John Patrick Madda

Treatment of hepatitis C virus genotype 4-related cirrhosis: Ribavirin and interferon combination compared with interferon alone

Background Response to treatment with interferon alfa, with or without concomitant ribavirin, varies with the viral genotype and the degree of fibrosis in patients with chronic hepatitis C virus (HCV). Goals To determine the response of HCV type 4–related cirrhosis to interferon and ribavirin combination treatment compared with interferon alone. Study Patients living in Kuwait were assigned to take either interferon alone at a dosage of 5 million units thrice weekly (26 patients) or interferon 5 million units thrice weekly combined with ribavirin 1,000 mg/d (21 patients) for 24 weeks. Biochemical response was defined as normal alanine aminotransferase (ALT) at end of therapy. Sustained biochemical response was defined as normal ALT 6 months after the end of therapy. Sustained virologic response was defined as negative serum HCV RNA 6 months after the end of therapy. Results Only 2 (8%) of 26 patients showed biochemical response after interferon alone, whereas 11 (52%) of 21 showed biochemical response after interferon combined with ribavirin (p < 0.01). Only 2 (8%) of 26 patients showed sustained biochemical response after interferon alone, whereas 5 (23%) of 21 showed sustained biochemical response after interferon combined with ribavirin (not significant, p > 0.1). None of the 26 patients showed virologic response after interferon alone, whereas 3 (14%) of 21 showed sustained virologic response after interferon combined with ribavirin (not significant, p > 0.1). Conclusion These results suggest that patients with cirrhosis caused by HCV type 4 show no response to interferon alone and only slightly better response to 24 weeks of interferon combined with ribavirin.

Papillary Thyroid Carcinoma and Its Variants in Fine Needle Aspiration Smears

OBJECTIVE To study the fine needle aspiration (FNA) cytologic features of papillary thyroid carcinoma (PTC) with special reference to its tall cell variant (TCV), which is the most aggressive of the variants. STUDY DESIGN Fifty-four PTC cases were classified into variants, and the frequency of well-known morphologic criteria was determined. Four parameters were quantitatively analyzed based on a study of 200 consecutive neoplastic follicular cells: shape of cells, color of cytoplasm, intranuclear cytoplasmic inclusion (INCI) and nuclear grooves. RESULTS The PTC cases included 6 TCV (> or = 30% tall cells), 8 cases with a significant tall cell component (sig. TCC) having 10-29% tall cells, 17 usual variant (UV), 17 follicular variant (FV) and 6 miscellaneous variants. TCV differed significantly from UV and FV in having a higher tall cell count, higher count of cells with reddish cytoplasm and INCI, and higher frequency of cases with lymphocytic infiltration. PTC (with significant tall cell component [TCC]) differed significantly from TCV with regard to tall cell count and lymphocytic infiltration, from UV with respect to tall cell count and monolayered sheets, and from FV with respect to tall cells, INCI, grooved nuclei, acinar formation, fire-flare appearance and giant cells. CONCLUSION TCV was cytologically distinct from other variants. The biologic behavior of PTC cases with significant TCC, which morphologically seem to be a group intermediate between TCV on the one hand and UV and FV on the other, however, needs to be carefully monitored.

Pelvic Abscess from Enterobius vermicularis Report of a Case with Cytologic Detection of Eggs and Worms

BACKGROUND Enterobius vermicularis is known to produce perianal and ischioanal abscesses and invade the peritoneal cavity via the female reproductive system, causing pelvic peritonitis. However, there are only rare case reports on the cytodiagnosis of these parasitic lesions. CASE A 28-year-old woman was admitted with a tender left iliac fossa mass and greenish vaginal discharge. Ultrasonogram and computed tomography scan confirmed the presence of a mass lesion suggestive of a tuboovarian abscess. Cytologic examination of the pus obtained during left salpingo-oophorectomy revealed the presence of ova of E vermicularis and fragments of the adult worm in an inflammatory exudate consisting predominantly of neutrophils, eosinophils and occasional epithelioid cell granulomas. Paraffin sections of the tuboovarian mass showed necrotizing epithelioid cell granulomas, but neither ova nor any worm section was identified. Although the possibility of tuberculosis was considered histologically, Ziehl-Neelsen (Z-N) stain for acid-fast bacilli was negative. Z-N staining of the smear and mycobacterial culture of the pus also did not yield positive results. CONCLUSION E vermicularis may cause tuboovarian abscess with necrotizing epithelioid granulomas mimicking tuberculosis. Cytologic examination of the pus is helpful in the diagnosis.

Hodgkin's lymphoma: Diagnostic difficulties in fine-needle aspiration cytology

It is commonly believed that cytodiagnosis of Hodgkins lymphoma (HL) is much easier than that of non‐Hodgkin lymphoma (NHL). However, recognition of certain NHL subtypes with Reed‐Sternberg (R‐S)‐like cells and results of immunohistochemical studies point to the contrary. To study the limitations of cytology in diagnosis of HL, fine‐needle aspiration (FNA) smears of 130 lymphoma or suspected lymphoma cases were reviewed. Initial and reviewed cytodiagnoses were compared with histopathology in 89 cases. Immunocytochemical and immunohistochemical studies were performed in 56 and 59 cases, respectively. Among histologically diagnosed HL cases, definitive cytodiagnosis of HL (initial as well as reviewed) was significantly less frequent than cytodiagnosis of NHL among histologically diagnosed NHL cases (P = 0.0328 and = 0.0001, respectively). On the other hand, cytologically diagnosed HL/NHL cases were significantly more frequent in the former group (P = 0.0001 and = 0.0018, respectively). ALCL and TCRBCL were the two NHL subtypes which created confusion with HL in FNA smears. Twenty‐one cytohistological concordant HL cases and equal number of discordant cases were compared. When compared with discordant group, the patients in concordant group were significantly younger (P = 0.045). Hodgkin/Hodgkin‐like cells and typical R‐S cells were significantly more frequent in FNA smears of the concordant group (P = 0.0478 and = 0.0431, respectively). Immunocytochemical and immunohistochemical studies showed good correlation with histological diagnosis of HL. It is suggested that proper interpretation of cytologic features, together with use of immunocytochemical parameters can help in reducing the margin of error in cytodiagnois of HL. Diagn. Cytopathol. 2009.

Crohn's disease presenting as pyogenic liver abscess with review of previous case reports.

A 40-yr-old male doctor from India presented with pyogenic liver abscesses as the first manifestation of Crohns disease. The Crohns disease itself was limited to the appendix and the adjacent cecum and could be diagnosed only 6 months after the presentation with liver abscess. This single case highlights three unusual features of Crohns disease, and stresses the importance of meticulous search for a cause for pyogenic liver abscess when it occurs in an otherwise healthy adult.

Combination of Immunosuppressive Agents in Treatment of Steroid-Resistant Minimal Change Disease and Primary Focal Segmental Glomerulosclerosis

Background. Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most prevalent histopathological lesions in idiopathic nephrotic syndrome (INS). The latter is associated with high morbidity and mortality due to symptomatic anasarca, bacterial infections, venous and arterial thromboembolism, and potential progression to end-stage renal disease in the case of FSGS. Traditionally, most patients are treated with corticosteroids, cyclophosphamide (CTX) or calcineurin-inhibitors (C-I). Unfortunately, many patients become steroid or C-I dependent, with the inherent risk of long-term side effects, or are resistant to both. The aim of this paper is to report on our experience with a new protocol of a combination of immunosuppressive agents added sequentially to improve the response of steroid and C-I refractory or resistant-INS and to minimize the long-term side-effects of single-agent treatment. Methods. Twenty-one patients with corticosteroid-resistant and C-I refractory INS (6 with MCD and 15 with FSGS) were treated prospectively over 6 and a half years. Our protocol consisted of an initial regimen of C-I followed by the addition of mycophenolate mofetil (MMF) and then by monthly intravenous CTX for 3 consecutive months. Dose reduction of C-I or/and MMF was attempted afterwards at 4-months intervals. Patients who remained refractory to the previously mentioned protocol were treated with an additional course of pulse Solu-Medrol given for 3 days followed by oral corticosteroids tapered over 6 months in addition to a second course of intravenous CTX given for 3 consecutive months. Results. With the initial regimen, two patients with MCD, remained in complete remission (CR) without any therapy after the course of CTX. Fifteen patients had variable response to C-I and MMF, but they achieved CR after CTX and their initial dosage of C-I and MMF were reduced to nearly one half. The remaining four patients had refractory form of FSGS even after the initial regimen, yet responded with CR to the additional course of steroid/CTX. However, no success with dose-reduction, in C-I and MMF, was achieved in the latter four patients. Conclusion. Our study represents the first clinical trial with prospective and adequate follow-up of combination therapy of immunosuppressive agents in INS. This method is effective and safe for treatment of patients who are refractory to the conventional single-agent therapy.

Glomerulopathy in Kuwait: the spectrum over the past 7 years.

There are few studies that examine, prospectively, the epidemiological profile of glomerulopathy (GP) and its clinicopathological correlation. All patients referred to Al-Amiri renal center in Kuwait from 01 1st, 1995 to 12 31st, 2001 were screened for GP. Detailed clinical data were collected and serological markers were done. Renal biopsy was performed whenever indicated. During those 7 years, a total of 584 patients were diagnosed, on histological basis, to have GP, 315 of whom were Kuwaiti nationals. During the same period of the study, 26 patients presented with bilateral small kidneys, history of proteinuria >2 g/day and lacked systemic manifestations of autoimmune disease. Furthermore, 164 patients with clinical manifestations of diabetic glomerulosclerosis were not subjected to kidney biopsy. Hence, the calculated annual incidence rate of GP in Kuwaiti nationals was 34.5 per 100,000 population (PTP). The calculated rate of diabetic glomerulosclerosis was 13.4 PTP and that of non-diabetic 21.1 PTP. The calculated incidence rates of GP increased with age and were twice as high in males compared to females. Vasculitis was more common in elderly males while SLE nephritis was a disease of adults, 88.7% of whom were females. In the subgroup of primary GP, focal segmental glomerulosclerosis was the most common histological lesion accounting for 18.0% of the total biopsies in Kuwaiti patients, yet only 36.8% of those who fulfilled the criteria of primary type. Minimal change disease was the second primary GP (13.0%), followed by immunoglobulin A deposition disease (7.9%) and membranous glomerulonephritis (5%). Autoimmune diseases such as systemic lupus erythematosus (SLE) and vasculitis were common. Interestingly, only 44 of 72 (61.1%) of patients with SLE and 11 of the 62 (17.7%) of patients with vasculitis presented with rapidly progressive glomerulonephritis. On the other hand, 10 of 58 (17.2%) patients with nephroangiosclerosis presented with renal failure and protein excretion >2 g/day simulating primary GP. Furthermore, only 21 of 40 (52.5%) patients with IgA nephropathy presented with “benign disease”. Prospective studies are essential to ascertain the actual incidence and etiology of GP. The loose clinicopathological correlation in GP dictates an aggressive diagnostic approach in its study and management.

Treatment of children with steroid refractory idiopathic nephrotic syndrome: the Kuwaiti experience.

Data on the treatment and outcome of Kuwaiti children with steroid refractory idiopathic glomerulonephritis (SRIGN), i.e. nephrotic syndrome who failed an eight-week course of prednisone, were collected retrospectively from the records of children attending the two renal centers of Kuwait between January 1, 1990 to December 31, 1996. During those seven years, a total of 34 Kuwaiti children were diagnosed to have SRIGN. Histologically, 22 (65%) of those patients had minimal change, 5 (15%) focal segmental GN, 2 (6%) non-IgA mesangioproliferative GN and one membranous GN. Twenty-two patients had manifested frequent relapses, six were steroid-dependent and six were steroid-resistant. Treatment options were in the following order: (a) small maintenance-dose of corticosteroids (< 0.5 mg/kg/alternate days); (b) cyclophosphamide and or chlorambucil for a single eight week-course or eight then 12 week courses (c) cyclosporin A for three months. The response to therapy was as follows: nine children were cured with low-dose corticosteroids; 17 with chlorambucil and/or cyclophosphamide; and five with cyclosporin A. At the end of study, only three children failed such drug therapy, two of who had focal segmental glomerulosclerosis.

Progressive ischemic gangrene in dialysis patients: a clinicopathological correlation

The syndrome of progressive ischemic gangrene (PIG) of the extremities was examined over 3.5 years in patients undergoing maintenance dialysis (MD) in Kuwait and was compared to that in a similar age group (> 40 years) in the general population. The incidence of PIG in MD patients was 15.4/1000 person years of observation (PYO) versus 0.086/1000 PYO in the general population. Patients with diabetes mellitus were found to be at particular risk. PIG developed in 41.4/1000 PYO of diabetic patients who received MD, compared to 7.1/1000 in nondiabetic patients on MD and 0.14/1000 in diabetics without renal disease. The clinical, biochemical, radiological, and histological findings in the 8 patients who developed PIG while on maintenance dialysis (MD) are presented. Two patients had severe hyperparathyroidism and their histological findings were consistent with systemic calciphylaxis. Histological examination, in the remaining patients, showed severe calcified atherosclerosis. Intimal hypertrophy was common especially in patients with long duration on dialysis. The three lesions produced a variable degree of luminal narrowing and were associated with arterial thrombosis. None of the patients showed evidence of iron deposition even in those with systemic calciphylaxis and excessive iron stores. Our study indicated a high incidence of PIG in patients undergoing MD, especially in those with diabetes mellitus. These findings constitute a cogent argument in favor of early parathyroidectomy in selected cases and concern with long-term consequences of atherosclerosis in this patient population.

Postmortem Biopsies: The Experience in Kuwait

Objective: To report our 4-year experience in postmortem needle biopsy of liver, heart, kidney and lung tissues when formal autopsy could not be performed. Subjects and Methods: In the period from January 2000 to December 2003, postmortem biopsies were done at Al-Amiri Hospital, Kuwait, in 19 cases where the original diagnosis or cause of death was not clear. The procedure was performed by a dedicated trained medical team using a biopsy needle or limited incisions guided by the knowledge of the clinical presentation and results of laboratory and radiological investigations. Results: The actual diagnosis was established in 8 cases by postmortem histological findings and corrected in another 9 cases. In the remaining 2 cases with systemic sepsis, autopsy only confirmed the antemortem clinical diagnosis. Conclusion: Our study shows that needle biopsy is an adequate technique for postmortem examination and should be considered as the minimum alternative to conventional autopsy.