Introduction
Many patients with mucinous appendiceal adenocarcinoma experience peritoneal recurrence despite complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy ...(HIPEC). Prior work has demonstrated that repeat CRS/HIPEC can prolong survival in select patients. We sought to validate these findings using outcomes from a high-volume center.
Patients and Methods
Patients with mucinous appendiceal adenocarcinoma who underwent CRS/HIPEC at MD Anderson Cancer Center between 2004 and 2021 were stratified by whether they underwent CRS/HIPEC for recurrent disease or as part of initial treatment. Only patients who underwent complete CRS/HIPEC were included. Initial and recurrent groups were compared.
Results
Of 437 CRS/HIPECs performed for mucinous appendiceal adenocarcinoma, 50 (11.4%) were for recurrent disease. Patients who underwent CRS/HIPEC for recurrent disease were more often treated with an oxaliplatin or cisplatin perfusion (35%/44% recurrent vs. 4%/1% initial,
p
< 0.001), had a longer operative time (median 629 min recurrent vs. 511 min initial,
p
= 0.002), and had a lower median length of stay (10 days repeat vs. 13 days initial,
p
< 0.001). Thirty-day complication and 90-day mortality rates did not differ between groups. Both cohorts enjoyed comparable recurrence free survival (
p
= 0.82). Compared with patients with recurrence treated with systemic chemotherapy alone, this select cohort of patients undergoing repeat CRS/HIPEC enjoyed better overall survival (
p
< 0.001).
Conclusions
In appropriately selected patients with recurrent appendiceal mucinous adenocarcinoma, CRS/HIPEC can provide survival benefit equivalent to primary CRS/HIPEC and that may be superior to that conferred by systemic therapy alone in select patients. These patients should receive care at a high-volume center in the context of a multidisciplinary team.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Moderately and poorly differentiated adenocarcinoma of the appendix represents an aggressive histological variant with a high risk of recurrence and death.
Methods
Overall, 178 patients ...with moderately and poorly differentiated appendiceal adenocarcinoma were identified from a prospective database. Clinical, pathologic, and treatment factors were analyzed for outcomes.
Results
Diagnostic laparoscopy (DL) identified radiographic occult peritoneal metastasis in 25 (42%) patients. These patients had a significantly lower peritoneal carcinomatosis index (PCI) and improved overall survival (OS) compared with those with radiographic disease. Twenty-seven (41%) patients were excluded from cytoreductive surgery (CRS) because of findings on DL, while 116 (65%) patients underwent CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), with a median disease-free survival (DFS) of 23 months. Mucinous histology (hazard ratio HR 0.52,
p
= 0.04) and PCI (HR 1.054,
p
= 0.02) were independent predictors of DFS. The median OS following CRS and HIPEC was 48 months. Mucinous histology (HR 0.352,
p
= 0.018), signet ring cells (HR 3.34,
p
= 0.02), positive peritoneal cytology (HR 0.081,
p
= 0.04), and PCI (HR 1.076,
p
= 0.004) were independently associated with OS. Eight-five (73.3%) patients received neoadjuvant chemotherapy, and 40 (47.1%) patients achieved a radiographic response; 36 (42.3%) had stable disease, while 9 (10.6%) had progressive disease. Stable or responsive disease was associated with improved median OS of 44 months, compared with 21 months for those with progressive disease (
p
= 0.011).
Conclusions
In selected patients, long-term survival can be obtained. Mucinous histology, absence of signet ring cells, negative peritoneal cytology, PCI ≤ 20, and response/stable disease after neoadjuvant chemotherapy are important selection criteria for CRS and HIPEC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background Patients with colorectal cancer and peritoneal carcinomatosis (CRC/PC) may benefit from cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC). Nutritional ...support is frequently required for patients after CRS/HIPEC. It remains unclear if placement of feeding access is of benefit in regard to improving postoperative nutrition in this patient population. Materials and methods Patients with CRC/PC who underwent complete cytoreduction were evaluated. Preoperative and postoperative nutritional data and discharge outcomes were retrospectively recorded. The presence of a feeding tube and PCI scores were recorded by review of operative notes. Readmission rates were calculated for patients at 30 d and 60 d after discharge from hospital. Results Forty-one patients underwent CRS/HIPEC, 25 had feeding tube placement at the time of surgery. Weight loss was common after HIPEC as 38 of 41 patients demonstrated weight loss. The mean weight loss was 7.6%. total parenteral nutrition was required at discharge in four patients (7.9%); three of these patients had feeding access placed. There was no difference in the degree of weight loss between groups (7.1 ± 3.7% no tube versus 7.9 ± 5.8% patients with tube; P = 0.608). The mean decrease in albumin was 12.7% but was not significantly different in patients with feeding access and those without (10.0% versus 14.75%; P = 0.773). Sixty-day readmission rates were higher in patients with feeding tubes (36% compared with 0%, P < 0.01). Conclusions Significant nutritional loss is common after CRS/HIPEC for patients with CRC/PC. Feeding tube placement does not prevent this and appears to be related to higher readmission rates and longer length of stay.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Radiofrequency ablation (RFA) has become a common treatment of patients with unresectable primary and secondary hepatic malignancies. We performed this prospective analysis to determine early (within ...30 days) and late (more than 30 days after) complication rates associated with hepatic tumor RFA.
All patients treated between January 1, 1996 and June 30, 2002 with RFA for hepatic malignancies were entered into a prospective database. Patients were evaluated during RFA treatment, throughout the immediate post RFA course, and then every 3 months after RFA to assess for the development of treatment-related complications.
A total of 608 patients, 345 men (56.7%) and 263 women (43.3%), with a median age of 58 years (range 18-85 years) underwent RFA of 1225 malignant liver tumors. Open intraoperative RFA was performed in 382 patients (62.8%), while percutaneous RFA was performed in 226 (37.2%). The treatment-related mortality rate was 0.5%. Early complications developed in 43 patients (7.1%). Early complications were more likely to occur in patients treated with open RFA (33 8.6% of 382 patients) compared with percutaneous RFA (10 4.4% 226 patients, P < 0.01), and in patients with cirrhosis (25 12.9% complications in 194 patients) compared with noncirrhotic patients (31 7.5% complications in 414 patients, P < 0.05). Late complications arose in 15 patients (2.4%) with no difference in incidence between open and percutaneous RFA treatment. The combined overall early and late complication rate was 9.5%.
Hepatic tumor RFA can be performed with low mortality and morbidity rates. Though relatively rare, late complications can develop and physicians performing hepatic RFA must be cognizant of these delayed treatment-related problems.
The primary objective is to evaluate the safety and effectiveness of Stryker second generation Target
Nano Coils in the treatment of ruptured and unruptured small (<7 mm) intracranial aneurysms.
The ...TARGET Registry is a prospective, two-arm study with independent medical event monitoring and core-lab adjudication. This paper describes the second arm of the TARGET registry. Patients with
intracranial aneurysms were embolized with 2nd generation TARGET Nano coils in 12 US centers. The primary efficacy outcome was adequate aneurysm occlusion (RR occlusion grade I-II) on follow-up. Primary safety outcome was treatment-related morbidity and mortality. Secondary outcomes included aneurysm packing density immediately post-procedure, immediate adequate occlusion, aneurysm re-access rate, retreatment rate and clinical outcomes using modified ranking scale. A secondary analysis investigated the influence of using Nano-predominant coils (≥2/3 of total coil-length) vs. non-Nano-predominant coils (<2/3 of total length).
150 patients with 155 aneurysms met the inclusion and exclusion criteria. (31%) patients with ruptured and (69%) with unruptured aneurysms were treated using TARGET coils. Median age was 58.8 (SD 12.7), 74.7% were females, and 80% were Caucasians. Mean follow-up was 5.23 (SD 2.27) months. Peri-procedural mortality was seen in 2.0% of patients. Good outcome at discharge (mRS 0-2) was seen in 81.3% of the cohort. The median packing density (SD) was 29.4% (14.9). Mid-term complete/near complete occlusion rate was seen in 96% of aneurysms and complete obliteration was seen in 75.2% of aneurysms. Patients treated predominantly with Nano coils had higher PD (32.6% vs. 26.1%,
< 0.001). There was no significant difference in clinical and angiographic outcomes. The mid-term mRS0-2 was achieved in 106/109 (97.2%) patients. All-cause mortality was 5/115 (4.3%).
In the multicenter TARGET Registry, 75.8% of aneurysms achieved mid-term complete occlusion, and 96% achieved complete/near complete occlusion with excellent independent functional outcome.
Background
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is the preferred treatment for selected patients with mucinous appendiceal adenocarcinoma. Frequently, the ...hemidiaphragms are infiltrated with tumor, requiring partial diaphragm resection (DR) in order to obtain complete cytoreduction (CC-0). The clinical significance of diaphragmatic invasion and the optimum management to prevent transmission of disease from abdomen to chest is largely unknown.
Methods
This was a retrospective review of 78 patients with mucinous appendiceal adenocarcinoma undergoing cytoreduction and partial DR at a single institution between 2010 and 2014.
Results
Partial DR was necessary in 31 (39.7 %) patients in order to obtain CC-0. DR was not associated with increased morbidity or poor survival. Of the 31 patients who had a DR, 26 (83.9 %) were treated with thoracoabdominal chemoperfusion. The remaining five (16.1 %) patients had the diaphragm closed prior to HIPEC. Thoracoabdominal chemoperfusion was not associated with increased 30-day grade III/IV morbidity or respiratory complications. Overall, five (20 %) patients with a DR developed thoracic recurrence. There were two (8 %) thoracic recurrences in the 26 patients treated with thoracic chemoperfusion compared with three (60 %) in the five patients who had their diaphragm closed prior to HIPEC (
p
= 0.002). In univariate analysis histology, CC-0 and thoracoabdominal chemoperfusion were associated with thoracic disease-free survival; however, none of these were significant on multivariate analysis.
Conclusion
DR is not associated with increased morbidity and should be performed, if needed, to obtain a CC-0. Following DR, patients remain at significant risk of developing thoracic recurrence. Thoracoabdominal chemoperfusion reduces this risk without increasing morbidity.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide ...treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease.
To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma.
This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021. The data collection cutoff was May 2022. Enrollment of up to 30 patients was planned. Eligible patients had histological evidence of a metastatic low-grade mucinous appendiceal adenocarcinoma, with radiographic imaging demonstrating the presence of mucinous peritoneal carcinomatosis and were not considered candidates for complete cytoreductive surgery. Key exclusion criteria were concurrent or recent investigational therapy, evidence of bowel obstruction, and use of total parenteral nutrition. Data were analyzed from November 2021 to May 2022.
Patients were randomized to either 6 months observation followed by 6 months of chemotherapy, or initial chemotherapy followed by observation.
The primary end point was the percentage difference in tumor growth in treatment and observation groups. Key secondary end points included patient-reported outcomes in the chemotherapy and observation periods, objective response rate, rate of bowel complications, and differences in overall survival (OS).
A total of 24 patients were enrolled, with median (range) age of 63 (38 to 82) years, and equal proportion of men and women (eg, 12 men 50%); all patients had ECOG performance status of 0 or 1. A total of 11 patients were randomized to receive chemotherapy first, and 13 patients were randomized to receive observation first. Most patients (15 patients 63%) were treated with either fluorouracil or capecitabine as single agent; 3 patients (13%) received doublet chemotherapy (leucovorin calcium folinic acid, fluorouracil, and oxaliplatin or folinic acid, fluorouracil, and irinotecan hydrochloride), and bevacizumab was added to cytotoxic chemotherapy for 5 patients (21%). Fifteen patients were available to evaluate the primary end point of difference in tumor growth during treatment and observation periods. Tumor growth while receiving chemotherapy increased 8.4% (95% CI, 1.5% to 15.3%) from baseline but was not significantly different than tumor growth during observation (4.0%; 95% CI, -0.1% to 8.0%; P = .26). Of 18 patients who received any chemotherapy, none had an objective response (14 patients 77.8% had stable disease; 4 patients 22.2% had progressive disease). Median (range) OS was 53.2 (8.1 to 95.5) months, and there was no significant difference in OS between the observation-first group (76.0 8.6 to 95.5 months) and the treatment-first group (53.2 8.1 to 64.1 months; hazard ratio, 0.64; 95% CI, 0.16-2.55; P = .48). Patient-reported quality-of-life metrics identified that during treatment, patients experienced significantly worse fatigue (mean SD score, 18.5 18.6 vs 28.9 21.3; P = .02), peripheral neuropathy (mean SD score, 6.67 12.28 vs 38.89 34.88; P = .01), and financial difficulty (mean SD score, 8.9 15.2 vs 28.9 33.0; P = .001) compared with during observation.
In this prospective randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma, patients did not derive clinical benefit from fluorouracil-based chemotherapy, given there were no objective responses, no difference in OS when treatment was delayed 6 months, and no difference in the rate of tumor growth while receiving chemotherapy.
ClinicalTrials.gov Identifier: NCT01946854.
AIM To investigate the importance of a three-tiered histologic grade on outcomes for patients with mucinous appendiceal adenocarcinoma(MAA).METHODS Two hundred and sixty-five patients with MAA ...undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were identified from a prospective database from 2004 through 2014. All pathology was reviewed by our gastrointestinal subspecialty pathologists and histological grade was classified as well-differentiated, moderately differentiated, and poorly differentiated. Survival analysis was performed using Cox proportional hazards regression.RESULTS There were 201(75.8%) well-, 45(16.9%) moderatelyand 19(7.2%) poorly-differentiated tumors. Histological grade significantly stratified the 5-year overall survival(OS), 94%, 71% and 30% respectively(P < 0.001) as well as the 5-year disease-free survival(DFS) 66%, 21% and 0%, respectively(P < 0.001). Independent predictors of DFS included tumor grade(HR = 1.78, 95%CI: 1.21-2.63, P = 0.008), lymph node involvement(HR = 0.33, 95%CI: 0.11-0.98, P < 0.02), previous surgical score(HR = 1.31, 95%CI: 1.1-1.65, P = 0.03) and peritoneal carcinomatosis index(PCI)(HR = 1.05, 95%CI: 1.02-1.08, P = 0.002). Independent predictors of OS include tumor grade(HR = 2.79, 95%CI: 1.26-6.21, P = 0.01), PCI(HR = 1.10, 95%CI: 1.03-1.16, P = 0.002), and complete cytoreduction(HR = 0.32, 95%CI: 0.11-0.92, P = 0.03). Tumor grade and PCI were the only independent predictors of both DFS and OS. Furthermore, histological grade and lymphovascular invasion stratified the risk of lymph node metastasis into a low(6%) and high(40%) risk groups. CONCLUSION Our data demonstrates that moderately differentiated MAA have a clinical behavior and outcome that is distinct from well-and poorly-differentiated MAA. The threetier grade classification provides improved prognostic stratification and should be incorporated into patient selection and treatment algorithms.
Background
The amount of protection that condoms provide for HIV and other sexually transmitted infections is unknown. Cohort studies of sexually active HIV serodiscordant couples with follow‐up of ...the seronegative partner, provide a situation in which a seronegative partner has known exposure to the disease and disease incidence can be estimated. When some individuals use condoms and some do not, namely some individuals use condoms 100% of the time and some never use (0%) condoms, condom effectiveness can be estimated by comparing the two incidence rates. Condom effectiveness is the proportionate reduction in disease due to the use of condoms.
Objectives
The objective of this review is to estimate condom effectiveness in reducing heterosexual transmission of HIV.
Search methods
Studies were located using electronic databases (AIDSLINE, CINAHL, Embase, and MEDLINE) and handsearched reference lists.
Selection criteria
For inclusion, studies had to have: (1) data concerning sexually active HIV serodiscordant heterosexual couples, (2) a longitudinal study design, (3) HIV status determined by serology, and (4) contain condom usage information on a cohort of always (100%) or never (0%) condom users.
Data collection and analysis
Studies identified through the above search strategy that met the inclusion criteria were reviewed for inclusion in the analysis. Sample sizes, number of seroconversions, and the person‐years of disease‐free exposure time were recorded for each cohort. If available, the direction of transmission in the cohort (male‐to‐female, female‐to‐male), date of study enrollment, source of infection in the index case, and the presence of other STDs was recorded. Duplicate reports on the same cohort and studies with incomplete or nonsepecific information were excluded. HIV incidence was estimated from the cohorts of "always" users and for the cohorts of "never" users. Effectiveness was estimated from these two incidence estimates.
Main results
Of the 4709 references that were initially identified, 14 were included in the final analysis. There were 13 cohorts of "always" users that yielded an homogeneous HIV incidence estimate of 1.14 95% C.I.: .56, 2.04 per 100 person‐years. There were 10 cohorts of "never" users that appeared to be heterogeneous. The studies with the longest follow‐up time, consisting mainly of studies of partners of hemophiliac and transfusion patients, yielded an HIV incidence estimate of 5.75 95% C.I.: 3.16, 9.66 per 100 person‐years. Overall effectiveness, the proportionate reduction in HIV seroconversion with condom use, is approximately 80%.
Authors' conclusions
This review indicates that consistent use of condoms results in 80% reduction in HIV incidence. Consistent use is defined as using a condom for all acts of penetrative vaginal intercourse. Because the studies used in this review did not report on the "correctness" of use, namely whether condoms were used correctly and perfectly for each and every act of intercourse, effectiveness and not efficacy is estimated. Also, this estimate refers in general to the male condom and not specifically to the latex condom, since studies also tended not to specify the type of condom that was used. Thus, condom effectiveness is similar to, although lower than, that for contraception.
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Background: Malignant peritoneal mesothelioma (MPeM) is a rare cancer (incidence of 0.12 per 100,000) and an arduous diagnostic challenge, requiring skillful evaluation by expert pathologists. ...Subjective and experiential immunophenotyping coupled with inattention to this rare entity causes delayed or misdiagnosis and leads to suboptimal treatment and outcomes. Gene-expression-based cancer classification offers an objective molecular assessment of the tissue of origin for cancers with uncertain diagnosis and improves diagnostic accuracy for MPeM compared to standard pathology. Methods: We retrospectively evaluated 23 patients (pts) with cancer of unknown primary (CUP) or uncertain diagnoses, with peritoneal/retroperitoneal carcinomatosis and reported as malignant mesothelioma using a 92-gene assay (CancerTYPE ID), a validated classifier for predicting tumor types, between January 2013 to December 2016. Pathology was verified by central review. Clinicopathologic data including immunohistochemistry (IHC) was collected using archived pathology specimens and reports. Results: Pts had a median age of 64 years (range: 39 – 93) at diagnosis, 57% were females and 74% had biopsy from omentum/peritoneum. Original histopathology was reported as poorly differentiated in 81% and as adenocarcinoma, carcinoma and malignant neoplasm in 10 (43%), 7 (30%) and 6 (27%) of cases, respectively. The number of IHC stains performed ranged between 0 and 28 (median: 10). Key IHC stains are shown in the table. Conclusions: In this cohort of CUP or uncertain diagnoses with a molecular cancer classification of malignant mesothelioma, we found huge variability and critical gaps in pathological work-up. Integration of molecular cancer classification using the 92-gene assay helped resolve this diagnostic uncertainty, further supporting its clinical utility to complement standard pathology. The impact of these findings goes beyond just MPeM and may benefit numerous pts with orphan cancers, who account for nearly 20% of all cancers diagnosed globally. Table: see text
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