Microsatellite Instability Is Associated With a Better Prognosis for Gastric Cancer Patients After Curative Surgery

Background

Microsatellite instability (MSI) is one of the leading mechanisms for the carcinogenesis of gastric cancer. Its prognostic value is controversial.

Methods

Between May 1988 and Oct 2003, a total of 214 gastric cancer patients undergoing curative surgery were enrolled, and their MSI statuses were classified as MSI-H (high) or MSI-L/S (low/stable). The clinicopathologic characteristics of MSI-H and MSI-L/S gastric cancers were compared.

Results

The MSI-H tumors accounted for 11.7?% (n?=?25) of the 214 total gastric cancers. Although not statistically significant, the MSI-H gastric cancers were more frequently located in the lower third of the stomach (64?% vs. 49.2?%) and were more often the intestinal type (72?% vs. 61.4?%) compared to the MSI-L/S gastric cancers. The MSI-H gastric cancers had a significantly better 5-year overall survival (OS) rate (68?% vs. 47.6?%, p?=?0.030) and a trend of a better 3-year disease-free survival rate (71.8?% vs. 55.2?%, p?=?0.076) compared to the MSI-L/S gastric cancers. A multivariate analysis revealed that pathologic TNM stage and MSI status were the independent prognostic factors for OS after curative surgery.

Conclusions

Compared to MSI-L/S tumors, MSI-H tumors are associated with a better OS rate for gastric cancer patients after R0 resection.     

Factors Associated with Recurrence Within 2 Years After Curative Surgery for Gastric Adenocarcinoma

Background

Despite curative surgery for gastric cancer, many patients die of recurrent cancer. Few studies have investigated the time to recurrence after curative resection for gastric cancer.

Methods

Data were collected prospectively between December 1987 and December 2006. A total of 1,549 patients underwent curative resection of adenocarcinoma of the stomach at Taipei Veterans General Hospital. Among them, 419 patients had recurrence; they were divided into early recurrence (<2?years) and late recurrence (??2?years). The clinicopathological characteristics, survival time after recurrence, and recurrence patterns were compared between the two groups.

Results

Multivariate analysis showed that stage III gastric cancer patients with early recurrence had larger tumors and more lymph node metastasis than patients with late recurrence, while no difference between early and late recurrence was observed in stage I and II patients. Early recurrence was associated with more distant metastasis than was late recurrence. Patients with advanced TNM stage tended to die within 2?years after recurrence.

Conclusions

Gastric cancer patients with larger tumors and more lymph node metastasis tended to have early recurrence, especially stage III patients. Advanced TNM stage was associated with early cancer death after recurrence.     

Graft patency is not the only clinical predictor of success after exclusion and bypass of popliteal artery aneurysms

PURPOSE: The traditional measure of success after exclusion and bypass of popliteal artery aneurysm (PAA) is graft patency. In addition to fate of the bypass, we hypothesize that late outcome after surgical treatment of PAA is influenced by completeness of exclusion. METHODS: Thirty patients who underwent 41 reconstructions for PAA over a 10-year period were reviewed. RESULTS: Excluded PAAs were examined with duplex ultrasound scan for size, patency, and patent feeding branches; bypass grafts and native inflow and outflow arteries were examined for patency and size. Thirty-six limbs were available for follow-up (mean follow-up period, 46 +/- 42 months). Only two aneurysms (5.6%) appeared patent on duplex ultrasound scan, but five limbs had patent arterial branches communicating with thrombosed excluded PAAs. PAA diameter decreased from 2.5 +/- 0.8 cm to 1.7 +/- 0.5 cm (P <.0001) in most. However, 12 excluded PAAs (33%) showed significant enlargement from 2.2 +/- 0.9 cm to 2.8 +/- 1.0 cm (P =.002). A quarter of enlarging excluded PAA were associated with new compressive symptoms. Three methods of PAA exclusion were used: proximal and distal ligation with short segment isolation (type 1), proximal and distal ligation with long segment isolation (type 2), and single ligature (type 3). In univariate analysis, type of exclusion significantly influenced late size of excluded PAA (P =.004). Type 1 exclusion was superior to both type 2 and 3 exclusions in producing aneurysm diameter reduction. Type 3 exclusion resulted in aneurysm growth. In addition, excluded aneurysms with visualized feeding branches were associated with significant growth compared with PAAs without feeding branches (P =.006). Graft primary and assisted primary patency rates at 5 years were 86% +/- 9.4% and 92% +/- 7.4%, respectively. Although graft diameter and native donor artery diameter significantly increased, this did not adversely affect graft patency. CONCLUSION: Enlargement of excluded PAA after surgical treatment can cause compressive symptoms. Exclusion requires adequate vascular isolation to prevent late PAA enlargement, with proximal and distal arterial ligation best performed adjacent to the aneurysm. Vein graft enlargement occurs, but this enlargement does not adversely influence patency.     

Glucose-Regulated Protein 78 Is a Novel Contributor to Acquisition of Resistance to Sorafenib in Hepatocellular Carcinoma

Background  

Sorafenib is a newly established cancer drug found to be an effective systemic treatment for advanced hepatocellular carcinoma (HCC). However, little is known about any potential effectors that modify tumor cell sensitivity towards sorafenib. Here, we present the first evidence that glucose-regulated protein 78 (GRP78) is intimately associated with acquisition of resistance towards sorafenib.     

Emergence of a virulent porcine reproductive and respiratory syndrome virus in Taiwan in 2018

In March 2018, an abortion storm caused by porcine reproductive and respiratory syndrome virus was confirmed in a farrow‐to‐finish pig herd in Taiwan. Open reading frame 5 and non‐structural protein 2 of the virus confirmed that the virus is closely related to the virulent strains circulating in the United States.     

Characteristics and outcome of patients with dual hepatitis B and C‐associated hepatocellular carcinoma: are they different from patients with single virus infection?

Background: Patients with hepatocellular carcinoma (HCC) caused by dual hepatitis B and C virus (HBV, HCV) infection may constitute a distinct disease group that is different from patients with single virus infection. This study compared the clinical characteristics and outcomes of patients with HBV, HCV and dual virus infection. Methods: A prospective database of 1215 HCC patients with chronic hepatitis B, C or dual virus infection was investigated. Results: Patients with HCV infection (n=388) were significantly older (mean age, 69 years) than patients with dual virus (n=75, 65 years) and HBV (n=752; 60 years) infection (P<0.0001). The male‐to‐female ratios for the HBV, dual virus and HCV groups were 5.2, 3.4 and 1.3 respectively (P<0.0001). Patients in the HBV group more often had higher total tumour volume (mean, 409 cm³) than those in the dual virus group (244 cm³) and HCV (168 cm³) group (P<0.0001). No significant differences of the severity of liver cirrhosis, performance status, cancer staging and tumour cell differentiation were noted among the three groups. Patients in the HCV group had a significantly poor survival in comparison with the HBV group only in the subset of patients with small tumour volume (<50 cm³) in the Cox proportional hazards model (relative risk, 1.44; P=0.041). Conclusions: Dual HBV and HCV virus infection does not accelerate the speed of HCC formation in patients with chronic hepatitis B, and appears to have a modified course of carcinogenesis pathway that is diverted away from the biological behaviour of HBV and HCV infection.     

Spontaneous Achilles tendon rupture in a patient with systemic lupus erythematosus due to ischemic necrosis after methyl prednisolone pulse therapy

Spontaneous tendon rupture in a patient with systemic lupus erythematosus (SLE) is a rare but potentially disabling complication. Minor trauma, local inflammation and long term corticosteroid therapy are regarded as possible causes. However, ischemic necrosis of the tendon resulting from hypercoagulability and methyl prednisolone (MTP) pulse therapy has not been reported. We present a 20-year old female, newly diagnosed with lupus, who has high titer antiphospholipid antibodies, hyperhomocysteinemia and protein S deficiency. Her severe clinical symptoms of lupus were improved after MTP pulse therapy. Several days later, cold sensation over the right lower leg developed. On day 15 after pulse therapy, acute onset of right heel pain occurred when she was ascending stairs. Rupture of the right Achilles tendon was demonstrated by sonography and MRI. A Doppler sonography revealed narrowing and abrupt cessation of blood flow in the right popliteal artery. Heparin treatment was started. The angiography performed two days after heparinization revealed narrow caliber and decreased flow of the right tibial artery below the right ankle. Surgical repair of the tendon was successful and the pathology of the resected tendon revealed focal necrosis, degeneration and capillary proliferation. MTP pulse therapy in a lupus patient with hypercoaguable state with hyperhomocysteinemia, protein S deficiency and high titer antiphospholipid antibodies may cause spontaneous tendon rupture.     

An essential role for an inositol polyphosphate multikinase, Ipk2, in mouse embryogenesis and second messenger production

Phospholipase C and several inositol polyphosphate kinase (IPK) activities generate a branched ensemble of inositol polyphosphate second messengers that regulate cellular signaling pathways in the nucleus and cytoplasm. Here, we report that mice deficient for Ipk2 (also known as inositol polyphosphate multikinase), an inositol trisphosphate and tetrakisphosphate 6/5/3-kinase active at several places in the inositol metabolic pathways, die around embryonic day 9.5 with multiple morphological defects, including abnormal folding of the neural tube. Metabolic analysis of Ipk2-deficient cells demonstrates that synthesis of the majority of inositol pentakisphosphate, hexakisphosphate and pyrophosphate species are disrupted, although the presence of 10% residual inositol hexakisphosphate indicates the existence of a minor alternative pathway. Agonist induced inositol tris- and bis-phosphate production and calcium release responses are present in homozygous mutant cells, indicating that the observed mouse phenotypes are a result of failure to produce higher inositol polyphosphates. Our data demonstrate that Ipk2 plays a major role in the synthesis of inositol polyphosphate messengers derived from inositol 1,4,5-trisphosphate and uncovers a role for their production in embryogenesis and normal development.     

Gray-scale and color Doppler ultrasonographic manifestations of papillary thyroid carcinoma: analysis of 51 cases

The purpose of this study is to assess the specific ultrasonic characteristics of papillary thyroid carcinoma and to determine the relative frequency of various patterns of papillary carcinoma on gray-scale ultrasonography (US) and color Doppler ultrasonography (CDU).

Methods

We retrospectively reviewed US features in 51 patients with confirmed papillary thyroid carcinoma. The features were analyzed based on tumor size, echogenicity, echotexture, boundary, margin, shape, and calcification pattern on gray-scale US imaging, and on patterns of vascularity on CDU. We obtained the relative frequency of features and classified these features into three categories: common (≥50% of lesions), less common (>10% but <50%), and uncommon (≤10%). Individual differences and combinations of features were also analyzed.

Results

In total, 67 nodules were enrolled in our study. The sizes of 76% of nodular lesions were <20.0 mm. Common US features of papillary carcinoma included: a homogeneous hypoechoic solid picture; a poorly defined boundary; an irregular margin; the absence of halo; the absence of calcifications or microcalcifications; and mixed perinodular and intranodular blood flow patterns. Less common features included: a heterogeneous hypoechoic or very hypoechoic picture; microcalcifications; a well-defined boundary; a regular margin; a halo with uneven thickness or an incomplete halo; and a taller-than-wide shape. Uncommon features included: an isoechoic picture; solid with cystic components; coarse calcifications; mixed coarse calcifications and microcalcifications; “inferno”-type blood flow; and absence of blood flow. On average, each nodule had 4.9 US features considered common, 1.8 US features considered less common, and 0.4 US feature considered uncommon. Features such as predominantly cystic composition, hyperechoic texture, and hypoechoic halo with even thickness were never found in our study. The top two common manifestations of papillary carcinoma were solid architecture and mixed perinodular and intranodular blood flow signals.

Conclusion

All lesions in our series had a predominantly solid characteristic on gray-scale US.