Ezzeldin M. Ibrahim

Fatty infiltration of the liver: analysis of prevalence, radiological and clinical features and influence on patient management

Over a 6-year period, in 1425 adult computed tomographic studies, radiological evidence of fatty infiltration of the liver (FIL) was found in 138 patients (9.7%). Patients with FIL had a mean age +/- SD of 45.9 +/- 15.7 years and 57% were males; the majority were Saudis (73%). Most patients (95%) had one or more underlying aetiological causes. Haematological and non-haematological malignancies with or without liver involvement were the most frequently encountered aetiological factors (66% of patients). FIL contributed to hepatomegaly or was associated with abnormality in one or more of the liver function tests in 30% and 39% of patients, respectively. Assessment of the various radiological patterns showed diffuse fatty changes in 68% of patients and solitary or multiple focal changes in 9% and 22%, respectively. 13 patients (9%) showed sparing of the caudate lobe within a diffuse fatty process. Patients with diffuse FIL had significantly higher values for alkaline phosphatase (p = 0.0016) and serum asparate aminotransferase (p = 0.0251) than those who had the focal pattern. FIL in 20 patients (14%) imposed a difficulty in making an appropriate diagnosis, led to inaccurate impressions, or forced unnecessary invasive or non-invasive investigations. We conclude from our large series of patients that FIL is not uncommon in hospital practice and among those at risk should always be considered as an appropriate diagnosis.

Primary intestinal diffuse large B-cell non-Hodgkin's lymphoma: Clinical features, management, and prognosis of 66 patients

BACKGROUND In Saudi Arabia, primary gastrointestinal non-Hodgkins lymphoma (NHL) is common. Recently we have reported one of the largest series of primary gastric (PG) diffuse large B-cell lymphoma (DLCL). This has prompted the analysis of another series of patients with primary intestinal DLCL to depict the clinical features and the outcome of that disease and to compare those with that for PG involvement. PATIENTS AND METHODS The data of 66 adult patients with primary intestinal NHL having DLCL histology were retrospectively reviewed. RESULTS Patients had a median age of 45 years. Of 64 treated patients, 16% and 84%, received single and multiple modality treatment, respectively. Seventy-six percent, ten percent, and fourteen percent attained complete remission (CR), partial remission (PR), and no response/progressive disease, respectively. Multivariate analysis failed to identify any variable that predict the likelihood of attaining CR. Over a median follow-up of 81 months for all 66 patients, 32 (48%) were alive and disease-free, 5 (8%) were alive with evidence of disease, and the remaining 29 (44%) were dead. The median overall survival (OS) was 101 months and it was 58% (+/- 6%) and 48% (+/- 7%) at 5- and 10-year, respectively. Of the 54 patients who achieved CR or PR, the median event-free survival (EFS) was not reached, but the predicted 5- and 10-year EFS was 61% (+/- 7%) and 52% (+/- 7%), respectively. Only low serum albumin (<30 g/l) was associated with adverse OS and EFS in a univariate analysis, however, multivariate analysis was not possible. Our analysis showed that compared with single-modality management, multi-modality strategy attained significantly higher CR, and advantageous EFS, but without a significant superior effect on OS. In comparison with patients with PG DLCL, those with primary intestinal disease demonstrated more adverse prognostic features, but had an equivalent survival. CONCLUSIONS This series characterized the clinico-pathologic features and outcome of patients with primary intestinal DLCL. While surgical resection in primary intestinal NHL seems beneficial, only prospective randomized studies can ascertain its precise role. Compared with patients with PG NHL, patients with primary intestinal disease had more prevalence of adverse prognostic features.

Pregnancy-associated breast cancer: a case-control study in a young population with a high-fertility rate.

Pregnancy-associated breast cancer (PABC) is not a rare event. The association frequently imposes a management challenge. We intended to review the clinical features, therapy, and outcome of patients with PABC seen at a single institution over a five-year period and to compare those with that seen in a matched control group.Data of all patients with PABC diagnosed during pregnancy were retrospectively reviewed (Group I). For each patient in Group I, three matched controls with breast cancer without pregnancy were identified (matched for age, stage, and year of diagnosis, Group II).72 patients in Group I and 216 in Group II were identified. Their median age was similar (34 vs 35 y, respectively). The median number of prior pragnancies for patients in Groups I and II was 5. Patients had shorter duration of symptoms prior to diagnosis as compared with their controls (5.6 vs 9.4 months,P<0.0001). 3%, 31%, 40%, and 26% of patients had Stage I to IV, respectively. A pattern that was similar to that seen in our breast cancer population. Pregnancy was terminated in 34 patients (47%), while 38 (53%) had normal spontaneous vaginal delivery. 47 patients in Group I had surgery; 37 (52%) had modified radical mastectomy and 10 (14%) had conservative surgery. In 37 patients surgery was performed after termination of pregnancy and 10 had surgery performed during pregnancy. The median number of positive lymph nodes in Group I was 4 as compared with 2 for patients in Group II. No patients in Group I had systemic chemotherapy during first trimester, while only 4 (6%) and 3 (4%) received adjuvant or neoadjuvant during second and third trimester, respectively. No congenital malformation in the newborns was diagnosed. None of the patients in Group I received radiotherapy during pregnancy.

Magnetic resonance imaging of tuberculous spondylitis.

Study Design This retrospective study analyzed the magnetic resonance imaging characteristics of tuberculous spondylitis. Objective To describe the magnetic resonance imaging characteristics of tuberculous spondylitis and compare the diagnostic yield of magnetic resonance imaging versus other modalities. Summary of Background Data Tuberculous spondylitis is not an uncommon occurrence with extrapulmonary disease. It requires prompt diagnosis and management. In the pre-magnetic resonance imaging era, computed tomography was used to delineate the associated radiologic changes. Data are limited that describe the magnetic resonance imaging pattern of tuberculous spondylitis and the effect of post-contrast enhancement. Methods The magnetic resonance imaging characteristics of 28 vertebrae in 12 patients with tuberculous spondylitis were studied. Results The thoracic spine was the most commonly involved region, with involvement occurring in the thoracic spine alone in 12 vertebrae (43%) and with other areas of the spine in an additional five (18%). Partial involvement was detected in the majority of the vertebral lesions (24; 86%). Magnetic resonance imaging evidence of disc space involvement was apparent in only 46% of the lesions. Paraspinal abscess and epidural extension were documented by magnetic resonance imaging in 71% and 61% of lesions, respectively. Decreased signal intensity on T1-weighted images was demonstrated in 13 vertebrae (46%), with increased signal intensity on T2-weighted images seen only in five (18%). Conclusion Magnetic resonance imaging is a useful diagnostic modality for patients with suspected tuberculous spondylitis. Partial vertebral involvement and paraspinal and epidural extension were delineated. Study of the signal intensity on T1− and T2-weighted images revealed a pattern that may be dissimilar to that commonly reported. Post-contrast enhancement adds more certainty to the diagnosis of tuberculous spondylitis.

Past, Present and Future of Colorectal Cancer in the Kingdom of Saudi Arabia

Background/Aims: The crude frequency of colorectal cancer (CRC) is second to breast cancer in the Kingdom of Saudi Arabia (KSA). To assess the future burden of CRC in the country, we designed a model that takes into consideration the recent lifestyle pattern and the growth and aging of the population. Methods: We compared CRC statistics for KSA (using data from the National Cancer Registry) with that from the Surveillance, Epidemiology and End Results (SEER) databases of the United States of America (USA). We used the Joinpoint regression program to identify changes in secular trends, while the GLOBOCAN 2002 software was used to project future incidence and mortality. Results: Between 1994 and 2003, age-standardized rates (ASRs) for CRC in KSA almost doubled, as compared to a nonsignificant decline in USA. Between 2001 and 2003, while the annual percent change (APC) of CRC incidence in the USA showed a nonsignificant decrease in females, APC in Saudi females showed a nonsignificant rise of six percent. On the other hand, the rising incidence among Saudi males, during the years 1999 to 2003, was significant, with an APC of 20.5%. The projection model suggested that the incidence of CRC in KSA could increase fourfold in both genders by the year 2030. Conclusions: In KSA, the present and expected increase in CRC rates is alarming. Pragmatic recommendations to face that challenge are discussed. The present work could serve as a model to study other prevalent types of cancer, particularly in developing countries.

Breast cancer in the eastern province of Saudi Arabia.

In the Kingdom of Saudi Arabia (KSA), hospital and population based statistics have shown that breast cancer has the highest crude frequency rate among Saudi women. The scarcity of reports about the disease in the KSA has been the impetus to this analysis about breast cancer in the eastem province of KSA. Data on female patients with invasive breast carcinoma seen at King Fahd Hospital of the University in the eastern province of KSA, were retrospectively reviewed. The analysis intended to examine the pattern of the disease and the outcome for patients. Between 1985 and 1995, 292 patients were identified. Their median age±SD (standard deviation) was 42±10.5 years. Most patients were younger than 50 years (78%) and were predominantly premenopausals (79%). Only 25 (9%) of patients had stage I cancer, whilst 130 (44%), 90 (30%), and 47 (16%) had stage II, III, and IV, respectively. Among patients with known axillary nodal status (242 patients), only 37% were node-negative whilst 32% and 31% had 1–3, and ≥4 positive nodes, respectively. Adjuvant chemotherapy and tamoxifen were commonly offered; nonetheless, other adjuvant modalities were rarely utilised. The median follow-up ±SD of all patients was 62.3±8.9 months: 152 patients (52%) were alive with no evidence of disease, 25 (9%) were alive with evidence of disease, and 115 (39%) were dead from breast cancer or its related complications. The median survival of the entire group was not obtained, but the 10-year projected survival was 55%. For stage I and II patients, 118 (76%) were alive with a projected 10-year actuarial survival of 64%. On the other hand, only 51 (57%) of patients with stage III disease were alive with a median survival of 41.5 months (95% Confidence interval (CI), 18.9 to 51.3). Patients with stage IV disease demonstrated a poor outcome with a median survival of 23.5 (95%, CI 12.2 to 31.4). Multivariate analyses were performed to explore the influence of independent variables on overall survival (OS) for patients with non-metastatic disease. Besides the expected adverse effect of disease progression, the favourable influence of adjuvant chemotherapy and tamoxifen prevailed. The amount of benefit gained from tamoxifen, however, was small. Similar analyses were undertaken to determine the influence of independent variables on progression-free survival (PFS). These analyses ascertained the adverse effects of advanced stage and the favourable impact of adjuvant chemotherapy. Breast cancer in the KSA has features that are distinctive from those of industrialised countries. Survival data, however, were comparable. The favourable influence of adjuvant chemotherapy was evident on both OS and PFS. Adjuvant tamoxifen, however, had little effect. Due to its infrequent use, the role of other adjuvant modalities could not be asserted.

Decreased axillary lymph node retrieval in patients after neoadjuvant chemotherapy

BACKGROUND The purpose of this study was to assess our clinical impression that fewer lymph nodes are retrieved after level I and II axillary dissection after neoadjuvant chemotherapy and whether there is a positive correlation between the total number of lymph nodes retrieved and the number of diseased lymph nodes. METHODS Patients included those with stage IIB, IIIA, and IIIB breast cancer of whom 77 had neoadjuvant chemotherapy and 58 had initial surgery only. All had modified radical mastectomy with in continuity level I and II axillary dissection. RESULTS Patients after neoadjuvant chemotherapy had 14.3 +/- 6.7 lymph nodes detected versus 16.9 +/- 8.8 (mean +/- SD; P <0.057) for those with initial surgery only. The number of positive nodes were 3.7 +/- 4.7 versus 6.6 +/- 8.7 (mean +/- SD; P <0.033) respectively and the number of negative nodes were 10.6 +/- 7.5 versus 10.4 +/- 8 (mean +/- SD; P <0.9). The correlation between the number of positive lymph nodes and the total number of lymph nodes was r = 0.58; P <0.001. CONCLUSIONS It appears that fewer lymph nodes are retrieved after level I and II axillary dissection after neoadjuvant chemotherapy. The total number of lymph nodes retrieved increases directly with the number of positive lymph nodes in patients not treated with chemotherapy.

Effect of granulocyte-macrophage colony-stimulating factor on chemotherapy-induced oral mucositis in non-neutro-penic cancer patients

Objective: The study was designed to assess prospectively the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of chemotherapy-induced oral mucositis in non-neutropenic cancer patients. Material and Methods: In a prospective open study, adult cancer patients with chemotherapy-induced, neutropenia-independent oral mucositis were treated with GM-CSF (Schering Plough Corporation, Kenilworth, NJ) prepared as mouthwash solution (5 to 10 μgm /ml). GM-CSF was administered within 24 hours of occurrence of oral mucositis at a frequency of 4 to 6 times daily. Systemic GM-CSF was not permissible. Oral mucositis was graded according to the modified Radiation Therapy Oncology Group criteria. Results: Forty-nine patients were recruited but nine were subsequently excluded as they experienced neutropenia during GM-CSF therapy. The remaining 40 patients were all evaluable. Most patients had either Grade 3 or 4 gross (71%) or functional (70%) mucositis. The mean ± SEM gross oral mucositis scores for all 40 patients combined decreased from 3.3 ± 0.11 at baseline to 2.1 ± 0.12 (p<0.0001) after 2 days, 0.95 ± 0.11 (p<0.0001) after 5 days and 0.23 ± 0.07 (p <0.0001) after 10 days of therapy. Likewise, the mean ± SEM functional oral mucositis scores decreased from 3.03 ± 0.13 at baseline to 1.58 ± 0.13 (p<0.0001) after 2 days, 0.68 ± 0.11 (p<0.0001) after 5 days, and 0.15 ± 0.06 (p<0.0001) after 10 days of therapy. The duration of severe oral mucositis was also shortened as Grade 0 or 1 (gross mucositis grading score) was evident in 12 (30%), 29 (73%), and 40 (100%) patients by the 2nd, 5th and 10th day of therapy, respectively. Similarly, Grade 0 or 1 (functional mucositis grading score) reported in 19 (48%), 31 (78%), and 40 (100%) patients by the 2nd, 5th and 10th day of therapy, respectively. The use of GM-CSF mouthwash was not associated with any apparent ill effect. Conclusion: GM-CSF mouthwash as used in this study has a significant recuperative efficacy on the severity, morbidity, and duration of chemotherapy-induced oral mucositis. A large randomized, placebo-controlled study is warranted to ascertain that benefit and determine the optimal dosage and schedule.

Risk of second breast cancer in female Hodgkin’s lymphoma survivors: a meta-analysis

BackgroundWomen treated for Hodgkin’s lymphoma (HL) have an elevated risk of developing second breast cancer (SBC) compared with the general population. We planned this meta-analysis to quantify the long-term risk of SBC and analyze the contributing risk factors among HL survivors.MethodsAccording to predefined selection criteria, literature search identified 34 studies that were included in the analyses.ResultsAfter eliminating overlapping or duplicate data, 957 incidences of SBC were encountered in 24,505 females with HL over a median follow-up of 14.9 years. The medians: age at the diagnosis of HL, age at diagnosis of SBC, and latency since HL treatment to the development of SBC were 23.7, 35.0, and 17.7 years, respectively. The pooled relative risk (RR) of SBC was 8.23 (95% CI, 5.43-12.47, I2 = 96%), with a median absolute excess rate of 22.9 per 10,000 person-years. The RR was found inversely related to age at diagnosis of HL with the highest rate (68.7; [95%CI, 28.08-168.11], I2 = 79%), occurred in young patients (≤ 15 years old), where the RR in older women (≥ 40 years old) was not significant (0.55; [95% CI, 0.09-3.52]). Analysis of RR by 5-year increments since the treatment of HL showed that the risk was highest after 15–19 years of latency (13.87; [95% CI, 7.91-24.30], I2 = 89%). Analysis of the effect of treatment modalities showed that the RR rates were (4.70; [95% CI, 3.28-6.75], I2 = 74%), (5.65; [95%CI, 2.94-10.88], I2 = 91%), and (1.19; [95% CI, 0.50-2.82], I2 = 65%), for radiotherapy (RT) only, combined RT and chemotherapy (CT), and CT only, respectively. To investigate the demonstrated heterogeneity, meta-regression analysis was performed when feasible. In most such analyses, the natural logarithm of RR was inversely associated with age at HL diagnosis.ConclusionsWe conclude that, the current meta-analysis provided the most recent comprehensive estimate of the risk of SBC in a broad-range of HL survivors. Younger age at diagnosis proved to be a dominant risk factor. The obtained results would serve providing breast cancer screening recommendations for HL survivors.

Primary gastric non-Hodgkin's lymphoma: Clinical features, management, and prognosis of 185 patients with diffuse large B-cell lymphoma

BACKGROUND Primary gastric non-Hodgkins lymphoma (PG-NHL) is common in Saudi Arabia. This has prompted the analysis of a large series of patients with PG-NHL having high-grade diffuse large B-cell lymphoma (DLCL) in order to define the clinical features and outcome of this disease. PATIENTS AND METHODS The data of all adult patients in the series with PG-NHL having DLCL histology were retrospectively reviewed. Patients were eligible if they had biopsy-confirmed diagnoses obtained by endoscopy or following laparotomy. RESULTS Over a 16-year period, 185 patients with DLCL PG-NHL were identified and their data were reviewed. Patients had a median age of 54 years. In 53% of them only one initial therapeutic modality was given, while 47% were managed by a multi-modality approach. One hundred forty patients (76%), 19 (10%), and 26 (14%) attained complete remission (CR), partial remission, and no response/progressive disease, respectively. Multivariate analysis showed that poor performance status and advanced stage were negatively associated with the likelihood of attaining CR. Over a median follow-up of 54 months, 118 (64%) of the patients were alive and disease-free, 17 (9%) were alive with evidence of disease, and the remaining 50 (27%) were dead. The projected 5-year and 10-year overall survivals (OS) (+/- SD) were 68% (+/- 4%) and 61% (+/- 6%), respectively. The Cox proportional hazards model identified the same variables of response as adverse prognostic factors of survival. Using the influence of performance status, and stage, a prognostic index was constructed to recognize three prognostically distinctive risk categories with overall survival proportions of 87%, 61%, and 45%, respectively. The unadjusted International Prognostic Index, however, failed to classify patients into prognostically meaningful risk strata. Of the 140 patients who achieved CR, the median disease-free survival (DFS) was not reached, but the predicted 5- and 10-year DFS were 82% and 75%, respectively. A multivariate analysis identified poor performance status as the only independent prognostic covariate that adversely influenced DFS. Our analysis showed that compared with single-modality management, multi-modality strategy attained significantly higher CR, and advantageous OS and DFS. CONCLUSIONS This large series characterized the clinico-pathologic features and outcome of patients with DLCL PG-NHL. Performance status, and stage significantly influenced patient outcome. A prognostic index was developed and it identified three prognostically distinctive risk groups; however, prospective validation is warranted.