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Background: Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a multimodal therapeutic option for the management of peritoneal metastases (PM). Treatment outcomes for patients with colorectal cancer (CRC) PM undergoing CRS+HIPEC with microsatellite instability (MSI) remain unknown. We examined the patient characteristics and outcomes in patients with MSI CRC after CRS+HIPEC., Methods: This was a retrospective cohort study of a prospectively maintained database of all patients with CRC PM undergoing CRS+HIPEC (2010-2020). Categorical and continuous variables were analyzed using the chi-square test and independent samples t test, respectively. Survival was evaluated with the Kaplan-Meier analysis., Results: There were 324 patients diagnosed as having CRC PM undergoing CRS+HIPEC (MSI, n = 23; microsatellite stable [MSS], n = 301). There was no statistically significant difference in patient demographics, tumor characteristics, or perioperative factors between the 2 groups. There was a trend toward improved survival in the MSI group with a median overall survival (OS) of 96.7 month compared with patients with MSS disease (median OS, 51.4 months; P = .10). Patients with MSI demonstrated median progression-free survival (PFS) 8.5 months compared with 11.4 months in the MSS cohort (P = .28)., Conclusion: Patients with CRC PM, regardless of MSI or MSS status, demonstrate similar OS and PFS after CRS+HIPEC. MSI status should not change a patient's candidacy for CRS+HIPEC., (Copyright © 2024. Published by Elsevier Inc.)

Background: Appendiceal cancer with peritoneal metastases (ACPM) is a complex disease requiring multidisciplinary care. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS HIPEC) can significantly improve survival but requires evaluation by a surgical oncologist and significant treatment endurance. The impacts of socioeconomic status (SES) and other social determinants of health on rates of surgical evaluation and treatment have not been examined., Methods: We conducted a retrospective cohort study examining all patients with ACPM from 2010 to 2018 in a regional healthcare system. Patient characteristics, oncologic details, treatment strategies, and survival were examined. The primary outcomes of interest were referral to Surgical Oncology, receipt of CRS HIPEC, and survival., Results: Of 194 patients identified, 94% had synchronous ACPM. The majority of patients (95%) were referred to surgical oncology. Advanced age was the only predictor of nonreferral (p < 0.001). A total of 147 patients (76%) ultimately underwent CRS HIPEC. After adjusting for medical and tumor characteristics, CRS HIPEC was less likely for patients who were unmarried [odds ratio (OR) 0.253, p = 0.004] or of low SES (OR 0.372, p = 0.03). On subanalysis of patients undergoing CRS HIPEC, median overall survival was worse for patients of low SES [51 months versus not reached (NR), p = 0.05], and this disparity persisted on multivariate analysis [hazard ratio (HR) = 2.278, p = 0.001]., Conclusions: This analysis is the first to evaluate barriers to CRS HIPEC for ACPM. While most patients were evaluated by a multidisciplinary team, nonmedical factors may play a role in the treatment received and ultimate outcomes. Addressing these disparities is crucial for ensuring equitable outcomes and improving patient care., (© 2022. Society of Surgical Oncology.)

Aims: Peritoneal spread is the most common route of metastasis in appendiceal goblet cell adenocarcinoma. The aim of this study was to assess the prognostic significance of the World Health Organization (WHO) 5th edition grading criteria in peritoneal metastases of goblet cell adenocarcinoma., Methods and Results: We evaluated the clinicopathological features and survival of 63 patients with peritoneal metastasis of goblet cell adenocarcinoma who underwent cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC), stratified according to the WHO 5th edition and the Tang et al. grading schemes. The patients were also compared with 120 patients with peritoneal metastasis of appendiceal mucinous neoplasia. Most (73%) peritoneal metastases of goblet cell adenocarcinoma were WHO Grade 3 (G3), there being fewer cases of Grade 2 (G2) (16%) and Grade 1 (G1) (11%) disease. No significant differences in overall survival were observed between WHO G1 and G2 tumours or between the three Tang grades. In the multivariable model of survival, WHO G3 [hazard ratio (HR) 2.81, 95% confidence interval (CI) 1.02-7.70] and the presence of >50% extracellular mucin (HR 2.30, 95% CI 1.09-4.88) were associated with reduced overall survival for patients with goblet cell adenocarcinoma. As compared with patients with peritoneal metastasis of mucinous neoplasia, patients with goblet cell adenocarcinoma had significantly reduced survival (median overall survival of 37 months versus 102 months, P < 0.001), which was attributed to the reduced survival of patients with G1/G2 goblet cell adenocarcinoma as compared with patients with G1 mucinous neoplasia (median survival of 98 months versus 204 months, P < 0.001)., Conclusions: Grade of peritoneal goblet cell adenocarcinoma determined according to the WHO 5th edition criteria is a clinically relevant measure that independently predicts survival in patients treated with CRS-HIPEC., (© 2020 John Wiley & Sons Ltd.)

Despite their association with DNA mismatch repair (MMR) protein deficiency, colonic adenocarcinomas with mucinous, signet ring cell, or medullary differentiation have not been associated with improved survival compared with conventional adenocarcinomas in most studies. Recent studies indicate that increased T-cell infiltration in the tumor microenvironment has a favorable prognostic effect in colonic adenocarcinoma. However, the prognostic effect of tumor-associated T cells has not been evaluated in histologic subtypes of colonic adenocarcinoma. We evaluated CD8-positive T-cell density in 259 patients with colonic adenocarcinoma, including 113 patients with tumors demonstrating mucinous, signet ring cell, or medullary differentiation, using a validated automated quantitative digital image analysis platform and correlated CD8-positive T-cell density with histopathologic variables, MMR status, molecular alterations, and survival. CD8-positive T-cell densities were significantly higher for MMR protein-deficient tumors (P<0.001), BRAF V600E mutant tumors (P=0.004), and tumors with medullary differentiation (P<0.001) but did not correlate with mucinous or signet ring cell histology (P>0.05 for both). In the multivariable model of factors predicting disease-free survival, increased CD8-positive T-cell density was associated with improved survival both in the entire cohort (hazard ratio=0.34, 95% confidence interval, 0.15-0.75, P=0.008) and in an analysis of patients with tumors with mucinous, signet ring cell, or medullary differentiation (hazard ratio=0.06, 95% confidence interval, 0.01-0.54, P=0.01). The prognostic effect of CD8-positive T-cell density was independent of tumor stage, MMR status, KRAS mutation, and BRAF mutation. Venous invasion was the only other variable independently associated with survival in both the entire cohort and in patients with tumors with mucinous, signet ring cell, or medullary differentiation. In summary, our results indicate that the prognostic value of MMR protein deficiency is most likely attributed to increased tumor-associated CD8-positive T cells and that automated quantitative CD8 T-cell analysis is a better biomarker of patient survival, particularly in patients with tumors demonstrating mucinous, signet ring cell, or medullary differentiation.

Peritoneal metastasis in colorectal carcinoma is associated with a dismal prognosis; however, features that correlate with patterns of metastatic spread are not well characterized. We analyzed the clinicopathologic and molecular features of 166 patients with colorectal carcinomas stratified by metastases to the peritoneum or liver. Mucinous and signet ring cell differentiation were more frequently observed in colorectal carcinoma with peritoneal dissemination compared to colorectal carcinoma with liver metastasis (mucinous differentiation: 62% vs 23%, P < .001; signet ring cell differentiation: 21% vs 0%, P < .0001). The significant association of mucinous differentiation with peritoneal dissemination compared with liver metastasis was identified in patients with both synchronous and metachronous development of metastasis ( P < .01). In contrast, colorectal carcinomas with liver metastasis were more frequently low-grade (90% vs 72%, P = .005) and associated with dirty necrosis (81% vs 56%, P = .001) compared with colorectal carcinomas with peritoneal dissemination. No significant differences were identified between colorectal carcinoma with peritoneal metastasis versus liver metastasis with respect to KRAS mutations, BRAF mutation, or high levels of microsatellite instability. Patients with tumors involving the peritoneum had a significantly worse overall survival in comparison to patients with liver metastasis lacking peritoneal involvement ( P = .02). When including only those patients with peritoneal metastasis, the presence of any mucinous or signet ring cell differentiation was associated with a significantly worse overall survival ( P = .006). Our findings indicate that mucinous and signet ring cell differentiation may be histologic features that are associated with an increased risk of peritoneal dissemination and poor overall survival in patients with peritoneal metastasis.

Aims: The prognostic significance of histological subtyping of epithelioid pleural mesotheliomas has been recently reported, but similar data are lacking for peritoneal mesotheliomas. The aim of this study was to investigate possible relationships between histological growth patterns of epithelioid peritoneal mesotheliomas, clinicopathological features, and patient outcome., Methods and Results: Eighty-four cases of chemotherapy-naive epithelioid peritoneal mesothelioma were classified into tubulopapillary, micropapillary, papillary, tubular, solid and trabecular growth patterns. Pathological features such as depth of invasion, lymphocytic host response, mitotic count, nuclear grade, lymphovascular invasion, lymph node metastasis and stromal desmoplasia were analysed. The most common histological patterns were solid (n = 37, 44%), tubulopapillary (n = 24, 29%), and micropapillary (n = 11, 13%). The overall median survival was 36 months. Patients with solid mesothelioma had shorter overall survival (median, 29 months) than patients with tubulopapillary and micropapillary growth patterns (median, 51 and 53 months, respectively; P = 0.053). A high mitotic index (>5 in 50 high-power fields) was found to be associated with poor survival (P < 0.03). A moderate to severe lymphocytic host response was associated with longer median survival (P = 0.13)., Conclusions: Our study highlights the prognostic importance of the solid growth pattern among diffuse epithelioid peritoneal mesotheliomas, and reaffirms mitotic index as a predictor of overall survival., (© 2015 John Wiley & Sons Ltd.)

Background: High-grade (HG) mucinous appendiceal neoplasms (MAN) have a worse prognosis than low-grade histology. Our objective was to assess the safety and efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) in patients with high-grade, high-volume (HG-HV) peritoneal metastases in whom the utility of this aggressive approach is controversial., Methods: Prospectively collected perioperative data were compared between patients with peritoneal metastases from HG-HV MAN, defined as simplified peritoneal cancer index (SPCI) ≥12, and those with high-grade, low-volume (HG-LV; SPCI <12) disease. Kaplan-Meier curves and multivariate Cox regression models identified prognostic factors affecting oncologic outcomes., Results: Overall, 54 patients with HG-HV and 43 with HG-LV peritoneal metastases underwent CRS/HIPEC. The HG-HV group had longer operative time, increased blood loss/transfusion, and increased intensive care unit length of stay (p < 0.05). Incomplete macroscopic cytoreduction (CC-1/2/3) was higher in the HG-HV group compared with the HG-LV group (68.5 vs. 32.6 %; p = 0.005). Patients with HG-HV disease demonstrated worse survival than those with HG-LV disease (overall survival [OS] 17 vs. 42 m, p = 0.009; time to progression (TTP) 10 vs. 14 m, p = 0.024). However, when complete macroscopic resection (CC-0) was achieved, the OS and progression-free survival of patients with HG-HV disease were comparable with HG-LV disease (OS 56 vs. 52 m, p = 0.728; TTP 20 vs. 19 m, p = 0.393). In a multivariate Cox proportional hazard regression model, CC-0 resection was the only significant predictor of improved survival for patients with HG-HV disease., Conclusions: Although patients with HG-HV peritoneal metastases from MAN have worse prognosis compared with patients with HG-LV disease, their survival is comparable when complete macroscopic cytoreduction is achieved.

Background: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) are used to treat peritoneal carcinomatosis from a variety of primary tumor sites. Little is known about the in vivo effects of CRS and HIPEC., Methods: We examined tumor and non-neoplastic peritoneal tissue samples from 38 patients undergoing CRS and HIPEC for appendiceal or colorectal carcinomatosis, using conventional histologic analysis and immunohistochemical analysis for markers of early DNA damage (phosphorylated H2AX, γH2AX) and early necrosis (extracellular HMGB1). Findings were correlated with clinicopathologic features and oncologic outcome., Results: Histologic findings corresponding with CRS and HIPEC included extensive submesothelial inflammatory infiltrate, endothelial activation, mesothelial karyolysis and surface fibrin deposition. Endothelial activation in submesothelial vessels exhibited high specificity for samples obtained following HIPEC relative to samples obtained following CRS but prior to HIPEC. Mesothelial nuclear γH2AX staining and submesothelial extracellular HMGB1 staining increased progressively following CRS and HIPEC, consistent with DNA damage and necrosis. No significant increase in tumor staining for markers was seen with CRS or HIPEC. Submesothelial HMGB1 staining was associated with increased progression-free survival on univariate analysis., Conclusions: The immediate histologic effects of CRS and HIPEC are defined and provide evidence that DNA damage and early steps of necrosis are underway in mesothelial tissues at the conclusion of the procedure. Further research will be necessary to investigate the impact of these findings on long-term oncologic outcome, and may provide insight into the downstream effects of CRS and HIPEC that could facilitate refinement of regional therapeutic regimens for carcinomatosis.

Background: Postoperative pancreatic fistulas (POPFs) are potentially morbid complications that often require therapeutic interventions. Distal pancreatectomy performed during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) puts patients at risk for POPF. The authors hypothesized that POPFs are more severe after CRS/HIPEC than after pancreatectomy alone., Methods: Clinicopathologic and perioperative details, including POPF by International Study Group of Pancreatic Fistula criteria (ISGPF), and oncologic outcomes for patients undergoing distal pancreatectomy during CRS/HIPEC for peritoneal carcinomatosis of appendiceal (n = 31) or colorectal (n = 23) origin (HIPEC group) were compared with those for patients undergoing minimally invasive or open distal pancreatectomy without HIPEC (n = 66) for locally resectable pancreatic adenocarcinoma (non-HIPEC group)., Results: The incidence of POPF was similar between the HIPEC and non-HIPEC groups (26 %). The severity of POPF according to the ISGPF criteria was significantly worse in the HIPEC group. The HIPEC patients had 13 grade B fistulas and 1 grade C fistula compared with 12 grade A fistulas and 4 grade B fistulas in the non-HIPEC group. The HIPEC patients with POPF did not differ in the extent of their CRS, peritoneal cancer index, length of hospital stay, or other postoperative complications from the the HIPEC patients without POPF. The HIPEC patients with colorectal carcinomatosis who experienced POPF had higher disease recurrence in the first year after CRS/HIPEC than those without POPF., Conclusion: The findings showed that POPFs are more severe when distal pancreatectomy is combined with CRS/HIPEC. Moreover, selective use of distal pancreatectomy is important during CRS/HIPEC because POPFs may increase early disease recurrence for patients with colorectal carcinomatosis.

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemoperfusion (HIPEC) is routinely used to treat certain peritoneal carcinomatoses (PC), but it can be associated with relatively high complication rates, prolonged hospital length of stay, and potential mortality. Our objective was to determine the learning curve (LC) of CRS/HIPEC in our high-volume institution., Methods: A total of 370 patients with PC from mucinous appendiceal neoplasms (MAN = 282), malignant peritoneal mesothelioma (MPM = 60), and gastric cancer (GC = 24) were studied. Outcomes analyzed included incomplete cytoreduction (IC), severe morbidity (SM), 60-day mortality, progression-free survival (PFS), and overall survival (OS). Risk-adjusted sequential probability ratio test (RA-SPRT) was employed to assess the LC of CRS/HIPEC for IC and SM using prespecified odds ratio (OR) boundaries derived from previously published data. Risk adjusted-cumulative average probability (RA-CAP) was used to analyze 1-year PFS and 2-year OS., Results: Complete cytoreduction, severe morbidity, and 60-day mortality were 84.2, 30, and 1.9 % respectively. Higher simplified peritoneal cancer index was the major independent risk factor for IC, whereas high-grade histology, IC, and diagnosis of MPM and GC (compared with MAN) were predictors of SM after CRS/HIPEC (p < 0.05). RA-SPRT showed that approximately 180 cases are needed to achieve the lowest risk of IC and SM. Ninety cases were needed to achieve a steady 1-year PFS and 2-year OS in RA-CAP plots., Conclusions: The completeness of cytoreduction, morbidity, and mortality rates for CRS/HIPEC at our institution are comparable to previously reported data. Approximately 180 and 90 procedures are required to improve operative and oncologic outcomes respectively.

Background: Obesity has been described as a risk factor for surgical complications and may play a prominent role in the progression, recurrence, and survival rates of various cancers. Our objective was to investigate the impact of being overweight or obese on perioperative and oncologic outcomes after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) for peritoneal carcinomatosis (PC) from mucinous appendiceal neoplasms (MAN)., Methods: From a prospectively maintained database (2001-2010) of CRS/HIPEC for PC from MAN, we evaluated the body mass index (BMI) of patients, categorizing them into normal weight (NW < 25 kg/m(2)), overweight (OW = 25 to 29.9 kg/m(2)), and obese (OB ≥ 30 kg/m(2)). We compared the perioperative and oncologic outcomes among groups., Results: Of the 282 patients in the database, 234 had BMI data available, and 81, 79, and 74 patients were categorized as NW, OW, and OB, respectively. Although there was a trend toward increased risk of overall complications, wound infections, deep vein thrombosis, respiratory and renal complications, and anastomotic leaks in the OW and OB groups, these differences only achieved statistical significance for renal (p = 0.03) and pulmonary (p = 0.02) complications in the OW and OB groups, respectively. The 5-year survival rate for NW, OW, and OB patients was 63.9, 48, and 54.4 %, respectively (p = 0.63). The median time to progression was 21.1 (NW), 21.7 (OW), and 23.9 (OB) months (p = 0.83)., Conclusions: OW and OB patients may have an increased risk of renal and pulmonary complications, respectively. Obesity has no major impact on perioperative mortality and long-term oncologic outcomes in patients undergoing CRS/HIPEC for MAN.

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) for peritoneal carcinomatosis (PC) of colorectal origin increases survival (OS) compared to systemic chemotherapy alone. Signet ring histology demonstrates aggressive behavior with poor survival. We sought to determine whether CRS/HIPEC increases survival in this subset of patients., Methods: We reviewed 67 patients with PC of appendiceal (AP, n = 37) or colorectal origin (CRC, n = 30) with signet cell histology from a prospective database between May 2001 and August 2011. Survival analysis and multivariate Cox regression were used to determine prognostic factors for survival., Results: Complete CRS (CC-0/1) was achieved in 77 % (CRC) and 73 % (AP) of patients. Progression-free survival (PFS) and OS were 9 and 12 months in CRC and 12 and 21 months in AP patients. In the CRC group, univariate predictors of poor survival included female gender, age, American Society of Anesthesiologists score, preoperative albumin, completeness of cytoreduction, and morbidity. In a multivariate Cox regression model, incomplete cytoreduction (CC-2/3) and female gender were joint significant predictors of poor survival. In the AP group, significant univariate predictors of poor survival included higher EBL and PCI score. In a multivariate Cox regression model, blood loss of >500 ml and a body mass index of <25 kg/m(2) were joint significant predictors of poor survival., Conclusions: AP signet cell tumors demonstrate a more favorable outcome than CRC signet cell tumors after CRC/HIPEC for carcinomatosis, suggesting an underlying difference in biology. CRS/HIPEC does not confer survival benefit in colorectal signet ring carcinomatosis unless complete cytoreduction can be achieved, whereas appendiceal signet ring carcinomatosis may benefit, regardless of resectability.

Background: Peritoneal carcinomatosis from gastric cancer (GPC) responds poorly to systemic chemotherapy. Limited published data demonstrate improved outcomes after aggressive locoregional therapies. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in GPC., Methods: We prospectively analyzed 23 patients with GPC undergoing CRS/HIPEC between 2001 and 2010. Kaplan-Meier survival curves and multivariate Cox regression models identified prognostic factors affecting oncologic outcomes., Results: CRS/HIPEC was performed for synchronous GPC in 20 patients and metachronous GPC in 3 patients. Adequate CRS was achieved in 22 patients (CC-0 = 17; CC-1 = 5) and median peritoneal cancer index was 10.5. Most patients received preoperative chemotherapy (83 %) and total gastrectomy (78 %). Pathology revealed diffuse histology (65 %), signet cells (65 %) and LN involvement (64 %). Major postoperative morbidity occurred in 12 patients, with 1 in-hospital mortality at postoperative day 66. With median follow-up of 52 months, median overall survival (OS) was 9.5 months (95 % confidence interval 4.7-17.3), with 1- and 3- year OS rates of 50 and 18 %. Median progression-free survival (PFS) was 6.8 months (95 % confidence interval 3.9-14.6). In a multivariate Cox regression model, male gender [hazard ratio (HR) 6.3], LN involvement (HR 1.2), residual tumor nodules (HR 2.4), and >2 anastomoses (HR 2.8) were joint significant predictors of poor OS (χ (2) = 18.2, p = 0.001), while signet cells (HR 8.9), anastomoses >2 (HR 5.5), and male gender (HR 2.4) were joint significant predictors of poor progression (χ (2) = 16.3, p = 0.001)., Conclusions: Aggressive CRS/HIPEC for GPC may confer a survival benefit in select patients with limited lymph node involvement and completely resectable disease requiring less extensive visceral resections.

Background: Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM., Methods: We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes., Results: Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001)., Conclusions: Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC.

Despite significant improvements in systemic therapy for patients with colorectal liver metastases (crlms), response rates in the first-line setting are not optimal, and response rates in the second-line setting remain disappointing. Hepatic arterial infusion pump (haip) chemotherapy has been extensively studied in patients with crlms, but it remains infrequently used. We convened an expert panel to discuss the role of haip in the contemporary management of patients with crlm. Using a consensus process, we developed these statements: haip chemotherapy should be given in combination with systemic chemotherapy.haip chemotherapy should be offered in the context of a multidisciplinary program that includes expertise in hepatobiliary surgery, medical oncology, interventional radiology, nursing, and nuclear medicine.haip chemotherapy in combination with systemic therapy should be considered in patients with unresectable crlms who have progressed on first-line systemic treatment. In addition, haip chemotherapy is acceptable as first-line treatment in patients with unresectable colorectal liver metastases.haip chemotherapy is not recommended in the setting of extrahepatic disease outside the context of a clinical trial.haip chemotherapy in combination with systemic therapy is an option for select patients with resected colorectal liver metastases. These consensus statements provide a framework that clinicians who treat patients with crlm can use when considering treatment with haip.

Background: Peritoneal carcinomatosis (PC) in the setting of mucinous appendiceal neoplasms is characterized by the intraperitoneal accumulation of mucinous ascites and mucin-secreting epithelial cells that leads to progressive compression of intra-abdominal organs, morbidity, and eventual death. We assessed postoperative and oncologic outcomes after aggressive surgical management by experienced surgeons., Methods: We analyzed clinicopathologic, perioperative, and oncologic outcome data in 282 patients with PC from appendiceal adenocarcinomas between 2001 and 2010 from a prospective database. Kaplan–Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting oncologic outcomes., Results: Adequate cytoreduction was achieved in 82% of patients (completeness of cytoreduction score (CC)-0: 49%; CC-1: 33%). Median simplified peritoneal cancer index (SPCI), operative time, and estimated blood loss were 14 (range, 0–21), 483.5 min (range, 46–1,402), and 800 ml (range, 0–14,000), respectively. Pathology assessment demonstrated high-grade tumors in 36% of patients and lymph node involvement in 23% of patients. Major postoperative morbidity occurred in 70 (25%) patients. Median overall survival was 6.72 years (95% confidence interval (CI), 4.17 years not reached), with 5 year overall survival probability of 52.7% (95% CI, 42.4, 62%). In a multivariate Cox-regression model, tumor grade, age, preoperative SPCI and chemo-naïve status at surgery were joint significant predictors of overall survival. Tumor grade, postoperative CC-score, prior chemotherapy, and preoperative SPCI were joint significant predictors of time to progression., Conclusions: Aggressive management of PC from mucinous appendiceal neoplasms, by experienced surgeons, to achieve complete cytoreduction provides long-term survival with low major morbidity.

Background: Generally, colorectal and high-grade appendiceal cancers are treated similarly; treatment approach is primarily based on tumor histology and stage of disease. Patients with adenocarcinoma of the lower gastrointestinal tract frequently experience diffuse metastases isolated to liver or peritoneum and have a poor survival. Identification of novel molecular pathways in metastases from these patients may identify novel targets and prognostic factors., Methods: Microarray analyses of 20 metastatic tumors from patients with colorectal adenocarcinoma isolated to liver or peritoneum and eight high-grade appendiceal adenocarcinoma metastatic to peritoneum were performed using oligonucleotide microarray., Results: In an unsupervised hierarchical cluster analysis of 2-fold upregulated or downregulated genes, there was a clear site-specific segregation of liver versus peritoneal metastases. Genes primarily involved in metastasis, angiogenesis, cell cycle regulation, cell proliferation, and cell adhesion were distinctly altered between these two metastatic sites. Among the metastasis genes, the average expression levels of LI-cadherin, ALCAM, CD2, and CD14 were significantly higher in both metastatic sites. TIMP1 was overexpressed in both sites where as TIMP-2, IGF-1, and HIF-1alpha were upregulated only in peritoneal metastases demonstrating the potential benefit of metastasis site-specific treatments. Subsets of genes significantly associated with poor survival were defined, a RET proto-oncogene interacting gene, GOLGA5, was highly predictive for survival in patients with colorectal adenocarcinoma., Conclusions: These results demonstrate that liver and peritoneal metastases of lower GI adenocarcinoma have distinct gene expression patterns; these distinctions may help in the development of therapies based on site of metastases.

Taken together, these reports provide very provocative and encouraging data that have prompted some to conclude that cytoreduction and HIPEC represents a "new standard of care" for patients with MPM [26]. Certainly, for selected patients who have good performance status (low operative risk) and in whom complete or near complete cytoreduction can be achieved, this form of therapy is associated with a very notable overall survival ranging from 67 to 92 months in 2 larger series. Patient selection remains the central criteria for successful outcome. Patients should be carefully evaluated for co-morbid illnesses that would make them an unacceptable operative risk. Subsequently, CT scan and possibly laparoscopy should be performed to assess resectability with the appreciation that patients with suboptimal resection do very poorly. Pre-operative assessment of disease resectability is difficult to ascertain but some useful information can be obtained from a careful review of the CT scan; some investigators have advocated routine laparoscopy. Technically, details of HIPEC vary from center to center to some degree with respect to type of chemotherapy, dose of chemotherapy, duration of HIPEC, degree of hyperthermia, and method of recirculating the chemotherapy using either the open or closed technique. The use of the HIPEC technique, however, is considered the optimal method of ensuring complete distribution of therapeutic agents to the peritoneal cavity. Hyperthermia is routinely used for its synergistic actions with chemotherapy and its direct tumoricidal activity in experimental models. However, the therapeutic contribution of HIPEC above the effects of successful cytoreduction cannot be determined with available data although palliation of ascites is observed with HIPEC even without cytoreduction. There are no data indicating that one intra-operative chemotherapy regimen is superior to any other. The centers that report use of prolonged induction or post-operative intraperitoneal chemotherapy do not appear to have superior outcomes to those centers that use a more simple treatment regimen. Finally, although the intensity of therapy is considerable, once recovered, the patients appear to enjoy a good HRQOL. Although not specific for patients with MPM, 2 reports have convincingly demonstrated that HRQOL is significantly improved after HIPEC.

Purpose: To determine whether mesothelin, a cell surface protein highly expressed in mesothelioma and ovarian cancer, is shed into serum and if so to accurately measure it., Experimental Design: We developed a sandwich ELISA using antibodies reacting with two different epitopes on human mesothelin. To quantitate serum mesothelin levels, a standard curve was generated using a mesothelin-Fc fusion protein. Sera from 24 healthy volunteers, 95 random hospital patients, 56 patients with mesothelioma, and 21 patients with ovarian cancer were analyzed. Serum mesothelin levels were also measured before and after surgical cytoreduction in six patients with peritoneal mesothelioma., Results: Elevated serum mesothelin levels were noted in 40 of 56 (71%) patients with mesothelioma and in 14 of 21 (67%) patients with ovarian cancer. Serum mesothelin levels were increased in 80% and 75% of the cases of mesothelioma and ovarian cancer, respectively, in which the tumors expressed mesothelin by immunohistochemistry. Out of the six patients with peritoneal mesothelioma who underwent surgery, four had elevated serum mesothelin levels before surgery. Out of these four patients, three had cytoreductive surgery and the serum mesothelin level decreased by 71% on postoperative day 1 and was undetectable by postoperative day 7., Conclusions: We developed a serum mesothelin assay that shows that mesothelin is elevated in patients with mesothelioma and ovarian cancer. The rapid decrease in mesothelin levels after surgery in patients with peritoneal mesothelioma suggests that serum mesothelin may be a useful test to monitor treatment response in mesothelin-expressing cancers.

We conducted a retrospective review of all patients who underwent surgical extirpation for stage III, stage IV, or recurrent carcinoma of the gallbladder. Between 1991 and 1999 ten patients underwent surgical resection for advanced gallbladder cancer. All patients received adjuvant therapy either pre- or postoperatively. Radiotherapy was used in all patients and chemotherapy in 90 per cent of patients. Two patients subsequently underwent resection for locally recurrent disease. An additional patient with stage II disease initially was also treated surgically for a local recurrence. Surgical management involved cholecystectomy and resection of various amounts of liver surrounding the gallbladder bed and regional lymphadenectomy. Contiguously involved structures were resected en bloc. Resection of recurrent disease included excision of all gross tumor. The median overall survival excluding the one 30-day mortality was 53.6 months (range 8-73 months). Four patients have survived 4 or more years, and currently four patients are alive and disease free at 73, 49, 33, and 8 months. Median disease-free interval after each resection of recurrent disease was 13.8 months (range 4-28 months). We conclude that trimodality therapy in selected patients with stage III, IV, or recurrent carcinoma of the gallbladder is possible and may result in prolonged survival.

Objectives: To identify any risk factors for incidental parathyroidectomy and to define its association with symptomatic postoperative hypocalcemia., Design: Retrospective study., Setting: Tertiary referral cancer center., Patients: Consecutive patients who underwent thyroid surgery between 1991 and 1999. Patients who underwent procedures for locally advanced thyroid cancer requiring laryngectomy, tracheal resection, or esophagectomy were excluded., Interventions: All pathology reports were reviewed for the presence of any parathyroid tissue in the resected specimen. Slides were reviewed, and information regarding patient demographics, diagnosis, operative details, and postoperative complications was collected., Main Outcome Measure: Identification of parathyroid tissue in resected specimens and postoperative symptomatic hypocalcemia., Results: A total of 141 thyroid procedures were performed: 69 total thyroidectomies (49%) and 72 total thyroid lobectomies (51%). The findings were benign in 68 cases (48%) and malignant in 73 cases (52%). In the entire series, incidental parathyroidectomy was found in 21 cases (15%). Parathyroid tissue was found in intrathyroidal (50%), extracapsular (31%), and central node compartment (19%) sites. The performance of a concomitant modified radical neck dissection was associated with an increased risk of unplanned parathyroidectomy (P =.05). There was no association of incidental parathyroidectomy with postoperative hypocalcemia (P =.99). Multivariate analysis identified total thyroidectomy as a risk factor for postoperative hypocalcemia (P =.008). In the entire study group, transient symptomatic hypocalcemia occurred in 9 patients (6%), and permanent hypocalcemia occurred in 1 patient who underwent a total thyroidectomy and concomitant neck dissection., Conclusions: Unintended parathyroidectomy, although not uncommon, is not associated with symptomatic postoperative hypocalcemia. Modified radical neck dissection may increase the risk of incidental parathyroidectomy. Most of the glands removed were intrathyroidal, so changes in surgical technique are unlikely to markedly reduce this risk.