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Background Jackhammer esophagus (JE) is a hypercontractile esophageal motility disorder diagnosed using high-resolution manometry (HRM). We sought to determine the clinical presentation and therapeutic data of patients with JE in Japan. Methods The study included patients with JE, diagnosed through HRM performed for suspicious esophageal motility disorders. Demographics, esophagogastroduodenoscopy, radiology, and therapy data were collected from patient charts. Results Among the 4,412 HRM tests performed, 89 patients (61.6 ± 13.4 years; 64 males, 25 females) were diagnosed with JE (2.0%). Dysphagia was the most frequent symptom (80%), followed by chest pain (40%) and heartburn (25%). Esophagogastroduodenoscopy showed abnormal findings in 32% of patients: corkscrew/rosary beads appearance in 26%, narrowing in 11%. Eosinophilic infiltration (> 15 eosinophils/high power field) was diagnosed in 21%. Esophagography showed abnormal findings in 9% of the patients. For the initial therapy, 47 patients received medical treatment followed by peroral endoscopic myotomy (21 patients) and laparoscopic myotomy (two patients). Thirteen patients did not receive any treatment and 10 of those (77%) reported spontaneous resolution of symptoms. Patients who required invasive treatment experienced severe disability in their quality of life and greater maximal distal contractile integral than those who did not. Conclusions HRM showed that the prevalence of JE was very low (2%). Esophagogastroduodenoscopy revealed some characteristic features of JE in patients. Some patients showed improvement of symptoms without invasive treatments. Follow-up with/without medical treatment should be considered before performing invasive treatment in patients whose distal contractile integral is relatively low and the quality of life is not impaired.

Background/aims No screening test for esophageal motility disorder (EMD) has been established, the objective of this study is to examine the potential usefulness of our newly developed "Onigiri esophagography" combined with an obstruction level (OL) classification system in screening for EMD. Methods A total of 102 patients with suspected EMDs who underwent both high-resolution manometry (HRM) and Onigiri esophagography between April 2017 and January 2019 were examined. The EMD diagnosis was performed based on the Chicago classification version 3.0 by HRM. Onigiri esophagography was performed using a liquid medium (barium sulfate) followed by a solid medium, which consisted of an Onigiri (a Japanese rice ball) with barium powder. The extent of medium obstruction was assessed by the OL classification, which was defined in a stepwise fashion from OL0 (no obstruction) to OL4 (severe obstruction). Results Thirty-two percent of the patients with OL0 (32.3%), OL1 (50.0%), OL2 (88.0%), OL3 (100.0%), and OL4 (100.0%) were diagnosed EMDs by HRM. The area under the curve, as determined by a receiver operating characteristic analysis, for the OL classification was 0.86. Using the cutoff value of OL1, the sensitivity and specificity were 87.3% and 61.3%, respectively, while using a cutoff value of OL2, the sensitivity and specificity were 73.2% and 90.3%, respectively. Conclusion In conclusion, Onigiri esophagography combined with the OL classification system can be used as a screening test for EMDs with a cutoff value of OL1.

Efficacy of hybrid endoscopic submucosal dissection with SOUTEN in gastric lesions: An ex vivo porcine model basic study

Background A clutch cutter is a scissor-type knife used in endoscopic submucosal dissection (ESD) for gastrointestinal tract tumors. The assistant during the ESD using a clutch cutter (ESD-C) needs to rotate the device and grasp the target tissue appropriately; therefore, the assistant's skill may affect the technical outcomes of ESD-C. Aim To determine how assistant skill level affected the technical outcomes of gastric ESD-C using an ex vivo porcine training model. Methods In this pilot study, mock lesions of 15-30 mm in diameter were created in the middle or lower third of the porcine stomach. A total of 32 ESD-C procedures were performed by 16 trainees. Each trainee operator performed two ESD-C procedures; one ESD-C was assisted by an expert (ESD-C-E), and the other was assisted by a non-expert (ESD-C-NE). The total procedure time of the ESD was set as the primary outcome, and en bloc resection rate, complete procedure rate, perforation rate, and each procedure time/speed for mucosal incision or submucosal dissection were set as the secondary outcomes. In addition, we investigated factors associated with the difficulty of ESD including incompletion of ESD procedure, a long procedure time (≥ 20 min) or intraoperative perforation. Results The median total procedure time of the ESD-C-E was significantly shorter than that of the ESD-C-NE (12.9 min vs 21.9 min, P = 0.001). The en bloc resection rate was 100% in both groups. Complete resection rates of the ESD-C-E and ESD-C-NE groups were 100% and 93.8%, respectively. No intraoperative perforation was observed in both groups. In the multivariate analysis, assistant skill was significantly associated with the difficulty of ESD, with the highest odds ratio of 16.5. Conclusion Assistance by an expert is an important factor when trainees perform ESD-C procedures.

High-resolution manometry (HRM) is the gold standard for diagnosing esophageal motility disorders (EMDs); however, it requires specialized equipment. The development of more accessible screening examinations is expected. We evaluated the utility of barium esophagography (BE) screening using two novel findings to diagnose EMDs.Between January 2013 and October 2020, 244 patients with suspected EMDs who underwent both HRM and BE were analyzed. The EMD diagnosis was based on HRM findings using Chicago Classification version 3.0. BE was performed using sequential esophagography with barium sulfate. Three conventional BE findings (air-fluid level, rosary-bead/corkscrew appearance, and absent/weak peristalsis) and two novel BE findings (wave appearance and supra-junctional ballooning) were used for diagnosis.The sensitivity and specificity of BE screening using the two novel findings and conventional findings to diagnose EMDs were 79.4% and 88%, respectively [area under the receiver-operating characteristic curve (AUC) = 0.837]. Without these novel findings, they were 63.9% and 96%, respectively (AUC = 0.800), respectively. Achalasia was highly correlated with the air-fluid level (88.7%). Absent contractility was highly correlated with absent/weak peristalsis (85.7%). Relatively high correlations were observed between distal esophageal spasm and rosary-bead/corkscrew appearance (60%), and between achalasia and wave appearance (59.7%). The intra-observer reproducibility and inter-observer agreement for individual BE findings were 84.4% and 75%, respectively. Wave appearance was associated with higher integrated relaxation pressure (IRP) and shorter distal latency. Supra-junctional ballooning was associated with higher IRP.BE screening using two additional novel findings to diagnose EMDs could be useful in general practice.

Background/aims Endoscopic submucosal dissection (ESD) of recurrent esophageal carcinoma is technically difficult to perform due to submucosal fibrosis that develops after definitive chemoradiation therapy. Therefore, our aim was to evaluate the usefulness of clip-with-thread traction for ESD of esophageal lesions with submucosal fibrosis. Materials and methods Four endoscopists excised 16 lesions by ESD in an ex vivo pig training model. Mock lesions (30 mm in diameter) were created, including a 10-mm area of submucosal fibrosis in the center of each lesion. Each endoscopist performed two ESDs with traction (ESD-T) and two without traction (ESD-N). The primary outcome was the time required for submucosal dissection. Secondary outcomes were the rate of en bloc (complete) resection and perforation during the procedure, and the total amount of solution injected. Results All esophageal ESDs were completed. The median dissection time was significantly shorter for the ESD-T group (median 12.5 min, interquartile range 10.2-14.5) when comparing to the ESD-N group (median 18.0 min, interquartile range 14.6-19.2) (P=0.040). The en bloc resection rate was 100% in both groups, with a rate of complete resection of 87.5% and a rate of perforation of 37.5% for both groups. The median amount of solution injected was not significantly different between the ESD-T (18.0 ml) and ESD-N (20.5 ml) groups (P=0.526). Conclusion Clip-with-thread traction improved the performance of ESD for lesions with submucosal fibrosis. However, the method might not reduce the risk of perforation, which remains an important clinical issue to resolve.

Background: Endoscopic submucosal dissection (ESD) is a standard treatment for tumors of the gastrointestinal tract. We developed a self-completion method of ESD using Endosaber to eliminate the need for an additional device or human assistance during the procedure. The aim of this study was to evaluate the technical feasibility and outcomes of this method in an ex vivo porcine training model. Methods: This was a pilot study, and the procedures were performed by 4 experts. Mock lesions measuring 15 mm in diameter were prepared at the posterior wall in the middle or lower esophagus obtained from domestic pigs. Each operator performed ESD on the mock lesions in 3 models. The primary outcome was ESD completion rate using the self-completion method. The secondary outcomes were procedure time, en bloc resection rate, perforation rate, and number of injections during the procedure. Results: All 12 ESDs were completed using the self-completion method. The median procedure time (interquartile range) was 483.5 (399–619.3) s (median incision time: 240.4 [168.3–332.5] s; median dissection time: 222 [182.8–257] s). En bloc resection rate was 100%. No perforation was noted during any of the procedures. The median number of injections was 10.5 (9–14.3). The procedure time decreased significantly with increase in experience (p = 0.020). Conclusions: The self-completion ESD method using one Endosaber without any assistance achieved a 100% en bloc resection rate without any perforation. The need for an additional device or assistance was successfully eliminated. This method may prove to be a simple and cost-effective ESD procedure for lesions in humans.

Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P Conclusions Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

We have found that an altered lower esophageal sphincter (LES) accommodation response is an underlying cause of esophagogastric junction outflow obstruction (EGJOO). The objective of this study was to examine the treatment effect of acotiamide, a prokinetic agent which improves impaired gastric accommodation in functional dyspepsia, in patients with EGJOO. A prospective observational longitudinal study was conducted between October 2014 and March 2020. Acotiamide (100 mg, 3 times a day) was administered to 25 patients with EGJOO for 4 weeks. High-resolution manometry (HRM) was performed just before and after 4 weeks of treatment. As the primary outcome, the extent of integrated relaxation pressure (IRP) after treatment (14.6, 12.1–22.0 mmHg) was significantly lower than that before treatment (19.4, 17.1–27.4 mmHg). The extent of LES accommodation index after treatment (32.7, 21.0–40.0 mmHg) was also significantly lower than that before treatment (39.3, 31.2–50.2 mmHg). Acotiamide normalized the IRP (

The preparatory accommodation response of lower esophageal sphincter (LES) before swallowing is one of the mechanisms involved in LES relaxation during wet swallows, however, the physiological and/or pathological roles of LES accommodation remain to be determined in humans. To address this problem, we conducted a prospective observational study of 38 patients with normal high-resolution manometry (HRM) and 23 patients with idiopathic esophagogastric junction outflow obstruction (EGJOO) to assess dry and wet swallows. The LES accommodation measurement was proposed for practical use in evaluating the LES accommodation response. Although swallow-induced LES relaxation was observed in both dry and wet swallows, LES accommodation (6.4, 3.1–11.1 mmHg) was only observed in wet swallows. The extent of LES accommodation was impaired in idiopathic EGJOO (0.6, − 0.6–6 mmHg), and the LES accommodation measurement of patients with idiopathic EGJOO (36.8, 29.5–44.3 mmHg) was significantly higher in comparison to those with normal HRM (23.8, 18–28.6 mmHg). Successful LES relaxation in wet swallowing can be achieved by LES accommodation in combination with swallow-induced LES relaxation. Impaired LES accommodation is characteristic of idiopathic EGJOO. In addition to the IRP value, the LES accommodation measurement may be useful for evaluating the LES relaxation function in clinical practice.

Background Endoscopic submucosal dissection (ESD) is widely accepted as a local treatment for gastrointestinal tract tumors. As a simplified endoscopic procedure, hybrid ESD (H-ESD) has been performed for colorectal neoplasms in recent times. However, whether H-ESD is superior to conventional ESD (C-ESD) for patients with early gastric neoplasms (EGN) remains unclear. In this trial, we will compare the treatment outcomes of H-ESD and C-ESD. We hypothesize that the procedure time for H-ESD is shorter than that for C-ESD. Methods This is an investigator-initiated, multi-center, prospective, randomized, open-label, parallel-group trial to be conducted beginning in August 2020 at nine institutions in Japan. We will determine if H-ESD is superior to C-ESD in terms of procedure time in patients with EGN diagnosed as macroscopically intramucosal (T1a) differentiated carcinoma ≤ 20 mm in diameter without ulcerative findings according to current Japanese gastric cancer treatment guidelines. A total of 82 patients will be recruited and randomly assigned to either the C-ESD or the H-ESD group. The primary outcome is ESD procedure time. Secondary outcomes include mucosal incision, time and speed of submucosal dissection, en bloc resection, complete resection, curability, adverse events related to the ESD procedure, extent of dissection before snaring, volume of injection solution, number and time of hemostasis, thickness of the submucosal layer in the resected specimen, and handover to another operator. The stated sample size was determined based on the primary outcome. According to a previous report comparing the procedure times of C-ESD and H-ESD, we hypothesized that H-ESD would provide a 0.2 reduction in logarithmically concerted procedure time (−37%). We estimated that a total of 82 participants were needed to reach a power of 80% for a t-test with a significance level of 0.05 and considering a 10% dropout. Discussion This trial will provide high-quality data on the benefits and risks of H-ESD for EGN patients. The results of this study could lead to improved outcomes in patients with EGN undergoing ESD. The results will be presented at national and international meetings and published in peer-reviewed journals. Trial registration UMIN-CTR UMIN000041244. Registered on July 29, 2020.

BACKGROUND Hybrid endoscopic submucosal dissection (ESD) that comprises mucosal incision and partial submucosal dissection followed by snaring in a planned manner, has been developed for endoscopic resection of gastrointestinal neoplasms to overcome the technical barrier of ESD. Although the superiority of hybrid ESD with SOUTEN, a single multifunctional device, over conventional ESD has been indicated, the actual effect of snaring itself remains unclear since SOUTEN could be applied to hybrid ESD group, but not to the conventional ESD group, due to ethical issue in clinical practice. AIM To determine whether and how hybrid ESD was superior to conventional ESD in the endoscopic treatment of gastric lesions in an ex vivo porcine model basic study. METHODS Sixteen endoscopists participated in this basic study in August 2020 at Kyushu University, performing 32 procedures each for hybrid ESD and conventional ESD. Mock lesions (10-15 mm, diameter) were created in the porcine stomach. The primary outcome was total procedure time and secondary outcomes were en bloc or complete resection, perforation, procedure time/speed for both, mucosal incision, and submucosal dissection. Factors associated with difficulty in ESD including longer procedure time, incomplete resection, and perforation, were also investigated. Categorical and continuous data were analyzed using the chi-square test or Fisher’s exact test and the Mann-Whitney U test, respectively. RESULTS The median total procedure time of hybrid ESD was significantly shorter than that of conventional ESD (median: 8.3 min vs 16.2 min, P < 0.001). Time, speed, and the amount of hyaluronic acid during submucosal dissection were more favorable in hybrid ESD than conventional ESD (time, 5.2 min vs 10.4 min, P < 0.001; speed, 43.7 mm2/min vs 23.8 mm2/min, P < 0.00; injection volume, 1.5 mL vs 3.0 mL, P < 0.001), although no significant differences in those factors were observed between both groups during mucosal incision. There was also no significant difference between both groups in the en bloc/complete resection rate and perforation rate (complete resection, 93.8% vs 87.5%, P = 0.67; perforation, 0% vs 3.1%, P = 1). Selection of conventional ESD as the treatment method was significantly associated with difficulties during ESD (odds ratio = 10.2; highest among factors). CONCLUSION Hybrid ESD with SOUTEN improves the treatment outcomes of gastric lesions. It also has the potential to reduce medical costs since SOUTEN is a single multifunctional device that is inexpensive.

A 76-year-old woman suffered from repeated postprandial syncope of unknown cause. Computed tomography scanning revealed an enlarged hiatal hernia sac with food residues that compressed both the left atrium and inferior vena cava. As soon as the hernia cavity expanded during an upper gastrointestinal X-ray examination, she experienced a deterioration of her level of consciousness. Therefore, we diagnosed her of a swallow syncope due to left atrium compression by the huge hernia sac. The sac also compressed the inferior vena cava, and she experienced a transient elevation of her hepatobiliary enzyme level probably due to the influence of the congestive liver. Thus, clinicians should always keep this condition in mind when encountering patients with post-meal syncope.

Background The standard surgical method for symptomatic submucosal tumors (SMTs) or tumors with unclear biological behavior is enucleation. Minimally invasive approaches are usually considered appropriate for surgical enucleation; thus, thoracoscopic and laparoscopic enucleation is performed widely and safely. However, it is sometimes difficult to enucleate large and complicated esophageal tumors using thoracoscopic surgery, and even if rare, there is the risk of requiring thoracotomy or esophagectomy. In the present case, we enucleated a large and complicated leiomyoma safely using a new combined method with endoscopic and thoracoscopic procedures. Case presentation A 42-year-old woman presented to our hospital for a detailed examination of an abnormal finding in her health check-up chest X-ray images. She complained of upper abdominal pain after eating, and computed tomography revealed an esophageal tumor measuring 60 mm in length surrounding her lower thoracic esophagus. Esophagogastroduodenoscopy revealed a huge complicated SMT at the esophagogastric junction. Cytological examination with endoscopic ultrasound-guided fine-needle aspiration showed that the tumor was a leiomyoma. To enucleate this large and complicated esophageal SMT safely and without damaging the esophageal mucosa, we performed endoscopic and thoracoscopic procedures. We created a submucosal tunnel, endoscopically, and then performed thoracoscopic surgery to enucleate the tumor completely from the esophageal muscularis. Using these combined procedures, we were able to easily mobilize even a complicated tumor of this size from the mucosa and completed the surgery thoracoscopically without difficulty. As a result, the tumor was dissected safely with a minimal defect in the muscularis and without damaging the mucosa. Finally, we closed the defect in the esophageal muscularis with continuous sutures, thoracoscopically, and closed the entry of the submucosal tunnel using clips, endoscopically. Conclusions Using these combined procedures, we safely enucleated a huge complicated esophageal SMT. The increased mobility of the tumor after creating the submucosal tunnel contributed to the minimal defect in the muscular layer and prevented injury to the esophageal mucosa, possibly leading to fewer postoperative complications such as esophageal stenosis and local infection.

There have been few reports regarding the improvement of hyperammonemic hepatic encephalopathy after the extirpation of a large uterine leiomyoma. We present a case of a 53-year-old postmenopausal woman who experienced a clouding of consciousness. She had been suffering from mild hepatitis and a large uterine leiomyoma. On admission, she had experienced constipation for seven days and exhibited a high serum ammonia level (251 μg/dL). She was diagnosed with liver cirrhosis as a result of autoimmune hepatitis, combined with Sjogren's syndrome. A total hysterectomy was performed 29 days after admission. Severe diarrhea lasted for three days after surgery. By the sixth postoperative day, the patient's consciousness level had normalized and her serum ammonia level had fallen to 47 μg/dL. Although the true mechanism of hyperammonemia in this case is unclear, we speculate that organic constipation following chronic obstruction of the colon might have played a role in the development of the condition.

There have been few reports regarding the improvement of hyperammonemic hepatic encephalopathy after the extirpation of a large uterine leiomyoma. We present a case of a 53-year-old postmenopausal woman who experienced a clouding of consciousness. She had been suffering from mild hepatitis and a large uterine leiomyoma. On admission, she had experienced constipation for seven days and exhibited a high serum ammonia level (251 μg/dL). She was diagnosed with liver cirrhosis as a result of autoimmune hepatitis, combined with Sjögren's syndrome. A total hysterectomy was performed 29 days after admission. Severe diarrhea lasted for three days after surgery. By the sixth postoperative day, the patient's consciousness level had normalized and her serum ammonia level had fallen to 47 μg/dL. Although the true mechanism of hyperammonemia in this case is unclear, we speculate that organic constipation following chronic obstruction of the colon might have played a role in the development of the condition.

An 81 year-old woman whose chief complaint was fever and general fatigue was admitted to our hospital in Kamiamakusa City, Kumamoto Prefecture in October 2013. She was suspected to have Japanease spotted fever, which is a local pandemic disease in Kamiamakusa, because wide-spreaded skin erythema appeared on the palms of her hands and soles of her feet several days after admission. Though there was a delay of more than 6 days after onset, we treated her with minocycline (MINO) and levofloxacin (LVFX). Unfortunately, she died following the occurrence of disseminated intravascular coagulation (DIC). We could conclude that the delay of proper treatment was most related to her death. In addition, despite of the severity of the disease, cases in whom treatment, survival cases were likely to treat with MINO could be started in the early stage (that is, within 5 days after onset) were likely to survive our hospital. Rickettsia japonica was detected from genetic (PCR analysis from blood and urine) and a serological test in this case. We report herein on the first fatal case of Japanease spotted fever in Kumamoto Prefecture.

A 19-year-old man was admitted to another hospital. Pulmonary suppuration was diagnosed and was treated with antibiotics. However, he developed acute respiratory failure, which required intubation and ventilation with 100% oxygen. After treatment with nitric oxide inhalation and corticosteroid pulse therapy, the patient's condition stabilized and he gradually regained a satisfactory pulmonary function. He was discharged about 3 months after admission with a pulmonary function close to normal. Approximately 1 month later, the patient was admitted to our hospital because of a 2-week history of fever and chest and ocular pain. A chest radiograph obtained upon admission showed a nodule with a cavity in the upper lobe of the right lung. Pulmonary suppuration was again suspected, and antibiotics were given. The fever persisted and chest radiograph on hospital day 19 showed marked extension of the nodules. At that time, the patient complained of nasal obstruction and hoarseness and his sclera showed intense congestion, indicating episcleritis. Wegener's granulomatosis was diagnosed on the basis of the clinical picture, PR3-ANCA titer (63 EU) and nasal biopsy findings. After treatment with prednisolone and cyclophosphamide, his condition stabilized, and he recovered gradually. However, his condition remains poor despite continued therapy. This is an extremely rare case of Wegener's granulomatosis presenting as severe acute respiratory failure.

Milk vetch dwarf virus (MDV) is a member of the proposed genus Nanovirus, and its genome is composed of multiple, circular ssDNA components of about 1 kb. We have cloned and sequenced ten ssDNA components and designated them MDV-C1 to C10. Each DNA component contains one potential major open reading frame, and contains a putative stem-loop structure in the non-coding region. Notably, four components (C1, C2, C3 and C10) encode distinct replication-associated (Rep) proteins of 33 kDa, which show only limited (42-57%) amino acid identity. The six other components encode proteins with calculated molecular masses ranging from 12.7 to 19.7 kDa. Comparison of the sequences with those of other nanoviruses reveals that MDV is closely related to faba bean necrotic yellows virus (FBNYV) and subterranean clover stunt virus (SCSV). Six putative MDV genome products, including one Rep and five non-Rep proteins, show high (70.4-90.9%) amino acid identity to the corresponding six FBNYV proteins, whereas two other Rep proteins encoded by MDV-C2 and C3 are 82.3% and 73.0% identical to those encoded by SCSV-C2 and C6, respectively. These results indicate that MDV, FBNYV and SCSV have diverged from a common origin, which had multiple Rep components. In addition, the putative proteins encoded by MDV-C4 and its homologues contain a consensus retinoblastoma-binding motif, suggesting that they may be involved in controlling the host cell cycle.

Growth disorders induced by long term steroid hormone treatment are well known. We present here three cases of nephrotic syndrome treated with GH for severe short stature induced by long term steroid hormone therapy. Steroid hormone on alternate days (30 mg of predonisolone or 24 mg of methylpredonisolone) simultaneously for the treatment of three patients with nephrotic syndrome was necessary. Height growth before the beginning of the GH therapy was 1.5 cm, 3.0 cm and 2.6 cm per year. Height growth one year after the beginning of the GH therapy was 6.7 cm, 7.6 cm and 7.4 cm per year, respectively. Our data suggest that GH therapy is effective and safe for some cases of severe short stature patient with nephrotic syndrome.