Variations in the cystic duct: frequency and the relationship among insertion sides and heights on the bile duct.

BACKGROUND: Evaluation of the cystic duct anatomy prior to bile duct or gallbladder surgery is important, to decrease the risk of bile duct injury. This study aimed to clarify the frequency of cystic duct variations and the relationship between them. METHODS: Data of 205 patients who underwent cholecystectomy after imaging at Sada Hospital, Japan, were analyzed. The Chi-square test was used to analyze the relationships among variations. RESULTS: The lateral and posterior sides of the bile duct were the two most common insertion points (92 patients, 44.9%), and the middle height was the most common insertion height (135 patients, 65.9%). Clinically important variations (spiral courses, parallel courses, low insertions, and right hepatic duct draining) relating to the risk of bile duct injury were observed in 24 patients (11.7%). Regarding the relationship between the insertion sides and heights, we noticed that the posterior insertion frequently existed in low insertions (75.0%, P < 0.001) and did not exist in high insertions. In contrast, the anterior insertion coexisted with high and never low insertions. Spiral courses have two courses: anterior and posterior, and anterior ones were only found in high insertion cases. CONCLUSIONS: The insertion point of the cystic duct and the spiral courses tended to be anterior or lateral superiorly and posterior inferiorly. Clinically significant variations in cystic duct insertions are common and surgeons should be cautious about these variations to avoid complications.

Usefulness of several factors and clinical scoring models in preoperative diagnosis of complicated appendicitis.

BACKGROUND: The preoperative distinction between uncomplicated and complicated appendicitis is important to determine the appropriate treatments, such as antibiotics, surgery, or interval appendectomy. Computed tomography (CT) plays an important role; however, combining clinical and imaging factors may make preoperative evaluation more reliable. This study evaluated and analyzed cases and the usefulness of several preoperative factors and clinical scoring models to detect complicated appendicitis. METHODS: A total of 203 patients preoperatively diagnosed with acute appendicitis at our facility were included. Complicated appendicitis was defined as appendicitis with gangrene, perforated appendix, and/or abscess formation. Preoperative factors were collected from published clinical scoring models; patient information, symptoms, signs, results of laboratory tests, and findings of CT. Factors were analyzed using a chi-squared test and the Mann-Whitney U test. RESULTS: The preoperative factors were compared between 151 uncomplicated and 52 complicated appendicitis patients. The significant factors were age ≥40, duration of symptoms >24 hours, body temperature ≥37.3°C, high levels of CRP, findings in CT scan (appendix diameter ≥10 mm, stranding of the adjacent fat, presence of fluid collection, and suspicion of abscess or perforation). We also evaluated the usefulness of clinical scoring models for the detection of complicated appendicitis and found the Appendicitis Inflammatory Response score and two prediction models (Atema score and Imaoka score) showed significance (p < 0.05). High serum CRP level was significantly associated with complicated appendicitis (p < 0.001), and the predicted existence rates of complicated appendicitis were 52.7% for serum CRP level ≥50mg/L, 74.4% for ≥100mg/L, and 82.6% for ≥150mg/L. CONCLUSION: The results demonstrated several preoperative factors and clinical scoring models to increase suspicion of complicated appendicitis. Specifically, high serum levels of CRP may be a useful factor in predicting complicated appendicitis prior to surgery when supported by clinical findings and imaging; however, further research is needed.

Effect of gallbladder polyp size on the prediction and detection of gallbladder cancer.

BACKGROUND: Gallbladder polyps are relatively common. Although most gallbladder polyps are benign, some are malignant. Current guidelines state that malignancy should be suspected for polyps ≥ 10 mm in diameter. We clarified the cancer detection rates in accordance with the size distribution of gallbladder polyps, and evaluated the effectiveness of the reported risk factors in predicting malignancy. METHODS: In this retrospective case-control study, our institutional database was searched to identify patients who underwent laparoscopic cholecystectomy for benign or malignant gallbladder polyps at Sada Hospital, Japan. The chi-squared test was used to analyze the risk factors for malignancy. RESULTS: There were 227 protruding gallbladder lesions. The 206 benign polyps had a diameter of 2-21 mm, while the 21 malignant polyps were 7-60 mm. The cancer detection rates were 16.4% for lesions ≥ 10 mm, 55.9% for lesions ≥ 15 mm, and 94.1% for lesions ≥ 20 mm. Of the benign lesions, cholesterol polyps were the most frequent (50-100%) in all size ranges, even in large lesions (≥ 15 mm). The sessile lesion morphology was significantly more frequent in malignant (60%) than benign lesions (3.4%, p < 0.00001). Multiple polyps were frequently diagnosed not only as cholesterol polyps (81.1%), but also as adenomas (60%); adenomas were found as a single adenoma within other types of polyps. There were two cases of malignant small gallbladder polyps (< 10 mm); these lesions met the surgical indications of a size increase during observation or a sessile morphology. CONCLUSIONS: The cancer detection rate increased significantly with an increase in the lesion size. Risk factors such as a sessile polyp morphology or an increase in lesion size were effective in predicting malignancy for small gallbladder polyps. It might be difficult to accurately predict the pathologic diagnoses of gallbladder polyps preoperatively, as cholesterol polyps were most frequent, even in the large size range.

Preoperative diagnoses and identification rates of unexpected gallbladder cancer.

BACKGROUND: Unexpected gallbladder cancer (UGBC) is sometimes found in the resected gallbladder of patients during or after surgery. Some reports have indicated UGBC identification rates for all gallbladder surgeries, but scarce data are available for the UGBC identification rates for specific gallbladder diseases. The present study was performed to clarify UGBC rates and the factors suspicious for UGBC categorized according to preoperative diagnoses, in patients undergoing laparoscopic cholecystectomy (LSC). METHODS: We recorded data for all LSC surgeries performed in the Department of Surgery, Sada Hospital, Japan since 1991, and analyzed the 28-year data. We used the chi-square test and Kaplan-Meier analysis for this retrospective case-control study. RESULTS: The UGBC identification rate was 0.69% (63/9186 patients). The UGBC identification rates categorized according to the preoperative diagnoses were 1.3% (13/969) for acute cholecystitis, 2.4% (16/655) for benign tumor, 2.0% (28/1383) for chronic cholecystitis or cholecystitis, and 0.054% (3/5585) for cholecystolithiasis. The percentage of older patients (≥ 60 years) was significantly higher in UGBCs compared with cases finally diagnosed as benign in each group categorized according to the preoperative diagnoses (p≤0.0014), except for cholecystolithiasis. In cases pre-diagnosed as benign tumor, UGBCs were associated with higher rates of thickened gallbladder wall compared with benign tumor (69.2% vs. 27.9%, respectively; p = 0.0011). UGBCs pre-diagnosed as acute cholecystitis had higher T2-T4 rates (100% vs. 64.3%, respectively; p<0.05) and lower survival rates (p = 0.0149) than UGBCs pre-diagnosed with chronic cholecystitis. CONCLUSIONS: UGBC identification rates depend on the preoperative diagnosis and range from 0.054% to 2.4%. Older age (≥ 60 years) could be related to UGBC, and a pre-diagnosis of acute cholecystitis might indicate more advanced cancer compared with a pre-diagnosis of chronic cholecystitis.

An additional suture secures against pitfalls in delta-shaped gastroduodenostomy after laparoscopic distal gastrectomy.

Laparoscopic gastrectomy is widely used as a minimally invasive surgery for gastric cancer. Laparoscopic distal gastrectomy must be followed by either a gastroduodenostomy or gastrojejunostomy to restore continuity of the alimentary tract. The intraabdominal delta-shaped gastroduodenostomy using endoscopic linear staplers, which was developed by Kanaya et al., is one of the feasible reconstructive procedures. However, the clinical results still remain uncertain. In 71 patients treated between February 2008 and February 2009, we found that anastomotic failure occurred in six patients and there was an intraabdominal abscess around the anastomosis in two patients, findings which might be associated with technical pitfalls in the procedure. After considering the mechanisms underlying these unfavorable complications, we developed a modification of the procedure to successfully overcome these complications by reinforcement of the anastomosis using simple suturing at the closed common channel on the greater curvature. This modified Kanaya's procedure will be safer and should provide a better intracorporeal gastroduodenostomy after laparoscopic distal gastrectomy.

Lymphadenectomy along the left recurrent laryngeal nerve by a minimally invasive esophagectomy in the prone position for thoracic esophageal cancer.

BACKGROUND: A thoracoabdominal esophagectomy for esophageal cancer is a severely invasive procedure. A thoracoscopic esophagectomy may minimize injury to the chest wall and reduce surgical invasiveness. Conventional thoracoscopic procedures are performed in the left lateral-decubitus position. Recently, procedures performed in the prone position have received more attention because of improvements in operative exposure or surgeon ergonomics. However, the efficacy of the prone position in an aggressive thoracoscopic esophagectomy with an extensive lymphadenectomy has not been fully documented. METHODS: We successfully performed a thoracoscopic esophagectomy with a three-field extensive lymphadenectomy in 43 esophageal carcinoma patients in the prone position from December 2007 to December 2009. We describe our procedures with the patients in the prone position, focusing especially on a lymphadenectomy along the left recurrent laryngeal nerve where the nodes are frequently involved and precise dissection is technically challenging. To determine further the advantages of this position, we retrospectively compared surgical outcomes in 43 patients to those of 34 patients who underwent a thoracoscopic esophagectomy in the left lateral decubitus position as a historical control from January 2006 to November 2007. RESULTS: It was easier to explore the operative field around the left recurrent laryngeal nerve during a thoracoscopic esophagectomy in the prone position. The mean duration of the aggressive thoracoscopic procedure in the prone position was 307 min, which was significantly longer than in the left lateral decubitus position, but the total estimated blood loss in the prone position was significantly lower. There was no difference in the incidence of postoperative complications between the two procedures. CONCLUSIONS: A thoracoscopic esophagectomy in the prone position is technically safe and feasible and provides better surgeon ergonomics and better operative exposure around the left recurrent laryngeal nerve during an aggressive esophagectomy.

Multiple lysine methylation of PCAF by Set9 methyltransferase.

The molecular functions of several non-histone proteins are regulated through lysine modification by histone methyltransferases. The p300/CBP-associated factor (PCAF) is an acetyltransferase that has been implicated in many cellular processes. Here, we report that PCAF is a novel substrate of Set9 methyltransferase. In vitro mapping experiments revealed six lysine residues could be methylated by Set9. A comparison of amino acid sequences of target sites revealed the novel consensus motif which differs from previously identified Set9-consensus sequence. Further methyltransferase assays focusing on the six lysine residues showed that K78 and K89 are preferentially methylated in full-length PCAF in vitro. Using specific antibodies recognizing mono-methylated K89, in vivo PCAF methylation and its nuclear localization were demonstrated. Our data may lead to a new insight into PCAF functions and provide additional information to identify unknown targets of Set9.

Association of Polycomb group SUZ12 with WD-repeat protein MEP50 that binds to histone H2A selectively in vitro.

SUZ12 is a Polycomb group protein that forms Polycomb repressive complexes (PRC2/3) together with EED and histone methyltransferase EZH2. Although the essential role of SUZ12 in regulating the activity of the PRC2/3 complexes has been demonstrated, additional function of this protein was suggested. Here, we show that SUZ12 interacts with WD-repeat protein MEP50 in vitro and in vivo. We show that the MEP50 binds histone H2A selectively among core histones, and mediates transcriptional repression of protein arginine methyltransferase PRMT5, which is known to methylate H2A and H4. These results suggest that SUZ12 might have a role in transcriptional regulation through physical interaction with MEP50 that can be an adaptor between PRMT5 and its substrate H2A.

Thyroid evaluation in patients with primary hyperparathyroidism.

We evaluated the efficacy of preoperative high-resolution ultrasonography (US) for diagnosing possible concomitant thyroid disease which affects the surgical management in patients with primary hyperparathyroidism (pHPT). One hundred and nine patients with sporadic pHPT underwent US with or without ultrasound-guided fine-needle aspiration biopsy (US-FNAB). Diagnosis of concomitant thyroid nodules by US and US-FNAB were compared with the histopathological findings. Of the 109 patients, 19 (17.4%) had malignant thyroid nodules, 26 (23.9%) had benign thyroid nodules alone, and 12 (11.0%) had diffuse goiter. The sensitivity, specificity, and accuracy of diagnosing 72 thyroid nodules were 91.3%, 91.8%, and 91.7% for US, 57.9%, 94.3%, and 81.5% for US-FNAB, and 95.7%, 91.8%, and 93.1% for combined US and US-FNAB, respectively. True positive/false negative ratio of US-FNAB diagnosis was significantly lower in nodules of 5-9 mm than nodules of 10 mm or more. Four unexpected thyroid cancers existed at a different site in 3 of the 39 patients with palpable thyroid disease. Five thyroid cancers were histopathologically confirmed in 5 (7.1%) of 70 patients without palpable thyroid disease. Eight (88.9%) of the 9 non-palpable thyroid cancers were accurately diagnosed by combined US and US-FNAB. Preoperative US is useful for evaluation of possible concomitant thyroid disease, especially for prediction of malignancy.

Significant clinical differences in primary hyperparathyroidism between patients with and those without concomitant thyroid disease.

PURPOSE: We evaluated the differences in diagnosis and treatment for primary hyperparathyroidism (pHPT) in patients with and those without concomitant thyroid disease. METHODS: One hundred and ten patients with pHPT underwent parathyroid localization and thyroid examination by ultrasonography (US) and sestamibi scintigraphy (MIBI). The clinical and biochemical findings, parathyroid localization, and operations performed were compared in 49 patients without thyroid disease and 61 patients with thyroid disease. RESULTS: Asymptomatic hypercalcemia was significantly more prevalent in patients with concomitant thyroid disease (88.5%) than in those without thyroid disease (49.0%) (P < 0.01). The mean serum calcium was significantly higher and the inorganic phosphate level was significantly lower in patients without concomitant thyroid disease than in those with concomitant thyroid disease (P < 0.05, P < 0.01, respectively). The pathologic parathyroid gland was identified significantly more often in patients without concomitant thyroid disease than in those with concomitant thyroid disease both by US and MIBI (P < 0.05). Unilateral exploration was performed more often in patients without thyroid disease than in those with thyroid disease (P < 0.01). CONCLUSION: Primary hyperparathyroidism was diagnosed at an earlier stage in patients with concomitant thyroid disease. Thyroid disease concomitant with pHPT influenced parathyroid localization as well as the indication for minimally invasive parathyroidectomy.

Crank-shaped sternotomy for upper mediastinal lymph node dissection in patients with differentiated thyroid cancer.

We describe our modification of the reversed T-shaped sternotomy. The conventional technique consists of a limited upper sternotomy with transverse division of the sternum. Our modification involves shifting the transverse division lines one costal space between the right and left sides for perfect apposition of the divided upper and lower sternum. This technique can be used for patients with thyroid cancer and mediastinal lymph node metastasis and for those with a mediastinal tumor or certain cardiac disorders.

Liver cyst with biliary communication successfully treated with laparoscopic deroofing: a case report.

A 71-year-old Japanese woman complained of right upper abdominal fullness and pain. Computed tomography revealed a huge cyst in the right lobe of the liver, measuring 16 cm in diameter. She underwent laparoscopic deroofing of the liver cyst. On operation, needle aspiration of the cyst yielded clear serous fluid without any bile contamination. However, after the cyst was deroofed with laparoscopic coagulating shears, bile leakage was recognized from a tiny orifice in the cyst cavity. A catheter was inserted via the orifice for cholangiography, which demonstrated a communication with the biliary tract. The orifice was easily closed with a laparoscopic suturing device. Operation time was 5 hours and 30 minutes, and blood loss was 300 grams. Pathological examination of the liver cyst was consistent with a simple cyst. The postoperative course was uneventful, and the patient has had no recurrence to date at 13 months. Laparoscopic deroofing is a recommended treatment for a liver cyst even in the presence of cystobiliary communication.

Influence of renal function on clinico-pathological features of primary hyperparathyroidism.

OBJECTIVE: Disturbed renal function may play an important role in the clinico-pathological presentation of primary hyperparathyroidism (pHPT). We studied the influence of renal function on the clinico-pathological characteristics of 141 patients (123 women and 18 men) with surgically proven pHPT. METHODS: The 141 patients were assigned to one of two groups based on creatinine clearance (C(cr)) level: a renal insufficiency group (n=37) in which C(cr) of patients was <70 ml/min and a normal renal function group (n=104) in which C(cr) was > or =70 ml/min. Clinical presentation and biochemical indices were evaluated and compared between the two groups. RESULTS: Age, and frequency of hypertension and of diabetes mellitus were significantly (P<0.001, P<0.05 and P<0.05 respectively) higher in the renal insufficiency group than in the normal renal function group. Serum levels of calcium, intact parathyroid hormone and bone Gla protein were significantly (P<0.05) higher and the excised parathyroid weighed significantly more (P<0.05) in the renal insufficiency group than in the normal renal function group; however, serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and 24 h urinary calcium excretion were significantly (P<0.001 and P<0.05 respectively) lower in the former than in the latter group. There was a significant inverse correlation between C(cr) level and serum calcium (r=0.315, P<0.001) and a significant positive correlation between C(cr) level, 1,25(OH)(2)D (r=0.315, P<0.001), and 24 h calcium excretion (r=0.458, P<0.0001). CONCLUSIONS: Clinico-pathological features of pHPT were notably influenced by even moderate renal insufficiency. Urinary calcium excretion decreased according to the decrease in glomerular filtration rate. Therefore, endocrinologists need to appraise urinary calcium excretion and renal function of pHPT patients when considering surgery or in discriminating familial hypocalciuric hypercalcemia.

Serous cystadenoma of the pancreas associated with pancreas divisum.

Pancreas divisum is an embryologic anomaly of the pancreas that is characterized by a lack of fusion of the dorsal and ventral pancreatic ducts. It is rarely associated with pancreatic neoplasms. We report herein a rare association of pancreas divisum and serous cystadenoma of the pancreas. A 46-year-old Japanese woman presented with epigastralgia. Ultrasonography, computed tomography (CT) and magnetic resonance cholangiopancreatography revealed a multilocular cystic mass, measuring 7 cm in diameter, with a central stellate scar, in the body and tail of the pancreas. Angiography demonstrated a relatively hypervascular mass, suppressing the splenic vein. No arterial encasement was evident. Endoscopic retrograde pancreatography through the major papilla demonstrated only the duct of Wirsung; cannulation into the minor papilla was unsuccessful. In addition, CT showed a mildly dilated main pancreatic duct draining into the minor papilla. Distal pancreatectomy and splenectomy were performed, with the tentative diagnosis being serous cystic neoplasm of the pancreas, possibly malignant, and pancreas divisum. The cut surface of the resected specimen had a honeycomb-like appearance and the specimen consisted of multiple cysts of various sizes. Histopathological examination showed multiple cysts lined by a single layer of flat or cuboidal epithelial cells with glycogen in the cytoplasm. There was no evidence of malignancy. The histopathological diagnosis was serous cystadenoma of the pancreas. To the best of our knowledge, only three cases of serous cystadenoma of the pancreas associated with pancreas divisum have been reported. We report the fourth case of such an association, and briefly review the literature.

Mucinous cystadenoma of the pancreas resected 11 years after cystgastrostomy.

There have been numerous reports that mucinous cystadenoma of the pancreas can transform to mucinous cystadenocarcinoma after cystenterostomy, but few authors have reported morphological changes long after cystenterostomy for mucinous cystadenoma. A 41-year-old Japanese woman had undergone cystgastrostomy at a nearby hospital 11 years before undergoing the treatment reported here. The preoperative diagnosis at the time of cystgastrostomy was a pancreatic cyst. At laparotomy a cyst, measuring 10cm in diameter, was found in the body and tail of the pancreas. The histopathological diagnosis of the cyst wall was mucinous cystadenoma of mild dysplasia. Computed tomography 10 years after the cystgastrostomy showed that the cyst had decreased in diameter from 10 cm to 5cm. Gastroscopy showed a scar at the cystgastrostomy site in the stomach. A complete resection of the mucinous cystadenoma was done, 11 years after the cystgastrostomy, because of the malignant potential. The resected specimen showed mucinous cystadenoma of mild dysplasia with structural and cellular atypia similar to that in the previous specimen. There was no malignant change. The patient was discharged after an uneventful postoperative course and no recurrence has been evident for 6 months to date. This case showed imaging and histopathological evidence of the slow-growing nature of mucinous cystadenoma of the pancreas.

Vitamin D status in Japanese patients with hyperparathyroidism: seasonal changes and effect on clinical presentation.

The disturbance of vitamin D metabolism plays an important role in determining the clinical presentation of hyperthyroidism. We studied 72 patients (65 women, 7 men) with primary hyperparathyroidism (pHPT). Clinical presentation, biochemical indices, and bone mineral density (BMD) were compared in three patient groups classified according to their serum 25-hydroxyvitamin D (25OHD) levels: 23 patients whose 25OHD level was <25 nmol/L comprised the low group, 26 whose level was 25 to 40 nmol/L made up the intermediate group, and 23 whose level was > 40 nmol/L comprised the high group. The mean serum calcium level was 10.8 +/- 0.9 mg/dl, and the mean weight of the resected parathyroids was 684 +/- 749 mg. The mean serum 25OHD level was 36.5 +/- 16.3 nmol/L (normal 25-100 nmol/L). Levels were below normal in 23 patients (32%). No between-group differences existed for clinical presentation, biochemistry, or BMD. Only differences in mean patient age were statistically significant between groups. Vitamin D deficiency is common among Japanese patients with pHPT, but the effects of HPT on clinical, biochemical, and densitometric indices are not pronounced. Our study population was at an early stage of pHPT, so the vitamin D deficiency may not be associated with the effects of HPT.