (LV) 200 mg/m²] on day 1, followed by fluorouracil (5-FU) 3200 mg/m² infused as a 46-h continuous infusion starting on day 1) repeated every 2 weeks as first-line treatment of RAS wild-type mCRC patients. A decrease in CPT-11 dose was planned (started at level 1: CPT-11 165 mg/m²).

Results

Seven patients were enrolled, and six were assessed for safety and efficacy. Maximum tolerated dose was not reached at level 1; all patients were treated at these levels. The common Grade 3 or 4 relevant toxicities were diarrhea (50%), hypokalemia (33%) and stomatitis (33%). No treatment-related deaths occurred. Of the six patients assessed four had partial response and the two others had stable disease; hence, the response rate was 66.7% (95% confidence interval 28.9–100%) and the disease control rate was 100%. Time to protocol treatment failure was 7.2 (1.4–7.3) months.

Conclusion

The FOLFOXIRI + panitumumab chemotherapy regimen was well tolerated by our patients with mCRC and showed promising anti-tumor activity. The recommended phase II dose was determined to be the same as the standard doses of this regimen used worldwide.

     

Primary leiomyosarcoma of the lesser sac

A case of leiomyosarcoma arising in the lesser sac in a 64-year-old man is presented. A second operation was required because of local recurrence 6 years following the first operation. A review of the literature revealed that only eight cases of leiomyosarcoma arising in the lesser sac, including our case, were reported. Almost all of these patients had symptoms of abdominal pain or distension. The tumor tended to grow to a large size and about 90 percent were over 10 cm in the maximal diameter. The prognosis of these series was poor and our own patient seems to be the second 5 year survivor. Presented at the Kyushu Regional meeting of the Japan Surgical Society, Oita, July 2–3, 1983     

Low-copy transgene detection using nested digital polymerase chain reaction for gene-doping control

Gene doping is prohibited for fair competition in human and horse sports. One style of gene doping is the administration of an exogeneous gene, called a transgene, to postnatal humans and horses. Although many transgene detection methods based on quantitative polymerase chain reaction (PCR), including real-time PCR and digital PCR, have been recently developed, it remains difficult to reliably detect low-copy transgenes. In this study, we developed and validated a nested digital PCR method to specifically detect low-copy transgenes. The nested digital PCR consists of (1) preamplification using conventional PCR and (2) droplet digital PCR detection using a hydrolysis probe. Using 5, 10, 20, 60 and 120 transgene copies as template, 496.0, 1089.7, 1820.7, 4313.3 and 7840.0 copies per microlitre, respectively, were detected using our nested digital PCR. Although high concentrations of phenol, proteinase K, ethanol, EDTA, heparin and genomic DNA all inhibited preamplification, their effects on the digital PCR detection were limited. Once preamplification was successful, even substitution of bases within the primers and probes had minimal effects on transgene detection. The nested digital PCR developed in this study successfully detected low-copy transgenes and can be used to perform a qualitative test, indicating its usefulness in the prevention of false positives and false negatives in gene-doping detection.     

Transpulmonary Echocardiography to Guide Stent Implantation into Coarctation of the Aorta

Although stent implantation into aortic coarctation has been performed solely under fluoroscopy, we successfully applied intracardiac echocardiography (ICE) to guide this procedure in a 13‐year‐old patient. Placing an intracardiac echocardiographic catheter in the left pulmonary artery facing upward, we readily visualized the precise anatomy of coarctation, measured the pressure gradient, and monitored the stent inflation process. This report suggests a new application of ICE for intervention with structural and vascular diseases other than interatrial septum.     

Phase Ib/II Study of Biweekly TAS-102 in Combination with Bevacizumab for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies (BiTS Study)

Lessons Learned

• A biweekly TAS‐102 plus BEV schedule in patients with heavily pretreated mCRC showed equivalent efficacy with less toxicity compared with the current schedule of TAS‐102 plus BEV combination.
• Biweekly TAS‐102 plus BEV combination could reduce unnecessary dose reduction of TAS‐102, maintain higher doses, and possibly be effective even in cases without chemotherapy‐induced neutropenia (CIN).
• The prespecified subgroup analysis of this study showed an obvious association between CIN within the first two cycles and prognosis of biweekly TAS‐102 plus BEV.

BackgroundTAS‐102 (trifluridine/tipiracil) plus bevacizumab (BEV) combination therapy has shown promising activity in patients with metastatic colorectal cancer (mCRC). However, the previously reported dose and schedule for the TAS‐102 (70 mg/m²/day on days 1–5 and 8–12, every 4 weeks) plus BEV (5 mg/kg on day 1, every 2 weeks) regimen is complicated by severe hematological toxicities and difficult administration schedules. Here, we evaluated the efficacy and safety of a more convenient biweekly TAS‐102 plus BEV combination.MethodsPatients with mCRC who were refractory or intolerant to standard chemotherapies were enrolled. Patients received biweekly TAS‐102 (twice daily on days 1–5, every 2 weeks) with BEV (5mg/kg on day 1, every 2 weeks). The primary endpoint was progression‐free survival rate at 16 weeks (16‐w PFS rate).ResultsFrom October 2017 to January 2018, 46 patients were enrolled. The recommended phase II dose was determined to be TAS‐102 (70 mg/m²/day). Of the 44 eligible patients, the 16‐w PFS rate was 40.9% (95% confidence interval, 26.3%–56.8%), and the null hypothesis was rejected (p < .0001). Median progression‐free survival (PFS) and overall survival were 4.29 months and 10.86 months, respectively. Disease control rate was 59.1%. Common grade 3 or higher adverse events were hypertension (40.9%), neutropenia (15.9%), and leucopenia (15.9%).ConclusionBiweekly TAS‐102 plus BEV showed promising antitumor activity with safety.     

A prospective study of XELIRI plus bevacizumab as a first-line therapy in Japanese patients with unresectable or recurrent colorectal cancer (KSCC1101)

Background

This study was designed to evaluate the efficacy and toxicity of XELIRI plus bevacizumab for the treatment of Japanese patients with unresectable or recurrent colorectal cancer (CRC).

Methods

This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated unresectable or recurrent CRC, presence of measurable lesions, ≥20 years of age, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELIRI (irinotecan 200 mg/m² on day 1 plus capecitabine 800 mg/m² b.i.d. on days 1–14) every 3 weeks. The primary endpoint was the objective tumor response rate.

Results

A total of 36 patients were enrolled in this study from July 2011 to September 2012. One patient did not fulfill the eligibility criteria and one patient withdrew their consent before the start of the treatment protocol. The confirmed objective response rate was 58.8% (95% CI 35.1–70.2%). The median progression-free survival was 9.6 months (95% CI 5.1–11.1 months) and the median overall survival was 23.1 months (95% CI 11.3–36.7 months). The grade ≥3 adverse events that were frequently encountered in this study were neutropenia (31.4%), leukopenia (22.9%), diarrhea (22.9%), anemia (20.0%), anorexia (20.0%) and febrile neutropenia (17.2%). The frequency of grade 3/4 adverse events, such as neutropenia and leukopenia, was much higher in patients with a UGT1A1 polymorphism.

Conclusions

A first-line therapy comprising XELIRI plus bevacizumab yielded a promising response rate. However, careful attention should be given to adverse clinical events in Japanese patients receiving treatment with unresectable or recurrent CRC.