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Peritoneal Carcinomatosis (PC) is a late stage manifestation of several gastrointestinal malignancies including appendiceal, colorectal, and gastric cancer. In PC, tumors metastasize to and deposit on the peritoneal surface and often leave patients with only palliative treatment options. For colorectal PC, median survival is approximately five months, and palliative systemic therapy is able to extend this to approximately 12 months. However, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with a curative intent is possible in some patients with limited tumor burden. In well-selected patients undergoing complete cytoreduction, median survival has been reported as high as 63 month. Identifying patients earlier who are either at risk for, or who have recently developed PC may provide them with additional treatment options such as CRS/HIPEC. PC is diagnosed late by imaging findings or often times during an invasive procedures such as laparoscopy or laparotomy. In order to improve the outcomes of PC patients, a minimally invasive, accurate, and specific PC screening method needs to be developed. By utilizing circulating PC biomarkers in the serum of patients, a " liquid biopsy, " may be able to be generated to allow a tailored treatment plan and early intervention. Exosomes, stable patient-derived nanovesicles present in blood, urine, and many other bodily fluids, show promise as a tool for the evaluation of labile biomarkers. If liquid biopsies can be perfected in PC, manifestations of this cancer may be more effectively treated, thus offering improved survival.
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Oncotarget1 Oncotarget, Advance Publications 2017
Peritoneal carcinomatosis: limits of diagnosis and the case for
liquid biopsy
James R.W. McMullen1, Matthew Selleck2, Nathan R. Wall1 and Maheswari Senthil2
1 Department of Basic Sciences, Center for Health Disparities & Molecular Medicine, Division of Biochemistry, Loma Linda
University Medical Center, Loma Linda, CA, USA
2 Department of Surgery, Division of Surgical Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
Correspondence to: Nathan R. Wall, email:
Correspondence to: Maheswari Senthil, email:
Keywords: peritoneal carcinomatosis, liquid biopsy, biomarker, exosomes
Received: January 21, 2017 Accepted: March 15, 2017 Published: March 22, 2017
Peritoneal Carcinomatosis (PC) is a late stage manifestation of several
gastrointestinal malignancies including appendiceal, colorectal, and gastric cancer.
In PC, tumors metastasize to and deposit on the peritoneal surface and often leave
patients with only palliative treatment options. For colorectal PC, median survival
is approximately ve months, and palliative systemic therapy is able to extend this
to approximately 12 months. However, cytoreductive surgery with hyperthermic
intraperitoneal chemotherapy (CRS/HIPEC) with a curative intent is possible in
some patients with limited tumor burden. In well-selected patients undergoing
complete cytoreduction, median survival has been reported as high as 63 month.
Identifying patients earlier who are either at risk for, or who have recently developed
PC may provide them with additional treatment options such as CRS/HIPEC. PC is
diagnosed late by imaging ndings or often times during an invasive procedures such
as laparoscopy or laparotomy. In order to improve the outcomes of PC patients, a
minimally invasive, accurate, and specic PC screening method needs to be developed.
By utilizing circulating PC biomarkers in the serum of patients, a “liquid biopsy,” may
be able to be generated to allow a tailored treatment plan and early intervention.
Exosomes, stable patient-derived nanovesicles present in blood, urine, and many
other bodily uids, show promise as a tool for the evaluation of labile biomarkers.
If liquid biopsies can be perfected in PC, manifestations of this cancer may be more
eectively treated, thus oering improved survival.
Peritoneal Carcinomatosis (PC) is a late stage
manifestation of several gastrointestinal malignancies
characterized by tumor deposition across the peritoneal
surface [1]. This can be entirely asymptomatic in its early
stages, or as the disease progresses, symptoms such as
nausea, diarrhea, abdominal pain, bloating, and weight
loss may develop [1]. The disease is often discovered
when ascites or intestinal obstruction develop, occurring
generally with greater tumor burden which is more
dicult to treat [2]. Early PC detection when there is
limited tumor burden may increase the eectiveness of
current treatment options [3].
Colorectal cancer (CRC), the third most common
cancer in the world, provides a good case study of PC. In
2016 there will be an estimated 95,270 cases of colorectal
cancer in the United States and nearly 1.4 million cases
worldwide [4]. Synchronous PC is diagnosed around the
time of diagnosis of primary tumor while metachronous
PC is diagnosed at a later time, typically months to
years after the original diagnosis [5]. The incidence
of synchronous isolated peritoneal carcinomatosis in
patients with CRC varies somewhat in the literature from
4%-18% [6-9]. This may even be a low estimate given
the lack of sensitivity of imaging for PC and that it may
not be discovered until surgical exploration. Meanwhile,
metachronous PC has been reported in 5-19% of patients
following denitive treatment.
PC used to be considered a lethal disease with
no curative surgical options. However, the growing
acceptance of CRS with hyperthermic intraperitoneal
chemotherapy (HIPEC), has oered the possibility of
improved survival for carefully selected patients [3].
This method makes use of “cytoreduction” to surgically
remove gross visible tumor deposits followed by direct
contact of heated cytotoxic chemotherapy agents to
aect any residual disease. Given during surgery, this
protocol maximizes potential contact with the peritoneal
surface while minimizing systemic toxicity. Specically,
hyperthermia between 41 and 43 degrees centigrade is
combined with large molecular weight drugs that penetrate
between a few cells deep to 3mm causing cytotoxic eects
[10]. Dr. Paul Sugarbaker is credited with developing this
treatment option by combing these elements into a curative
approach to peritoneal dissemination of gastrointestinal
malignancies [11, 12]. Median survival of CRC PC
without any treatment is approximately 4-7 months, while
palliative systemic therapy may extend this to 12-23
months based on several series [13-15]. Median overall
survival with CRS/HIPEC has been reported to range
from 22 to 63 months with a 5-year survival of 40-51%
in selected patients [13, 15, 16]. The outcomes of CRS/
HIPEC are strongly inuenced by careful patient selection
and complete cytoreduction (CC-0) (see Table 1) [17].
Survival of patients with colorectal cancer who receive
less than complete cytoreduction (CC-1 or CC-2) or have
a higher burden of disease as indicated by the peritoneal
carcinomatosis index (PCI) (see Figure 1) is signicantly
diminished compared to that of a CC-0 resection [17-19].
Extensive disease burden at identication often leaves
patients with only palliative treatment options [20].
Despite the benet of CRS/HIPEC, only about 25% of
patients with PC will be eligible for this approach given
the late presentation and burden of disease. In order to
expand patient eligibility and oer treatment with a
curative intent, early detection of PC, before signicant
tumor burden develops, is essential.
Traditional imaging, such as CT and MRI lack
sensitivity to both detect and estimate disease burden
in PC. Classic computed tomography (CT) signs of PC
such as “omental caking,” thickening of the omentum,
and peritoneal nodules are not common radiographic
ndings in “early” disease states. Several studies designed
to determine the specicity and accuracy of CT scans in
assessing tumor burden for PC found that CT signicantly
underestimated the amount of disease present in the
peritoneal cavity [21-24]. Sensitivity for CT detection
of tumor nodules less than 0.5 cm and 1cm had been
reported to be 11% and 25-50% respectively [23]. This
is particularly important in colorectal PC, where PCI is
a critical determinant of complete cytoreduction and
Figure 1: Peritoneal Cancer Index (PCI) scoring system. PCI is a diagnostic and prognostic tool that is a sum of scores in thirteen
abdominal regions. Each receives a score of 0-3 based on the largest tumor size in each region. Scores range from 0 to 39. Higher scores
indicate more widespread and/or larger tumors in the peritoneal cavity.
long-term outcomes [25]. In a study by Koh et al looking
specically at CRC PC they determined CT signicantly
underestimated clinical PCI [23]. In fact sensitivity of
small bowel involvement in each region ranged from
8-17%. Despite this, the Fifth International Workshop on
Peritoneal Surface Malignancy in Milan, identied CT as
the principal imaging modality to assess suitability for
CRS [26]. Ultrasound also has very limited sensitivity
for detecting PC nodules [27-29]. Magnetic resonance
imaging (MRI), and particularly diusion weighted
images, has been demonstrated in prospective studies to
have increased accuracy in detection of carcinomatosis
within certain areas of the abdomen [30]. This however
carries its own limitations due to the motion artifacts
of peristalsis, cost, and the need for radiologists trained
in their interpretation and inter-observer variation.
Additionally, positron emission technology (PET) may
have increased sensitivity, but similar limitations and
absence of added clinical value often precludes its use for
determining resectability [24, 31-33]. These diculties,
especially limited sensitivity, lack of meaningful clinical
correlation and high cost, reduce the utility of non-
invasive imaging in the early detection of PC. With the
current technology, laparoscopy or exploratory surgery is
often necessary to conrm the diagnosis and extent of PC
(see Table 2) [34].
Given the narrow subset of patients who are oered
CRS/HIPEC, a potentially life-saving treatment, we are
in need of a paradigm change. Patients who are either at
risk for developing PC or who are in the earliest stage
of this disease process may signicantly benet from
expanded treatment options. The term “liquid biopsy” has
reached prolic use as large-scale investigations seek to
identify tumor markers in the serum. This usually refers to
molecular diagnostic studies that are performed on blood
or body uid as opposed to cancerous tissue itself [35].
Multiple serum tumor markers: carcinoembryonic antigen
(CEA), carbohydrate antigen CA 19-9, and CA 125, are
commonly elevated in patients with PC and the degree of
elevation tends to correlate with the extent of PC [36].
However, these serum tumor markers are inadequate for
early detection of PC. Moreover, they lack specicity to
predict the presence or risk of PC in patients with CRC.
There is a critical clinical need to identify circulating
tumor biomarkers of aggressiveness, likelihood of
recurrence, risk of metastasis such as PC, or even the
presence of a malignancy to better tailor therapy for
patients. For example, if a patient with a newly diagnosed
stage III colorectal cancer is known to be at signicant risk
for peritoneal recurrence due to the presence of a specic
set of biomarkers in their serum, they may benet from
prophylactic HIPEC. This is just one example of how this
Table 1: CC is the completeness of cytoreduction score. It indicates the size of the largest tumor that remains after
cytoreductive surgery.
Completeness of Cytoreduction scores
Score Size of largest post-surgery residual tumor
CC-0 No visible tumor
CC-1 Less than 0.25 cm
CC-2 Between 0.25 cm and 2.5 cm
CC-3 > 2.5 cm or conuent
Table 2: This table summarizes the pros and cons of each non-invasive imaging modality in assessing PC
Non-Invasive Imaging Utility in PC Detection
Modality Pros Cons
Sensitivity/Specicity as
compared to surgical analysis References
Eective for
ascites detection
Limited PC nodule
sensitivity, highly operator
Non-specic [26] [24, 25]
Standard staging
Limited small PC nodule
sensitivity, Inter-observer
25-100%/78-100% with only 11-
48% sensitivity for tumors less
than 5 mm [26] [18-21]
High PC
Relatively Expensive, slight
peristalsis motion artifact,
inter-observer variability
90%/95.5% (diusion weighted)
[26] [28]
High PC
Relatively Expensive,
Peristalsis motion artifact 78-97%/55-90% [26] [27, 28]
technology may be applied.
If blood-borne biomarkers for PC with high
sensitivity and specicity are discovered, patients
developing PC may be quickly identied with a blood test,
a liquid biopsy. One such type of biomarker, microRNAs
(miRs), short, non-coding RNAs that regulate mRNAs, has
demonstrated diagnostic utility by correctly identifying
several cancers of unknown primary with reasonable
accuracy [37]. The diagnostic miR prole that was used
in this study was generated from miR analysis in well
dierentiated primary tumors [37]. Several miRs, such as
miR-21, have been linked to gastrointestinal cancers as
potential diagnostic targets and prognostic indicators [38].
However these miRs and other types of RNAs are rapidly
degraded in the plasma [39-41].
Exosomes, small cell-derived vesicles (Figure 2),
can protect RNAs and miRNAs, from being degraded [42-
46]. When researchers exposed miRs to RNase, the miRs
that were in exosomes and cells were protected while the
free RNAs were degraded [42]. When exosomes were
exposed to RNase the contained RNAs were protected
from degradation while cellular RNA was degraded by the
same RNase [45]. Exosomes hold great potential for both
diagnosis and prognosis of diseases and are exceptionally
useful as cancer biomarkers [47]. When a panel of lung
cancer associated miRs was examined in solid tumors and
tumor exosomes from patient plasma, most of the miRs
were found to have highly comparable expression levels
(see Table 3 for the miRs) [48, 49]. Cervical cancer cell
line tumor derived exosomes (TEXs) contain survivin,
which contributes to cancer aggressiveness and metastatic
potential [50, 51]. In a study of ovarian cancer, greater
numbers of cancer exosomes were found in the serum
as more advanced cancer stages were examined [52].
Furthermore, approximately four times more serum
exosomes were discovered in lung cancer patients as
compared to cancer free controls and the exosomes
contained more than twice the miRs [48]. In our research,
we found increased serum exosome levels in patients with
prostate and breast cancers as compared to disease free
controls [53-55]. TEXs are prevalent in patient serum from
Table 3: These lung cancer associated miRs were discovered in both solid tumor and in tumor exosomes.
miR-17-3p miR-21 miR-106a miR-146 miR-155 miR-191
miR-192 miR-203 miR-205 miR-210 miR-212 miR-214
Table 4: Gastric Cancer PC associated exosomal miRs and their prevalence in various cancers.
Gastric Cancer Lung
Cancer Adrenal Cancer
miR 1202
↔malignant ascites,
peritoneal lavage
uid, cell culture
[54] XX↑Ø tumor tissue [62]
miR 1207-
↔malignant ascites,
peritoneal lavage
uid, cell culture
[52], ↓tNm tumor
tissue [63],
↓ tumor tissue [64]
tumor [56]
[54] ↑ serum [65]
[66] X
miR 1225-
↑tnM peritoneal
lavage uid [52],
↓ cancer tissue [53] X↓ blood
↑ blood [68],
↓ solid tumor
tumor [70]
multiple types of
solid tumors [71]
miR 320c
↔malignant ascites,
peritoneal lavage
uid, cell culture
[72] X X X X X
miR 4270
↔malignant ascites,
peritoneal lavage
uid, cell culture
[54] X X X
All data is from human studies
↑, ↓-increased/decreased expression associated with cancer
↑tnM, ↓tnM -increased/decreased expression associated with metastatic cancer
↑tNm, ↓tNm -increased/decreased expression associated with lymph node metastasis
↑ Ø, ↓Ø -increased/decreased expression associated with shorter patient survival
↔-present but no signicant dierential regulation
X -no research discovered in literature
multiple cancer types and protect labile biomarkers from
degradation [42, 45, 48, 53-55].
Exosomes have not been extensively studied in
PC diagnostics. Andre and colleagues examined ascites
exosomes from patients with PC and found that the tumor
specic markers Her2/Neu, TRP1, and Mart1 were present
in ascites tumor exosomes [56]. Tokuhisa and colleagues
have identied several RNAs present in exosomes within
peritoneal ascites, peritoneal lavage, and PC metastatic
cell lines [57]. After exosome miR screening, 5 miRNAs
were selected as a panel of signicantly dierentially
regulated RNAs: miR 1202, 1207-5p, 1225-5p, 320c, and
4270 [57]. miR 21 had the strongest signal intensity in
malignant ascites [57]. Exosomes from peritoneal lavage
were probed for miR 21, 1225-5p, and 320c; miR 21 and
1225-5p were found to be upregulated in later stages of
gastric cancer and correlated with serosal invasion [57]. In
a study on primary gastric cancer tissue, miR 1255-5p was
generally downregulated and was found to inhibit cancer
cell growth, motility, as well as cancer invasion [58]. This
apparently contradictory result suggests that miR 1225-
5p in peritoneal lavage either is being released by non-
cancerous tissue in an attempt to stop abnormal growths
or is being used by cancers in order to facilitate better
attachment to the peritoneum. In apparently contradictory
results to the above study, in gastric cancer cell lines and
in vivo, miR 1255-5p was generally downregulated and
was found to inhibit cell growth and motility as well as
cancer invasion [58].
The prospective gastric PC miR biomarkers
described in the study by Tokuhisa and colleagues [57]
have been found to be associated with other cancers as
well (see Table 4). Notably, miR 1202, 1207-5p, 1225-5p,
and 4270, were found circulating in the blood of breast
cancer patients [59]. In human bladder cancer tissue
samples, miR 320c was signicantly downregulated [60].
In hepatocellular carcinoma tissue samples, miR 1207-
5p was found to be signicantly downregulated [61].
In adrenocortical carcinoma tissue samples, increased
miR 1202 expression was found to be associated with
signicantly reduced patient lifespan [62]. The gaps in our
knowledge of RNA signaling in cancer are immediately
apparent from Table 4. The observation that these miRs,
either individually or in a group, are associated with
multiple types of cancer and are found in exosomes from
the peritoneal cavity suggest the potential of exosomal
diagnosis of PC.
RNAs are found to be globally downregulated in
cancer [37]. Upregulated RNAs and miRs are likely to
be related to cancer growth and function or the body’s
response to cancer. miR 320c inhibited cell growth and
motility in bladder cancer [60]. miR 1207-5p functioned
to inhibit cell growth and invasion in liver cancer but
functions to increase stemness in colorectal cancer [61,
63]. Since these exosomal-associated miRs have known
functions in tumors, the possibility emerges of tailoring
PC treatment based on what biomarkers are discovered
in a patient’s exosomes. miR 320c inhibited cell growth
and motility and miR 1207-5p functioned to inhibit cell
Figure 2: Tumor Cells release nanovesicles called exosomes which carry RNAs, including microRNAs and messenger
RNAs, and proteins.
growth and invasion. The observation that these exosomal-
associated miRs have known functions in tumors opens
up the possibility of utilizing these biomarkers to tailor an
individual patient’s treatment. [60, 61]
Additional research is needed to identify biomarkers
in peritoneal carcinomatosis. Distinguishing metastatic
disease of peritoneal origin from solid organ metastases
should be both biologically feasible and clinically
useful. As we look to exosomes to provide insight into
the eld, shared challenges in nanovesicle isolation and
validation will need to be addressed. Reliable and ecient
methods as well as recognized standards will need to be
established for clinical use. Future clinical work in this
eld should include the prospective collection of samples
for retrospective investigation. This will be instrumental
in establishing clinical validity and utility. We are hopeful
that the shared work of many will continue to yield
advances in reducing the burden of life lost from this
aggressive malady.
Recently, TEXs have been implicated in facilitating
metastasis. TEXs can be taken up by multiple cell types,
including endothelial cells, bone marrow progenitor
cells, and other cancer cells [64-67]. These exosomes
demonstrated the ability to deliver functional RNAs
and proteins to recipient cells, modifying their growth
patterns to be pro-oncogenic [65, 66]. Further, TEXs have
demonstrated the ability to greatly increase metastatic
tumor burden in a mouse model [64]. Studying TEXs
in the context of metastasis is a promising eld. PC is
currently dicult to detect at its onset. Late PC detection
usually leaves the disease incurable. PC must be detected
sooner for better patient outcomes. Non-invasive imaging
is impractical for early PC detection. Detection of PC by
means of markers within a patient’s biouids, such as a
serum “liquid biopsy” would be ideal. Both serum and
ascites contain biomarkers released by PC. Exosomes
are released into serum by multiple types of cancers and
protect their contents from degradation in the blood. These
provide us with a likely source of a sensitive and specic
diagnostic modality to detect PC in its earliest most
treatable from.
The authors would like to thank the Center for
Health Disparities & Molecular Medicine for its support.
They would also like to thank members of the Wall
Laboratory for careful review of this manuscript.
Research reported in this publication was supported
by NIH award P20MD006988 (NRW).
The Authors declare no conicts of interest.
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... Radiologists must specify each site of peritone matosis in order to provide the most accurate staging possible. To obtain an a sessment of PC and to map peritoneal implants, radiologists should common Sugarbaker-proposed assessment system, which allows calculation of the Perit cer Index (PCI) [98,99]. ...
... Radiologists must specify each site of peritoneal carcinomatosis in order to provide the most accurate staging possible. To obtain an accurate assessment of PC and to map peritoneal implants, radiologists should commonly use the Sugarbaker-proposed assessment system, which allows calculation of the Peritoneal Cancer Index (PCI) [98,99]. ...
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Peritoneal carcinosis is a condition characterized by the spread of cancer cells to the peritoneum, which is the thin membrane that lines the abdominal cavity. It is a serious condition that can result from many different types of cancer, including ovarian, colon, stomach, pancreatic, and appendix cancer. The diagnosis and quantification of lesions in peritoneal carcinosis are critical in the management of patients with the condition, and imaging plays a central role in this process. Radiologists play a vital role in the multidisciplinary management of patients with peritoneal carcinosis. They need to have a thorough understanding of the pathophysiology of the condition, the underlying neoplasms, and the typical imaging findings. In addition, they need to be aware of the differential diagnoses and the advantages and disadvantages of the various imaging methods available. Imaging plays a central role in the diagnosis and quantification of lesions, and radiologists play a critical role in this process. Ultrasound, computed tomography, magnetic resonance, and PET/CT scans are used to diagnose peritoneal carcinosis. Each imaging procedure has advantages and disadvantages, and particular imaging techniques are recommended based on patient conditions. Our aim is to provide knowledge to radiologists regarding appropriate techniques, imaging findings, differential diagnoses, and treatment options. With the advent of AI in oncology, the future of precision medicine appears promising, and the interconnection between structured reporting and AI is likely to improve diagnostic accuracy and treatment outcomes for patients with peritoneal carcinosis.
... This method has the remarkable capability to not only limit systemic toxicities but also increase the exposure of tumors to chemotherapy. 6 In one of the largest cohorts investigating aggressive surgical management of peritoneal metastasis of HCC, it was found that the overall survival from surgery is 46.7 months. This result is highly variable to the medical management which includes Sorafenib and/or systemic chemotherapy, where overall survival is 6 and 14 months. ...
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Hepatocellular carcinoma (HCC) is a common malignancy of the liver. It is frequently diagnosed in the male gender with a racial predilection towards Asian and African populations. In addition to distant metastasis, large tumors can result in direct extrahepatic metastasis to the peritoneum and diaphragm through rupture of exophytic tumor hepatocellular carcinoma in peritoneal cavity. We report a case of a 55-year-old male having hepatocellular carcinoma secondary to hepatitis C with peritoneal metastasis. The CT abdomen with contrast triphasic study was suggestive of alarming features of chronic liver disease with multicentric hepatoma formation predominantly in segment VIII with the localized subcapsular collection. Additionally, an extensive omental thickening and nodularity were also seen in subhepatic space. Multiple nodules were seen in right cardiophrenic angle, right lower abdomen, and rectovesical pouch. In contrast to conventional chemotherapy with sorafenib, cytoreduction surgery with hyperthermic intraperitoneal chemotherapy has been shown to dramatically improve survival in patients
... PC is the metastatic involvement of the peritoneum, the thin membrane that encircles abdominal organs [1,2]. In gastrointestinal (e.g., colorectal and gastric cancers) and gynecological (e.g., ovarian cancer) malignancies, the average survival time for PC is less than six months [3][4][5][6][7]. PC occurs in around 15% of colorectal cancer patients [2] and up to 50% of patients with recurrent gastric cancer [8]. ...
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Simple Summary Peritoneal carcinomatosis is a challenging condition that affects many cancer patients, and conventional therapies have limited efficacy in treating it. However, recent advances in the field of immunotherapy have shown promise in improving treatment outcomes. One promising approach is immune checkpoint inhibitors, which block proteins that inhibit T-cell activity and promote an anti-tumor immune response. Another approach involves the use of CAR-T cells, which are genetically modified T cells engineered to recognize and target cancer cells expressing specific antigens. In addition, dendritic cells and vaccine-based therapeutics are also designed to stimulate the immune system to recognize and attack cancer cells. The authors also discuss the potential benefits of combining different immunotherapeutic approaches to improve treatment efficacy. While there is still much to be learned about the use of immunotherapy for peritoneal carcinomatosis, the available evidence suggests that it holds promise as a potentially effective and well-tolerated treatment option. Abstract Peritoneal metastasis, also known as peritoneal carcinomatosis (PC), is a refractory cancer that is typically resistant to conventional therapies. The typical treatment for PC is a combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Recently, research in this area has seen significant advances, particularly in immunotherapy as an alternative therapy for PC, which is very encouraging. Catumaxomab is a trifunctional antibody intraperitoneal (IP) immunotherapy authorized in Europe that can be used to diminish malignant ascites by targeting EpCAM. Intraperitoneal (IP) immunotherapy breaks immunological tolerance to treat peritoneal illness. Increasing T-cell responses and vaccination against tumor-associated antigens are two methods of treatment. CAR-T cells, vaccine-based therapeutics, dendritic cells (DCs) in combination with pro-inflammatory cytokines and NKs, adoptive cell transfer, and immune checkpoint inhibitors are promising treatments for PC. Carcinoembryonic antigen-expressing tumors are suppressed by IP administration of CAR-T cells. This reaction was strengthened by anti-PD-L1 or anti-Gr1. When paired with CD137 co-stimulatory signaling, CAR-T cells for folate receptor cancers made it easier for T-cell tumors to find their way to and stay alive in the body.
... Advanced intra-abdominal malignancies are prone to peritoneal metastasis (PM), namely, peritoneal carcinomatosis, which is characterized by cancer metastasis to the peritoneal surface and the spread of malignant tumors in the peritoneal cavity (Coccolini et al., 2013). PM was previously considered to be a fatal disease with little opportunity for a cure because it has a lower response rate to normal systemic chemotherapy than other organ-specific metastases (McMullen et al., 2017). ...
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Background: Peritoneal metastasis (PM) is an advanced stage of intra-abdominal malignancy with a very poor prognosis. In recent years, hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) has been utilized as an active treatment in the prevention and treatment of PM, with encouraging results. However, compared with CRS alone, the results of the CRS plus HIPEC strategy in the treatment of patients with intra-abdominal malignancies are still controversial. This study sought to determine the impact of HIPEC + CRS on patient survival and adverse events (AEs) by reviewing randomized controlled trials (RCTs) for all types of intra-abdominal malignancies. Methods: A PubMed, Embase, Cochrane Library, Web of Science and Clinical search extracted all RCTs until 12 October 2022, examining the CRS + HIPEC vs. CRS alone strategies in the treatment of various types of intra-abdominal malignancies. The outcomes included overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), progression-free survival (PFS) and AEs. The dichotomous data were pooled and reported as odds ratios (ORs) with 95% confidence intervals (CIs). The survival outcome data were pooled using hazard ratios (HRs) and corresponding 95% CIs. The Cochrane Collaboration’s Risk of Bias Tool was used to assess the risk of bias in the included studies. Results: A total of 12 RCTs were included in this meta-analysis, including 873 patients in the CRS + HIPEC group and 878 patients in the CRS alone group. The studies included 3 (617 patients) on colorectal cancer, 4 (416 patients) on gastric cancer, and 5 (718 patients) on ovarian cancer. Our analysis showed no difference in OS between the CRS + HIPEC and CRS alone groups (HR: 0.79, 95% CI 0.62–1.01). Subgroup analysis showed that CRS + HIPEC improved the OS of gastric cancer patients (HR: 0.49, 95% CI 0.32–0.76) compared with CRS alone. However, CRS + HIPEC did not significantly improve the OS of colorectal cancer (HR: 1.06, 95% CI 0.81–1.38) and ovarian cancer (HR: 0.82, 95% CI 0.62–1.07) patients. In addition, there was no significant difference in DFS/RFS (HR: 0.78, 95% CI 0.57–1.07) or PFS (HR: 1.03, 95% CI 0.77–1.38) between the two groups. Compared with CRS alone, CRS with HIPEC had greater nephrotoxicity (OR: 0.45, 95% CI 0.21–0.98), while other AEs did not differ significantly between the two groups. Conclusion: Our results suggest that CRS + HIPEC may improve OS in gastric cancer patients compared with CRS alone, but we did not observe a benefit for DFS/RFS. For patients with ovarian and colorectal cancers, our results suggest that HIPEC + CRS does not appear to improve survival outcomes. In addition, CRS + HIPEC has higher nephrotoxicity than CRS alone. More evidence from RCTs is needed to evaluate whether the use of CRS + HIPEC is an appropriate option.
... They can also be isolated from patient blood samples [12], which can be screened for tumor biomarkers to discriminate between Tumor Derived Exosomes (TDEs) and normal tissue exosomes [5]. Many potential biomarkers for CRC have been studied in vitro, but their use in the clinical setting is still being explored [13]. Many of CRC's most common oncogenic mutations are proliferative and/ or anti-apoptotic [14], giving rational for looking at modulators of these pathways specifically as biomarkers for this disease. ...
... Peritoneal carcinomatosis represents a metastatic stage from which patients often die within 2 to 6 months after the condition becomes apparent in imaging studies. To improve such a dismal prognosis, current research focuses on two major strategies: i) improving the early diagnosis of PCa, 53 and ii) discovering novel interventions with an advantageous therapeutic index. Within the peritoneal cavity, the omentum represents a favorable site for metastasis, which eventually becomes subjugated to the tumor and contributes to its growth. ...
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Previous studies have shown that local delivery of tumor antigen-specific CD8⁺ T lymphocytes engineered to transiently express single-chain IL-12 mRNA is highly efficacious. Peritoneal dissemination of cancer is a frequent and often fatal patient condition usually diagnosed when the tumor burden is too large and hence uncontrollable with current treatment options. In this study, we have modeled intracavitary adoptive T cell therapy with OVA-specific OT-I T cells electroporated with IL-12 mRNA to treat B16-OVA and PANC02-OVA tumor spread in the peritoneal cavity. Tumor localization in the omentum and the effects of local T-cell encounter with the tumor antigens were monitored, the gene expression profile evaluated, and the phenotypic reprogramming of several immune subsets was characterized. Intraperitoneal administration of T cells promoted homing to the omentum more effectively than intravenous administration. Transient IL-12 expression was responsible for a favorable reprogramming of the tumor immune microenvironment, longer persistence of transferred T lymphocytes in vivo, and the development of immunity to endogenous antigens following primary tumor eradication. The efficacy of the strategy was at least in part recapitulated with the adoptive transfer of lower affinity transgenic TCR-bearing PMEL-1 T lymphocytes to treat the aggressive intraperitoneally disseminated B16-F10 tumor. Locoregional adoptive transfer of transiently IL-12-armored T cells appears to offer promising therapeutic advantages in terms of anti-tumor efficacy to treat peritoneal carcinomatosis.
Colorectal cancer peritoneal metastases (CRC-PM) are present in 5 to 15% of instances of CRC, and the overall survival (OS) of patients with CRC-PM is much lower than that of patients with other isolated metastatic locations. In recent years, the introduction of cytoreductive surgery (CRS) in conjunction with hyperthermic intraperitoneal chemotherapy has resulted in a significant improvement in CRC-PM patients' OS. Despite this, a significant proportion of CRS patients continue to suffer complications of grades III to V or even die during the perioperative period. Early diagnosis, optimization of patient selection criteria, and refining of individualized combination therapy are necessary for these patients. In this review, we evaluate studies examining the relationship between molecular status and CRS in CRC-PM. Our objective is to gain a comprehensive understanding of how the altered molecular status of CRC-PM impacts CRS, which could increase the likelihood of tailored therapy in the future.
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Peritoneal metastasis occurs in a number of heterogeneous tumors originating from the ovaries, stomach, intestines, pancreas, lungs, breast, and melanoma. Peritoneal carcinomatosis significantly reduces overall survival. While being almost unresponsive to treatment, dissemination of tumor cells along the peritoneum aggravates the course of the disease. Despite the use of locoregional treatment, peritoneal carcinomatosis is still considered to be an aggravating factor with a poor prognosis. Peritoneal carcinomatosis cannot be defined as a separate locoregional process with its own biology and oncogenesis due to the lack of clear understanding the molecular and biological features of peritoneal metastasis, as well as generally recognized standards for diagnosis and treatment of malignant neoplasms with various localizations. Addressing peritoneal carcinomatosis as a separate developing molecular event will enhance the understanding of its morpho- and oncogenesis and strengthen the search for therapeutic, diagnostic and preventive approaches to its management. Th e paper presents a bibliographic study of publications on exploring peritoneal metastases from various sites, including the abdominal and pelvic organs. Th e known mechanisms of tumors metastasis to the peritoneum are characterized in the paper. Diagnostic approaches to peritoneal carcinomatosis were assessed and compared. Th e collected data analysis revealed the main gaps in the understanding of peritoneal carcinomatosis oncogenesis.
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A longstanding problem with conventional cancer therapy is the nonspecific distribution of chemotherapeutics. Monitoring drug release in vivo via noninvasive bioimaging can thus have value, but it is difficult to distinguish loaded from released drug in live tissue. Here, this work describes an injectable supramolecular hydrogel that allows slow and trackable release of doxorubicin (Dox) via photoacoustic (PA) tomography. Dox is covalently linked with photoacoustic methylene blue (MB) to monitor Dox before, during, and after release from the hydrogel carrier. The conjugate (MB‐Dox) possesses an IC50 of 161.4 × 10⁻⁹ m against human ovarian carcinoma (SKOV3) cells and loads into a DNA‐clad hydrogel with 91.3% loading efficiency due to MB‐Dox's inherent intramolecular affinity to DNA. The hydrogel is biodegradable by nuclease digestion, which causes gradual release of MB‐Dox. This release rate is tunable based on the wt% of the hydrogel. This hydrogel maintains distinct PA contrast on the order of days when injected in vivo and demonstrates activatable PA spectral shifts during hydrogel degradation. The released and loaded payload can be imaged relative to live tissue via PA and ultrasound signal being overlaid in real‐time. The hydrogel slowed the rate of the murine intraperitoneal tumor growth 72.2% more than free Dox.
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Purpose: Peritoneal carcinomatosis (PC), metastasized from colorectal cancer (CRC), remains a highly lethal disease. Outcomes of PC is significantly influenced by the amount of intra-abdominal tumor burden and therefore diagnostic tests that facilitate earlier diagnosis could improve PC treatment and patient outcomes. Experimental design: Using mass-spectrometry-based proteomics, we characterized the protein features of circulating exosomes in the context of CRC PC, CRC with liver metastasis, and primary CRC limited to the colon. We profiled exosomes isolated from patient plasma to identify exosome-associated protein cargoes released by these cancer types. Results: Analysis of the resulting data identified metastasis-specific exosome protein signatures. Bioinformatic analyses confirmed enrichment of proteins annotated to vesicle-associated processes and intracellular compartments, as well as representation of cancer hallmark functions and processes. Conclusion and clinical relevance: This research yielded distinct protein profiles for the CRC patient groups and suggests the utility of plasma exosome proteomic analysis for a better understanding of PC development and metastasis. This article is protected by copyright. All rights reserved.
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Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called " exosomal shuttle RNA " (esRNA). Exosomes are small (50–90 nm) membrane vesicles of endocytic origin that are released into the extracellular environment on fusion of multivesicular bodies (MVB) with the plasma membrane 1. Many cells have the capacity to release exosomes, including reticulo-cytes 2 , dendritic cells 3 , B cells 4 , T cells 5 , mast cells 6 , epithelial cells 7 and tumour cells 8. The functions of exosomes are not completely understood, although it has been shown that exosomes can participate in the signalling events contributing to antigen presentation to T cells 4 and the development of tolerance 9. Several mechanisms have been hypothesized describing the interactions of exosomes and recipient cells. Exosomes can bind to cells through recep-tor–ligand interactions, similar to cell–cell communication mediating , for example, antigen presentation 4. Alternatively, exosomes could putatively attach or fuse with the target-cell membrane, delivering exosomal surface proteins and perhaps cytoplasm to the recipient cell 10,11. Finally, exosomes may also be internalized by the recipient cells by mechanisms such as endocytosis 12. Exosomes were isolated from a mast-cell line (MC/9), primary bone marrow-derived mast cells (BMMC) and a human mast-cell line (HMC-1) through a series of microfiltration and ultracentrifugation steps modified from what has been previously described 4. To confirm that the structures studied indeed are exosomes, they were examined by electron microscopy (Fig. 1a), flow cytometric analysis (FACS; Fig. 1b), and proteomic analysis (see Supplementary Information, Table S1). The electron micrographs of the exosomes revealed rounded structures with a size of approximately 50–80 nm, similar to previously described exo-somes 4,13–15. The identity of the studied vesicles was further confirmed as exosomes by FACS analysis (Fig. 1b), which show the presence of the surface protein CD63 — a commonly used marker of exosomes. Finally, extensive protein analysis of the MC/9 exosomes was performed on multiple samples using LC-MS/MS technology. A total of 271 proteins were identified (see Supplementary Information, Table S1) from three preparations of the isolated vesicles, of which 47 proteins were present in all three samples. More importantly, a large number of the proteins found in the preparations were the same as proteins previously identified in exosomes produced by other cells (that is, exosomes derived from intestinal epithelial cells, urine, dendritic cells, microglia, melanoma, T-cells and B-cells). In particular, 60% of the 47 proteins found in all samples of mast-cell exosomes have been previously found in other types of exosomes. Moreover, 39% of the 271 total proteins found in the analysed exosome samples have also been previously found in other types of exosomes. Thus, the electron microscopy, the FACS, and the detailed protein analyses each provided significant evidence in favour of the identification of the isolated vesicles as exosomes. The presence of nucleic acids was examined in exosomes derived from MC/9, BMMC and HMC-1 cells to define a potential mechanism by which exosomes may mediate cell–cell communication. These assessments showed that isolated exosomes contain no DNA (see Supplementary Information, Fig. S1). However, substantial amounts of RNA were detected by agarose gel electrophoresis, spectrophotometry
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Breast cancer (BC) is the most common cancer type and the second cause of cancer-related death among women. Therefore, better understanding of breast cancer tumor biology and the identification of novel biomarkers is essential for the early diagnosis and for better disease stratification and management choices. Herein we developed a novel approach which relies on the isolation of circulating microRNAs through an enrichment step using speed-vacuum concentration which resulted in 5-fold increase in microRNA abundance. Global miRNA microarray expression profiling performed on individual samples from 23 BC and 9 normals identified 18 up-regulated miRNAs in BC patients (p(corr) < 0.05). Nine miRNAs (hsa-miR-4270, hsa-miR-1225-5p, hsa-miR-188-5p, hsa-miR-1202, hsa-miR-4281, hsa-miR-1207-5p, hsa-miR-642b-3p, hsa-miR-1290, and hsa-miR-3141) were subsequently validated using qRT-PCR in a cohort of 46 BC and 14 controls. The expression of those microRNAs was overall higher in patients with stage I, II, and III, compared to stage IV, with potential utilization for early detection. The expression of this microRNA panel was slightly higher in the HER2 and TN compared to patients with luminal subtype. Therefore, we developed a novel approach which led to the identification of a novel microRNA panel which was upregulated in BC patients with potential utilization in disease diagnosis and stratification.
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Although African-Americans (AAs) have a higher incidence of colorectal cancer (CRC) than White people, the underlying biochemical mechanisms for this increase are poorly understood. The current investigation was undertaken to examine whether differences in self-renewing cancer stem/stem-like cells (CSCs) in the colonic mucosa, whose stemness is regulated by certain microRNAs (miRs), could partly be responsible for the racial disparity in CRC. The study contains 53 AAs and 47 White people. We found the number of adenomas and the proportion of CD44(+) CD166(- ) CSC phenotype in the colon to be significantly higher in AAs than White people. MicroRNAs profile in CSC-enriched colonic mucosal cells, expressed as ratio of high-risk (≥3 adenomas) to low-risk (no adenoma) CRC patients revealed an 8-fold increase in miR-1207-5p in AAs, compared to a 1.2-fold increase of the same in White people. This increase in AA was associated with a marked rise in lncRNA PVT1 (plasmacytoma variant translocation 1), a host gene of miR-1207-5p. Forced expression of miR-1207-5p in normal human colonic epithelial cells HCoEpiC and CCD841 produced an increase in stemness, as evidenced by morphologically elongated epithelial mesenchymal transition( EMT) phenotype and significant increases in CSC markers (CD44, CD166, and CD133) as well as TGF-β, CTNNB1, MMP2, Slug, Snail, and Vimentin, and reduction in Twist and N-Cadherin. Our findings suggest that an increase in CSCs, specifically the CD44(+) CD166(-) phenotype in the colon could be a predisposing factor for the increased incidence of CRC among AAs. MicroRNA 1207-5p appears to play a crucial role in regulating stemness in colonic epithelial cells in AAs.
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Recent evidences indicate that circulating microRNAs (miRNAs) exhibit aberrant expression in the plasma of patients suffering from cancer compared to normal individuals, suggesting that it may be a useful noninvasion diagnostic method. MiR-21 plays crucial roles in carcinogenesis and can be served as a biomarker for the detection of various cancers. Therefore, the aim of this meta-analysis is to assess the potential role of miR-21 for digestive system cancer. By searching the PubMed, Embase, and Web of Science for publications concerning the diagnostic value of miR-21 for digestive system cancer, total of 23 publications were included in this meta-analysis. Receiver operating characteristic curves (ROC) were used to check the overall test performance. For prognostic meta-analysis, pooled hazard ratios (HRs) of circulating miR-21 for survival were calculated. Totally 23 eligible publications were included in this meta-analysis (15 articles for diagnosis and 8 articles for prognosis). For diagnostic meta-analysis, the summary estimates revealed that the pooled sensitivity and specificity were 0.76(95% CI = 0.70–0.82) and 0.84 (95% CI = 0.78–0.89). Besides, the area under the summary ROC curve (AUC) is 0.87. For prognostic meta-analysis, the pooled HR of higher miR-21 expression in circulation was 1.94 (95% CI = 0.99–3.82, P = 0.055), which indicated higher miR-21 expression could be likely to predict poorer survival in digestive system cancer. The subgroup analysis implied the higher expression of miR-21 was correlated with worse overall survival in the Asian population in digestive system cancer (HR = 2.41, 95% CI = 1.21–4.77, P = 0.012). The current evidence suggests circulating miR-21 may be suitable to be a diagnostic and prognostic biomarker for digestive system cancer in the Asians.
Background: Circulating RNA in plasma/serum is an emerging field for noninvasive molecular diagnosis. Because RNA is widely thought to be labile in the circulation, we investigated the stability and various preanalytical factors that may affect RNA concentrations in blood specimens. Methods: Blood samples were collected from 65 healthy volunteers. The effects of two preanalytical variables were studied: (a) time delay in processing of EDTA blood and clotted blood after venesection, and (b) freezing and thawing of plasma and serum. The lability of free added RNA in plasma was also investigated. Plasma/serum RNA was measured by a real-time quantitative reverse transcription-PCR assay for glyceraldehyde 3-phosphate dehydrogenase mRNA, whereas DNA was measured by a real-time quantitative PCR assay for the β-globin gene. Results: No significant difference was found for plasma RNA concentrations obtained from uncentrifuged EDTA blood that had been left at 4 °C for 0, 6, and 24 h (P =0.182). On the other hand, the serum RNA concentrations increased significantly over 24 h when uncentrifuged clotted blood was stored at 4 °C (P <0.05). In comparison, >99% of the free added RNA could no longer be amplified after incubation in plasma for 15 s. Never-frozen plasma, freeze-thawed plasma, and thawed plasma left at room temperature for 1 h showed no significant differences in RNA concentration (P =0.465). No significant difference was observed for freeze-thawed serum (P = 0.430). Conclusions: Plasma RNA is stable in uncentrifuged EDTA blood stored at 4 °C, but to obtain a stable serum RNA concentration, uncentrifuged clotted blood should be stored at 4 °C and processed within 6 h. A single freeze/thaw cycle produces no significant effect on the RNA concentration of plasma or serum.
Fatty acid synthase (FASN) has emerged as a unique oncologic target for the treatment of cancers, including hepatocellular carcinoma (HCC). However, effective inhibitors of FASN for cancer treatment are lacking. MicroRNAs (miRNAs) have emerged as novel and endogenic inhibitors of gene expression. In the present study, we aimed to investigate the role of miR‑1207‑5p in HCC and the regulation of FASN through miR‑1207‑5p. The expression of miR-1207-5p was markedly reduced in HCC tissues and cell lines as detected with real‑time quantitative polymerase chain reaction (qPCR). Overexpression of miR-1207-5p significantly suppressed the cell growth and invasion of HCC cells. By contrast, inhibition of miR‑1207‑5p exhibited an opposite effect. Bioinformatics analysis showed that FASN is a predicted target of miR‑1207‑5p which was validated by dual‑luciferase reporter assay, qPCR and western blot analysis. Overexpression of miR‑1207‑5p inhibited the Akt/mTOR signalling pathway, and promotion of this pathway was noted following inhibition of miR‑1207‑5p. Rescue experiments showed that the restoration of FASN expression partially reversed the inhibitory effect of miR‑1207‑5p on cell growth, invasion and Akt phosphorylation. In conclusion, our study suggests that miR‑1207‑5p/FASN plays an important role in HCC, and provides novel insight into developing new inhibitors for FASN for therapeutic interventions for HCC.
The expression and functions of microRNA (miR)-320 have been previously investigated in various types of cancer. However, to the best of our knowledge, no previous studies have investigated miR-320 in human lung cancer. The current study determined the expression, biological functions and molecular mechanisms of miR‑320 in human lung cancer. The expression level of miR‑320 in human non‑small cell lung cancer (NSCLC) and normal adjacent tissue samples (NATs), NSCLC cell lines and non‑tumorigenic bronchial epithelial cells was measured by reverse transcription‑quantitative polymerase chain reaction. Following transfection with miR‑320 mimics, 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide, cell migration and cell invasion assays, western blot analysis and luciferase assay were performed in human NSCLC cell lines. The results demonstrated that miR‑320 was significantly downregulated in NSCLC tissue samples and cell lines compared with NATs and a control cell line, respectively. Statistical analysis demonstrated that expression of miR‑320 was significantly associated with the TNM classification and metastasis. It was also observed that miR‑320 inhibited cell growth, migration and invasion in NSCLC cells. Additionally, the present study provided evidence that miR‑320 may directly target fatty acid synthase. These results suggest that miR‑320 may serve as a therapeutic biomarker of NSCLC in the future.
Objectives To evaluate and compare the ability of DW-MRI and CT to detect sites of peritoneal dissemination in gynecologic malignancies. The reproducibility of DW-MRI and CT interpretation between radiologists was also assessed. Methods Single institution prospective cohort study of women with suspected advanced gynecologic cancer who underwent surgical staging from 2010 to 2013. Participants underwent both DW-MRI and contrast-enhanced CT prior to surgery. Radiologists and surgeons were blinded, respectively, to surgical and DW-MRI results. The area under the receiver operator characteristic curve (AUC) was calculated for each disease site for CT and DW-MRI and compared to surgical findings. Kappa statistics quantified interobserver agreement between both radiologists. Results Twenty seven patients were enrolled. Mean age at surgery was 59 years. Ninety percent of participants had stage IIIC/IV disease. For right diaphragm disease, the AUC for DW-MRI was 0.95 compared to 0.81 for CT. For left diaphragm disease, the AUC was 0.89 for DW-MRI compared to 0.74 for CT. The AUC was similar for DW-MRI and CT for omental disease (0.79 versus 0.64); the liver surface (0.61 versus 0.67); bowel mesentery (0.73 versus 0.64); and cul de sac (0.75 versus 0.64). Interobserver agreement for DW-MRI was greater than CT for omental, Morrison's pouch, liver surface, and right diaphragm disease. Conclusions DW-MRI detects right diaphragmatic disease found at surgery with greater accuracy than CT. For other disease sites key to surgical planning, DW-MRI is equivalent to CT. Interobserver agreement was superior for a majority of disease sites evaluated by DW-MRI compared to CT.
Peritoneal spread of tumors is a major problem in cancer management. Patients develop a marked deterioration in quality of life and shortened survival. This is in part due to bowel obstructions, marked ascites, and overall increase debilitation. Standard medical management has shown to be inadequate for the treatment of these problems. Surgery can palliate symptoms, however, it is unable to be complete at the microscopic level by a significant spillage of tumor cells throughout the abdomen. Chemotherapy can have some improvement in symptoms however it is short lived due to poor penetration into the peritoneal cavity. The role of intraperitoneal chemotherapy is to maximize tumor penetration and optimize cell death while minimizing systemic toxicity. Hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC) are two treatment methods that serve this role and have been shown to improve survival. This review will discuss different chemotherapies used for both of these treatment options.
Since the benefit of prostate-specific antigen (PSA) screening remains controversial, new non-invasive biomarkers for prostate carcinoma (PCa) are still required. There is evidence that microRNAs (miRNAs) in whole peripheral blood can separate patients with localized prostate cancer from healthy individuals. However, the potential of blood-based miRNAs for the differential diagnosis of PCa and benign prostatic hyperplasia (BPH) has not been tested. We compared the miRNome from blood of PCa and BPH patients and further investigated the influence of the tumor volume, tumor-node-metastasis (TNM) classification, Gleason score, pretreatment risk status, and the pretreatment PSA value on the miRNA pattern. By microarray approach, we identified seven miRNAs that were significantly deregulated in PCa patients compared to BPH patients. Using quantitative real time PCR (qRT-PCR), we confirmed downregulation of hsa-miR-221* (now hsa-miR-221-5p) and hsa-miR-708* (now hsa-miR-708-3p) in PCa compared to BPH. Clinical parameters like PSA level, Gleason score, or TNM status seem to have only limited impact on the overall abundance of miRNAs in patients' blood, suggesting a no influence of these factors on the expression of deregulated miRNAs.