Mridula Shukla

Glutamine: A novel approach to chemotherapy-induced toxicity

Treatment of cancer is associated with short- and long-term side-effects. Cancer produces a state of glutamine deficiency, which is further aggravated by toxic effects of chemotherapeutic agents leading to increased tolerance of tumor to chemotherapy as well as reduced tolerance of normal tissues to the side-effects of chemotherapy. This article reviews the possible role of glutamine supplementation in reducing the serious adverse events in patients treated with anticancer drugs. The literature related to the possible role of glutamine in humans with cancer and the supportive evidence from animal studies was reviewed. Searches were made and the literature was retrieved using PUBMED, MEDLINE, COCHRANE LIBRARY, CENAHL and EMBASE, with a greater emphasis on the recent advances and clinical trials. Glutamine supplementation was found to protect against radiation-induced mucositis, anthracycline-induced cardiotoxicity and paclitaxel-related myalgias/arthralgias. Glutamine may prevent neurotoxicity of paclitaxel, cisplatin, oxaplatin bortezomib and lenolidamide, and is beneficial in the reduction of the dose-limiting gastrointestinal toxic effects of irinotecan and 5-FU-induced mucositis and stomatitis. Dietary glutamine reduces the severity of the immunosuppressive effect induced by methotrexate and improves the immune status of rats recovering from chemotherapy. In patients with acute myeloid leukemia requiring parenteral nutrition, glycyl-glutamine supplementation could hasten neutrophil recovery after intensive myelosuppressive chemotherapy. Current data supports the usefulness of glutamine supplementation in reducing complications of chemotherapy; however, paucity of clinical trials weakens the clear interpretation of these findings.

Helicobacter species are associated with possible increase in risk of hepatobiliary tract cancers

BACKGROUND Attempts at early identification of hepatobiliary cancers have failed due to non-availability of a sensitive test. Prevention offers the best chance to reduce the morbidity and mortality from these. Identification of an etiological agent and especially if the potentially identified cause can be eradicated like Helicobacter sp. infection, will not only reduce incidence but also the mortality. METHODS This article reviews 15 studies on Helicobacter species in hepatobiliary cancers identified on pubmed, scopus and google scholar search. Of these, Five were single group and 10 were case control. These 10 case control studies were included in the meta analysis, which was carried out using odds ratio and both a fixed and random effect model, 95% confidence intervals for odds ratio was calculated. Chi square test for heterogeneity was employed. The overall effect was calculated using Z test. RESULTS The cumulative sample size of cases was 205, of which 115 were positive (56%) for Helicobacter, while among 263 controls 53 (20%) were found to be positive for Helicobacter infection. The positivity rate in case control studies was higher than that observed in single group studies. The cumulative odds ratio for the study sample was 8.72 (95% CI 4.78-15.91) (Z=7.07; p<0.00001). CONCLUSIONS There is enough evidence to suggest a possible role of Helicobacter species in hepatobiliary tract cancers. However, the results from different regions of the world differ. Studies also differ on method of Helicobacter detection, subsite of cancer with in the hepatobiliary tract and choice of controls thus introducing heterogeneity. Further case control studies with larger sample size are required to settle the question.

Pattern of Lymphatic Spread From Carcinoma of the Buccal Mucosa and Its Implication for Less Than Radical Surgery

PURPOSE With emerging evidence, focus is shifting to conservative neck procedures aimed at achieving good shoulder function without compromising oncologic safety. PATIENTS AND METHODS Retrospective analysis of 100 consecutive neck dissections for carcinoma of the buccal mucosa was carried out to evaluate the pattern of lymphatic spread. Pathologic results were correlated with clinical/radiologic findings. Survival was calculated with the Kaplan-Meier method and log-rank test. RESULTS Only 36 patients were found to harbor metastasis in the lymph nodes on pathologic examination. Most of these were present in levels I and II only. Skip metastasis was not detected in any patient. None of the patients was found to have involvement of level V nodes, whereas 1 patient had involvement of level IV. Thirty-four patients developed recurrences; 3-year disease-free survival was 48%. CONCLUSIONS Lymphatic spread from carcinoma of the buccal mucosa is low. Involvement of level IV is seen in only 1% of patients. A more conservative approach to the neck in patients with carcinoma of the buccal mucosa is recommended.

Mandibular conservation in oral cancer.

Surgery is one of the established modes of initial definitive treatment for a majority of oral cancers. Invasion of bony or cartilaginous structures by advanced upper aero-digestive tract cancer has been considered an indication for primary surgery on the basis of historic experience of poor responsiveness to radiation therapy [1]. The mandible is a key structure both in the pathology of intra-oral tumours and their surgical management. It bars easy surgical access to the oral cavity, yet maintaining its integrity is vital for function and cosmesis. Management of tumours that involve or abut the mandible requires specific understanding of the pattern of spread and routes of tumour invasion into the mandible. This facilitates the employment of mandibular sparing approaches like marginal mandibulectomy and mandibulotomy, as opposed to segmental or hemimandibulectomy which causes severe functional problems, as the mandibular continuity is lost. Accurate preoperative assessment that combines clinical examination and imaging along with the understanding of the pattern of spread and routes of invasion is essential in deciding the appropriate level and extent of mandibular resection in oral squamous cell carcinoma. Studies have shown that local control rates achieved with marginal mandibulectomy are comparable with that of segmental mandibulectomy. In carefully selected patients, marginal mandibulectomy is an oncologically safe procedure to achieve good local control and provides a better quality of life. This article aims to review the mechanism of spread, evaluation and prognosis of mandibular invasion, various techniques and role of mandibular conservation in oral squamous cell carcinoma.

Cyclin D1, retinoblastoma and p16 protein expression in carcinoma of the gallbladder.

BACKGROUND Cancer of the gallbladder is a relatively rare neoplasm with a poor prognosis. The exact mechanisms of its genesis are not known and very little information is available on molecular events leading to labeling this as an orphan cancer. MATERIALS AND METHODS In this prospective case control study we evaluated the expression of p16, pRb and cyclin D1 by immunohistochemistry to study the G1-S cell-cycle check point and its possible role in gallbladder carcinogenesis. A total of 25 patients with gallbladder carcinoma (group I), 25 with cholelithiasis (group II) and 10 normal controls. were enrolled. RESULTS Cyclin D1 expression was seen in 10 (40%) patients each with carcinoma and cholelithiasis while only in 2 (20%) of the normal gallbladders but differences were not statistically significant (p value=0.488). p16 was expressed in 12% patients of carcinoma of the gallbladder and 28% of cholelithiasis, however this difference was not statistically significant (p value=0.095). Retinoblastoma protein was found to be expressed in 50% of normal gallbladders and 6 (24%) of carcinoma and 8 (32%) of gallstones. The present study failed to demonstrate any conclusive role of cyclin D1/RB/ p16 pathway in carcinoma of the gallbladder. CONCLUSIONS The positive relation observed between tumor metastasis and cyclinD1 expression and p16 with nodal metastasis suggested that higher cyclin D1/p16 expression may act as a predictive biomarker for aggressive behavior of gallbladder malignancies.

Sternocleidomastoid island flap preserving the branch from superior thyroid artery for the reconstruction following resection of oral cancer

INTRODUCTION Sternocleidomastoid muscle has been described as a myocutaneous skin island flap where a skin paddle is taken over the lower aspect of the muscle for reconstruction of defect following resection of oral cavity cancer; however, its routine use is not recommended because of number of disadvantages including loss of flap. It is a superior pedicle based flap on the branch of occipital artery and lower arterial pedicle is sacrificed to gain the full length of the muscle. The oral part of the skin undergoes total or partial necrosis in many of the cases as this skin paddle receives its blood supply from a segment which is very far from the superior arterial pedicle. PATIENTS AND METHODS We describe a technique in which we preserve the branch from superior thyroid artery to the lower half of the muscle while raising the flap which leads to augmentation of the blood supply of the flap and reduces the incidence of necrosis and superficial sloughing. A total of 32 cases underwent reconstruction with this flap. RESULTS The flap was used for floor of mouth defects in 8, tongue in 7, buccal mucosa in 8, base of tongue defects in 5 and lateral pharyngeal wall in two cases. Total flap loss occurred in 2, and loss of skin paddle in 5. Partial skin loss was seen in 3 cases. None of these 10 cases required secondary reconstruction as the mucosal defects healed by itself on prolonged nasogastric feeding and antibiotic cover. The final cosmesis was good. CONCLUSIONS Preserving the branch of superior thyroid artery supplements supply of blood and increases the viability of the flap. This flap may be a good option in select cases of oral cancer.

Tumor stage and resection margins not the mandibular invasion determines the survival in patients with cancers of oro-mandibular region

INTRODUCTION Mandibular involvement in patients with oro-mandibular cancers is very common and is seen in up to 50% of the patients. Evidence suggests that preservation of uninvolved mandible does not reduce survival; however, evidence on effect of mandibular involvement on survival is sparse. We carried out this study to evaluate the effect of various factor including mandibular bone involvement on survival in patients with oro-mandibular cancers. PATIENTS AND METHODS In an open prospective study 51 patients with oral cancer undergoing mandibular excision were studied. Five year later, the survival information was collected on these patients from computerized database. Survival analysis was carried out by Kaplan Meier method and difference in survival was estimated using log-rank test. Predictors of survival were estimated using Cox proportional hazard model. RESULTS The 3 and 5 year survival was 62.6% and 46.9% respectively. Tumor stage (HR 8.7, p=0.02), margin of surgical excision (HR 1.8, p=0.007) and nodal stage (HR 2.2, p=0.04) were found to be significant independent predictors of survival. CONCLUSIONS In absence of randomized controlled trial which are difficult to design and conduct, the results of present study shows that mandibular conservation may be carried out, even in presence of involved mandible if negative resection margins could be achieved.

Fever, anemia, and splenomegaly: A rare presentation of splenic angiosarcoma

Splenic angiosarcoma is a rare neoplasm that often remains asymptomatic till the onset of massive intra abdominal bleeding that require emergency splenectomy. We report here a case of 60 year old male who presented with on and off fever and a splenomegaly was found on clinical examination suggesting a lymphoproliferative disorder. A contrast enhanced computerized tomography suggested splenic trauma with intracapsular bleed. A splenectomy was carried out that revealed splenic angiosarcoma. Splenomegaly and fever is a very rare presentation of angiosarcoma. Though rare it should be kept in mind when investigating pyrexia of unknown origin.

Synchronous occurrence of adenocarcinoma of the rectum with squamous cell carcinoma of a retrorectal cyst: report of a case and review of the literature

Retrorectal cysts are rare congenital anomalies which are more common in females. Rarely, malignant transformation can occur in these cysts. We report here the case of a middle-aged man who had synchronous presentation of adenocarcinoma of the rectum and squamous cell carcinoma in a retrorectal cyst. The patient presented with rectal bleeding and constipation, and underwent abdominoperineal resection and complete excision of the cyst. Postoperative histopathological examination showed adenocarcinoma of the rectum and squamous cell carcinoma of the cyst. The patient received adjuvant chemotherapy and after 18 months of follow-up is free of any local or metastatic disease. Synchronous occurrence of rectal cancer with carcinoma in a retrorectal cyst has not been previously reported in the literature in English.

Phaeohyphomycosis masquerading as a palatal neoplasm in a patient who is immunocompetent.

A female patient presented with facial pain, discharge and headache. She had undergone excision of a palatal swelling 2 weeks previously, following which she had developed an oroantral fistula with necrosis of the palate. Imaging studies were suggestive of chronic sinusitis. A biopsy from the maxillary antrum revealed phaeohyphomycosis, a group of fungal infections caused by saprophytic fungi. The patient was treated with antifungal treatment and had a complete response. Phaeohyphomycosis is of rare occurrence in the paranasal sinus and in patients who are immunocompetant. There are only eight previous reports of this occurrence in the literature worldwide.