Impact of CYP2D6 Polymorphisms on Tamoxifen Treatment in Patients With Retroperitoneal Fibrosis: A First Step Towards Tailored Therapy?

OBJECTIVE: To investigate the influence of CYP2D6 polymorphisms on outcomes and health-related quality of life of patients with retroperitoneal fibrosis (RPF) receiving tamoxifen (TMX). TMX is an effective alternative to corticosteroids for patients with RPF. Conversion of TMX to more potent endoxifen is dependent on enzyme activity of CYP2D6. MATERIALS AND METHODS: CYP2D6 genotyping and phenotype prediction of all patients treated with TMX between 02/2007 and 01/2018 was assessed using multiplex polymerase chain reaction (PCR). Groups were classified by phenotype: extensive (EM) vs poor and intermediate (PM + IM) vs ultrarapid metabolizer (UM). Retrospective evaluation of outcome (including magnetic resonance imaging and positron emission tomography-computed tomography) and health-related quality of life using the SF-36 was performed. RESULTS: A total of 63/194 patients received TMX, 40/63 with complete follow-up were sequenced: Twenty-nine patients with EM phenotype, 8 PM + IM and 3 UM. The median therapy duration was 364.5 days with a mean follow-up of 62.9 months. Seven therapy terminations occurred due to lack of response (17.5%), including all UM patients (P <.001). Magnetic resonance imagings showed a regression of fibrosis for EM and PM + IM in 69% and 62.5% of cases and a progression for UM in 100% (P = .004). In positron emission tomography-computed tomography, glucose utilization of RPF decreased significantly for EM and PM + IM. The physical sum-score of SF-36 improved for EM and PM + IM and decreased for UM (P <.05). The removal of DJ-stents was successful for EM, PM + IM, and UM in 48.3%, 75%, and 0% of cases (P = .0581). CONCLUSION: Contrary to expectations, UM showed the lowest success rate, which concludes that genotyping of RPF-patients may be useful in the sense of a tailored-therapy.

Remission of "mistletoe sign" after treatment.

We described a 55-year-old man, in whom the first manifestation of retroperitoneal fibrosis (RPF) was only coronary arterial involvement, which had no periaortic or peri-iliac and urinary system retroperitoneum involvement in general and other systemic clinical manifestations. Coronary manifestation was called "mistletoe sign" on the images. Here, we report a case of IgG4-related RPF remission that was only coronary arterial involvement after treatment.

Characterization of a hemophore-like protein from Porphyromonas gingivalis.

The porphyrin auxotrophic pathogen Porphyromonas gingivalis obtains the majority of essential iron and porphyrin from host hemoproteins. To achieve this, the organism expresses outer membrane gingipains containing cysteine proteinase domains linked to hemagglutinin domains. Heme mobilized in this way is taken up by P. gingivalis through a variety of potential portals where HmuY/HmuR of the hmu locus are best described. These receptors have relatively low binding affinities for heme. In this report, we describe a novel P. gingivalis protein, HusA, the product of PG2227, which rapidly bound heme with a high binding constant at equilibrium of 7 × 10(-10) M. HusA is both expressed on the outer membrane and released from the organism. Spectral analysis indicated an unusual pattern of binding where heme was ligated preferentially as a dimer. Further, the presence of dimeric heme induced protein dimer formation. Deletional inactivation of husA showed that expression of this moiety was essential for growth of P. gingivalis under conditions of heme limitation. This finding was in accord with the pronounced increase in gene expression levels for husA with progressive reduction of heme supplementation. Antibodies reactive against HusA were detected in patients with chronic periodontitis, suggesting that the protein is expressed during the course of infection by P. gingivalis. It is predicted that HusA efficiently sequesters heme from gingipains and fulfills the function of a high affinity hemophore-like protein to meet the heme requirement for growth of P. gingivalis during establishment of infection.

The efficiency of Sairei-to for retroperitoneal fibrosis: two case reports.

The conventional approach for management of retroperitoneal fibrosis (RF), an inflammatory process of retroperitoneal fibro-adipose tissue, leading to the compression and obstruction of the ureters and other adjacent organs is ureterolysis with omental wrapping, and an effective alternative to surgery is immunosupressive medication such as oral corticosteroids. Sairei-to (TJ-114) is a traditional herbal medicine used for the treatment of RF in Japan. It has both anti-inflammatory and anti-allergic effects. Here we report two cases of RF successfully treated with Sairei-to. One case was idiopathic and the other was caused by artificial graft-induced vasculitis. Both cases were treated with Sairei-to following the decompression of uremia by precutaneous nephrostomy or indwelling ureteral stents. There was hardly any ureteral obstruction three months after the administration of Sairei-to. They have been doing well for 12 and 26 months. Sairei-to rarely causes side effects such as immunodeficiency, gastro-duodenal ulcer and osteoporosis that often accompany long-term administration of corticosteroids. Sairei-to is a safe and effective medicine for the treatment of RF. We therefore recommend Sairei-to as an alternative for corticosteroid therapy.

Visceral organ involvement is infrequent in oral submucous fibrosis (OSF).

Associated visceral organ involvement evidence by systemic fibrosis has not been explored in oral submucous fibrosis (OSF). The investigations in this aspect were limited to loco-regional sites of naso/oropharynx and oesophagus. The study of whether the oral fibrosis is part of a systemic spectrum of disease involving multiple organs is an interesting pursuit. With this intention the patients diagnosed on clinical and histological grounds for OSF were concurrently tested by biophysical means for the presence of endomyocardial fibrosis (EMF), pancreatic (PF) and retroperitoneal fibrosis (RPF), which are endemic to the area studied. Twenty-five (n = 25) cases of OSF who visited the Department of Oral pathology & Microbiology. Govt. Dental College, Trivandrum, India for symptomatic relief of their illness comprised the study group. Ten (n = 10) age and sex matched healthy volunteers comprised the control. All the subjects have had undergone cardiologic and gastrointestinal investigations to rule out the possibility of concurrent EMF and PF. The patients were all of Indian ethnic extraction and mostly (> 90%) were from low socio economic classes. The mean age of the patients was 54.16 +/- 14.6 years, including 18 females and 7 males (F:M = 2.57:1). The severity of fibrosis was unrelated to the age of patients (P > 0.05). All the patients were chewers of areca quid (12%)/tobacco (88%). In addition to quid chewing 3/25 (12%) patients smoked 'bidi' and 6/25 (24%) consumed home brewed liquor (arrack/toddy) which contain about 40-50% ethanol. Statistically no relationship was observed between the clinical stages of OSF and severity of epithelial dysplasia in this study (P > 0.05). Out of the 25 patients, 5 (20%) showed sclerotic aortic value which may be an age related finding. Also 7 (28%) patients were found to be hypertensive and interstitial lung disease was present in 2 (8%). The possibility of EMF in one female patient who showed thickened RV apical endocardium was ruled out by cardiac catheterisation. Thus none of the patients showed evidence of endomyocardial fibrosis. The pancreas was found to be hyperchoic in 8(32 1/4) by ultra sonography. Liver was found to be hyperchoic in 6 (24%). Fat stain in stool samples was found to be positive in 13(58%). The hyperchogenecity of pancreas may be due to alcoholism or an underlying endocrine pancreatic insufficiency like diabetes and not due to pancreatic fibrosis. The positivity of fat stain could be due to fatty liver/alcoholism. Thus the study fails to reveal any evidence of pancreatic fibrosis in the group. The lack of any evidence of an associated visceral organ fibrosis in OSF made it prudent to believe that this is a loco-regional disease, initiated by local factors and propagated under their influence without systemic involvement.

[A case of idiopathic retroperitoneal fibrosis causing acute renal failure and markedly responsive to drug therapy].

We report a case of idiopathic retroperitoneal fibrosis in a 66-year-old man. He was admitted to our hospital because of acute renal failure, and emergent hemodialysis was performed. Computed tomography scanning showed a retroperitoneal mass surrounding the abdominal aorta and bilateral common iliac arteries. The mass involved bilateral ureters and acute renal failure was caused by bilateral hydronephrosis. Magnetic resonance imaging demonstrated that the mass was slightly high intensity on T2 weighted image. It was considered to be idiopathic retroperitoneal fibrosis. After inserting ureteral catheters into bilateral ureters, his renal function recovered. The layer of the fibrosis became thin by steroids and traditional Chinese medicine, and bilateral ureteral catheters could be removed two months later. At ten months after the treatment, no ureteral obstruction was observed and renal function is preserved.

Retroperitoneal fibrosis: unusual localization.

Six cases of retroperitoneal fibrosis, each with a different pathogenesis and unusual localization were observed from 1980 to 1996. Four patients had had previous surgery for a neoplasm, one patient had idiopathic retroperitoneal fibrosis, and the last patient was hardly classifiable due to the complexity of the clinical pattern. The mean survival in 3 patients with malignant retroperitoneal fibrosis was 7 months. Two patients treated with medical therapy are still alive and in good clinical condition. The aspecificity of the symptoms makes early diagnosis difficult. CT and NMR are essential procedures for differential diagnosis of abdominal masses. Histology differentiates benign from malignant retroperitoneal fibrosis. The choice between medical or surgical therapy depends on the general condition of each patient.

Retroperitoneal fibrosis mimicking a rectal tumor: report of a case.

PURPOSE: The study contained herein was undertaken to report an original case of retroperitoneal fibrosis that resembled a rectal tumor both symptomatically and radiologically. METHOD: Reported is a case of retrorectal fibrosis with a brief literature review of the topic. RESULT: Although many forms of retroperitoneal fibrosis have been reported, extension below the pelvic rim is very unusual. Compression of the rectum and right ureter, with constipation as a chief complaint, made this case presentation unusual. Although computerized tomographic findings and needle biopsies supported the diagnosis of retroperitoneal fibrosis, an exploratory laparotomy was necessary to rule out a malignancy and to release the ureter. CONCLUSION: A fibrotic mass involving the retrorectal region may mimic a rectal tumor. To reach a final diagnosis, an exploratory laparotomy may be necessary, despite sophisticated evaluation techniques, because it is difficult to differentiate whether the mass is malignant.

[Clinical efficacy of sairei-to in various urinary tract diseases centering on fibrosis].

A joint multi-institution study was conducted on the efficacy of Sairei-to, centering on urinary tract fibrosis. The subjects consisted of 18 patients with retroperitoneal fibrosis (including 3 women), 77 patients with plastic induration of penis, 5 patients with sclerotic lipogranuloma (all men), and 67 patients with hemorrhagic cystitis (including 6 men). As a rule, Sairei-to was administered in monotherapy for periods of 4 weeks or longer. Efficacy was most pronounced in the patients with sclerotic lipogranuloma and plastic induration of penis, with overall improvement rates (percentage of patients with ratings of effective or better) of 80% in the former and 77.9% in the latter group. The overall improvement rate in the patients with retroperitoneal fibrosis was 61.1%. In the above diseases, there were numerous patients concurrently administered drugs such as antiinflammatory enzyme preparations and corticoid preparations, and the improvement rates were somewhat higher in these patients treated concurrently with other drugs. Outstanding efficacy was also seen in hemorrhagic cystitis. Dividing the patients into irradiation and non-irradiation groups, respective overall improvement rates of 77.8% and 82.8% were obtained, with the non-irradiation group showing a slightly higher rate. The non-irradiation group showed slightly higher improvement rates in the subjects treated concurrently with drugs such as antibacterial drug. Conversely, the irradiation group showed significantly superior rates for monotherapy. Side effects such as mild gastrointestinal disturbances were seen in only 13 of 167 patients (7.8%), and the utility of this drug in treatment of the above diseases should be held in high regard.

[Retroperitoneal fibrosis due to barium]. / Fibrose rétropéritonéale sur baryte.

The authors report two cases of retroperitoneal fibrosis secondary to rectal perforation occurring during barium enema. In view of the variable interval between the radiological accident and the urological complications, a long patient follow-up is recommended. If ureteric obstruction occurs, ureteric catheterisation is a temporary alternative, but surgery is the treatment of choice. When ureterolysis cannot be performed, the authors propose ureteroileoplasty to restore continuity of the urinary tract.

Retroperitoneal fibrosis presenting as colonic dysfunction: CT diagnosis.

In a patient who presented with pelvic pain and changed bowel habits, barium enema and sigmoidoscopic examinations demonstrated a nonspecific asymmetric narrowing of the colon at the rectosigmoid junction with normal mucosal appearance. Computed tomography revealed the etiology to be retroperitoneal fibrosis with pelvic extension and entrapment of the colon at this level. The importance of CT in diagnosis of this unusual manifestation of retroperitoneal fibrosis is discussed.

Computed tomography in the differential diagnosis of the enlarged retrorectal space.

The value of computed tomography (CT) in the differentiation of an enlarged retrorectal space was analyzed in 132 cases. Classification of barium enema findings into those with simultaneous mucosal alterations and those without any visible lesions of the rectal mucosa seems to be useful. Computed tomography helps in those cases without mucosal changes to differentiate between retrorectal fibrosis, tumorous masses, and inflammatory diseases of the colon. It also demonstrates the lack of pathologic lesions in equivocal cases of pelvic lipomatosis and so-called "normal variants." If simultaneous mucosal involvement on barium enema--especially in rectal carcinoma or recurrent carcinoma of the rectum--is found, CT may show the perirectal extension of tumorous masses and thus help to clarify local operability.

Retroperitoneal fibrosis: an alternative therapy.

A case of retroperitoneal fibrosis satisfactorily treated with indwelling double J catheters is presented. This method, although reserved for special cases, is an adequate alternative treatment as it allows efficient long-term drainage of kidneys without aggressive surgical dissection of ureters.

[Iatrogenic secondary retroperitoneal fibrosis (secondary Ormond disease) caused by contrast medium enema, and the treatment of the resulting hydronephrosis with endourethral splinting ("endoprosthesis")]. / Iatrogene sekundäre retroperitoneal Fibrosierung (sekundärer Morbus Ormond) durch Kontrastamitteleinlauf und die Behandlung der entstandenen Harnstauungsnieren mit der endoureteralen Schienung ("Endoprothese").

A case of secondary retroperitoneal fibrosis with bilateral hydronephrosis, following a barium enema is presented. The mechanism of perforation and the ways of perforation are being discussed. The importance of early surgical intervention is stressed. For treatment of the hydronephrosis an endoureterine splinting was indicated.

Retroperitoneal barytoma.

A rare case of retroperitoneal fibrosis after rectal perforation during a barium enema is reported. Pelvic cellulitis due to infiltration of barium and fecal matter is a serious complication and needs an energetic treatment. Urologic complications appear later and result from the formation of a foreign body granuloma.

Juvenile colonic polyposis with villous adenoma and retroperitoneal fibrosis: Report of a case.

A 25-year-old Nigerian black woman was found to have polyps involving the rectum, rectosigmoid, and sigmoid colon on air-contrast barium-enema examination. Resection of a segment of sigmoid colon revealed numerous polyps that were predominantly of the juvenile type, in keeping with the diagnosis of juvenile polyposis of the colon. This case is unusual because of the coexistence of retroperitoneal fibrosis with juvenile polyposis of the colon. In addition, one of the colonic polyps was a villous adenoma. The implications these findings are discussed in relation to polyposis syndromes reported previously.

Pelvic lipomatosis.

Although usually in the domain of the urologist, pelvic lipomatosis sometimes first may present to the general surgeon. Often called perivesical lipomatosis, this process of unknown etiology has been defined as a nonmalignant overgrowth of normal fatty tissue limited primarily to the perirectal and perivesical spaces in the pelvis. Typically it occurs in middle-aged, nonobese, men presenting with dysuria and sometimes with suprapubic fullness. High position of the prostate may be noted on rectal examination. Urinary tract roentgenograms show a high, gourd-shaped bladder with the surrounding radiolucency of fatty tissues. Elongation of the urethra usually makes cystoscopy difficult. Sigmoidoscopy and barium enema may reveal extrinsic pressure on the rectum. Pelvic venography rarely shows external venous compression; arteriography does not suggest neoplastic vessels. Fat metabolism studies are of little value. The absence of adequate cleavage planes renders direct surgical management difficult. The frequently progressive lower ureteral obstruction eventually may require urinary diversion. Four biopsy-proved cases from the Eastern Virginia Medical School Hospitals are reported, and the 57 previous cases from the literature are reviewed.

[Radiologic diagnosis of retroperitoneal fibrosis (author's transl)]. / Zur röntgenologischen Diagnostik der retroperitonealen Fibrose

The value of the various radiologic techniques for the diagnosis and follow-up of retroperitoneal fibrosis are discussed on the basis of two case reports and an analysis of 48 patients. The most important technique is the IVP with breathing and profile exposures. AP and lateral pre-operative retrograde pyelography is often essential for the diagnosis. Cavography and arteriogram should always be done in this condition, since they permit assessment of vascular compression and extension distally of the fibrosis. MDP and contrast enema should be employed, if the signs warrant it. These radiologic techniques permit, when positive, combined surgical planning by various surgical specialists.