Stromal tumors of the small intestine. Retrospective analysis of 9 cases surgically treated

The authors report on their experience with 9 patients with small bowel stromal tumours who underwent surgical treatment over the period 1974-2001. Seven were males and 2 females, with an average age of 63.1 years (range: 49-72 years). Histologically, 4 tumours showed evidence of differentiation towards smooth muscle elements (1 benign and 3 malignant), 4 towards neural elements (all malignant) and 1 lacked differentiation towards either cell type. Five tumours were located in the ileum, 3 in the jejunum and 1 in the duodenum. The main symptoms were abdominal pain and an abdominal mass, and the most sensitive diagnostic technique was abdominal CT scan. In the 8 jejunal or ileal stromal tumours we performed a typical intestinal resection, while undifferentiated duodenal stromal tumours were managed by pancreaticoduodenectomy. The diagnosis was only histological. There was no operative mortality, while 2 postoperative complications (1 pancreatic fistula and 1 myocardial infarction) occurred. The patient with jejunal benign muscular stromal tumour is still alive and in good health 73 months after the operation. Of the 3 patients with malignant muscular ileal stroma tumours, 1 is alive and free from disease 63 months after the operation, while the other 2 died of metastatic disease 39 and 29 months after surgery. Of the 4 patients with malignant neural stromal tumours (2 jejunal and 2 ileal) 1 with jejunal and 1 with ileal tumour were lost to follow-up, while 1 is still alive and in good health 101 months postoperatively; the 4th patient, with jejunal disease, developed liver metastasis 14 months after small bowel resection and died 12 months later. The patient with undifferentiated duodenal stromal tumour died of liver metastases 38 months after pancreaticoduodenectomy. Small bowel stromal tumours are more often than not malignant. The most frequent symptoms are abdominal pain and a palpable mass, but no specific signs have been detected. Abdominal CT scan is the most sensitive diagnostic technique in the evaluation of the location, size, invasion of adjacent organs and metastases. The treatment must be intestinal resection, and prognostic prediction on the basis of histological findings is difficult.     

Gastric stromal tumors. Our experience in 21 cases surgically managed

BACKGROUND: A retrospective review on 21 patients with gastric stromal tumors who underwent surgical treatment in the period 1974-2001, is presented. METHODS: The patients were 8 males and 13 females, with an average age of 62.6 years. Histological examination showed 15 smooth muscle tumors (9 benign and 6 malignant), 5 neural tumours (3 benign and 2 malignant) and 1 undifferentiated tumor. Main symptoms were abdominal pain and palpable abdominal mass and the most sensible diagnostic techniques were endoscopy and abdominal CT-scan. Surgical procedures performed were: local resection (15 cases), partial gastric resection (3 cases), subtotal gastrectomy (2 cases) and total gastrectomy (1 case). RESULTS: There were no operative mortality and morbidity. Among 12 patients with benign GSTs, 1 died for causes not related to the disease, while 11 patients are still alive and in good health after a mean follow-up of 148.5 months (range 6-262). Among patients with malignant muscular GSTs, 3 were lost to follow-up and 3 are alive and free from disease after a median follow-up of 58 months (range 3-108). The 2 patients with malignant neural GSTs are still alive and in good health 140 and 24 months after surgical procedure, while the patient with undifferentiated GST died for liver metastases 43 months after total gastrectomy. CONCLUSIONS: The authors conclude that the most frequent symptoms are abdominal pain and a palpable mass, but no specific signs have been detected. Endoscopy plays a very important diagnostic role and CT-scan is the most sensible technique in the evaluation of location, size, invasion of adjacent organs and metastasis. The aim of treatment must be the complete resection of the tumor and the prognostic prediction on the basis of histologic findings is quite difficult.     

The impact of incidental gastrointestinal stromal tumours on patients undergoing resection of upper gastrointestinal neoplasms

Background

Emerging data suggest asymptomatic gastrointestinal stromal tumours (GISTs) of the upper gastrointestinal (UGI) tract are not uncommon. We sought to determine their incidence in patients undergoing resection for UGI neoplasms and their impact on surgical and adjuvant treatment.

Methods

We accessed a database prospectively listing all patients undergoing resection of non-GIST neoplasms of the stomach and esophagus at a single university centre over a 4.5-year period and reviewed pathology reports for the presence of synchronous GISTs in the UGI tract. We compared patient demographic and tumour characteristics, operative procedures and postoperative outcomes.

Results

In all, 207 patients undergoing gastrectomy or esophagectomy for non-GIST neoplasms were included. We identified 15 synchronous GISTs in the UGI tract of 11 (5.3%) patients (1 preoperatively, 4 intraoperatively and 10 on final pathology), with an average age of 67 years. Most patients were men. Additional resections were required for GISTs identified pre- or intraoperatively. Final pathology revealed completely resected c-kit positive tumours of an average size of 0.5 (range 0.1–4.0) cm with low or very low risk of malignant potential. No patients received adjuvant therapy for the GISTs. After a median follow-up of 11 (range 2–36) months, 5 patients died from their primary cancer, 3 were alive with primary cancer recurrence, and 3 were alive without disease. No patients experienced GIST recurrence.

Conclusion

Incidentally finding a synchronous GIST during resection of UGI neoplasms is not uncommon; it may alter surgical treatment but is unlikely to impact long-term survival.     

Gastrointestinal stromal tumours of the stomach: personal experience

Gastrointestinal stromal tumours are a relatively new nosological entity with an increasing incidence. CD117 positivity at immunohistochemical analysis is mandatory to distinguish them from other mesenchymal tumours. A gastric localisation is observed in more than 70% of cases. In the present paper 11 primary gastrointestinal stromal tumours of the stomach operated during the last decade at our institution were retrospectively reviewed. Hospital files and histological slides of 11 patients with gastrointestinal stromal tumours of the stomach undergoing surgical resection at our institution over the period from 1993 to 2003 were reviewed retrospectively. The variables analysed were: morphological and immuno-histochemical characteristics of the tumours, demographic data, type of surgical treatment and postoperative course. Long-term survival was evaluated on the basis of clinical and/or telephone follow-up in all patients. Immunohistochemical analysis for CD11 7 proved positive in all patients. The size of the tumours ranged from 3 to 23 cm: tumour size was > 5 cm and > 10 cm in 8 and 3 patients, respectively. Nodal involvement was detected in one patient and another had liver metastases. Surgical treatment consisted of wedge resection in 3 cases, distal subtotal gastrectomy in 4 and total gastrectomy in 4. In 2 patients surgical excision was extended to other organs. No postoperative mortality or major postoperative complications were observed. Nine patients were still alive at follow-up; 1 patient died as a result of a neoplastic relapse (38 months) and 1 died of other causes (48 months). The median survival was 42 months. Gastrointestinal stromal tumours are characterised by slow growth and therefore clinical signs are delayed. For that reason large tumours are often observed at the time of diagnosis. Surgical resection is the only potential curative treatment; but the risk of recurrence (local or at distance) remains high.     

Surface gastric cancer. Lymphatic metastases

We present 10 cases of early gastric carcinoma with lymph node invasion in a series of 40 cases early gastric cancer operated between 1974 and 1984 in our unit. Two tumours were mucosal and 8 were submucosal. One tumour was polypoid, 5 were superficiel and 4 were ulcerated. The mean number of invaded lymph nodes was 2.7. We performed a total gastrectomy in two patients and a distal gastrectomy in the other eight patients. Two patients died 26 and 27 months after the operation. The others are alive and tumour free. We believe that early gastric cancer must be treated aggressively by means of total or partial gastrectomy with resection of the N1 and N2 lymph node chains, when ever possible.     

Segmental resection of tumoral invasion of the inferior vena cava without reconstruction

STUDY AIM: Oncological complete surgery of retroperitoneal tumours may require segmental resection of part of the invaded inferior vena cava. The aim of this retrospective study was to assess whether reconstruction of the inferior vena cava is necessary and presents any advantage. PATIENTS AND METHODS: This study included four patients who underwent partial resection of the inferior vena cava invaded by a retroperitoneal tumour, without reconstruction. Tumours were one renal cancer, one malignant phaeochromocytoma, one malignant retroperitoneal histiofibroma and one undifferentiated retroperitoneal carcinoma. The resection was located at the level of the renal confluence, associated with right nephrectomy, in 3 patients, and above this confluence, at the level of the retrohepatic inferior vena cava in 1 patient. RESULTS: Only one case of transient acute renal failure was observed during the postoperative course. One patient developed right deep vein thrombosis after three months and another one after 30 months. One patient died from cancer recurrence after 19 months. The other 3 patients were alive with anticoagulant therapy and without sequelae after 3, 6 and 15 years.     

胃肠道间质瘤的诊治：附100例报告

目的:探讨胃肠道间质瘤的临床病理诊断与治疗方法.方法:回顾性分析100例胃肠道间质瘤的临床病理资料.结果:CT平扫探查发现所有患者肿块均为单发,79例良性肿块可见软组织密度肿块,密度均匀;21例恶性肿块内可见大小不等的低密度坏死区,呈分叶状.双期增强扫描见肿块腔内侧大小不一的溃疡,其中7例恶性间质瘤的溃疡程度大而深;增强扫描肿块呈不均匀明显强化,囊变坏死区无强化.病变发生在胃部56例,十二指肠26例,小肠10例,结肠及直肠6例,肠系膜2例.术中标本的病理学检测发现由梭形瘤细胞形成的细胞团巢是胃肠道间质瘤的特征排列.所有病例均完整切除,均未发现淋巴结转移,术中及术后均无死亡,平均住院时间15.2 d.随访期6～24个月,其中5例恶性肿瘤患者死亡,均死于肝转移;28例复发(28.0％),其中肿瘤类型:交界性肿瘤12例,恶性肿瘤16例;复发部位:局部复发16例,腹膜复发12例;再次进行切除手术后随访3个月,均存活.结论:胃肠道间质瘤可根据其临床表现、CT等影像学检查以及病理学检测等明确诊断,早行手术切除效果良好.     

Population-based study of the diagnosis and treatment of gastrointestinal stromal tumours

BACKGROUND: The aim of this retrospective population-based study, which was conducted before the introduction of imatinib, was to evaluate the role of surgery in patients with gastrointestinal stromal tumours (GISTs) and clarify which subgroups might benefit from adjuvant treatment. METHODS: Two hundred and fifty-nine patients with clinically detected GISTs were studied. Univariate and multivariate analyses were performed to identify predictors for recurrent disease and survival. RESULTS: Thirty of 48 patients with high-risk GISTs and all of those with overtly malignant tumours developed recurrent tumour after complete (R0) resection. Thirty-four of 38 first recurrences occurred within 36 months of surgery. No recurrence was observed after 72 months. R0 resection, achieved in 48 (80 per cent) of 60 patients with high-risk tumours, was significantly associated with a decreased risk of death from tumour recurrence (P = 0.008). CONCLUSION: Completeness of surgical resection is an independent prognostic factor in patients with high-risk GISTs. A period of adjuvant treatment with imatinib is recommended in patients with high-risk or overtly malignant GISTs who have undergone R0 resection and have a tumour-free interval of less than 6 years.     

Our experience regarding biologically inactive gastroenteropancreatic neuroendocrine tumors

The Authors present 9 cases of gastro-enteropancreatic neuro-endocrine biologically inactive tumors. In 5 cases the tumor site was appendicular. In 4 patients an appendectomy was performed, in one patient a right hemicolectomy and the patients after a period of 3-9 years are well and disease free. In a patient with a gastric carcinoid and a single hepatic metastasis a total gastrectomy with an hepatic metastasectomy were performed but the patient died 16 months thereafter. In a case localized to the right colon with a single hepatic metastasis a right hemicolectomy was performed with a metastasectomy but the patient died after 12 months. In a case localized to an ileal loop a segmental resection was performed followed by a medical therapy with octreotide and the patient is well and disease free after 3 years. In a case localized to the pancreas with widespread lymphatic metastasis it was performed a simple biliary diversion (coledocho-duodenostomy) followed by medical therapy with octreotide. Surprisingly after 4 years the patient is alive and a TC control shows a decrease of the pancreatic tumor and of the lympho glandular tumefactions.     

Laparoscopic management of gastrointestinal stromal tumours: review at a Canadian centre

Background

Laparoscopic wedge resection has been widely accepted for small benign gastric tumours. Large gastrointestinal stromal tumours (GISTs), however, can be difficult to manipulate laparoscopically and are at risk for capsule disruption, which can then result in peritoneal seeding. Some authors have suggested that large GISTs (> 8 cm) are best approached using an open technique. However, there has been no consensus as to what the cut-off size should be. We conducted one of the largest Canadian series to date to assess outcomes and follow-up of the laparoscopic management of GISTs.

Methods

All patients with gastric GISTs presenting to Vancouver General Hospital and University of British Columbia Hospital between 2000 and 2008 were reviewed. Most lesions were resected using a wedge technique with closure of the stomach facilitated by an endoscopic linear stapling device.

Results

In all, 23 patients presented with GISTs; 19 patients underwent laparoscopic resection and, of these, 15 had a purely laparoscopic operation and 4 had a hand-assisted laparoscopic resection. Mean tumour size was 3.2 cm, with the largest tumour measuring 6.8 cm. There were no episodes of tumour rupture or spillage and no major intraoperative complications. All margins were negative. Mean follow-up was 13.3 (range 1–78) months. There was no evidence of recurrence or metastasis.

Conclusion

The laparoscopic management of gastric GISTs is safe and effective with short hospital stays and good results over a mean follow-up of 13.3 months. We believe that it should be the preferred technique offered to patients.     

Gastric pseudolymphoma. A challenging clinical problem.

Gastric pseudolymphoma is a benign inflammatory condition that is usually associated with chronic gastric ulcer and often mimics gastric carcinoma or malignant lymphoma. Our experience with 12 histologically documented gastric pseudolymphomas at the Medical College of Virginia is presented with an emphasis on the approach to both diagnosis and surgical management. Preoperative diagnoses in this series ranged from benign gastric ulcer to gastric cancer. Treatment was by gastric resection in all cases and it included, as a minimum, antrectomy and excision of the lesion with an adequate gross margin. Of 11 cases with adequate follow-up, there are eight asymptomatic patients without recurrence and one patient who died of other causes without recurrence 5 years after gastrectomy. One patient developed recurrent pseudolymphoma in the proximal gastric remnant 39 months after a distal subtotal gastrectomy for pseudolymphoma. Another patient subsequently developed Hodgkin's disease of the gastric remnant, with regional lymph node and liver involvement, and died 35 months after the earlier subtotal gastrectomy for pseudolymphoma. Our clinical experience with this confusing and uncommon entity is compared with that previously reported in the medical literature.     

Haemorrhage from smooth muscle tumours of the upper gastro-intestinal tract

Eight patients with haemorrhage from smooth muscle tumours of the upper gastro-intestinal tract were treated during a 10 year period from 1973 to 1982. Seven of the tumours were benign and one a malignant leiomyoblastoma. Seven tumours were sited in the stomach and there was one duodenal lesion. Endoscopy was performed in all eight cases and made the diagnosis definitively in four. In two cases the diagnosis was confirmed on barium meal and in the other two, diagnosis was eventually made at laparotomy. Two patients were shocked on admission and required emergency surgery. In one case a diameter greater than 10 cm suggested malignant potential and wide local resection was performed. In one other case with a tumour in the antrum, a distal partial gastrectomy was performed, and in the case with leiomyoblastoma a proximal gastrectomy was performed. One case was lost to follow-up. The mean follow-up in six cases free of disease with benign tumour was 2.6 years. The patient with a tumour of greater than 10 cm in diameter remains well at 18 months follow-up and the patient with a malignant leiomyoblastoma died 2 years after surgery.     

Surgical management of gastrointestinal stromal tumors of the stomach

Background: Gastrointestinal stromal tumors (GISTs) are rare tumors of the GI tract with varying degree of dignity and prognosis. Intramural or extragastral growth of gastric GISTs is associated with diagnostic difficulties and uncertainty about the type and extent of surgical therapy. Based on our experience, we tried to formulate management guidelines for gastric GISTs. Methods: Five patients with gastric GIST (36–85 years old) underwent subserosal excision with subsequent B-II resection (1×), full-thickness partial gastric resection (2×), gastrotomy with submucosal excision (1×), or gastrectomy for carcinoma with an incidental finding of a leiomyoma (1×). Results: Tumor size ranged from 2×2×1 cm to 9×6×4 cm. These tumors were classified as epithelioid leiomyosarcoma (1×), GIST (3×), or leiomyoma (1×). The prognosis of risk ranged from no risk (leiomyoma) to low-malignancy (leiomyosarcoma) depending on tumor size and mitotic index. No recurrent disease has been noted so far during follow-up ranging from 3 months to 6 years. Conclusions: Staging of gastric disease should include the probability of gastric GIST. Surgical resection is the therapy of choice for potential malignant GISTs to ensure a local radical removal. Metachronic metastases should be resected if possible. Depending on tumor stage and prognostic parameters, an individual follow-up with endoscopic and radiologic examinations is recommended. Further studies should be undertaken to elaborate prognostic determinants and stage-adapted treatment. Received: 25 August 1999 In revised form: 4 January 2000 Accepted: 15 January 2000     

Simultaneous operations in thoraco-abdominal clinical oncology.

OBJECTIVE: To increase radical operability of cases with synchronous multiple primary malignant tumours (SMPTM) of the thorax and abdomen, and of cancer patients with concomitant severe heart disease simultaneous operations are implemented in the clinical practice. METHODS: Twenty-seven simultaneous operations for SMPMT (17) and for cancers of different sites and concomitant cardiac disease (10) were performed at the Surgical Department of Thoraco-Abdominal Oncology, N.N. Blokhin Memorial Cancer Research Centre. All SMPMT cases had lung cancer. The second tumours were gastric cancer (6), oesophageal cancer (7), laryngeal cancer (3) and opposite lung cancer (1). Coronary artery bypass grafting for ischaemic heart disease was made in nine cases simultaneously with lung resection (4), tracheal resection (1), resection of the stomach or gastrectomy (4). Mitral valve commissurotomy and left pneumonectomy for lung cancer was made in one case. RESULTS: Two patients died from therapeutic complications early postoperatively. Median survival after simultaneous operations for SMPMT was 26 months. One patient undergoing simultaneous operation for cardiac disease and lung cancer died from cancer progression at 1 year following surgery. The remaining patients were followed up for 2 years free from evidence of cancer or heart disease. CONCLUSION: Simultaneous operations increase resectability, radicality and functional operability and therefore promise improvement of follow-up results in the most serious category of cancer patients in question.     

Gastric Neuroendocrine Tumors in Our Institutions According to the WHO 2010 Classification

In 2010, World Health Organization classified gastric neuroendocrine tumor (NET) as follows: NET grade (G) 1, NET G2, neuroendocrine carcinoma (NEC). We reviewed 22 gastric NETs that were encountered in our institutions. Nine, 6, and 4 were NET G1, G2, and NEC, respectively. We also encountered 3 NET G3. NET G1 was treated with observation in 2 patients, endoscopic mucosal resection (EMR) in 3, and gastrectomy in 4 patients. No recurrence was experienced during a median of 53 months of follow-up. All NET G2 was treated with gastrectomy. No patient experienced recurrence during a median of 25 months of follow-up. NET G3 was treated with gastrectomy. One patient died of liver metastasis 52 months after gastrectomy. For NEC, gastrectomy was performed in 3 cases and no patients died of tumor-related death. We conclude that the prognoses of NET G1 and G2 were good. We also experienced long-term survivors of NEC. An accumulation of more patients is needed for further investigation.     

Gastrointestinal stromal tumors: analysis of clinical and pathologic factors

Gastrointestinal mesenchymal tumors have been classified as benign (leiomyoma) or malignant (leiomyosarcomas). More recently, these tumors have been termed gastrointestinal stromal tumors (GISTs). GISTs have a highly variable clinical course. This review analyzes the clinical presentation, pathologic examination, and long-term follow-up of patients with GIST. A retrospective analysis of the clinical course of patients with GIST at a single institution from 1986 to 1998 was performed. Nineteen patients with GIST (12 gastric, two duodenal, three jejunal, and two rectal) were treated. The most common clinical presentation was gastrointestinal bleed. CT scans, contrast studies, and endoscopy were used to identify a tumor mass. Diagnosis of GIST was made in only two patients preoperatively. Tumor size ranged from 0.8 to 23 cm. Histology of the tumors was variable. All patients underwent surgical resection with curative intent. Follow-up ranged from 2 to 55 months. There were two perioperative deaths. Local recurrence occurred in one patient. GISTs are uncommon. Preoperative diagnosis can be difficult, and often the diagnosis is made at the time of surgery. With complete resection of the tumor the clinical course is favorable with very few local recurrences. Therefore complete resection of the tumor is recommended.     

Laparoscopic Management of Gastrointestinal Stromal Tumours

Gastrointestinal stromal tumours (GISTs) represent the most common non-epithelial tumour of the digestive tract. Laparoscopic approach may be considered ideal for the resection of these tumours. Their particular biological behaviour allows for a curative resection even without large resection margins and extensive lymphadenectomies. Method: Over a period of five years, eight patients benefited from laparoscopic resections (six patients with primary gastric GIST and two patients with small bowel GIST). Pathological features were analyzed including tumour size, surgical margin status, immunohistochemical staining profile, and tumour mitotic index. All cases were confirmed GISTs by immunohistochemical staining.

Results: The mean age of the patients was 61.6 years (range 48–71years). Of these patients, five initially presented to hospital with acute gastrointestinal haemorrhage (four cases) or occult bleeding (one case). Gastric or small bowel tumours were identified during subsequent investigation. A presumptive diagnosis of gastric GIST was made in gastric lesions based on endoscopic, ultrasonic, and CT scan characteristics. Small bowel tumours were identified and presumed to be GIST based on information gathered from video capsule endoscopy, enteroscopy and CT scan. Complete resection was obtained with laparoscopic approach in six cases, while in two cases resection was laparoscopically assisted, with added oncology safety margins as preoperative definitive diagnosis was not available. Tumours varied in dimension from 2.5cm to 9 cm and their malignant risk score using Fletcher criteria was low in three cases, intermediate in three cases and high in two cases. Mean postoperative stay was 3.8 days and there were no complications, nor postoperative mortality. After a mean follow-up of 26 months (range 1 to 60 months) all patients are symptom free and free of recurrent disease.

Conclusions: A selective approach to laparoscopic resection of gastro-intestinal GISTs allows safe resection and very good results, on the condition that a clear diagnosis of GIST has been established on preoperative assessment. The laparoscopic feasible and safe considering the biological particularities of GIST, and it carries no additional risks.     

胃肠道间质瘤的诊断和治疗

目的 总结胃肠道间质瘤的诊断与治疗经验。方法 回顾性总结分析27例胃肠道间质瘤的临床和病理资料。结果 本组胃间质瘤21例,十二指肠间质瘤4例,小肠间质瘤2例。临床表现为消化道出血者16例(59.3％),其中腹痛伴消化道出血者7例;腹痛13例(48.1％),其中上腹部疼痛者6例;以腹部肿块就诊者5例(18.5％)。25例行胃镜检查,确诊为间质瘤2例,发现病变部位22例。2例伴消化道大出血者急诊数字式减法血管造影(DSA)发现病变部位。病理诊断为良性间质瘤12例、交界性13例、恶性2例;良性间质瘤核分裂像和肿瘤直径均显著小于交界性和恶性者(P<0.05)。本组均行手术局部切除治疗,术后发生肺部感染2例,胃排空障碍1例。21例患者术后随访3～24个月,除1例小肠恶性间质瘤患者术后20个月腹壁切口复发外,其余20例均无肿瘤转移复发。结论 内镜和影像学检查对胃肠道间质瘤病变定位有重要作用,胃肠道间质瘤的确诊依靠病理学检查。手术局部切除是治疗胃肠道间质瘤的有效手段。     

Gastric tumours

The majority of gastric tumours are adenocarcinomas. Rarer types include gastrointestinal stromal tumours (GISTs), carcinoids and lymphomas. Gastric adenocarcinoma is a common cancer worldwide with the highest rates in the Far East. In the UK the majority of patients with gastric adenocarcinoma present with advanced, incurable disease. Accurate disease staging is essential to identify those patients suitable for curative treatment. Staging involves the use of endoscopy, CT, PET–CT, endoscopic ultrasound, staging laparoscopy and bone scintigraphy. A fitness assessment is an essential part of the staging process. Early gastric adenocarcinoma may be treated with endoscopic mucosal resection. The mainstay of curative treatment is surgery commonly in the form of subtotal or total gastrectomy. Patients with locally advanced tumours should be considered for peri-operative chemotherapy. In the West this is according to the MAGIC trial. The overall prognosis from gastric adenocarcinoma is poor. In patients who undergo surgery, 5-year survival rates of 45% can be achieved. Gastric GISTs are managed according to the risk of malignant behaviour. The majority of carcinoids and lymphomas are managed non-operatively.