Risk Factors that Predict Levothyroxine Medication after Thyroid Lobectomy.

CONTEXT AND OBJECTIVE: The risk of needing lifelong thyroid hormone supplementation is an important factor affecting treatment decisions for both patients and clinicians ahead thyroid lobectomy. The purposes of this study were to assess the predictive factors of levothyroxine medication after thyroid lobectomy. METHODS: We retrospectively reviewed 252 patients who had undergone lobectomy for benign thyroid nodules between April 2009 and April 2017. We conducted two independent analyses: patients who started taking levothyroxine after surgery were compared with those who did not, and patients who did not need levothyroxine at last follow-up were compared with those who required continued treatment. We investigated the correlations of patient clinicopathological characteristics and levothyroxine medication after lobectomy. RESULTS: Ninety-eight patients started levothyroxine after surgery. Of these, 34 patients successfully ceased medication and 64 patients continued treatment as of their last follow-up. In multivariate analysis, older age and preoperative TSH ≥2.0mIU/L were associated with levothyroxine initiation after surgery. In terms of continuity of levothyroxine, both older age and TSH ≥ 3.0mIU/L showed a significant correlation with continuous medication. We created a risk-scoring system to predict likelihood of starting and maintaining levothyroxine using the two significant factors in each comparison. A risk score of 3 or more indicated an increased risk of starting levothyroxine (specificity = 81.8%; sensitivity = 48.0%). A risk score of 3 or more indicated increased risk of continuous medication, (specificity = 94.2%; sensitivity = 35.9%). CONCLUSIONS: Greater age and higher preoperative TSH levels correlated with initiation and continuity of levothyroxine medication after lobectomy.

Thyroid FNA cytology in Asian practice-Active surveillance for indeterminate thyroid nodules reduces overtreatment of thyroid carcinomas.

Although Asian thyroid practices have implemented the American Thyroid Association guidelines, significant deviations in actual risk of malignancy (ROM) have been reported. With review of the literature from Asia, the authors examine the underlining reasons for actual ROMs reported in Asia being so different from western practice based on the author's perspective. Although the most popular diagnostic system for thyroid cytology used in Asian countries is the Bethesda system, the Japan Thyroid Association published clinical guidelines, including a national reporting system for thyroid cytology, to adapt conservative clinical management (active surveillance and strict triage patients for surgery) for low-risk thyroid carcinomas. As less aggressive clinical management is favoured in Asian societies, strict triage of patients with indeterminate thyroid nodules for surgery is usually applied, which ultimately reduces overtreatment of indolent thyroid tumours. As a result, low resection rates and high ROMs for indeterminate nodules were achieved in Asian practices using the same Bethesda system. Recently, borderline thyroid tumours were introduced in the thyroid tumour classification and significant decreases in ROMs have been reported in the indeterminate categories in western practice. However, ROM of indeterminate nodules remained high in Asian practice even after borderline tumours were deemed benign. These results suggested that the diagnostic threshold of papillary thyroid carcinoma-type nuclear features varied among practices (stricter in Asia than in western practice), and diagnostic surgery was not performed for a significant number of indeterminate nodules with benign clinical features in Asian practice, resulting in low rates of borderline tumours in surgically-treated patients.

The distance between the carina and the distal margin of the right upper lobe orifice measured by computerised tomography as a guide to right-sided double-lumen endobronchial tube use.

Our hypothesis was that the incidence of malposition of a right-sided double-lumen endobronchial tube and right upper lobe collapse may increase when the distance between the carina and the distal margin of the right upper lobe orifice is less than 23 mm, measured from a computerised tomography scan. A total of 76 patients undergoing left-sided thoracic surgery were enrolled. Patients with a measured distance of <23 mm (n=38) were compared with age-, sex- and body mass index-matched patients with a distance≥23 mm (n=38). Right-sided double-lumen endobronchial tubes were used universally. We monitored endobronchial tube malposition and incidence of right upper lobe collapse throughout surgery. There was a significantly higher incidence of bronchial cuff herniation in patients with a distance<23 mm in both the supine position and the lateral decubitus position (p<0.001). The incidence of intra-operative malposition in the <23 mm group was also significantly higher than in the ≥23 mm group (31 (82%) vs 8 (21%), respectively, p<0.001). Right upper lobe collapse was detected postoperatively in five patients (13%) in the distance<23 mm group, compared to none in the ≥23 mm group. We recommend that the distance between the carina and the distal margin of the right upper lobe bronchus should be routinely measured on the pre-operative computerised tomography scan, and if it is <23 mm, consideration should be given to using a left-sided endobronchial double-lumen tube in preference to a right-sided one.

Safety and efficacy of trastuzumab biosimilar plus irinotecan or gemcitabine in patients with previously treated HER2 (ERBB2)-positive non-breast/non-gastric solid tumors: a phase II basket trial with circulating tumor DNA analysis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) (ERBB2)-directed agents are standard treatments for patients with HER2-positive breast and gastric cancer. Herein, we report the results of an open-label, single-center, phase II basket trial to investigate the efficacy and safety of trastuzumab biosimilar (Samfenet®) plus treatment of physician's choice for patients with previously treated HER2-positive advanced solid tumors, along with biomarker analysis employing circulating tumor DNA (ctDNA) sequencing. METHODS: Patients with HER2-positive unresectable or metastatic non-breast, non-gastric solid tumors who failed at least one prior treatment were included in this study conducted at Asan Medical Center, Seoul, Korea. Patients received trastuzumab combined with irinotecan or gemcitabine at the treating physicians' discretion. The primary endpoint was the objective response rate as per RECIST version 1.1. Plasma samples were collected at baseline and at the time of disease progression for ctDNA analysis. RESULTS: Twenty-three patients were screened from 31 December 2019 to 17 September 2021, and 20 were enrolled in this study. Their median age was 64 years (30-84 years), and 13 patients (65.0%) were male. The most common primary tumor was hepatobiliary cancer (seven patients, 35.0%), followed by colorectal cancer (six patients, 30.0%). Among 18 patients with an available response evaluation, the objective response rate was 11.1% (95% confidence interval 3.1% to 32.8%). ERBB2 amplification was detected from ctDNA analysis of baseline plasma samples in 85% of patients (n = 17), and the ERBB2 copy number from ctDNA analysis showed a significant correlation with the results from tissue sequencing. Among 16 patients with post-progression ctDNA analysis, 7 (43.8%) developed new alterations. None of the patients discontinued the study due to adverse events. CONCLUSIONS: Trastuzumab plus irinotecan or gemcitabine was safe and feasible for patients with previously treated HER2-positive advanced solid tumors with modest efficacy outcomes, and ctDNA analysis was useful for detecting HER2 amplification.

Increased incidence of colorectal malignancies in renal transplant recipients: a case control study.

This study was to evaluate the frequency of colorectal neoplasia in renal transplant recipients and to investigate the association with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection. We compared the frequency of colorectal neoplasia among renal transplant recipients with that of the healthy subjects. Specimens of colorectal neoplasia were examined for EBV and CMV using in situ hybridization and immunohistochemistry, respectively. Of 796 renal transplantation cohorts, 315 were enrolled. The frequency of colorectal neoplasia among the patients was 22.9%. Compared with the healthy subjects, the odds ratio (OR) for advanced adenoma was 3.32 (95% CI, 1.81-6.10). The frequency of cancer among the patients was 1.9% (OR, 12.0; 95% CI, 1.45-99.7). A long interval between transplantation and colonoscopy was a significant factor in the development of advanced colorectal neoplasia. EBV positivity was detected in 30.6% of colorectal neoplasia specimens from renal transplant recipients, which was higher than that for the controls (p = 0.002). CMV was not detected in any lesions of patients or controls. In conclusion, renal transplant recipients have a significantly increased risk of advanced colorectal neoplasia. EBV was more frequently found in specimens of advanced colorectal neoplasm obtained from the renal transplant recipients.

Pathological validation of supracricoid partial laryngectomy in laryngeal cancer.

OBJECTIVES: To validate pathologically whether supracricoid partial laryngectomy is an oncologically sound procedure in cases with invasion of the thyroid cartilage, paraglottic space, pre-epiglottic space, anterior commissure, or subglottis. DESIGN: A retrospective review of case notes was performed. SETTING: Patients treated at a single institute in the Republic of Korea. PARTICIPANTS: Sixty-three patients who underwent supracricoid partial laryngectomy for laryngeal squamous cell carcinoma between June 1994 and May 2005 who were followed for at least 2 years. MAIN OUTCOME MEASURES: Local control and overall survival rates. Pathological invasion of the thyroid cartilage, anterior commissure, pre-epiglottic space, paraglottic space, or subglottis was also investigated as a cause of recurrence. Prognostic factors for local control and survival were evaluated with univariate and multivariate models. RESULTS: Invasion of the anterior commissure, paraglottic space, thyroid cartilage, pre-epiglottic space, or subglottis had no significant impact on the recurrence or overall survival rates. The presence of a positive resection margin was significantly associated with recurrence in the univariate and multivariate analyses (P = 0.026, 0.028, respectively). When considering the prognostic factors influencing survival, the univariate analysis showed that N stage, a positive resection margin and recurrence had significant influences on the overall survival rate (P = 0.010, 0.0004 and 0.000 respectively). In the multivariate analysis, only recurrence affected the survival rate (P = 0.002). CONCLUSION: Supracricoid partial laryngectomy can be used with oncological safety in selected cases of laryngeal cancer with invasion of the anterior commissure, thyroid cartilage, pre-epiglottic space, paraglottic space, or subglottis.

Decentration and tilt: silicone multifocal versus acrylic soft intraocular lenses.

PURPOSE: To compare differences in decentration and tilt between a silicone multifocal and an acrylic intraocular lens (IOL) by evaluating postoperative changes. SETTING: Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Korea. METHODS: Forty eyes of 20 patients with IOL implantation were randomized into 2 groups according to IOL type: 3-piece silicone multifocal IOL or 3-piece acrylic IOL. All lenses were implanted in the capsular bag through a clear corneal incision after continuous curvilinear capsulorhexis and phacoemulsification. The amount of the decentration and the degree of the tilt of each IOL were measured using the EAS-1000 anterior eye segment analysis system 1 day and 1 and 2 months after surgery. RESULTS: No significant difference in decentration and tilt was found among the 3 follow-ups or between lens types. CONCLUSION: Neither IOL decentration nor tilt showed significant progression up to 2 months in eyes with a silicone multifocal or acrylic IOL when the IOLs were placed properly in the capsular bag. The amount of decentration and tilt was similar between lens types.

An unusual presentation of aggressive epithelial-myoepithelial carcinoma of the nasal cavity with high-grade histology.

BACKGROUND: Epithelial-myoepithelial carcinoma is an uncommon, low-grade carcinoma that generally occurs in the salivary glands. A few cases of epithelial-myoepithelial carcinoma arising in the nasal cavity have been reported. We describe a unique case of aggressive epithelial-myoepithelial carcinoma in the nasal cavity. CASE REPORT: A 36-year-old woman presented with a mass in her left nasal cavity. Histopathological evaluation revealed it to be an epithelial-myoepithelial carcinoma with overt nuclear atypia, frequent mitoses and necrosis. The tumour recurred in the contralateral nasal cavity 15 months following primary excision. Medial maxillectomy and radiation therapy were performed. Seven-month follow up revealed extensive bone metastases. CONCLUSION: We report a rare case of aggressive epithelial-myoepithelial carcinoma in the nasal cavity, with high-grade histology.

Impact of tumor infiltration pattern into the surrounding tissue on prognosis of the subserosal gastric cancer (pT2b).

BACKGROUND: The aim of this study was to clarify the impact of infiltration pattern on prognosis in patients with gastric carcinoma invading subserosa. METHODS: Clinicopathologic findings in patients with ssgamma pattern (n = 144) were compared with those in patients with ssalpha/ssbeta cancers (n = 222). Prognostic factors of pT2b patients were analyzed by univariate and multivariate analysis. RESULTS: Compared with the ssalpha/beta group, ssgamma gastric cancer exhibited more frequent undifferentiated histology, disseminated lymph node metastasis and perineural invasion. Frequency of postoperative peritoneal recurrence was significantly higher in ssgamma gastric cancer (P < 0.05). The 5-year survival rate for patients with ssgamma gastric cancer was significantly lower compared with ssalpha/beta group (63.2% vs. 74.8%, respectively; P < 0.05). Lymph node metastasis, vein invasion and infiltrative pattern (ssgamma) were significant independent prognostic factors affecting survival in pT2b patients. CONCLUSION: In patients with gastric cancer invading the subserosa, infiltrative type growth pattern is closely related to carcinomatosis and poorer prognosis.

Case report. Lipomatous haemangiopericytoma (fat-forming solitary fibrous tumour) involving the perineum: CT and MRI findings and pathological correlation.

Lipomatous haemangiopericytoma (a fat-forming solitary fibrous tumour) is a rare soft-tissue tumour histologically characterized by haemangiopericytomatous vasculature and the presence of mature adipocytes. We report the CT and MRI findings of a case of lipomatous haemangiopericytoma involving the perineum. CT showed a well-circumscribed soft-tissue density mass containing a small area of fat density and a punctuate calcification. On MR images, the mass was mostly isointense to the muscle on T(1) weighted images, with heterogeneous signal intensity on T(2) weighted images, and showed strong contrast enhancement except for the fatty and dense collagenous components. This is the first case report of imaging findings of a lipomatous haemangiopericytoma in the radiological literature. Although rare, lipomatous haemangiopericytoma should be considered as a differential diagnosis of fat-containing, hypervascular soft-tissue tumours with variable signal intensity on T(2) weighted images.

MRI features of ovarian fibromas: emphasis on their relationship to the ovary.

AIM: To evaluate the magnetic resonance (MR) imaging features of ovarian fibromas, emphasizing the presence and shape of the ovary on the same side of the fibroma. MATERIALS AND METHODS: MR images from 23 patients with 24 histologically proven ovarian fibromas were reviewed by two radiologists. Eleven were pre-menopausal and 12 were postmenopausal. The presence and shape of the ovarian tissue on the same side of the fibroma were evaluated on T2-weighted MR images. RESULTS: In 11 (46%) of the 24 ovarian fibromas, the ipsilateral ovary was detected on T2-weighted images. The ovary was crescent-shaped along the periphery of the fibroma in six (55%) of 11 fibromas and had a normal, oval shape in five (45%). Of these five tumours, the ovary was connected to the fibromas by a pedicle-like structure in three and was closely attached to the periphery of the fibromas in two. The ipsilateral ovary was detected in 10 (83%) of 12 fibromas in pre-menopausal patients, and in one (8%) of 12 fibromas in postmenopausal patients. There was a statistically significant difference (p=0.001) in the presence of detectable ipsilateral ovary between pre-menopausal and postmenopausal women. CONCLUSIONS: Detection of the remaining ovary on the same side as the fibroma is not unusual on MRI, especially in pre-menopausal women, and the shape of the ovary may be normal in cases of fibromas with exophytic growth from the periphery of the ovary.

Transient trisomy 8 abnormality in Philadelphia-negative cells during imatinib mesylate treatment of chronic myelogenous leukemia.

We investigated chronic myelogenous leukemia (CML) patients who developed trisomy 8 abnormalities in Philadelphia-negative (Ph-) cells during imatinib mesylate treatment to evaluate the clinical outcome and laboratory features. Of the 470 CML patients, 1.5% (n = 7) developed trisomy 8 chromosomal abnormalities in Ph- cells. The median interval of the first trisomy 8 observation was 12 months. Our follow-up cytogenetic evaluations revealed that six of the patients demonstrated a complete or partial cytogenetic response and that all of the six patients revealed no dysplastic changes following a bone marrow examination. Moreover, the percentage of trisomy 8 in metaphase karyotyping has decreased in five of the seven subjects. In conclusion, these results suggest that the emergence of trisomy 8 in Ph- cells is transient and not related to therapy-related myelodysplasia or acute leukemia.

Search for coherent charged pion production in neutrino-carbon interactions.

We report the result from a search for charged-current coherent pion production induced by muon neutrinos with a mean energy of 1.3 GeV. The data are collected with a fully active scintillator detector in the K2K long-baseline neutrino oscillation experiment. No evidence for coherent pion production is observed, and an upper limit of is set on the cross section ratio of coherent pion production to the total charged-current interaction at 90% confidence level. This is the first experimental limit for coherent charged pion production in the energy region of a few GeV.

Evidence for muon neutrino oscillation in an accelerator-based experiment.

We present results for nu(mu) oscillation in the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment. K2K uses an accelerator-produced nu(mu) beam with a mean energy of 1.3 GeV directed at the Super-Kamiokande detector. We observed the energy-dependent disappearance of nu(mu), which we presume have oscillated to nu(tau). The probability that we would observe these results if there is no neutrino oscillation is 0.0050% (4.0 sigma).

Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro.

In this article we present validation of a real-time RT-PCR method to quantitate mRNA expression levels of atrial natriuretic peptide and c-fos in an in vitro model of cardiac hypertrophy. This method requires minimal sample and no postreaction manipulation. In real-time RT-PCR a dual-labeled fluorescent probe is degraded concomitant with PCR amplification. Input target mRNA levels are correlated with the time (measured in PCR cycles) at which the reporter fluorescent emission increases beyond a threshold level. The use of an oligo(dt) magnetic bead protocol to harvest poly(A) mRNA from cultured cells in 96-well plates minimized DNA contamination. We show that the GAPDH gene chosen for normalization of the RNA load is truly invariant throughout the biological treatments examined. We discuss two methods of calculating fold increase: a standard curve method and the DeltaDelta Ct method. Real-time quantitative RT-PCR was used to determine the time course of c-fos induction and the effect of varying doses of four known hypertrophy agents on atrial naturitic factor messenger RNA expression in cultured cardiac muscle cells. Our results agree with published data obtained from Northern blot analysis.

Epstein-Barr virus infection, drug resistance and prognosis in Korean T- and NK-cell lymphomas.

T-cell lymphomas are a biologically heterogeneous group of diseases with varying clinical presentations and outcomes. We tried to understand the effect of Epstein-Barr virus (EBV) on lymphogenesis, prognostic factors and drug resistance of T-cell lymphomas, and to establish their relationship with international prognostic factors. Formalin-fixed paraffin-embedded tissue sections from 35 patients (12 women and 23 men) with T-cell lymphomas were examined to detect the presence of EBV using RNA in situ hybridization for EBV-encoded small nuclear RNA (EBER) 1/2 and immunohistochemical stain for latent membrane protein (LMP)-1. We also tried to establish the expression of p53 and P-glycoprotein (P-gp) using immunohistochemistry. The distribution according to the subgroup was: two T-lymphoblastic lymphomas, 13 NK/T-cell lymphomas, one angioimmunoblastic T-cell lymphoma, 17 peripheral T-cell lymphomas, unspecified, and two anaplastic large cell lymphomas. The EBER was detected in 15 of 35 T-cell lymphomas (42.9%) and among these it was detected in five of 17 nodal lymphomas (29.4%) and 10 of 18 extranodal lymphomas (55.6%). There was close correlation between EBER positivity and NK/T-cell lymphoma (P = 0.032). Expression of LMP was found in a proportion of tumor cells in seven of the 15 EBER-positive cases (46.7%). There was no correlation between EBER expression and complete response (CR rate), but coexpression of EBER and p53 was associated with treatment failure (P = 0.047). The 18 patients (51.4%) with p53 expression had significantly poorer outcomes compared with the 17 patients without p53 expression (CR rate, P < 0.0005; overall survival, P = 0.0102). Twenty of 35 patients (57.1%) were positive for P-gp expression. P-gp expression was significantly associated with treatment failure (P = 0.001) and overall survival (P = 0.0089). Seventeen of 35 patients (48.6%) treated with systemic chemotherapy or radiation therapy achieved a CR after initial treatment. When the prognostic factors were grouped using the international prognostic index, the CR rate was 58.8% for the low risk group, 50.0% for the low-intermediate risk group, 14.3% for the high-intermediate risk group, and 0% for the high risk group. In conclusion, high incidence of EBV was detected among Korean patients with T-cell lymphomas. Our study supports the prediction that patients who express p53 and P-gp have a poorer prognosis than those who do not and this should be considered when treatment strategies for individual patients are selected.

Shunt-independent surgical treatment of middle cranial fossa arachnoid cysts in children.

The best operative intervention for children with arachnoid cysts remains the subject of controversy. Recent reports stress that craniotomy for cyst fenestration is associated with a low incidence of morbidity and mortality and may leave the child shunt-independent. Among a total of 66 intracranial arachnoid cysts operated on in the authors' department from 1985 to 1997, 44 cases (67%) were located in the middle cranial fossa. A higher incidence in the first decade of life (53 cases) and a marked male predominance (45 cases) were recognized. Headache, cranial deformities, symptoms of raised intracranial pressure, and seizures constituted the most frequent features of the clinical presentation. To determine which treatment provides the greatest benefit with the lowest incidence of complications, the records of the 44 patients with arachnoid cysts in the middle cranial fossa were reviewed. The mean age of these patients was 4.6 years (range 0-16 years). Different types of initial surgical procedures were performed. In 33 patients with middle cranial fossa arachnoid cysts (MCFAC) the initial surgery took the form of craniotomy with excision of the cyst walls and fenestration into the basal cisterns. Shunting procedures were performed in 9 patients: cysto-peritoneal shunts (CPS) were placed in 4 patients and ventriculo-peritoneal shunts (VPS), in 3 patients, and cyst excision was performed in addition to CPS in 2 patients. Excision of the cyst membrane alone without fenestration was performed in 2 patients. The initial treatment was successful in terms of reduced symptoms and decreased cyst size, with no additional treatment needed for the cyst, in 79% (26/33) of patients who had undergone excision of the cyst walls and fenestration into the basal cisterns, compared with 66% (6/9) of patients who had undergone shunting procedures. Cyst membrane excision was not successful in any of the patients who underwent this procedure alone. No significant difference in morbidity was noted between these different treatment options. On follow-up CT scan and MRI, cysts of types I and II (Galassi classification) exhibited a steady tendency to reduction or obliteration. These results confirm that radical excision of the outer and inner membranes of the cyst wall with fenestration into the basal cistern is a safe and effective shunt-independent procedure for MCFAC, especially for those of types I and II.

Tumors of the orbit. Pitfalls of the surgical approach in 37 children with orbital tumor.

The authors review their experience with 37 children with orbital tumors, summarizing their surgical techniques, the indications applied, and the pitfalls of each surgical approach. Tumors located in the retro-ocular or intraorbital space were surgically excised through a transcranial approach (28 cases), while for tumors in other sites lateral orbitotomy (5 cases), medial orbitotomy (1 case) and biopsy (3 cases) were performed. A transcranial approach was used for tumors with intracranial extension and for those located in the orbital apex and deep medial orbital compartment. Lateral orbitotomy was used for tumors located in the superior, temporal or inferior compartment of the orbit and those in the lateral apex. A medial orbitotomy was used for tumors located medial to the optic nerve. Outcomes of the surgical intervention varied, depending on the pathology, location and extent of the individual tumors. To obtain optimal exposure and minimize functional deficits, the pitfalls of surgical approaches to orbital tumors are discussed.

Perioperative specific management of blood volume loss in craniosynostosis surgery.

Accurate assessment and replacement of blood loss and fluid-electrolyte deficit during craniosynostosis repair is difficult owing to patient size and the diversity of surgical technique. Forty-three patients undergoing primary craniosynostosis repair over a 10-year period were studied retrospectively to determine blood loss and fluid deficit and to assess blood transfusion practices during both intraoperative and postoperative periods. Blood loss was calculated on the basis of estimated red cell mass (ERCM) and fluid-electrolyte imbalance was investigated with blood samplings. Blood transfusion was considered appropriate if the postoperative or posttransfusion ERCM was within 12% of the preoperative value. Estimated fluid requirement (EFR) was used in 4 ml kg(-1) h(-1) except for neonates. Intraoperatively, 80% of all patients were appropriately managed with respect to blood transfusion and EFR. Postoperatively only 20% of the patients receiving transfusions were transfused appropriately. In 23.3% of these patients (10/43) unexpected respiratory distress developed immediately after their recovery from the anesthesia. With the measurement of estimated blood volume and allowable blood loss, appropriate transfusion could be achieved for the successful treatment of the primary craniosynostosis.

Indications of neutrino oscillation in a 250 km long-baseline experiment.

The K2K experiment observes indications of neutrino oscillation: a reduction of nu(mu) flux together with a distortion of the energy spectrum. Fifty-six beam neutrino events are observed in Super-Kamiokande (SK), 250 km from the neutrino production point, with an expectation of 80.1(+6.2)(-5.4). Twenty-nine one ring mu-like events are used to reconstruct the neutrino energy spectrum, which is better matched to the expected spectrum with neutrino oscillation than without. The probability that the observed flux at SK is explained by statistical fluctuation without neutrino oscillation is less than 1%.