Clinical Effectiveness of Preoperative 18F-FDG PET/CT in Predicting Pathological Tumor Grade in Patients with Pseudomyxoma Peritonei Originating from Appendix: A Retrospective Cohort Study.

BACKGROUND: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the standard treatment for patients with pseudomyxoma peritonei (PMP). In some malignancies, the standard uptake value of positron emission tomography with 2-deoxy-2-18F-fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) is now accepted as a reliable indicator of neoplastic behavior. This study aimed to evaluate the association between the maximum standardized uptake value (SUVmax) and pathological grade in patients with PMP and to investigate the significance of SUVmax in the preoperative assessment of these patients. PATIENTS AND METHODS: In this retrospective single-center study, consecutively enrolled patients diagnosed with PMP of appendiceal origin underwent preoperative 18F-FDG PET/CT. SUVmax was calculated as the highest SUVmax value in the abdomen excluding the primary site. SUVmax was compared with the pathological grade (low or high grade) of PMP tumors according to the World Health Organization classification and further analyzed with respect to the estimated cutoff point, sensitivity, specificity, and receiver operating characteristic. RESULTS: In total, 160 patients were included. CRS was successfully performed in 93 patients and palliative debulking surgery in 67 patients. The pathological grade was high in 45 patients and low in 115. High-grade patients had a higher median SUVmax on 18F-FDG PET/CT than did low-grade patients (3.83 versus 2.34, p < 0.001). The highest area under the curve was 0.81, with a sensitivity of 77.8%, specificity of 72.3%, and cutoff point of 2.63. CONCLUSION: This study suggests that the SUVmax of preoperative 18F-FDG PET/CT is associated with the pathological grade in patients with PMP.

Genome-wide analysis of DNA methylation in pseudomyxoma peritonei originated from appendiceal neoplasms.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites produced by neoplasms in the abdominal cavity. Since the prognosis of patients with PMP remain unsatisfactory, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported. METHODS: To clarify the genetic background of the 15 PMP tumors, we performed genetic analysis using AmpliSeq Cancer HotSpot Panel v2. We further investigated global DNA methylation in the 15 tumors and eight non-cancerous colonic epithelial cells using Methylation EPIC array BeadChip (Infinium 850k) containing a total of 865,918 probes. RESULTS: This is the first report of comprehensive DNA methylation profiles of PMPs in the world. We clarified that the 15 PMPs could be classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME), and that genes associated with neuronal development and synaptic signaling may be involved in the development of PMPs. In addition, we identified a set of hypermethylation marker genes such as HOXD1 and TSPYL5 in the 15 PMPs. CONCLUSIONS: These findings may help the understanding of the molecular mechanism(s) of PMP and contribute to the development of therapeutic strategies for this life-threatening disease.

Intraperitoneal paclitaxel combined with FOLFOX/CAPOX plus bevacizumab for colorectal cancer with peritoneal carcinomatosis (the iPac-02 trial): study protocol of a single arm, multicenter, phase 2 study.

BACKGROUND: The safety of intraperitoneally administrated paclitaxel (op PTX) was demonstrated in the phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis. Moreover, the median survival time was 29.3 months, which was longer than that observed in previous studies. Here, we planned the phase II trial of ip PTX: the iPac-02 trial. METHODS: This multicenter, open-label, single assignment interventional clinical study includes patients with colorectal cancer with unresectable peritoneal carcinomatosis. FOLFOX-bevacizumab or CAPOX-bevacizumab is administered concomitantly as systemic chemotherapy. PTX 20 mg/m2 is administered weekly through the peritoneal access port in addition to these conventional systemic chemotherapies. The response rate is the primary endpoint. Progression-free survival, overall survival, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, safety, and response rate to peritoneal metastases are the secondary endpoints. A total of 38 patients are included in the study. In the interim analysis, the study will continue to the second stage if at least 4 of the first 14 patients respond to the study treatment. The study has been registered at the Japan Registry of Clinical Trials (jRCT2031220110). RESULTS: We previously conducted phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis [1]. In the study, three patients underwent mFOLFOX, bevacizumab, and weekly ip PTX, and the other three patients underwent CAPOX, bevacizumab, and weekly ip PTX treatment. The dose of PTX was 20 mg/m [2]. The primary endpoint was the safety of the chemotherapy, and secondary endpoints were response rate, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, progression-free survival, and overall survival. Dose limiting toxicity was not observed, and the adverse events of ip PTX combined with oxaliplatin-based systemic chemotherapy were similar to those described in previous studies using systemic chemotherapy alone [3, 4]. The response rate was 25%, peritoneal cancer index improvement rate was 50%, and cytology in peritoneal lavage turned negative in all the cases. The progression-free survival was 8.8 months (range, 6.8-12 months), and median survival time was 29.3 months [5], which was longer than that observed in previous studies. CONCLUSION: Here, we planned the phase II trial of ip paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: the iPac-02 trial.

Immunohistochemical staining as supportive diagnostic tool for pseudomyxoma peritonei arising from intraductal papillary mucinous neoplasm: A report of two cases and literature review.

BACKGROUND/OBJECTIVES: Pseudomyxoma peritonei (PMP) arising from an intraductal papillary mucinous neoplasm of the pancreas (IPMN) is a rare condition. The diagnosis of IPMN as the origin of PMP is mainly inferred from the clinical course and the exclusion of PMP from other organs. The pathological diagnosis has not yet been established. To evaluate the usefulness of immunohistochemical staining for the diagnosis of the primary lesion of PMP as IPMN. METHODS: There are 2 cases of PMP arising from IPMN between March 2010 and December 2019 at National Center for Global Health and Medicine. A PubMed search that reported PMP arising from IPMN identified 16 additional cases. Diagnostic methods and clinicopathological features of 18 cases were compared. RESULTS: Four cases including our two cases used immunohistochemical staining for the diagnosis of PMP arising from IPMN. The correspondence of the immunohistochemical staining between PMP and IPMN was shown in the three cases including previously reported two cases and one of our two cases to identify the primary lesion of PMP as IPMN. In addition, we revealed that the comparison of the immunostaining pattern of PMP with the representative immunostaining pattern of the candidate primary lesions is helpful for the diagnosis of the primary lesion of PMP. CONCLUSIONS: Immunohistochemical staining is helpful to identify the primary lesion of PMP as IPMN.

Pseudomyxoma peritonei: visceral scalloping on CT is a predictor of recurrence after complete cytoreductive surgery.

OBJECTIVES: Pseudomyxoma peritonei (PMP) is characterized by peritoneal dissemination of gelatinous ascites following rupture of a mucinous tumor. Treatment by cytoreductive surgery (CRS) has improved its prognosis. Although visceral scalloping, notably liver scalloping, on computed tomography (CT) is a typical feature of PMP, its prognostic value remains unknown. We aimed to investigate the efficacy of liver scalloping in predicting recurrence in PMP patients. METHODS: Among 159 consecutive patients with PMP who had contrast-enhanced CT between September 2012 and December 2018, 64 treatment-naïve patients who subsequently underwent CRS with complete resection (i.e., completeness of cytoreduction score (CC)-0 or CC-1), were included in analysis. Presence of liver scalloping and maximum thickness of mucin deposition at the liver surface were evaluated on CT. Disease-free survival (DFS) was determined based on the combination of postoperative CT features and tumor marker values. RESULTS: Median follow-up was 24.3 months. CT revealed liver scalloping in 40/64 (63.4%) patients. Kaplan-Meier analysis showed significantly shorter DFS in patients with scalloping than in those without (p = 0.001; hazard ratio, 4.3). In patients with scalloping, greater mucin deposition (thickness ≥ 20 mm) significantly correlated with poorer DFS (p = 0.042). In multivariate Cox proportional hazards regression including CC status, pathologic type, and tumor markers, the presence of scalloping independently and significantly correlated with DFS (p = 0.031). CONCLUSIONS: Liver scalloping was an independent predictor even after adjusting for clinical covariates. The presence of liver scalloping can lead to a high recurrence rate after CRS. KEY POINTS: • The presence of liver scalloping is a prognostic factor independent of histological grade and tumor markers. • Greater mucin deposition (thickness ≥ 20 mm at the liver surface) is associated with higher recurrence rates in patients with liver scalloping.

Development of an MSI-positive colon tumor with aberrant DNA methylation in a PPAP patient.

Polymerase proofreading-associated polyposis (PPAP) is a disease caused by germline variations in the POLE and POLD1 genes that encode catalytic subunits of DNA polymerases. Studies of cancer genomes have identified somatic mutations in these genes, suggesting the importance of polymerase proofreading of DNA replication in suppressing tumorigenesis. Here, we identified a germline frameshift variation in the POLE gene (c.4191_4192delCT, p.Tyr1398*) in a case with multiple adenomatous polyps and three synchronous colon cancers. Interestingly, one of the colon cancers showed microsatellite instability-high (MSI-H) and another microsatellite stable. Immunohistochemical staining revealed that the MSI-H tumor cells lost the expression of MLH1 protein. Whole genome sequencing of the MSI-H tumor did not find pathogenic somatic mutations in mismatch repair genes but found frameshift mutations in the TET genes that catalyze 5-methylcytosine hydroxylation. Bisulfite sequencing of the tumor corroborated an increase in the number of hypermethylated regions including the MLH1 promoter. These data indicate that PPAP patients might develop MSI-positive tumors through epigenetic silencing of MLH1. These findings will contribute to comprehensive understanding of the molecular basis of tumors that involve deficiency of proofreading activity of DNA polymerases.

Impact of a modified peritoneal cancer index using FDG-PET/CT (PET-PCI) in predicting tumor grade and progression-free survival in patients with pseudomyxoma peritonei.

OBJECTIVES: The peritoneal cancer index (PCI) is widely used for assessing pseudomyxoma peritonei (PMP) in surgery. The aim of this study was to evaluate the utility of a modified PCI using 18F-fluorodeoxyglucose (18F-FDG)-PET/CT (PET-PCI) for predicting pathologic grade and progression-free survival (PFS) in patients with PMP. METHODS: Thirty-five patients who underwent 18F-FDG-PET/CT before cytoreductive surgery and/or hyperthermic intraperitoneal chemotherapy were enrolled. PET-PCI was determined by summing up the visually scored 18F-FDG uptake of PMP lesions in 13 specific abdominal-pelvic regions. Uptake score was defined as 0, no lesion or lesion without uptake; 1, slight uptake less than or equivalent to mediastinal blood pool; 2, moderate uptake above mediastinal but below or equal to liver; and 3, intense uptake moderately to markedly higher than liver. SUVmax of the lesion was also evaluated. RESULTS: Pathologic diagnosis revealed 19 patients with low-grade PMP and 16 patients with high-grade PMP. Patients with high-grade PMP showed significantly higher PET-PCI and SUVmax than patients with low-grade PMP (PET-PCI 14.8 vs. 8.7, p = 0.007; SUVmax 3.6 vs. 2.6, p = 0.013). Using a cutoff PET-PCI of 12, Kaplan-Meier analyses showed a significant difference in PFS between patients with high and low PET-PCI (p < 0.001; hazard ratio (HR), 12.4). For SUVmax, the optimal cutoff was 2.7 and the correlation with PFS was also significant (p = 0.008; HR, 4.7). In multivariate Cox proportional-hazards regression, PET-PCI was independently and significantly correlated with PFS. CONCLUSIONS: PET-PCI can reflect histopathologic features and appears useful for predicting recurrence in patients with PMP. KEY POINTS: • Peritoneal cancer index using 18F-FDG-PET/CT (PET-PCI) has great potential for predicting progression-free survival in patients with pseudomyxoma peritonei. • PET-PCI provides higher prognostic performance than maximum standardized uptake value (SUVmax). • PET-PCI shows high correlation with histopathologic grade of pseudomyxoma peritonei.

Hepatectomy for metachronous colorectal liver metastases following complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases: a report of three cases.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis (PM) from colorectal cancer (CRC) has been reported to substantially improve the prognosis and the quality of life of patients in comparison to systemic chemotherapy or palliative approaches. This study aimed to demonstrate the safety and feasibility of hepatectomy for metachronous liver metastases from CRC following CRS and HIPEC for PM on the basis of three case reports. CASE PRESENTATION: We describe three cases involving patients who underwent hepatectomy for metachronous liver metastases from CRC after CRS and HIPEC for PM. All patients underwent CRS and HIPEC after primary tumor resection, and hepatectomy was performed for the metachronous liver metastases after CRS and HIPEC. The hepatectomy procedures for cases 1, 2, and 3 were left hemihepatectomy and partial resection of S5, posterior sectionectomy, and left-lateral sectionectomy and partial resection of S5 and S8, respectively. Although adhesion of surrounding organs to the liver surface was observed on a broad level, dissections and hepatectomy could be performed safely. No recurrence was detected in cases 1 and 2 after hepatectomy. In case 3, liver metastases were detected from the time of the initial diagnosis of the primary tumor, and complete remission was achieved once with systemic chemotherapy. Although we performed hepatectomy for the recurrence of liver metastases after complete remission, early re-recurrence was observed after hepatectomy. CONCLUSIONS: Hepatectomy for metachronous liver metastases after CRS and HIPEC for PM could be a multi-modality treatment option for CRC recurrence.

Pseudomyxoma peritonei of a mature ovarian teratoma caused by mismatch repair deficiency in a patient with Lynch syndrome: a case report.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease with an estimated incidence of 1-2 cases per million individuals per year. PMP is characterized by the accumulation of abundant mucinous or gelatinous fluid derived from disseminated tumorous cells. Most of the tumorous cells are originated from rupture of appendiceal neoplasms, but some are from the metastasis of cancer of the colon, ovary, fallopian tube, urachus, colorectum, gallbladder, stomach, pancreas, lung and breast. Although frequent mutations in KRAS and/or GNAS genes have been reported, precise molecular mechanism underlying PMP remains to be elucidated. It is of note that mucinous tumour is one of the frequent histological features of colorectal cancer (CRC) in Lynch syndrome (LS), an autosomal dominantly inherited disease caused by a germline mutation of the DNA mismatch repair (MMR) genes including human mutL homolog 1 (MLH1), human mutS homolog 2 (MSH2), human mutS homolog 6 (MSH6), and postmeiotic segregation increased 2 (PMS2). Therefore, typical LS-associated tumours show mismatch repair instability. Although LS patients are most strongly predisposed to CRC, PMPs from mucinous CRC have not been reported in LS patients. CASE PRESENTATION: In this report, we report a case of PMP originating from an ovarian teratoma in a LS patient. The patient had surgical treatment of PMP arising from an ovarian teratoma at the age of 38 years, and later developed a transverse colon cancer at the age of 40. The patient's family history fulfilled the Amsterdam criteria, and genetic analysis of the peripheral leukocytes identified a germ line mutation in the MLH1 gene (MLH1 c.1546dupC p.Q516PfsX3). Interestingly, immunohistochemical staining showed that the expression of MLH1 was lost in the colon cancer as well as the ovarian teratoma. Consistent with the loss of MLH1 expression, both tumours showed high microsatellite instability (MSI-H). CONCLUSION: This case suggested that LS patients may develop various types of tumours including ovarian PMP, and that mismatch repair deficiency may play a role in the development of PMP derived from, at least, a part of ovarian teratomas.

A case of pseudomyxoma peritonei arising from a perforated intraductal papillary mucinous neoplasm that underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Pseudomyxoma peritonei (PMP) of pancreatic origin arising from an intraductal papillary mucinous neoplasm (IPMN) is rare. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established as the optimal treatment for PMP. However, the benefits and safety of CRS with HIPEC for treating PMP of pancreatic origin remain unclear. Herein, we describe a case of PMP of pancreatic origin that was treated with CRS and HIPEC without postoperative complications. A 75-year-old woman was referred to our department. Computed tomography (CT) revealed a multilocular cystic tumor in the pancreatic tail, notable mucinous ascites in the abdominal cavity, and scalloping of the liver and spleen. CT did not reveal the appendix, and the ovaries were normal in size. The patient was diagnosed with PMP of pancreatic origin, and CRS and HIPEC were performed. Intraoperatively, the pancreatic tumor was perforated, and there was a large amount of mucinous ascites. We performed distal pancreatectomy in addition to CRS and HIPEC, with no intraoperative complications. The postoperative course was uneventful, and the patient survived after 6 months without recurrence. CRS with HIPEC may be a feasible treatment option for PMP of pancreatic origin.

Single-incision laparoscopic surgery for benign multicystic mesothelioma of the peritoneum in a young man: A case report.

Benign multicystic peritoneal mesothelioma (BMPM) is a rare condition, particularly in men, and the preoperative diagnosis poses a challenge. Here, we present a case involving single-incision laparoscopic surgery (SILS) for BMPM in a 24-year-old man with a pelvic mass and a history of ulcerative colitis. Pelvic imaging revealed multifocal cysts, prompting the performance of SILS. The tumor was successfully resected with no residual lesions, and pathology confirmed the diagnosis of BMPM. This case represents the first documented instance of SILS being employed for BMPM in a man. BMPM, characterized by pelvic multifocal cysts, is a differential diagnosis, and SILS emerges as a viable option for both diagnosis and treatment.

Usefulness of real-time navigation using intraoperative ultrasonography for rectal cancer resection.

INTRODUCTION: At our institute, we usually perform robot-assisted surgery for rectal cancer as minimally invasive surgery. It is necessary to recognize the tumor edge accurately when deciding where to place the distal cutting line of the rectum. In this article, with video presentation, we demonstrate the usefulness of intraoperative sonography (IOUS) for detecting the rectal tumor site in robotic surgery. This is the first report to discuss the IOUS image of rectal cancer. MATERIALS AND SURGICAL TECHNIQUE: After mobilization of the rectum in robotic procedure, the rectum should be straightened. Drop the laparoscopic ultrasonography probe through the 12-mm assistant port and place it at the anterior wall of the rectum. By presenting operative and ultrasound findings simultaneously on a single monitor, the operator can recognize the tumor location accurately and decide on the cutting line. We report three cases in the supporting video presentation. DISCUSSION: Rectal tumors can be detected by IOUS, and this modality is effective for determining the cutting line of the rectum. Real-time navigation by IOUS can be performed noninvasively and easily, so it is expected to be helpful in cases of robotic rectal cancer resection.

Association of intraoperative gross hematuria with acute kidney injury after cytoreductive surgery.

Objectives: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has been established in the management of peritoneal carcinomatosis. Although it is still necessary to take adequate measures against major postoperative complications including acute kidney injury (AKI), consensus is lacking on how to assess and stratify risk for patients with postoperative AKI after CRS-HIPEC. The aim of this retrospective cohort study was to investigate the association of intraoperative gross hematuria as a surrogate marker of ureter injury with postoperative AKI incidence. Methods: This retrospective cohort study investigated patients without impaired preoperative kidney function who underwent CRS-HIPEC at a single referral center, and evaluated the relationship between intraoperative gross hematuria and incidence of postoperative AKI as defined by the Kidney Disease Improving Global Outcomes practice guidelines. Logistic regression analysis was performed to calculate the odds ratio of intraoperative gross hematuria for AKI, adjusting for confounding factors and other risk factors for AKI. Results: We enrolled 185 patients (males, 37%). Twenty-five patients developed intraoperative gross hematuria. Postoperative AKI occurred in 10 (40%) of 25 patients with hematuria and 28 (17.5%) of 160 patients without hematuria. The crude odds ratio for exposure to hematuria was 3.14 (95% confidence interval, 1.30-7.60; p=0.020) for postoperative AKI. Adjusted odds ratio as estimated by multivariate logistic regression was 4.57 (95% confidence interval, 1.55-13.45; p=0.006). Conclusions: Intraoperative gross hematuria is significantly associated with postoperative AKI incidence after CRS-HIPEC.

A case of pseudomyxoma peritonei successfully treated with trifluridine/tipiracil (TAS-102) and bevacizumab after palliative debulking surgery.

Pseudomyxoma peritonei is a rare disease with a reported prevalence of about 1-3 per million people annually. Cytoreductive surgery and perioperative hyperthermic intraperitoneal chemotherapy are considered as treatment options improving disease control or long-term survival. However, for patients with incomplete cytoreduction or debulking surgery, outcomes are significantly poorer compared with patients who have obtained complete or optimal cytoreduction. In cases of high-grade pseudomyxoma peritonei that are considered inoperable and/or unresectable, combination chemotherapy regimen with a neo-angiogenesis inhibitor such as bevacizumab is recommended. In this report, a 62-year-old Japanese man presented with abdominal distention. Examination of ascites demonstrated a jelly-like consistency and peritoneal pseudomyxoma was suspected. To relieve progressive symptoms, palliative debulking surgery with total colectomy was performed. Postoperative pathology confirmed high-grade appendiceal mucinous neoplasm with high-grade pseudomyxoma peritonei. In our case, combination chemotherapy with trifluridine/tipiracil (TAS-102) and bevacizumab was initiated after palliative debulking surgery. As a result, carcinoembryonic antigen level was kept stable and the volume of ascites remained almost the same as at the beginning of treatment for more than 2 years. In conclusion, combination chemotherapy comprising TAS-102 and bevacizumab in patients with palliative debulking could be a useful option for patients with high-grade mucinous appendiceal neoplasm and high-grade pseudomyxoma peritonei.

The primary tumor location in colorectal cancer: A focused review on its impact on surgical management.

The primary tumor location (PTL) has attracted increasing attention in recent years for colorectal cancer (CRC) patients. Although the underlying mechanisms for differences caused by PTL remain still unclear, right-sided colon (RCC) and left-sided colon (LCC) are now considered as distinct entities because of their different molecular profile and clinical response to surgery and chemotherapy. In this article, we review the influence of PTL particularly on surgical management of primary and metastatic CRC settings. For nonmetastatic CRC, RCC could be a slightly superior prognostic factor after curative resection in stage I-II CRC, while RCC could be an inferior prognostic factor in stage III CRC with worse survival after recurrence, suggesting the oncological aggressiveness of recurrent RCC. For metastatic CRC, RCC could be a predictor of worse survival after hepatectomy of liver metastases from CRC with aggressive recurrence pattern and lower chance of re-resection. In lung metastases from CRC, the role of PTL still remains uncertain because of the limited number of studies. As to the impact of PTL on survival outcome after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for peritoneal metastases from CRC, a discrepancy exists among studies and further investigation will be needed. The very simple clinical factor of PTL could provide important information for the prediction of the survival outcome after surgery in CRC. Further clinical and basic research will facilitate the clinical application of PTL in a more specified and personalized manner.

Prognostic value of 18F-FDG PET/CT with texture analysis in patients with rectal cancer treated by surgery.

PURPOSE: The aim of this study was to evaluate the ability of texture analysis using pretreatment 18F-FDG PET/CT to predict prognosis in patients with surgically treated rectal cancer. METHODS: We analyzed 94 patients with pathologically proven rectal cancer who underwent pretreatment 18F-FDG PET/CT and were subsequently treated with surgery. The volume of interest of the primary tumor was defined using a threshold of 40% of the maximum standardized uptake value (SUVmax), and conventional (SUVmax, metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and textural PET features were extracted. Harmonization of PET features was performed with the ComBat method. The study endpoints were overall survival (OS) and progression-free survival (PFS), and the prognostic value of PET features was evaluated by Cox regression analysis. RESULTS: In the follow-up period (median 41.7 [interquartile range, 30.5-60.4] months), 21 (22.3%) and 30 (31.9%) patients had cancer-related death or disease progression, respectively. Univariate analysis revealed a significant association of (1) MTV, TLG, and gray-level co-occurrence matrix (GLCM) entropy with OS; and (2) SUVmax, MTV, TLG, and GLCM entropy with PFS. In multivariate analysis including clinical characteristics, GLCM entropy (≥ 2.13) was the only relevant prognostic PET feature for poor OS (hazard ratio [HR]: 4.16, p = 0.035) and PFS (HR: 2.70, p = 0.046). CONCLUSION: GLCM entropy, which indicates metabolic intratumoral heterogeneity, was an independent prognostic factor in patients with surgically treated rectal cancer. Compared with conventional PET features, GLCM entropy has better predictive value and shows potential to facilitate precision medicine.

Diagnostic performance of 18F-FDG PET/CT using point spread function reconstruction on initial staging of rectal cancer: a comparison study with conventional PET/CT and pelvic MRI.

BACKGROUND: Accurate staging is crucial for treatment selection and prognosis prediction in patients with rectal cancer. Point spread function (PSF) reconstruction can improve spatial resolution and signal-to-noise ratio of PET imaging. The aim of this study was to evaluate the effectiveness of 18F-FDG PET/CT with PSF reconstruction for initial staging in rectal cancer compared with conventional PET/CT and pelvic MRI. METHODS: A total of 59 patients with rectal cancer underwent preoperative 18F-FDG PET/CT and pelvic MRI. The maximum standardized uptake value (SUVmax) and lesion to background (L/B) ratio of possible metastatic lymph nodes, and metabolic tumor volumes (MTVs) of primary tumors were calculated. For N and T (T1-2 vs T3-4) staging, sensitivities, specificities, positive predictive values, negative predictive values, and accuracies were compared between conventional PET/CT [reconstructed with ordered subset expectation maximization (OSEM)], PSF-PET/CT (reconstructed with OSEM+PSF), and pelvic MRI. Histopathologic analysis was the reference standard. RESULTS: For N staging, PSF-PET/CT provided higher sensitivity (78.6%) than conventional PET/CT (64.3%), and pelvic MRI (57.1%), and all techniques showed high specificity (PSF-PET: 95.4%, conventional PET: 96.7%, pelvic MRI: 93.5%). SUVmax and L/B ratio were significantly higher in PSF-PET/CT than conventional-PET/CT (p < 0.001). The accuracy for T staging in PSF-PET/CT (69.4%) was not significantly different to conventional PET/CT (73.5%) and pelvic MRI (73.5%). MTVs of PSF and conventional PET showed a significant difference among T stages (p < 0.001), with higher values in advanced stages. In M staging, both PSF and conventional PET/CT diagnosed all distant metastases correctly. CONCLUSIONS: PSF-PET/CT produced images with higher lesion-to-background contrast than conventional PET/CT, which allowed improved detection of lymph node metastasis without compromising specificity, and showed comparable diagnostic value to MRI in local staging. PSF-PET/CT is likely to have a great value for initial staging in rectal cancer.

Molecular profiles of high-grade and low-grade pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare disease exhibiting a distinct clinical feature caused by cancerous cells that produce mucinous fluid in the abdominal cavity. PMPs originate most frequently from the appendix and less frequently from the ovary. This disease can range from benign to malignant, and histologically, PMP is classified into two types: disseminated peritoneal adenomucinosis (DPAM) representing the milder phenotype, and peritoneal mucinous adenocarcinomas (PMCA) representing the aggressive phenotype. Although histological classification is clinically useful, the pathogenesis of PMP remains largely unknown. To elucidate the molecular mechanisms underlying PMP, we analyzed 18 PMP tumors comprising 10 DPAMs and 8 PMCAs. DNA was extracted from tumor and matched non-tumorous tissues, and was sequenced using Ion AmpliSeq Cancer Panel containing 50 cancer-related genes. Analysis of the data identified a total of 35 somatic mutations in 10 genes, and all mutations were judged as pathological mutations. Mutations were frequently identified in KRAS (14/18) and GNAS (8/18). Interestingly, TP53 mutations were found in three of the eight PMCAs, but not in the DPAMs. PIK3CA and AKT1 mutations were also identified in two PMCAs, but not in the DPAMs. These results suggested that KRAS and/or GNAS mutations are common genetic features of PMP, and that mutations in TP53 and/or genes related to the PI3K-AKT pathway may render malignant properties to PMP. These findings may be useful for the understanding of tumor characteristics, and facilitate the development of therapeutic strategies.