Missed Pancreaticobiliary Malignancy: The Flaw of the Expedited Cholecystectomy

Background: Early cholecystectomy has been recommended for patients with acute cholecystitis and gallstone pancreatitis. However, patients with pancreaticobiliary malignancy may present acutely with similar symptoms. We hypothesize that the diagnoses of these malignancies may potentially be delayed as an unintended consequence of expedited cholecystectomies. This study reviews a cohort of patients who underwent pancreaticoduodenectomy (PD) to identify those who underwent a separate cholecystectomy before their PD. Methods: We retrospectively reviewed 162 PDs performed between 2012 and 2022. Data collected included: demographics, disease etiology and the presence of cholelithiasis. We identified patients who had a previous cholecystectomy and the time elapsed before PD as well as procedures done during the interval. We reported detailed case summaries on those patients who had a cholecystectomy within 1 year of PD. Results: In the entire cohort, mean age was 65 years, 54% were males, and 83% had a malignant reason for PD. Thirty-one patients had cholelithiasis with 23 (14%) patients having had previous cholecystectomy. Six patients had cholecystectomy within 1 year of PD. They had the following malignancies: ampullary—3, pancreas—1, cholangiocarcinoma—1 and neuroendocrine—1. Four of these patients had expedited cholecystectomy on their index hospital admission and were later found to have a periampullary malignancy with further work up. Conclusions: Pancreaticobiliary malignancies can be difficult to diagnose, and surgeons should not overlook these potential diagnoses when considering expedited cholecystectomy. Future studies in large cohorts are needed to identify high risk candidates who should undergo more detailed testing to exclude malignancy before proceeding with cholecystectomy.

Clinicopathological analysis of small intestinal metastasis from extra-abdominal/extra-pelvic malignancy

BACKGROUND The metastatic tumors in the small intestine secondary to extra-abdominal/extrapelvic malignancy are extremely rare.However,the small intestine metastases are extremely prone to misdiagnosis and missed diagnosis due to the lack of specific clinical manifestations and examination methods,thus delaying its treatment.Therefore,in order to improve clinical diagnosis and treatment capabilities,it is necessary to summarize its clinical pathological characteristics and prognosis.AIM To summarize the clinicopathological characteristics of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy,and to improve the clinical capability of diagnosis and treatment for rare metastatic tumors in the small intestine.METHODS The clinical data of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy were retrieved and summarized,who admitted to and treated in the Air Force Medical Center,Chinese People’s Liberation Army.Then descriptive statistics were performed on the general conditions,primary tumors,secondary tumors in the small intestine,diagnosis and treatment processes,and prognosis.RESULTS Totally 11 patients(9 males and 2 females)were enrolled in this study,including 8 cases(72.3%)of primary lung cancer,1 case(9.1%)of malignant lymphoma of the thyroid,1 case(9.1%)of cutaneous malignant melanoma,and 1 case(9.1%)of testicular cancer.The median age at the diagnosis of primary tumors was 57.9 years old,the median age at the diagnosis of metastatic tumors in the small intestine was 58.81 years old,and the average duration from initial diagnosis of primary tumors to definite diagnosis of small intestinal metastases was 9 months(0-36 months).Moreover,small intestinal metastases was identified at the diagnosis of primary tumors in 4 cases.The small intestinal metastases were distributed in the jejunum and ileum,with such clinical manifestations as hematochezia(5,45.4%)and abdominal pain,vomiting and other obstruction(4,36.4%).In addition,2 patients had no obvious symptoms at the diagnosis of small intestinal metastases,and 5 patients underwent radical resection of small intestinal malignancies and recovered well after surgery.A total of 3 patients did not receive subsequent treatment due to advanced conditions.CONCLUSION Small intestinal metastases of extra-abdominal/extra-pelvic malignancy is rare with high malignancy and great difficulty in diagnosis and treatment.Clinically,patients with extra-abdominal/extra-pelvic malignancy should be alert to the occurrence of this disease,and their prognosis may be improved through active surgery combined with standard targeted therapy.

Risk of hepatic decompensation from hepatitis B virus reactivation in hematological malignancy treatments

In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton’s tyrosine kinase(BTK)inhibitor therapy.First of all,we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response,focusing our attention on the protective role of anti-HBs.We then carefully analyzed literature data on the risk of HBV reactivation(HBVr)in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies.Based on literature data,we suggested that several factors may contribute to the different risks of HBVr:The type of hematologic malignancy;the type of therapy(BTK inhibitors,especially second-generation,seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors);previous exposure to an anti-CD20 as first-line therapy;and ethnicity and HBV genotype.Therefore,the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.

Investigation on quality of life of hospitalized patients in China with digestive system malignancy

Background: The purpose of this study is to evaluate the quality of life(QoL) of hospitalized patients in China suffering from digestive system malignancies and to identify potential risk factors for a decrease in QoL.Methods: The European Organization for Research and Treatment Core Quality of Life questionnaire(EORTC QLQ-C30) was applied to evaluate the QoL of 23,519 patients with six digestive malignancies(esophageal cancer, gastric cancer, colorectal cancer, liver cancer, biliary tract cancer, and pancreatic cancer). A t test or analysis of variance was employed to analyze the total EORTC QLQ-C30 scale scores and domain scores of the EORTC QLQ-C30 scale among patients in different subgroups.Results: The average QoL score was 50.4 ± 10.8. The tumor type, age, sex, and TNM stage al had an impact on QoL ratings. Colorectal cancer patients had a better total QoL score(49.3 ± 10.3) and scores in the domains of functioning, with milder symptoms, except for diarrhea. Patients with biliary tract cancer(54.2 ± 12.3) and pancreatic cancer(54.2 ± 12.3) reported a poorer QoL, significant functional impairment, and more pronounced symptoms. Patients with esophageal cancer experienced the most severe financial difficulties(35.2 ± 27.5). Patients aged ≥65 years, women, and those with TNM stage Ⅲ/Ⅳ reported lower QoL. In addition, the disparities in total QoL scores and scores in specific domains were significant among patients with some types of tumors, and based on ethnicity, educational level, occupation, treatment(s) received, and place of residence.Conclusions: There is a need to focus on elderly individuals, those with low educational levels, and patients with progressive malignant tumors and to improve routine disease monitoring and symptom management to enhance the quality of life for patients with malignancies of the digestive system.

Clinical Course Of Patients with Small Cell Lung Cancer As Second Primary Malignancy

Objective： To evaluate the clinical course of patients with small cell lung cancer （SCLC） as second primary malignancy. Methods： Among the 355 patients diagnosed with SCLC at Helen and Harry Gray Cancer Center of Hartford Hospital Connecticut USA between 1988 and 1998, the records of 48 patients, which had been diagnosed with other malignancies before their diagnosis of SCLC, were retro- spectively reviewed. Results： Forty-eight patients （13.5%） were diagnosed with other malignancies prior to their SCLC among which 43 had documented smoking history and 93% of them （40/43） were current/former smokers. Of the 28-second primary SCLC patients who were treated with standard method, 11 （39.3%） achieved CR. 12 （42.8%） achieved PR, and the RR was 82.1%. The median survival of the 28 treated with standard method was 11.3 months （5.1-77.7 months）, while that of the rest 19 untreated patients （1 of 20 was lost to follow-up） was only 2.0 months （0.5 34.0 months）. There was no significant difference in the median survival and RR between 165 treated first primary SCLC （13.5 months and 77.6% respectively） and 28 treated secondary primary SCLC （11.3 months and 82.1% respectively） （P〉0.05）. The patients who had prostate cancer were older and subjected to less treatments than those with skin cancer, so their survival was shorter than the latter （3.5 months vs. 15 months, P〈0.05）. Conclusion： The response and survival of the treated patients with SCLC as a second malignancy showed no difference as compared to the treated ones with SCLC only. Therefore, an active medical treatment is important to relieve symptom and prolong survival of the second primary SCLC patients.

Post-transplant malignancy:Focusing on virus-associated etiologies,pathogenesis,evidence-based management algorithms,present status of adoptive immunotherapy and future directions

Modern immunosuppression has led to a decrease in rejection rates and improved survival rates after solid organ transplantation.Increasing the potency of immunosuppression promotes post-transplant viral infections and associated cancers by impairing immune response against viruses and cancer immunoediting.This review reflects the magnitude,etiology and immunological characteristics of various virus-related post-transplant malignancies,emphasizing the need for future research.A multidisciplinary and strategic approach may serve best but overall literature evidence targeting it is sparse.However,the authors attempted to provide a more detailed update of the literature consensus for the prevention,diagnosis,management and surveillance of post-transplant viral infections and associated malignancies,with a focus on the current role of adoptive immunotherapy and the way forward.In order to achieve long-term patient and graft survival as well as superior post-transplant outcomes,collaborative research on holistic care of organ recipients is imperative.

Adjusting CA19-9 values to predict malignancy in obstructive jaundice:Influence of bilirubin and C-reactive protein

AIM:To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice(BJ) and malignant jaundice(MJ).METHODS:All patients admitted for obstructive jaundice,in the period 2005-2009,were prospectively enrolled in the study,obtaining a total of 102 patients.On admission,all patients underwent complete standard blood test examinations including C-reactive protein(CRP),bilirubin,CA19-9.Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels(total bilirubin > 2.0 mg/dL).The standard cut-off level for CA19-9 was 32 U/mL,whereas for CRP this was 1.5 mg/L.The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value.The patients were divided into 2 groups,MJ and BJ,and after the adjustment a comparison between the 2 groups of patients was performed.Sensitivity,specificity and positive predictive values were calculated before and after the adjustment.RESULTS:Of the 102 patients,51 were affected by BJ and 51 by MJ.Pathologic CA19-9 levels were found in 71.7% of the patients.In the group of 51 BJ patients there were 29(56.9%) males and 22(43.1%) females with a median age of 66 years(range 24-96 years),whereas in the MJ group there were 24(47%) males and 27(53%) females,with a mean age of 70 years(range 30-92 years).Pathologic CA19-9 serum level was found in 82.3% of MJ.CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ.Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ(P = 0.000 and P = 0.02),while the CRP level was significantly higher in BJ(P = 0.000).Considering a CA19-9 cut-off level of 32 U/mL,82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9(P = 0.002).A CA19-9 cut-off of 100 U/mL increases the difference between the two groups:35.3% in BJ and 68.6% in MJ(P = 0.0007).Adjusting the CA19-9 value by dividing it by serum bilirubin level meant that 21.5% in the BJ and 49% in the MJ group remained with a positive CA19-9 value(P = 0.003),while adjusting the CA19-9 value by dividing it by serum CRP value meant that 31.4% in the BJ group and 76.5% in the MJ group still had a positive CA19-9 value(P = 0.000004).Sensitivity,specificity,positive predictive values of CA19-9 > 32 U/mL were 82.3%,45% and 59.1%;when the cutoff was CA19-9 > 100 U/mL they were,respectively,68.6%,64.7% and 66%.When the CA19-9 value was adjusted by dividing it by the bilirubin or CRP values,these became 49%,78.4%,69.4% and 76.5%,68.6%,70.9%,respectively.CONCLUSION:The present study proposes CRP as a new and useful correction factor to improve the diag-nostic value of the CA19-9 tumor marker in patients with cholestatic jaundice.

Prediction of malignancy and adverse outcome of solid pseudopapillary tumor of the pancreas

Since solid pseudopapillary tumor of the pancreas(SP-TP) was officially classified by the World Health Org-anization in 1996,SPTP has recently received special attention in the literature.Studies have shown that SPTP is a heterogeneous tumor,with a small percentage of patients harboring aggressive behaviors.However,cri-teria for malignancy grade in SPTP have not been well established.The prognosis of SPTP is generally good,with cases having a chance for long-term survival even with recurrence and/or metastasis after surgical resection.The current American Joint Committee on Cancer/Union for International Cancer Control tumor,node,metastasis staging system is not specific to SPTP.The lack of a pre-dictive staging classification that accurately describes the heterogeneity of this disease hinders meaningful research into optimal individualized therapy.Here we summarize and discuss the associated factors proposed for appraisal of the malignant potential and adverse outcome of SPTP.

Quadruple primary malignancy patient with survival time more than 20 years

Multiple primary carcinoma (MPC) is defined as two or more carcinomas without subordinate relationship detected in the same or other organs of an individual patient. The diagnosis of MPC must comply with the following standards: each of the tumors must present a definite picture of malignancy, each tumor must be histologically distinct, and the probability of one being a metastasis of the other must be excluded. MPC often occurs in the digestive system, but its pathogenesis remains unclear involving genetic susceptibility, tumor immunity and iatrogenic factors, including radiotherapy and chemotherapy. Most MPC patients are double primary malignancy; the occurrence of quadruple primary malignancy is below 0.1%. Here we present a rare case of quadruple primary malignancy involving the small intestine, descending colon, renal pelvis and pancreas. Due to its rarity, the relevant literature is also reviewed. In general, the incidence of MPC is rising, so prevention, early diagnosis and treatment will become necessary and important. Therefore, further research should focus on the etiology and mechanism of MPC.

Portal vein thrombosis: Etiology and clinical outcome of cirrhosis and malignancy-related non-cirrhotic, non-tumoral extrahepatic portal venous obstruction

The etiology and pathogenesis of portal vein thrombosis are unclear. Portal venous thrombosis presentation differs in cirrhotic and tumor-related versus non-cirrhotic and non-tumoral extrahepatic portal venous obstruction (EHPVO). Non-cirrhotic and non-tumoral EHPVO patients are young and present with well tolerated bleeding. Cirrhosis and tumor-related portal vein thrombosis patients are older and have a grim prognosis. Among the 118 patients with portal vein thrombosis, 15.3% had cirrhosis, 42.4% had liver malignancy (primary or metastatic), 6% had pancreatitis (acute or chronic), 5% had hypercoagulable state and 31.3% had idiopathy, 12% had hypercoagulable state in the EHPVO group.

Laparoscopic liver resection for malignancy:A review of the literature

AIM: To review the published literature about laparoscopic liver resection for malignancy.

Role of microRNA-7 in digestive system malignancy

There are several malignancies of the digestive system(including gastric, pancreatic and colorectal cancers, and hepatocellular carcinoma), which are the most common types of cancer and a major cause of death worldwide. MicroRNA(miR)-7 is abundant in the pancreas, playing an important role in pancreatic development and endocrine function. Expression of miR-7 is downregulated in digestive system malignancies compared with normal tissue. Although there are contrasting results for miR-7 expression, almost all research reveals that miR-7 is a tumor suppressor, by targeting various genes in specific pathways. Moreover, miR-7 can target different genes simultaneously in different malignancies of the digestive system. By acting on many cytokines, miR-7 is also involved in many gastrointestinal inflammatory diseases as a significant carcinogenic factor. Consequently, miR-7 might be a biomarker or therapeutic target gene in digestive system malignancies.

Risk of malignancy in Caroli disease and syndrome: A systematic review

BACKGROUND Congenital intrahepatic bile duct dilatation without fibrosis is called Caroli disease(CD),and is called Caroli syndrome(CS)when it has fibrotic and cirrhotic liver morphology.The development of intrahepatic carcinoma is described in both conditions,but the reported incidence varies extensively.Potential risk factors for the malignant transformation were not described.Furthermore,conservative or surgical treatment is performed depending on the extent of cystic malformation,hepatic dysfunction and structural hepatic changes,but little is known about which treatment should be offered to patients with CD or CS and cancer.AIM To further investigate the malignant transformation in these conditions.METHODS A systematic review of the current literature until January 2019 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.A search using Medline(PubMed)was performed using a combination of Medical Subject Headings terms“caroli disease”,“caroli syndrome”,“tumor”,“malignant”,and“cholangiocarcinoma”.Only human studies published in English were used for this systematic review.The following parameters were extracted from each article:year of publication,type of study,number of patients,incidence of malignant tumor,duration of symptoms,age,sex,diagnostics,identification of tumor,surgical therapy,survival and tumor recurrence.RESULTS Twelve retrospective studies reporting the courses of 561 patients(53%females)were included in this systematic review.With a mean age of 41.6 years old(range 23 to 56 years old),patients were younger than other populations undergoing liver surgery.Depending on the size of the study population the incidence of cholangiocarcinoma varied from 2.7%to 37.5%with an overall incidence of 6.6%.There were only few detailed reports about preoperative diagnostic work-up,but a multimodal work-up including ultrasound of the liver,computed tomography,magnetic resonance imaging and endoscopic retrograde cholangiopancreatography was used in most studies.Disease duration was variable with up to several years.Most patients had episodes of cholangitis,sepsis,fever or abdominal pain.Tumor detection was an incidental finding of the surgical specimen in most cases because it is currently often impossible to detect tumor manifestation during preoperative diagnostics.Liver resection or liver transplantation was performed depending on the extent of the biliary pathology and additional alterations of the liver structure or function.No postoperative adjuvant chemotherapy was reported,but chemotherapy was administered in selected cases of tumor recurrence.Overall survival rates after one year were low at 36%and a high recurrence rate of up to 75%during the observation period.CONCLUSION Only few retrospective studies reported a low tumor incidence.Despite the high rate of mortality and tumor recurrence,definite surgical treatment should be offered as soon as possible.

Peutz-Jeghers syndrome with small intestinal malignancy and cervical carcinoma

We report a case of 30-year-old woman with Peutz- Jeghers syndrome (PJS). Because of small intestinal obstruction, she received the small intestinal polypectomy in 2001, and the pathological diagnosis was Peutz-Jeghers polyp canceration (mucinous adenocarcinoma, infiltrating full-thickness of the intestine). The patient did not feel uncomfortable after 6 mo of chemotherapy and other management. We kept a follow-up study on her and found that she suffered from cervical cancer in 2007, with a pathological diagnosis of cervical adenosquamous carcinoma.The patient presented with typical features of PJS, but without a family history. The PJS accompanied with both small intestinal and cervical malignancies has not been reported so far in the world.

Predictors of malignancy in chronic calcific pancreatitis with head mass

AIM: To prospectively analyse the clinical, biochemical and radiological characteristics of the mass lesions arising in a background of chronic calcific pancreatitis (CCP). METHODS: Eighty three patients, who presented with chronic pancreatitis (CP) and a mass lesion in the head of pancreas between February 2005 and December 2011, were included in the study. Patients who were identified to have malignancy underwent Whipple' s procedure and patients whose investigations were suggestive of a benign lesion underwent Frey's procedure. Student t-test was used to compare the mean values of imaging findings [common bile duct (CBD), main pancreatic duct (MPD) size] and laboratory data [Serum bilirubin, carbohydrate antigen 19-9 (CA 19-9)] between the groups. Receiver operating characteristic curve (ROC curve) analysis was done to calculate the cutoff valves of serum bilirubin, CA 19-9, MPD and CBD size. The sensitivity, specificity, positive predictive valve (PPV) and negative predictive value (NPV) were calculated using these cut off points. Multivariate analysis was performed using logistic regression model. RESULTS: The study included 56 men (67.5%) and 27 women (32.5%). Sixty (72.3%) patients had tropical calcific pancreatitis and 23 (27.7%) had alcohol related CCP. Histologically, it was confirmed that 55 (66.3%) of the 83 patients had an inflammatory head mass and 28 (33.7%) had a malignant head mass. The mean age of individuals with benign inflammatory mass and those with malignant mass was 38.4 years and 45 years respectively. Significant clinical features that predicted a malignant head mass in CP were presence of a head mass in CCP of tropics, old age, jaundice, sudden worsening abdominal pain, gastric outlet obstruction and significant weight loss (P ≤ 0.05). The ROC curve analysis showed a cut off value of 5.8 mg/dL for serum bilirubin, 127 U/mL for CA 19-9, 11.5 mm for MPD size and 14.5 mm for CBD size. CONCLUSION: Elevated Serum bilirubin and CA 19-9, and dilated MPD and CBD were useful in predicting malignancy in patients with CCP and head mass.

Second primary malignancy risk after radiotherapy in rectal cancer survivors

AIM To investigate second primary malignancy(SPM) risk after radiotherapy in rectal cancer survivors METHODS We used Taiwan's National Health Insurance Research Database to identify rectal cancer patients between 1996 and 2011. Surgery-alone, preoperative short course, preoperative long course, and post-operative radiotherapy groups were defined. The overall and sitespecific SPM incidence rates were compared among the radiotherapy groups by multivariate Cox regression, taking chemotherapy and comorbidities into account. Sensitivity tests were performed for attained-year adjustment and long-term survivors analysis. RESULTS A total of 28220 patients were analyzed. The 10-year cumulative SPM incidence was 7.8% [95% confidence interval(CI): 7.2%-8.2%] using a competing risk model. The most common sites of SPM were the lung, liver, and prostate. Radiotherapy was not associated with increased SPM risk in multi-variate Cox model(hazard ratio = 1.05, 95%CI: 0.91-1.21, P = 0.494). The SPM hazard remained unchanged in 10-yearsurvivors. In addition, no SPM risk difference was found between the preoperative radiotherapy and postoperative radiotherapy groups.CONCLUSION In this large population-based cohort study, we demonstrated that radiotherapy had no increase in SPM.

RELATIONSHIP BETWEEN PROLIFERATING CELL NUCLEARANTIGEN EXPRESSION AND ITS MALIGNANCY POTENTIAL IN COLORECTAL CARCINOMA

Objective: To study the relationship between proliferating cell nuclear antigen expression and its malignancy potential in colorectal carcinoma. Methods: Paraffin sections of 86 patients with advanced colorectal carcinoma were assessed by immunohistochemical study, using a mouse monoclonal antibody (pc-10, DAKO Co. USA) to check proliferating cell nuclear antigen (PCNA). To compare PCNA with conventional clinicopathologic factor, including p53 overexpression, tissue carcinoembnyonic antigen immunoreactivity pattern and flow cytometric DNA ploidy for assessing tumor malignancy potential. In addition, recurrence and survival of patients with advanced colorectal carcinoma after curative resection were analyzed in accordance with degree of PCNA expression. Results: PCNA-labeling index (PCNA-LI) increased significantly as the tumor stage advanced (p=0.0001). Strong correlations were observed between PCNA-LI and various pathologic parameters, including histologic differentiation (P=0.0027), lymphatic invasion (P=0.0001), vascular invasion (P=0.0001), lymph node metastasis (P=0.0001), and liver metastasis (P=0.0036). Mean PCNA-LI was also significantly higher in tumor with DNA aneuploidy (P=0.0006) and negative (P=0.01). Linear relationships were demonstrated between PCNA-LI and clinical outcomes; Recurrence rate was significantly greater in the group with higher than the mean PCNA-LI, who underwent curative resection (P<0.01), and three-year survival rates for curative cases with higher than the mean PCNA-LI were significantly poorer than those with lower than mean PCNA-LI (P<0.005). Conclusion: There were correlations between PCNA-LI and various pathologic parameters, PCNA-LI increased significantly as the tumor stage advanced in colorectal carcinoma, the rates of recurrence and death got higher as PCNA-LI increased after curative resection for colorectal carcinoma.

Nuclear imaging for functional evaluation and theragnosis in liver malignancy and transplantation

Currently, nuclear imaging such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) is increasingly used in the management of liver malignancy. 18F-fluorodeoxyglucose (FDG)-PET is the most widely used nuclear imaging in liver malignancy as in other cancers, and has been reported to be effective in diagnosis, response monitoring, recurrence evaluation, and prognosis prediction. Other PET imaging such as 11C-acetate PET is also used complementarily to FDG-PET in diagnosis of liver malignancy. Additionally, image-based evaluation of regional hepatic function can be performed using nuclear imaging. Those imaging modalities are also effective for candidate selection, treatment planning, and perioperative evaluation in liver surgery and transplantation. Recently, nuclear imaging has been actively adopted in the transarterial radioembolization therapy of liver malignancy, according to the concept of theragnosis. With the development of new hybrid imaging technologies such as PET/magnetic resonance imaging and SPECT/CT, nuclear imaging is expected to be more useful in the management of liver malignancy, particularly regarding liver surgery and transplantation. In this review, the efficacy and roles of nuclear imaging methods in diagnosis, transplantation and theragnosis are discussed.

Diagnostic value of whole-body MRI with diffusion-weighted sequence for detection of peritoneal metastases in colorectal malignancy

Objective：To assess the diagnostic accuracy of whole-body MRI using diffusion-weighted sequence（WB-DWI）to determine the peritoneal cancer index（PCI）in correlation with surgical and histopathological findings.Methods：Twenty-seven patients underwent preoperative WB-MRI,followed by cytoreductive surgery for primary tumors of the appendix（n=15）,colorectum（n=12）,and associated peritoneal disease.A total of 351 regions were retrospectively reviewed.The sensitivity,specificity,and accuracy were calculated at 13 anatomical sites.The WB-DWI PCI and PCI type were compared with surgical and histopathological findings.Results：No statistical difference was found between the WB-DWI PCI and surgical PCI（P=0.574）.WB-DWI correctly predicted the PCI type in 24 of 27 patients with high accuracy（88.9%）,including 10 of 10 patients with small-volume tumor,12 of 14 with moderate-volume tumor,and 2 of 3 with large-volume tumor.WB-DWI correctly depicted tumors in 163 of 203 regions,with 40false-negative and 23 false-positive regions.The overall sensitivity,specificity,and accuracy of WB-DWI for the detection of peritoneal tumors were 80.3%,84.5%,and 82.1%,respectively.For lesions＆lt;0.5 cm in diameter,WB-DWI demonstrated good sensitivity（69.4%）.Conclusions：WB-DWI accurately predicted PCI before surgery in patients undergoing evaluation for cytoreductive surgery.

Synergistic inhibition of MEK and reciprocal feedback networks for targeted intervention in malignancy

The RAS-RAF-MEK-ERK signaling pathway(MAPK signaling pathway) plays a significant role in multiple pathological behaviors and is most frequently dysregulated in more than 30% of human cancers.As key elements in this pathway, MEK1/2 play crucial roles in tumorigenesis and the inhibition of apoptosis, which makes their inhibition an attractive antitumor strategy.Dozens of potent non-ATP-competitive allosteric MEK1/2 inhibitors have been developed that have produced substantial improvement in clinical outcomes over the past decade.However, the efficacy of these agents is limited, and response rates are variable in a wide range of tumors that harbor RAS and RAF mutations due to the development of resistance, which is derived mainly from the persistence of MAPK signaling and increased activation of the mutual feedback networks.Both intrinsic and acquired resistance to MEK inhibitors necessitates the synergistic targeting of both pathways to restore the therapeutic effects of a single agent.In this review, the significant role of the MAPK pathway in carcinogenesis and its therapeutic potential are comprehensively examined with a focus on MEK inhibitors.Then, the activation of feedback networks accompanying MEK inhibition is briefly reviewed.Combination strategies that involve the simultaneous inhibition of the original and resistance pathways are highlighted and elaborately described on the basis of the latest research progress.Finally, the obstacles to the development of MEK-related combination systems are discussed in order to lay the groundwork for their clinical application as frontline treatments for individual patients with MAPK-hyperactivated malignancies.