Fluorescence cholangiography for detection of a cystic duct drained into an accessory hepatic duct: A case report.

INTRODUCTION: Laparoscopic cholecystectomy is a safe and standard procedure, but serious bile duct injury may occur due to anatomical anomalies of the biliary tract, especially the accessory hepatic duct. The use of intraoperative fluorescence cholangiography with indocyanine green during laparoscopic cholecystectomy can reportedly prevent bile duct injury. PRESENTATION OF CASE: A 55-year-old woman with upper abdominal pain was referred to our hospital. Laboratory investigations revealed elevated leukocytes and biliary enzymes, while computed tomography demonstrated increased fatty tissue density around the gallbladder. Magnetic resonance cholangiopancreatography and drip infusion cholangiographic-computed tomography showed that the cystic duct drained into an accessory hepatic duct. Due to the diagnosis of cholelithiasis with a biliary anomaly, we performed laparoscopic cholecystectomy using fluorescence cholangiography with indocyanine green. We were able to recognize the accessory hepatic duct and cystic duct, then safely dissect the cystic duct without bile duct injury. DISCUSSION: Laparoscopic cholecystectomy is generally regarded as a safe procedure, but complications and even mortalities can arise in patients with anatomical anomalies of the biliary tract. The aid of intraoperative fluorescence cholangiography with indocyanine green allowed to recognize and identify the accessory hepatic duct and cystic duct, allowing us to operate without injury to the bile duct. CONCLUSIONS: Our experience supports the ease of use, safety, and effectivity of fluorescence cholangiography with indocyanine green. This may become the optimal standard technique to prevent bile duct injury.

Impact of pathological complete response following neoadjuvant chemotherapy (gemcitabine, nab-paclitaxel, S-1) and radiation for borderline resectable pancreatic cancer: a case report and review of literature.

BACKGROUND: Pancreatic cancer (PC) is a highly lethal malignancy, even if surgical resection is possible (median survival: < 30 months). The prognosis of borderline resectable pancreatic cancer (BR-PC) is even worse. There is no clear consensus on the optimal treatment strategy, including pre/postoperative therapy, for BR-PC. We report a patient with BR-PC who achieved clinical partial response with neoadjuvant chemoradiation therapy (NACRT) and underwent curative resection, resulting in pathological complete response (pCR). CASE PRESENTATION: A 71-year-old man with jaundice and liver dysfunction was referred to our department because of a 48-mm hypo-vascular mass in the pancreatic head with obstruction of the pancreatic and bile ducts and infiltration of superior mesenteric vein and portal vein. The lesion was identified as atypical cells which suggested adenocarcinoma by biopsy, and he was administered NACRT: gemcitabine and nab-paclitaxel, following S-1 and intensity modulated radiation therapy. After reduction in the tumor size (clinical partial response), pancreaticoduodenectomy was performed, and pCR achieved. Postoperative adjuvant chemotherapy with S-1 was initially administered and the patient is currently alive with no recurrence as of 2 years after surgery. CONCLUSIONS: NACRT is a potentially useful treatment for BR-PC that may lead to pCR and help improve prognosis.

Effects of Acupuncture Therapy on Drug-Resistant Fibromyalgia: An Exploratory Single-Arm Nonrandomized Trial.

Introduction: Fibromyalgia is a chronic illness that causes symptoms such as pain. In Japan, although pregabalin and duloxetine are the drugs of choice for fibromyalgia, they may be ineffective or may cause side-effects. Studies have reported on the efficacy of acupuncture against fibromyalgia. However, acupuncture is not always effective in clinical practice, and the reason for this is thought to be the dysfunction of the descending pain control system. This study aimed to determine whether the combined use of electro-scalp acupuncture and conventional electroacupuncture reduces fibromyalgia symptoms and drug dosage requirements. Methods: Patients with intractable fibromyalgia (visual analog scale [VAS] score ≥50 mm; Japanese version of the Fibromyalgia Impact Questionnaire [JFIQ] score ≥50) receiving pregabalin were recruited in this single-arm nonrandomized uncontrolled study. They underwent electroacupuncture on four limbs plus electro-scalp acupuncture once a week for 5 weeks. Drug intake, pain (as determined using VAS), quality of life (QOL; as determined using JFIQ), anxiety, depression, catastrophic thoughts, and sleep were assessed. Results: Although there was no increase in drug intake, 42.8% (3/7) of patients reduced pregabalin intake by approximately 10% (a moderate though insignificant effect). Pain levels significantly declined (VAS 75.4 ± 11.7 mm to 64.3 ± 17.3 mm; P = 0.05) and QOL significantly improved (JFIQ 67.0 ± 13.4 to 50.9 ± 18.3; P = 0.02). The parameters for anxiety, depression, catastrophic thoughts, and sleep did not significantly change. Conclusion: The combination of conventional electroacupuncture plus electro-scalp acupuncture may effectively alleviate pain, improve QOL, and reduce pregabalin dosage requirements in patients with fibromyalgia.

A successful operation for giant intra-abdominal desmoid tumors associated with familial adenomatous polyposis: A case report.

Desmoid tumors are benign proliferations of spindle cells originating in fibro-aponeurotic tissue. Many patients with familial adenomatous polyposis (FAP) die from desmoid tumors, which can arise spontaneously but often appear to be surgically induced by prophylactic colectomy. Desmoid tumors are the second most common cause of death in patients with FAP, second to colorectal cancer. Many patients can live a long life with desmoid tumors without symptoms, but when symptoms (ranging from bowel or ureteric obstruction to bowel perforation with abscess and fistula) appear or there is a risk of functional impairment, a wide spectrum of therapies (local and systemic) are valuable in improving the symptoms and controlling the disease. A half-Japanese, half-Caucasian male, who had been diagnosed with intra-abdominal desmoid tumors associated with FAP at age 13, was treated using abdominal wall incision for decompression and chemotherapy from the age of 38. The therapeutic outcome was progressive disease, based on the modified response evaluation criteria in solid tumors (mRECIST), and when he visited our hospital at age 41 the desmoid tumor had invaded the small bowel with a fistula to the abdominal wall. We performed a palliative operation to improve his symptoms, which were fever, abdominal pain, vomiting, and difficulty eating. As the tumor was extremely large and had invaded the small intestine, massive resection including the small intestine was required. To prepare for anticipated massive bleeding, a balloon catheter was placed in the superior mesenteric artery just prior to surgery. Although the operation was extremely difficult, following surgery the patient regained his ability to eat and when discharged was ambulatory and without short-bowel syndrome. We report our experience treating one of the largest reported intraperitoneal desmoid tumors. Resection resulted in a good postoperative course, with improved quality of life and prognosis.

[A Case of Gallbladder Cancer with Long Survival Treated with Resection after Downstaging with GC Therapy].

A 68-year-old woman with a chief complaint of obstructive jaundice was referred to our hospital. She was diagnosed with gallbladder cancer with invasion to the liver, extrahepatic bile duct, right hepatic artery and portal vein. After endoscopic retrograde biliary drainage, she received chemotherapy with gemcitabine and cisplatin. After 9 courses, the size of the tumor and the lymph nodes decreased, and we planned surgery. There were no unresectable factors, and the right hepatic artery and portal vein were detached from the tumor. We performed a subtotal stomach-preserving pancreaticoduodenectomy and gallbladder bed resection. We then performed adjuvant chemotherapy with S-1 for 1 year. The patient remains alive without recurrence, 5 years after the surgery. We report the case of advanced gallbladder cancer with downstaging after GC therapy.

Mesh repair under the anterior lamina of the rectus sheath (MUAR) for abdominal incisional hernia.

PURPOSE: Abdominal incisional hernia is a frequent complication of major abdominal operations. Our method of performing mesh repair under the anterior lamina of the rectus sheath (MUAR) involves placing mesh between the dorsal surface of the anterior rectus sheath and the rectus abdominis muscle. We evaluated the short-term and long-term outcomes of our MUAR method. METHODS: The subjects of this retrospective study were 80 patients with abdominal incisional hernia, who underwent MUAR at our hospital between August, 2009 and September, 2018. We investigated the rate of recurrence and postoperative complications in these patients, who were followed-up postoperatively for at least 18 months. Patients who completed all visits were then followed-up further with questionnaires. RESULTS: The recurrence rate after MUAR was 0%. Postoperative complications consisted of subcutaneous wound infections in two patients (2.5%), successfully treated with wound cleansing and antibiotics; and subcutaneous hematoma in three patients (3.8%), which was spontaneously absorbed in two patients, and removed in one. There were no other complications, such as seroma, intestinal obstruction, mesh infection and bulging, or prolonged postoperative pain. CONCLUSION: Mesh repair under the anterior lamina of the rectus sheath is simple and safe with positive short-term and long-term outcomes, suggesting that it is a good option for incisional hernia repair.

A Multicenter, Prospective, Randomized, Placebo-Controlled, Double-Blind Study of a Novel Pain Management Device, AT-02, in Patients with Fibromyalgia.

OBJECTIVES: Existing treatments for fibromyalgia have limited efficacy, and only a minority of individuals clinically respond to any single intervention. This study was a prospective, multicenter, randomized, double-blind, controlled clinical trial to evaluate the feasibility of alternating magnetic field therapy in fibromyalgia patients by comparing the Angel Touch device (AT-02) with a sham control (S-01). METHODS: Two sites enrolled 44 subjects with diagnosed fibromyalgia. After informed consent, subjects taking prohibited concomitant drugs underwent a washout period of two or more weeks. All subjects then began a one-week run-in period. Numerical rating scale (NRS) pain scores were collected without device intervention for one day, followed by S-01 application to four or more painful sites for 10 minutes at each site, twice daily for six days. Subjects were then randomized to AT-02 or S-01, applied to four or more painful sites for 10 minutes at each site, twice daily for eight weeks. NRS scores were obtained twice daily during the entire treatment period. RESULTS: The primary end point (change in NRS ± SD at week 8 vs baseline) was -0.94 ± 1.33 in the AT-02 group and -0.22 ± 1.38 in the S-01 group. A trend toward a between-group difference in eight-week NRS scores favored the AT-02 group (-0.73, 95% confidence interval = -1.56 to 0.11, P = 0.086). An adjusted repeated measure analysis detected a significant difference in NRS scores (P = 0.039). CONCLUSIONS: The reduction in NRS scores for AT-02 relative to sham was comparable to reductions observed in meta-analyses of fibromyalgia drug therapy. The unadjusted results and the persistence of the pain score reductions remain encouraging.

An evidence-based review of pregabalin for the treatment of fibromyalgia.

OBJECTIVES: Pregabalin, an α2-δ agonist, is approved for the treatment of fibromyalgia (FM) in the United States, Japan, and 37 other countries. The purpose of this article was to provide an in-depth, evidence-based summary of pregabalin for FM as demonstrated in randomized, placebo-controlled clinical studies, including open-label extensions, meta-analyses, combination studies and post-hoc analyses of clinical study data. METHODS: PubMed was searched using the term "pregabalin AND fibromyalgia" and the Cochrane Library with the term "pregabalin". Both searches were conducted on 2 March 2017 with no other date limits set. RESULTS: Eleven randomized, double-blind, placebo-controlled clinical studies were identified including parallel group, two-way crossover and randomized withdrawal designs. One was a neuroimaging study. Five open-label extensions were also identified. Evidence of efficacy was demonstrated across the studies identified with significant and clinically relevant improvements in pain, sleep quality and patient status. The safety and tolerability profile of pregabalin is consistent across all the studies identified, including in adolescents, with dizziness and somnolence the most common adverse events reported. These efficacy and safety data are supported by meta-analyses (13 studies). Pregabalin in combination with other pharmacotherapies (7 studies) is also efficacious. Post-hoc analyses have demonstrated the onset of pregabalin efficacy as early as 1-2 days after starting treatment, examined the effect of pregabalin on other aspects of sleep beyond quality, and shown it is effective irrespective of the presence of a wide variety of patient demographic and clinical characteristics. CONCLUSIONS: Pregabalin is a treatment option for FM; its clinical utility has been comprehensively demonstrated.

A mesenteric solid tumor with unusual features in a young male: A case report.

The current study presents a mesenteric mesenchymal tumor case, with unusual features in diagnostic imaging and histology. A 16-year-old male was admitted to the hospital with abdominal pain. Computed tomography (CT) revealed an abdominal mass, 2 cm in diameter. The results of contrast-enhanced CT, magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography indicated no specific features suggestive of its histology. Two arteries branching from the superior mesenteric artery were observed feeding the hypervascular tumor. After endoscopic and other laboratory findings revealed no additional lesions, the lesion was diagnosed as a primary mesenteric tumor. As the possibility of malignancy and future bleeding from this tumor could not be ruled out, a resection of the tumor was performed. During the surgery, the tumor, which was well circumscribed and hypervascular, was located in the mesentery of the jejunum. The resected tumor did not exhibit typical histological characteristics, and was labeled as 'myxoid smooth muscle neoplasm of uncertain biologic potential'. At 2 years after surgery, the patient remained well without evidence of recurrence. As primary mesenteric tumors are rare, particularly in young patients, it is considered important that this type of unusual tumor be included in the differential diagnosis for mesenteric tumors.

Case of ileal herniation through the foramen of Winslow diagnosed preoperatively by CT and treated with laparoscopic surgery.

A previously healthy 35-year-old man visited the emergency room complaining of epigastric pain and vomiting. The pain was sudden in onset. His blood tests were within normal limits except for a mild neutrophilia of 14 300/µL. Enhanced abdominal CT scan showed the small intestine dilated into the space between the portal vein and inferior vena cava from the foramen of Winslow. Under the diagnosis of herniation through the foramen of Winslow (HFW), we performed emergency laparoscopic surgery. Laparoscopy revealed an internal herniation of the dilated small intestine through the foramen of Winslow. Because the herniated small intestine was viable, intestinal resection was unnecessary. We released the incarceration under laparoscopy. HFW is very rare and often overlooked, but abdominal CT examination enabled a precise preoperative diagnosis because of characteristic findings. We should consider the possibility of HFW in patients with internal herniation of unknown origin. Laparoscopic surgery for HFW is effective.

Efficacy of mirtazapine for the treatment of fibromyalgia without concomitant depression: a randomized, double-blind, placebo-controlled phase IIa study in Japan.

To evaluate the efficacy and safety of mirtazapine in Japanese patients with fibromyalgia (FM), a parallel-group, randomized, double-blind, placebo-controlled phase IIa study was conducted at 57 sites between November 2012 and February 2014. Patients aged 20 to 64 years who met the American College of Rheumatology 1990 diagnostic FM criteria and had stably high pain scores during a placebo run-in period were randomly assigned (1:1) by a computer-generated allocation sequence (block size 4) to receive mirtazapine orally (15 mg/d for 1 week and then 30 mg/d) or matching placebo for 12 weeks. The primary endpoint was change in mean numerical rating scale (NRS) pain score from baseline to endpoint (week 12 or early discontinuation). Of the 430 patients randomized (n = 215 each group), 422 (n = 211 each group) were analyzed for the primary endpoint. At the study endpoint, mirtazapine caused a significantly greater reduction in the mean NRS pain score compared with placebo (difference, 0.44; 95% confidence interval, -0.72 to -0.17; P = 0.0018). The reduction by mirtazapine remained significantly greater compared with placebo from week 6 onward. More patients treated with mirtazapine had their NRS pain score reduced by ≥30% from baseline (45.5% vs 30.8%). Mirtazapine also improved pain-related quality of life assessed by the Japanese version of the Fibromyalgia Impact Questionnaire and the Short-Form 36 Questionnaire. Adverse events were more common with mirtazapine than placebo (68.8% vs 56.7%), including somnolence (32.1% vs 7.4%), weight gain (17.7% vs 0.9%), and increased appetite (11.6% vs 3.3%). In conclusion, mirtazapine was an effective and safe treatment for Japanese patients with FM.

Inactivation of Airborne Bacteria and Viruses Using Extremely Low Concentrations of Chlorine Dioxide Gas.

Infectious airborne microbes, including many pathological microbes that cause respiratory infections, are commonly found in medical facilities and constitute a serious threat to human health. Thus, an effective method for reducing the number of microbes floating in the air will aid in the minimization of the incidence of respiratory infectious diseases. Here, we demonstrate that chlorine dioxide (ClO2) gas at extremely low concentrations, which has no detrimental effects on human health, elicits a strong effect to inactivate bacteria and viruses and significantly reduces the number of viable airborne microbes in a hospital operating room. In one set of experiments, a suspension of Staphylococcus aureus, bacteriophage MS2, and bacteriophage ΦX174 were released into an exposure chamber. When ClO2 gas at 0.01 or 0.02 parts per million (ppm, volume/volume) was present in the chamber, the numbers of surviving microbes in the air were markedly reduced after 120 min. The reductions were markedly greater than the natural reductions of the microbes in the chamber. In another experiment, the numbers of viable airborne bacteria in the operating room of a hospital collected over a 24-hour period in the presence or absence of 0.03 ppm ClO2 gas were found to be 10.9 ± 6.7 and 66.8 ± 31.2 colony-forming units/m3 (n = 9, p < 0.001), respectively. Taken together, we conclude that ClO2 gas at extremely low concentrations (≤0.03 ppm) can reduce the number of viable microbes floating in the air in a room. These results strongly support the potential use of ClO2 gas at a non-toxic level to reduce infections caused by the inhalation of pathogenic microbes in nursing homes and medical facilities.

Cutaneous manifestations of patients with relapsing polychondritis: an association with extracutaneous complications.

The aim of this study was to determine the prognostic characteristics of patients with relapsing polychondritis (RP) accompanying cutaneous manifestations in Japan. We analyzed a cohort of 239 patients with RP in view of cutaneous and extracutaneous complications. Thirty three cases (14%) developed cutaneous manifestations and 23 cases had both cutaneous and extracutaneous manifestations. Five RP patients developed myelodysplastic syndrome (MDS) and all of the five patients had cutaneous manifestations, including Sweet's syndrome. Only one patient died of MDS among the five patients, suggesting rather better prognosis as compared with ordinary MDS. Five RP patients developed Behcet's disease and all the five patients had cutaneous manifestations. Death rate of the RP patients with cutaneous manifestations (15%) was slightly higher than that of whole Japanese RP patient cohort (9.2%). RP patients with cutaneous manifestations had a slightly higher death rate, than those without cutaneous manifestations. MDS of RP patients had a rather better prognostic impact in Japan. Further studies are needed to elucidate the pathophysiology of RP, which brings about development of extracutaneous manifestations, especially MDS and Behcet's disease.

A case of intraductal tubulopapillary neoplasm of pancreas with severe calcification, a potential pitfall in diagnostic imaging.

We experienced a case of intraductal tubulopapillary neoplasms (ITPN) of the pancreas with severe calcification, which complicated image diagnosis. A pancreas head tumor was detected in a Japanese female in her 50s. Early enhancement by contrast-enhanced CT and coarse calcification suggested a neuroendocrine tumor, although the obstruction and dilation of the main pancreatic duct appeared to be an intraductal tumor. An endoscopic ultrasound-guided fine needle aspiration biopsy specimen revealed adenocarcinoma tissue. Pancreaticoduodenectomy was performed, and the patient has been well without evidence of recurrence for over 10 months. Pathological examination on the resected specimen revealed that the tumor showed papillary and tubulo-cribriform growth patterns. Together with typical immunohistochemical results, the final diagnosis of ITPN was made. Characteristically, this case showed extensive calcification of both psammoma body-type and non psammoma body-type with foamy macrophage aggregation. This is the first report of ITPN with two types of calcification and macrophage. Since calcification might be one of the characteristic histological findings in ITPN as shown in our case, the possibility of ITPN should be also considered when calcification is detected in pancreatic lesions by various imaging modalities.

A planar gastrointestinal stromal tumor replacing the proper muscle layer causing fecaloma and perforation in the sigmoid colon: a case report and literature review.

A 72-year-old Japanese male with acute abdomen underwent emergency surgery for a preoperative diagnosis of stercoral colonic perforation of the sigmoid colon. A pathological examination revealed a proliferating spindle cell lesion that surrounded the perforation and replaced the muscularis propria without any mass formation. The spindle cells were positive for KIT and CD34 by immunohistochemistry, and somatic mutation of the c-kit gene was found using genomic DNA extracted from the lesion. We diagnosed the spindle cell lesion as a planar gastrointestinal stromal tumor (GIST). We speculate that perforation of the sigmoid colon in this case may be caused by the stasis of stool resulting from abnormal peristalsis of the lesional site. Two other similar cases have been reported in the literature, and showed good prognoses. Although their pathogenesis is unclear, planar GISTs should be considered as a possible cause of idiopathic or stercoral colonic perforation.

[A case of synchronous cancer of the gall bladder, common bile duct, and the papilla of vater].

A 58-year-old man was diagnosed with liver dysfunction during a health exam and subsequently visited a doctor. Abdominal ultrasonography revealed space-occupying lesions in the gall bladder and bile duct, and he was hospitalized for further examination and treatment. Computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and magnetic resonance cholangiopancreatography (MRCP) revealed double cancer of the gall bladder and bile duct with pancreaticobiliary maljunction (PBM), and we performed a pancreatoduodenectomy. Pathological examination revealed gall bladder and bile duct cancer, and severe dysplasia of the papilla of Vater. We diagnosed synchronous triple cancer because none of the cancers had continuity or vascular invasion. Each cancer was at Stage I, and the patient has survived for 2 years and 6 months without recurrence and no additional treatment. PBM is a mutation of the junction of the pancreatic and bile ducts outside of the duodenal wall, and is a known complication of biliary tract cancer due to the reflux of pancreatic juice and bile. Because K-ras and p53 gene mutations occur in the biliary tract mucosal epithelium, PBM increases the risk of developing multicentric cancer. It is important to consider the existence of double cancer when biliary tract cancer is detected in a PBM patient.

[A case of postpancreaticoduodenectomy local recurrence successfully treated with extended resection].

A 68 -year-old man underwent a pancreaticoduodenectomy after being diagnosed with primary duodenal cancer. The postoperative pathological diagnosis was tub2, SE, ly1, v1, panc3, pn+, N0. Although adjuvant chemotherapy was administered, local recurrence in the portal region was detected 18 months later. The recurrent tumor pressed against the region of the bile duct anastomosis, which caused obstructive jaundice. After serum bilirubin levels were reduced, resection of the recurrent tumors was performed. This required resection of the transverse colon, parts of the portal vein, and the inferior vena cava. The bile duct anastomotic region, which had been infiltrated by the tumor, was excised and rebuilt. The postoperative pathological diagnosis was tub2. The patient continued to receive adjuvant chemotherapy and showed no signs of recurrence 9 months after surgery. Extended resection for local recurrences of primary duodenal cancer may be an effective means of disease control.

[A case of extragastrointestinal stromal tumor with peritoneal dissemination].

Here, we present the case of a 60-year-old man in whom abdominal computed tomography showed a solid abdominal tumor (11 cm in diameter) in the pelvic space, with widely disseminated nodular lesions. Emergency surgery was performed following the rapid onset of intense abdominal pain. Peritoneal disseminations were widespread and the tumor was confirmed to be in the pelvic space. The tumor was not connected to any segment of the intestinal tract but rather to the retroperitoneum. Immunohistochemical staining was positive for c-kit (exon 11 mutation) and CD34 but negative for S-100 protein. Careful postoperative examination did not reveal any lesions in the upper or lower alimentary tract. On the basis of these findings we diagnosed the tumor as an extragastrointestinal stromal tumor (EGIST) originating from the retroperitoneum. After surgery, intravenous infusion of imatinib was started at a full dose of 400mg/day; however, owing to strong adverse effects, the dose was reduced to 200mg/day. Despite halving the dose, the patient has remained lesion-free according to computed tomography for 36 months after the operation. Low-dose imatinib chemotherapy remained efficacious in controlling progression in this case.

An open-label long-term phase III extension trial to evaluate the safety and efficacy of pregabalin in Japanese patients with fibromyalgia.

OBJECTIVES: To assess the long-term safety and efficacy of pregabalin for the treatment of Japanese patients with fibromyalgia (FM). METHODS: This 53-week, open-label extension study was conducted at 20 study sites in Japan in patients with FM who had completed a preceding 16-week, placebo-controlled, double-blind trial. Patients received pregabalin, starting at 150 mg/day and increasing to a maintenance dose of 300 or 450 mg/day. The primary endpoint was safety, and secondary endpoints included measures of pain, sleep, and physical functioning. RESULTS: 106 patients entered the trial and received at least one dose of the study drug. The most common treatment-related adverse events were somnolence, dizziness, increased weight, and constipation. There were no treatment-related serious or severe adverse events. There were five (4.7%) discontinuations due to adverse events, of which three (2.8%) were considered related to the study drug. Most adverse events resolved over time and could be managed without dose reduction or treatment discontinuation. Improvements in secondary efficacy endpoints of pain, sleep, and physical functioning emerged early in the study and were maintained for the duration of treatment. CONCLUSIONS: These data indicate that the long-term treatment of Japanese FM patients with pregabalin may be both safe and effective.

A randomized, double-blind, multicenter, placebo-controlled phase III trial to evaluate the efficacy and safety of pregabalin in Japanese patients with fibromyalgia.

INTRODUCTION: Fibromyalgia is a chronic disorder characterized by widespread pain and tenderness. Prior trials have demonstrated the efficacy of pregabalin for the relief of fibromyalgia symptoms, and it is approved for the treatment of fibromyalgia in the United States. However, prior to this study, there has not been a large-scale efficacy trial in patients with fibromyalgia in Japan. METHODS: This randomized, double-blind, multicenter, placebo-controlled trial was conducted at 44 centers in Japan to assess the efficacy and safety of pregabalin for the symptomatic relief of pain in fibromyalgia patients. Patients aged ≥18 years who had met the criteria for fibromyalgia were randomized to receive either pregabalin, starting at 150 mg/day and increasing to a maintenance dose of 300 or 450 mg/day, or placebo, for 15 weeks. The primary efficacy endpoint was mean pain score at final assessment. Secondary endpoints included Patient Global Impression of Change (PGIC) together with measures of sleep, physical functioning and quality of life. RESULTS: A total of 498 patients (89% female) were randomized to receive either pregabalin (n = 250) or placebo (n = 248). Pregabalin significantly reduced mean pain score at final assessment (difference in mean change from baseline, compared with placebo -0.44; P = 0.0046) and at every week during the study (P <0.025). Key secondary endpoints were also significantly improved with pregabalin treatment compared with placebo, including PGIC (percentage reporting symptoms "very much improved" or "much improved", 38.6% vs 26.7% with placebo; P = 0.0078); pain visual analog scale (difference in mean change from baseline, compared with placebo -6.19; P = 0.0013); Fibromyalgia Impact Questionnaire total score (-3.33; P = 0.0144); and quality of sleep score (-0.73; P <0.0001). Treatment was generally well tolerated, with somnolence and dizziness the most frequently reported adverse events. CONCLUSIONS: This trial demonstrated that pregabalin, at doses of up to 450 mg/day, was effective for the symptomatic relief of pain in Japanese patients with fibromyalgia. Pregabalin also improved measures of sleep and functioning and was well tolerated. These data indicate that pregabalin is an effective treatment option for the relief of pain and sleep problems in Japanese patients with fibromyalgia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00830167.