Phase II trial of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors

Background: Photodynamic therapy (PDT) combines photosensitizer drug, oxygen, and laser light to kill tumor cells on surfaces. This is the initial report of our phase II trial, designed to evaluate the effectiveness of surgical debulking and PDT in carcinomatosis and sarcomatosis. Methods: Fifty-six patients were enrolled between April 1997 and January 2000. Patients were given Photofrin (2.5 mg/kg) intravenously 2 days before tumor-debulking surgery. Laser light was delivered to all peritoneal surfaces. Patients were followed with CT scans and laparoscopy to evaluate responses to treatment. Results: Forty-two patients were adequately debulked at surgery; these comprise the treatment group. There were 14 GI malignancies, 12 ovarian cancers and 15 sarcomas. Actuarial median survival was 21 months. Median time to recurrence was 3 months (range, 1-21 months). The most common serious toxicities were anemia (38%), liver function test (LFT) abnormalities (26%), and gastrointestinal toxicities(19%), and one patient died. Conclusions: Photofrin PDT for carcinomatosis has been successfully administered to 42 patients, with acceptable toxicity. The median survival of 21 months exceeds our expectations; however, the relative contribution of surgical resection versus PDT is unknown. Deficiencies in photosensitizer delivery, tissue oxygenation, or laser light distribution leading to recurrences may be addressed through the future use of new photosensitizers

Resection of primary leiomyosarcoma of the inferior vena cava (IVC) with reconstruction: a case series and review of the literature.

BACKGROUND: Leiomyosarcoma of the inferior vena cava (IVC) is a rare tumor which presents a unique surgical challenge. We present a series of six cases of leiomyosarcoma resection performed with IVC reconstruction. METHODS: Retrospective chart review was performed for patients undergoing initial operative resection of primary leiomyosarcoma with IVC reconstruction, at a tertiary care center. RESULTS: Between 2005-2013, six patients underwent resection with reconstruction. Half were female, and the mean age at presentation was 57 ± 15.4 years. Three patients required en bloc resection with adjacent organs. Three patients were resected on venovenous bypass, and one on cardiopulmonary bypass. Three underwent IVC patch repair (bovine pericardium, n = 2; saphenous vein, n = 1), and three had IVC reconstruction with graft (Dacron, n = 1; PTFE, n = 1; aortic homograft, n = 1). All achieved grossly negative margins. Median disease-free survival was 34 months (IQR 7-52 months), and median disease-specific survival was 51 months (IQR 20-108). Five year disease-free and disease-specific survival rates were 30% and 66.7%, respectively. CONCLUSIONS: Leiomyosarcomas of the IVC present a technical challenge to the surgeon. Careful preoperative workup and a collaborative team consisting of experienced cardiac and vascular surgeons and surgical oncologists can allow for a safe and successful operation despite extensive tumor involvement

Outcomes after resection of leiomyosarcomas of the inferior vena cava: a pooled data analysis of 377 cases.

BACKGROUND: Primary leiomyosarcomas of the inferior vena cava (IVC) pose unique surgical challenges. Due to the rarity of the disease, little definitive data exists on prognosis and treatment options. METHODS: A pooled data analysis was performed on all cases of initial IVC leiomyosarcoma resection identified by literature search (n = 371) and our institutional database (n = 6). Kaplan-Meier and Cox regression analyses were performed to identify factors associated with disease-free survival (DFS) and overall survival (OS). RESULTS: Patients were predominantly female (76%, n = 286); the median age of presentation was 55 years. Five-year DFS and OS were 6% and 55%, respectively. Preoperative factors independently associated with decreased OS included older age (HR:1.05, 95% CI:1.00-1.09), larger tumor size (HR:1.14, 95% CI:1.04-1.24), resection of adjacent organ(s) (HR:3.62, 95% CI:1.34-9.77), and R2 resection (HR:7.80, 95% CI:1.94-32.05). Isolated involvement of the suprarenal infrahepatic IVC was associated with longer OS (HR:0.22, 95% CI:0.06-0.78). A scoring system incorporating independent predictors of OS stratified outcomes: score 4-5 (n = 10, median OS 6 months), score 2-3 (n = 88, median OS 23 months) compared to a score of 0-1 (n = 44, median OS 29 months). CONCLUSIONS: Following resection of IVC leiomyosarcomas, recurrence is a near certainty; long-term survival, however is possible. The dominant predictors of survival include margin status, tumor size and radical resection. These can be combined into a risk score that has prognostic value

Successful venous repair and reconstruction for oncologic resections.

OBJECTIVE: We report our institutional experience of various venous reconstruction methods during oncologic resections, especially examining the patency of venous reconstructions and the conduits used. METHODS: All patients undergoing venous repair or reconstruction for oncologic resections between 2008 and 2014 were identified by a retrospective search of a prospectively maintained database at a single university hospital. Extent and manner of venous reconstruction and conduit or patch material were recorded. Need for intraoperative venovenous bypass or cardiopulmonary bypass was also recorded. Whereas no prescribed follow-up protocol has been instituted, patency and survival data as available were analyzed. RESULTS: During the study period, 127 patients were identified. Five patients had primary ligations, without limb loss. Of the remaining 122 patients, 77 (63%) underwent primary repairs, 23 (19%) had patch repair, and 22 (18%) had bypasses. Of these, 27 (22%) were for portal vein reconstruction during a Whipple procedure, 47 (39%) were for caval repair during caval thrombectomy in the setting of renal cell cancer, and 28 (23%) were for caval repair during resection for other abdominal malignant neoplasms. Venovenous bypass was used in 16 repairs and cardiopulmonary bypass in 10. The 1-year patency rates were 100% for primary and patch repairs and 86% for bypass graft reconstructions. Occlusions were suffered only in the prosthetic grafts group. There was no limb loss or significant long-term morbidity in patients with occluded grafts. Rate of infection was 0%, and there was no evidence of an increased infection rate in prosthetic or bioprosthetic conduits or patches. Perioperative mortality was 5.5%. CONCLUSIONS: Overall, venous reconstruction for oncologic resection can be done safely with very low complication rates and low perioperative mortality. Prosthetic grafts can be used for most reconstructions with no infections and good patency rates

Technique and Outcomes of Concomitant Aortic and Caval Resection and Reconstruction for Retroperitoneal Tumors.

OBJECTIVES: Major vascular involvement is often considered a contraindication to resection of malignant tumors, but in highly selected patients it can be performed safely, with results that are highly dependent upon the tumor biology. Resection of both the aorta and inferior vena cava (IVC) is a rare undertaking, requiring both favorable tumor biology and a patient fit for a substantial surgical insult; nevertheless, it provides the possibility of a cure. METHODS: Patients requiring resection and reconstruction of both the aorta and IVC from 2009 through 2019 at two university medical centers were included. Patient characteristics, operative technique, and outcomes were retrospectively collected. RESULTS: We identified nine patients, all with infrarenal reconstruction or repair of the aorta and IVC. All cases were performed with systemic heparinization and required simultaneous aortic and caval cross-clamping for tumor resection. No temporary venous or arterial bypass was used. Since arterial reperfusion with the IVC clamped was poorly tolerated in one patient, venous reconstruction was typically completed first. Primary repair was performed in one patient, while eight required replacements. In two patients, aortic homograft was used for replacement of both the aortoiliac and iliocaval segments in contaminated surgical fields. In the remaining six, Dacron was used for arterial replacement; either Dacron (n=2) or PTFE (n=4) were used for venous replacement. Patients were discharged after a median stay of 8 days (range: 5-16). At median follow up of 17 months (range 3-79 months), two patients with paraganglioma and one patient with Leydig cell carcinoma had cancer recurrences. Venous reconstructions occluded in three patients (38%), though symptoms were minimal. One patient presented acutely with a thrombosed iliac artery limb and bilateral common iliac artery anastomotic stenoses, treated successfully with thrombolysis and stenting. CONCLUSIONS: Patients with tumor involving both the aorta and IVC can be successfully treated with resection and reconstruction. En bloc tumor resection, restoration of venous return before arterial reconstruction, and most importantly, careful patient selection, all contribute to positive outcomes in this otherwise incurable population

Omission of Adjuvant Therapy After Gastric Cancer Resection: Development of a Validated Risk Model

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer recommend adjuvant chemotherapy with or without radiotherapy following after resection of gastric adenocarcinoma (GA) for patients who have not received neoadjuvant therapy. Despite frequent noncompliance with NCCN Guidelines nationally, risk factors underlying adjuvant therapy omission (ATom) have not been well characterized. We developed an internally validated preoperative instrument stratifying patients by incremental risk of ATom. The National Cancer Data Base was queried for patients with stage IB-III GA undergoing gastrectomy; those receiving neoadjuvant therapy were excluded. Multivariable models identified factors associated with ATom between 2006 and 2011. Internal validation was performed using bootstrap analysis; model discrimination and calibration were assessed using k-fold cross-validation and Hosmer-Lemeshow procedures, respectively. Using weighted β-coefficients, a simplified Omission Risk Score (ORS) was created to stratify ATom risk. The impact of ATom on overall survival (OS) was examined in ORS risk-stratified cohorts. In 4,728 patients (median age, 70 years; 64.8% male), 53.7% had ATom. The bootstrap-validated model identified advancing age, comorbidity, underinsured/uninsured status, proximal tumor location, and clinical T1/2 and N0 tumors as independent ATom predictors, demonstrating good discrimination. The simplified ORS, stratifying patients into low-, moderate-, and high-risk categories, predicted incremental risk of ATom (30% vs 53% vs 80%, respectively) and progressive delay to adjuvant therapy initiation (median time, 51 vs 55 vs 61 days, respectively). Patients at moderate/high-risk of ATom demonstrated worsening risk-adjusted mortality compared with low-risk patients (median OS, 26.4 vs 29.2 months). This ORS may aid in rational selection of multimodality treatment sequence in GA

Omission of adjuvant therapy after gastric cancer resection: development of a validated risk model.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer recommend adjuvant chemotherapy with or without radiotherapy following after resection of gastric adenocarcinoma (GA) for patients who have not received neoadjuvant therapy. Despite frequent noncompliance with NCCN Guidelines nationally, risk factors underlying adjuvant therapy omission (ATom) have not been well characterized. We developed an internally validated preoperative instrument stratifying patients by incremental risk of ATom. The National Cancer Data Base was queried for patients with stage IB-III GA undergoing gastrectomy; those receiving neoadjuvant therapy were excluded. Multivariable models identified factors associated with ATom between 2006 and 2011. Internal validation was performed using bootstrap analysis; model discrimination and calibration were assessed using k-fold cross-validation and Hosmer-Lemeshow procedures, respectively. Using weighted β-coefficients, a simplified Omission Risk Score (ORS) was created to stratify ATom risk. The impact of ATom on overall survival (OS) was examined in ORS risk-stratified cohorts. In 4,728 patients (median age, 70 years; 64.8% male), 53.7% had ATom. The bootstrap-validated model identified advancing age, comorbidity, underinsured/uninsured status, proximal tumor location, and clinical T1/2 and N0 tumors as independent ATom predictors, demonstrating good discrimination. The simplified ORS, stratifying patients into low-, moderate-, and high-risk categories, predicted incremental risk of ATom (30% vs 53% vs 80%, respectively) and progressive delay to adjuvant therapy initiation (median time, 51 vs 55 vs 61 days, respectively). Patients at moderate/high-risk of ATom demonstrated worsening risk-adjusted mortality compared with low-risk patients (median OS, 26.4 vs 29.2 months). This ORS may aid in rational selection of multimodality treatment sequence in GA