Prediction of survival and analysis of prognostic factors for hepatocellular carcinoma: a 20-year of imaging diagnosis in Upper Northern Thailand.

BACKGROUND: To evaluate survival rates of hepatocellular carcinoma (HCC), the Chiang Mai Cancer Registry provided characteristics data of 6276 HCC patients diagnosed between 1998-2020 based on evolution of imaging diagnosis. Evolution can be separated into four cohorts, namely, cohort 1 (1990-2005) when we had ultrasound (US) and single-phase computed tomography (CT), cohort 2 (2006-2009) when one multi-phase CT and one magnetic resonance imaging (MRI) were added, cohort 3 (2010-2015) when MRI with LI-RADS was added, and finally, cohort 4 (2016-2020) when two upgraded MRIs with LI-RADS were added. METHODS: Cox proportional hazard models were used to determine the relation between death and risk factors including methods of imagining diagnosis, gender, age of diagnosis, tumor stages, history of smoking and alcohol-use, while Kaplan-Meier curves were used to calculate survival rates. RESULTS: The median age of diagnosis was 57.0 years (IQR: 50.0-65.0) and the median survival time was 5.8 months (IQR: 1.9-26.8) during the follow-up period. In the univariable analysis, all factors were all associated with a higher risk of death in HCC patients except age of diagnosis. In a multivariable analysis, elderly age at diagnosis, regional and metastatic stages and advanced methods of imagining diagnosis during cohorts 2 and 3 were independently associated with the risk of death in HCC patients. The survival rate of patients diagnosed during cohort 4 was significantly higher than the other cohorts. CONCLUSION: As a significantly increasing survival rate of HCC patients in cohort 4, advanced methods of diagnostic imaging can be a part of the recommendation to diagnose HCC.

Efficacy and safety of pinaverium bromide as an add-on therapy in refractory dyspepsia: A randomized controlled trial.

Background and Aim: Functional dyspepsia (FD) remains a therapeutic challenge, and the efficacy of antispasmodic agents as adjunctive therapy is not well established. This study aimed to evaluate the efficacy and safety of pinaverium bromide added to omeprazole in treating refractory FD. Methods: We conducted a randomized, placebo-controlled trial in patients with refractory dyspepsia. Participants were randomly assigned to receive pinaverium (50 mg, 3 times/day, n = 36) or placebo (n = 36) in addition to omeprazole for 8 weeks. The primary endpoint was the responder rate for adequate relief. Secondary outcomes included the Global Overall Symptom Scale (GOSS), quality of life, and safety profile. Results: No statistically significant differences were observed in the adequate relief response rate between the pinaverium bromide and control group at week 2 (58.3% vs. 62.9%, P = 0.697), week 4 (62.9% vs. 78.1%, P = 0.173), week 6 (64.7% vs. 75.0%, P = 0.363), and week 8 (64.7% vs. 75.0%, P = 0.363). Additionally, there were no significant differences observed in the decline of symptom score between the two groups at week 4 (8.4 ± 7.6 vs. 7.7 ± 7.1, P = 0.702) and week 8 (10.9 ± 8.2 vs. 8.4 ± 7.2, P = 0.196). Similarly, there were no significant differences in terms of quality of life between the two groups. Adverse event rates were also comparable between the two groups. Conclusion: Pinaverium bromide was found to be safe in the treatment of refractory dyspepsia, but it did not demonstrate a significant benefit in improving symptoms.

Prediction of Esophageal Varices in Viral Hepatitis C Cirrhosis: Performance of Combined Ultrasonography and Clinical Predictors.

Objectives: This study is aimed at evaluating the diagnostic performance of clinical predictors and the Doppler ultrasonography in predicting esophageal varices (EV) in patients with hepatitis C-related cirrhosis and exploring the practical predictors of EV. Methods: We conducted a prospective study from July 2020 to January 2021, enrolling 65 patients with mild hepatitis C-related cirrhosis. We obtained clinical data and performed grayscale and the Doppler ultrasound to explore the predictors of EV. Esophagogastroduodenoscopy (EGD) was performed as the reference test by the gastroenterologist within a week. Results: The prevalence of EV in the study was 41.5%. Multivariable regression analysis revealed that gender (female, OR = 4.04, p = 0.02), platelet count (<150000 per ml, OR = 3.13, p = 0.09), splenic length (>11 cm, OR = 3.64, p = 0.02), and absent right hepatic vein (RHV) triphasicity (OR = 3.15, p = 0.03) were significant predictors of EV. However, the diagnostic accuracy indices for isolated predictors were not good (AUROC = 0.63-0.66). A combination of these four predictors increases the diagnostic accuracy in predicting the presence of EV (AUROC = 0.80, 95% CI 0.69-0.91). Furthermore, the Doppler assessment of the right hepatic vein waveform showed good reproducibility (κ = 0.76). Conclusion: Combining clinical and Doppler ultrasound features can be used as a screening test for predicting the presence of EV in patients with hepatitis C-related cirrhosis. The practical predictors identified in this study could serve as an alternative to invasive EGD in EV diagnosis. Further studies are needed to explore the diagnostic accuracy of additional noninvasive predictors, such as elastography, to improve EV screening.

Minilaparotomy, Cyfra21-1, and Other Predicting Factors for Suboptimal Cytoreductive Surgery in Advanced Epithelial Ovarian Cancer: A Pilot Study.

BACKGROUND: Currently, there is no reliable method to predict the result of the primary cytoreduction to decide whether to go on primary cytoreductive surgery or receive neoadjuvant chemotherapy. This study aimed to identify candidate predicting factors from clinical data, serum biomarkers, CT/MRI imaging, and minilaparotomy for suboptimal cytoreduction in women with advanced epithelial ovarian cancer. METHODS: Women who were clinically suspicious of advanced-stage epithelial ovarian, fallopian tube, and peritoneal cancer undergoing primary cytoreductive surgery were recruited. Clinical data, abdominopelvic CT/MRI, and serum biomarkers, including CA125, HE4, and Cyfra21-1, were collected preoperatively. At the start of the surgery, a minilaparotomy incision was made, the peritoneal cavity was assessed, and the operating surgeons gave the impression of whether the optimal cytoreductive surgery would be attainable. Subsequently, the incision was extended as necessary, and the standard cytoreductive surgery was attempted. After the procedure completion, the surgical outcome (optimal vs. suboptimal cytoreduction) and other operative outcomes were recorded. The association between the potential predicting factors and the surgical outcome was examined. RESULTS: Fourteen patients were included in this pilot study. Twelve patients were diagnosed with primary ovarian or fallopian tube cancer, while two had ovarian metastasis from colorectal cancer. The optimal cytoreduction was achieved in eight women. After minilaparotomy, the surgeons could predict suboptimal surgery correctly in five out of six cases (OR: 24.12, 95%CI: 2.34-Inf., p<0.01). Moreover, no patient with the finding of rectosigmoid invasion from CT had optimal surgery (OR: 12.96, 95%CI: 1.26-Inf., p=0.03). Lastly, increased serum cyfra21-1(>8 ng/mL) and HE4 (>83 pmol/L) were significantly associated with suboptimal cytoreduction, with OR: 35.00, 95%CI: 1.74-702.99, p=0.02 and OR: 15.00, 95%CI: 1.03-218.30, p=0.05, respectively. CONCLUSION: The finding of rectosigmoid invasion from abdominal CT, increased serum cyfra21-1 and HE4, and the initial minilaparotomy impression were potentially associated with suboptimal cytoreduction.

Open-labeled pilot study of cysteine-rich whey protein isolate supplementation for nonalcoholic steatohepatitis patients.

BACKGROUND AND AIMS: Glutathione (GSH) depletion contributes to liver injury and development of steatohepatitis. Undenatured cysteine-rich whey protein isolate has been clinically proven to raise GSH in several patient groups. The aim of this study was to evaluate the effect of oral supplementation with whey protein on patients with nonalcoholic steatohepatitis (NASH). METHODS: In an open-labeled clinical trial, 38 patients (18 male, 20 female; mean age 48 +/- 14 years) with NASH confirmed by computed tomography measurements and liver biochemistries were given with a daily dose of 20 g whey protein isolate for 12 weeks. RESULTS: A significant reduction in alanine aminotransferase (ALT) (64 +/- 72 vs 46 +/- 36, P = 0.016) and aspartate aminotransferase (AST) (45 +/- 49 vs 33 +/- 18, P = 0.047) were observed. Plasma glutathione and total antioxidant capacity increased significantly at the end of study (53 +/- 11 vs 68 +/- 11, P < 0.05 and 1.26 +/- 0.10 vs 2.03 +/- 0.10, P < 0.05). Liver attenuation index improved from -13.4 +/- 11.1 to -9.7 +/- 13.1 (P = 0.048). Hepatic macrovesicular steatosis decreased significantly after 12 weeks of supplementation (33.82 +/- 12.82 vs 30.66 +/- 15.96, P = 0.046). Whey protein isolate was well tolerated. No serious adverse events were observed. CONCLUSIONS: The results indicate that oral supplementation of cysteine-rich whey protein isolate leads to improvements in liver biochemistries, increased plasma GSH, total antioxidant capacity and reduced hepatic macrovesicular steatosis in NASH patients. The results support the role of oxidative stress in the pathogenesis of this disease.

Carcinoma of extrahepatic bile ducts and gallbladder metastatic to the ovary: a report of 16 cases.

Information on ovarian metastasis of carcinoma of the extrahepatic bile ducts and gallbladder is limited. Sixteen examples are reported; 3 primary tumors were hilar cholangiocarcinomas, 5 common bile duct carcinomas, and 8 gallbladder carcinomas. The patients ranged from 21 to 87 years (mean, 59 years); 7 presented to gynecologists with nonspecific pelvic symptoms similar to primary ovarian neoplasms. The primary tumor was identified before the detection of the ovarian lesions in 5 cases, was simultaneously detected with the ovarian metastases in 9, and was diagnosed postoperatively in 2. All but one case had bilateral ovarian involvement. The thirty-one ovarian lesions included twenty-nine grossly abnormal ovaries that were enlarged (range, 3.0-16.5 cm, mean, 9.4 cm) and 2 ovaries with only microscopic involvement. The sectioned surface was solid in 9, solid-cystic in 15, and multicystic in 5. Microscopically, ovarian surface implants were seen in 66%, multinodular growth in 58%, and infiltrative stromal invasion in 81%. Mucinous epithelial differentiation was seen in 81%, sometimes with foci of benign-like or borderline-like epithelium simulating primary ovarian mucinous neoplasia. Cystadenoma and cystadenofibroma of nonmucinous type was even mimicked strikingly in some cases because of flattening of epithelium lining glands and cysts. Signet ring cells were present in sufficient quantity for a diagnosis of Krukenberg tumor in four tumors. Colloid-type carcinoma was observed at least focally in 3 tumors. Nonmucinous carcinomatous components included adenocarcinoma with high-grade endometrioid-like morphology in 2 cases, papillary adenocarcinoma simulating mixed müllerian epithelial adenocarcinoma in 1, and undifferentiated carcinoma in 2. Immunohistochemical studies in 8 cases showed a positive reaction for cytokeratin 7 in all and for cytokeratin 20 in 4 cases. The high rate of bilaterality, surface involvement, multinodular growth, and heterogeneity of patterns were the most helpful features for indicating a metastatic nature, with signet ring cells also being helpful in the minority of cases in which they were present. Although the diagnosis of a metastatic tumor to the ovary is possible in most of the cases based on standard diagnostic criteria, problems in the differential diagnosis may be posed by morphologic patterns that overlap strikingly with primary ovarian neoplasms, benign, borderline, and malignant, as discussed herein.

Intrahepatic cholangiocarcinoma metastatic to the ovary: a report of 16 cases of an underemphasized form of secondary tumor in the ovary that may mimic primary neoplasia.

The potential for adenocarcinoma metastatic to the ovary to mimic primary mucinous neoplasms is a well-known issue to surgical pathologists, most of the recent literature emphasizing pancreatic and various other origins for the ovarian metastases. Although an origin in the gallbladder or extrahepatic bile ducts is acknowledged for some cases little information exists on tumors originating within the intrahepatic bile ducts. Sixteen cases of this type were retrieved from the surgical pathology files of the Chiang Mai University Hospital between January 1992 and December 2006. The patients ranged from 38 to 74 years (mean 52). Thirteen presented with nonspecific pelvic symptoms similar to primary ovarian neoplasms. The hepatic tumors were radiologically detected before the ovarian lesion in 2 cases. Hepatic and ovarian masses were simultaneously detected by preoperative radiologic studies or at exploratory laparotomy in 10 cases. In the remaining 4 cases, the hepatic lesions were detected postoperatively. There were a total of 26 metastatic ovarian lesions which included 22 clinically recognized ovarian masses (range 3 to 20 cm, mean 11.8 cm). Bilateral involvement was present in 10 cases (62%) and unilateral involvement in 6 (38%). The cut surfaces of the 22 grossly enlarged ovaries were predominantly solid in 5, solid-cystic in 10, and multicystic in 7. Microscopically, surface implants were observed in 80% of tumors, multinodular growth in 48%, and infiltrative stromal invasion (including microinvasionlike foci as it would be applied if the tumors were primary) in 86%. The neoplastic epithelium typically formed glands that ranged from small to large and cystically dilated, but small clusters of cells and individual cells were also seen. The epithelium ranged from tall, columnar, and mucinous in appearance to cuboidal or flattened and nonspecific. The tumors most closely mimicked primary mucinous neoplasms although a resemblance to other mullerian neoplasms was also seen. Foci often mimicked mucinous borderline tumors of typical type or with intraepithelial carcinoma and benign-appearing mucinous epithelium was seen in 62% of tumors. Immunohistochemical studies in 15 cases showed a positive reaction for cytokeratin 7 in all and for cytokeratin 20 in 5 cases. Intrahepatic cholangiocarcinoma should be included in the list of origins of possible ovarian metastatic tumors that mimic primary ovarian mucinous neoplasia, particularly in parts of the world where cholangiocarcinoma of the liver is relatively common.

Surgically relevant normal and variant renal parenchymal and vascular anatomy in preoperative 16-MDCT evaluation of potential laparoscopic renal donors.

OBJECTIVE: Using 16-MDCT, we describe and quantify the frequency and types of renal anatomic variants and findings relevant for preoperative evaluation and surgical planning for potential laparoscopic renal donors. MATERIALS AND METHODS: On 16-MDCT, 126 consecutive potential donors underwent scanning before contrast administration and after i.v. power injection of nonionic contrast material during the arterial, nephrographic, and excretory phases. On a 3D workstation, CT images were evaluated retrospectively in consensus by three abdominal imagers. The number and branching pattern of bilateral renal arteries and veins, including anomalies of the inferior vena cava and lumbar-gonadal axis, were categorized along with the frequency of incidental findings of the renal parenchyma and collecting system. RESULTS: Major arterial variants including supernumerary and early branching arteries were present in 16% and 21%, respectively, of left kidneys and 22% and 15%, respectively, of right kidneys. Major and minor venous variants were detected in 11% and 58% of left kidneys and 24% and 3% of right kidneys. Late confluence of the venous trunk was identified in 17% of left kidneys and 10% of right kidneys. Incidental parenchymal and urothelial abnormalities, most commonly cysts and calyceal calcifications, were identified in 30% of the kidneys. Other relevant incidental findings included focal infarcts, cortical scars, atrophic scarred kidney, and bilateral papillary necrosis. Urothelial variants included bilateral simple ureteroceles and rightsided complete duplicated collecting system. CONCLUSION: 16-MDCT angiography and urography allow confident detection and classification of a variety of anatomic and incidental anomalies relevant to the preoperative selection of potential laparoscopic renal donors and to surgical planning.

Utility of 16-MDCT angiography for comprehensive preoperative vascular evaluation of laparoscopic renal donors.

OBJECTIVE: Our objective was to determine the efficacy of 16-MDCT angiography in preoperative evaluation of vascular anatomy of laparoscopic renal donors. METHODS AND MATERIALS: Fifty-five consecutive renal donors (25 men and 30 women) underwent 16-MDCT angiography followed by donor nephrectomy. In the arterial and nephrographic phases, images were acquired with 60% overlap and 0.6-mm reconstruction in both phases after 120 mL of iohexol was injected at 4 mL/sec. On a 3D workstation, images were evaluated retrospectively by two abdominal imagers blinded to surgical results with respect to number and branching pattern of renal arteries and major and minor renal veins. These CT angiography results were compared with surgical findings. RESULTS: The surgically confirmed sensitivity of both reviewers (1 and 2) using the MDCT data for detection of renal arteries was 98.5% (65 of 66), and accuracies were 97.0% for reviewer 1 and 95.5% for reviewer 2. Sensitivity and accuracy detection of renal veins was 97% (61 of 63) and 98% (62 of 63) for reviewer 1 and reviewer 2, respectively. Sensitivity and accuracy detection of early arterial bifurcation (< 2 cm from aorta) was 100% (14 of 14), and sensitivity in detection of late venous confluence (< 1.5 cm from aorta) was 100% (8 of 8). All major renal venous variants were identified; reviewer 1 identified 78% (18 of 23) minor venous variants, and reviewer 2 identified 83% (19 of 23) minor venous variants. There were no hemorrhagic complications at surgery. Excellent agreement between reviewers (kappa = 0.92-0.97) was achieved for detection of normal and variant anatomy. CONCLUSION: 16-MDCT angiography enabled excellent preoperative detection of arterial anatomy and venous laparoscopic donor nephrectomy.

Chinese herbal recipe versus diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial [ISRCTN70292892].

BACKGROUND: Duhuo Jisheng Wan (DJW) is perhaps the best known and most widely used Chinese herbal recipe for arthralgia, but the clinical study to verify its efficacy is lacking. The purpose of this study was to compare the efficacy of DJW versus diclofenac in symptomatic treatment of osteoarthritis (OA) of the knee. METHODS: This study was a randomized, double-blind, double-dummy, controlled trial. The 200 patients suffering from OA of the knee, were randomized into the DJW and diclofenac group. The patients were evaluated after a run-in period of one week (week 0) and then weekly during 4 weeks of treatment. The clinical assessments included visual analog scale (VAS) score that assessed pain and stiffness, Lequesne's functional index, time for climbing up 10 steps, as well as physician's and patients' overall opinions on improvement. RESULTS: Ninety four patients in each group completed the study. In the first few weeks of treatment, the mean changes in some variables (VAS, which assessed walking pain, standing pain and stiffness, as well as Lequesne's functional index) of the DJW group were significantly lower than those of the diclofenac group. Afterwards, these mean changes became no different throughout the study. Most of the physician's and patients' overall opinions on improvement at each time point did not significantly differ between the two groups. Approximately 30% of patients in both groups experienced mild adverse events. CONCLUSION: DJW demonstrates clinically comparable efficacy to diclofenac after 4 weeks of treatment. However, the slow onset of action as well as approximately equal rate of adverse events to diclofenac might limit its alternative role in treatment of OA of the knee.

Electroacupuncture versus diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial.

BACKGROUND: The purpose of this study was to compare the efficacy of electroacupuncture (EA), diclofenac and their combination in symptomatic treatment of osteoarthritis (OA) of the knee. METHODS: This study was a randomized, single-blind, placebo controlled trial. The 193 out-patients with OA of the knee were randomized into four groups: placebo, diclofenac, EA and combined (diclofenac plus EA). Paracetamol tablets were prescribed as a rescue analgesic during the study. The patients were evaluated after a run-in period of one week (week 0) and again at the end of the study (week 4). The clinical assessments included the amount of paracetamol taken/week, visual analog scale (VAS), Western Ontario and McMaster Universities (WOMAC) OA Index, Lequesne's functional index, 50 feet-walk time, and the orthopedist's and patient's opinion of change. RESULTS: One hundred and eighty six patients completed the study. The improvement of symptoms (reduction in mean changes) in most outcome parameters was greatest in the EA group. The proportions of responders and patients with an overall opinion of "much better" were also greatest in the EA group. The improvement in VAS was significantly different between the EA and placebo group as well as the EA and diclofenac group. The improvement in Lequesne's functional index also differed significantly between the EA and placebo group. In addition, there was a significant improvement in WOMAC pain index between the combined and placebo group. CONCLUSION: EA is significantly more effective than placebo and diclofenac in the symptomatic treatment of OA of the knee in some circumstances. However, the combination of EA and diclofenac treatment was no more effective than EA treatment alone.

CA 19-9 in combination with abdominal CT scan for the diagnosis of mass-forming intrahepatic cholangiocarcinoma.

AIM: Cholangiocarcinoma (CCA) is a common form of cancer in Thailand. The diagnosis of CCA by pathology is widely accepted. Unfortunately, tissue diagnosis of mass-forming intrahepatic cholangiocarcinoma is difficult to perform due to the risk of the procedure and accessibility. The aim of this study is to assess the diagnostic utility of CA19-9 in combination with CT scan for the diagnosis of mass-forming cholangiocarcinoma. MATERIALS & METHODS: The medical records of patients with a diagnosis of CCA and hepatocellular carcinoma (HCC) during January 2005-December 2009 were reviewed. Only cases with pathology and CT scan reports from Maharaj Nakorn Chiang Mai Hospital were included. Demographic data, clinical manifestations and laboratory results, including CA19-9 and CT scans of the liver, were carefully examined in order to establish their diagnostic utility in mass-forming CCA without a pathological diagnosis. RESULTS: A total of 79 CCA patients and 66 HCC patients were included in CA19-9 cut-off level analyses. A total of 31 CCA patients and 44 HCC patients were included in the CT scan evaluation and scored according to the Chiang Mai CT score for CCA. The specificity of a CA19-9 value of 500 U/ml for the diagnosis of CCA was 95.5% with a sensitivity of 50.6%, positive predictive value of 91.8% and likelihood ratio of positive (LR+) of 11.24. A CT score greater than 2 demonstrates a positive predictive value of more than 90% in diagnosis of CCA. The CA19-9 level of 140 U/ml in combination with a CT score of 2 demonstrated LR+ as high as 57.09. A CA19-9 level of 280 U/ml in combination with a CT score of 1 demonstrated LR+ of 58.4. CONCLUSION: A CA19-9 level combined with the Chiang Mai CT score for CCA are good diagnostic tools for the diagnosis of mass-forming cholangiocarcinoma with high specificity, high positive predictive value and high likelihood ratio of positive.

Primary and metastatic mucinous adenocarcinomas of the ovary: Evaluation of the diagnostic approach using tumor size and laterality.

OBJECTIVE: To evaluate the usefulness of the recently proposed algorithm (Seidman JD, Kurman RJ, Ronnett BM. Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis. Am J Surg Pathol 2003; 27: 985-93 [5]) that classifies mucinous adenocarcinomas of the ovary as primary when they were unilateral > or =10 cm and as metastatic when they were unilateral <10 cm or bilateral. METHODS: Malignant ovarian neoplasms, which were resected in Chiang Mai University Hospital between 1992 and 2003, were histologically reviewed. Mucinous adenocarcinomas involving the ovary were identified. The medical records and radiologic materials were reviewed in correlation with the pathologic features to identify the primary site. RESULTS: There were 74 cases of mucinous adenocarcinomas; 16 were primary ovarian; 52, metastatic; and 6 of indeterminate primary site (primary versus metastatic). Primary mucinous adenocarcinomas had a mean size of 16.4 cm and bilateral involvement in 13%. Metastatic mucinous adenocarcinomas had a mean size of 11.7 cm and bilateral involvement in 77%. Excluding the 6 tumors of indeterminate primary site, the proposed algorithm correctly classified primary and metastatic tumors in 84% of 68 cases. Of 21 unilateral mucinous adenocarcinomas > or =10 cm, 62% were primary ovarian. Of 5 unilateral tumors <10 cm, 80% were metastatic. Of 42 bilateral mucinous adenocarcinomas, 95% were metastatic. CONCLUSION: The algorithm provided high accuracy in the overall prediction of primary and metastatic mucinous adenocarcinomas of the ovary, with major strength in the identification of metastatic tumors by bilaterality or size <10 cm. However, the prediction of primary mucinous adenocarcinomas by unilaterality and size > or =10 cm was less reliable than previously reported. Due to the overlapping features between primary and metastatic tumors and the higher frequency of the latter, the possibility of metastases should always be borne in mind in the evaluation of mucinous adenocarcinomas of the ovary.