Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Management of Colorectal Cancer with Peritoneal Dissemination: 30 Years of Experience at a Single Institution.

BACKGROUND: Cytoreductive surgery (CRS) is at the forefront of treatment for colorectal cancer with peritoneal metastasis or "carcinomatosis" (CRC-PC). We report outcomes of the operative management of CRC-PC at a single center. STUDY DESIGN: We retrospectively reviewed our database from 1992 through 2021. The Kaplan-Meier method was used to estimate survival. Proportional hazards regression and multivariable models were used for assessments. RESULTS: This study included 345 patients with mean age 53.5 years. Multivariate analysis revealed performance and resection status were associated with overall survival (OS; p < 0.001). Within the R0/R1 group, adverse impact on OS was found with increasing Peritoneal Cancer Index (PCI) score starting at 9 (hazard ratio [HR] = 1.98, CI 1.39-2.82, p = 0.0001) with the most significant hazard noted at PCI >14 (HR = 2.35, CI 1.52-3.63, p = 0.0001). Incomplete resection (R2) had significantly worse OS compared with complete CRS 33.4 (n = 206) vs R2: 12.7 months (n = 139; p < 0.0001. When stratified by PCI for the R0/R1 group, median OS for PCI less than 10, 10 to 15, and greater than 15 was 38.2, 19.7, and 22.2 m, respectively (p = 0.0007 comparing PCI less than 10 and greater than 15). Ten-year increments-1991 through 2000, 2001 through 2010, 2011 through 2020-revealed improvement in median OS (13.4 [n = 66], 19.3 [n = 139], and 29.1 months [n = 140]). However, by resection status, median OS remained stable for R0/R1 (32.3 [n = 23], 31.1 [n = 76], and 34.1 months [n = 107]) and improved for R2 (5.2 [n = 43], 14.4 [n = 63], and 14.6 months [n = 33]). Clavien-Dindo complication rate (greater than or equal to grade III) was 29.4%. CONCLUSION: CRS improves outcomes for CRC-PC compared with historic outcomes with nonoperative management. This benefit is greatest with complete resection and lower disease burden. Results of CRS (with or without heated intraperitoneal chemotherapy) are improving, and surgery for CRC-PC should be routinely considered.

Primary care referrals to nephrology in patients with advanced kidney disease.

OBJECTIVES: Optimizing care for patients with advanced kidney disease requires close collaboration between primary care physicians (PCPs) and nephrologists. Factors associated with PCP referral to nephrology were assessed in patients with estimated glomerular filtration rates (eGFRs) less than 30 mL/min/1.73 m2. STUDY DESIGN: Electronic health record review at an integrated health care network. METHODS: Factors associated with referral status were identified using Fisher's exact tests, t tests, and multivariable logistic regression. RESULTS: Of 133,913 patients regularly seeing PCPs between October 2017 and September 2019, 1119 had a final eGFR less than 30 mL/min/1.73 m2 and were not on renal replacement therapy. Care was provided by 185 PCPs (61 practices). Analyses were restricted to the 97.1% (n = 1087) of patients who were African American or European American. Of these, 54.6% had not been referred to nephrology. Nonreferred patients had higher numbers of PCP visits (P = .004). In contrast, referred patients were younger, were more often African American, and had PCPs at the academic medical center (all P < .0001). Referred patients had more complex medical histories with higher Charlson Comorbidity Index scores, more hospitalizations, and greater numbers of inpatient days (all P < .0001). Analyses restricted to patients with serum creatinine concentration of at least 2 mg/dL yielded similar results. Age, number of hospitalizations, ancestry, academic physician, diabetic end-organ damage, peripheral vascular disease, and tumor status were independent predictors of nephrology referral. CONCLUSIONS: Impediments to appropriately timed nephrology referrals persist in patients with high likelihoods of progression to end-stage kidney disease. Improved access to nephrology care should be rapidly addressed to meet targets in the 2019 Executive Order on Advancing American Kidney Health.

Goals and Adverse Effects: Rate of Concordance Between Patients and Providers.

PURPOSE: Adequate understanding of the goals and adverse effects of cancer treatment has important implications for patients' decision making, expectations, and mood. This study sought to identify the degree to which patients and clinicians agreed upon the goals and adverse effects of treatment (ie, concordance). METHODS: Patients completed a demographic questionnaire, the National Comprehensive Cancer Network Distress Thermometer, the Medical Outcomes Study Social Support Survey, the Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-General questionnaire, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being questionnaire, and a 13-item questionnaire about the goals and adverse effects of treatment. Providers completed a 12-item questionnaire. RESULTS: One hundred patients (51 female) and 34 providers participated (questionnaire return rate mean difference, 5 days; SD, 16 days). Patient and provider dyads agreed 61% of the time regarding the intent of treatment. In cases of nonagreement, 36% of patients reported more optimistic therapy goals compared to providers. Patients and providers agreed 69% of the time regarding the patient's acknowledgement and understanding of adverse effects. Patients who reported an understanding of likely adverse effects endorsed significantly lower distress scores (mean, 2.5) than those who endorsed not understanding associated adverse effects (mean, 4.1; P = .008). CONCLUSION: Timely data capturing of patient-provider dyadic ratings is feasible. A significant discrepancy exists between a substantial percentage of patients' and providers' views of the intent and adverse effects of treatment. Patients were almost always more optimistic about the intent of treatment. Higher rates of distress were noted in cases of discordance. Providers may benefit from conversational feedback from patients as well as other integrated feedback systems to inform them about patient understanding.

Quality-of-Life Evaluation After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases can alleviate symptoms and prolong survival at the expense of morbidity and quality of life (QoL). This study aimed to monitor QoL and outcomes before and after HIPEC. METHODS: A prospective QoL trial of patients who underwent HIPEC for peritoneal metastases from 2000 to 2015 was conducted. The patients completed the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the Functional Assessment of Cancer Therapy + Colon Subscale (FACT-C), the Brief Pain Inventory, the Center for Epidemiologic Studies Depression scale, and the Eastern Cooperative Oncology Group (ECOG) performance status at baseline, then 3, 6, 12, and 24 months after HIPEC. The trial outcome index (TOI) was analyzed. Proportional hazards modeled the effect of baseline QoL on survival. RESULTS: The 598 patients (53.8 % female) in the study had a mean age of 53.3 years. The overall 1-year survival rate was 76.8 %, and the median survival period was 2.9 years. The findings showed a minor morbidity rate of 29.3 %, a major morbidity rate of 21.7 %, and a 30-day mortality rate of 3.5 %. The BPI (p < 0.0001) and worst pain (p = 0.004) increased at 3 months but returned to baseline at 6 months. After CS + HIPEC, FACT-C emotional well-being, SF-36 mental component score, and emotional health improved (all p < 0.001). Higher baseline FACT-General (hazard ratio [HR], 0.92; 95 % confidence interval [CI], 0.09-0.96), FACT-C (HR, 0.73; 95 % CI 0.65-0.83), physical well-being (HR, 0.71; 95 % CI 0.64-0.78), TOI (HR, 0.87; 95 % CI 0.84-0.91), and SF-36 vitality (HR, 0.88; 95 % CI 0.83-0.92) were associated with improved survival (all p < 0.001). Higher baseline BPI (HR, 1.1; 95 % CI 1.05-1.14; p < 0.0001), worst pain (HR, 1.06; 95 % CI 1.01-1.10; p = 0.01), and ECOG (HR, 1.74; 95 % CI 1.50-2.01; p < 0.0001) were associated with worse survival. CONCLUSIONS: Although HIPEC is associated with morbidity and detriments to QoL, recovery with good overall QoL typically occurs at or before 6 months. Baseline QoL is associated with morbidity, mortality, and survival after HIPEC.

Plasma FGF23 and Calcified Atherosclerotic Plaque in African Americans with Type 2 Diabetes Mellitus.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in disorders of serum phosphorus concentration and vitamin D. The role of FGF23 in vascular calcification remains controversial. METHODS: Relationships between FGF23 and coronary artery calcified atherosclerotic plaque (CAC), aortoiliac calcified plaque (CP), carotid artery CP, volumetric bone mineral density (vBMD), albuminuria, and estimated glomerular filtration rate (eGFR) were determined in 545 African Americans with type 2 diabetes (T2D) and preserved kidney function in African American-Diabetes Heart Study participants. Generalized linear models were fitted to test associations between FGF23 and cardiovascular, bone, and renal phenotypes, and change in measurements over time, adjusting for age, gender, African ancestry proportion, body mass index, diabetes duration, hemoglobin A1c, blood pressure, renin-angiotensin-system inhibitors, statins, calcium supplements, serum calcium, and serum phosphate. RESULTS: The sample was 56.7% female with a mean (SD) age of 55.6 (9.6) years, diabetes duration of 10.3 (8.2) years, eGFR 90.9 (22.1) ml/min/1.73 m2, urine albumin:creatinine ratio (UACR) 151 (588) (median 13) mg/g, plasma FGF23 161 (157) RU/ml, and CAC 637 (1,179) mg. In fully adjusted models, FGF23 was negatively associated with eGFR (p < 0.0001) and positively associated with UACR (p < 0.0001) and CAC (p = 0.0006), but not with carotid CP or aortic CP. Baseline FGF23 concentration did not associate with changes in vBMD or CAC after a mean of 5.1 years follow-up. CONCLUSIONS: Plasma FGF23 concentrations were independently associated with subclinical coronary artery disease, albuminuria, and kidney function in the understudied African American population with T2D. Findings support relationships between FGF23 and vascular calcification, but not between FGF23 and bone mineral density, in African Americans lacking advanced nephropathy.

Metastatic colorectal cancer: survival comparison of hepatic resection versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Liver resection has long been considered the standard of care for resectable colorectal hepatic metastases (HM). Patients with colorectal peritoneal surface disease (PSD) are now also being treated with aggressive therapy in the form of cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A retrospective comparison of optimally-treated colorectal cancer patients with HM or PSD obtained from prospectively maintained databases (1991-2010). RESULTS: Liver resection was performed on 179 patients with HM, while 93 PSD patients received a complete cytoreduction followed by HIPEC. Patients differed in terms of age, performance status, site of primary cancer, T stage, and the use of perioperative chemotherapy. Five-year overall survival for HM patients was 36 %, with a median survival of 46 months, compared with 26 % and 34 months in patients with PSD (p = 0.024). When stratified by resection status, R0 HM (n = 170) and R0 PSD (n = 48) patients had similar median survival (49 vs. 41 months; p = 0.39). Median survival following R1 resection was also similar among HM (n = 9) and PSD (n = 45) patients (28 vs. 23 months; p = 0.68). Multivariate analysis identified distinctly different independent prognostic factors between HM and PSD patients. Major morbidity was 21 and 23 % (p = 0.88), while mortality was 3.9 versus 5.4 % (p = 0.55) in the HM and PSD patients, respectively. CONCLUSION: Colorectal HM and PSD are distinct biologic diseases with different presentations and unique prognostic factors. However, long-term survival following CS/HIPEC is comparable to liver resection when stratified by completeness of resection. Furthermore, perioperative morbidity and mortality are similar.

Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1,000 patients.

BACKGROUND: Peritoneal dissemination of abdominal malignancy (carcinomatosis) has a clinical course marked by bowel obstruction and death; it traditionally does not respond well to systemic therapy and has been approached with nihilism. To treat carcinomatosis, we use cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A prospective database of patients has been maintained since 1992. Patients with biopsy-proven peritoneal surface disease were uniformly evaluated for, and treated with, CS and HIPEC. Patient demographics, performance status (Eastern Cooperative Oncology Group), resection status, and peritoneal surface disease were classified according to primary site. Univariate and multivariate analyses were performed. The experience was divided into quintiles and outcomes compared. RESULTS: Between 1991 and 2013, a total of 1,000 patients underwent 1,097 HIPEC procedures. Mean age was 52.9 years and 53.1% were female. Primary tumor site was appendix in 472 (47.2%), colorectal in 248 (24.8%), mesothelioma in 72 (7.2%), ovary in 69 (6.9%), gastric in 46 (4.6%), and other in 97 (9.7%). Thirty-day mortality rate was 3.8% and median hospital stay was 8 days. Median overall survival was 29.4 months, with a 5-year survival rate of 32.5%. Factors correlating with improved survival on univariate and multivariate analysis (p ≤ 0.0001 for each) were preoperative performance status, primary tumor type, resection status, and experience quintile (p = 0.04). For the 5 quintiles, the 1- and 5-year survival rates, as well as the complete cytoreduction score (R0, R1, R2a) have increased, and transfusions, stoma creations, and complications have all decreased significantly (p < .001 for all). CONCLUSIONS: This largest reported single-center experience with CS and HIPEC demonstrates that prognostic factors include primary site, performance status, completeness of resection, and institutional experience. The data show that outcomes have improved over time, with more complete cytoreduction and fewer serious complications, transfusions, and stomas. This was due to better patient selection and increased operative experience. Cytoreductive surgery with HIPEC represents a substantial improvement in outcomes compared with historical series, and shows that meaningful long-term survival is possible for selected carcinomatosis patients. Multi-institutional cooperative trials are needed to refine the use of CS and HIPEC.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from small bowel adenocarcinoma.

Peritoneal carcinomatosis arising from small bowel adenocarcinoma (PCSBA) carries a dismal prognosis. Presently, limited data have been published on the outcome of PCSBA treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). This series represents the largest series published to date examining our experience with 17 patients. From 1995 to 2011, 17 patients underwent HIPEC with mitomycin for PCSBA. Patients in this study were identified from a prospectively maintained database. Twenty HIPEC procedures were performed on 17 patients with a mean age of 52.2 years. Patients have achieved a mean overall postoperative survival of 18.4 months after progression on chemotherapy with an overall postoperative one- and three-year survival of 52 and 23 per cent, respectively. The mean total length of hospital stay was 10 days. There was no treatment-related mortality. Six patients were readmitted to the hospital within 30 days of discharge (35%). Eight patients (47%) experienced postoperative complications, in which two patients had major postoperative complications in the form of intra-abdominal abscess requiring interventions (12%). HIPEC has encouraging survival results for patients with PCSBA compared with similar patients treated with conventional treatments. However, even with such advancement in management, treatment for small bowel adenocarcinoma still remains a challenge.

Outcomes of repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal surface malignancy.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the survival of patients with peritoneal surface malignancy. On recurrence, a repeat CRS/HIPEC is a treatment option. STUDY DESIGN: A retrospective analysis of 868 CRS/HIPEC procedures was performed. Type of primary, functional status, completion of resection, hospitalization, morbidity, mortality, and survival were reviewed. RESULTS: Sixty-two patients (7.7%) underwent a second CRS/HIPEC, including 33 patients with appendiceal primaries, 8 ovarian, 7 mesotheliomas, 4 colon cancers, and 10 various malignancies. Median follow-up was 60.8 months. Median overall survival in months was 85.3 for appendiceal cancer, 52.9 for mesothelioma, 60.1 for ovarian, and 137.4 for colon cancer. R1 resection was achieved in 43.5% after both procedures. Median survival after the second cytoreduction was 52.1 months for appendiceal cancer, 21.8 for mesothelioma, 53.9 for ovarian, and 55.7 for colon cancer. Median survival was 55.7 months for R1 resection, 20.3 months for R2a resection, and 15.5 months for R2b-R2c. Median ICU and hospital stay was 1 and 7.5 days, respectively. The 30-day morbidity after the second CRS/HIPEC was 48.4% and mortality was 3.2%. In multivariate analysis, the R status of the second CRS/HIPEC (p = 0.013) and the interval between the 2 procedures (p = 0.009) were significant in predicting improved survival. CONCLUSIONS: In experienced tertiary centers and for selected patients, a repeat CRS/HIPEC procedure has morbidity and mortality similar to the initial cytoreduction. Survival depends primarily on the completion of the repeat cytoreduction and favorable biology of the tumor.

Patient rated outcomes and survivorship following cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CS + HIPEC).

BACKGROUND: Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CS + HIPEC) is a treatment combining cytoreductive surgery with hyperthermic chemotherapy directly into the peritoneal cavity. Recipients may gain extended life when compared with best supportive care; yet results often are achieved with substantial morbidity and health-related quality of life (HRQOL) deficits. The purpose of this study was to record patient rated outcomes and the HRQOL of long-term survivors. METHODS: One hundred and two patients living 12+ months post-treatment completed a survey including the Medical Outcomes Study 36-item Short Form Health Survey (SF-36), Functional Assessment of Cancer Therapy-Colon (FACT-C), and Pittsburgh Sleep Quality Index. RESULTS: SF-36 Physical Component scores were significantly lower than general population norms (46.7, z= -2.943, P=0.003), while Mental Component scores were significantly higher (53.6, z=4.208, P ≤ 0.001). FACT scores were higher than general FACT normative scores. The majority (56%) of these survivors reported significant sleep quality impairment. CONCLUSION: Although most HRQOL scores were comparable to or higher than those of the general population, long-term physical and functional deficits remain. These deficits, along with the poor sleep quality of recipients, may be improved by survivorship programs or targeted psychosocial interventions.

Yin Yang 1 plays an essential role in breast cancer and negatively regulates p27.

Yin Yang 1 (YY1) is highly expressed in various types of cancers and regulates tumorigenesis through multiple pathways. In the present study, we evaluated YY1 expression levels in breast cancer cell lines, a breast cancer TMA, and two gene arrays. We observed that, compared with normal samples, YY1 is generally overexpressed in breast cancer cells and tissues. In functional studies, depletion of YY1 inhibited the clonogenicity, migration, invasion, and tumor formation of breast cancer cells, but did not affect the clonogenicity of nontumorigenic cells. Conversely, ectopically expressed YY1 enhanced the migration and invasion of nontumorigenic MCF-10A breast cells. In both a monolayer culture condition and a three-dimensional Matrigel system, silenced YY1 expression changed the architecture of breast cancer MCF-7 cells to that resembling MCF-10A cells, whereas ectopically expressed YY1 in MCF-10A cells had the opposite effect. Furthermore, we detected an inverse correlation between YY1 and p27 expression in both breast cancer cells and xenograft tumors with manipulated YY1 expression. Counteracting the changes in p27 expression attenuated the effects of YY1 alterations on these cells. In addition, YY1 promoted p27 ubiquitination and physically interacted with p27. In conclusion, our data suggest that YY1 is an oncogene and identify p27 as a new target of YY1.

Survival and quality of life following cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis of colonic origin.

BACKGROUND: Peritoneal carcinomatosis of colonic origin (PCC) is a life-threatening diagnosis. Cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) offers patients the prospect of long-term survival with alleviation of symptoms. METHODS: Patients underwent HIPEC for PCC and completed questionnaires preoperatively (T1) and after surgery at 3 (T2), 6 (T3), and 12 (T4) months. Questionnaires included the Functional Assessment of Cancer Therapy-Colon (FACT-C), Brief Pain Inventory (BPI), SF-36 Medical Outcomes Study Survey (SF-36), Center for Epidemiologic Studies-Depression Scale (CES-D), and the ECOG Performance Status Rating. RESULTS: A total of 62 patients were assessed before surgery. Median overall survival was 18 months, with 71.3 ± 6.3% survival at 1 year. Emotional well-being (P = .0007) improved after HIPEC. Social/family well-being (P = .065) and the colon subscale (P = .061) of the FACT worsened at T2, but recovered by T3. One-third to one-half of patients reported depressive symptoms over the course of the study. Pain scores increased above BL at T2, but decreased below BL at T3 and T4. CONCLUSIONS: Emotional well being is improved after CS + HIPEC despite complications that may affect short-term recovery. Most patients remaining in the study recover to preoperative levels of functioning between 3 and 6 months after surgery. For some, survival can be attained without major decrement in QOL at 1 year. QOL concerns must be a key component in the evaluation for patients with PCC for CS and HIPEC.

Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for malignant peritoneal mesothelioma: mitomycin versus cisplatin.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare, rapidly fatal disease. Because traditional treatments offer little benefit, there has been increasing interest in cytoreductive surgery (CS) with intraperitoneal hyperthermic chemotherapy (IPHC). The most efficacious chemotherapy regimen is not established. Herein we report clinical outcomes of MPM patients treated with CS and IPHC and contrast results using two chemoperfusates: mitomycin and cisplatin. METHODS: Thirty-four patients were treated for MPM. Following CS, 19 patients underwent IPHC with mitomycin and 15 received cisplatin. Overall survival, disease-free survival, and progression-free survival were compared between the two groups. RESULTS: Overall survival was 56 and 17% at 3 and 5 years, with median survival of 40.8 months. Those perfused with cisplatin were more likely to be alive at 1, 2, and 3 years (P < 0.05, 0.05, and 0.04, respectively). Median survival for mitomycin and cisplatin was 10.8 and 40.8 months, respectively (P = 0.22). Median disease-free survival and progression-free survival were 10.3 and 9.1 months, respectively. There was a trend toward improved disease-free and progression-free survival using cisplatin. CONCLUSIONS: CS with IPHC is a promising modality for patients with MPM, and clinical outcomes appear to be improved using cisplatin. We recommend using high-dose intraperitoneal cisplatin following cytoreductive surgery when treating malignant peritoneal mesothelioma.

Restorative yoga for women with breast cancer: findings from a randomized pilot study.

OBJECTIVES: Restorative yoga (RY) is a gentle type of yoga that may be beneficial for cancer patients and post-treatment survivors. Study goals were: to determine the feasibility of implementing a RY intervention for women with breast cancer; and to examine group differences in self-reported emotional, health-related quality of life, and symptom outcomes. METHODS: Women with breast cancer (n=44; mean age 55.8 years) enrolled in this study; 34% were actively undergoing cancer treatment. Study participants were randomized to the intervention (10 weekly 75-minute RY classes) or a waitlist control group. Participants completed questionnaires at Week 0 (baseline) and Week 10 (immediately post-intervention for the yoga group). RESULTS: Group differences favoring the yoga group were seen for mental health, depression, positive affect, and spirituality (peace/meaning). Significant baseline*group interactions were observed for negative affect and emotional well-being. Women with higher negative affect and lower emotional well-being at baseline derived greater benefit from the yoga intervention compared to those with similar values at baseline in the control group. The yoga group demonstrated a significant within-group improvement in fatigue; no significant difference was noted for the control group. CONCLUSIONS: Although limited by sample size, these pilot data suggest potential benefit of RY on emotional outcomes and fatigue in cancer patients. This study demonstrates that a RY intervention is feasible for women with breast cancer; implications for study design and implementation are noted with an emphasis on program adoption and participant adherence.

Peritoneal surface disease from colorectal cancer: comparison with the hepatic metastases surgical paradigm in optimally resected patients.

BACKGROUND: Surgical resection is the treatment of choice for colorectal hepatic metastases (HM). In contrast, metastatic disease to the peritoneum is treated with systemic therapy. We examined our experience with cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC) for peritoneal surface disease (PSD) compared with liver resection for HM. METHODS: A review of prospective databases of colorectal cancer patients undergoing surgery for metastatic disease to the peritoneum or liver (1992-2005) was carried out. RESULTS: One hundred and twenty-one patients underwent CS + IPHC and 101 patients underwent hepatic resection with median follow-up of 86 and 56 months, respectively. Fifty-five (45%) patients in the IPHC group had complete resection of all gross tumor. Ninety-five (94%) of the HM patients had negative surgical margins. Comparison of the R0/R1 PSD and margin-negative HM group demonstrated significant differences in age, performance status, and preoperative chemotherapy. The 1-, 3-, and 5-year overall survival for the R0/R1 PSD patients was 91, 48, and 26%; while it was 87, 59, and 34% for the HM patients (P = 0.32). Perioperative morbidity was 42% versus 34% (P = 0.38) and mortality was 5.5% versus 4.2% (P = 0.71) between the PSD and HM patients, respectively. CONCLUSION: R0/R1 resection during CS + IPHC compared with margin-negative hepatic resection demonstrated no significant difference in overall survival and for select patients should be considered a viable treatment option. Further studies to improve the resectability of PSD patients and define the role of neoadjuvant and adjuvant drug strategies are needed.

Survival and health outcomes after cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for disseminated peritoneal cancer of appendiceal origin.

BACKGROUND: Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis of appendiceal origin can alleviate symptoms and prolong survival. This aggressive therapy may impair patient quality of life (QOL). The purpose of this study was to monitor health outcomes before and after treatment. METHODS: Patients underwent cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal cancer. Patients completed questionnaires consisting of demographic information and the Functional Assessment of Cancer Therapy, the SF-36 Medical Outcomes Study survey, the Center for Epidemiologic Studies-Depression Scale, and the ECOG Performance Status Rating before (T1) and after surgery at 3 (T2), 6 (T3), 12 (T4), and 24 (T5) months. Time trends were assessed with the mixed model (SAS PROC MIXED) to allow use of all the observed data as well as to account for missing data. RESULTS: Fifty-eight patients (50% female) with a mean age 52.4 years (SD 12.6; range, 28-80) were assessed before surgery. Overall survival at 1 year was 78.7%. Emotional well-being improved over the study period, while physical well-being and physical functioning declined at T2 and then improved to near baseline levels at T3 and T4. Percentage of patients with depressive symptoms was as follows: T1 = 24%, T2 = 30%, T3 = 24%, and T4 = 33%. QOL scores improved over time. CONCLUSIONS: Although complications can affect short-term recovery, survival in appendix cancer patients with peritoneal cancer is good and for some can be achieved without major decrements in QOL at 1 year. Depressive symptoms and some physical limitations remain in surviving patients.

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: experience with 501 procedures.

BACKGROUND: Peritoneal dissemination of abdominal malignancy (PSD) has a clinical course marked by bowel obstruction and death. We have been using aggressive cytoreductive surgery with intraperitoneal hyperthermic chemotherapy (IPHC) to treat PSD. The purpose of this article was to review our experience with IPHC. STUDY DESIGN: A prospective database of patients undergoing IPHC has been maintained since 1991. Patients were uniformly evaluated and treated. Demographics, performance status, resection status, primary site, and experience quartile were compared with outcomes. Univariate and multivariate analyses were performed. RESULTS: A total of 460 patients underwent 501 IPHC procedures. Average age was 53.0 years, and 50.4% were women. The 30-day mortality rate was 4.8%, the complication rate was 43%, and median hospital stay was 9 days. Median followup was 55.4 months, median survival was 22.2 months, and 5-year survival rate was 27.8%. Factors correlating with improved survival were performance status (p=0.0001), primary tumor (p=0.0001), resection status (p=0.0001), complications (p=0.002), previous IPHC (p=0.006), and experience quartile (p=0.031). On multivariate analysis, primary tumor site, performance status, resection status, and development of complications (p < 0.001) predicted outcomes. CONCLUSIONS: Our experience demonstrated that preoperative criteria for better outcomes include primary tumor site and performance status. Completeness of resection and development of postoperative complications are also crucial, and outcomes have improved over time. Cytoreductive surgery and IPHC represent substantial improvements in outcomes compared with historic series and best-available systemic therapy. Longterm survival is possible for selected patients who undergo the procedure.

Monitoring health outcomes following cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for peritoneal carcinomitosis (PC) is an aggressive treatment designed to alleviate symptoms and prolong life. It is associated with physical and psychological morbidity. The purpose of this study was to monitor health outcomes related to treatment. METHODS: Patients completed a questionnaire before and after surgery at 3, 6 and 12 months. The questionnaire consisted of basic demographic items as well as the Functional Assessment of Cancer Therapy-Colon Scale (FACT-C), SF-36 Medical Outcomes Study Health Survey, Center for Epidemiologic Studies-Depression Scale (CES-D), Brief Pain Inventory-Short Form, and ECOG Performance Status Rating. Time trends were assessed with mixed models (SAS PROC MIXED) so as to use all data and to account for missing data. RESULTS: Ninety-six patients (49% females, 9% African Americans) of an average age of 52.9 (SD = 12.5) years were assessed before surgery. PC originated in primary lesions of the appendix (n = 36); colon/rectum (n = 24); mesothelium (n = 9); ovary (n = 5); stomach (n = 4); and miscellaneous (n = 18). Quality of life (QOL) and pain scores improved from baseline to 12 months. Physical functioning changed over the 12-month study period with improvement recorded at 6 months. The percentage of patients reporting significant depressive symptom at each time point was; baseline = 32%; 3 months = 19%; 6 & 12 months = 24%. CONCLUSIONS: Acceptable QOL, return of functional status, and reduced pain can be attained between 3 and 6 months following treatment although some deficits in general health remain. Depressive symptoms are common and should be monitored.

Appendiceal neoplasms with peritoneal dissemination: outcomes after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy.

BACKGROUND: Appendiceal neoplasms frequently present with peritoneal dissemination (PD) and have a clinical course marked by bowel obstruction and subsequent death. Few data have correlated outcome with appendiceal histology after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC). We have reviewed our experience with cytoreductive surgery and IPHC for PD from the appendix. METHODS: A total of 110 cases of PD from proven appendiceal neoplasms treated with IPHC were identified from a prospectively managed database. Tumor samples were classified on pathologic review as disseminated peritoneal adenomucinosis (n = 55), peritoneal mucinous carcinomatosis (PMCA) with intermediate features (n = 18), PMCA (n = 29), or high-grade nonmucinous lesions (n = 8). A retrospective review was performed with long-term survival as the primary outcome measure. RESULTS: A total of 116 IPHCs were performed on 110 patients for appendiceal PD between 1993 and 2004. The 1-, 3-, and 5-year survival rates for all cases were 79.9% +/- 4.1%, 59.0% +/- 5.7%, and 53.4% +/- 6.5%, respectively. When stratified by histology, disseminated peritoneal adenomucinosis and intermediate tumors had better 3-year survival rates (77% +/- 7% and 81% +/- 10%) than PMCA and high-grade nonmucinous lesions (35% +/- 10% and 15% +/- 14%; P = .0032 for test of differences between groups). Age at presentation (P = .0134), performance status (P < .0001), time between diagnosis and IPHC (P = .0011), resection status (P = .0044), and length of hyperthermic chemoperfusion (P = .0193) were independently associated with survival. CONCLUSIONS: The data show that long-term survival is anticipated in most patients who are treated with cytoreduction and IPHC for appendiceal PD. The findings presented herein underscore the important prognostic characteristics that predict outcome after IPHC in patients with PD. In all, this work establishes a framework for the consideration of IPHC in future trials for appendiceal PD.

Long-term survivorship and quality of life after cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy with mitomycin C for peritoneal carcinomatosis is used as a palliative treatment for a variety of malignancies. The purpose of this study was to measure the quality of life (QOL) of survivors (>3 years) after treatment. METHODS: Patients were interviewed by telephone with the following tools: (1) the Functional Assessment of Cancer Therapy-Colon (FACT-C), (2) the Short Form of the Medical Outcomes Study Questionnaire, (3) the Center for Epidemiologic Studies-Depression scale, (4) the Life Appreciation scale, (5) the Psychosocial Concerns Questionnaire, and (6) performance status rating. RESULTS: Seventeen (10 appendix, 5 large intestine, 1 ovarian, and 1 peritoneum) of 109 patients were interviewed from 3.1 to 8.0 years after treatment. Ten patients (62.5%) described their health as excellent or very good. No limitations on moderate activity were reported in 94% of cases. Paired t-tests were used to compare 10 patients who had baseline QOL data. FACT mean difference scores and P values (positive difference scores indicate improved QOL) were functional well-being: 4.9, P =.01; physical well-being: 3.3, P =.05; and FACT total: 14.3, P =.02. CONCLUSIONS: Long-term survival with good QOL is possible for selected patients with peritoneal carcinomatosis after cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy.