Efficacy and Safety of Ramucirumab in Patients with Unresectable Hepatocellular Carcinoma with Progression after Treatment with Lenvatinib

Objective A survival benefit was demonstrated for ramucirumab (RAM) in patients with unresectable hepatocellular carcinoma (uHCC) and α-fetoprotein (AFP) concentrations ≥400 ng/mL who had previously received sorafenib (SOR). However, it is unclear whether RAM has a similar efficacy in patients with uHCC that progresses after lenvatinib (LEN) treatment. This study aimed to evaluate the early anti-tumor response to RAM as a second-line treatment for advanced uHCC after LEN treatment. Methods We retrospectively assessed the efficacy and safety of RAM at 6 weeks after initiation. The therapeutic effects were evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Patients We evaluated 7 patients with uHCC who received RAM as a second- or third-line treatment after LEN failure. Results The disease control rate (DCR) was 28.6% (2 of 7 patients). After the initiation of RAM, a rapid disease progression resulted in 1 patient death after 19 days. The median progression-free survival (PFS) was 41 days. There were no grade 3 or 4 treatment-related adverse events. At 6 weeks, there was no deterioration in the modified albumin-bilirubin (mALBI) grade. In patients with an imaging response of stable disease (SD), the rate of AFP production decreased from the baseline. Conclusion RAM may have a therapeutic potential for the suppression of uHCC progression in patients previously treated with LEN, as well as for maintaining the liver function during treatment. Evaluating the AFP trends may therefore be useful for predicting RAM effectiveness.     

Short-term Changes in Self-rating Depression Scale Scores after Smoking Cessation in Neurotic Patients

Objective The psychological status is a key factor in smoking continuance. However, details on short-term changes in mild depressive states after smoking cessation (SC) are still unknown. The purpose of the present study was to investigate these short-term changes. Methods A total of 989 patients who visited our SC Clinic were assessed using the Zung Self-Rating-Depression-Scale (SDS), an official instrument to measure depressive tendencies. The participants were classified into normal and neurotic groups based on their SDS scores during their initial visit; they were assessed again 2, 4, 8, and 12 weeks thereafter. Results The majority of patients in the neurotic group were women. These patients were also younger, with a higher nicotine dependence, and presented with a lower successful SC rate than the patients in the normal group. A decrease in SDS scores after starting the SC treatment was observed only in the neurotic group, especially during the first two weeks. In patients who continued to smoke, no improvement in depressive tendencies was noted in this period. Conclusion Depressive tendencies of patients with neurosis improve in the initial stages of the SC treatment (i.e., within two weeks after starting the treatment). This finding fills the mentioned knowledge gap regarding the effects of SC on mild depressive states in the short term.     

Comprehensive genetic characterization of rectal cancer in a large cohort of Japanese patients: differences according to tumor location

Journal of Gastroenterology - In clinical practice, rectal cancer (RC) is classified according to tumor location. However, RC’s genetic characteristics according to tumor location remain...     

Exacerbation of Ulcerative Colitis with Tocilizumab: A Report of Two Cases,One with Takayasu Arteritis and the Other with Relapsing Polychondritis

Tocilizumab (TCZ), a biologic that blocks the signal transduction of interleukin-6, has been used for the treatment of various autoimmune diseases. Many of these cases are sometimes complicated by ulcerative colitis (UC). However, the effect of TCZ on UC is unclear. We experienced two cases with concomitant UC that were treated with TCZ, one for Takayasu arteritis (TAK) and the other for relapsing polychondritis (RP). TCZ did not improve UC in either of these cases. TCZ might have adverse effects on the intestinal tract, since interleukin-6 signaling plays an important role in intestinal epithelium maintenance. Treatment with TCZ should therefore be carefully provided in patients complicated with UC.     

Pathways for the development of multiple epithelial types of intraductal papillary mucinous neoplasm of the pancreas

Journal of Gastroenterology - Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is categorized into four distinct types: the gastric, intestinal, pancreatobiliary, and oncocytic. Each...     

Large-duct pattern invasive adenocarcinoma of the pancreas–a variant mimicking pancreatic cystic neoplasms: A minireview

Pancreatic cancer currently has no subtypes that inform clinical decisions; hence, there exists an opportunity to rearrange the morphological and molecular taxonomy that guides a better understanding of tumor characteristics. Nonetheless, accumulating studies to date have revealed the large-duct type variant, a unique subtype of pancreatic ductal adenocarcinoma (PDA) with cystic features. This subtype often radiographically mimics intraductal papillary mucinous neoplasms (IPMNs) and involves multiple small cysts occasionally associated with solid masses. The “bunch-of-grapes” sign, an imaging characteristic of IPMNs, is absent in large-duct PDA. Large-duct PDA defines the mucin profile, and genetic alterations are useful in distinguishing large-duct PDA from IPMNs. Histologically, neoplastic ducts measure over 0.5 mm, forming large ductal elements. Similar to classic PDAs, this subtype is frequently accompanied by perineural invasion and abundant desmoplastic reactions, and KRAS mutations in codon 12 are nearly ubiquitous. Despite such morphological similarities with IPMNs, the prognosis of large-duct PDA is equivalent to that of classic PDA. Differential diagnosis is therefore essential.     

Hepatic resection under in situ hypothermic hepatic perfusion

BACKGROUND/AIMS: Temporary inflow occlusion of the portal triad has been used frequently in hepatectomy to minimize bleeding. On the other hand, Pringle's maneuver produces ischemic-reperfusion injury especially in patients with underlying liver disease. METHODOLOGY: Thirty-seven cases of hepatic resections were performed with intermittent Pringle's maneuver (IP group; n = 17) and in situ hypothermic perfusion (CP group; n = 20). In the CP group, hepatic inflow was continuously occluded, and 4-degree Centigrade Ringer's lactate was administered by drip during resection. Hepatic outflow occlusion was not performed. RESULTS: All patients tolerated the procedures well. Cold perfusion technique significantly decreased both the times required and the blood loss in hepatectomy (p < 0.05). Serum hyaluronic acid levels gradually increased after the induction of hepatectomy and peaked 10 minutes after reperfusion in the both groups. Thereafter, it decreased and showed a significantly lower level in the CP group until 60 minutes after reperfusion (p < 0.05). Hepaplastin levels remained significantly higher in the CP group one week after operation (p < 0.05). CONCLUSIONS: Using the technique of in situ hypothermic perfusion, we can prolong the ischemic time safely with minimal systemic influence even in cases with underlying liver diseases. This may compare favorably with intermittent Pringle's maneuver in terms of reducing hepatic sinusoidal endothelial cell damage during hepatectomy and reperfusion.     

Usefulness of simultaneous evaluations of contractile reserve, perfusion, and metabolism during dobutamine stress for predicting wall motion reversibility (myocardial stunning) after successful PTCA

The optimal diagnostic approaches using contractile reserve, perfusion, and free fatty acid metabolism together for identifying myocardial stunning after reperfusion have not been clarified in the clinical setting. We investigated the usefulness of simultaneous evaluation of these parameters during myocardial stunning to predict the functional recovery in infarct-related myocardium after reperfusion. In 43 patients (60.7 +/- 10.4 years) with successful coronary angioplasty early after a first myocardial infarction, low-dose (5 to 10 microg/kg/min) dobutamine stress thallium-201/iodine-123 beta-methyl-iodophenyl pentadecanoic acid (BMIPP) dual-isotope single photon emission computed tomography was performed with echocardiography in the acute phase within 1 week after reperfusion. Regional wall motion and the uptake of each tracer were obtained simultaneously in the infarct-related segments. In 93 segments with dyssynergy in the acute phase after reperfusion, the sensitivity, specificity, and accuracy using contractile reserve for predicting the final functional recovery in the chronic phase more than 3 months after PTCA were 81.3%, 67.2%, and 72%, respectively. More accurate predictions were obtained by simultaneous measurements of thallium-201 and BMIPP uptakes (93.8%, 66.7%, and 79.4%, respectively). The final functional recovery in the stunned myocardium after early reperfusion following acute myocardial infarction was predicted more accurately by simultaneous evaluation of these parameters at dobutamine stress testing.