Prevalence estimates of Helicobacter species infection in pancreatic and biliary tract cancers.

BACKGROUND: Helicobacter pylori infection is a well-established risk factor for gastric cancer and has been linked to other gastrointestinal diseases, including pancreatic and biliary tract cancers; however, the relevance of enterohepatic non-H. pylori helicobacters to the pathophysiology of these diseases remains unclear. MATERIALS AND METHODS: We estimated the prevalence of two enterohepatic non-H. pylori helicobacters (Helicobacter hepaticus and Helicobacter bilis) in the framework of a hospital-based case-control study involving 121 patients with biliary tract cancer, pancreatic cancer, or other gastrointestinal diseases. Bile and blood samples were collected from the patients undergoing endoscopic retrograde cholangiopancreatography. The presence of H. bilis, H. hepaticus, and other Helicobacter spp. was examined using bacterial culture, PCR-based detection, and serological tests. RESULTS: Culture of Helicobacter spp. from biliary brush samples was unsuccessful. Approximately 13.0% (15/115) of the bile samples collected from patients with a variety of gastrointestinal cancers, including pancreatic and biliary tract cancers, tested positive for one of the enterohepatic non-H. pylori helicobacter species as determined by PCR. Specifically, H. bilis and H. hepaticus DNA were detected in 11 and 4 bile samples, respectively. Approximately 20%-40% of the patients tested positive for serum non-H. pylori helicobacter IgG antibodies. The seroprevalence of H. bilis and H. hepaticus in the patients without evidence of H. pylori infection appeared to be higher in the pancreatic cancer group than in the control group. CONCLUSION: Our findings suggest a role for Helicobacter spp., especially H. bilis and H. hepaticus, in the etiology of pancreatic and biliary tract cancers.

Analysis of clinical factors and reasons that influence the disposition of cryopreserved embryos in Japanese patients with infertility treated in our clinic.

AIM: To investigate the clinical factors and factors that affect the decisions regarding storage of cryopreserved embryos obtained using assisted reproductive technology. METHODS: Clinical characteristics affecting the decisions regarding cryopreserved embryos were analyzed in 5724 Japanese couples who underwent in vitro fertilization (IVF) or intra-cytoplasmic sperm insemination (ICSI) and embryo transfer over 4 years since April 2015 at our clinic. Statistical analysis was carried out using JMP software. RESULTS: The number of oocytes retrievals and embryos stored, outcomes and number of children, and age of the female patients and male partners were related to the decision-making regarding cryopreserved embryos. Childbearing and no wish for another child were the major reasons for discontinuing embryo storage. The number of oocytes retrievals and embryos in storage, age of the female patients, and sex of the child were independently associated with this decision-making in 2682 patients with a single child. Women with male children were more likely to choose discontinuation of embryo storage than those with female children. CONCLUSION: Already having a child and not wishing for further treatment due to age along with the presence of a male child affect the decision to continue or discontinue embryo storage in Japanese patients with infertility.

[Left Ventricular Thrombectomy in Patients with Dilated Cardiomyopathy Accompanied by Cerebral Embolism:Report of Two Cases].

Left ventricular thrombus( LVT) formation is a known complication of ischemic heart diseases including acute myocardial infarction, dilated cardiomyopathy (DCM) and myocarditis. Among them, few cases involve DCM. Two DCM patients with LVT developed acute cerebral infarction and underwent thrombectomy. Both patients presented with sinus rhythm and neither had previous thromboembolic event. However, their transthoracic echocardiography (TTE) showed left ventricular ejection fractions<35% and left ventricular diastolic diameters≥60 mm, indicating high possibilities of LVT formation. The TTE findings suggest that DCM patients require anticoagulation therapy and frequent imaging examination, even with sinus rhythm and no history of thromboembolic events. Once a thromboembolic event occurs, thrombectomy is urgently needed.

Contraction-associated proteins expression by human uterine smooth muscle cells depends on maternal serum and progranulin associated with gestational weight gain.

Pregnant women with obesity are at increased risk of parturition dysfunction; however, the biological mechanism has remained unknown. We hypothesized that molecules circulating in the serum of pregnant women with obesity may induce the aberrant expression of contraction-associated proteins (CAPs), leading to insufficient uterine contractions. This study aimed to investigate the effects of maternal serum on CAPs expression by human uterine smooth muscle cells (UtSMCs) and elucidate the influence of maternal obesity. Blood samples were collected from singleton pregnant women at 36-41 weeks of gestation before the onset of labor. UtSMCs were incubated in the serum, and the mRNA expressions of PTGFR, OXTR, GJA1, and PTGS2 were examined by RT-PCR. Progranulin (PGRN) is a circulating glycoprotein associated with insulin resistance characterized by the accumulation of visceral fat. The serum PGRN levels of the samples were measured by ELISA. After incubated with PGRN (100-1,000 ng/mL), mRNA expression of PTGFR, OXTR, and GJA1 and protein expression of CX43 were examined by RT-PCR and western blotting, respectively. The mRNA expressions of PTGFR, OXTR, and GJA1 showed significantly negative correlations with gestational weight gain (GWG). Serum PGRN levels showed a significantly positive correlation with GWG. High levels of PGRN suppressed the mRNA expression of GJA1 and the protein expression of CX43. The change in maternal serum induced by GWG suppressed the CAPs expression by UtSMCs. PGRN is one of the factors in the serum responsible for inhibiting the expression of CX43.

[A Case of Synchronous Double Lung Cancer Including Intestinal Adenocarcinoma Complicated with Colonic Adenoma].

The patient was a 73-year-old man who was referred to our hospital for increasing bilateral lung nodules. Video-assisted left S9-10 segmentectomy and right S1, S3 partial resection were performed separately for suspect of synchronous double lung cancer. Colonoscopy was performed because left lung tumor was difficult to distinguish between primary lung cancer and metastatic lung cancer. Colonoscopy did not find advanced cancer lesion. We diagnosed the left lung tumor as pT1b, cN0, cM0, Stage ⅠA2 intestinal adenocarcinoma. The right lung tumor was diagnosed as pT1c, cN0, cM0, Stage ⅠA3 papillary adenocarcinoma. Intestinal adenocarcinoma is a rare tissue subtype of lung adenocarcinoma and colonoscopy is useful modality for ruling out metastatic colorectal cancer.

A poor long-term neurological prognosis is associated with abnormal cord insertion in severe growth-restricted fetuses.

OBJECTIVE: To clarify and compare if the neurological outcomes of fetal growth restriction (FGR) cases with abnormal cord insertion (CI) are associated with a higher risk of a poor neurological outcome in subjects aged 3 years or less versus those with normal CI. METHODS: A multicenter retrospective cohort study was conducted among patients with a birth weight lower than the 3rd percentile, based on the standard reference values for Japanese subjects after 22 weeks' gestation, who were treated at a consortium of nine perinatal centers in Japan between June 2005 and March 2011. Patients whose birth weights were less than the 3rd percentile and whose neurological outcomes from birth to 3 years of age could be checked from their medical records were analyzed. The relationship between abnormal CI and neurological outcomes was analyzed. Univariate and multivariate models of multivariate logistic regression were employed to estimate the raw and odds ratio (OR) with 95% confidence intervals comparing marginal (MCI) and velamentous cord insertion (VCI) to normal CI. RESULTS: Among 365 neonates, 63 cases of MCI and 14 cases of VCI were observed. After excluding 24 cases with neonatal or infant death from the total FGR population, the assessment of the outcomes of the infants aged 3 years or younger showed the following rates of neurological complications: 7.3% (n=25) for cerebral palsy, 8.8% (n=30) for developmental disorders, 16.7% (n=57) for small-for-gestational-age short stature (SGA), 0.6% (n=2) for impaired hearing, 0.9% (n=3) for epilepsy, 1.2% (n=4). The ORs (95% confidence intervals) based on multivariate analysis were as follows: cerebral palsy=10.1 (2.4-41.5) in the VCI group and 4.3 (1.6-11.9) in the MCI group, developmental disorders=6.7 (1.7-26) in the VCI group and 3.9 (1.1-14.2) in the single umbilical artery (SUA) group, 5.1 (1.4-18.7) for birth weight <1000 g and 2.8 (1.2-6.7) for placental weight <200 g. CONCLUSIONS: The present results indicate that growth-restricted fetuses diagnosed with a birth weight below the 3rd percentile exhibiting abnormal umbilical CI are at a high risk for poor neurological outcomes, including cerebral palsy and/or developmental disorders.

Significance of gestational weight gain in spontaneous onset of labor at term.

AIM: To investigate the significance of gestational weight gain (GWG) in association with the spontaneous onset of labor at term. METHODS: A retrospective cohort study on 985 pregnant women (629 nullipara and 356 pluripara) who delivered singleton babies at term was conducted. We reviewed the maternal demographics (age, parity, prepregnancy body mass index [BMI]) and the perinatal outcomes (gestational age [GA] and the type [spontaneous or induced] of labor onset, and GWG). The subjects were categorized by prepregnancy BMI and GWG. The rates of spontaneous onset of labor were compared between the nullipara and pluripara groups. Kaplan-Meier survival analysis was applied to evaluate the time to spontaneous labor according to prepregnancy BMI and GWG. A Cox proportional hazards model was used to determine the independent predictive factor for spontaneous onset of labor. RESULTS: In both the nullipara and pluripara group, women with prepregnancy obesity were less likely to enter spontaneous labor. In nullipara, women with excessive weight gain were less likely to enter spontaneous labor. In pluripara, women with poor gain were more likely to enter spontaneous labor. In the multivariate model, GWG was independently associated with the spontaneous onset of labor in both nullipara (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.75-0.98, P = 0.03) and pluripara (HR 0.82, 95% CI 0.64-0.93, P = 0.005). CONCLUSION: Greater maternal weight gain was significantly associated with longer gestation and a decreased likelihood of spontaneous onset of labor at term.

Influence of maternal obesity on fetal growth at different periods of pregnancies with normal glucose tolerance.

AIM: We aimed to examine the influence of maternal obesity on fetal growth in utero at different periods of pregnancies with normal glucose tolerance. METHODS: A retrospective cohort study on 356 pregnant women with normal glucose tolerance was conducted. The women were categorized by pre-pregnancy body mass index (BMI) as obese (OB; BMI ≥ 25.0 kg/m2 ) or non-obese (n-OB). Z-scores of the fetal abdominal circumference (AC) and the rate of fetal macrosomia (AC ≥ 90th percentile) at 19, 30, and 36 gestational weeks (GW) were compared between the two groups. Maternal demographics (age, parity, height, pre-pregnancy BMI, history of prior large-for-gestational-age delivery) were compared between the pregnancies with and without fetal macrosomia at each gestational age. Multiple logistic regression analysis was performed to determine the independent risk factors for fetal macrosomia. RESULTS: Birthweights of the neonates were significantly higher in the OB group. Z-scores of the fetal AC were significantly higher in the OB group at 30 and 36 GW, while no significant difference was found at 19 GW. The rates of fetal macrosomia in the OB group were also higher at 30 and 36 GW, while maternal obesity was not associated with fetal macrosomia at 19 GW. Pre-pregnancy BMI was detected as the independent predictor of fetal macrosomia at 30 GW (odds ratio, 1.19 [95% CI]) and 36 GW (odds ratio, 1.13 [95% CI]). CONCLUSION: Maternal pre-pregnancy obesity has a promoting effect on fetal growth from the third trimester through birth.

Increased maternal insulin resistance promotes placental growth and decreases placental efficiency in pregnancies with obesity and gestational diabetes mellitus.

AIM: Homeostasis model assessment for insulin resistance (HOMA-IR) was measured during pregnancy to analyze placental weight and efficiency in relation to maternal insulin resistance. METHODS: A retrospective study of 510 pregnant women (130 with gestational diabetes mellitus [GDM], 380 with normal glucose tolerance) was conducted. We reviewed the patients' demographic data (age, parity, pre-pregnancy body mass index [BMI]) and perinatal outcomes (birth weight, placental weight, BMI at delivery, maternal weight gain, HOMA-IR). The birth weight to placental weight (B/P) ratio was calculated for placental efficiency. The subjects were categorized by BMI at delivery, and maternal, neonatal and placental characteristics were compared between the groups to investigate the determinants of placental weight and B/P ratios. RESULTS: Obesity was significantly associated with heavier placental weight and lower B/P ratios. The presence of GDM did not affect placental weight, whereas the B/P ratios in women with GDM were significantly lower than in women with normal glucose tolerance. HOMA-IR was positively correlated with placental weight (ρ = 0.217, P < 0.001) and negatively with B/P ratio (ρ = -0.181, P < 0.001). CONCLUSIONS: Increased maternal insulin resistance promoted placental growth and inhibited placental efficiency. Maternal insulin resistance may be one of the pathophysiological conditions responsible for altered placental size and function in pregnancies with obesity and GDM.

Non-essential and branched-chain amino acids differentially regulate insulin-like growth factor binding protein-1 production and phosphorylation in HepG2 cells.

Deprivation of branched-chain amino acids (BCAAs) induces insulin-like growth factor binding protein-1 (IGFBP-1) production in HepG2 cells, while the role of non-essential amino acids (NEAAs) remains unknown. We investigated changes in IGFBP-1 production and phosphorylation induced by NEAAs and also examined its significance on IGF-I activity in HepG2 cells. We demonstrated that decreased BCAAs and increased NEAAs stimulated phosphorylated IGFBP-1 secretion. We also revealed that decreased BCAA-to-NEAA ratios enhanced phosphorylated IGFBP-1 secretion, while changes in the total amount of amino acids (AAs) had no effect. Phosphorylation of IGF-I receptor ß-subunits mediated by exogenous IGF-I in HepG2 cells was inhibited by decreased BCAAs, increased NEAAs, and decreased BCAA-to-NEAA ratios, while the total amount of AAs had no effect. In addition to BCAAs, NEAAs are also responsible for the regulation of IGFBP-1 secretion and phosphorylation in HepG2 cells. Moreover, the balance of BCAAs and NEAAs regulated IGFBP-1 secretion and phosphorylation.

Histologic grade and peritoneal cytology as prognostic factors in type 1 endometrial cancer.

BACKGROUND: Prognostic clinicopathological factors for type 1 endometrial cancer are unknown and the purpose of the current study was to determine the independent prognostic variables for type 1 endometrial cancer. METHODS: We performed a retrospective study of 168 patients with type 1 endometrial cancer primarily treated with comprehensive staging surgery. The median follow-up time was 68 (12-100) months. Independent risk factors for disease-free survival (DFS) and overall survival (OS) were determined using multivariate Cox regression models. Sub-group analysis of stage I was also performed. We also assessed the patterns of failure among patients with recurrences and investigated the associations with the prognostic variables determined by multivariate analysis. RESULTS: Twenty patients (11.9%) had recurrence and 13 patients (7.7%) died of the disease overall. Multivariate analysis revealed that grade 2 (G2) histology (p = 0.008) and positive peritoneal cytology (p = 0.001) predicted the recurrent event in type 1 endometrial cancer. G2 histology (p = 0.007) and positive peritoneal cytology (p = 0.003) were also found to be independent risk factors for tumor-related deaths. Among stage I patients, G2 histology and positive peritoneal cytology were also independent prognostic variables for DFS and OS. Patients with G2 histology and/or positive peritoneal cytology were more likely to have recurrence at distant sites. CONCLUSIONS: G2 histology and positive peritoneal cytology were independent prognostic factors for DFS and OS in type 1 endometrial cancer.

Branched-chain amino acids regulate insulin-like growth factor-binding protein 1 (IGFBP1) production by decidua and influence trophoblast migration through IGFBP1.

STUDY QUESTION: Do branched-chain amino acids (BCAAs) influence the migration of human extravillous trophoblast (EVT) cells through changes in insulin-like growth factor-binding protein 1 (IGFBP1) production in decidual cells? STUDY FINDING: Decidua-derived IGFBP1 had a stimulating effect on migration of EVT. WHAT IS KNOWN ALREADY: IGFBP1 is abundantly secreted from human decidual cells and influences trophoblast migration in human placenta of early pregnancy. In hepatic cells, the expression of IGFBP1 is influenced by nutritional status and BCAAs regulate IGFBP1 production. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: This is a laboratory-based study using human decidual cells and trophoblast cells isolated from placental tissue of early pregnancy (n = 50) and grown as primary cultures. Production of IGFBP1 from decidual cells was examined by enzyme-linked immunosorbent assay and immunoblotting after incubation with or without BCAAs. EVT migration was evaluated using the media conditioned by decidual cells. The effect of conditioned media on phosphorylation of focal adhesion kinase (FAK) in EVT was also analyzed by immunoblotting. The same experiments were repeated in the presence of RGD peptide, which inhibits IGFBP1 binding to α5ß1 integrin. An EVT migration assay and the immunoblotting of phosphorylated FAK were also conducted with exogenous IGFBP1. The effect of the conditioned media on cytotrophoblast cell number was also assessed using WST-1 in a cell proliferation assay. MAIN RESULTS AND THE ROLE OF CHANCE: Deprivation of BCAAs on decidual cells significantly suppressed IGFBP1 secretion (P < 0.05, versus BCAA+). Exogenous IGFBP1-stimulated EVT migration (P < 0.05) and phosphorylation of FAK (P < 0.05), and the RGD peptide inhibited these effects. EVT migration and phosphorylation of FAK were stimulated by the conditioned media, presumably by IGFBP1 in the media. RGD treatment abrogated the stimulating effects of conditioned media. The conditioned media deprived of BCAAs had suppressive effects on EVT migration (P < 0.05, versus BCAA+) and phosphorylation of FAK (P < 0.05, versus BCAA+). The conditioned media did not affect number of cytotrophoblast cells. LIMITATIONS, REASONS FOR CAUTION: The conclusions are based on in vitro experiments with human decidual cells and trophoblast cells isolated from placental tissue of early pregnancy, and we were unable to ascertain whether these mechanisms actually operate in vivo. We investigated the effect of decidua-derived IGFBP1 on EVT migration, however, we cannot completely rule out the possibility that endogenous IGF could also influence cell migration. WIDER IMPLICATIONS OF FINDINGS: Interruption of the BCAA supply to uterine decidual cells in early pregnancy may suppress EVT migration through reduced IGFBP1 secretion, which may be one of the pathophysiological conditions responsible for pre-eclampsia. LARGE SCALE DATA: None. STUDY FUNDING/ AND COMPETING INTERESTS: All funds were obtained through Kyorin University School of Medicine. The authors have no conflict of interest to declare.

Significance of oligohydramnios in preterm small-for-gestational-age infants for outcome at 18 months of age.

AIM: The aim of this study was to evaluate the association between oligohydramnios and other perinatal factors in preterm small-for-gestational-age (SGA) infants who had cerebral palsy at 18 months of age or who had died before this age. METHODS: This retrospective study included 320 infants with birthweights < 3rd percentile delivered between 22 and 33 complete weeks of gestation. We evaluated the incidence of CP at 18 months of age and of death before this age. The significant risk factors, including oligohydramnios, of CP or death of preterm SGA infants were evaluated by logistic regression analysis. RESULTS: The incidence of CP or death was 47/320 (14.7%), consisting of 24/320 (7.5%) cases of CP and 23/320 (7.2%) cases of death. Oligohydramnios (adjusted odds ratio, 2.18; 95% confidence interval, 1.07-4.45) and gestational age (adjusted odds ratio, 0.76; 95% confidence interval, 0.66-0.87) were independently correlated with outcome. CONCLUSION: The incidence of adverse outcomes was approximately 15% in preterm SGA infants. SGA infants born with oligohydramnios may be at increased risk for CP or death compared to those with normal amniotic volume.

Sonographic features of congenital infantile fibrosarcoma that appeared as a sacrococcygeal teratoma during pregnancy.

We experienced an extremely rare case of congenital infantile fibrosarcoma originating from the fetal sacrococcygeal region in pregnancy. At first, we suspected fetal sacrococcygeal teratoma; however, the following ultrasonography findings of the tumor complicated this diagnosis: (i) laterality; (ii) no cystic component; (iii) hypervascularity, with the feeding vessels not derived from the middle sacral artery; and (iv) a skin covering. The pathological findings indicated that the tumor was an infantile fibrosarcoma, not a teratoma. Thus, we believe that these sonographic features may aid the prenatal diagnosis of congenital infantile fibrosarcoma, which, in turn, may contribute to a better prognosis and may be useful for parental counseling.

Antepartum reversible cerebral vasoconstriction syndrome with pre-eclampsia and reversible posterior leukoencephalopathy.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe headache and diffuse segmental constriction of the cerebral arteries that resolves spontaneously within a few months. Pregnancy is one of the precipitating factors of RCVS and most of the reported cases occurred in the post-partum period. We report a case of RCVS that occurred in a pregnant women with pre-eclampsia during her antepartum period. A 34-year-old woman in full-term pregnancy presented with a severe and acute headache. Magnetic resonance angiography (MRA) showed multiple segmental constrictions of the cerebral arteries. Magnetic resonance imaging revealed a high-intensity lesion in the left occipital lobe, consistent with reversible posterior leukoencephalopathy syndrome, on fluid attenuated inversion recovery sequences. The case was also complicated by severe pre-eclampsia and the patient underwent emergency cesarean section. Although her symptoms resolved rapidly, MRA revealed new lesions of arterial constriction 4 days after onset. The vasoconstriction completely resolved on MRA after 10 days and the patient was discharged without neurological sequelae.

Uterine cervical cancer with brain metastasis as the initial site of presentation.

Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis.

[Heparin-induced thrombocytopenia with pseudo-pulmonary embolism in a patient who was newly introduced to hemodialysis treatment].

Pseudo-pulmonary embolism (PPE) superimposed on heparin-induced thrombocytopenia (HIT) is an important complication in patients undergoing hemodialysis (HD) treatment. We report the clinical profile of an HD patient with acute respiratory distress induced by PPE and HIT. A 67-year-old man with diabetic nephropathy and end-stage renal failure developed congestive heart failure. He was admitted to Kitasato University Hospital. He was introduced to HD treatment using low-molecular-weight heparin as an anticoagulant for an HD session on day 1 of admission. On day 11 after admission, he suddenly developed respiratory distress and hypoxia at 30 min after the start of the fifth HD session. The HD session was immediately discontinued, and oxygen inhalation improved his complaints and hypoxia. The platelet count decreased from 220 x 10(9)/L at the start of the HD session to 80 x 10(9)/L at the end of the HD session. We suspected HIT when blood clotting occurred in his hemodialyzer and blood circuit for HD during the HD session on day 12. Chest X-ray, electrocardiogram, echocardiography, and pulmonary microcirculation scintigraphy were normal. Serum analysis was positive for heparin-platelet factor 4 (PF4) antibody. We then diagnosed him with PPE superimposed on HIT. After the anticoagulant agent for HD was changed from low-molecular-weight heparin to nafamostat mesilate, his clinical symptoms and thrombocytopenia disappeared. PPE superimposed on HIT appeared approximately 7-10 days after the initial use of heparin for the HD session. PPE also led to acute respiratory distress, blood coagulation in the hemodialyzer and blood circuit for HD, as well as thrombocytopenia with less than a 50% decrease in platelet counts. The prognosis of PEE and HIT is good after discontinuing the use of heparin.

[Unresectable Gallbladder Cancer Successfully Treated with Gemcitabine Chemotherapy].

We report a case of unresectable gallbladder cancer successfully treated with gemcitabine (GEM). A 77-year-old man was admitted to our hospital in April 2010 with jaundice. He was diagnosed as having gallbladder cancer that had invaded the liver and hepatic artery, along with lymph node metastasis. The tumor was considered unresectable, and he received chemotherapy with GEM. Each course of treatment consisted of 1,000 mg/m2 GEM administered once a week for 3 weeks followed by a week of no treatment. After the 3rd course, computed tomography revealed reduction in liver invasion and disappearance of lymph node metastasis. After the 18th course, the tumor had completely disappeared, and the patient achieved a complete response. GEM monotherapy was continued for 5 years, even though the tumor had disappeared. The patient is alive and has been disease-free for more than 5 years.