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Re: Splenectomy in cystic fibrosis

Dear Editor,

Splenectomy in cystic fibrosis (CF) remains controversial mainly because the spleen is considered indispensable in this disease for its important immunological function in the defence against the frequent infections. Furthermore centres which perform liver transplantation prefer this approach, even early after CF related liver disease (CFLD), becomes obvious, since it seems more ethiological.

The article by Linnane et al. (1) is an interesting contribution in this debate. Our recently published findings (2) largely confirm the present publication although we have, doubts on the correctness of the mentioned indications. While several of the more than 500 patients, we followed over the past fifty years, had a gigantic spleen, splenic rupture was never observed and at splenectomy the surgeons each time recorded a firm thickening of the splenic capsule. In literature spontaneous splenic rupture is mostly described in association with infections, inflammatory disease or malignancy i.e. conditions where the spleen enlarges over a short period of time while none is reported in CF. We therefore question “risk of rupture” in se as a right indication for splenectomy.It must by the way be difficult to decide on the appropriate timing for operation when this is the main indication since no information is available on the fragility of variably enlarged spleens.

While we agree that low platelets are indeed, no single indication for splenectomy, it can be justified in individual cases because of the risk for complications. A 19 y. old patient recently underwent splenectomy with splenorenal shunt out of fear for cerebral haemorrhage. He had a thrombopenia of 35 000/mm³, and frequent cutaneous bleeding following severe cough attacks. His spleen span was 25 cm and placement of TIPS had not resulted in any amelioration. Four months after removal of a 1.7 kg heavy spleen platelets are at 550000/mm³ and all skin signs have disappeared. Even if it can be debated that the trombopenia is no real reason for concern, knowing that it has normalised is reassuring. We confirm improvement of pulmonary function and a positive effect on nutritional status which was maintained even 5 years later. From the present article and our own it is clear that splenectomy can have many beneficial effects while delaying the need for liver transplantation during several years.

It should however only be performed in highly controlled conditions, also providing a rigorous follow-up constantly aware of the danger of an overwhelming sepsis.

References:

1. Linnane B, Oliver MR, Robinson PJ. Does splenectomy in cystic fibrosis related liver disease improve lung function and nutritional status? A case series. Arch Dis Child 2006; 91: 771-3

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Re: Enteric origins to hepatic and pulmonary dysfunction in cystic fibrosis?

Dear Editor,

I have considered the possiblity that asthma might have an enteric origin in the past (1) but did not include some of the more compelling data (2,3). Nielsen et al's data are particularly compelling demonstrating in addition the possible relevance of gut dysfunction in the evolution of hepatic diseases.

The demonstration that the pH of breath condensate is significantly lower in patients with asthma or cystic fibrosis than in controls (4) is also of interest in this regard for it raises the possibility that translocation of toxins and/or the cytokines they release might be transmitted to the lungs via lymphatic pathways that bypass the liver and induce a fall in alveolar pH in the same way that endotoxin causes a fall in intestinal intramucosal pH when administered systemically(5). Not only might this be an indication of a decline in Daniel Atkinson energy charge but the activity of xanthine oxidase implicated in free radical release appears to rise from zero at about 7.60 to 100% as the pH falls below 6.80. What is more the conversion of xanthine dehydrogenase, whose activity appears to be confined to pHs above 7.40, is induced by a rise in ionized [Ca++] which is known to occur when the pH falls.

I think there might be much to be gained from measuring the gastric intramucosal pH in conjunction with the alveolar pH in response to enteric stress tests in patients with cystic fibrosis. What is more it is just possible that a splenectomy might have improved pulmonary function in this case by eliminating an enteric cause. We have reported that the abnormal gastric intramucosal pH (6.84 +/- .04) in the patient with massive splenomegaly who had bled from erosionswhose pH was restored to normal levels (7.48 +/- .03, t = 9.69, p<0.0001) and the bleeding stopped by a central splenorenal shunt [which includes a splenectomy] even though it may have thrombosed (6). It will be interesting to see what happens to the hepatic disease in this patient.

References:

1. Asthma: might it have an enteric origin? Richard G Fiddian-Green bmj.com, 28 Sep 2004 eLetter re: Gary W K Wong, Fanny W S Ko, David S C Hui, Tai F Fok, David Carr, Erika von Mutius, Nan S Zhong, Yu Z Chen, and Christopher K W Lai Factors associated with difference in prevalence of asthma in children from three cities in China: multicentre epidemiological survey BMJ 2004; 329: 486

2. Fiddian-Green RG, Baker S. Nosocomial pneumonia in the critically ill: product of aspiration or translocation? Crit Care Med. 1991 Jun;19(6):763-9.

3. Nielsen VG, Tan S, Baird MS, McCammon AT, Parks DA. Gastric intramucosal pH and multiple organ injury: impact of ischemia-reperfusion and xanthine oxidase. Crit Care Med. 1996 Aug;24(8):1339-44.

4. 4. Direct vs indirect measurements of alveolar tissue pH. Richard G Fiddian-Green Chest Online, 4 Jul 2004 eLetter re: Giovanna E. Carpagnano, Peter J. Barnes, Jackie Francis, Nicola Wilson, Andrew Bush, and Sergei A. Kharitonov Breath Condensate pH in Children With Cystic Fibrosis and Asthma: A New Noninvasive Marker of Airway Inflammation? Chest 2004; 125: 2005-2010

5. Fink MP, Cohn SM, Lee PC, Rothschild HR, Deniz YF, Wang H, Fiddian -Green RG. Effect of lipopolysaccharide on intestinal intramucosal hydrogen ion concentration in pigs: evidence of gut ischemia in a normodynamic model of septic shock. Crit Care Med. 1989 Jul;17(7):641-6.

Send letter to journal:
Re: Re: spenectomy in cystic fibrosis

Dear Editor,

Not only might the risk of overwhelming sepsis after splenectomy have been exaggerated (1) even in children but any impairment in immune function might have an enteral rather than an asplenic origin. A fall in gut intramucosal pH, which may induced not only by endotoxaemia and sepsis but also by haemorrhage, may be accompanied by significant reductions in the number of T lymphocytes in the villi and increases of macrophages in the mucosa and mesenteric lymph nodes (2). Gut-Associated Lymphoid Tissue (GALT) may account for some 70% of the body's immunity ( Wikipedia). If, however, splenectomy reverses an intramucosal acidosis the cause of any overwhelming sepsis might have preceded the splenectomy.

References:

1. Richard G Fiddian-Green The rise of the dangerous cult of splenic preservation http://jcp.bmjjournals.com/cgi/eletters/57/4/407#77, 20 Apr 2004