Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

Extramammary Paget's Disease of the Penis and Scrotum.

Extramammary Paget's disease (EMPD) is an adenocarcinoma arising from the skin or skin appendages which is sometimes associated with an underlying malignancy. EMPD is most commonly seen in the vulva, followed by perianal region, and the male genitalia. In most cases, patient presents with eczematous lesion persisting for long duration. A 77-year-old gentleman had a history of chronic eczematous lesion over penis and scrotum for the last 10 years. Examination revealed an erythematous plaque like eczematous lesion over the penis and scrotum. Biopsy with IHC of lesion is suggestive of EMPD. Wide local excision of lesion and left inguinal lymph node dissection with pedicled left superficial circumflex iliac perforator flap cover was done. The final histopathology with IHC confirmed the diagnosis of EMPD. The postoperative period was uneventful, and patient was discharged. EMPD of the penis and scrotum is a rare presentation, and it is ideally treated with wide excision.

Expression Profile of KRAS and p16 in Periampullary Cancer.

Activating point mutations in codons 12, 13, and 61 of the KRAS gene and loss of p16 expression, a tumor suppressor gene, are common genetic alterations in periampullary cancer (PAC). The present study explores expression profile of KRAS and p16 genes in PAC and its prognostic relevance. A total of 50 patients with PAC who underwent potentially curative pancreaticoduodenectomy were included in the study. Formalin-fixed, paraffin-embedded tissue samples were analyzed for point mutations in codons 12 and 13 of KRAS and codon 9 of p16 using polymerase chain reaction. KRAS mutation in codon 12/13 was found in 32 (64%) and loss of p16 expression in 36 (72%) cases. KRAS mutation was significantly associated with higher grade, higher pathological tumor (pT) stage, lymphovascular invasion (LVI), perineural invasion (PNI), and pathological lymph nodes (pN) involvement on univariate analysis. On multivariate analysis, significant association of KRAS remained with higher grade (p = 0.031), pT stage (p = 0.09), and LVI (p = 0.028). On univariate analysis, loss of p16 expression was significantly associated with higher grade, pN involvement, LVI, PNI, and pT stage whereas on multivariate analysis, statistical significant association of p16 was found with higher grade of tumor only (p = 0.04). Patients with KRAS mutation had significantly (p = 0.018) worse disease-free survival (DFS) whereas no significant association was found in overall survival (OS). Loss of p16 expression had no association with either DFS or OS. The presence of p16 and KRAS alterations in patients with PAC suggests aggressive tumor biology. KRAS mutations confer a significantly poor DFS in PAC.

Clinical Significance of Frequently Down-Regulated Phosphatidylethanolamine-Binding Protein-1 in Gallbladder Cancer.

BACKGROUND: Promoter hypermethylation of tumor suppressor genes has been demonstrated to be one of the major mechanisms of their epigenetic regulation in various reports. We have studied the promoter methylation status of PEBP1 and evaluated its correlation with gallbladder carcinogenesis. AIMS: PEBP1, an endogenous inhibitor of Raf/MEK/ERK signaling pathway, is a tumor suppressor gene. We aimed to study the expression profile of PEBP1 and understand the mechanism and significance of its deregulation in gallbladder cancer. METHODS: PEBP1 expression analysis and its promoter methylation status were investigated in 77 gallbladder carcinoma (GBC) and tissue biopsies from 28 patients of gallstone disease by RT-PCR and MS-PCR, respectively. RESULTS: Our results of the mRNA expression profiling demonstrate that PEBP1 is down-regulated in 62.3% (48/77), while 31.2% (24/77) of the gallbladder cancer biopsies show no significant change and 6.5% (5/77) show up-regulated expression compared to tissue samples of gallstone diseases. In GBC, 48.1% (N = 37) GBC biopsy samples exhibited significantly heterozygous promoter hypermethylation compared to tissue samples from gallstone diseases which show promoter hypermethylation in 3 (10.7%) samples only. In gallbladder cancer, the PEBP1 methylation is significantly associated with lymph node metastasis and shorter period of survival. CONCLUSION: PEBP1 is frequently down-regulated and hypermethylated in gallbladder cancer and its promoter hypermethylation is a frequent and early inactivating mechanism in GBC.

Octreotide and postoperative pancreatic fistula after pancreaticoduodenectomy: What we know so far? A narrative review.

Postoperative pancreatic fistula (POPF) is the most feared complication following pancreatic resection. Octreotide, a synthetic somatostatin analog, has been widely used by pancreatic surgeons worldwide after pancreatic resections, often as per surgeon's discretion, to prevent POPF especially in cases at high risk of developing POPF. We herein analyze the data available till date of the subject. A PubMed search with keywords "somatostatin OR octreotide OR somatostatin analogues AND postoperative pancreatic fistula" was made. Further filters were applied in the search "Clinical Trial, Meta-Analysis, Randomized Controlled Trial, Systematic Review, from 1990 - 2021," and the 68 results thus obtained were analyzed and included in this narrative review. There is considerable heterogeneity among the studies assessing the role of octreotide in the prevention of POPF making data comparison difficult, and hence results remain inconclusive. Most of the earlier studies used different definitions of POPF and other complications; included patients with varied pancreatic pathologies such as cancer, chronic pancreatitis, and benign lesions; surgical techniques such as pancreaticoduodenectomy, distal pancreatectomy, and other procedures; use of somatostatin and its analogs such as octreotide, lanreotide, pasireotide, and vapreotide; varied surgeon and institutional volume; and so on. Besides, pancreatic surgery is per se a complex surgical procedure and has its own inherent biases related to patient and the pancreas itself affecting the overall outcome. Data indicate favorable role of newer somatostatin analogs, and further studies are urgently needed. The question about the efficacy of prophylactic octreotide to reduce POPF after pancreaticoduodenectomy remains open to debate.

Invasive Cancer in Accessory Axillary Breast: a Rare Presentation.

Accessory breast tissue has an incidence of 0.3-6% and primary cancer arising in it is even rarer 0.2-0.6%. It may have aggressive course with tendency for early metastasis. Due to its rarity, variety of differentials, and lack of clinical awareness, treatment is usually delayed. We present here an interesting case of a 65-year-old lady with a 8 × 7-cm hard lump in right axillary region for 3 years with fungation for 3 months and with no concomitant breast lesion or axillary lymphadenopathy. Biopsy revealed invasive ductal carcinoma with no systemic metastasis. Management of accessory breast cancer follows same guidelines with primary treatment being wide excision and lymphadenectomy. Adjuvant therapies include radiotherapy and hormonal therapy.

Clinical Significance of Overexpression of Oct4 in Advanced Stage Gallbladder Carcinoma.

BACKGROUND: Oct4 has critical role in maintaining pluripotency, proliferative potential, and self-renewal capacity in embryonic stem and germ cells. Although Oct4 has been shown to be upregulated in many cancers, its clinical significance in gallbladder carcinoma is poorly understood. METHODS: We studied the expression profile of Oct4 in 61 GBC and 30 chronic cholecystitis (as control) using real time RT-PCR, western blotting, and immunohistochemistry. The expression data was correlated with clinico-pathological parameters. The diagnostic utility was assessed through ROC curve, and prognostic value was analyzed by Kaplan-Meier method. RESULTS: Oct4 was significantly upregulated at mRNA as well as protein levels. The higher mRNA expression shows significant association with late stage, late T stage, and higher grade of tumor. A significant positive correlation was also observed with stage, T stage, and tumor grade. Sum score analysis of protein expression shows positive correlation with stage and the presence or absence of gallstone in tumor samples. The ROC curve analysis revealed the moderate diagnostic potential of Oct4. Kaplan-Meier analysis showed that patients having higher expression of Oct4 were having low mean survival compared with the patients with lower Oct4 expression. CONCLUSION: In conclusion, our data suggests that higher expression of Oct4 may serve as potential biological indicator for tumor aggressiveness and poor prognosis of GBC.

Epigenetic Silencing of p16INK4a gene in Sporadic Breast Cancer.

Epigenetic alterations of tumor suppressor genes (TSG) involved in the onset and progression of Breast Cancer (BC) may serve as biomarkers for early detection and prediction of disease prognosis. We have herein tried to determine the methylation status of TSG, p16INK4a, in our 50 BC patients and their association with clinicopathological parameters. The methylation status of the p16INK4a gene in fresh tissue samples from 50 patients with BC was assessed by methylation-specific polymerase chain reaction (MS-PCR). The mean age of BC patients was 49.30 ± 9.75 years. Of 50 BC samples tested, 21 (42%) had methylated p16INK4a gene. p16INK4a gene hypermethylation was significantly associated with age ≤ 50 years, premenopausal status and advanced BC stage. Multivariate analysis revealed a strong association between advanced BC stage (Stage III and Stage IV) and p16INK4a hypermethylation (P = 0.008, RR = 5.996, 95% CI = 1.581-22.739). p16INK4a methylation was significantly associated with Triple Negative BC (TNBC) (P = 0.045, OR = 4.181, 95% CI = 1.030-16.981). These findings indicate that p16INK4a hypermethylation frequently occurs in BC. Hypermethylation of p16INK4a in young, premenopausal, TNBC and with advance stage in BC patients suggests its association with aggressive BC.

Transcription factor 4 expression and correlation with tumor progression in gallbladder cancer.

Background: Dysregulation in Wnt/ß-catenin signaling has been associated with the initiation and metastasis of cancer cells. Transcription factor 4 (TCF4) (also named as transcription factor 7-like 2) is a key transcriptional factor of the Wnt signaling pathway, which, when interact with ß-catenin activates Wnt genes which plays an essential role in tumor development. The expression pattern and clinical significance of TCF4 in gallbladder cancer (GBC) are not yet established. Aims: This study was performed to assess the expression pattern of TCF4 in GBC tissue and attempted to correlate its expression with different clinicopathological parameters. Materials and Methods: The study was conducted on 33 surgically resected specimens of gallbladder carcinoma (GBC) and 12 cases of chronic cholecystitis (CC) as control, which had been confirmed from histology. The expression of TCF4 was performed by the reverse transcription polymerase chain reaction and immunohistochemistry. Results: Relative mRNA expression levels of ß-catenin and TCF4 in GBC tissues were significantly (P < 0.05) higher than in CC samples. TCF4 protein expression was observed in 81.82% (27/33) GBC cases. Specifically, among GBC samples, 21.21% (7/33) was graded as strongly positive, 60.61% (20/33) graded as moderately positive, whereas 18.18% (6/33) graded as negative. All 12 CC samples graded as negative. Overall, TCF4 expression in GBC tissues was statistically significant over CC samples (P < 0.05). Moreover, we observed that TCF4 expression was significantly higher (P < 0.05) in high tumor grades than low grade, higher (P < 0.05) in Stage 2 and Stage 3 than Stage 1. Conclusion: The present study suggests that TCF4 may exert an oncogenic role in the progression of GBC and may serve as a new potential candidate biomarker for tumor progression, and it might be a potential therapeutic target against GBC.

Design, synthesis and evaluation of 4,7-disubstituted 8-methoxyquinazoline derivatives as potential cytotoxic agents targeting ß-catenin/TCF4 signaling pathway.

Overactivation of Wnt/ß-catenin signaling by accumulated ß-catenin in the nucleus has been shown to play a crucial role in the etiology of cancer. Interaction of ß-catenin with Transcription factor 4 (TCF4) is a key step for the activation of Wnt genes in response to upstream signals of the Wnt/ß-catenin pathway. Hence, down regulation of Wnt/ß-catenin signaling or targeting downstream events by selective ß-catenin/TCF4 protein-protein interaction inhibitors could be a potential therapeutic strategy against such cancers. In this study structure-based drug design approach was followed to design novel 4,7-disubstituted 8-methoxyquinazoline-based derivatives which could act as potential cytotoxic agents inhibiting the ß-catenin/TCF4 protein-protein interactions. Fifteen compounds possessing 4,7-disubstituted 8-methoxyquinazoline scaffold were synthesized. Cytotoxic potential of the synthesised derivatives were determined against constitutively activated ß-catenin/TCF4 signaling pathway cancer cells (HCT116 and HepG2) using the sulforhodamine B assay. The most potent compound (18B) was selected for detailed biological evaluation. Cell morphology, Hoechst 33342 and Annexin V/PI staining were used to detect apoptosis, while inhibition of cell migration was assessed by in vitro wound healing assay against HCT116 and HepG2 cells. Effect on ß-catenin/TCF mediated transcriptional activity was assessed by TOPFlash/FOPFlash assay, TCF4 and ß-catenin protein expression by immunocytofluorescence, and Wnt target genes (like c-MYC and Cyclin D1) mRNA levels by RT-PCR against HCT116 cells. Cytotoxic potency of the most potential compound (18B) against primary human gallbladder cancer cells was also evaluated. The derivatives showed interactions with active site residues of ß-catenin and were capable of hindering the TCF4 binding, thereby disrupting ß-catenin/TCF4 interactions. Cytotoxic potencies (IC50) of these derivatives ranged from 5.64 ± 0.68 to 23.18 ± 0.45 µM against HCT116 and HepG2 cells respectively. Compound (18B), the most potent compound among the series, induced apoptosis and inhibited cell migration against HCT116 and HepG2 cells. Mechanistic studies indicated that compound (18B) downregulated ß-catenin/TCF4 signaling pathway, ß-catenin and TCF4 protein expression, and mRNA levels of c-MYC andCyclin D1 in HCT116 cells and showed cytotoxicity against primary human gallbladder cancer cells with IC50 value of 8.50 ± 1.44 µM. Thus, novel 4,7-disubstituted 8-methoxyquinazoline derivatives were identified as potential cytotoxic agents with potencies comparable to that of imatinib mesylate. Compound (18B) represents a promising lead molecule as anticancer agent against colon, hepatocellular and gallbladder cancers targeting ß-catenin/TCF4 signaling pathway.

Frequent promoter hypermethylation and down regulation of BNIP3: An early event during gallbladder cancer progression.

BACKGROUND: Epigenetic alterations have been reported as one of the risk factors of gallbladder cancer. Promoter hypermethylation is associated with high incidence and poor prognosis of GBC. Bcl-2/adenovirus E1B 19 kDa interacting protein 3 is a pro-apoptotic protein member of Bcl-2 family. AIMS: Present study was aimed to investigate expression profile and promoter methylation status of BNIP3 in GBC and its correlation with clinico-pathological parameters. METHODS: The expression analysis and methylation status of BNIP3 was performed by semi-quantitative reverse transcription polymerase chain reaction and Methylation-specific polymerase chain reaction respectively in 84 GBC patients and 29 gallstone tissues (used as normal controls). RESULTS: We demonstrate down regulation of BNIP3 in 56% of the GBC samples. BNIP3 promoter is also frequently hypermethylated (69%) in GBC samples. Interestingly, we found that 69% (40/58) of the BNIP3 promoter hypermethylated samples had also reduced expression of BNIP3. Our data demonstrate significant correlation of the mRNA expression and promoter hypermethylation with late stage and nodal metastasis. Hypermethylation of BNIP3 promoter is associated with low overall survival period. CONCLUSION: Our results suggest that promoter hypermethylation is an early event and can be a frequent mechanism for downregulation of BNIP3 in GBC.

Frequent Downregulation and Promoter Hypermethylation of DLC1: Relationship with Clinical Outcome in Gallbladder Cancer.

INTRODUCTION: Down regulation of DLC1 is associated with poor prognosis in many cancers, however, its role in gallbladder cancer (GBC) is still unclear. In present study, we investigated the expression profile and promoter methylation status of DLC1. METHODS: Expression profiles of DLC1 in 55 GBC and their paired adjacent control samples were analyzed through real time RT-PCR and immunohistochemistry. The mRNA data was correlated with clinico-pathological parameters. Promoter hypermethylation was analyzed through MSP. RESULTS: DLC1 shows downregulation in 76.4%, upregulation in 10.9% whereas no change in 12.7% of GBC samples. Its underexpression shows significant correlation with tumor grade and nodal spread. IHC shows cytoplasmic expression of DLC1 in normal as well as tumor samples. IHC result was concordant to mRNA result. Samples having downregulated DLC1 expression show heterozygous methylation in 83.3% of samples and homozygous methylation in 9.5% of samples whereas 7% of samples have no methylation. Kaplan-Meier analysis shows patient with decreased mRNA of DLC1 have significant low mean survival compared to patients with higher mRNA expression of DLC1. CONCLUSION: Our findings suggested that dysregulated expression of DLC1 and its hypermethylation may be one of the events playing roles in tumorigenesis of GBC and may serve as a potential target for development of future GBC gene therapy.

Influence of adjuvant therapy on pattern of failure and survival in curatively resected gallbladder carcinoma.

PURPOSE: The study was done to evaluate the role of adjuvant therapy in curatively resected Stage II and III gallbladder carcinoma (GBC). MATERIALS AND METHODS: This was a retrospective analysis of patients of GBC registered between 2008 and 2017 in outpatient department of a tertiary cancer hospital in India. Patients who had any of the following adjuvant treatment after radical surgery: (a) external beam radiotherapy (RT) alone, (b) chemotherapy (CT) alone, and (c) RT with CT (CRT) were considered for the study. RESULTS: A total of fifty patients could meet the selection criteria. It was seen that seven patients were treated with RT, 20 with CT, and 23 with CRT. Median follow-up for patients who were alive was 26.7 months. Nineteen patients had locoregional failure while eight had distant failure. Patients treated with CRT had a significantly better mean overall survival compared to those treated with RT or CT (44.0 months, 12.5 months, and 15.1 months, respectively; P = 0.003). Similarly, mean disease-free survival was superior in CRT arm compared to RT and CT arms (43.6 months, 9.6 months, and 12.4 months, respectively; P = 0.002). CONCLUSIONS: Adjuvant CRT had better survival outcome compared to patients treated with either RT or CT with Stage II and III disease after curative cholecystectomy.

Mediating Role of Affective Experiences in the Relationship between Perceived Social Support and Life Satisfaction among Breast Cancer Patients.

AIM: The role of social support network in managing psychological symptoms in cancer patients is widely acknowledged. The purpose of this study was to investigate the potential mediating role of Affective experiences in the relationship between perceived social support (PSS) and life satisfaction (LS) among breast cancer patients in India. METHODS: A total of 100 breast cancer patients from S. S. Hospital, Banaras Hindu University participated in the study. They were tested using the PGI Social Support questionnaire, Satisfaction with Life Scale and Scale of Positive and Negative Experiences. RESULTS: Co-relational results indicated that PSS was positively associated with positive affect and LS, while inversely related to negative affect. Affect was also associated with LS. Results showed that the mediation of affective experiences in the relationship between PSS and LS was significant (P <.01 level). CONCLUSION: Both PSS played a big role in LS among breast cancer patients. Besides focusing on improvement of the social support network, the psychologists and counsellors should adopt an integrated approach for evidence-based intervention strategies to enhance their ability to effectively balance their positive and negative emotions to promote LS among cancer patients.

Revisiting the role of TRAIL/TRAIL-R in cancer biology and therapy.

TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, can induce apoptosis in cancer cells, sparing normal cells when bound to its associated death receptors (DR4/DR5). This unique mechanism makes TRAIL a potential anticancer therapeutic agent. However, clinical trials of recombinant TRAIL protein and TRAIL receptor agonist monoclonal antibodies have shown disappointing results due to its short half-life, poor pharmacokinetics and the resistance of the cancer cells. This review summarizes TRAIL-induced apoptotic and survival pathways as well as mechanisms leading to apoptotic resistance. Recent development of methods to overcome cancer cell resistance to TRAIL-induced apoptosis, such as protein modification, combination therapy and TRAIL-based gene therapy, appear promising. We also discuss the challenges and opportunities in the development of TRAIL-based therapies for the treatment of human cancers.

Pancreatic exocrine insufficiency occurs in most patients following pancreaticoduodenectomy.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is a well-defined complication of malignant diseases and pancreatic resection; however, study results of PEI are less consistent. Assessment of PEI by estimation of fecal elastase (FE)-1 in stool by enzyme-linked immunosorbent essay (ELISA) is a relatively inexpensive, noninvasive, and simple test. This study assessed exocrine function of pancreas following pancreaticoduodenectomy (PD) by estimating FE-1. METHODS: This prospective hospital-based study involved 30 patients who had undergone PD for malignancy. All 30 patients had an uneventful postoperative period under the unit's enhanced recovery after surgery (ERAS) protocol with no Grade B, C postoperative pancreatic fistula/postpancreatectomy hemorrhage as per the International Study Group of Pancreatic Surgery (ISGPS) definitions. Stool samples were collected postoperatively 3 months after surgery from all patients irrespective of clinical symptoms. The analysis was based on a solid phase ELISA used for the quantitative determination of human elastase 1 in feces. Fecal elastase was considered normal if >200 µg/gm stool, moderately reduced if 100-200 µg/gm stool, and severely reduced if <100 µg/gm stool. RESULTS: Among 30 patients included, fecal elastase levels were moderately reduced in 10 (33.33%) and severely reduced in 20 (66.67%) patients (P <0.0001). Mean (± standard deviation) of fecal elastase was 87.12 ± 38.76 with median of 74.6 µg/gm stool. There was no significant difference in the fecal elastase levels between men and women (P = 0.057), age (P = 0.48), pancreatic duct diameter (P = 0.609), pancreatic texture (P = 0.286), and presence or absence of clinical symptoms (P = 0.181). CONCLUSIONS: PD was frequently associated with PEI. Unfortunately PEI is an under recognized and under treated long-term sequel of PD. Fecal elastase 1 should be performed routinely in both symptomatic and asymptomatic patients. Pancreatic enzyme replacement therapy should be considered in every patient after PD.

TRAIL receptors are differentially regulated and clinically significant in gallbladder cancer.

Deregulation of the receptors of TNF-related apoptosis inducing ligand (TRAIL) has been reported in various cancers. In an effort to define the role of these receptors we profiled their expression in gallbladder cancer (GBC) and explored their clinical significance. Expression of TRAIL receptors' mRNA in GBC was analysed through reverse transcriptase polymerase chain reaction (RT-PCR), and protein through western blotting, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). mRNA data show frequent higher expression of TRAIL receptors in GBC samples. Death receptors DR4 and DR5 showed significant negative correlation with tumour stage, T stage and tumour grade; DcR1 transcript showed positive correlation with tumour stage, N stage, M stage and tumour grade. Similarly, IHC showed frequent positive staining for DR4, DR5 and DcR1in GBC samples. Cytoplasmic and nuclear DR4 protein showed negative correlation with T stage and tumour grade, whereas cytoplasmic DcR1 protein showed positive correlation with tumour stage and N stage. Nuclear DcR1 showed positive correlation with N stage. ELISA results showed significantly higher expression of secretory DcR1 in GBC patients. Kaplan-Meier analysis demonstrated significantly decreased mean survival of patients with positive staining of cytoplasmic DcR1. High level of death receptors identified the patients with early gallbladder cancer, whereas high DcR1 expression served as a prognostic factor for poor outcome.

Assessment of Exocrine Function of Pancreas Following Pancreaticoduodenectomy.

Pancreatic exocrine insufficiency (PEI) is a common long-term complication after pancreaticoduodenectomy (PD) and is observed in 23-80% of patients. As the postoperative mortality after PD has substantially decreased, it warrants more attention on the diagnosis and treatment of functional long-term consequences after PD. These include PEI and endocrine insufficiency that can result in significant nutritional impairment and often adversely impacts quality of life (QOL) of the patient. A PubMed search was performed for articles using key words "pancreatic exocrine insufficiency"; "pancreaticoduodenectomy"; "quality of life after pancreaticoduodenectomy"; "stool elastase"; "direct, indirect tests for pancreatic exocrine insufficiency"; "pancreatic enzyme replacement therapy." Relevant studies were shortlisted and analyzed. This review summarizes relevant studies addressing PEI following PD. We also discuss functional changes after PD, risk factors and predictive factors for postoperative PEI, clinical symptoms, direct and indirect tests for estimation of PEI, pancreatic enzyme replacement therapy (PERT), and QOL after pancreatic resection for malignancy. It was found that significant PEI occurs in most patients following PD. Fecal elastase 1 is an easy indirect test and should be performed routinely in both symptomatic and asymptomatic patients after PD. PERT should be considered in every patient after PD with the aim to improve the QOL and perhaps even their long time survival.

Outcome of 150 Consecutive Blumgart's Pancreaticojejunostomy After Pancreaticoduodenectomy.

Postoperative pancreatic fistula (POPF) is the most feared complication after pancreaticoduodenectomy (PD) that leads to intra-abdominal abscess, sepsis, or bleeding and remains the single most important source of morbidity and mortality after PD. To minimize this dreaded complication, various surgical techniques and modifications of pancreaticoenteric reconstruction have been proposed. However, still POPF does occur even in experienced hands. We herein describe the outcome of 150 post PD patients who underwent duct-to-mucosa (DM) pancreaticojejunostomy (PJ) using a special technique, Blumgart's "through & through" U transpancreatic sutures. The technique is described in detail. Postoperative octreotide and metoclopramide were used in all patients for 3 days. An enhanced recovery (ERAS) protocol was followed in a subset of patients. All patients were ASA grade 1 and had adenocarcinoma of the periampullary region/pancreatic head and underwent standard pylorus resecting PD after due optimization. Eighty-eight (58.7%) patients had pancreatic duct < 3 mm and pancreatic texture was soft to very soft in 112 (74.6%) patients. There was only one International Study Group of Pancreatic Surgery (ISGPS) grade C POPF with concomitant hemorrhage. Five patients developed ISGPS grade B and two grade C, delayed gastric emptying (DGE). There was no 30-day mortality. The average length of hospital stay was 7.3 ± 4.2 days with a median of 6 days in the ERAS subset of patients. Blumgart's "through & through" DMPJ technique is very helpful in reducing the POPF and other complications even in high-risk pancreas (i.e., soft with a small pancreatic duct) and is easy to learn and perform.