High Expression of DARPP-32 in Colorectal Cancer Is Associated With Liver Metastases and Predicts Survival for Dukes A and B Patients: Results of a Pilot Study

The purpose of this study was to investigate prognostic significance of Dopamine and cAMP-Regulated neuronal Phosphoprotein 32 (DARPP-32) expression in primary colorectal cancer. The study material consisted of clinical and histopathological data of 100 patients operated for colorectal cancer between 1994 and 1997. For immunohistochemical analysis, specific rabbit antibodies for DARPP-32 were used and the percentage of stained tumor cells was calculated under gross magnification (400 times) on a sample of 500 tumor cells. DARPP-32 expression in the primary tumor was significantly greater in patients with distant metastases compared to patients with no distant metastases (p=0.002). In multivariate regression analysis, DARPP-32 expression in the primary tumor was a significant predictor of distant metastases. With a cut-off point of 76.5%, DARPP-32 expression in the primary tumor significantly influenced both overall and disease free survival, especially for Dukes A and B patients (p=0.037). The results of this study indicate that DARPP-32 may be a potential marker of worse prognosis and a valuable tool for managing further adjuvant treatment in patients with stages Dukes A and B colorectal cancer.Key words: Colorectal neoplasms, Dopamine and cAMP-regulated phosphoprotein 32, Humans, Nerve tissue proteins, Liver metastasesColorectal cancer is the second most common cause of cancer related death in Western Europe and the United States, with the incidence of 50/100,000 population.¹ In spite of significant developments in surgery and new chemotherapy drugs and protocols as well as radiotherapy regimens, this malignancy still has high mortality.²The 5-year survival rate of colorectal cancer patients with Dukes A cancer ranges from 74 to 93%. Patients with Dukes B cancer have a 5-year survival of 40 to 82%, and those with positive lymph nodes (Dukes C) have a 5-year survival rate of 30 to 59%.^3,4 Recurrences are observed in as much as 34% of patients with Dukes A and B stage, compared with 59% in patients with lymph node metastases.⁵Liver metastases are a well proven major determinant of survival in patients with colorectal cancer.^2,6 Therefore, better selection of patients with potential to develop liver metastases or those having occult metastases may increase the survival of those patients in whom adjuvant therapies would not otherwise be indicated.^2,5,7Recently, overexpression of dopamine and 3′5′-cyclic adenosine monophosphate regulated neuronal phosphoprotein 32 (DARPP-32) has been found in several gastrointestinal adenocarcinomas.⁸ Although most of the research on this protein focused on its role in the central nervous system,^9–11 the finding of overexpression of this protein in cancer tissues brought up the hypothesis of its role in carcinogenesis.^8,12 Genetic studies led to the discovery of frequent 17q DNA amplifications in gastric cancer.⁸ Subsequently, the gene located at this site, called PPP1R1B, has been sequenced and found to encode DARPP-32 molecule, that was brought into connection with several malignancies.^8,13–18 The DARPP-32 molecule is a protein with molecular mass of 32 kDa, consisting of 204 amino acids and 4 phosphorylation sites: Thr34, Thr75, Ser102, and Ser137. Depending on the phosphorylation of 1 of these 4 amino acids, the DARPP-32 molecule is acting as the signal integrator and as the regulator of the phosphorylase and kinase activities in eukaryotic cells.¹⁹Basic research indicates that DARPP-32 may be associated with worse prognosis in some carcinomas.²⁰ However, it is remains unknown if evaluation of DARPP-32 expression in colorectal cancer patients may aid to evaluate prognosis.The purpose of this study was to investigate possible associations of DARPP-32 expression in primary colorectal cancer with known prognostic determinants of colorectal cancer and therefore set the basis for further clinical research.     

Perioperative Allogeneic Blood Transfusion Is Associated With Surgical Site Infection After Abdominoperineal Resection—a Space for the Implementation of Patient Blood Management Strategies

Allogeneic blood transfusion (ABT) has been reported as a major risk factor for surgical site infection (SSI) in patients undergoing colorectal surgery. However, the association of ABT with SSI in patients undergoing abdominoperineal resection (APR) and total pelvic exenteration (TPE) still remains to be evaluated. Here, we aim to elucidate this association. The medical records of all patients undergoing APR and TPE at our institution in the period between January 2000 and December 2012 were reviewed. Patients without SSI (no SSI group) were compared with patients who developed SSI (SSI group), in terms of clinicopathologic features, including ABT. In addition, data for 262 patients who underwent transabdominal rectal resection at our institution in the same period were also enrolled, and their data on differential leukocyte counts were evaluated. Multivariate analysis showed that intraoperative transfusion was an independent predictive factor for SSI after APR and TPE (P = 0.004). In addition, the first–operative day lymphocyte count of patients undergoing APR, TPE, and transabdominal rectal resection was significantly higher in nontransfusion patients compared with transfusion ones (P = 0.026). ABT in the perioperative period of APR and TPE may have an important immunomodulatory effect, leading to an increased incidence of SSI. This fact should be carefully considered, and efforts to avoid allogeneic blood exposure while still achieving adequate patient blood management would be very important for patients undergoing APR and TPE as well.Key words: Colorectal cancer, Abdominoperineal resection, Surgical site infection, Allogeneic blood transfusion, Patient blood managementPostoperative surgical site infection (SSI) is one of the most frequent complications associated with various surgical procedures, and it results in adverse outcomes, including longer hospital stay, higher health care costs, and increased surgical mortality.¹ It is one of the most frequent nosocomial complications, accounting for almost one fifth of all health care–associated infections.² Colon surgery and rectal surgery are associated with higher SSI rates compared with most other abdominal procedures, with 5% to 25% of colon and rectal surgery patients developing incisional and organ/space SSI.^3–5 Moreover, the incidence of overall SSI was reported to be higher in rectal surgery patients (17%–28%) than in colonic surgery patients (9%–23%),^3,5,6 with especially higher overall SSI rates observed in patients undergoing abdominoperineal resection (APR; 12%–51%).^7–9 These are attributed to the high infection rates of the perineal wound, reported to be as high as 21%.¹⁰ Thus, the incidence of SSI associated with APR should be the highest among the various abdominal operative procedures.Various risk factors for postoperative SSI in colorectal surgery were reported previously. Open surgery,^10–12 perioperative allogeneic blood transfusion (ABT),^4,10,12 and prolonged operation time^4,9 have been found to be risk factors for SSI in a number of studies. Although several preceding reports have investigated the risk factors for SSI associated with APR, the reported independent risk factors varied among the studies. Although a number of studies have reported on the role of ABT as a strong risk factor for incisional SSI in colorectal surgery,^13,14 only one study has investigated on its relevance to the onset of incisional SSI after APR procedure; but this study failed to demonstrate a significant association. Presently, therefore, the role of ABT as a potential risk factor for incisional SSI in APR remains to be elucidated, and doing so will be very important for the implementation of measures to achieve patient blood management in this group of patients.In this study, we aimed to elucidate the risk factors for SSI in patients receiving APR, especially focusing on ABT.     

Medullary Carcinoma of the Thyroid With Axillary Metastasis: A Case Report

We report a case of axillary lymph node metastasis as a consequence of medullary thyroid carcinoma (MTC) in a 42-year-old man. On January 2009, the patient was referred to us for the management of right cervical lymph node enlargement. Total thyroidectomy was performed with right-sided functional neck dissection. Postoperative histopathology revealed MTC in the right lobe of the thyroid, with extrathyroidal extension and right-sided neck metastases. Multiple left cervical, mediastinal, and right axillary lymphadenopathies were detected at the third year follow-up exam. Left-sided functional neck dissection, axillary lymph node dissection, and mediastinal lymph node dissection were performed, and the pathologic outcomes revealed as the metastatic dissemination of MTC. After a disease-free term for 1 year, multiple metastatic lesions were detected in the patient.Key words: Medullary thyroid cancer, Lymph node metastasis, Axillary involvementMedullary thyroid cancer (MTC) is a rare tumor originating from the parafollicular C cells of the thyroid gland. MTC accounts for approximately 3% to 5% of all thyroid cancers.¹ The frequently used prognostic markers in the follow-up period of MTC patients are serum calcitonin and carcinoembryonic antigen (CEA) levels. Calcitonin hormone is a specific and sensitive biomarker for parafollicular C-cell disorders. The CEA produced by neoplastic C cells is generally considered a marker of dedifferentiation and is associated with worse prognosis for MTC.^2,3 MTC may occur sporadically or may be inherited. Hereditary forms of this cancer account for 25% of all cases and include familial MTC and multiple endocrine neoplasia syndromes (MEN 2A, MEN 2B). Seventy-five percent of cases are sporadic.⁴ The overall prognosis of MTC is affirmative, with a 10-year overall survival rate of approximately 95% for patients with tumors confined to the thyroid gland. However, for patients with distant metastasis at presentation, the 10-year overall survival rate is estimated to be only 40%.⁵ For metastatic cases, lymph node involvement is very common throughout the clinical course. During initial staging, the incidence of pathologically proven cervical lymph node metastasis has been reported as 71% to 80%^6–8; the corresponding value for mediastinal involvement is 36%.^6,8 Whereas, distant metastases have been reported in 20% of MTC patients.⁹ Considering the spectrum of MTC, axillary lymph node metastasis (LNM) is rare, and there are reports of isolated cases.^10–12     

Phase I Dose-Escalation Study of Docetaxel,Cisplatin, and 5-Fluorouracil Combination Chemotherapy in Patients With Advanced Esophageal Carcinoma

A dose-escalation study of docetaxel (DOC), cisplatin (CDDP), and 5-fluorouracil (5-FU; DCF combination regimen) was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in advanced esophageal carcinoma. Eighteen patients with esophageal carcinoma were enrolled and received DCF combination therapy at different dose levels. DLTs included febrile neutropenia and oral mucositis. DLT occurred in 2 out of 6 patients at level 2 and 3. The study proceeded to level 4, according to the protocol. The level 4 dose was defined as the MTD and the level 3 dose was defined as the RD. The RD for DCF combination chemotherapy for advanced esophageal carcinoma in the present study was 70 mg/m² DOC plus 70 mg/m² CDDP on day 1 plus 700 mg/m² 5-FU on days 1–5 at 4-week intervals. This regimen was tolerable and highly active. A phase II study has been started.Key words: Docetaxel, Cisplatin, Fluorouracil, Esophagus, Phase ILocally advanced esophageal carcinoma is often refractory to current therapeutic approaches, and its prognosis is grim.^1,2 Patients with unresectable or inoperable disease are usually treated with chemotherapy or chemoradiotherapy.^3,4 Although various chemotherapy regimens are available, esophageal cancer carries a very poor prognosis, with a survival time of less than 8.1 months with current chemotherapies used singly or in combination with 5-fluorouracil (5-FU), vindesine, mitomycin, docetaxel (DOC), paclitaxel, cisplatin (CDDP), irinotecan, vinorelbine, or capecitabine.⁵ 5-FU and CDDP combination therapy (PF) is regarded as standard,⁶ for which the median survival time is reported to be 9.2 months for responders and 5.3 months for nonresponders.⁷In recent years, a new combined chemotherapeutic regimen consisting of DOC, CDDP, and 5-FU (DCF) has received much attention for the treatment of esophageal cancer.⁸ The DCF regimen exploits the strong clinical effects of each component. However, there are few reports describing the use of a combination of DOC, CDDP, and 5-FU (DCF) for esophageal carcinoma.⁹ Therefore, we conducted a phase I clinical trial of a DCF regimen in patients with advanced esophageal carcinoma. Our aim was to determine the recommended dose (RD), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) of DCF combination chemotherapy for patients with esophageal carcinoma. Secondary objectives were to assess treatment-related toxicity and efficacy.     

Giant Extraluminal Leiomyoma of the Colon: Rare Cause of Symptomatic Pelvic Mass

Leiomyomas (LMs) may appear throughout the entire gastrointestinal tract but are rarely seen in the colon-rectum and only 5 of those measured greater than 15 cm in diameter. Pain and palpable abdominal mass are the most common symptoms. Surgical resection is the treatment of choice for most LMs. We here describe a case of a 46-year-old woman who presented with a 3-month history of abdominal pain associated with worsening constipation and abdominal distension. A pelvic solid, polylobulate, left-sided mass was noted on examination. Preoperative findings revealed a dishomogeneous sigmoid mass with calcified spots compressing small intestine and bladder. At laparotomy, a large polylobulate and well-circumscribed mass arising from the descending colon mesentery and displacing small intestine, uterus, and ovaries. A segmental colon resection was performed. An extraluminal 18- × 12- × 5-cm paucicellular sigmoid colon leiomyoma was histologically diagnosed. Our case is one of the few giant (>15 cm) sigmoid colon LMs reported in the literature. Although rare and benign in nature, LMs of the colon can cause life-threatening complications that could require emergency treatment and they should be included in the differential diagnosis of large abdominopelvic masses. Follow-up after surgery is necessary for tumors with any atypia or mitotic activity.Key words: Leiomyoma, Digestive tract, Bowel obstruction, Pelvic massPrimary leiomyomas (LMs) present most commonly in the female genital tract and skin but they are rarely seen in the colon-rectum. Macroscopically, LMs may be intraluminal, intramural, extramural, or dumbbell.^1,2 The majority of LMs remain asymptomatic until they have reached a large size: most common symptoms are pain and palpable abdominal mass.^1,2 Symptomatic left colon LMs are uncommon and only 5 of those reported in the literature measured greater than 15 cm in diameter.¹ Histologically, most of them arise from the muscularis propria.^1,3 The most important differential diagnoses are malignant leiomyosarcoma and gastrointestinal stromal tumors (GIST).^1,3 Surgical resection is the treatment of choice for large LMs: complete excision should be always attempted and follow up is necessary for tumors with any atypia or mitotic activity.^1,2 Although rare and benign in nature, LMs of the colon can cause life-threatening complications that require emergency treatment.^1–3 We here describe a case of large extraluminal sigmoid colon LM causing pain and worsening bowel obstruction.     

Fecoflowmetric Analysis of Anorectal Motor Function in Postoperative Anal-Preserving Surgery Patients With Low Rectal Cancer Comparison With the Wexner Score and Anorectal Manometry

The aim of this study was to elucidate whether fecoflowmetry (FFM) could evaluate more detailed evacuative function than anorectal manometry by comparing between FFM or anorectal manometric findings and the clinical questionnaires and the types of surgical procedure in the patients who received anal-preserving surgery. Fifty-three patients who underwent anal-preserving surgery for low rectal cancer were enrolled. The relationships between FFM or the manometric findings and the clinical questionnaires and the types of procedure of anal-preserving surgery were evaluated. There were significant differences between FFM markers and the clinical questionnaire and the types of the surgical procedure, whereas no significant relationship was observed between the manometric findings and the clinical questionnaire and the types of the surgical procedure. FFM might be feasible and useful for the objective assessment of evacuative function and may be superior to manometry for patients undergoing anal-preserving surgery.Key words: Anorectal manometry, Anal-preserving surgery, Fecoflowmetry, Incontinence, Rectal cancerSphincter preservation has been one of the key issues of rectal cancer surgery. Low anterior resection (LAR)¹ and internal and external sphincter resection (ISR and ESR) are anal-preserving surgeries.^2,3 The aim of these procedures is to restore the normal process of defecation, along with its function, and to improve the quality of life of patients by avoiding permanent colostomy. However, anal-preserving surgery is often associated with evacuative dysfunction and various degrees of incontinence.^4–7Most studies that have assessed the evacuation function have used clinical questionnaires, which are subjective and may vary according to the patient perception.⁷ There are many factors that can affect the evacuative function, such as the stool consistency, rectal capacity, anal sphincters, pelvic floor muscles, and intra-abdominal pressure. Although manometry with or without the clinical score has also commonly been used, fecoflowmetry (FFM) has been reported to be more accurate and useful for assessing the postoperative anorectal motor function.^8–13 FFM was first introduced by Shafik and is a dynamic method for examining the anorectal motor activity that simulates the natural act of defecation.¹⁴ Some studies have shown its usefulness in postoperative patients with anorectal disease,^8–11 but only a few studies have been performed to examine the evacuative function following anal-preserving surgery.^12,13 The aim of this study was to evaluate the evacuative function in the postoperative period following anal-preserving surgery in patients with low rectal cancer using FFM, and to compare the results with the Wexner score and anorectal manometry.¹⁵     

Preoperative Carcinoembryonic Antigen and Prognosis of Colorectal Cancer. An Independent Prognostic Factor Still Reliable

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient''s prognosis, although this—to date—has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging.Key words: Colorectal carcinoma, Preoperative carcinoembryonic antigen, Disease-free survival, Independent prognostic factorIn the world today, more than 1 million cases of patients with colorectal neoplasia are identified each year. Forty percent of these will have a poor prognosis for which targeted therapeutic strategies could most likely be more effective.^1–3 For this reason, finding prognostic factors that are early, reliable, and related to the extent of the tumor is of the utmost importance. Among these, the most that are considered even to this day are T and N parameters.^1,2,4,5 Less relied upon, however, is the M parameter, which is often understaged due to inadequate pretreatment diagnostic methods.⁶ However, these parameters, which are available to us only after surgery, do not represent the gold standard. In fact, the prognosis of patients with the same staging is often various and that the need to continually implement ever-changing variables in an already excessively fragmented staging is still present.^2,4,7–9Recently, in light of these needs, great attention has been paid to the study of molecular and genetic markers. At present, these markers still have not found a regular application due to the complexity of their determination, the difficulty of standardization and, last but not least, the low cost-benefit ratio.^1,3,4,9,10With this in mind, in our opinion, the carcinoembryonic antigen (CEA) maintains its position, as for over 30 years it has continued to be the most widely used marker¹¹ and whose validity, with regard to colorectal follow-up, has been sanctioned by leading organizations such as the American Society of Clinical Oncology (ASCO)¹² and the European Group on Tumor Markers.¹³ Moreover, as Herrera¹⁴ and Wanebo¹⁵ had already reported by the end of the ‘70s, the preoperative determination of the CEA (p-CEA) seems to be related both to the staging of colorectal neoplasia and to the patient''s prognosis. However, to date, none of this has been conclusively demonstrated and is still a matter of intense debate both in prestigious scientific journals^{4,7,11,16–21} as well as in different guidelines.²²The American Society of Clinical Oncology itself, if on the one hand suggests using the determination of the CEA in the preoperative staging thus justifying a worse prognosis when increased,¹² on the other, does not validate using the p-CEA in the determination of an adjuvant or neo-adjuvant therapeutic strategy.²³Regarding this issue, we believe it still pertinent to evaluate whether in a sample of patients radically treated for colorectal carcinoma, the determination of the p-CEA may have a prognostic value and constitute an independent risk factor in relation to disease-free survival (DFS).     

Our Contrivances to Diminish Complications After Pylorus-Preserving Pancreaticoduodenectomy

The objective of this study is to diminish postoperative complications after pylorus-preserving pancreaticoduodenectomy. Pylorus-preserving pancreaticoduodenectomy is still associated with major complications, especially leakage at pancreatojejunostomy and delayed gastric emptying. Traditional pylorus-preserving pancreaticoduodenectomy was performed in group A, while the novel procedure, an antecolic vertical duodenojejunostomy and internal pancreatic drainage with omental wrapping, was performed in group B (n = 40 each). We compared the following characteristics between the 2 groups: operation time, blood loss, time required before removal of nasogastric tube and resumption of food intake, length of hospital stay, and postoperative complications. The novel procedure required less time and was associated with less blood loss (both P < 0.0001). In the comparison of the 2 groups, group B showed less time for removal of nasogastric tubes and resumption of food intake, shorter hospital stays, and fewer postoperative complications (all P < 0.0001). The novel procedure appears to be a safe and effective alternative to traditional pancreaticoduodenectomy techniques.Key words: Pylorus-preserving pancreaticoduodenectomy (PPPD), Internal stent, Omental wrapping, Postoperative stayPylorus-preserving pancreaticoduodenectomy (PPPD) has replaced conventional pancreaticoduodenectomy (PD) as the standard operation for both benign and malignant conditions.^1,2 Pylorus-preserving pancreaticoduodenectomy was first reported by Watson in 1944 and popularized by Traverso in 1978. Mortality related to PD has been reduced, or even eliminated^3–5; however, in comparison with other abdominal operations such as gastrectomy and rectal surgery, PPPD has a high morbidity rate.^6–9 Pancreatic fistula is one of the most difficult complications to eradicate in both PD and PPPD. In addition, delayed gastric emptying is a specific complication of PPPD. These complications may extend the duration of hospital stay required after the operation.Sugiyama et al¹⁰ first reported that delayed gastric emptying can be prevented by a vertical duodenojejunostomy. Since then, antecolic reconstruction and vertical stomach reconstruction have also been reported to be useful procedures for minimizing the adverse effects in both pancreaticojejunostomy and pancreaticogastrostomy.^11,12 The likelihood of a pancreatic fistula can also be reduced, by a duct-to-mucosa pancreaticojejunostomy^3,13,14 and by the use of omental wrapping.¹⁵ However, none of the studies have examined whether the complications after PPPD would be diminished if vertical reconstruction, antecolic reconstruction, internal drainage, and omental wrapping were simultaneously performed.To address this problem, we developed a new reconstruction method for preventing delayed gastric emptying and pancreatic fistula. Here, we describe this new technique for the first time, and compare the efficacy of this technique with that of our classical method.     

Elevated Platelet Count as Predictor of Recurrence in Rectal Cancer Patients Undergoing Preoperative Chemoradiotherapy Followed by Surgery

The impact of systemic inflammatory response (SIR) on prognostic and predictive outcome in rectal cancer after neoadjuvant chemoradiotherapy (CRT) has not been fully investigated. This retrospective study enrolled 89 patients with locally advanced rectal cancer who underwent neoadjuvant CRT and for whom platelet (PLT) counts and SIR status [neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR)] were available. Both clinical values of PLT and SIR status in rectal cancer patients were investigated. Elevated PLT, NLR, PLR, and pathologic TNM stage III [ypN(+)] were associated with significantly poor overall survival (OS). Elevated PLT, NLR, and ypN(+) were shown to independently predict OS. Elevated PLT and ypN(+) significantly predicted poor disease-free survival (DFS). Elevated PLT was identified as the only independent predictor of DFS. PLT counts are a promising pre-CRT biomarker for predicting recurrence and poor prognosis in rectal cancer.Key words: Platelet, Neutrophil/lymphocyte ratio, Platelet/lymphocyte ratio, Rectal cancer, Prognosis, ChemoradiotherapyPreoperative chemoradiotherapy (CRT) and total mesorectal excision for the management of locally advanced rectal cancer (LARC) have significantly decreased local recurrence rates and improved sphincter preservation and patient survival.^1,2 However, distant recurrence remains the major cause of mortality in patients who undergo preoperative CRT followed by Total Mesorectum Excision (TME). Further improvements in the survival rate cannot be achieved without the control of postsurgical distant recurrence.Postoperative histopathologic features such as surgical margins (achievement of R0 resection) and lymph node metastases are recognized as predictors of local and distant recurrence in rectal cancer patients treated by preoperative CRT.^3–5 However, preoperative serum markers that could predict recurrence and/or poor prognosis⁶ might present a convenient tool to permit intensification of either preoperative neoadjuvant or postoperative adjuvant chemotherapeutic strategies.Aberrant activation of platelets (PLT) and the coagulation pathway are associated with malignancies. Increased PLT count may indicate poor prognosis in cancer patients,^7,8 nearly a third of whom have thrombocytosis at diagnosis and before treatment,⁹ although the mechanisms by which thrombocytosis develops in malignancies remains unknown. Particularly in colorectal cancer, the prognostic significance of thrombocytosis was recently reported by Ishizuka et al and Cravioto-Villanueva et al.^10,11 Pretreatment thrombocytosis is also a predictor for CRT response and local recurrence in rectal cancer patients.¹²However, the systemic inflammatory response (SIR), which is thought to be secondary to hypoxia or tumor necrosis, is associated with anti-apoptotic characteristics in cancer cells¹³ and has been shown to act as a biomarker of outcome in a variety of malignancies.¹⁴ Neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) are two representative indexes of systemic inflammation; their prognostic values have been studied in many cancer types.¹⁵ High NLR or PLR reportedly predicts poor outcomes in colorectal cancer patients who undergo primary resection without lymph node metastases and who undergo hepatectomy for liver metastasis.^16–18 Recently, the clinical significance of NLR in rectal cancer patients undergoing CRT followed by surgery has been demonstrated, showing that it was predictor for recurrence and overall survival.¹⁹In this study, we investigated the correlations between levels of PLT, NLR, and PLR in pretreatment blood tests, and clinicopathologic features in patients who undergo CRT followed by TME for locally advanced rectal cancer, and evaluated and compared their potentials as prognostic biomarkers.     

Substernal Goiter: When is a Sternotomy Required?

The presence of substernal goiter is, per se, an indication for surgical management. Surgical approach of substernal goiter can most commonly be performed using the cervical access, but at times, a sternotomy or thoracotomy is necessary. The aim of this study was to identify the preoperative predictors of a sternotomy in the management of substernal goiter in order to provide better preoperative planning and patient consent. Between 2005 and 2012, 665 patients were referred to our clinic for thyroidectomy, 42 patients (6.3%) had substernal goiter and were included in this study. All substernal goiters were treated surgically, 38 (90.5%) by a cervical approach and 4 (9.5%) by full median sternotomy. All surgeries were successful, with no major postoperative complications. Minor postoperative complications of transient hypocalcemia and transient paralysis of the recurrent laryngeal nerve occurred in 5 (11.9%) and 2 (4.7%) cases, respectively. Indication of median sternotomy was as follows: extension of goiter below the aortic arch, large thyroid tissue extending towards tracheal bifurcation, and ectopic thyroid tissue in the mediastinum. Substernal goiter can be removed through a cervical incision, but on rare occasions, a median sternotomy may be required.Key words: Sternotomy, Substernal goiter, Surgery, TreatmentSubsternal goiter (SG) was first described by Haller in 1749 and first surgically removed by Klein in 1820.¹⁻⁴ There is no uniform definition of substernal goiter.¹⁻³ However, various different criteria have been suggested by authors. These include a thyroid gland extending 3 cm below the sternal notch or extension of the gland below the fourth thoracic vertebra.^5,6 An extension of the thyroid gland below the thoracic inlet has been defined as substernal, retrosternal, intrathoracic, or mediastinal goiter. Drawing upon the relationship of the intrathoracic extension of SG to the arcus aorta and the right atrium and findings from imaging methods, diagnostic classifications have been established that take into account the percentage of goitrous thyroid in the mediastinum.^7,8 Substernal goiters are common, with a reported incidence of 1−20% of all patients undergoing thyroidectomy.^3,5,9−14 Diagnosis of substernal goiter is most frequently made in the fifth or sixth decade of life, with a female/male rate of 4:1.^11,14,15 The vast majority of SGs (85−90%) are located in the anterior mediastinum with the remainder (10−15%) located in the posterior mediastinum.^1,10,16,17Substernal goiters show, in most cases, a slow-growing enlargement, which usually remain asymptomatic for many years; about 20−40% of substernal goiters are discovered as an incidental finding on a radiographic examination.^2,11,18 Patients with mediastinal goiter are rarely asymptomatic. The most common symptoms are related to compression of the airways and the esophagus, and represented by dyspnea, choking, inability to sleep comfortably, dysphagia, and hoarseness.^2,12,14,18 In the diagnostic management of mediastinal goiter, chest computed tomography (CT) was of the highest value. CT scanning is, at present, the most exhaustive examination for assessment of the extent of the goiter and compression effects on adjacent anatomic structures. A preoperative CT scan should be routinely performed in every suspicion of a substernal goiter.^12,19−21 Magnetic resonance imaging (MRI) adds little additional information to that obtained with CT and is not routinely used.¹¹Substernal goiter must be removed surgically due to relation to compressive symptoms, potential airway compromise, and the possibility of an association with thyroid malignancy.¹⁷ There is a general consensus that most can be successfully removed via a cervical approach and that thoracic access is rarely necessary.^9,11,12 Various factors have been reported to increase the likelihood of a median sternotomy being required. These factors include involvement of the posterior mediastinum, extension of the goiter to the aortic arch, recurrent goiter, superior vena cava obstruction, malignancy with local involvement, and emergent airway obstruction.^{6,10,12,16,17,19} In addition, inability to palpate the lowermost extent of the gland also is considered to be an indication for median sternotomy. The incidence of sternotomy in substernal goiter is variable, ranging between 0−11 %.^2,9,11,12 This wide range in incidence might be related to variation in the definition of substernal goiter.In order to improve preoperative planning and patient consent, we aimed to identify the preoperative predictors of a sternotomy in the management of substernal goiter.     

Anti-CD27 Antibody Potentiates Antitumor Effect of Dendritic Cell–Based Vaccine in Prostate Cancer–Bearing Mice

In the current study, we investigated whether anti-CD27 monoclonal antibody can enhance the antitumor efficacy of a dendritic cell–based vaccine in prostate cancer–bearing mice. The overall therapeutic effect of a dendritic cell–based vaccine for prostate cancer remains moderate. A prostate cancer model was established by subcutaneous injection of RM-1 tumor cells into male C57BL/6 mice on day 0. After 4 days, tumor-bearing mice were treated with RM-1 tumor lysate–pulsed dendritic cells (i.e., dendritic cell–based vaccine), anti-CD27 monoclonal antibody, or a combination of RM-1 tumor lysate–pulsed dendritic cells with anti-CD27 monoclonal antibody. Mice were killed at 21 days after tumor cell implantation. Tumor size was measured for assessment of antitumor effect. Spleens were collected for analysis of antitumor immune responses. The antitumor immune responses were evaluated by measuring the proliferation and activity of T cells, which have the ability to kill tumor cells. The combination therapy with RM-1 tumor lysate–pulsed dendritic cells and anti-CD27 antibody significantly enhanced T-cell proliferation and activity, and significantly reduced tumor growth, compared with monotherapy with RM-1 tumor lysate–pulsed dendritic cells or anti-CD27 antibody. Our results suggest that combined treatment can strengthen antitumor efficacy by improving T-cell proliferation and activity.Key words: Anti-CD27 antibody, Dendritic cell vaccine, Prostate cancer, Mouse tumor modelProstate cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related death among men in the United States.¹ Up to 20% to 40% of patients with primarily localized prostate cancer will experience disease recurrence after radical prostatectomy or radiation therapy.^2–4 Although disease recurrence can be temporarily controlled with androgen deprivation therapy, recurrent prostate cancer inevitably progresses to metastatic castration-resistant prostate cancer.^5,6 Patients with metastatic castration-resistant prostate cancer have traditionally been treated with chemotherapeutic agents. However, chemotherapy has a limited impact on overall survival and is associated with severe side effects.⁷ Therefore, novel therapeutic strategies for the management of metastatic castration-resistant prostate cancer are urgently needed.Prostate cancer is regularly infiltrated by dendritic cells and T lymphocytes, and it is considered susceptible to immunotherapy.^8,9 The recent trend in prostate cancer immunotherapy has been directed toward dendritic cell–based vaccines. Dendritic cells, the most potent antigen-presenting cells, have the capability to process and present antigens derived from tumor cells to CD4⁺ and CD8⁺ T cells.¹⁰ The interaction between dendritic cells and T cells leads to expansion and activation of T cells.¹¹ Activated CD8⁺ T cells become cytotoxic T lymphocytes with the ability to destroy tumor cells expressing the same antigen on the cell surface.¹² Activated CD4⁺ T cells have been shown to provide help for CD8⁺ T-cell activation by releasing cytokines, such as interferon-γ and interleukin-2.¹³ A total of 181 patients with metastatic castration-resistant prostate cancer were treated with dendritic cell–based vaccine in 17 clinical trials.⁹ Clinical responses to vaccine were evaluated according to the World Health Organization criteria: complete response was defined as complete disappearance of tumor; partial response was defined as ≥50% decrease in tumor size without the appearance of new metastases; stable disease was defined as <25% increase or <50% decrease in tumor size; and progressive disease was defined as ≥25% increase in tumor size or the appearance of a new metastasis.¹⁴ Of the 181 patients treated, 97 (54%) had a clinical response, with 1 complete response, 12 partial responses, 83 disease stabilizations, and 1 mixed response.⁹ The dendritic cell–based vaccine in these clinical trials was in general well tolerated, with minimal toxicity observed. Most adverse effects were local reactions at the injection site, fever, and flulike symptoms. Although dendritic cell–based vaccine therapy in patients with metastatic castration-resistant prostate cancer has encouraging results, the overall clinical benefit of this vaccine remains moderate. Methods to enhance the immune response induced by dendritic cell–based vaccine will potentially augment the therapeutic efficacy of this vaccine.CD27, a member of the tumor necrosis factor receptor family, is expressed on most peripheral blood T cells.¹⁵ Upon T-cell activation, CD27 expression is strongly enhanced.¹⁶ Ligation of CD27 by anti-CD27 monoclonal antibody provides a costimulatory signal to T cells and promotes T-cell proliferation and activation.¹⁷ It has been reported that anti-CD27 antibody can mediate antitumor efficacy.^18–21 We postulated that dendritic cell–based vaccine and anti-CD27 antibody may act as therapeutically synergistic partners against prostate cancer. The reason is as follows. Dendritic cell–based vaccine activates T cells by presenting tumor antigen to T cells. Activated T cells up-regulate CD27 expression. Subsequent addition of anti-CD27 antibody further enhances T-cell proliferation and activation via ligation of CD27 on T cells, thereby potentiating antitumor efficacy. To test this hypothesis, we investigated the combined action of dendritic cell–based vaccine with anti-CD27 antibody in mouse prostate cancer model.     

Improved Health-Related Quality of Life After Surgical Management of Severe Refractory Constipation-Dominant Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is the most common of the functional gastrointestinal disorders (FGIDs). Despite its prevalence and health-care costs, there are few effective therapies for patients with severe symptoms. Our objective was to determine whether surgical management would improve health-related quality of life (HRQOL) in severe refractory constipation-dominant FGIDs. From 2003 to 2005, 6 patients underwent total colectomy with end ileostomy or primary anastomosis. They completed Short Form 36 (SF-36) and IBS-36 questionnaires preoperatively and postoperatively. HRQOL was compared with age- and sex-matched Canadian norms using Welch''s unpaired t test. Preoperative SF-36 physical and mental health summary scores were significantly lower than Canadian norms (P < 0.0001), while postoperative scores were not significantly different than Canadian norms (P = 0.50 and P = 0.57, respectively). After surgical management, HRQOL in patients with severe constipation-dominant IBS improved from drastically below that of Canadian norms to a comparable level. This finding questions the convention of avoiding operations in IBS patients and demonstrates that surgical management may be suitable for the appropriately screened patient.Key words: Health-related quality of life, Surgery, Irritable bowel syndromeIrritable bowel syndrome (IBS) is one of 20 functional gastrointestinal disorders (FGIDs). These are a heterogeneous group of chronic disorders in which the presenting gastrointestinal (GI) symptoms cannot be explained by structural or biochemical abnormalities.^1,2 IBS is characterized by abdominal pain associated with defecation, change in bowel habit, bloating, and distension.^3,4 The ROME III committee developed a set of diagnostic criteria for each FGID separately.^3,4 However, it has become increasingly accepted that the FGIDs overlap considerably and therefore, IBS should not be considered as a single entity but rather on a spectrum of related disorders.^1,5IBS is the most common of the FGIDs with a prevalence rate in the United States anywhere from 3% to 20%, with most studies quoting around 10%.^1,2 Although up to 70% of IBS sufferers in the United States do not seek medical attention, the total health-care costs and burden to the health-care system is substantial.^5,6 In fact, in the United States, among GI illnesses, IBS was second only to gastroesophageal reflux disease in prevalence in a comprehensive assessment of burden of illness.⁵ In addition, the estimated direct and indirect annual health-care costs of IBS in the United States are $1.6 billion and $19.2 billion, respectively.^1,5 Despite the high expenditure for this illness, there are very limited effective treatment options, and patients continue to demonstrate poor health-related quality of life (HRQOL), which is comparable to that seen in patients with organic disease.^1,7–12Treatment options have largely been directed at symptom relief and vary depending on symptom severity. They include any and all of the following: education and reassurance, diet and lifestyle modification, pharmacotherapy directed at relief of bowel-specific symptoms with medications (such as anticholinergics, antispasmodics, antidiarrheals, and laxatives), as well as antidepressants and narcotics, along with referrals to mental health and pain services.^2,5,13 A combination of the above therapies has been somewhat effective in patients with mild to moderate symptoms; however, in moderate to severe cases, patients often have symptoms that are refractory and persistent despite exhaustive use of the above modalities.Patients who suffer from severe symptoms of IBS commonly present with a picture of acute severe abdominal and/or pelvic pain and frequently undergo unnecessary emergent abdominopelvic surgeries.^14–17 As the literature would suggest, these surgeries are often nontherapeutic, and thus it is a general convention to avoid operating on patients with IBS and other FGIDs for the purpose of symptom control.^14–17 Nevertheless, there are some motility-disordered patients who have such intractable symptoms as to severely diminish their quality of life. These patients have received operative management aimed at ameliorating their symptoms and thus improving their lives. At our tertiary care center, we have identified a group of such motility-disordered patients. Patient accounts of their disease experience relate severe pain and constipation leading to debilitating loss of daily functioning, emotional distress, disability, and impaired quality of life. The objective of this study was to determine whether surgical management of severe refractory constipation-dominant motility disorders in adult patients would result in improved HRQOL.     

Effect of Intraoperative Valsalva Maneuver Application on Bleeding Point Detection and Postoperative Drainage After Thyroidectomy Surgeries

The purpose of this paper was to analyze the effect of Valsalva maneuver application before finalizing thyroidectomy operations on the identification of bleeding points and postoperational drainage. One hundred patients (age range, 24–76 years) with multinodular goiter, recurrent multinodular goiter, toxic diffuse multinodular goiter, or papillary thyroid cancer were included in the study and were divided into 2 groups of 50 randomly. Both groups underwent thyroidectomy operation, only 1 group received intraoperative Valsalva maneuver application (twice, 30 seconds of 30-cm PEEP). The size of the thyroid gland, the duration of operation, hospital stay, and drain usage were reported. Postoperational occurrences of drainage, hematoma, reoperation, and additional complications were compared between the groups. Valsalva maneuver application helped to identify minor bleeding points in 32% of the cases. There was no significant difference between the study groups regarding the thyroid gland size, operation duration, hospital stay, and the duration of drain usage (P > 0.05 for all). The amount of drainage as well as the frequencies of hematoma, reoperation, and further complications was not significantly different between the study groups (P > 0.05 for all). Intraoperative application of Valsalva maneuver is only useful to detect minor bleeding points in some patients during thyroidectomy operations, but it had no effect on the duration of postoperative drain usage, the amount of drainage, and risk of hematoma. Therefore, intraoperative application of Valsalva maneuver has no beneficial effect on postoperative hemorrhagic complication after thyroidectomy operations.Key words: Drainage, Hemostasis, Thyroidectomy, Valsalva maneuverThyroidectomy is one of the most commonly performed operations worldwide.¹ Though a series of improvements were introduced to the operation process, still several postoperative complications remain to be faced such as seroma, wound infection, skin flap complications, and hematoma.^2,3Despite the richness of the blood vessels in the thyroid area,⁴ the rate of postoperational bleedings thus hematoma events are low (1–5% of the cases).⁵ However, once not controlled, hematoma can result in airway compression and create a life-threatening situation for the patient.⁶ Hence, preventive measures have been emphasized and employed to avoid postoperational bleedings after thyroidectomy. These approaches range from exercises to avoid Valsalva maneuver kind of forces such as coughing or straining at opening bowel⁷ to the use of drains after the operation. However, recent literature indicates that the drain usage does not have a significant effect on the recovery period or on the duration of the hospital stay.^3,5,8,9 Furthermore, it may cause wound infection and contribute to the discomfort of the patients.^5,8,10,11 Thus a proper hemostasis and an early detection of potential bleeding sites are crucial steps for a successful operation and a steady recovery period.⁴ Several techniques have been used to detect and treat bleeding points immediately after the operation to prevent postoperational hematoma. These techniques involve the use of hydrogen peroxide, water in the wound, Valsalva maneuver, and Trendelenburg tilt.^4,7 Recently, the success of Valsalva maneuver and Trendelenburg tilt application on bleeding point detection was demonstrated by Moumoulidis et al.⁴ However, no further information is provided until now regarding the postoperational evaluation of the patients.In this paper, we aim to analyze the effect of the Valsalva maneuver application on the identification of bleeding points before finalizing the surgery and its influence on the postoperative drainage, complications, and recovery process.     

Emergency Presenting Colon Cancer Is an Independent Predictor of Adverse Disease-Free Survival

Twenty percent of colon cancers present as an emergency. However, the association between emergency presentation and disease-free survival (DFS) remains uncertain. Consecutive patients who underwent elective (CC) and emergent (eCC) resection for colon cancer were included in the analysis. Survival outcomes were compared between the 2 groups in univariate/multivariate analyses. A total of 439 patients underwent colonic resection for colon cancer during the interval 2000−2010; 97 (22.1%) presented as an emergency. eCC tumors were more often located at the splenic flexure (P = 0.017) and descending colon (P = 0.004). The eCC group displayed features of more advanced disease with a higher proportion of T4 (P = 0.009), N2 tumors (P < 0.01) and lymphovascular invasion (P< 0.01). eCC was associated with adverse locoregional recurrence (P = 0.02) and adverse DFS (P < 0.01 ) on univariate analysis. eCC remained an independent predictor of adverse locoregional recurrence (HR 1.86, 95% CI 1.50–3.30, P = 0.03) and DFS (HR 1.30, 95% CI 0.88–1.92, P = 0.05) on multivariate analysis. eCC was not associated with adverse overall survival and systemic recurrence. eCC is an independent predictor of adverse locoregional recurrence and DFS.Key words: Emergency presentation, Colon cancer, Disease free survival, Locoregional recurrenceColorectal cancer (CRC) is a significant cause of mortality, with over 40,000 new cases diagnosed annually in the UK contributing to over 16,000 deaths (Bowel Cancer UK).^1,2 Up to 20% of colon cancers (CC) present as an emergency (eCC) necessitating emergent surgery.^3,4 Although eCC has been shown to be associated with poorer overall survival (OS), much discrepancy exists in the literature regarding its association with disease-free survival (DFS).⁵⁻⁷Studies reporting the oncologic outcomes of CRC presenting as an emergency consist of heterogeneous populations of patients with colon and rectal cancers.^3,5 Colon and rectal cancers are 2 distinct entities with different molecular, clinical, pathologic, and biologic characteristics and treatment modalities.^8,4,9−11 Since the incorporation of combined multimodal treatment and total mesorectal excision the disparity in OS and DFS between colon and rectal cancer has increased.¹²⁻¹⁷ Rectal cancer patients may alter the impression of outcomes in emergency presenting colon cancer. Consequently, previous studies assessing outcomes in eCC may be flawed. Furthermore, the negative impact of eCC has previously been attributed to immediate postoperative complications with an inpatient hospital mortality of approximately 15%. Inclusion of such cases in studies assessing long-term outcomes may have overestimated the negative impact of eCC.¹⁸The aim of the current study was to determine the association between eCC and disease-free/overall survival.     

Pneumoretroperitoneum and Pneumomediastinum Revealing a Left Colon Perforation

Left colon perforation usually occurs in complicated diverticulitis or cancer. The most frequent signs are intraperitoneal abscess or peritonitis. In cases of retroperitoneal colonic perforation, diagnosis may be difficult. A 59-year-old woman presented with left thigh pain and with abdominal discomfort associated with mild dyspnea. Computed tomography scan showed air bubbles and purulent collection in the retroperitoneum, with subcutaneous emphysema extending from the left thigh to the neck. Computed tomography scan also revealed portal vein gas and thrombosis with multiple liver abscesses. An emergency laparotomy revealed a perforation of the proximal left colon. No masses were found. A left colectomy was performed. The retroperitoneum was drained and washed extensively. A negative pressure wound therapy was applied. A second-look laparotomy was performed 48 hours later. The retroperitoneum was drained and an end colostomy was performed. Intensive Care Unit postoperative stay was 9 days, and the patient was discharged on the 32nd postoperative day. Pneumoretroperitoneum and pneumomediastinum are rare signs of colonic retroperitoneal perforation. The diagnosis may be delayed, especially in the absence of peritoneal irritation. Clinical, laboratory, and especially radiologic parameters might be useful. Surgical treatment must be prompt to improve prognosis.Key words: Pneumomediastinum, Retroperitoneum, Colonic, PerforationColonic perforation can be caused by either benign or malignant diseases. Left colon perforation is generally due to diverticular disease or cancer.^1–3 Uncommon causes are iatrogenic ischemia, colonic ischemia, trauma, or toxic megacolon.^1,3,4 Symptoms are usually due to abscesses or peritonitis. However, retroperitoneal ruptures can be difficult to diagnose because their presentation can vary widely.^1,2,4–6Through this case of retroperitoneal colonic perforation we aim to describe the presentation and therapeutic management of this entity.     

Prevention of Incisional Surgical Site Infection Using a Subcuticular Absorbable Suture in Elective Surgery for Gastrointestinal Cancer

This study examined whether subcuticular absorbable sutures actually reduce incisional SSI in patients undergoing surgery for gastrointestinal (GI) cancer. Surgical site infection (SSI) is still a source of major complications in digestive tract surgery. Reportedly, incisional SSI can be reduced using subcuticular suturing. We performed subcuticular suturing using a 4-0 absorbable monofilament in patients undergoing elective surgery for GI cancer beginning in 2008. Using an interrupted technique, sutures were placed 1.5-2.0cm from the edge of the wound, with everted subcuticular sutures created at intervals of 1.5-2.0cm. The control group consisted of cases in which the common subcutaneous suture method using clip. One hundred cases were examined in the subcuticular group. The incidence of SSI was 0% in the subcuticular suture group, compared with 13.9% in the control group; this difference was significant. Incisional SSI can be prevented using the devised subcuticular absorbable sutures in patients undergoing elective surgery for GI cancer.Key words: Surgical site infection, Subcuticular suture, Absorbable monofilament, Gastrointestinal cancer surgerySurgical site infection (SSI) is still a source of major complications in digestive tract surgery. The Centers for Disease Control and Prevention (CDC) National Nosocomial Infection Surveillance System (NNIS) risk adjustment index is an internationally recognized method of stratifying the risk of SSI according to three major factors.¹ First, the American Society of Anesthesiologists'' score reflects the patient''s state of health before surgery.² Second, the wound classification reflects the degree of wound contamination. And third, the duration of the operation reflects the technical aspects of surgery. The infection rate increases with an increasing risk index score.^1,3 Excellent surgical technique is widely believed to reduce the risk of SSI.^4–7 In the case of wound closure, such techniques include the maintenance of effective hemostasis while preserving an adequate blood supply, preventing hypothermia, gently handling the tissues, avoiding inadvertent entries into a hollow viscus, removing devitalized (e.g., necrotic or charred) tissues, the appropriate use of drains and suture materials, the eradication of dead space, and the appropriate postoperative management of incisions. Hematoma at the site of a surgical wound is a relatively common complication in elective surgical procedures. In most cases, the hematoma is caused by incomplete preoperative hemostasis, and not the omission of a subcutaneous fat layer suture.^1,8 According to current knowledge, seroma formation is caused by the ultrafiltration of blood serum, lymphatic secretion, the fibrinolytic activity of plasmin (causing the decay of fibrin complexes in the surrounding injured vessels), and tissue exudate formed during early inflammation reactions.^3,9,10 A large dead space also appears to contribute to the formation or a seroma.³ According to some authors, the presence of suturing material (as extraneous material) in tissues can also increase the risk of surgical site infections.^11–13Subcuticular suturing was recently reported to reduce incisional SSI.^14–16 Subcuticular sutures are thought to enable a maintained blood supply and to eradicate dead space in the subcutaneous environment. Therefore, we investigated whether the devised subcuticular suturing actually reduces incisional SSI, compared with the common subcutaneous sutures with clip, in patients undergoing elective surgery for gastrointestinal cancer.     

Impact of Glissonean Pedicle Approach for Centrally Located Hepatocellular Carcinoma in Mongolia

Approaches to surgical resection of centrally located HCC remain controversial. Traditionally, hemi- or extended hepatectomy is suggested. However, it carries a high risk of postoperative complications in patients with cirrhosis. An alternative approach is Glissonean pedicle transection method. This study was conducted to assess the surgical and survival outcomes associated with central liver resection using the Glissonean pedicle transection. Sixty-nine patients with centrally located HCC were studied retrospectively. They were divided into conventional approach group with hemi- or extended hepatectomy, and Glissonean approach group with multisegmental central liver resection using the Glissonean pedicle transection. Glissonean pedicle transection method has comparable or superior surgical and survival outcomes to conventional hemi- or extended hepatectomy with regard to intraoperative bleeding, complications, hospital stay, and postoperative mortality and survival outcomes in patients with centrally located HCC. The 1-, 3-, and 5-year overall survival rates of the conventional approach group were 74%, 64%, and 55% respectively. For the Glissonean approach group, the 1 and 3-year overall survival rates were 86% and 61%, respectively. Glissonean pedicle transection method is a safe and effective surgical procedure in patients with centrally located HCC.Key words: Centrally located HCC, Glissonean approach, Glissonean pedicle transection, Central hepatectomyHepatocellular carcinoma (HCC) is the first leading cause of cancer-related mortality in both men and women in Mongolia, and its incidence is among the highest worldwide.¹ Surgical resection remains the first-line therapeutic strategy for HCC despite recent advancements in treatment modalities.^2-4 However, underlying liver diseases significantly limit the number of HCC patients eligible for surgical resection. This is especially problematic, where the prevalence of chronic hepatitis B and C is over 10% in the general population, and 86.8% of HCC patients have cirrhosis.⁵ Therefore, refining surgical techniques to preserve as much liver parenchyma as possible could potentially improve treatment prospects for cirrhotic HCC patients, particularly in cases when the tumor is centrally located.Traditionally, hemi- or extended hepatectomy is suggested for the treatment of centrally located HCC.⁶ However, such a major hepatic resection sacrifices a large volume of noncancerous liver parenchyma, which carries a high risk of postoperative liver failure in patients with cirrhotic background.^6-8 Preservation of functioning liver parenchyma to a maximum extent possible is crucial to avoid postoperative liver failure in cirrhotic patients. Therefore, Glissonean pedicle transection method is increasingly considered as an effective alternative to hemi- or extended hepatectomies in such cases.^9-16 Nonetheless, multisegmental central liver resection has not been widely used since its introduction for gallbladder cancer in 1972.^17,18 Conventional central liver resection method is technically demanding, and may require prolonged surgical time in order to dissect and confirm each branch of hepatic artery, portal vein, and bile duct to the anterior section.^19,20 This often results in increased risk of bleeding, bile leakage or parenchymal necrosis, and therefore, central liver resection particularly in cirrhotic patients remains controversial.^21,22 The answer to the dilemma could lie with the Glissonean pedicle transection method, which was introduced in the mid-1980s owing to a better understanding of the surgical anatomy of the liver.^20,23 When using this resection method, Glissonean pedicle supplying the target area is ligated and divided at the hepatic hilum prior to resection without exposing the vessels individually.²³ This simplifies hepatic resection, shortens operation time and reduces intraoperative bleeding.²³⁻²⁵ Our previous experience with using this method for hemihepatectomy has resulted in considerable reduction of blood loss during resection, a major determinant of patient outcome.This approach has allowed the ability to adapt the size of resection to the extent of the tumor and to preserve the maximum amount of liver parenchyma, which is crucial for the prevention of postoperative liver failure especially in patients with cirrhotic background. However, it remains unclear whether central liver resection using the Glissonean pedicle transection improves long-term survival. Therefore, the current retrospective study of patients with centrally located HCC, who underwent either hemi- or extended hepatectomy or multisegmental central liver resection, was conducted to assess the perioperative and long-term outcomes associated with central liver resection using the Glissonean pedicle transection.     

Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer: Does Time to Surgery Matter?

The objective of this paper was to evaluate whether delaying surgery following long-course chemoradiotherapy for rectal cancer correlates with pathologic complete response. Pre-operative chemoradiotherapy (CRT) is standard practice in the UK for the management of locally advanced rectal cancer. Optimal timing of surgery following CRT is still not clearly defined. All patients with a diagnosis of rectal cancer who had undergone long-course CRT prior to surgery between January 2008 and December 2011 were included. Statistical analysis was performed using Stata 11. Fifty-nine patients received long-course CRT prior to surgery in the selected period. Twenty-seven percent (16/59) of patients showed a complete histopathologic response and 59.3% (35/59) of patients had tumor down-staging from radiologically-assessed node positive to histologically-proven node negative disease. There was no statistically significant delay to surgery after completion of CRT in the 16 patients with complete response (CR) compared with the rest of the group [IR: incomplete response; CR group median: 74.5 days (IQR: 70–87.5) and IR group median: 72 days (IQR: 57–83), P = 0.470]. Although no statistically significant predictors of either complete response or tumor nodal status down-staging were identified in logistic regression analyses, a trend toward complete response was seen with longer delay to surgery following completion of long-course CRT.Key words: Interval to surgery, Rectal cancer, Long-course chemoradiotherapyIn the multimodal management of rectal cancer, surgical resection remains the mainstay of treatment. Total mesorectal excision (TME) has become the standard operative technique resulting in reduced rates of local recurrence compared with previous conventional surgery.^1,2 Apart from surgery, neoadjuvant radiotherapy is employed in resectable rectal cancer to reduce the risk of local recurrence, and in locally-advanced rectal cancer, to downsize the tumor and facilitate subsequent successful R0 resection or sphincter-preserving surgery.^3,4 Two meta-analyses have reported that preoperative radiotherapy plus surgery when compared with surgery alone significantly reduced the 5-year overall mortality rate, cancer-related mortality rate, and local recurrence rates in resectable rectal cancer.^5,6Preoperative radiotherapy is usually given either as a short- or long-course treatment schedule. Short-course radiotherapy typically involves 25 Gy in 5 fractions given in 1 week,⁷ whereas long-course treatment consists of 45 Gy given in 25 fractions over 5 weeks as standard⁸ with concomitant chemotherapy as a radiosensitizer. The Swedish Rectal Cancer Trial showed statistically significant reduction in the local recurrence rates and increase in the overall survival rates at a median follow-up of 13 years in the group receiving short-course preoperative radiotherapy compared with surgery alone.⁷ The Dutch trial also confirmed that short-course radiotherapy reduced the risk of local recurrence in patients who underwent a standardized TME.⁹ Although no chemotherapy was considered in the above studies, the EORTC Radiotherapy Group trial concluded that long-course preoperative radiotherapy with chemotherapy given either preoperatively or postoperatively conferred significant benefit in terms of local control, but did not improve survival.⁸ Finally, the German Rectal Cancer Study Group showed that preoperative chemoradiotherapy (CRT) compared with postoperative CRT improved local recurrence rates and was associated with reduced toxicity.¹⁰A 6 to 8 week interval to surgery from completion of neoadjuvant CRT has become standard practice since the results of the Lyons R90-01 study were published.¹¹ In this trial, a longer interval of 6 weeks when compared to 2 weeks post-CRT was associated with increased tumor down-staging.¹¹ However, it is not clear whether a yet longer delay before surgery might result in further tumor down-staging or in higher rates of pathologic complete response. The aim of our retrospective study was to evaluate whether a longer interval between completion of long-course CRT and surgery for locally-advanced rectal cancer might maximize the effectiveness of CRT in achieving complete response.