Tawee Tanvetyanon

Herpes zoster during treatment with arsenic trioxide

In vitro data suggest that arsenic compounds can suppress cell-mediated immunity by inducing apoptosis of T helper lymphocytes. We describe an occurrence of herpes zoster during treatment with arsenic trioxide (ATO) in two patients who were already in remission from acute promyelocytic leukemia and received ATO as consolidation treatment. During this complication, their leukocyte counts and differentials were within normal limits. Our report suggested the immunosuppressive effect of ATO in vivo. Both patients responded well to an oral antiviral. Clinicians should be aware of this complication during treatment with ATO since early antiviral treatment may help avoid complications including post-herpetic neuralgia.

Recurrent steroid-responsive pancreatitis associated with myelodysplastic syndrome and transformations

Several paraneoplastic inflammatory conditions, particularly autoimmune diseases, have been described in association with myelodysplastic syndromes (MDS). However, to date, recurrent acute pancreatitis has never been described in association with MDS. A 44-year-old man presented with prolonged fever and fatigue. Aortitis and pericarditis were diagnosed simultaneously with MDS, refractory anemia with excess blast type 2. His erythrocyte sedimentation rate and c-reactive protein were markedly elevated. The vasculitic syndrome responded rapidly to corticosteroids, but soon after tapering of corticosteroids, acute pancreatitis developed. Pain and pancreatic enzymes, however, improved rapidly with escalation of corticosteroid dosage. Multiple attempts at discontinuing the drug resulted in symptomatic flare-ups. Finally, his MDS transformed into acute myeloid leukemia (AML); severe acute pancreatitis closely accompanied. Induction chemotherapy and high-dose corticosteroids, however, controlled both conditions. A subsequent pancreatitis attack with pseudocyst formation occurred, but again was controlled with corticosteroids, although this was followed closely by another relapse of AML. All etiologies for recurrent acute pancreatitis were ruled out. The dramatic response of his pancreatitis attacks to immunosuppression suggested its autoimmune origin, while the close relationship in both the timing and severity of acute pancreatitis and MDS/AML suggested that the autoimmune pancreatitis was a paraneoplastic phenomenon related to MDS.

Neoadjuvant therapy: An emerging concept in oncology

Neoadjuvant therapy, an adjunctive therapy given before the main therapy, has become an integral part of modern multidisciplinary cancer management. Organized by the primary organ involved by cancer, this review summarizes the outcomes of neoadjuvant therapy for common malignant solid tumors, based on large, randomized, controlled trials. In locally advanced rectal, laryngeal, and breast cancer, neoadjuvant therapy enables organ preservation; however, it does not improve overall survival when compared with definitive treatment followed by adjuvant therapy. In locally advanced bladder and cervical cancer, patients who undergo neoadjuvant therapy before radical surgery appear to have better survival than those receiving definitive therapy alone; however, it is unclear if the neoadjuvant approach will be superior to definitive therapy followed by adjuvant therapy. To date, the survival benefits of neoadjuvant therapy for resectable non-small cell lung, esophageal, gastric, and prostate cancer remains under investigation.

Proton pump inhibitors and iron deficiency: is the connection real?

Iron therapy has been used for centuries, perhaps dating back to 1500 BCE, even though recognition of iron deficiency has been more recent. The main causes of iron deficiency remain blood loss from the gastrointestinal and genitourinary tracts and, in poorer countries, lack of dietary iron. Gastrointestinal malabsorption of iron is a well-recognized but uncommon cause of this malady. Many factors influence the absorption of iron, which takes place in the duodenum. Heme iron, derived from animal blood and muscle, is absorbed more readily than the nonheme iron found in plants and iron salts. Most nonheme iron is in the ferric form, which is poorly soluble and needs to be reduced to the ferrous form before its absorption. This is accomplished with the help of a ferric reductase protein, controlled by the gene for DCYTB (a duodenal protein that bears homology to b-type cytochromes). DCYTB localizes to the intestinal brush border and its expression is amplified during iron deficiency, ineffective erythropoiesis, and hypoxia. Gastric acid also facilitates the conversion of ferric iron to ferrous form. In addition, the acid lowers the pH of upper duodenal contents, which improves iron absorption. If acidic environment in the stomach is important for iron absorption, will a hypochlorhydric or achlorhydric state alone lead to iron deficiency? There are no clear-cut data to support this contention. Iron deficiency has been described in patients with partial or total gastrectomy, vagotomy, and atrophic gastritis, but these conditions are more than a simple lack of gastric acid. Wintrobe stated in 1956 that “alone achlorhydria does not lead to iron deficiency.” Proton pump inhibitors (PPIs) are powerful inhibitors of gastric acid secretion, but have not been shown to cause iron deficiency. In this issue of the Southern Medical Journal, Sharma et al describe two patients with iron deficiency anemia from gastrointestinal bleeding. Both patients received omeprazole to control their gastritis and oral iron for the anemia for six months. Their symptoms and bleeding resolved, but their hemoglobin levels failed to rise. Discontinuation of omeprazole therapy, however, rectified the situation, and hemoglobin levels improved to near normal. In one patient, iron absorption studies demonstrated a blunted response to oral iron during omeprazole therapy. Iron absorption improved after withdrawl of this agent. The authors suggest that omeprazole therapy may render iron replacement therapy ineffective if the patient is already iron deficient. How does one explain these observations? Additional information would have been of help. Did the patients’ diet provide enough heme iron? Why was omeprazole continued for six months? Both patients were given ferrous sulfate, hence the need for acid-facilitated conversion to ferrous form was obviated (although acidic milieu is important to maintain the ferrous state). It is possible that the PPIs impede iron absorption, but the effect is minimal and will not become easily apparent in iron-replete subjects. In such a scenario, longer duration of achlorhydria, for example lasting six months but not two months, could prolong (or perhaps cause) iron deficiency. The PPIs may also have resulted in a higher pH in the duodenum affecting absorption of iron. A definitive answer about the relationship between PPI therapy and iron absorption can be provided only through a large, controlled trial with simultaneous studies of iron absorption. If such an association is confirmed, the findings of Sharma et al may influence clinical practice, and patients with iron deficiency anemia requiring long-term acid-suppressive therapy may need parenteral iron supplementation.

Pancytopenia in hereditary haemorrhagic telangiectasia

A 54-year-old man had suffered recurrent epistaxes and multiple mucocutaneous telangiectases since childhood. Both his father and his brother had been diagnosed with hereditary haemorrhagic telangiectasia (HHT). When aged 52 years, the patient suffered recurrent strokes, resulting in dysphasia. Magnetic resonance imaging of the brain revealed multiple cerebral infarctions (left). Chest radiograph and computerized tomography (CT) scan showed a nodular density in the right lower lobe of lung. Pulmonary angiography was performed and showed a large saccular arteriovenous malformation (AVM) (right). This was successfully treated by coil embolization. The patient has chronic iron deficiency anaemia. Over the last 2 years, he has also developed thrombocytopenia and leucopenia. His last blood count showed: haemoglobin 8Æ1 g/dl, leucocyte count 2Æ1 · 10/l, neutrophil count 1Æ4 · 10/l and platelet count 63 · 10/l. Coagulation studies were unremarkable; bone marrow biopsy showed normal haematopoiesis but CT of the abdomen demonstrated splenomegaly and multiple hepatic telangiectases. Hypersplenism was diagnosed. The blood counts have remained stable for 10 months. HHT or Rendu–Osler–Weber syndrome is an autosomaldominant disorder with variable penetrance, caused by mutations in the activin-receptor-like kinase-1 gene or the endoglin gene. Driven by abnormal angiogenesis, this disease is characterized by AVMs and bleeding telangiectases – recurrent gastrointestinal or nose bleeding is universal. Pulmonary AVM, seen in about 30% of patients, can lead to left-to-right shunt, causing stroke or polycythemia. Cerebral AVM also occurs in 10% of patients. In addition, hepatic AVM, although often asymptomatic, can result in high-output cardiac failure, portal hypertension and hypersplenism. Treatment of hepatic AVM is largely supportive; liver transplantation has been successful in selected patients with advanced disease. Splenectomy has been reported to resolve severe pancytopenia from hypersplenism or splenic AVM. By far the most common haematological problem, however, is iron deficiency anaemia – often requiring chronic iron therapy and blood transfusions. Tranexamic acid, aminocaproic acid or ethinylestradiol/norethisterone can be used to slow the ongoing blood loss. Among patients with pulmonary and cerebral AVMs, embolization may prevent complications. Prophylactic antibiotics are indicated before any dental or surgical procedures.

Octreotide for Refractory Diarrhea Associated with Capecitabine

Objective: To describe the effect of low-dose subcutaneous octreotide on refractory diarrhea associated with capecitabine. Case Summary: A 67-year-old white woman with recurrent metastatic breast cancer received monotherapy with capecitabine after failing docetaxel. The first 2 consecutive capecitabine cycles were well tolerated. The patient, however, developed severe watery diarrhea after the third cycle. Diphenoxylate, atropine, loperamide, and attapulgite, along with conventional supportive measures, did not significantly improve the diarrhea, resulting in prolonged hospitalization. Octreotide 100 μg every 8 hours was administered subcutaneously. Immediate relief in stool frequency was observed during the first day. The stool became more formed on the next day. The patient was ready for discharge after learning how to perform subcutaneous injections. Octreotide was continued at home for 3 more days. After discontinuation of octreotide, no recurrent diarrhea occurred. Capecitabine was not reinitiated. Discussion: Diarrhea is a potentially life-threatening complication from treatment with capecitabine, an oral fluoropyrimidine analog. Octreotide has shown efficacy for diarrhea from many conditions, including chemotherapy with irinotecan and intravenous fluoropyrimidines such as fluorouracil. Our report suggests that octreotide also is effective for diarrhea associated with capecitabine. The patients rapid response shortened her hospital stay and improved her quality of life. Conclusions: In our patient, subcutaneous octreotide, along with other conventional antidiarrheal therapies, was associated with rapid resolution of refractory diarrhea attributed to capecitabine.