Is Peritoneal Tumor Penetration of Prognostic Importance in Gastrointestinal Stromal Tumors?

BACKGROUND: Peritoneal tumor penetration (PP) strongly affects prognosis in gastrointestinal carcinomas. In gastrointestinal stromal tumor (GIST), its significance in the absence of tumor rupture has not been subjected to detailed analysis. METHODS: Patients undergoing complete resection for non-metastatic GIST from 2000 to 2017 were identified in the regional sarcoma database at Oslo University Hospital. Patients with extraperitoneal tumors (esophagus, rectum) or ruptured tumors were excluded from the study. Rupture was defined according to the Oslo criteria, and PP was assessed via routine histopathologic examination by sarcoma pathologists. RESULTS: The study enrolled 341 patients. The median follow-up period was 51 months (range 0-175) months. In 82 (24%) of the 341 patients, PP was recorded. There were 32 recurrences, 9 in patients with PP and 23 in patients without PP. Despite statistically significant associations between PP and established risk factors (size, mitotic index, non-gastric location), the 5-year recurrence-free survival rate did not differ between the patients with PP (86%) and those without PP (90%) (hazard ratio 1.25; 95% confidence interval 0.58-2.70; P = 0.577). Adjuvant imatinib was administered to 53 of 97 patients in the high-risk category. The recurrence rates did not differ between the PP-positive and PP-negative patients in either group. CONCLUSIONS: In GIST, PP without tumor rupture appears not to influence prognosis. This lack of prognostic significance may reflect unexplored differences between epithelial and mesenchymal malignancies.

Relationship between R1 resection, tumour rupture and recurrence in resected gastrointestinal stromal tumour.

BACKGROUND: According to guidelines, adjuvant treatment or re-excision should be considered after R1 resection of gastrointestinal stromal tumours (GISTs). However, the prognostic significance of R1 resection is uncertain and tumour rupture confounds its assessment. Here, the impact of positive margins was examined and related to rupture in a population-based cohort. METHODS: Patients undergoing surgery for non-metastatic GIST since 2000 were identified in the sarcoma database of Oslo University Hospital. Margins were coded according to the residual tumour (R) classification and tumour rupture defined according to the Oslo criteria. RESULTS: Among 410 patients, there were 47 who underwent R1 resection and 52 had tumour rupture. The relative risk of R1 resection with rupture was 3·55 (95 per cent c.i. 2·09 to 6·03; P < 0·001). In patients without rupture, there was no difference in estimated 5-year recurrence-free survival after R0 versus R1 resection (87·6 versus 93 per cent; hazard ratio (HR) 0·71, 95 per cent c.i. 0·17 to 2·98; P = 0·638); nor was there any difference among patients with rupture (37 versus 31 per cent; HR 1·31, 0·68 to 2·54; P = 0·420). In multivariable analysis, tumour rupture but not R1 resection was independently associated with recurrence. Twenty-four patients at very low, low or intermediate risk did not receive adjuvant imatinib after R1 resection and remained recurrence-free. CONCLUSION: Positive resection margins are strongly associated with tumour rupture. R1 resection does not independently influence prognosis. Adjuvant imatinib may not be justified after R1 resection in the absence of tumour rupture or other high-risk features.

Genotype and risk of tumour rupture in gastrointestinal stromal tumour.

BACKGROUND: Tumour rupture is a strong predictor of poor outcome in gastrointestinal stromal tumours (GISTs) of the stomach and small intestine. The objective was to determine whether tumour genotype was associated with risk of rupture. METHODS: Rupture was classified according to the definition proposed by the Oslo Sarcoma Group. Since January 2000, data were registered retrospectively for all patients at Oslo University Hospital undergoing surgery for localized GIST of the stomach or small intestine. Tumour genotype was analysed by Sanger sequencing. RESULTS: Two hundred and nine patients with mutation data available were identified. Tumour rupture occurred in 37 patients. Among the 155 patients with KIT exon 11 mutations, an increased risk of rupture was observed with a deletion or insertion-deletion (25 of 86, 29 per cent) compared with substitutions (5 of 50, 10 per cent) or duplications/insertions (2 of 19, 11 per cent) (P = 0·014). Notably, rupture occurred in 17 of 46 tumours (37 per cent) with deletions involving codons 557 and 558 (del557/558) versus 15 of 109 (13·8 per cent) with other exon 11 mutations (P = 0·002). This association was confined to gastric tumours: 12 of 34 (35 per cent) with del557/558 ruptured versus six of 77 (8 per cent) with other exon 11 mutations (P = 0·001). In multivariable logistic regression analysis, del557/558 and tumour size were associated with an increased likelihood of tumour rupture, but mitotic count was not. CONCLUSION: Gastric GISTs with KIT exon 11 deletions involving codons 557 and 558 are at increased risk of tumour rupture. This high-risk feature can be identified in the diagnostic evaluation and should be included in the assessment when neoadjuvant imatinib treatment is considered.

Definition and clinical significance of tumour rupture in gastrointestinal stromal tumours of the small intestine.

BACKGROUND: Tumour rupture is a risk factor for recurrence of gastrointestinal stromal tumour (GIST). In this study, patterns of recurrence after potential tumour seeding were investigated, and a new definition of tumour rupture, based on major and minor defects of tumour integrity, is proposed. METHODS: Patients undergoing surgery for non-metastatic small intestinal GIST from 2000 to 2012 were included in the study. Tumour spillage, tumour fracture or piecemeal resection, bowel perforation at the tumour site, blood-tinged ascites, microscopic tumour infiltration into an adjacent organ, and surgical biopsy were defined as major defects of tumour integrity. Peritoneal tumour penetration, iatrogenic peritoneal laceration and microscopically involved margins were defined as minor defects. RESULTS: Seventy-two patients were identified. Median follow-up was 58 (range 7-122) months. Radical surgery was performed in 71 patients. A major defect was recorded in 20 patients, and a minor defect in 21. The 5-year recurrence rate was 64, 29 and 31 per cent in patients with major, minor and no defect respectively (P = 0·001). The hazard ratio (HR) for major defect versus no defect was 3·55 (95 per cent c.i. 1·51 to 8·35). Peritoneal recurrence rates for major, minor and no defect were 52, 25 and 19 per cent respectively (P = 0·002), and the HR for major defect versus no defect was 4·98 (1·69 to 14·68). On multivariable analysis, mitotic index, major defect of tumour integrity, tumour size and age were independently associated with risk of recurrence. CONCLUSION: Recurrence rates were increased after major, but not minor tumour ruptures.

Clinical prediction of survival by surgeons for patients with incurable abdominal malignancy.

BACKGROUND AND AIM: Accurate prognosis facilitates decision-making and counselling in incurable cancer. However, predictions of survival are frequently inaccurate and survival is consistently overestimated. The prognostic skills of surgeons are sparsely documented, and the present study was undertaken to assess their prognostic accuracy for patients with advanced abdominal malignancy. PATIENTS AND METHODS: Clinical predictions of survival were made by three consultant surgeons independently in consecutive patients with incurable abdominal cancer. Survival was predicted in intervals ranging from <1 week to 18-24 months. Prognoses were considered accurate when actual survival fell within the expected range. Performance status was classified according to the Eastern Cooperative Oncology Group (ECOG). RESULTS: 243 assessments were made in 178 patients. Prognoses were accurate in 27%, over-optimistic in 42% and over-pessimistic in 31%. Accuracy was inversely related to length of actual survival and did not differ between surgeons (P = 0.466). The proportion of over-optimistic prognoses differed significantly between surgeons (P < 0.001). Prognostic accuracy was 44% in gastric cancer patients, 29% in pancreatic cancer patients and 22% in colorectal cancer patients (P = 0.052). ECOG performance status correlated well with survival. CONCLUSIONS: Surgeons' accuracy in determining prognosis is poor. There are considerable individual differences between surgeons, and accuracy is reduced in cases with prolonged life expectancy.

Introducing national guidelines on perioperative chemotherapy for gastric cancer in Norway: a retrospective audit.

BACKGROUND: In 2006, perioperative chemotherapy with epirubicin, cisplatin/oxaliplatin, and capecitabine was recommended in the National Guidelines for patients with resectable gastric cancer in Norway. We conducted a national audit related to clinical aspects, local organisation and the implementation of this multimodal treatment. PATIENTS AND METHODS: All Norwegian departments of oncology were asked to submit aggregated data on gastric cancer patients who had started perioperative chemotherapy for cure; departments of surgery were asked to report on patients undergoing resection after preoperative chemotherapy. Data were retrospectively collected. RESULTS: All 20 departments of oncology and 20 of 21 departments of surgery responded. Of 336 patients operated on for gastric cancer and reported by surgeons, 144 (43%) received preoperative chemotherapy. 169 patients were reported by departments of oncology. 152 (90%) completed the preoperative cycles; 92 (54%) started the postoperative cycles; and 68 (40%) completed all cycles. Toxicity grade >or= 3, overall and haematological, increased during postoperative compared to preoperative cycles, 50 vs. 34% (P = 0.012) and 35 vs. 20% (P = 0.012), respectively. Surgical morbidity and mortality were 26 and <2%, respectively. R0 resection was achieved in 86% of surgically treated patients. Five per cent had a complete pathological response (ypT0) and 48% were node negative (ypN0). Within the first year, the National Guidelines were implemented in 19 of 25 hospitals (76%). CONCLUSIONS: In this population-based series, the tolerability of perioperative chemotherapy reported in the MAGIC trial was reproduced. Toxicity grade >or= 3 was considerable and significantly increased related to postoperative cycles. The National Guidelines were rapidly adopted.

Surgery for pilonidal disease.

BACKGROUND AND AIMS: Surgery for pilonidal disease carries a considerable risk of complications, recurrence, and cosmetic sequelae. The present study evaluates the four procedures performed in our institution. MATERIAL AND METHODS: Operations from 1999 through 2002 were retrospectively assessed. Cosmetic result and overall satisfaction were reported on visual analogue scales. RESULTS: Seventy-three procedures were performed in 71 patients: excision with open granulation in nine; excision and primary suture in 25; rhomboid plasty in 23; and lay-open in 16 patients. Infections were as frequent after rhomboid plasty (40%) as after excision and primary suture (43%). Nineteen recurrences (26%) were observed during a median follow-up of 20 months, and the estimated five-year actuarial recurrence rate was 44%. Recurrence occurred in 1/9 (11%) after excision with granulation, in 4/23 (17%) after excision and suture, in 5/25 (20%) after rhomboid plasty, and in 9/16 patients (56%) after lay-open. The cosmetic result was satisfactory only in 22/53 (42%) patients; the result was poor in 16/53 (30%) patients. CONCLUSION: Results after surgery for pilonidal disease are modest and should be compared to conservative management in a randomised trial.