Omalizumab treatment in Samter's triad: case series and review of the literature.

OBJECTIVE: Samter's triad is the combination of asthma, aspirin sensitization, and nasal polyposis. Few data are available on the use of omalizumab in this disease. The study aimed to describe the impact of omalizumab on clinical and functional parameters and the quality of life of a series of patients with Samter's triad. Moreover, we aimed to provide a review of the literature on this topic. PATIENTS AND METHODS: We retrospectively described four patients with Samter's triad undergoing omalizumab therapy. Clinical, functional, and immunological data of these patients were collected at baseline and follow-up. RESULTS: Reduction of asthma exacerbations and salbutamol rescue therapy were observed in all patients after anti-IgE treatment together with an improvement in the quality of life. A significant improvement in FEV1, FVC, and FEF25-75 was observed. No major side-effects were observed. A total of 14 studies regarding omalizumab in aspirin-exacerbated respiratory diseases were included in the review, comprising 78 patients. All studies reported a good efficacy in improving asthma control; restoration of aspirin tolerance was repeatedly reported. CONCLUSIONS: The results of our case series and review of the literature suggest that omalizumab effectively improves asthma control, lung function tests, and quality of life in patients with Samter's triad.

Validation of five contemporary prognostication systems for primary pancreatic endocrine neoplasms: results from a single institution experience with 61 surgically treated cases.

BACKGROUND: Presently, several systems for the prognostication of pancreatic endocrine neoplasms (PENs) exist and the most appropriate classification system has not been clearly defined. This study aims to validate the performance of the 2004 World Health Organization (WHO), European Neuroendocrine Tumor Society (ENETS), Memorial Sloan-Kettering Cancer Center (MSKCC), American Joint Committee for Cancer (AJCC) TNM staging and Bilimoria criteria in a cohort of patients with PENs who underwent surgery at a single institution. METHODS: This study is a retrospective review of 61 consecutive patients who underwent surgical treatment for PEN. Actuarial disease-specific survival (DSS) of all 61 patients and recurrence-free survival (RFS) of 53 patients who had curative resection were analysed. RESULTS: On univariate analyses, tumour size ≥50 mm, non-curative resection, lymph node involvement, presence of distant metastases, presence of necrosis, mitotic count ≥2/10 hpf and poor differentiation were associated with decreased DSS. Tumour size ≥50 mm, lymph node involvement, lymphovascular invasion, presence of necrosis and mitotic count ≥2/10 hpf were associated with decreased actuarial RFS. All five staging systems were useful in stratifying the 61 patients according to actuarial DSS. However, the MSKCC grading and ENETS grading systems were not statistically significant in stratifying DSS in the 61 patients. In the 53 patients who underwent curative resection, the WHO, ENETS, MSKCC, AJCC staging and the MSKCC grading systems were successful in stratifying the patients according to actuarial RFS. However, the Bilimoria scoring and ENETS grading systems were not useful in prognosticating these 53 patients. CONCLUSION: All five classification systems were useful for the prognostication of surgically treated PENs in our patient cohort.

Impact of the introduction of laparoscopic wedge resection as a surgical option for suspected small/medium-sized gastrointestinal stromal tumors of the stomach on perioperative and oncologic outcomes.

BACKGROUND: The present study is designed to determine the feasibility and impact of the introduction of laparoscopic wedge resection as a surgical option for the treatment of suspected small/medium-sized (<7 cm) gastric gastrointestinal stromal tumors (GISTs). METHODS: The study involved a retrospective review of 53 consecutive patients who underwent laparoscopic or open wedge resection of a suspected gastric GIST. It was divided into two consecutive time periods wherein laparoscopic resection was a surgical option only in the latter period. Comparisons were made between the outcomes of patients who underwent laparoscopic versus open wedge resection and the outcomes of patients treated during the two consecutive time periods (to determine the impact of the introduction of laparoscopic wedge resection), RESULTS: Fourteen patients (26%) underwent laparoscopic wedge resection with 1 conversion. The pathological exam showed that 41 patients (77%) had a GIST. Laparoscopic resection was significantly associated with a longer operative time, an earlier return of bowel function, earlier resumption of liquid and solid diet, decreased duration of parenteral or epidural analgesia use, and shorter postoperative hospitalization compared to open resection. There was no statistical difference in the rate of R1 resection and actuarial recurrence-free survival for the two approaches. Comparison between the two time periods demonstrated that the introduction of the laparoscopic approach in the latter period resulted in an earlier return of bowel function, earlier resumption of liquid and solid diet, and decreased duration of parenteral or epidural analgesia. CONCLUSIONS: Laparoscopic wedge resection for gastric GIST can be safely adopted. It is associated with a more favorable perioperative outcome than the open approach. Its introduction as a surgical option has resulted in an improvement in perioperative outcomes without compromising oncologic safety at our institution.

Outcome after curative resection of large (>or=10 cm) gastric gastrointestinal stromal tumors: how frequent is adjacent organ involvement and is concomitant distal pancreatectomy necessary?

INTRODUCTION: Complete tumor resection with clear margins including adjacent organs is the treatment of choice for gastrointestinal stromal tumors (GISTs). However, true tumor invasion of adjacent organs has been reported to be rare. Concomitant distal pancreatectomy (DP) for suspected tumor infiltration is not infrequently performed during resection of large gastric GISTs. This study aims to determine the true frequency of adjacent organ involvement by large gastric GISTs with particular attention to the pancreas and compares the outcome after curative resection with and without a concomitant DP in order to determine if DP is truly necessary. METHODS: A retrospective review of 37 patients who underwent curative resection of large (>or=10 cm) gastric GISTs was conducted. RESULTS: Wedge resections were performed in 22, partial gastectomies in nine, and total gastrectomies in six patients. The median operative time was 180 min (range, 60-330 min), and the patients had a median postoperative stay of 8 days (range, 4-29 days). Overall, there were eight (22%) morbidities including two (5%) mortalities. Nineteen (51%) had concomitant adjacent organ resection, and these included 15 (41%) DPs with splenectomies. Direct organ invasion was demonstrated in 5/19 patients (26%) and 7/30 organs (23%) resected. Only 1/15 (6.7%) DP specimens demonstrated tumor infiltration. Comparison between the patients with and without a concomitant DP demonstrated that performance of a DP was associated with a longer operation time [225 min (range, 105-305 min) vs 158 min (60-330 min), P=.002)], increased postoperative stay [9 days (range, 7-29 days) vs 7.5 days (4-19 days), P=.042], and increased postoperative morbidity [6 (40%) vs 2 (9%), P=.025]. The DP cohort also had a statistically significant poorer 5-year recurrence free survival (22% vs 60%, P=.017). CONCLUSION: Although adjacent organ involvement is not uncommon with large gastric GISTs, concomitant DP is usually unnecessary as direct pancreatic invasion is rare. Furthermore, concomitant DP with splenectomy is associated with an increase in postoperative morbidity.

Accurate preoperative localization of insulinomas avoids the need for blind resection and reoperation: analysis of a single institution experience with 17 surgically treated tumors over 19 years.

INTRODUCTION: Presently, the need for and choice of preoperative localization tests for insulinomas remain controversial. We report the results from a single institution experience whereby the management policy adopted was that of accurate preoperative localization before surgical exploration. MATERIALS AND METHODS: From 1990 to 2008, 17 patients with a clinical and biochemical diagnosis of an insulinoma who underwent surgery were retrospectively reviewed. The diagnosis of all insulinomas were confirmed pathologically. RESULTS: All tumors were localized preoperatively and an average of 2.2 preoperative localization studies including 1.4 noninvasive studies and 0.8 invasive studies were utilized per patient. Invasive localization modalities were more sensitive (92%) than noninvasive modalities in localizing insulinomas (71%). Intra-arterial calcium stimulation with hepatic venous sampling was the most sensitive invasive modality (100%), whereas magnetic resonance imaging was the most sensitive noninvasive modality (63%). Fifteen of 17 tumors (88%) were localized intraoperatively via inspection/palpation and/or intraoperative ultrasonography. Both insulinomas which were not localized intraoperatively were localized correctly to the distal pancreas via preoperative transhepatic portal venous sampling. None of the patients required a blind resection or surgical reexploration for failed localization. All 17 patients underwent complete surgical resection which included eight enucleations and nine distal pancreatectomies with a cure rate of 94% (16/17) at a median follow-up of 35 (range, 1-217) months. The postoperative morbidity and long-term outcome of enucleation was similar to distal pancreatectomy despite a higher rate of microscopic margin involvement. CONCLUSION: Accurate preoperative localization of insulinomas is useful as it eliminates the need for blind distal pancreatectomy and avoids reoperation. Complete surgical resection is the treatment of choice, and whenever possible, a pancreas-sparing approach such as enucleation should be adopted.

A single-institution experience with eight CD117-positive primary extragastrointestinal stromal tumors: critical appraisal and a comparison with their gastrointestinal counterparts.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) arising from outside the gut wall also termed extragastrointestinal stromal tumors (EGISTs) are reported to be rare. Presently, their pathogenesis remains controversial, and recently, it has been proposed that EGISTs may be the result of extensive extramural growth of GISTs which lose contact with the gut wall. This study presents a single-institution experience with eight EGISTs and compares their clinicopathological features with mural GISTs in order to determine further insight to their possible origin. METHODS: Between 1997 and 2008, 156 patients with pathologically proven CD117-positive primary GISTs were retrospectively reviewed. Eight tumors were identified as EGISTs, 104 were gastric GISTs, and 44 were small-bowel GISTs. Mural GISTs were classified as extramural or intra/transmural according to their gross pattern of growth. RESULTS: There were five male and three female patients with a median age of 58 years (range, 42-81 years). All patients were symptomatic, and the tumors were located in the greater omentum (n = 2), lesser sac (n = 2), lesser omentum, retroperitoneum, small-bowel mesentery, and pancreas. The median tumor size was 140 mm (range, 55 to 220 mm). Seven of eight EGISTs were found to be in close association to the adjacent gut wall. Pathological examination demonstrated that two tumors demonstrated focal involvement of the muscularis propria of the adjacent gut wall. Four tumors demonstrated tumor abutting or adherent to the serosa but no muscle involvement and one tumor was separated from the serosa. Comparison between the clinicopathological features of EGISTs with extramural GISTs and intra/transmural GISTs demonstrated that EGISTs were significantly larger [140 range (55-220) mm vs 80 (5-260) mm vs 50 (15-190) mm, P = 0.049, P < 0.001 respectively]. CONCLUSION: The occurrence of true EGISTs is rare. Most cases demonstrate some form of communication or contact with the gut wall, and EGISTs are significantly larger than extramural or intra/transmural GIST. These observations suggest that most, if not all, cases of EGISTs are likely to represent mural GISTs with extensive extramural growth with eventual loss of contact with the muscle layer of the gut.

Which is the optimal risk stratification system for surgically treated localized primary GIST? Comparison of three contemporary prognostic criteria in 171 tumors and a proposal for a modified Armed Forces Institute of Pathology risk criteria.

BACKGROUND: This study aims to validate and compare the performance of the National Institute of Health (NIH) criteria, Huang modified NIH criteria, and Armed Forces Institute of Pathology (AFIP) risk criteria for gastrointestinal stromal tumors (GISTs) in a large series of localized primary GISTs surgically treated at a single institution to determine the ideal risk stratification system for GIST. METHODS: The clinicopathological features of 171 consecutive patients who underwent surgical resection for GISTs were retrospectively reviewed. Statistical analyses were performed to compare the prognostic value of the three risk criteria by analyzing the discriminatory ability linear trend, homogeneity, monotonicity of gradients, and Akaike information criteria. RESULTS: The median actuarial recurrence-free survival (RFS) for all 171 patients was 70%. On multivariate analyses, size >10 cm, mitotic count >5/50 high-power field, tumor necrosis, and serosal involvement were independent prognostic factors of RFS. All three risk criteria demonstrated a statistically significant difference in the recurrence rate, median actuarial RFS, actuarial 5-year RFS, and tumor-specific death across the different stages. Comparison of the various risk-stratification systems demonstrated that our proposed modified AFIP criteria had the best independent predictive value of RFS when compared with the other systems. CONCLUSION: The NIH, modified NIH, and AFIP criteria are useful in the prognostication of GIST, and the AFIP risk criteria provided the best prognostication among the three systems for primary localized GIST. However, remarkable prognostic heterogeneity exists in the AFIP high-risk category, and with our proposed modification, this system provides the most accurate prognostic information.

Agreement among insulin sensitivity indexes on the diagnosis of insulin resistance in polycystic ovary syndrome and ovulatory women.

OBJECTIVE: The objective was to compare agreement on the diagnosis of insulin resistance (IR) among insulin sensitivity indexes in both ovulatory women and those with polycystic ovary syndrome (PCOS). STUDY DESIGN: In an observational study, the 75-g oral glucose tolerance test was performed in 105 women with PCOS and 51 ovulatory women. The insulin sensitivity indexes used were insulin quantitative sensitivity check index (QUICKI), 1/homeostasis model assessment-insulin resistance (1/HOMA-IR), area under curve for insulin (AUC-I), and the Matsuda insulin sensitivity index (COMP). For the IR diagnosis we used cut-off values described in recent publications (insulin >12 microIU/ml, 1/HOMA-IR <0.47, QUICKI < or =0.333, AUC-I > or =7000 microIU/ml 120 min, and COMP <4.75. RESULTS: Excellent agreement was assessed among insulin, QUICKI, and 1/HOMA-IR. However, the rate of IR detected by these indexes in the PCOS group (44.8-51.4%) was lower than expected. New cut-offs were then determined based on COMP results. Using these values, 1/HOMA-IR and QUICKI showed excellent agreement (kappa=0.83) with COMP. CONCLUSION: The observed agreements among insulin, QUICKI and 1/HOMA-IR were higher than 93%. Therefore, clinicians may choose any of those obtaining similar results. For clinicians who prefer COMP, but are looking for a simpler test to detect IR in PCOS women, the use of QUICKI and 1/HOMA-IR with the new cut-offs seems reasonable.

A review of mucinous cystic neoplasms of the pancreas defined by ovarian-type stroma: clinicopathological features of 344 patients.

INTRODUCTION: Despite formal definitions of mucinous cystic neoplasms (MCNs) and intraductal papillary neoplasms (IPMNs) by the World Health Organization (WHO) and Armed Forces Institute of Pathology (AFIP), several controversies with regard to MCNs remain. The aim of this review was to determine the clinicopathological features of MCNs defined by ovarian-type stroma (OS) as proposed by the WHO and AFIP and to compare them with MCNs defined by less stringent criteria. METHODS: A MEDLINE search was conducted to identify English-language articles on pancreatic MCNs from 1996 to 2005. Twenty-five studies were identified. The studies were divided into 2 groups: group A included 10 studies with 344 patients whereby the presence of OS was a criteria for the diagnosis of MCNs, and group B, included 15 studies comprising 761 patients whereby the presence of OS was not mandatory for the diagnosis of MCNs. RESULTS: Patients in group A (MCNs as defined by OS) were almost always female (99.7%), with a mean age of 47 (range, 18-95) years. MCNs were located predominantly in the body or tail of the pancreas (94.6%) and had a mean size of 8.7 cm (range, 0.6-35 cm); 76% were symptomatic, 6.8% demonstrated ductal communication, and 27% were malignant. At a mean follow-up of 57.5 (range, 1-264) months and 43 (range, 2-257) months after surgery, 97.9% of benign and 61.9% of malignant neoplasms were disease free, respectively. Patients in group B were older and had a higher proportion of males. Neoplasms were more evenly distributed in the pancreas, were smaller, communicated more frequently with the pancreatic duct, and were composed of a higher proportion of malignant tumors compared with group A. Their clinicopathological features were intermediate between those of group A and patients with IPMN. CONCLUSION: Pancreatic MCNs with OS have unique and distinct clinicopathological features. MCNs should be defined by the presence of OS, as it is the most reliable way of distinguishing MCNs from IPMN. Adoption of "looser" criteria will result in misclassification of some IPMNs as MCNs.

Non-neoplastic cystic and cystic-like lesions of the pancreas: may mimic pancreatic cystic neoplasms.

BACKGROUND: Cystic lesions of the pancreas consist of a broad range of pathological entities. With the exception of the pancreatic pseudocyst, these are usually caused by pancreatic cystic neoplasms. Non-neoplastic pancreatic cystic and cystic-like lesions are extremely rare. In the present article, the surgical experience with these unusual entities over a 14-year period is reported. METHODS: Between 1991 and 2004, all patients who underwent surgical exploration for a cystic lesion of the pancreas were retrospectively reviewed. Patients with a pancreatic pseudocyst were excluded. There were 106 patients of whom 8 (7.5%) had a final pathological diagnosis consistent with a non-neoplastic pancreatic cystic or cystic-like lesion, including 3 patients with a benign epithelial cyst, 2 with a pancreatic abscess (one tuberculous and one foreign body), 2 with mucous retention cysts and 1 with a mucinous non-neoplastic cyst. These eight patients are the focus of this study. RESULTS: There were six female and two male patients with a median age of 61.5 years (range, 41-71 years). All the patients were of Asian origin including seven Chinese and one Indian. Four of the patients were asymptomatic and their pancreatic cysts were discovered incidentally on radiological imaging for other indications. All the patients underwent preoperative radiological investigations, including ultrasonography, computed tomography or magnetic resonance imaging, which showed a cystic lesion of the pancreas. Three patients, all of whom were symptomatic, were diagnosed preoperatively with a malignant cystic neoplasm on the basis of radiological imaging. Two patients were eventually found to have a pancreatic abscess, one tuberculous and the other, secondary to foreign body perforation. The third patient was found on final histology to have chronic pancreatitis with retention cysts. The remaining five patients had a preoperative diagnosis of an indeterminate cyst; on pathological examination, they were found to have a benign epithelial (congenital) cyst (n = 3), retention cyst (n = 1) and mucinous non-neoplastic cyst (n = 1). At a median follow up of 20 months (range, 3-34 months), none of the patients had any evidence of recurrent disease. CONCLUSION: Non-neoplastic cystic and cystic-like lesions of the pancreas are rare causes of pancreatic cystic lesions that are generally benign and do not require surgery when asymptomatic. However, despite advances in diagnostic investigations such as endoscopic ultrasound with fluid aspirate and magnetic resonance imaging, the preoperative diagnosis remains unreliable. Hence, the challenge for all clinicians is to recognize these lesions preoperatively and to avoid 'unnecessary' surgery.

Retroperitoneal schwannoma.

BACKGROUND: Retroperitoneal schwannomas are rare, benign tumors. The aim of this study is to present our surgical experience with 7 such tumors. METHODS: Between 1989 and 2004, 7 patients with pathologically proven retroperitoneal schwannomas were reviewed retrospectively. RESULTS: There were 6 male patients and 1 female patient, with a mean age of 43 years (range, 23 to 58 years). Two patients were symptomatic and presented with abdominal discomfort, and none of the patients suffered from von Recklinghausen's disease. All the patients underwent computed tomography scanning, which showed a heterogenous retroperitoneal mass, 4 of which were thought to arise from the adrenals. In 2 patients, calcification was seen in the tumors. All 7 of the patients had a preoperative diagnosis of a retroperitoneal tumor including 3 patients who were thought to have adrenal neoplasms (1 patient had a diagnosis of an adrenal neoplasm excluded on magnetic resonance imaging). Laparotomy and complete excision of tumors were performed in all the patients, and there was no morbidity or mortality. The schwannomas had a mean maximum diameter of 7.3 cm (range, 4 to 14 cm), and they were all benign. At a mean follow-up of 17 months (range, 3 to 48 months) postresection, all the patients remained free from recurrence. CONCLUSION: Retroperitoneal schwannomas are rare tumors that are difficult to diagnose preoperatively. Radiologic findings are usually nondiagnostic. The treatment of choice is complete surgical excision.

Surgical management of endoscopic retrograde cholangiopancreatography-related perforations.

BACKGROUND: A retrospective review was carried out of consecutive cases of endoscopic retrograde cholangiopancreatography (ERCP)-related perforation to identify risk factors and technique affecting surgical outcome. METHODS: Eighteen patients (0.45%) out of 4030 ERCP performed were operated on for ERCP-related perforation at Singapore General Hospital. RESULTS: The group's median age was 72.5 years and 14 patients had ductal stone disease. Five perforations were discovered at ERCP while 10 required computed tomography for diagnosis. Eight patients were operated on within 24 h whereas 10 patients had surgery after 24 h. Five of six with type I (lateral duodenal) perforations had early surgery versus one of seven with type II (peri-Vaterian; P = 0.03). There were four type III (bile duct) perforations and one type IV (retroperitoneal air). Five of six patients with type I perforation had simple repair compared with five of seven type II requiring the complex duodenal diversion procedure (P = 0.10). Three patients (16.7%) succumbed after surgery due to sepsis and myocardial infarction. Advanced age>70 years resulted in higher mortality of 30% versus none in patients <70 years (P = 0.22). CONCLUSIONS: Early diagnosis is important but difficult especially for the type II perforations. Duodenal diversion is used more frequently in patients with type II perforations and those operated on late. Advanced age contributes to poorer outcome in surgical treatment of ERCP perforations.

Primary reconstruction after extensive chest wall resection.

BACKGROUND: Chest wall resection and reconstruction has been proven to be a safe surgical procedure. This is particularly useful for breast cancer patients with chest wall recurrences or for those who first present with locally advanced cancer in the chest wall where there is both a large soft tissue and bony defect that need repair. In addition, many of these patients have had irradiation or chemotherapy, which can significantly impair wound healing. METHODS: Thirty-four patients underwent chest wall resection and primary reconstruction over an 8-year period. RESULTS: Twenty-three patients had breast carcinomas and six had breast and chest wall sarcomas. Of the breast carcinoma patients, 12 had local recurrences and 11 presented with locally advanced primary disease. Bony resection of the chest wall was required in 16 (47%) cases. Thirty myocutaneous flaps (18 rectus abdominis, four pectoralis major, eight latissimus dorsi) and three omental flaps were used for reconstruction. One required a deltovertebral skin flap. Skeletal reconstruction was necessary in four cases. All except one (97%) achieved primary wound healing. There was one mortality (3%) and three patients required further surgery for complications that were related to the reconstruction. Post-resection metastases occurred in 13 (42%) patients and only 2 (6%) had local recurrences. The 2-year survival rate was 78% with a mean survival time of 25.5 months. CONCLUSIONS: Primary reconstruction for curative or palliative purposes is a useful and safe surgical procedure for patients with recurrent or locally advanced chest malignancies after extensive chest wall resection. Pedicled myocutaneous flap is the preferred option for skeletal and soft-tissue coverage.