Mismatch repair deficiency, chemotherapy and survival for resectable gastric cancer: an observational study from the German staR cohort and a meta-analysis.

PURPOSE: In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. METHODS: Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. RESULTS: MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13-3.37, P = 0.63) and 1.44 (95% CI 0.66-3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14-0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89-1.58, P = 0.26). CONCLUSION: Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.

Efficacy of botulinum-A toxin bladder injections for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients: an objective and subjective analysis.

AIMS: We studied the use of botulinum-a toxin (BTX-A) injections into the bladder as an alternative approach in patients with neurogenic detrusor overactivity due to multiple sclerosis (MS) with drug-refractory overactive bladder (OAB) symptoms. METHODS: Sixteen MS patients--11 women, 5 men; mean age 48.6 years--with refractory OAB symptoms were included in a one-center prospective study. For outcome analysis, we used a bladder diary, a complete urodynamic study, and validated questionnaires for subjective assessment. We injected 300 U of BTX-A (Botox) into the bladder and into the external sphincter muscle to reduce the probability of posttreatment urine retention. RESULTS: There was an increase in residual volume from 81.3 +/- 23.8 to 126.3 +/- 32.9 ml after 4 weeks. In one woman, transient self-catheterization was unavoidable. Four weeks and 3 and 6 months after BTX-A injection, the significant results were as follows: daytime frequency was reduced by 29%, 44%, and 30%, respectively. Nocturia diminished by 33%, 72%, and 40%. Use of pads was be reduced by 38% after 4 weeks and by 64% after 3 months. Urodynamically, reflex volume and maximal cystometric bladder capacity increased by 73%, 77%, and 58% (at 6 months, the increase was not significant) and by 36%, 27%, and 36% (not significant). Maximal detrusor pressure decreased by 35%, 22%, and 57%. Subjective outcome indicated significant improvement of symptoms at 4 weeks and 3 months, but not at 6 months. Patient satisfaction with the therapy was very high. CONCLUSIONS: BTX-A detrusor injections are very effective in the treatment of drug-resistant OAB symptoms in MS patients as reflected in urodynamic measurements and in patient satisfaction. Build up of residual urine remains a problem of which patients must be informed.

A new option for the management of urethral trauma: primary reconstruction of posterior urethral disruption with a buccal mucosa transplant.

Up to now, the management of traumatic posterior urethral disruption ranges from primary realignment to delayed urethroplasty. However, we reconstructed the membranous part of the urethra with an onlay graft of buccal mucosa after traumatic complete disruption as a first line therapy. After 7 months followup, the clinical outcome is very good. Because primary reconstruction of the urethra with a buccal mucosa graft after traumatic disruption has not yet been reported, the question arises whether this technique should be routinely included as an option for primary urethral reconstruction after trauma of the posterior urethra.

[Subjective patient satisfaction after injection of botulinum-a toxin in detrusor overactivity]. / Subjektive Patientenzufriedenheit nach Botulinumtoxin-A-Injektionen bei Detrusorhyperaktivität.

PURPOSE: The established treatment for overactive detrusor function consists of anticholinergic drugs. But this treatment can fail or produce intolerable side effects. We therefore investigated the effect of botulinum-A toxin in treating overactive detrusor function in patients with neurogenic and nonneurogenic bladder dysfunction. We were particularly interested in patient satisfaction with this therapy. MATERIAL AND METHODS: The subjects were 38 patients who had overactive detrusor function of different origins and in whom therapy with anticholinergic drugs had failed. To measure results, we used urodynamic studies and a questionnaire that consisted of 27 validated questions ("Urogenital Distress Inventory UDI-6", "Symptom Severity Index" and "Symptom Impact Index") as well as a satisfaction questionnaire. We injected 200 - 300 U of botulinum-A toxin (Botox) cystoscopically. RESULTS: At least 4 weeks after injection, 90 % of the patients reported clear improvement of their voiding situation and 93 % stated that they would undergo this procedure again. The frequency of micturition decreased by 29 % in average, and the increased postvoid residual volume was clinically irrelevant. Patients reported side effects or complications in 6.7 % of cases. The satisfaction scale (0 - 10) averaged 6.9. Urodynamically, reflex volume increased by 85 %, maximal bladder capacity increased by 47 %, and bladder pressure decreased by 33 %. CONCLUSIONS: Botulinum-A toxin injection into the overactive detrusor muscle seems to be very effective. The effect is not only reflected in urodynamic studies but also in the subjective patient satisfaction.

Efficacy of botulinum-a toxin in children with detrusor hyperreflexia due to myelomeningocele: preliminary results.

OBJECTIVES: The established treatment of children with neurogenic bladder consists of the use of anticholinergic drugs, such as oxybutynin and tolterodine, and clean intermittent catheterization four or five times a day. If anticholinergic drugs and clean intermittent catheterization fail, surgery is often necessary. With the intent of avoiding surgery, we investigated the effect of botulinum-A toxin for treating detrusor hyperreflexia in this group of patients. METHODS: The subjects were 17 children (average age 10.8 years) who had detrusor hyperreflexia and were using clean intermittent catheterization four or five times a day. Urodynamic studies were followed by injection of 85 to 300 U of botulinum-A toxin into 30 to 40 sites in the detrusor muscle. Urodynamic follow-up was done 2 to 4 weeks after injection. RESULTS: The mean reflex volume increased by 112.1%, from 95.00 plus minus 34.54 mL (range 47 to 147) to 201.45 plus minus 68.57 mL (range 77 to 310) (P <0.005). The maximal bladder capacity increased by 56.5%, from 137.53 plus minus 59.96 mL (range 59 to 242) to 215.25 plus minus 96.36 mL (range 60 to 380) (P <0.005). The maximal detrusor pressure decreased by 32.6%, from 58.94 plus minus 32.32 cm H(2)O (range 19 to 149) to 39.75 plus minus 26.12 cm H(2)O (range 7 to 100) (P <0.005). Detrusor compliance increased by 121.6%, from 20.39 plus minus 26.5 mL/cm H(2)O (range 4.5 to 40) to 45.18 plus minus 45.4 mL/cm H(2)O (range 5.3 to 100) (P <0.01). CONCLUSIONS: Botulinum-A toxin injection into the hyperreflexive detrusor muscle seems to be very effective and might be a therapeutic alternative to anticholinergic drugs.

Association of maternal G protein beta3 subunit 825T allele with low birthweight.

Weight at birth has been associated with an increased risk for cardiovascular disease and type 2 diabetes in adult life. We found an association between the maternal G protein beta3 subunit 825T allele and low birthweight in babies born to women without other risks for reduced fetal growth.

[Malignant fibrous histiocytoma of the lung]. / Malignes fibröses Histiozytom der Lunge.

The malignant fibrous histiocytoma of the lung is one of the rarely diagnosed soft tissue sarcomas. With the presented case-history we want to remind of this kind of lung-tumour in particular of the possibility of pre-operative diagnostic and the radiological differential diagnosis.

Monozygotic triplets with Crohn's disease of the colon.

Female monozygotic triplets all developed Crohn's disease within a period of 11 mo. The monozygosity was demonstrated by analysis of 24 genetic markers of different chromosomal localization. Crohn's disease was diagnosed using clinical, radiologic, and endoscopic findings. Histologic evaluation of bowel tissue was consistent with Crohn's disease. All 3 patients had colon involvement; the terminal ileum appeared normal. The patient in whom Crohn's disease was first diagnosed had the severest course. Our observations support the role of a genetic influence in the manifestation of Crohn's disease. Nevertheless, environmental factors or microorganisms, or both, have to be taken into account, perhaps as factors promoting the outbreak of Crohn's disease.

Clinical features of inflammatory joint and spine manifestations in Crohn's disease.

167 patients with Crohn's disease were investigated for joint and spine inflammation. Arthritis was observed in 23 patients (14%), sacroiliitis in 24 (14%), and sacroiliitis in combination with arthritis in 11 patients (7%). 15 patients (9%) had ankylosing spondylitis; 9 of them were HLA-B27 positive (60%). A parallel pattern in the course of bowel disease and joint inflammation was observed in 22 out of 34 patients with arthritis (59%). An association between the localization of Crohn's disease and the type of spondylarthritis could not be demonstrated. Patients with arthritis alone developed erythema nodosum (35%) or aphthous stomatitis more often (21%) than patients without spondylarthritis+ (6% and 12%, respectively). Other extra-intestinal manifestations of Crohn's disease did not reveal any association with the development of spondyloarthritis.

[Intramural pseudodiverticulosis of the esophagus. Clinical aspects, morphologic changes and functional disorders]. / Die intramurale Pseudodivertikulose des Osophagus. Klinik, morphologische Veränderungen und Funktionsstörungen.

Oesophageal intramural pseudodiverticulosis, a rare benign disease with as yet unexplained aetiology, was observed in 4 patients during the course of 2 years. The main symptom is dysphagia. Radiographic and endoscopically detectable diverticula or diverticular orifices are pathognomonic. A prolongation in the duration of oesophageal contractions is the main manometric finding. At autopsy, a reduction in the number of oesophageal intramural ganglion cells was seen in one case. A prolonged pressure-effect on the oesophageal wall could be the cause of the wall pouches.

Reconstructive vascular surgery for hypertension in renal vascular dysplasia.

28 patients with renovascular hypertension caused by fibromuscular dysplasia involving one or more renal arteries underwent reconstructive surgery. The renal artery stenosis was bilateral in 5 patients. Total artery occlusion occurred in 3 cases. Arteriography was the most useful diagnostic procedure. The operative technique of choice was replacement using saphenous vein or hypogastric artery. All patients survived. On follow-up, 27 patients (96.4%) were either cured or improved. Isotope nephrography suggested restenosis in 1 case. Our results support an aggressive approach to the diagnosis and surgical treatment of renal artery fibromuscular dysplasia causing hypertension.

[Renal artery occlusion. Blood pressure and kidney function before and after surgical treatment]. / Nierenarterienverschluss. Blutdruck und Nierenfunktion vor und nach operativer Behandlung.

Angioplasty was performed in 16 patients with renal artery occlusion. It was successful in each of six acute occlusions, although four patients died later of their underlying disease. Two patients are long-term survivors and have normal or compensated renal function up to three years postoperatively. Vessel reconstruction was successful in eight of ten patients with chronic occlusion. In seven there was definite improvement or normalization of the hypertension, in six renal function returned to normal. Thus the success rate as to organ preservation with improvement in pressure and function was 60%.

[Diagnostic problems in the differentiation of achalasia and spasm of the oesophagus (author's transl)]. / Differentialdiagnostische Probleme bei der Abgrenzung von Achalasie und Osophagusspasmus.

In 15 patients suspected to have achalasia or diffuse spasm of the oesophagus we were unable to make the final diagnosis of their motility disorder in spite of radiologic, endoscopic, and manometric examinations. In 5 patients the radiologic and manometric results showed a discrepancy. In 4 patients only the lower oesophageal sphincter exhibited failure fo complete relaxations typical of achalasia; however, the motility of the body of the oesophagus was peristaltic in nature. In 6 patients the initial diagnosis had to be changed during follow-up. In conclusion, motility disorders occur in the oesophagus which cannot be classified according to existent definitions. It is possible therefore that achalasia and oesophageal spasm are different and not always fixed expressions of one nosologic entity.

[Esophageal stenosis in sjögren's syndrome]. / Osophagusstenose bei Sjögren-Syndrom.

Dysphagia in Sjögren's syndrome may be caused by xerostomy, pharyngoesophagitis and esophageal membranes. This is the first report on a tubular upper esophageal stenosis in a 71 year old woman with Sjögren's syndrome who developed progressive dysphagia. It is suggested, that this stenosis was due to chronic inflammatory processes and secondary sclerosis of deep layers in the esophageal wall. Bouginage was adequate symptomatic therapy. Tubular esophageal stenosis is regarded as gastrointestinal manifestation of Sjögren's syndrome.

[Localized retroperitoneal xanthofibrogranuloma simulating a pancreatic tumor]. / Lokalisiertes retroperitoneales Xanthofibrogranulom unter dem Bild eines Pankreastumors.

The diagnosis of xanthofibrogranuloma is difficult. This is examplified by observations in a 46-year-old man with a palpable tumor in the left upper abdomen. Even modern diagnostic procedures like ultrasound, angiography and ERCP were unable to clarify the diagnosis. Only when laparotomy demonstrated a circumscript tumor, 7 x 7 x 10 cm in size, below the pancreas which was enucleated, the suspicion of a pancreatic tumor could be dismissed. The different clinical pictures of xanthofibrogranuloma ware discussed. Etiology is still unknown. Therapy as a rule should be surgical.

[Chronic occlusion of a renal artery with aneurysms in the para-aortic collateral circulation and multiple aneurysms in both kidneys (author's transl)]. / Chronisch-zentraler Nierenarterienverschluss mit Aneurysmen in der paraaortalen Kollateralarterie und multiplen Aneurysmen beider Nieren.

Chronic occlusion of the main renal artery may be followed by the development of a collateral circulation through ureteric and para-aortic arteries, and through lumbar and suprarenal arteries. A patient with occlusion of the left main renal artery is described, who developed a collateral circulation between the common iliac artery and the distal portion of the renal artery. The para-aortic collateral vessel developed one large and several small aneurysms, and there were aneurysms in both kidneys.