Pelvic exenteration and composite sacral resection in the surgical treatment of locally recurrent rectal cancer.

BACKGROUND: The incidence of rectal cancer recurrence after surgery is 5-45%. Extended pelvic resection which entails En-bloc resection of the tumor and adjacent involved organs provides the only true possible curative option for patients with locally recurrent rectal cancer. AIM: To evaluate the surgical and oncological outcome of such treatment. PATIENTS AND METHODS: Between 2006 and 2012 a consecutive series of 40 patients with locally recurrent rectal cancer underwent abdominosacral resection (ASR) in 18 patients, total pelvic exenteration with sacral resection in 10 patients and extended pelvic exenteration in 12 patients. Patients with sacral resection were 28, with the level of sacral division at S2-3 interface in 10 patients, at S3-4 in 15 patients and S4-5 in 3 patients. RESULTS: Forty patients, male to female ratio 1.7:1, median age 45 years (range 25-65 years) underwent extended pelvic resection in the form of pelvic exenteration and abdominosacral resection. Morbidity, re-admission and mortality rates were 55%, 37.5%, and 5%, respectively. Mortality occurred in 2 patients due to perineal flap sepsis and massive myocardial infarction. A R0 and R1 sacral resection were achieved in 62.5% and 37.5%, respectively. The 5-year overall survival rate was 22.6% and the 4-year recurrence free survival was 31.8%. CONCLUSION: Extended pelvic resection as pelvic exenteration and sacral resection for locally recurrent rectal cancer are effective procedures with tolerable mortality rate and acceptable outcome. The associated morbidity remains high and deserves vigilant follow up.

When would we advocate a total thyroidectomy in cases of hypopharyngeal carcinoma?

BACKGROUND AND AIM: The incidence of invasion of the thyroid gland by hypopharyngeal carcinomas is reported to be up to 57%. Our aim was to analyze the frequency of thyroid gland invasion in hypopharyngeal carcinoma treated by thyroidectomy with total laryngopharyngectomy and to identify patients in whom preservation of the thyroid gland is oncologically feasible and hence reduces post-operative hypothyroidism. PATIENTS AND METHODS: This retrospective cohort study included 58 patients with hypopharyngeal squamous cell carcinoma treated by thyroidectomy with total laryngopharyngectomy at the National Cancer Institute, Cairo University between May 1996 and October 2005. Thyroid gland involvement was analyzed through review of charts and pathologic reports. Patients were assessed preoperatively by CT. The correlation between the thyroid gland involvement and the clinical and radiologic CT findings was meticulously examined. RESULTS: Thyroid gland involvement occurred in 37.9% (22/58) of all patients. T4 hypopharyngeal tumors were present in 29.3% (n=17/58) of patients, paratracheal LN invasion was present in 37.9% (22/58) of patients, thyroid cartilage invasion was obvious in 19% (11/58) of patients, and previous radiotherapy was present in 5.2% (3/58) of patients. All patients with T4 hypopharyngeal tumors (n=17/58) and with thyroid cartilage involvement (n=11/58) had thyroid gland invasion as well. T4 hypopharyngeal tumors, paratracheal LN invasion, and thyroid cartilage invasion were statistically significant factors (P<0.001, P=0.009 and P<0.001 respectively) in independent correlation. CONCLUSION: We would advocate a total thyroidectomy in cases of advanced stages of hypopharyngeal carcinoma, bilateral tumors, postcricoid carcinoma and in all patients with definite radiological evidence of thyroid gland invasion.

Breast cancer laterality among Egyptian patients and its association with treatments and survival.

BACKGROUND AND AIM: Breast cancers (BCs) involve the left side (LS) more than the right side (RS). Among the Egyptians, neither BC laterality nor its association with demographic factors, tumor locations, treatments and outcomes were previously reported. PATIENTS AND METHODS: Laterality was analyzed among 5459 BCs from the Gharbiah population-based cancer registry covering >5% of the Egyptian population. Cox proportional model was used to assess the independent effect of stage, ER, and laterality on overall survival (OS). RESULTS: In Egypt, BCs involve LS more than RS with LS-to-RS ratio (LRR) of 1.16. LS predominance was evident among men and women and both younger (< 45 years) and older patients. HER2 over-expression and ductal cancers were significantly more in RSBCs while lobular cancers were significantly more in LSBCs. There were no significant differences in localization within the breast between LSBCs and RSBCs (p = 0.51). LS predominance was noticed across all subgroups except in patients with HER2 positive tumors (LRR = 0.63; p = 0.02). OS was significantly better in stage II and ER positive tumors than stage III and ER negative tumors. Despite OS of LSBCs being generally lower than RSBCs, this was not statistically significant. The significant impact of stage on OS was lost in LSBCs. CONCLUSIONS: Among Egyptian patients, the left breast is at greater risk of cancer than the right one. Despite right-sided tumors seemed more aggressive, Left-sided ones tend to confer worse survival than right-sided tumors.

Outcome of fertility preserving surgery in early stage ovarian cancer.

AIM: To assess the role of fertility preserving surgery in treatment of patients with stage IA, G1 or G2 ovarian carcinoma without adjuvant chemotherapy. PATIENTS AND METHODS: From 2006 to 2008, a prospective non-randomized study recruited 150 women, with suspicious early malignant ovarian mass. RESULTS: Among the 150 explored patients, only 43 (28.6%) patients underwent exploration. Only 32/150 (21.3%) patients had proven stage IA, either G1 or G2, epithelial ovarian cancer. Among the 32 patients, 22 (68.7%) patients were nullipara while 10 (32.1%) had one child. All patients had unilateral tumors; 26 (81.25%) patients had G1 and 6 (18.75%) patients had G2 tumors; 24/32 (75.0%) tumors were serous, 6/32 (18.7%) were mucinous and 2/32 (6.2%) were endometrioid, and none was clear cell type. The median follow up period was 58.5 months (ranged: 48-72 months). Two patients (6.7%) were lost during follow up; data will be presented for the remaining 30 patients. One patient, at 27th month of follow up, had open abdominal exploration to investigate abnormal pelvic mass on routine ultrasound follow up examination. Frozen section revealed recurrent invasive mucinous tumor. She underwent radical surgery with pelvic and para-aortic lymph node dissection, followed by adjuvant chemotherapy, and remained free of disease, for the remaining 29 months of the follow up period. Neither distant metastases nor mortality were reported among our patients. CONCLUSION: Fertility preserving surgery can be considered a safe treatment strategy in patients with stage IA, G1 or G2 ovarian carcinoma.

Distribution of axillary lymph node metastases in different levels and groups in breast cancer, a pathological study.

BACKGROUND: It was observed during dissection of heavy deposits of axillary lymph nodes (LNs) in breast cancer that there were grossly positive LNs outside the confines of classical axillary dissection. AIM OF STUDY: To know the extent of LN metastases in these new basins by dissecting and labeling them separately, for pathological examination and proper staging of those patients. PATIENTS AND METHODS: From 2005 to 2009, 59 private patients with breast cancer who had positive axillary LNs were subjected to axillary dissection with accurate leveling according to its relation to pectoralis minor. In addition to the classical three levels, the brachial, thoracoacromial, humeral, scapular and Rotter's lymph nodes were dissected. RESULTS: Levels I, II and III axillary LNs were involved in 91.5%, 62.7%, and 52.5%, respectively. Skip metastases (without the involvement of level one) were found in 5/59 patients (8.4%). Brachial, acromiothoracic, humeral and Rotter's LNs were involved in 10.1%, 15.2%, 5% and 1.7%, respectively, with no metastatic deposits encountered in scapular LNs. In our patients, lymphedema of the ipsilateral upper limb was nearly of the same incidence as after classical axillary dissection. CONCLUSION: In addition to the classic complete axillary lymph node dissection (ALND) indicated in patients with breast cancer with axillary LNs metastases, dissection of the brachial, acromiothoracic, humeral, Rotter's and scapular LNs, is recommended for proper staging.

The role of surgical management in pediatric germ cell tumors (GCTs), NCI case series.

PURPOSE: To review the experience of a tertiary referral center in pediatric germ cell tumors (GCTs) in the last 8 years and to investigate the impact of surgery and site of disease on prognosis. PATIENTS AND METHODS: We retrospectively analyzed the cases of pediatric germ cell tumors at National Cancer Institute over an 8 years period. Data concerning diagnosis, surgery and medical decisions were reviewed and analyzed for all patients. A total of 34 children with (GCTS) were found, with a mean age, at presentation, of 6.7 years and a follow-up period ranging from 3-52 months. One patient with benign GCT was excluded during analysis of the results. RESULTS: Among the 34 patients, there were 14 males and 20 females with mean age of 6.7 years (range: 9 months-15 years), with male to female ratio 1:1.4. All patients were symptomatic at presentation, most commonly with abdominal swelling (18 patients; 52.9%). Anatomic distribution of GCTs according to sex organ involvement was either gonadal in 21 patients (61.8%) or extragonadal in 13 patients (38.2%). All patients had surgery either in the form of curative resection or biopsy after formal exploration and evidence of irresectability. No significant surgical morbidity or mortality were encountered in our patients. Yolk sac tumor and malignant teratoma were the commonest histologic subtypes in our series. Metastatic disease was encountered in nine out of 33 patients (27.2%). Adjuvant chemotherapy was administered in 28 out of 33 patients (84.8%), following surgery, including all patients with extragonadal disease. Our patients were followed-up to 52 months. Twenty-two patients (66.7%) had no recurrence while two patients (6.1%) died from disease. Pelvic extragonadal site was the worst site regarding resectability. Complete surgical resection showed better disease free survival, while those with irresectable disease had comparable overall survival while none could be rendered disease free with chemotherapy. CONCLUSION: The initial surgical approach to malignant GCTs at all sites should be complete resection when possible; the morbidity of extensive surgical resection should be weighed carefully against the good tumor control with chemotherapy. Surgical staging does not preclude preservation of fertility, which should always be considered in this young age. The site of primary disease plays a role in the prognosis of pediatric germ cell tumors with the extragonadal pelvic tumors being the worst regarding resectability. Good tumor response can be achieved with surgery and chemotherapy even for advanced stage and metastatic disease.

Delayed Cystectomy for T1G3 Transitional Cell Carcinoma (TCC) of the Urinary Bladder, NCI Retrospective Case Series.

AIM: We aim to evaluate the National Cancer Institute (NCI) treatment protocol and its outcome regarding recurrence, progression and survival in patients with T1G3 urinary bladder transitional cell carcinoma. PATIENTS AND METHODS: In a retrospective study, between January 2001 and December 2007, all 34 patients with T1G3 bladder transitional cell carcinoma (TCC), after complete transurethral resection (TURBT), received intravesical BCG as adjuvant therapy. A conservative approach was adopted, whereby those with superficial recurrences were eligible to TURBT, with delayed cystectomy for progression to muscle invasion. Overall, recurrence, and progression-free survival were analyzed. RESULTS: Thirty-three patients were included, 29 were males and 4 were females. The mean age was 61 years (range 35-89 years). Final analysis was made at median follow-up of 15 months (Range of 3-68 months, mean 18 months) for survival. Eleven (33.3%) patients had multifocal tumors. Associated schistosomiasis was present in 12 (36.6%) patients. Twenty-two (66.67%) patients showed recurrence. Eleven out of these 22 (50.0%) patients progressed to muscle invasion and underwent radical cystectomy. Ten out of 34 (30.3%) patients received postcystectomy radiotherapy. Two (20.0%) of them, were staged as TNM stage II, 6 (60.0%) as TNM stage III and 2 (20.0%) patients were TNM stage IV. Eight (72.7%) of these 11 patients had post-cystectomy radiotherapy alone; while the 2 (6.0%) other patients with stage IV had adjuvant concomitant Cisplatin and Gemcitabine chemotherapy. Five (14%) patients of those cystectomy patients died of TCC. Three (60%) patients died from metastatic disease (to lung, liver and bone), one patient died from advanced locoregional disease and another patient died from postoperative complications. Among those patients who received radiotherapy alone, 62.5% are alive. Although, we report a biologically more aggressive behavior of T1G3 than that reported by some authors, for this conservative approach, the overall survival (OS) was (84.4%) and the recurrence-free survival (RFS) was (41.3%), at 18 months; which are comparable to those reported in the literature for the delayed cystectomy approach. CONCLUSION: Adjuvant intravesical therapy with BCG with repeated cystoscopies, and delayed radical cystectomy until progression to the invasive disease carries a significant risk of mortality from invasive disease. This treatment policy may be acceptable for T1G3 bladder TCC, without concomitant carcinoma in situ (CIS), who don't recur after intravesical BCG, however, patients who progress to invasive disease may skip stage II disease and present with stage III or IV, with consequent poor survival. Therefore, due to the aggressive biologic behavior of T1G3 cancer, a determination of a cutoff number for recurrence(s) or better evaluation parameters are needed, to proceed with cystectomy without awaiting muscle invasion. KEY WORDS: Superficial bladder cancer - T1G3 TCC - Delayed cystectomy - BCG.

Assessment of the Proliferative Marker Ki-67 and p53 Protein Expression in HBV- and HCV-related Hepatocellular Carcinoma Cases in Egypt.

BACKGROUND: Chronic HBV and HCV infections are the major risk factors for the development of HCC through a multistep pathway that involves viral and non-viral dependent pathophysiological steps. Hepatic expression of the nuclear proliferative marker ki-67 and the p53 oncoprotein were found to be associated with poor outcome. So, the present study was done to evaluate the changes in expression of Ki-67 and p53 oncoprotein, and to determine p53 gene mutation in HBV/HCV-related HCC Egyptian patients. METHODS: Eight HBV-and 22 HCV-positive HCC cases have been examined for the presence of p53 mutation by immunohistochemistry (IHC) and single-strand conformation polymorphism (SSCP), followed by direct DNA sequencing. HCV were genotyped by LiPA-II. RESULTS: Our results have shown that the proliferative marker ki-67 LI and p53 were highly expressed and significantly related to tumor grade in the Egyptian HCC cases (p<0.05). Also, p53 mutation was found in 16 HCC cases by IHC and in 14 HCC cases by SSCP, only 11 patients showed p53 mutation by sequencing. The highest mutation rate was scored for exon 7 (7 mutations) at codon 249; 4 out of 8 (50%) of HBV-related HCC cases and 3 out of 22 (13.6%) of HCV-related HCC cases, followed by exon 5 (3 mutations) at codons 133, 146, 176 in HCV-related HCC cases, then exon 8 at codon 275 in HCV-related HCC cases. The concordance between the IHC and sequencing analysis was 69%. CONCLUSION: The present study demonstrates the association between the proliferative marker ki-67 and p53 expression with the tumor grade of Egyptian HBV/HCV-related HCC cases. Our results also support the hypothesis that p53 mutations are rather a late event in the carcinogenesis. Also, they suggest that the final steps of hepatocarcinogenesis are common and independent of the aetiology of the viral infection.

Gastrointestinal stromal tumor (GIST)'s surgical treatment, NCI experience.

PURPOSE: To review the clinical presentation, surgical management, and prognostic factors for gastrointestinal stromal tumors. PATIENTS AND METHODS: A prospective study which was carried out between January 2002 and March 2004 on thirty-three patients with gastrointestinal stromal tumor (GIST) at the National Cancer Institute, Cairo University. All patients were evaluated preoperatively and underwent exploratory laparotomy with a curative intent, they were followed up for period ranging between 14-35 months. RESULTS: Among the 33 patients there were 17 males and 16 females. The mean age of patients was 52.8 years. Clinical findings included gastrointestinal bleeding (42.4%), palpable mass (33.3%) and abdominal pain (24.3%). The stomach was the most common site of origin of the disease (39.4%), followed by the colorectal region (24.2%). Tumors were high grade in 63.6% of patients and low-grade in 36.4% of patients. Complete resection of all gross disease was accomplished in 26 patients (78.7%), among whom, multiple adjacent organ resection was required in 6 patients (22.2 %) and metastatic disease was identified in the liver in 3 patients at the time of exploratory surgery of these one could be resected. Immunohistochemical staining for CD117 was positive in 88.9% of patients. The median follow-up period was 20 months (range, 14-35 months). The overall median survival in this study was 25 months, and the cumulative survival at 30 months was 46.9%. Unfavorable prognostic factors were incomplete resection and, high-grade histological features (p<0.05). None of the patients received adjuvant or palliative chemotherapy. Twenty six patients (78.8%) are alive free of disease. Of the 7 patients with incomplete resections or biopsy only; 4 patients (12.1%) are alive with disease and 3 patients died. CONCLUSION: Surgical resection, including en bloc resection of locally advanced tumors, remains the only curative treatment. Overall survival is significantly affected by high-grade tumors and positive resection margin.

Cytoreductive surgery for advanced epithelial tumors of the ovary: technical considerations and outcome.

PURPOSE: To study the role of cytoreductive surgery in the management of advanced epithelial tumors of the ovary and its effect on survival. PATIENTS AND METHODS: A prospective study of fifty eight female patients presenting with stage III and VI epithelial ovarian tumors attending the National Cancer Institute, Cairo University during the period from January 2003 to of December 2004. All patients were evaluated clinically, radiologically (including plain chest-X-ray and abdomino-pelvic ultrasound and/or CT), laboratory work up and CA-125. Abdominal exploration under general anesthesia with intent of maximum surgical cytoreduction was performed for all patients. Patients were followed up during the period of the study by history and physical examination, CA-125 measurement and abdomino-pelvic ultrasound or CT. RESULTS: Our study included 58 female patients with advanced epithelial tumors of the ovary. Their age ranged from 18 to 73 years with a mean age of 49 years. Pathological distribution of the lesions were borderline malignancy in 5 patients (8.6%) and malignant in 53 patients (91.4%). According to FIGO classification there were 46 patients stage III (79%) and 12 patients stage VI disease (21%). Eighteen patients (31%) had surgery prior to admission to NCI. Cytoreductive surgery was done for 51 patients (88%), while 7 patients (12%) had exploration and biopsy only, one of whom had palliative colostomy for large bowel obstruction. Intraoperative surgical complications were encountered in 5 patients (8.6%), all were managed intraoperatively. We had no early postoperative mortalities and 8 postoperative morbidities (13.7%). All patients were referred for chemotherapy. Thirteen patients (22.4%) had local recurrence within the follow up period of the study which was between 8-24 months. One patient died from locally advanced disease and the rest of the patients were explored and lesions were surgically resected. CONCLUSION: Surgery remains a major line of therapy in ovarian cancer including advanced lesions. Extensive procedures to maintain a R0 result are crucial to reach a satisfactory local disease control. The NCI, as well as all tertiary cancer centers, has an important role in providing this quality of surgery especially in advanced cases. Chemotherapy remains the hope to ameliorate the survival especially in advanced cases. The close coordination between surgery and chemotherapy in the form of Intra- Peritoneal Hyperthermic Chemotherapy (IPHC) represents a hope for patients with advanced disease and should be introduced and established in all major cancer centers.