Incidentally detected ureteral fibroepithelial polyps in children: is endoscopic treatment of them really necessary?

Objective

Fibroepithelial polyps (FEPs) are the most common benign lesions of the ureter. However, FEPs of the ureter accompanied by calculi are rare. In this study, we reviewed our experiences with five children having FEP associated with ureteral calculi to define more clearly this entity and its outcome following observation.

Materials and Methods

We identified five children who were intraoperatively found to have FEP associated with ureteral calculi during the period 2000–2008.

Results

The patients included four males and one female, and the average age of these patients was 6.4 years (range 4–9). The main symptoms were flank pain (five patients), hematuria (four patients), and dysuria (two patients). Radiographically, all patients showed complete ureteral obstruction due to distal ureter stone and hydronephrosis. Fibroepithelial polyps and stones were located left distal ureter in all children. These polyps were 1–2 cm, with a mean size of 1.5 cm. Stone sizes ranged from 5 to 13 mm (mean 8.8 mm). The stones were smashed into smaller fragments using a pneumatic lithotriptor, and the pieces were removed with forceps. After the lithotripsy, the polyps were grasped with biopsy forceps and punch biopsies were done. FEPs were diagnosed in all cases by postoperative histological examination. During the follow-up period of these patients, none of the FEPs displayed any growth or symptom.

Conclusions

Due to the potential complications during the ureteroscopic resection, our opinion is to observe the small FEPs without joint symptoms and hydronephrosis.     

Factors affecting the treatment of multiple colorectal adenomas

Background

Currently, no guidelines exist for the treatment of patients with multiple colorectal adenomas (MCRAs) (>10 but <100 synchronous nondiminutive polyps of the large bowel). This retrospective study aimed to investigate the clinical and molecular factors related to different treatments for MCRAs.

Methods

Patients with MCRAs were consecutively enrolled from January 2003 to June 2011. Sequencing of their APC and MutYH genes was performed. The clinical, molecular, and family histories of the patients were collected using the Progeny database. The patient treatments were divided into three groups of increasing clinical weight: endoscopic polypectomy, segmental resection, and total colectomy. A logistic regression analysis of clinicomolecular factors related to different treatment options was performed.

Results

The study comprised 80 patients (32 women, 40 %) with a median age of 53 years (range 13–74 years). The median number of polyps was 33 (range 10–90).The cases included 62 diffuse polyposis, 18 segmental polyposis coli and synchronous colorectal carcinomas (CRC; 34 cases, 43%). The pathogenetic mutations were biallelic MutYH (n = 19, 24 %) and APC (n = 4, 5 %). The mean follow-up period was 74 months (median 43 months, range 1–468 months). Endoscopic polypectomy was performed in 25 cases (31 %), segmental resection in 16 cases (20 %), and total colectomy in 39 cases (49 %). The logistics regression analysis, considering all the patients, showed that the number of polyps, the presence of CRC, and mutation were correlated with more intensive treatment. For the patients without CRC, only the number of polyps was correlated with the severity of the treatment (p > 0.0166). “On the ROC (receiver operating characteristic) curve, 25 was the number of polyps that best discriminated between surgical and endoscopic therapy.

Conclusions

The majority of patients with MCRAs undergo surgery. For patients without CRC, only the number of polyps, and not the presence of a disease-causing mutation, is correlated with increased heaviness of treatment. Patients with more than 25 polyps are more likely to undergo a surgical resection.     

Urinary excretion of calcium,magnesium, phosphate,citrate, oxalate,and uric acid by healthy schoolchildren using a 12-h collection protocol

Background

Improving knowledge about normal urine composition in children is important for early prevention of lithiasis. We describe urinary excretion values of calcium (Ca), magnesium (Mg), phosphate (P), citrate (Cit), uric acid (Ur), and oxalate (Ox) in healthy children with and without a family history of lithiasis, using a 12-h urine collection protocol.

Methods

Urine samples were obtained from 184 children (5?12 years): a spot sample collected in the afternoon, and a 12-h overnight sample. Solute/creatinine (Cr) and 12-h solute excretion was calculated.

Results

Urinary excretion values of the studied solutes are presented as percentile values, separately for each type of sample. Due to age-related differences in the solute/creatinine ratios, except for Ca and Cit, results are described according to the child’s age. The presence of excretion values related to an increased risk of lithiasis was more common in children with a family history.

Conclusions

We report data from urine samples collected by using a simplified collection protocol. The observed differences between children with and without a family history of lithiasis could justify that in population studies aimed at setting reference values, the former are excluded.     

The impact of colonoscopy for colorectal cancer screening

Background

Colorectal cancer is the second leading cause of cancer-related death. Prevention of this neoplasm should be achievable by screening programs in asymptomatic patients. The objective of the present paper is to assess colonoscopic findings in asymptomatic people submitted to screening.

Methods

A prospective study was undertaken on 153 consecutive asymptomatic people submitted to colonoscopy. Sex, age, previous diseases, and familial cases of cancer, as well as tobacco and alcohol ingestion were assessed. Patients with rectal macro- or microscopic bleeding and colorectal diseases were excluded. Bowel cleansing, polyps, angioectasias, diverticular disease, inflammation, and neoplasm were also verified. Polyps were classified according to their size, number, and location.

Results

Colonoscopic alterations were detected in 99 individuals: polyps in 64.3?%, diverticular disease in 27.9?%, inflammatory mucosal alterations in 9.7?%, melanosis coli in 2.6?%, and angioectasias in 7.8?%. There was an increasing incidence of polyps in individuals older than 50?years. Multivariate logistic regression showed age and sex as predictive factors for polyps [odds ratio (OR)?=?1.43; 1.19?<?OR?<?2.67].

Conclusions

The results of this investigation revealed a significant incidence of colonoscopic alterations in asymptomatic people submitted to colonoscopy for colorectal cancer screening.     

Endoscopic piecemeal resection of large colorectal polyps with long-term followup

Background

Colonoscopic removal of large colorectal polyps is challenging and requires advanced endoscopic technique. Successful endoscopic management not only avoids the morbidity of surgery but also risks perforation, hemorrhage, and recurrence.

Methods

This study is a retrospective review of a prospectively maintained database of all patients undergoing cautery snare piecemeal polypectomy for large colorectal polyps by a single operator over 20 years with long-term followup.

Results

231 patients underwent 269 piecemeal polypectomies over a 20 year period. The complication rate was 4.3 %. Malignancy was identified in 25 (10.8 %) of patients. Local recurrences occurred in 24 % of patients with benign adenomas. The vast majority of these were managed with repeat endoscopy. Overall, benign large polyps were managed successfully endoscopically in 94.4 % of patients.

Conclusions

Piecemeal polypectomy is effective and safe for the management of large colorectal polyps. With long-term followup, the recurrence rate is appreciable, but most recurrences can be successfully managed with further endoscopic intervention. More complex techniques such as endoscopic submucosal dissection are usually unnecessary.     

Mastectomy and Contralateral Prophylactic Mastectomy Rates: An Institutional Review

Background

Breast conservation surgery (BCS) followed by radiation is as effective as mastectomy for long-term survival and is considered standard of care for early-stage breast cancer. An increasing number of patients are opting for cancer-side mastectomies (CM) and often contralateral prophylactic mastectomies (CPM). Our study investigates if there are increasing trends in our patient population toward CM and CPM and identifies common factors associated with those electing to have more extensive surgery.

Methods

A retrospective analysis was performed on 812 breast cancer surgeries between January 2001 and December 2009 at The George Washington University Breast Care Center. BCS-eligible patients who elected to have BCS were compared with those who chose CM. Patients who underwent CM were compared with patients undergoing CM and CPM.

Results

A personal or family history of breast cancer and larger tumor size were positively associated with choosing CM in BCS-eligible patients. A nonstatistically significant trend toward CM was seen in younger patients. Age, family history, fewer children, Caucasian race, and reconstructive surgery were positively associated with choosing CPM.

Conclusion

Mastectomy rates at this institution have not shown the recent sharp increase observed by some authors. The association of age, race, family history, and parity with CPM has been corroborated in multiple studies. However, there is disagreement between statistically significant findings among investigators evaluating factors associated with CPM, and there is limited data in the literature characterizing BCS-eligible patients who chose CM. Larger prospective studies are necessary to further evaluate CM and CPM rates.     

The prognostic nutritional index can be a prognostic indicator in colorectal carcinoma

Purpose

Preoperative assessments regarding a patient’s immunological and nutritional condition are required to predict the outcomes of patients with malignant tumors. The aim of the current study was to clarify the significance of Onodera’s prognostic nutritional index (OPNI), which can simply account for the immunological and nutritional conditions, in patients with colorectal carcinoma.

Methods

The correlations of the preoperative OPNI value with clinicopathological features were examined in 219 patients with colorectal carcinoma who had been surgically treated.

Results

Not only the tumor stage (P?=?0.028) and venous invasion (P?=?0.002), but also an OPNI of less than 40 (P?=?0.002) were found to be independently correlated with a worse prognosis of patients with colorectal carcinoma.

Conclusion

The preoperative OPNI can be used as a simple prognostic indicator in colorectal carcinoma.     

Small colorectal cystic metastases to the liver: still a diagnostic dilemma? A report of a case and a review of the literature

Background

Although cystic colorectal metastases are rare (1.8%), they are still a crucial challenge for the surgeon especially in terms of detection and differential diagnosis. Since prognosis after resection is very good (40% 5-year survival), early diagnosis is essential.

Case report

A 55-year-old man was admitted to our hospital with a suspected diagnosis of multiple small liver metastases. He had previously undergone left sided-cholectomy followed by chemotherapy for colonic carcinoma. Computed tomography (CT) revealed multiple small (<15?mm) intrahepatic biliary cysts, suspected for cystic colorectal liver metastases.

Conclusion

The diagnosis of cystic colorectal liver metastases is quite difficult and it is mostly based on the last-generation magnetic resonance (MR). In spite of this, we must often rely on histological results for a definitive diagnosis.     

A RAND/UCLA Appropriateness Study of the Management of Familial Gastric Cancer

Background

Hereditary diffuse gastric cancer (HDGC) represents a minority of gastric cancer (GC) cases. The goal of this study is to use a RAND/University of California Los Angeles (UCLA) appropriateness methodology to examine indications for genetic referral, CDH1 testing, and consideration of prophylactic total gastrectomy (PTG).

Methods

A multidisciplinary expert panel of 16 physicians from six countries scored 47 scenarios. Appropriateness of scenarios was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) of 1–3 were considered inappropriate, 4–6 uncertain, and 7–9 appropriate. Agreement was reached when 12 of 16 panelists scored the statement similarly. Appropriate scenarios agreed upon were subsequently scored for necessity.

Results

The panel felt that patients with family history of diffuse gastric cancer (DGC), lobular breast cancer, or multiple family members with GC should be referred for genetic assessment and multidisciplinary decision-making. The panel felt that it is appropriate for patients with DGC to have CDH1 mutation testing in a family with (1) ≥2 cases of GC, with at least one case of DGC diagnosed before age of 50 years; (2) ≥3 cases of GC diagnosed at any age, one or more of which is DGC; (3) a patient diagnosed with DGC and lobular breast carcinoma; or (4) patients diagnosed with DGC under age of 35 years. The panel felt that PTG should be offered to CDH1 mutation carriers 20 years or older.

Conclusions

Identification of genetic mutations in patients at risk for hereditary GC is important, and criteria for testing are suggested.     

Primary colorectal signet-ring cell carcinoma: Clinicopathological features and postoperative survival

Purpose

The objective of this study was to investigate the clinicopathological features and postoperative survival of primary colorectal signet-ring cell carcinoma.

Methods

Nineteen patients with primary colorectal signet-ring cell carcinoma were identified from a database of 5884 surgical patients with colorectal cancers treated surgically at Osaka University Hospital and affiliated hospitals between 1993 and 2007. The clinicopathological data of those patients were compared with those of 5792 patients with non-signet-ring cell colorectal carcinoma (5417 with well or moderately differentiated adenocarcinoma and 375 with poorly differentiated adenocarcinoma or mucinous carcinoma).

Results

All patients showed a tumor depth of over T3. Lymph node involvement occurred in 14 patients. Seven of 19 patients presented with distant metastasis at the time of diagnosis. The overall 5-year survival rate in primary signet-ring cell carcinoma was significantly lower at 24.1%, in comparison to 77.5% in well or moderately differentiated adenocarcinoma and 57.7% in poorly differentiated adenocarcinoma or mucinous carcinoma. Likewise, the postoperative survival in Stage III was also significantly worse. On the other hand, no significant difference was observed in Stage II or IV.

Conclusion

The most important feature of primary colorectal signet-ring cell carcinoma is the advanced stage at the time of diagnosis. In addition, the postoperative survival is worse than for other types of colorectal cancer.     

Long-term recurrence and complication rates after incisional hernia repair with the open onlay technique

Background

Family history, male gender and age are significant risk factors for inguinal hernia disease. Family history provides evidence for a genetic trait and could explain early recurrence after inguinal hernia repair despite technical advance at least in a subgroup of patients. This study evaluates if age and family history can be identified as risk factors for early recurrence after primary hernia repair.

Methods

We performed an observational cohort study for 75 patients having at least two recurrent hernias. The impact of age, gender and family history on the onset of primary hernias, age at first recurrence and recurrence rates was investigated.

Results

44% (33/75) of recurrent hernia patients had a family history and primary as well as recurrent hernias occurred significantly earlier in this group (p = 0.04). The older the patients were at onset the earlier they got a recurrent hernia. Smoking could be identified as on additional risk factor for early onset of hernia disease but not for hernia recurrence.

Conclusion

Our data reveal an increased incidence of family history for recurrent hernia patients when compared with primary hernia patients. Patients with a family history have their primary hernias as well as their recurrence at younger age then patients without a family history. Though recurrent hernia has to be regarded as a disease caused by multiple factors, a family history may be considered as a criterion to identify the risk for recurrence before the primary operation.     

A Safety and Feasibility Study of an Allogeneic Colon Cancer Cell Vaccine Administered with a Granulocyte–Macrophage Colony Stimulating Factor–Producing Bystander Cell Line in Patients with Metastatic Colorectal Cancer

Background

Despite recent advances in earlier detection and improvements in chemotherapy, the 5-year survival rate of patients with metastatic colorectal carcinoma remains poor. Immunotherapy is a potentially effective therapeutic approach to the treatment of colorectal carcinoma. Preclinical studies have supported the antitumor activity of immunization with a granulocyte–macrophage colony-stimulating factor (GM-CSF) producing murine colon tumor cell vaccine.

Methods

A novel colorectal cancer vaccine composed of irradiated, allogeneic human colon cancer cells and GM-CSF-producing bystander cells was developed and tested in combination with a single intravenous low dose of cyclophosphamide in a phase 1 study of patients with metastatic colorectal cancer.

Results

A total of nine patients were enrolled onto and treated in this study. Six patients had a history of colorectal adenocarcinoma hepatic metastases and underwent curative metastasectomy, while three other patients had unresectable stage IV disease. This study demonstrates the safety and feasibility of this vaccine administered in patients with metastatic colorectal cancer. At last follow-up, the six patients who underwent curative metastasectomy survived longer than 36 months, and four of these six patients were without disease recurrence. Immunologic correlate results suggest that the GM-CSF-producing colon cancer vaccine enhances the production of anti-MUC1 antibodies.

Conclusions

This vaccine is feasible and safe. Future investigation of the efficacy and antitumor immunity of this vaccine is warranted.     

Primary scrotal tuberculosis: A rare but intriguing entity

Introduction

Tuberculosis (TB) of the genitourinary tract is usually secondary to a primary site in another part of the body. Primary scrotal TB is an extremely rare condition and it may mimic viral orchitis, epididymitis, hydrocele, spermatocele, testicular torsion, scrotal trauma, or a tumour.

Case presentation

A 45-year-old man presented with a 3-month history of diffuse scrotal enlargement followed a month later by swelling in the left groin. Scrotal ultrasonography revealed a 4 cm x 4 cm hypoechoic, heterogeneous, inflammatory mass with multiple fistulae at the bottom of the scrotum without any extension to the deeper structures, and bilateral multiple inguinal adenopathy.

Discussion

Genitourinary TB may present with adrenal insufficiency, renal disease, obstructive uropathy and chronic cystitis with sterile pyuria. Although scrotal USG is very helpful, it is not a definitive diagnostic tool. Histopathology is mandatory either in the form of FNAB or formal biopsy. Most cases respond well to antitubercular drugs only.

Conclusion

An optimum diagnostic and therapeutic protocol is urgently needed for cases of primary scrotal TB to prevent misuse of costly investigations and treatments and to avoid unnecessary surgical interventions when the patient can be cured by antitubercular treatment only.     

Up-regulation of Neutrophil Gelatinase-Associated Lipocalin in Colorectal Cancer Predicts Poor Patient Survival

Background

Lipocalin-2 (Lcn-2) is expressed in human neutrophils and epithelial cells, particularly in the presence of inflammation or cancer. It was shown to be highly expressed in various human cancers. Increased protein levels were associated with decreased survival of patients with breast or gastric cancer. The main focus of this work was to analyze the implication of Lcn-2 up-regulation in the genesis of colon cancer.

Methods

Expression of Lcn-2 was analyzed in colorectal carcinoma cell lines, paired colorectal carcinoma tissues, and regular mucosa by Western blot analysis. Lcn-2 immunohistochemical staining was performed in 192 colorectal carcinoma resection specimens and correlated with clinicopathologic parameters.

Results

Western blot analysis of colorectal carcinoma tissues demonstrated Lcn-2 overexpression in carcinomas as compared with regular mucosa. Immunohistochemical staining revealed Lcn-2 expression in 179 (93.2 %) colorectal carcinoma tissues. Intense immunoreactivity was significantly correlated with metastasis (p = 0.042) and UICC stage (p = 0.027). Survival analysis according to the Kaplan–Meier method revealed a significant association between Lcn-2 overexpressing tumors and overall survival (p < 0.001) and disease-free survival (p < 0.001).

Conclusions

Our data provide evidence that Lcn-2 expression is up-regulated with tumor progression and was found to be a predictor of overall survival.     

A Nationwide Analysis of the Use and Outcomes of Epidural Analgesia in Open Colorectal Surgery

Introduction

Epidural analgesia has demonstrated superiority over conventional analgesia in controlling pain following open colorectal resections. Controversy exists regarding cost-effectiveness and postoperative outcomes.

Methods

The Nationwide Inpatient Sample (2002–2010) was retrospectively reviewed for elective open colorectal surgeries performed for benign and malignant conditions with or without the use of epidural analgesia. Multivariate regression analysis was used to compare outcomes between epidural and conventional analgesia.

Results

A total 888,135 patients underwent open colorectal resections. Epidural analgesia was only used in 39,345 (4.4 %) cases. Epidurals were more likely to be used in teaching hospitals and rectal cancer cases. On multivariate analysis, in colonic cases, epidural analgesia lowered hospital charges by US$4,450 (p?<?0.001) but was associated with longer length of stay by 0.16 day (p?<?0.05) and a higher incidence of ileus (OR?=?1.17; p?<?0.01). In rectal cases, epidural analgesia was again associated with lower hospital charges by US$4,340 (p?<?0.001) but had no effect on ileus and length of stay. The remaining outcomes such as mortality, respiratory failure, pneumonia, anastomotic leak, urinary tract infection, and retention were unaffected by the use of epidurals.

Conclusion

Epidural analgesia in open colorectal surgery is safe but does not add major clinical benefits over conventional analgesia. It appears however to lower hospital charges.     

A systematic review of clinical studies on hereditary factors in pelvic organ prolapse

Introduction and hypothesis

There is growing evidence that pelvic organ prolapse (POP) is at least partly caused by underlying hereditary risk factors. The aim of our study was to provide a systematic literature review and meta-analysis of clinical studies on family history of POP as a risk factor for POP in individual women.

Methods

The databases PubMed and Embase were searched. Clinical studies reporting on family history of POP in relation to POP in individual women were included.

Results

Sixteen studies were included, of which eight enabled us to calculate a pooled odds ratio (OR). The pooled OR of POP in case of a positive family history of POP was 2.58 (95?% confidence interval 2.12–3.15).

Conclusions

Women with POP are substantially more likely to have family members with the same condition compared to women without POP. This strengthens the hypothesis that genetic predisposition plays an important role in the development of POP.     

Association of collagen type I alpha 1 gene polymorphism with inguinal hernia

Purpose

A positive family history is an important risk factor for inguinal hernia development, suggesting a genetic trait for hernia disease. However, gene mutations responsible for abdominal wall hernia formation in humans have not yet been studied. We aimed to evaluate whether the functional Sp1 binding site polymorphism within intron 1 of the collagen type I, alpha 1 (COL1A1) gene was associated specifically with inguinal hernia disease.

Methods

85 participants with surgically diagnosed inguinal hernia disease, and 82 physically active controls without any history of connective tissue disease and hernia were recruited for this case–control genetic association study. Polymerase chain reaction and restriction fragment length polymorphism and agarose gel electrophoresis techniques were used to detect these polymorphisms.

Results

Significantly, more patients gave a positive family history for an inguinal hernia compared to healthy controls (OR 3.646, 95 % CI 1.375–9.670, P = 0.006). COL1A1 Sp1 SNP (rs 1800012) was identified. Results demostrated statistically significant deviation from HWE for cases (P = 0.007), but not for the controls (P = 0.276). Our results revealed an increased frequency of COL1A1 Sp1 Ss genotype in inguinal hernia patients (OR 3.593, 95 % CI 1.867–6.915, P = 0.000).

Conclusions

This results suggest that polymorphism of the COL1A1 Sp1 binding site is associated with an increased risk for developing inguinal hernias. So, rs 1800012 locus is a potential candidate region for susceptibility in molecular mechanism of inguinal hernia pathophysiology.     

Family history and its association to curve size and treatment in 1,463 patients with idiopathic scoliosis

Purpose

To study family history in relation to curve severity, gender, age at diagnosis and treatment in idiopathic scoliosis.

Methods

A self-assessment questionnaire on family history of scoliosis was administered to 1,463 untreated, brace or surgically treated idiopathic scoliosis patients.

Results

Out of the 1,463 patients, 51 % had one or more relatives with scoliosis. There was no significant difference between females and males, nor between juvenile and adolescent study participants in this respect (p = 0.939 and 0.110, respectively). There was a significant difference in maximum curve size between patients with one or more relatives with scoliosis (median 35°, interquartile range 25) and patients without any relative with scoliosis (median 32°, interquartile range 23) (p = 0.022). When stratifying patients according to treatment (observation, brace treatment or surgery), we found that it was more common to have a relative with scoliosis among the treated patients (p = 0.011). The OR for being treated was 1.32 (95 % CI 1.06–1.64) when the patient had a relative with scoliosis, compared to not having.

Conclusions

Larger curve sizes were found in patients with a family history of scoliosis than in the ones without. No relation between family history and gender or between family history and age at onset of idiopathic scoliosis was found. Although the presence of a family history of scoliosis may not be a strong prognostic risk factor, it indicates that these patients are at higher risk of developing a more severe curve.     

Risk of adhesive obstruction after colorectal surgery: the benefits of the minimally invasive approach may extend well beyond the perioperative period

Background

Risk of adhesive small-bowel obstruction (SBO) is high following open colorectal surgery. Laparoscopic surgery may induce fewer adhesions; however, the translation of this advantage to a reduced rate of bowel obstruction has not been well demonstrated. This study evaluates whether SBO is lower after laparoscopic compared with open colorectal surgery.

Methods

Patients who underwent laparoscopic abdominal colorectal surgery, without any previous history of open surgery, from 1998 to 2010 were identified from a prospective laparoscopic database. Details regarding occurrence of symptoms of SBO (colicky abdominal pain; nausea and/or vomiting; constipation; abdominal distension not due to infection or gastroenteritis), admissions to hospital with radiological findings confirming SBO, and surgery for obstruction after the laparoscopic colectomy were obtained by contacting patients and mailed questionnaires. Patients undergoing open colorectal surgery for similar operations during the same period and without a history of previous open surgery also were contacted and compared with the laparoscopic group for risk of obstruction.

Results

Information pertaining to SBO was available for 205 patients who underwent an elective laparoscopic procedure and 205 similar open operations. The two groups had similar age, gender, and sufficiently long duration of follow-up. Despite a significantly longer duration of follow-up for the laparoscopic group, admission to hospital for SBO was similar between groups. Patients who underwent laparoscopic surgery also had significantly lower operative intervention for SBO (8% vs. 2%, p = 0.006).

Conclusions

Although the rate of SBO was similar after laparoscopic and open colorectal surgery, the need for operative intervention for SBO was significantly lower after laparoscopic operations. These findings especially in the context of the longer follow-up for laparoscopic patients suggests that the lower incidence of adhesions expected after laparoscopic surgery likely translates into long-term benefits in terms of reduced SBO.