Palpable Adnexal Mass Research Articles

Progressive ovarian sertoli – leydig cell tumor: case report

Introduction: Ovarian Sertoli – Leydig Cell Tumor (SLCT) are one of sex cord tumor that has incidence rate less than 0,2% of all ovarian tumors. It occurs predominantly in second and third decades of lifetime. It has characteristics mostly low–grade malignant although poorly differentiated type may behave more aggressively. Clinical characterstic of ovarian SLCT usually hormonal changes, nevertheless in patients without hormonal changes, the manifestation of the disease consists of abdominal pain and abdominal enlargement, and palpable adnexal mass on physical diagnostic. Case: a 52 years woman that has been undergo right salpingooforectomy 5 months prior with PA result shows poorly differentiated sertoli – leydig cell tumor, and refusing to chemotherapy. She came with chief complaint of abdominal enlargement since 3 months accompanied with lower abdominal pain 2 weeks prior. Ultrasound examination shows cystic ovarian neoplasm with solid part size 9 x 9 x 9 cm from left adnexa. Tumor markers that arise are Alpha–Fetoprotein (AFP) 52 ng/mL and Lactate Dehydrogenase (LDH) = 432 U/mL which correspond to sex cord tumor. She has undergone Laparotomy Total Abdominal Hysterectomy Left Salpingooforectomy and chemotherapy afterward. Conclusion: Ovarian Sertoli – Leydig Cell Tumors (SLCT) are a rare sex cord ovarian tumor that may behave more aggressively as it poorly differentiated. It has manifestations of hormonal changes and also abdominal enlargement.

ODP537 A 1.6cm Androgen Secreting Ovarian Leydig Cell Tumor Evades Detection on Multiple Imaging Modalities

Abstract A 1.6cm Androgen Secreting Ovarian Leydig Cell Tumor Evades Detection on Multiple Imaging Modalities Background: Leydig Cell Tumors can present with marked virilization and yet may evade detection with common imaging modalities. This is a case of a patient with hyperandrogenism due to a 1.6cm ovarian Leydig cell tumor that could not be detected on transvaginal ultrasound, contrast enhanced CT or MRI with contrast. Clinical Case: A 61-year woman presented with virilization. She had a history of a right-sided borderline serous ovarian tumor status post right oophorectomy 23 years prior to presentation and a hysterectomy 16 years prior to presentation. She followed up with gynecologic-oncology for several years but eventually stopped as her condition was stable. On re-presenting to establish care with a gynecologist she complained of increased hair growth on her face, abdomen and buttocks as well as hair loss on the front and top of her scalp. On exam, she was noted to have clitoromegaly with no palpable adnexal masses. Labs revealed total testosterone 398ng/dL (8-60ng/dL), free testosterone 9.15ng/dL (0. 06–0.87ng/dL), 17-hydroxyprogesterone 204ng/dL (<51ng/dL) CA-125 of 6.2U/mL (<=38.1U/mL) and DHEAS 23.1mcg/dL (18.9 – 205mcg/dL). Transvaginal ultrasound showed a left ovary of 3cc with no mass or abnormality. She was referred to endocrinology and a CT abdomen and pelvis with contrast was obtained that again showed no adnexal mass but was notable for a 7mm isoattenuating nodule in the left adrenal gland. Additional labs were obtained including 24 hour urinary cortisol and metanephrines, late night salivary cortisol and serum aldosterone and renin activity, all of which were within normal limits. Suspicion remained high for an ovarian source of the hyperandrogenism so a pelvic MRI with and without contrast was performed which showed a normal appearing left ovary measuring 2.3cm×4.2cm×1.8cm. She was referred to gynecologic-oncology and it was decided to proceed with a left oophorectomy. This was performed and the pathology revealed a 1.6cm Leydig cell tumor in the left ovary. Testosterone and 17-hydroxyprogesterone subsequently normalized when checked seven weeks post-op. Conclusion Leydig cell tumors are rare ovarian tumors often presenting with hyperandrogenism in postmenopausal patients and can be difficult to identify on imaging. A review of published case reports revealed 8 cases in which Leydig cell tumors ranging from 1.2cm to 4.6cm could be detected using one of the imaging modalities employed in this case. There were 9 reports of tumors ranging from 0.8cm to 2cm that evaded detection on imaging. When significant hyperandrogenism is present in a postmenopausal patient a strong suspicion for an ovarian source should be maintained even when imaging is apparently normal. Presentation: No date and time listed

Diagnostic Accuracy of B-mode USG and Doppler Scan for Ovarian Lesions.

Ultrasonography (USG) is considered as the primary imaging modality for confirmation of ovarian mass and to differentiate them in to benign or malignant. The present study was conducted with the aim to evaluate accuracy of B- mode USG and Doppler scan (Colour Doppler + Spectral Doppler) for ovarian lesions. The patients included in the study were from those referred with either palpable adnexal mass or incidentally detected adnexal masses. Total 250 women were evaluated by USG, Doppler scan. Only fifty patients who had true ovarian mass intraoperatively and on histopathology were included in study, rest masses were excluded. Study parameters were morphological indexing on B- Mode USG, flow study, vessel arrangement, and vessel morphology and vessel location in Colour Doppler and resistive index and pulsatility index in spectral Doppler. Total 50 women were included in present study. Out of these 46% were pre-menopausal while 54% were menopaused women, 66.7% of post-menopausal women had malignant ovarian masses compared to 8.7% of premenopausal. Sensitivity, specificity, positive predictive value and negative predictive value of B-Mode USG for ovarian masses were 94.44%, 48.15%, 54.84% and 92.86% respectively, with p-value = 0.007, while sensitivity, specificity, positive predictive value and negative predictive value of Doppler scan were 85%, 90%, 85% and 90% respectively, with p-value = 0.0001. USG and its different techniques are accepted as the primary imaging modality for early stage diagnosis of an ovarian malignancy. Statistical analysis suggests that Doppler Scan (Colour + Spectral) was more accurate (88%) than B-Mode USG (67%), but author is in view that both of these modalities should be used in conjunction to screen the ovarian lesions.

Uterine leiomyosarcoma and Leser-Trélat sign

In December, 2010, a 79-year-old nulliparous woman presented to our outpatient clinic for investigation of a 6 month history of postmenopausal bleeding. She had experienced menopause at the age of 46 years and had never used hormonal replacement therapy. She had had surgery for a gastric ulcer when she was 39 years old and had been taking anti-hypertensives since 1990. She reported that she had had a few, small (<1 cm) warty lesions on her body for 20 years and that a rapid increase in their size and number had coincided with the postmenopausal bleeding. On examination, she had many seborrhoeic keratoses on her trunk and face consistent with the Leser-Trelat sign. Digital vaginal examination showed a 9 cm mobile uterus with no palpable adnexal masses. An ultrasound of the vagina showed an intracavitary lesion with myometrial invasion, highly suggestive of endometrial cancer. MRI of the pelvis showed a 5 cm, irregular, heterogeneous tumour of the uterine body that bulged into the uterine cavity. There was no lymphadenopathy. Full blood count, urea and electrolytes, liver function tests, radiography of the chest, and sonography of the abdomen were all normal. Pathological examination of a biopsy sample of the endometrium led to a diagnosis of leiomyosarcoma, and we did a total abdominal hyster ectomy and bilateral salpingo-oophorectomy. Gross examination of the specimen showed a 6·5 × 4 cm irregular, friable, infi ltrating tumour, which was tanwhite on section. Histological examination showed irregular fascicles of spindled cells with moderate anisonucleosis and irregular nucleoli. Mitotic index was greater than 10 per high powered fi eld and deep infi ltration reached more than four-fi fths of the uterine wall. The tumour was stage IC according to the Federation of Gynecology and Obstetrics (FIGO) staging Lancet 2013; 381: 88

Determining Which Adnexal Masses Are Likely to Be Malignant

As pelvic imaging with vaginal ultrasound and other modalities becomes more common, women's health clinicians frequently encounter patients with adnexal masses. In a study of 395 women (mean age, 52; 55% postmenopausal) with a palpable adnexal mass on pelvic examination who ultimately underwent surgery, investigators correlated vaginal sonographic findings (cystic, …

Combined positron emission tomography and computed tomography for the detection of recurrent ovarian mucinous adenocarcinoma

Background The role of combined positron emission tomography and computed tomography (PET-CT) in the diagnosis of recurrent ovarian mucinous adenocarcinoma is uncertain because of previous reports that PET has limited sensitivity in the detection of mucinous neoplasms. Case A 71-year-old white woman presented with complaints of right lower quadrant pain and a palpable adnexal mass. Physical examination and transvaginal ultrasonography revealed a 12 × 13 cm cystic mass in the left side of the pelvis. Exploratory laparotomy, optimal tumor-reductive surgery, total abdominal hysterectomy, bilateral salpingo-oophorectomy, appendectomy, and omentectomy were performed. The diagnosis was FIGO stage IIIC well-differentiated ovarian mucinous adenocarcinoma. The patient was treated with 6 cycles of carboplatin and paclitaxel. Four months after completing chemotherapy, the patient was noted to have an elevated serum CA125 level (72 U/mL), being otherwise asymptomatic. Findings on abdominal and pelvic CT were compatible with postsurgical changes. PET-CT was performed and revealed increased metabolism along the posterior aspect of the right rectus abdominis muscle and abutting the anterior wall of an adjacent loop of bowel. Conclusion PET-CT may identify clinically occult recurrent ovarian mucinous adenocarcinoma.

Epithelioid trophoblastic tumour: report of a case in the fallopian tube

A case of epithelioid trophoblastic tumour (ETT), occurring in a fallopian tube of a 39-year-old woman, is reported. The patient presented with a positive pregnancy test, but continued to have 'periods'. A palpable right adnexal mass was noted that was confirmed on ultrasound. The mass was removed together with the uterus, omentum and associated ovary. Careful examination of the uterus revealed no evidence of either an antecedent tumour or intra-uterine pregnancy. Histologically, the tubal mass displayed sheets and islands of large, relatively uniform, mitotically active polyhedral cells, with surrounding necrosis. The immunoprofile of the tumour was atypical in that alpha-inhibin and epidermal growth factor were weakly positive, but other results were consistent with the diagnosis of ETT. The patient received a foreshortened course of standard EMACO (etoposide, actinomycin-D, methotrexate, vincristine, and cyclophosphamide) combination chemotherapy for high-risk gestational trophoblastic disease. Serum beta-hCG fell from a pre-operative level of 52 000 U/mL to non-pregnant levels within two courses and she remains well and disease-free 12 months post-diagnosis.

Clinical management potential tumours of low malignancy

Approximately 3000 American women are diagnosed with borderline ovarian tumours annually. Common signs and symptoms include abdominal/pelvic pain and a palpable adnexal mass. Pelvic sonography may be helpful, although not specific, in the diagnosis. Serum CA 125 is abnormal in only about 50% of patients. Primary surgery is the principal treatment; it consists of resection of the primary tumour(s) (frequently in the form of fertility-sparing surgery), frozen-section analysis and consideration of comprehensive surgical staging. The role of surgical staging remains unclear; further research is necessary. For patients with stage I disease, surgery alone is the standard. For patients with stage II–IV disease (with non-invasive or invasive peritoneal implants), the role of post-operative therapy remains unclear. Approximately 20–30% of the latter will relapse, frequently after several years. Most so-called recurrences are low-grade carcinomas. Potential predictive or prognostic factors include age, FIGO stage, residual disease and the micropapillary pattern. After fertility-sparing surgery, most patients retain normal reproductive function.

Acute pelvic inflammatory disease in a gynecological casualty setting

This paper presents a prospective study on the validity of clinical diagnostic criteria of acute pelvic inflammatory disease (PID) in Sri Lanka over a period of 15 months. The study assessed 1817 consecutive gynecological admissions and acute PID was diagnosed according to the established clinical criteria. Clinical signs and symptoms of PID among women aged 18-22 years include abdominal pain abnormal vaginal discharge urinary symptoms irregular bleeding vomiting rectal symptoms fever an erythrocyte sedimentation rate of 15 mm/hour or higher abnormal adnexal tenderness and a palpable adnexal mass. The gynecological casualty admissions categorized into one of the following clinical groups are outlined. The study identified 29 visually confirmed acute PID cases with 41 patients with acute PID in the series. This indicates that there is a 2.26% acute PID incidence in the casualty gynecological setting (95% confidence interval 1.91-2.61). When the clinical diagnosis was equivocal the positive value for acute PID diagnosis was 76%. This indicates that if laparoscopy had not been used to confirm acute PID 24 patients with equivocal PID would have been overtreated with expensive broad-spectrum antibiotics. This article emphasizes that in the absence of contraindications and availability of facilities laparoscopy is very useful; and at the same time treatment of clinically equivocal cases must not be delayed as this may lead to serious consequences.

Pelvic Inflammatory Disease — an Evidence-based Approach to Diagnosis

Pelvic inflammatory disease (PID) is inflammation of the upper female genital tract and related structures. It may arise from blood borne infection, such as tuberculosis, or from spread from an area of intra-abdominal sepsis, but in practice these are rare sources and most cases result from ascending infection from the lower genital tract. PID may arise de novo or may be secondary to a breach of the cervical mucous barrier, in particular by surgical instrumentation and the events of pregnancy. There is a wide range of pathology from mild endometritis to generalized peritonitis. PID is important economically and socially because of its sequelae, tubal infertility, ectopic pregnancy and chronic pelvic pain.1 It is thus a major cause of short-term and long-term morbidity and the cost of assisted reproduction techniques to overcome tubal infertility is high. Infertile women and those with chronic pelvic pain may suffer considerable psychological distress. In addition, ectopic pregnancy still results in a number of maternal deaths every year. Traditionally, the diagnosis of PID has been based on the finding of bilateral tenderness of the uterine appendages in women complaining of lower abdominal or pelvic pain. Associated symptoms include deep dyspareunia, menstrual disturbances, vaginal discharge, urinary and bowel symptoms and features suggestive of a systemic illness, such as fevers and malaise. Associated physical signs include abdominal tenderness, pain on moving the cervix (excitation pain) and the presence of palpable adnexal masses. There may be objective signs of fever and tachycardia.

MR appearance of ruptured tubal ectopic pregnancy

The usual clinical course of ectopic pregnancy is punctuated by the onset of severe abdominal pain when rupture of the Fallopian tube leads to a pelvic haemorrhage [1]. Spontaneous rupture occurs in most patients, although the immediate cause of rupture may be trauma associated with coitus or vigorous bimanual examination [2,3]. The diagnosis is suggested by the typical history and physical examination revealing an overdue menstrual period and a palpable adnexal mass [4]. Torsion of the pedicle of ovarian tumors may simulate ruptured ectopic pregnancy clinically. The serum b-hCG determinations are crucial in diagnosis of ectopic pregnancy. However, imaging examinations make the diagnosis probable while awaiting confirmatory laboratory results. We describe magnetic resonance (MR) findings in a 25-year-old woman with acutely ruptured tubal ectopic pregnancy.

ENDOMETRIAL CANCER, CERVICAL CANCER, AND THE ADNEXAL MASS

Cancers of the endometrium, cervix, and ovaries account for nearly 25,000 annual deaths among women in the United States. In recent years, better understanding of the causes and risk factors associated with gynecologic malignancies has contributed to more effective screening and early diagnosis. Abnormal uterine bleeding, a palpable adnexal mass, or vague abdominal complaints in women older than 40 can be signs of cancer. Regular pelvic examination, combined with appropriate use of the Papanicolaou's smear, endometrial biopsy, transvaginal sonography, and other tests, is recommended.

Acute pelvic inflammatory disease: Associations of clinical and laboratory findings with laparoscopic findings

To assess the relation of clinical variables and laboratory data to pelvic laparoscopic observations of tubal occlusion, adnexal adhesions, and peritoneal exudate in women with acute salpingitis. Clinical and laboratory evaluations were performed systematically before laparoscopy in 155 women with suspected acute pelvic inflammatory disease (PID), 82% of whom proved to have acute salpingitis confirmed with laparoscopy. Laparoscopic findings were scored in three categories (tubal patency, adhesions, and exudate.) Two general categories of laparoscopic findings were present: 1) tubal occlusion and moderate to severe adhesions in 30 women, and 2) pelvic-abdominal exudate in 27 women. In the remaining 16 women, these laparoscopic findings occurred alone or in other combinations. Among women with acute salpingitis, tubal occlusion was associated positively with older age, palpable adnexal mass, and moderate to severe pelvic adhesions; negative associations were found with abdominal rebound tenderness, mean abdominal-pelvic tenderness score, pelvic-abdominal exudate, and isolation of either Neisseria gonorrhoeae or Chlamydia trachomatis. Moderate or severe pelvic adhesions were associated positively with increased duration of abdominal pain (5 versus 3 days) compared with limited or no pelvic adhesions, but they were associated negatively with mean abdominal-pelvic tenderness score and with pelvic-abdominal exudate (47% versus 73%). Free exudate in the pelvis or abdomen as compared with limited or no exudate was associated positively with abdominal rebound tenderness (86% versus 65%), abdominal-pelvic tenderness score, elevated white blood cell count (83% versus 52%), and recovery of N gonorrhoeae (79% versus 57%). Free exudate was associated negatively with the median duration of pain (3 versus 6 days), oral contraceptive use (4% versus 26%), and palpable adnexal mass (7% versus 25%). Analyses limited to women without a history of PID gave similar results. Although clinical and laboratory criteria traditionally used to judge the clinical severity of acute PID partially predict the degree of tubal or other pelvic abnormalities among women with acute salpingitis and tend to distinguish those with tubal occlusion or moderate to severe adhesions from those with peritonitis, these criteria have low predictive value and are not reliable in the individual patient.

Gynaecological tuberculosis since 1951

A study has been made of 711 patients with proved gynaecological tuberculosis investigated between 1 January 1951 and 31 December 1994. The main presenting symptoms in order of frequency were infertility, pelvic pain, excessive menstrual loss and amenorrhoea. The average age at first attendance was 31 years, only 16% of married women had been pregnant and palpable adnexal masses were found in 47%. Eight drug programmes were used, the best results being obtained with streptomycin, para-aminosalicyclic (PAS) acid and isoniazid or with rifampicin, ethambutol and isoniazid. Toxic drug reactions occurred in 114 patients, the drugs responsible in the majority being streptomycin and PAS. Where drug treatment failed, surgery under further drug cover was employed in 85 patients, with no deaths and no fistulae. After treatment, there were 95 pregnancies in 57 patients. In recent years there has been a rise in the incidence of tuberculosis in general in the Western world. Many factors play a part in this, by far the most important being the spread of AIDS.

Recognition of tubo-ovarian abscess in adolescents with pelvic inflammatory disease

Ultrasonography of the pelvis is commonly used to diagnose tubo-ovarian abscess (TOA) in patients with pelvic inflammatory disease (PID). Our objective was to determine whether the clinical features of PID differ in adolescents with and without TOA. A retrospective design was used to derive and validate a clinical model differentiating adolescents with PID who did and did not have TOA. The study population consisted of hospitalized adolescents with a discharge diagnosis of PID. Of the 208 patients discharged from January 1, 1990, to July 31, 1993, 87 (42%) met published criteria for PID and comprised the derivation set. Of the 63 patients from August 1, 1993, to June 24, 1994, 30 (48%) met criteria and comprised the validation set. All patients had pelvic ultrasonography performed during hospitalization. The ultrasonography records were reviewed retrospectively for TOA, ovarian and uterine size, clarity of tissue planes, and endometrial or cul-de-sac fluid. Medical records were reviewed for sociodemographic characteristics, medical and sexual history, physical examination, laboratory results, and hospital course. TOA was present in 17% of the derivation set and 20% of the validation set. A six-variable model developed on the derivation set performed best in differentiating the TOA and non-TOA groups: last menstrual period > 18 days prior to admission (60% and 17%), previous PID (53% and 22%), palpable adnexal mass (13% and 3%), white blood cell count > or = 10,500/microliters (33% and 64%), erythrocyte sedimentation rate > 15 mm/h (33% and 64%), and heart rate > 90/min (40% and 78%). In the derivation and validation sets, the model correctly identified 78 and 83% of the TOA groups and 88 and 77% of the non-TOA groups. The area under the receiver operating characteristic curve of the model was 0.92 in the derivation set and 0.87 in the validation set. We conclude that clinical characteristics help identify adolescents with acute PID who have TOA. These patients may have fewer signs of acute illness than those without TOA and may develop symptoms later in the menstrual cycle.

Gynaecological tuberculosis: analysis of a personal series of 710 cases.

A study has been made of 710 patients with proved gynaecological tuberculosis investigated between January 1, 1951 and March 31, 1985. The main presenting symptoms in order of frequency were infertility, pelvic pain, excessive menstrual loss and amenorrhoea. The average age was 31 years at first attendance, only 16% of married women had been pregnant and palpable adnexal masses were found in 47%. Seven drug programmes have been used, the best results being obtained with the current regimen employing rifampicin, ethambutol and isoniazid. Where drug treatment failed, surgery under further drug cover was successfully employed. Toxic drug reactions occurred in 114 patients.

429 SPONTANEOUS RESOLUTION UNDER ULTRASONIC OBSERVATION OF OVARIAN CYSTS CAUSING PRECOCIOUS PSEUDOPUBERTY IN YOUNG GIRLS

We report four episodes of unsustained precocious sexual development accompanied by palpable adnexal masses in three preschool aged girls. In each case serial pelvic ultrasound examinations revealed large ovarian cysts which spontaneously disappeared, with rapid regression of precocity, and fall in E2. At presentation, each girl had breast enlargement, labial hypertrophy with leukorrhea, hyperestrogenized vaginal cytology, and markedly elevated estradiol. Two patients had vaginal bleeding. None developed pubic hair. Patients 2 and 3 had negative cranial CT scans. Patient 2 had laparotomy which confirmed that ovaries had returned to normal. Patient 3 has been followed for 3.5 years without recurrance. Our data do not comment on whether these follicular cysts are truly autonomous since at least one patient had elevated gonadotrophins, but they do suggest that laparotomy and biopsy are not indicated in this situation when good ultrasonic surveillance is available.

Diagnosis and staging of ovarian cancer.

The diagnostic process in ovarian carcinoma is divided into the pre- and intraoperative procedures, examinations of tumor tissue, and follow-up. For preoperative diagnosis, the probability of a palpable adnexal mass being a malignant tumor should first be ascertained by sonography. This should be followed by an appropriate general examination, a search for tumor outside the abdominal cavity and in the liver parenchyma as well as by determination of markers. Intraoperative diagnosis determines the tumor stage and must be carried out all the more comprehensively when the ovarian carcinoma is more limited. Histologic subtype and degree of differentiation are in direct relation to the tumor stage, whereas the size of the primary tumor is often indirectly proportional to its extent. Besides the morphological analysis, the determination of possible chemoresistance and chemosensitivity, as well as further investigations on fresh tumor tissue are included in the tissue examination. Follow-up after a curative operation consists of gynecologic examination and Douglas lavages if tumor is still present in CT Scans and sonographs. To verify a relapse, laparoscopy can be used, but to ascertain a complete remission, a laparotomy is necessary.

The changing pattern of tuberculosis of the female genital tract. A thirty year survey.

Between 1st January, 1951 and 31st December, 1980, 704 women with proven tuberculosis of the genital tract were investigated. The previous obstetrical history, age incidence, presenting symptoms, and pelvic findings have been reviewed in 10-year periods. The incidence of previous pregnancies rose in successive periods and the average age increased. The main differences in the presenting symptoms were a lessening in the frequency of amenorrhoea and vaginal discharge and an increase in postmenopausal bleeding. The incidence of palpable adnexal masses decreased in successive 10-year periods. Short drug courses were mainly employed in the earlier years and longer courses in the later years. The drugs used initially were streptomycin, PAS and isoniazid, ethambutol and rifampicin being introduced later. The incidence of surgical treatment following failure of drug therapy was much higher in those who had received short drug courses than in those who had received longer ones.

Laparoscopy for presumed nonacute salpingitis: A new look at an old problem

The increased prevalence of venereal disease among adolescents has resulted in a rise in nonacute salpingitis. Laparoscopy was evaluated as an aid in the diagnosis and treatment of presumed nonacute salpingitis in 29 adolescents. The patients had a mean duration of symptoms of 5.5 months, 50% had a recent history of discharge and/or bilateral pelvic pain, and on examination 50% had pain on motion of the cervix, 75% had adnexal tenderness, and 50% had a palpable adnexal fullness or mass. Anatomic findings at laparoscopy included normal pelvic structures in 8, active salpingitis in 13 and nonacute disease in 8. The anaerobic, aerobic, and viral peritoneal cultures obtained at laparascopy from 22 patients resulted in no growth in 18. The four with positive cultures had one organism identified in three cases and two organisms in one case. Anatomic findings were more helpful in diagnosis than the bacteriologic analysis, and our results suggest that laparoscopy increases diagnostic accuracy in the management of presumed nonacute salpingitis.