Clinical prevention of gastric cancer by Helicobacter pylori eradication therapy: a systematic review

Helicobacter pylori (H. pylori) infection plays an important role in gastric carcinogenesis. We conducted a systematic review concerning gastric cancer development after H. pylori eradication therapy. In total 15 papers matched our criteria, the results were reviewed. The H. pylori eradication therapy statistically diminished the prevalence of clinical gastric cancer by approximately one-third. The studies from Japan supported this conclusion; however, studies from overseas reported conflicting results. The differences in these conclusions lie in the diagnostic ability of endoscopic examination, since the clinical stage was quite different between these studies. Gastric cancer that developed after eradication revealed a mainly intestinal type histology and depressed-type appearance. The following are possible reasons for reduced gastric cancer: (1) eradication therapy inhibits the new occurrence of gastric cancer, (2) eradication regresses or inhibits the growth of gastric cancer, and (3) eradication interferes with the discovery of gastric cancer. Considering the biological nature of cancer cell proliferation, a sufficiently long-term follow-up may clarify the effect of eradication therapy on inhibition of the development (not discovery) of gastric cancer and reduction of gastric cancer-related mortality.     

Immunohistochemical detection of neuroendocrine differentiation in non-small-cell lung cancer and its clinical implications

Purpose  The purpose of this study was to prospectively assess the clinical implications of neuroendocrine (NE) differentiation in non-small-cell lung cancer (NSCLC) tumors. Methods  This study accrued subjects suspected to have lung cancer who underwent diagnostic bronchoscopy. Bronchoscopically-biopsied specimens were subjected to routine pathologic examination, and immunohistochemical studies were then performed if lung cancer was diagnosed. Chromogranin-A, synaptophysin, neural cell adhesion molecule, and Leu7 were used to demonstrate NE differentiation. Results  A total of 280 subjects were accrued to this study over a period of 2 years. Among them, 149 subjects were assessable for this study, and 130 were diagnosed as having NSCLC tumors (55 adenocarcinomas, 50 squamous cell carcinomas, 24 NSCLCs not otherwise specified, and 1 typical carcinoid). Large cell NE carcinoma was not observed in this study. Immunohistochemically, NE differentiation was detected in 16% of NSCLC tumors excluding typical carcinoid. By status of NE differentiation of NSCLC tumors, progression-free survivals were similar in 73 patients undergoing non-surgical treatment (positive, n = 10; negative, n = 63) and 43 patients undergoing surgical resection (positive, n = 8; negative, n = 35), respectively. Overall survival of patients with NE-positive tumors appeared to be favorable both for those undergoing non-surgical treatment and those undergoing surgical resection, though the differences in survival were not significant (P = 0.11 and 0.35, respectively). Conclusions  NE differentiation was detected in 16% of NSCLC tumors in our study. However, the prognostic implications of the presence of this feature could not be clearly determined in this study.     

Sonic hedgehog relates to colorectal carcinogenesis

Aim

The activation of Hedgehog signaling, which is critical to normal mammalian gastrointestinal development, is implicated in the development of various tumors, including colorectal cancer. In the pancreas, a precursor lesion overexpresses the Sonic hedgehog (Shh) when compared with normal tissue and cancer. The present study was designed to investigate Shh related protein expression in hyperplastic polyps and the adenoma-carcinoma sequence in the colon and rectum.

Methods

Seventeen hyperplastic polyps, 24 adenomas of the colon, 69 adenocarcinomas (31 well-differentiated, 38 moderately-differentiated), and 30 normal colon samples were used in the study. We checked the expression of Shh, both patched (Ptch) and smoothened (Smo), by immunohistochemistry and compared the expression rate of each group.

Results

Almost all adenomas, 22 of 23 (96%), expressed Shh. In other groups, 4 of 17 hyperplastic polyps (24%), 7 of 31 well-differentiated adenocarcinomas (23%), 13 of 38 moderately-differentiated adenocarcinomas (34%) and none of the 30 normal samples expressed Shh. The rate of expression in Ptch and Smo gradually increased in accordance with tumor progression.

Conclusion

This result indicates that Shh-related carcinogenesis and Shh expression may be a trigger for the adenoma-carcinoma sequence. This study suggests a potential therapeutic target of hedgehog blockade in carcinogenesis.     

Modified liver hanging maneuver with extraparenchymal isolation of the middle hepatic vein in left hepatectomy

Background/purpose

The liver hanging maneuver has been employed mostly for right hepatectomy. After the space between the inferior vena cava and the liver parenchyma is bluntly dissected, a tape is passed through the space, with the upper end of the tape between the right hepatic vein and middle hepatic vein (MHV). We devised a modified maneuver with tape repositioning between the MHV and left hepatic vein (LHV) after extraparenchymal isolation of the MHV, in left hepatectomy with the caudate lobe and without the MHV.

Methods

The ligamentum venosum is divided. Traction of the cranial stump of the ligament in the cranial and left direction shows an avascular plane between the LHV and MHV, and enables the taping of each MHV and LHV. Finally, the upper end of the hanging tape is repositioned.

Results

This maneuver was successfully performed in three patients.

Conclusions

The present maneuver is feasible and useful in left hepatectomy.     

Falciform ligament in pancreatoduodenectomy for protection of skeletonized and divided vessels

Background/purpose

Pancreatic fistula, which is one of the main causes of late postpancreatectomy hemorrhage (PPH), is a common complication of pancreatoduodenectomy (PD). It may erode the anastomosis site and vascular wall in its vicinity, resulting in pseudoaneurysm formation and/or the rupture of major vessels. To protect the vessels near the area for pancreaticojejunostomy from potential pancreatic fistula, we have adopted a surgical option by which such vessels are separated from the pancreaticojejunostomy using a pedicled falciform ligament. We reviewed 36 patients who underwent PD that included this option.

Methods

After the PD was completed (before reconstructions), the pedicled falciform ligament was spread widely on the major vessels exposed during resection, and was fixed to the surrounding retroperitoneal connective tissue. These procedures enabled the complete separation of these vessels from the pancreaticojejunostomy.

Results

The mobilization and placement of the falciform ligament in the space between the pancreaticojejunostomy and the major vessels were successfully carried out without any complications. Although ten (28%) patients developed pancreatic fistula and three (8%) developed intraabdominal infection, none of the patients developed late PPH.

Conclusions

The present surgical option is technically simple and easy, and may be an effective prophylactic measure against late PPH following PD.     

A clinicopathological study of basaloid squamous carcinoma of the esophagus

We reviewed the clinicopathological characteristics of 14 patients who underwent resection of basaloid squamous carcinoma (BSC) of the esophagus. The mean age was 65.3 years, and all patients were male. Seven patients had superficial BSCs and 7 had advanced BSCs. BSCs were associated with high rates of lymph node metastases and venous invasion. With regard to immunohistochemistry, the rate of cyclin D1 expression was higher (13/14), and the preservation rate of E-cadherin expression was lower (4/14), than that seen in ordinary esophageal squamous cell carcinoma. Squamous cell carcinoma components were most often found at sites of lymph node metastases, whereas basaloid components predominated at sites of hematogenous metastases in 4 patients, including lung, brain, and liver. Seven of the 9 patients with stage I or II disease are alive without recurrence. All patients with stage III or IV tumors developed recurrent disease. Primary tumors responded well in 3 patients who received preoperative chemotherapy (5-fluorouracil plus cisplatin) and/or radiotherapy, but further studies are needed to clarify the role of chemoradiotherapy. We believe that control of the hematogenous spread of basaloid components may lead to improved outcomes in patients with esophageal BSC.     

Antialbuminuric advantage of cilnidipine compared with L-type calcium channel blockers in type 2 diabetic patients with normoalbuminuria and microalbuminuria

We evaluated the antialbuminuric advantage of cilnidipine, an N/L-type calcium channel blocker (CCB), compared with L-type CCBs in diabetic patients with normoalbuminuria and microalbuminuria. The study was a multicenter, non-randomized crossover trial. Participants were 90 type 2 diabetic patients exhibiting either normo- or microalbuminuria, and undergoing CCB treatment for ≥6 months prior to study entry. The CCB at the time of entry was continued for the first 6 months (Period 1). Treatment was subsequently switched from cilnidipine to an L-type CCB, or vice versa, for the second 6-month observation period (Period 2). During Period 1, the L-type CCB group showed a significant increase of urinary albumin excretion (UAE) over time, while the cilnidipine group showed no significant elevation. During Period 2, switching of the treatment from the L-type CCB to cilnidipine resulted in significant reduction of the UAE, whereas switching from cilnidipine to the L-type CCB resulted in no significant change in the UAE. This study demonstrated that the antialbuminuric effect of Cilnidipine, but not the L-type CCBs, was sustained even in patients treated for a long time. In addition, the antialbuminuric effect can be anticipated after switching from an L-type CCB to cilnidipine, but not vice versa.     

The benefits of endoscopic nasobiliary drainage without sphincterotomy for acute cholangitis

Objective: Endoscopic nasobiliary drainage for acute cholangitis is performed with or without endoscopic sphincterotomy. However, sphincterotomy carries a small but important risk of complications. We evaluated the benefits of endoscopic nasobiliary drainage without sphincterotomy for acute cholangitis.
Methods: A total of 166 patients underwent endoscopic nasobiliary drainage with sphincterotomy (73 patients, sphincterotomy group) or without (93 patients, nonsphincterotomy group). The indications were acute cholangitis due to choledocholithiasis (120 patients) or benign (10 patients) or malignant (36 patients) biliary stricture. Patient backgrounds were similar in the two groups. The outcomes of nasobiliary drainage were compared between the groups.
Results: Nasobiliary drainage was successful in 69 patients (95%) in the sphincterotomy group and in 89 (96%) in the nonsphincterotomy group. Efficient drainage was achieved in 67 patients (92%) in the sphincterotomy group and in 87 (94%) in the nonsphincterotomy group. Procedure-related complications developed in eight sphincterotomy-group patients (hemorrhage in three, acute cholecystitis in three, acute pancreatitis in one, catheter withdrawal in one) and in two nonsphincterotomy patients (pancreatitis in one, catheter withdrawal in one) (11% vs 2%;   p < 0.05  ). There were no deaths.
Conclusions: Endoscopic nasobiliary drainage without endoscopic sphincterotomy is a simple, safe, and effective treatment for acute cholangitis. This procedure is especially useful for critically ill patients and those with coagulopathy.     

Effect of a Change in the Sleep/Wake Cycle on the Diurnal Variation of Fibrinolytic Parameters

The mechanism underlying the circadian rhythm of fibrinolysis is not well understood. To evaluate the influences of wakefulness and of the intrinsic circadian rhythm on fibrinolytic activity, we examined diurnal changes (8:00 am vs. 8:00 pm) in plasminogen activator inhibitor-1 (PAI-1) activity, tissue plasminogen activator (t-PA) antigen levels, and t-PA activity, as well as in plasma serum cortisol levels, in 10 healthy males (21 ± 2 years) for two consecutive days. On the first day, subjects remained awake all day and night. They slept during the daytime (8:30 am to 5:30 pm) on the following day. PAI-1 activity and cortisol levels were significantly decreased, and t-PA activity tended to increase during the daytime on the first day. On the morning following overnight wakefulness, PAI-1 activity and cortisol levels did not return to the levels of the previous morning. On the second day, the afternoon decrease in PAI-1 activity, but not cortisol levels, was still observed, although its magnitude was substantially attenuated. No significant diurnal changes were observed in the levels of t-PA antigen throughout the study period. These findings suggest that the diurnal variation of fibrinolytic activity may be governed by an intrinsic circadian rhythm of PAI-1, which can be modified by a change in the time of wakefulness.