Is Systemic Chemotherapy Useful in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases? A Propensity-Score Analysis.

PURPOSE: Multimodal treatment of colorectal (CRC) peritoneal metastases (PM) includes systemic chemotherapy (SC) and surgical cytoreduction (CRS), eventually with hyperthermic intraperitoneal chemotherapy (HIPEC), in select patients. Considering lack of clear guidelines, this study was designed to analyze the role of chemotherapy and its timing in patients treated with CRS-HIPEC. METHODS: Data from 13 Italian centers with PM expertise were collected by a collaborative group of the Italian Society of Surgical Oncology (SICO). Clinicopathological variables, SC use, and timing of administration were correlated with overall survival (OS), disease-free survival (DFS), and local (peritoneal) DFS (LDFS) after propensity-score (PS) weighting to reduce confounding factors. RESULTS: A total of 367 patients treated with CRS-HIPEC were included in the propensity-score weighting. Of the total patients, 19.9% did not receive chemotherapy within 6 months of surgery, 32.4% received chemotherapy before surgery (pregroup), 28.9% after (post), and 18.8% received both pre- and post-CRS-HIPEC treatment (peri). SC was preferentially administered to younger (p = 0.02) and node-positive (p = 0.010) patients. Preoperative SC is associated with increased rate of major complications (26.9 vs. 11.3%, p = 0.0009). After PS weighting, there were no differences in OS, DFS, or LDFS (p = 0.56, 0.50, and 0.17) between chemotherapy-treated and untreated patients. Considering SC timing, the post CRS-HIPEC group had a longer DFS and LDFS than the pre-group (median DFS 15.4 vs. 9.8 m, p = 0.003; median LDFS 26.3 vs. 15.8 m, p = 0.026). CONCLUSIONS: In patients with CRC-PM treated with CRS-HIPEC, systemic chemotherapy was not associated with overall survival benefit. The adjuvant schedule was related to prolonged disease-free intervals. Additional, randomized studies are required to clarify the role and timing of systemic chemotherapy in this patient subset.

Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS. METHODS: Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS). RESULTS: The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4-51.2 months], and the median DFS was 13.6 months (95% CI, 12.3-14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4-24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS. CONCLUSION: For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal metastasis of non-primary origin.

PURPOSE: The objective of this study was to analyze the role of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy that has developed in the treatment of patients with peritoneal metastasis of non-primary origin. METHODS: Patients who underwent treatment for secondary gastrointestinal and ovarian malignancies over a 20-year period were reviewed. Survival curves were estimated by the Kaplan-Meier product limit method and the log-rank test was used to assess differences between subgroups. RESULTS: The study included 293 patients. The most common histology was ovarian cancer (56.3%). Median PCI was 16 and CC0-1 resection was obtained in 88.1% of cases. Grade III and IV complications occurred in 12 patients (4.1%) and 47 patients (16%), respectively. The 30- and 60-day mortality rate was 1.3% (4 patients) and 2.4% (7 patients). Five-year OS was 21.7%, 73.6%, 42.1%, and 0 for colorectal, appendiceal, ovarian, and gastric cancer (p = < 0.0001), respectively, whereas 5-year DFS was 12.4%, 48.4%, 24.3%, and 0 (p = < 0.0001), respectively. Survival outcomes were significantly higher for CC0 in each subgroup of patients. CONCLUSION: Despite being a complex procedure, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should be considered a safe treatment with acceptable postoperative morbidity and mortality rates, if performed in high-volume centers. Good survival outcomes have been increasingly obtained in selected patients with peritoneal metastasis of non-primary origin.

Standard versus eversion-modified double-staple technique for low colorectal anastomoses after resection of rectal cancer.

PURPOSE: The double-staple technique, performed as either the standard procedure or after eversion of the rectal stump, is a well-established method of performing low colorectal anastomoses following the resection of rectal cancer. Eversion of the tumor-bearing ano-rectal stump was proposed to allow the linear stapler to be fired at a safe distance of clearance from the tumor. We conducted this study to compare the results of the standard versus the eversion-modified double-staple technique. METHODS: The subjects of this retrospective study were 753 consecutive patients who underwent low stapled colorectal anastomosis after resection of rectal cancer. The patients were divided into two groups according to the method of anastomosis used: Group A comprised 165 patients (22%) treated with the modified eversion technique and group B comprised 588 patients (78%) treated with the standard technique. The primary endpoints of the study were postoperative mortality, surgery-related morbidity, the number of sampled lymph nodes in the mesorectum, and late disease-related survival. RESULTS: Postoperative mortality was 1.2% in group A and 1.7% in group B (p = 0.66). Postoperative morbidity was 12% in group A and 11% in group B (p = 0.75). The mean number of sampled lymph nodes in the mesorectum was 23 (range 17-27) in group A and 24 (range 19-29) in group B (p = 0.06). The 5-year disease-related survival was 73% in group A and 74% in group B (p = 0.75). CONCLUSION: The standard and eversion-modified double-staple techniques yield comparable results.

Uncommon retroperitoneal tumour: follicular dendritic cell sarcoma.

INTRODUCTION: Retroperitoneal Follicular Dendritic Cell Sarcomas represents rare tumours with aggressive biologic behaviour. Accurate diagnosis requires a combination of both morphological and immunohistochemical analyses. PATIENTS AND METHODS: A 61-year-old man was referred to our Department with a left perinephric mass. Computed tomography scan showed a 5.5 cm circumscribed mass in front of the left renal vein abutting the first jejunal loop, with moderate heterogeneous contrast enhancement. Positron emission/computed tomography showed increased focal uptake in the lesion. RESULTS: A retroperitoneal tumor located behind the first jejunal loop was found at laparotomy, encompassing the superior mesenteric vessels. Excision with en-bloc segmental small bowel resection was performed. Morphological and immunohistochemical analyses were consistent with Follicular Dendritic Cell Sarcoma. CONCLUSIONS: Complete surgical resection in specialized multidisciplinary centers represents the treatment of choice for both primary or recurrent lesions since there is still no consensus on the role of adjuvant radio-chemotherapy.

Mesothelial cyst of the round ligament of the liver.

A 34-year-old man was admitted in our department with a 3 months history of epigastric pain, abdominal distension and tenderness. Helical computed tomography scan and magnetic resonance imaging showed a 10 cm low-density fluid-filled polilobate cystic lesion with internal septations and calcifications located between the left lobe of the liver, shorter gastric curvature, pancreas and mesocolon. Laparoscopic exploration was performed. Macroscopically the lesion was a unilocular serous cyst with a thick fibrous wall. Histopathology revealed a thin fibrous wall with a single layer of flattened to cuboidal mesothelial cell lining lacking any cellular atypia. The patient is currently alive without evidence of recurrence at 6 months. Cysts of mesothelial origin are rare lesions seen more frequently in young and middle-aged women, mostly benign and located in the mesenteries or omentum. Diagnosis is usually based on clinical examination and radiographic imaging. Immunohistochemistry is used to differentiate histologic type, with simple mesothelial cysts being positive for cytokeratins and calretinin and negative for CD31. The laparoscopic approach appears safe, feasible and less-invasive without compromising surgical principles and today should be considered the gold standard in most cases.