Evidence for a role for IL-5 and eotaxin in activating and recruiting eosinophils in drug-induced cutaneous eruptions

BACKGROUND: Cutaneous drug reactions may be associated with increased numbers of eosinophils in the blood and tissue. However, the factors leading to the generation of eosinophilia have not been fully delineated. OBJECTIVE: The aim of this study was to investigate the in situ expression of IL-5, eotaxin, RANTES, monocyte chemoattractant protein 3, and IL-8 together with the appearance of eosinophils in acute cutaneous drug reactions. METHODS: Skin biopsy specimens were obtained from drug-induced maculopapular exanthems (n = 9), from normal skin of control subjects (n = 9), and from the skin of patients with psoriasis (n = 8). The in situ expression of IL-5, eotaxin, RANTES, monocyte chemoattractant protein 3, and IL-8 was analyzed by using immunohistochemistry. Furthermore, the corresponding numbers of eosinophils were determined in the blood and skin sections. RESULTS: Compared with normal skin and psoriatic skin, a significantly higher number of eosinophils was found both in the blood and tissue of patients with a drug-induced exanthem. In comparison with normal skin, immunoreactivity for IL-5 and all the chemokines was also significantly enhanced in drug-induced exanthem, whereas significant differences in psoriatic were only observed for IL-5 and eotaxin. CONCLUSION: Our data indicate that IL-5 and eotaxin may particularly contribute to the activation and recruitment of eosinophils and thereby play an important pathogenic part in the development of skin inflammation in drug-induced maculopapular exanthems.     

Histopathological study of regional lymph nodes in osteosarcoma.

This paper presents the histological appearance of the lymph nodes in cases of osteogenic sarcoma of the limb bones. The nodes were studied for the degree of sinus histiocytosis. Cases with no sinus histiocytosis showed a poor prognosis while cases with moderate to marked sinus histiocytosis showed a better rate of survival. Since the regional lymph nodes play an important part in the immunological process, preservation of regional nodes is suggested.     

Reoperative pancreaticoduodenectomy for periampullary carcinoma

BACKGROUND: Potentially resectable periampullary tumours may not be treated appropriately due to lack of local expertise in both assessment of resectability and resection in referring centres. Tata Memorial Hospital is a major referral centre for oncology and these patients are finally referred to this institution. In carefully selected patients, resection can be accomplished. The purpose of the present paper was to determine the perioperative morbidity and mortality for patients undergoing reoperative pancreaticoduodenectomy at a major comprehensive cancer centre. METHODS: Between January 1991 and December 2001 15 patients, who had undergone previous non-resectional surgery for operable periampullary carcinoma, underwent re-exploration. The perioperative morbidity and mortality were analysed and compared with that of the group of patients undergoing primary pancreaticoduodenectomy (143 patients) in the same period. RESULTS: All the 15 patients undergoing re-exploration had a successful resection by pancreaticoduodenectomy. In the reoperative group eight patients (53%) underwent classic pancreaticoduodenectomy and seven patients (46%) had a pylorus-preserving pancreaticoduodenectomy, as compared to 102 (71%) and 41 (29%) patients in the primary surgery group, respectively. Although the mean operative time and the estimated blood loss were higher in the reoperative group, the morbidity and mortality rates were similar in the two groups. The overall 30-day mortality rate was 6.6% and 6.9% in the reoperative and the primary surgery group, respectively. Major morbidity occurred in two of the 15 patients (13.3%), and one patient (6.6%) died following surgery in the reoperative group. CONCLUSION: Reoperative pancreaticoduodenectomy can be performed safely in carefully selected patients with resectable, localized periampullary tumours with similar morbidity and mortality to patients undergoing primary surgery.     

Effect of preoperative biliary stenting on immediate outcome after pancreaticoduodenectomy

BACKGROUND: Preoperative biliary stenting is associated with bacterial contamination of bile and an increased rate of infectious complications after pancreaticoduodenectomy. Preoperative drainage has been found to have conflicting effects on morbidity and mortality, and no studies have been published on the effect of stent complications and duration of stenting on postoperative outcome. This study examined the effects of preoperative biliary stenting on early outcome after pancreaticoduodenectomy. METHODS: Details of 144 patients undergoing pancreaticoduodenectomy from 1992 to 2001 were entered into a database. Variables included biliary stenting, duration of stenting, stent complications and bile culture results. Details of surgery and postoperative complications were noted. Patients were grouped as stented and non-stented. Factors likely to affect postoperative mortality and morbidity were analysed. RESULTS: Preoperative biliary stenting was performed in 74 of the 144 patients; post-stenting complications developed in 18 patients (24 per cent) before surgery. After surgery there were nine deaths (6.3 per cent) and 60 (41.7 per cent) of the 144 patients developed complications, with no significant difference in morbidity rate between stented and non-stented patients. Logistic regression showed that a positive intraoperative bile culture was the only factor significantly associated with operative morbidity (P < 0.001) and mortality (P = 0.019). Biliary stenting was not significantly associated with a positive culture (P = 0.073), but stenting that resulted in complications (P = 0.006) and drainage for less than 6 weeks (P = 0.011) was associated with significantly greater culture positivity. Stenting followed by complications was shown by logistic regression to be the only factor significantly associated with a positive culture (P = 0.012). CONCLUSION: A positive intraoperative bile culture was associated with higher morbidity and mortality rates following pancreaticoduodenectomy. A positive culture in the stented group was related to stent complications and duration of stenting. Uncomplicated stenting was not associated with increased morbidity or mortality.     

Novel method of pancreatojejunal reconstruction after spontaneous closure of previous lateral pancreatojejunostomy

Lateral pancreatojejunostomy is a well-documented procedure for pain relief in chronic pancreatitis with a dilated main pancreatic duct. However, a number of patients develop recurrence of pain at variable intervals after a successful drainage procedure. A 40-year-old patient with tropical chronic pancreatitis developed recurrence of pain 13 years after a lateral pancreatojejunostomy. Investigation demonstrated a dilated main pancreatic duct. Re-exploration revealed a near complete closure of the previous lateral pancreatojejunostomy. A novel method of pancreatojejunal reconstruction was performed. Patient is pain-free after a follow-up of 18 months since surgery. The long-term status of lateral pancreatojejunostomy remains unclear. Our case documents, probably for the first time in published literature, a near total spontaneous closure of a previous lateral pancreatojejunostomy that was responsible for recurrence of pain. Our method of pancreatojejunal reconstruction adds to the armamentarium of the pancreatic surgeon.     

Comparison of histological features and inflammatory cell reaction in alcoholic, idiopathic and tropical chronic pancreatitis

BACKGROUND: There is increasing evidence that immune mechanisms may be crucial in the development of alcoholic chronic pancreatitis. However, it is not known whether differences in underlying aetiology influence the inflammatory reaction in patients with chronic pancreatitis. The histological features and the pattern of inflammatory cell infiltration were studied in three aetiological forms of chronic pancreatitis: alcoholic, idiopathic and tropical pancreatitis. METHODS: Forty-three patients, ten with alcoholic, 12 with idiopathic and 21 with tropical chronic pancreatitis, were evaluated for the pattern of pancreatic inflammatory cell infiltration and histological features. Ten organ donors served as controls. Haematoxylin and eosin-stained tissue sections were used for histological evaluation. For immunohistochemical characterization of the inflammatory reaction, four antibodies-CD4, CD8, CD45 and CD68-were used. Quantitative evaluation of the various cell infiltrates was performed with computer-assisted image analysis. The inflammatory cell infiltration pattern was also evaluated. RESULTS: The degree of endophlebitis and the overall density of plasma cells were greater in tropical than in alcoholic chronic pancreatitis. The grade of intralobular fibrosis was significantly higher in tropical chronic pancreatitis compared with the idiopathic form. No significant quantitative differences in the specific cellular infiltrates (CD4, CD8, CD45, CD68) were observed in the three different groups. However, the perivascular inflammation number score was significantly higher in alcoholic compared with idiopathic pancreatitis (P = 0.037), and the perivascular inflammation area score was significantly lower in idiopathic than in alcoholic (P = 0.024) or tropical (P = 0.020) pancreatitis. CONCLUSION: Different aetiological forms of chronic pancreatitis result in similar histological features and a comparable inflammatory cell reaction, indicating that the disease, independent of the underlying aetiology, reaches a common immunological stage beyond which it appears to progress as a single distinctive entity.     

Increased coexpression of eotaxin and interleukin 5 in bullous pemphigoid

While the presence of eosinophils in the skin lesions of bullous pemphigoid is well documented, the chemotactic factors responsible for eosinophil recruitment into the tissue still remain to be defined. In this study, eotaxin and interleukin-5 (IL-5) concentrations were determined in the blister fluid and sera of patients with bullous pemphigoid (acute and remission phase, n=6) in comparison with normal healthy controls (n=6) using the enzyme-linked immunosorbent assay (ELISA) technique. Eotaxin and IL-5 levels were increased in the blister fluid compared with the acute and remission phase sera, as well as compared with the sera of normal controls. In addition, immunoreactivity for eotaxin was predominantly found in the inflammatory cell infiltrate of lesional bullous pemphigoid biopsy specimens. In conclusion, the data provide evidence that co-operation of eotaxin and IL-5 may play an essential role in activating and recruiting eosinophils, which ultimately contribute to the tissue damage in bullous pemphigoid.