M. S. Swaminathan (1925-2023).

Architect of India's green revolution.

Postmastectomy Immediate Implant-Based Breast Reconstruction with Scarless Latissimus Dorsi Flap-a Simple and Versatile Technique.

In low- and middle-income countries, breast reconstruction is not widely practiced due to a lack of specialized equipment, skilled personnel, and high costs. The scarless latissimus dorsi flap is a useful technique which can harvest a major portion of the latissimus dorsi muscle using the same mastectomy incision without requiring repositioning of the patient, to cover the lower pole of prosthesis for reconstruction. The aim of this study was to assess and evaluate the cosmetic results and complications of scarless LD flap used as a lower pole cover in post-mastectomy breast reconstruction with implants. This is a pilot study of 18 breast cancer patients who underwent implant-based scarless LD flap breast reconstructions during a period of 4 years from 2017 to 2021. A questionnaire based on relevant subscales of BREAST-Q scores was completed by all the patients and used for evaluation. A total of 18 patients who underwent 20 surgeries were evaluated for the study. The median age was 44.5 years. The mean operative time was observed to be 164.50 min. The mean length of hospital stay was 3.1 days. From the Breast Q subscales, the mean cosmetic score was 31 out of 36 (range 27-36) (higher score reflecting better cosmetic outcome), and the mean physical well-being score was 17.25 out of 54 (range 12-29) (lower score reflecting better outcome). Overall complications were observed to be 20% which included minimal flap necrosis in 2 patients which was managed conservatively, and seromas in 2 patients which needed ultrasound-guided aspirations twice. There were no major complications. The scarless LD flap provides an adequate lower pole muscle coverage for implants in breast reconstruction. It has less morbidity and good cosmetic outcomes. It is time and cost-effective, requires no patient repositioning, and uses standard breast instruments.

Novel Scoring Formula to Predict Survival in Patients of Primary Tongue Cancer Belonging to Tobacco Chewing Population.

Worldwide and in India head and neck malignancies are a major contributor to cancer mortality and morbidity. Tongue cancer predominates oral cavity cancers worldwide but in India it comes next to buccal mucosa. OPD patients after completing treatment tend to ask about the prognosis of their disease where they want an objective answer to "How long will I live?" His scoring system is intended to answer this question and guide patients for adjuvant therapy. This study enrolled all patients between 20 and 85 years old with a history of tobacco chewing at least for the last 1 year before diagnosis. Patients should have primary tongue cancer amenable to surgical resection. For survival calculation, date of diagnosis was taken as reference time. Using Kaplan-Meier survival analysis, clinicopathological factors significantly associated with survival were ascertained. Then using logit regression, a scoring system predicting patient survival in years based on clinicopathological risk factors was formulated and internal validation was done. A total 241 were enrolled and there were 69 cancer-related deaths. T stage, N stage, LVSI, and DOI were found to be significantly associated with cancer-related survival in tongue cancer patients. Another factor affecting survival was defaulting adjuvant radiation therapy. Using these variables, a survival predicting score was developed. On internal validation and regression, the score was found 80% accurate with error limits ± 6 months. It is a concise comprehensive score applicable on Indian population with history of tobacco chewing. It will not only help clinicians to tell patients about their survival expectancy but also help to counsel them for adjuvant therapy. However, external validation and if required recalibration incorporating other factors need to be done for this score.

Mesenteric leiomyosarcoma in a pregnant woman: A case report and review of literature.

We herein describe a case of primary leiomyosarcoma of descending mesocolon mesentery in a pregnant woman. A 31-year-old woman was referred to our clinic for the presence of a suspicious mass (solid heterogenous lesion with lobulated margins) detected during routine obstetric ultrasonography (USG), growing throughout her term. Imaging in her third trimester showed a considerable increase in the size of the mass and was suspected to be malignancy of uterine origin. Tru-cut biopsy performed post-partum indicated leiomyosarcoma. She underwent neoadjuvant chemotherapy with six cycles of dacarbazine and doxorubicin with partial response. Subsequently, she underwent surgery, and the tumor was found to be present in sigmoid colon mesentery extending in retroperitoneum involving 5 cm of ureter. The mass was resected along with part of the colon and ureter that was involved by disease. Patient had uneventful recovery post-surgery. Considering moderate response to chemotherapy and discussion in tumor board, she was not given adjuvant chemotherapy. At follow-up of 15 months, the patient is disease-free with a normal, healthy baby.

Does Preoperative Diagnosis Will Change the Treatment Plan of Clear Cell Carcinoma of Endometrium Masquerading as Desmoid Tumor of Anterior Abdominal Wall?: a Case Report.

Clear cell carcinoma (CCC) of the female genital tract can arise in the ovary, endometrium, cervicovaginal region, in peritoneal and other extra pelvic sites. However, CCC involving anterior abdominal wall is a very rare entity. We are reporting a case of 55-year-old postmenopausal lady with ECOG PS-I with no comorbidity had history of cesarean section about 30 years back and presented with pain in abdomen at periumbilical region about 9 months back. She underwent evaluation at outside clinic with finding of an anterior abdominal wall swelling of size approximately 3 × 3 cm which was completely neglected by the patient. In the next period of 2 months, the swelling suddenly increased in size. CECT/PET CT showed a solid cystic mass involving anterior abdominal wall with possibility of desmoid tumor. We had decided to plan for surgical excision of the tumor. Intraoperatively we found that there was bicornuate uterus. The lesion was arising from one of the cornue of uterus and it was extended anteriorly to anterior abdominal wall with no ascites, no pelvic, or retroperitoneal lymphadenopathy. She underwent hysterectomy with bilateral salpingo-oophorectomy and defect was closed with bioabsorbable mesh. Final histopathology report was clear cell endometrial carcinoma mostly mullerian tract origin arising from endometriosis focus. Tumor cells were diffusely positive for PAX-8 and Napsin-A and negative for WT 1 with patchy positivity for P53 (wild type expression). She had received adjuvant chemotherapy and she is disease free after 2 years of completion of the treatment. Clear cell endometrial carcinoma arising from malignant transformation of an endometriosis focus to anterior abdominal wall is a very rare phenomenon and it is a difficult task to reach its final diagnosis.

Cancer care in a Western Indian tertiary center during the pandemic: Surgeon's perspective.

INTRODUCTION: Following the nationwide lockdown in India, most hospitals shut down elective surgeries including cancer surgeries. We continued operating on patients with cancer at a tertiary referral center in Western India, which also served as a COVID care center. We also constructed a questionnaire, exclusive to surgeons, to determine the changes in treatment strategies as well as the response to the pandemic. METHODS: The complications of all cases operated in the study period (March 22, 2020-June 30, 2020) were graded using the Clavien-Dindo classification. Also, an anonymous structured questionnaire was constructed and e-mailed to all surgical oncologists working at our institute. RESULTS: Of the 118 patients having an operation, 18 had complications. There were 12 Grade I/II and 6 Grade III complications but none of our patients had Grade-IV/V complications. When the staff of the main operating theater tested COVID positive, the complex was shut down. However surgical oncology work continued at an affiliated institute about 10 km away from the main hospital. CONCLUSION: We had favorable outcomes while operating on cancer patients in a COVID care center. The results of our questionnaire proved that surgeons were willing to risk their personal safety to provide surgical oncology care.

Impact of the pandemic on cancer care: Lessons learnt from a rural cancer center in the first 3 months.

INTRODUCTION: The COVID-19 outbreak and the subsequent declaration of pandemic was an unprecedented event, which created different complex situations for treatment of cancer patients. A critical assessment of the response to this calamity and its impact on healthcare workers (HCWs) and patient care in a dedicated cancer hospital is analyzed. SITE OF STUDY: Indrayani Cancer Hospital, Alandi, Pune, India. MATERIALS AND METHODS: Due to the pandemic, standard operating protocols were decided on for each department. Analysis of the impact on healthcare was done by comparing the number of patients taking treatment in the lockdown period in India with the previous year's data in the same corresponding period in all three departments. The impact of COVID infection on the HCW and its repercussions were analyzed. RESULTS: There was a marked decrease in the total number of patients during the lockdown period. The most affected department was surgical oncology. None of our patients contracted COVID-19, but one HCW was found to be positive. CONCLUSION: Strict adherence to protocols along with the support of the government authorities can prevent the spread of this virus thus providing optimal patient outcomes. The treatment of patients with cancer should not be delayed, even in times of a pandemic.

A well-differentiated neuroendocrine tumor (Grade I) arising in a tailgut cyst.

Tailgut cysts are rare congenital lesions presenting as retrorectal space masses. They can occur in all age groups. Patients often present with ill-defined nonspecific symptoms and the diagnosis if often delayed. Malignancy arising in a tailgut cyst is an even rarer and unique occurrence. A precise diagnosis can be made only after complete excision and histopathological examination of the retrorectal space mass. We describe here a case of a 63-year-old male presenting with chronic constipation, who was diagnosed with a well-differentiated neuroendocrine tumor (Grade I) arising in a tailgut cyst after surgical excision.

Discovery of 5-(2-chloro-4'-(1H-imidazol-1-yl)-[1,1'-biphenyl]-4-yl)-1H-tetrazole as potent and orally efficacious S-nitrosoglutathione reductase (GSNOR) inhibitors for the potential treatment of COPD.

Endogenous nitrosothiols (SNOs) including S-nitrosoglutathione (GSNO) serve as reservoir for bioavailable nitric oxide (NO) and mediate NO-based signaling, inflammatory status and smooth muscle function in the lung. GSNOR inhibition increases pulmonary GSNO and induces bronchodilation while reducing inflammation in lung diseases. In this letter, design, synthesis and structure-activity relationships (SAR) of novel imidazole-biaryl-tetrazole based GSNOR inhibitors are described. Many potent inhibitors (30, 39, 41, 42, 44, 45 and 58) were identified with low nanomolar activity (IC50s: <15 nM) along with adequate metabolic stability. Lead compounds 30 and 58 exhibited good exposure and oral bioavailability in mouse pharmacokinetic (PK) study. Compound 30 was selected for further profiling and revealed comparable mouse and rat GSNOR potency, high selectivity against alcohol dehydrogenase (ADH) and carbonyl reductase (CBR1) family of enzymes, low efflux ratio and permeability in PAMPA, a high permeability in CALU-3 assay, significantly low hERG activity and minimal off-target activity. Further, an in vivo efficacy of compound 30 is disclosed in cigarette smoke (CS) induced mouse model for COPD.

Alleviating CYP and hERG liabilities by structure optimization of dihydrofuran-fused tricyclic benzo[d]imidazole series - Potent, selective and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-2.

In an effort to identify CYP and hERG clean mPGES-1 inhibitors from the dihydrofuran-fused tricyclic benzo[d]imidazole series lead 7, an extensive structure-activity relationship (SAR) studies were performed. Optimization of A, D and E-rings in 7 afforded many potent compounds with human whole blood potency in the range of 160-950 nM. Selected inhibitors 21d, 21j, 21m, 21n, 21p and 22b provided selectivity against COX-enzymes and mPGES-1 isoforms (mPGES-2 and cPGES) along with sufficient selectivity against prostanoid synthases. Most of the tested analogs demonstrated required metabolic stability in liver microsomes, low hERG and CYP liability. Oral pharmacokinetics and bioavailability of lead compounds 21j, 21m and 21p are discussed in multiple species like rat, guinea pig, dog, and cynomolgus monkey. Besides, these compounds revealed low to moderate activity against human pregnane X receptor (hPXR). The selected lead 21j further demonstrated in vivo efficacy in acute hyperalgesia (ED50: 39.6 mg/kg) and MIA-induced osteoarthritic pain models (ED50: 106 mg/kg).

Conservative treatment of postoperative chylothorax: a case report.

Background Chylothorax is a well-documented complication of thoracic trauma and is associated with high rates of morbidity and mortality. Treatment for chylothorax includes conservative measures (total parenteral nutrition, pleural drainage, and pleurodesis) and surgery (thoracic duct ligation). Case presentation We present the case of a 65-year-old man who developed chylothorax after an elective surgical procedure. In this report conservative treatment aims to reduce chyle flow, to drain the pleural cavity in an effective manner, and to prevent chronic sequelae. Optimal conservative treatment, started immediately upon diagnosis, effectively reduces the need for reoperation and long-term hospitalization, and it might prevent further sequelae of chylothorax. Conclusions The chylothorax was successfully treated conservatively, which may reduce the need for reoperation.

Discovery of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as potent and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-1.

This letter describes the synthesis and biological evaluation of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as novel mPGES-1 inhibitors, capable of inhibiting an increased PGE2 production in the disease state. Structure-activity optimization afforded many potent mPGES-1 inhibitors having <50 nM potencies in the A549 cellular assay and adequate metabolic stability in liver microsomes. Lead compounds 8l and 8m demonstrated reasonable in vitro pharmacology and pharmacokinetic properties over other compounds. In particular, 8m revealed satisfactory oral pharmacokinetics and bioavailability in multiple species like rat, guinea pig, dog and cynomolgus monkey. In addition, the representative compound 8m showed in vivo efficacy by inhibiting LPS-induced thermal hyperalgesia with an ED50 of 14.3 mg/kg in guinea pig.

Tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives as microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors: SAR and in vivo efficacy in hyperalgesia pain model.

A series of substituted tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives have been synthesized and their mPGES-1 biological activity has been disclosed in detail. Structure-activity relationship (SAR) optimization provided inhibitors with excellent mPGES-1 potency and low to moderate PGE2 release A549 cell potency. Among the mPGES-1 inhibitors studied, 7, 9 and 11l provided excellent selectivity over COX-2 (>200-fold) and >70-fold selectivity for COX-1 except 11l, which exhibited dual mPGES-1/COX-1 activity. Furthermore, the above tested mPGES-1 inhibitors demonstrated good metabolic stability in liver microsomes, high plasma protein binding (PPB) and no significant inhibition observed in clinically relevant CYP isoforms. Besides, selected mPGES-1 tool compounds 9 and 11l provided good in vivo pharmacokinetic profile and oral bioavailability (%F=33 and 85). Additionally, the representative mPGES-1 tool compounds 9 and 11l revealed moderate in vivo efficacy in the LPS-induced thermal hyperalgesia guinea pig pain model.

Discovery of 2-((2-chloro-6-fluorophenyl)amino)-N-(3-fluoro-5-(trifluoromethyl)phenyl)-1-methyl-7,8-dihydro-1H-[1,4]dioxino[2',3':3,4]benzo[1,2-d]imidazole-5-carboxamide as potent, selective and efficacious microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitor.

The discovery and SAR of potent, selective dioxane-fused tricyclic benz[d]imidazole derivatives as mPGES-1 inhibitor are herein described. Various amide modifications in this series afforded many potent mPGES-1 inhibitors, of which 17d proved to be suitable for further profiling in vivo. Compound 17d {2-((2-chloro-6-fluorophenyl)amino)-N-(3-fluoro-5-(trifluoromethyl)phenyl)-1-methyl-7,8-dihydro-1H-[1,4]dioxino[2',3':3,4]benzo[1,2-d]imidazole-5-carboxamide} exhibited excellent mPGES-1 enzyme (IC50: 8nM), cell (A549 IC50: 16.24nM) and human whole blood potency (IC50: 249.9nM). In rodent species, 17d strongly inhibited guinea pig mPGES-1 (IC50: 10.79nM), but not the rat and mouse enzyme. Furthermore 17d displayed excellent in vitro selectivity over mPGES-2, cPGES, COX-enzymes (COX-1, 2), selectivity against other prostanoid synthases, favorable hERG and CEREP panel profile. Likewise, our lead 17d demonstrated good oral pharmacokinetic profiles and good CNS B/P ratio in rat and guinea pig. Lead 17d also unveiled good efficacy in LPS-induced thermal hyperalgesia pain model with ED50 of 36.7mg/kg, respectively.

Risk Stratification in Paragangliomas with PASS (Pheochromocytoma of the Adrenal Gland Scaled Score) and Immunohistochemical Markers.

INTRODUCTION: Paragangliomas (PGLs) are rare tumours that arise in sympathetic and parasympathetic paraganglia and are derived from neural crest cells. Presence of metastasis is the only absolute criterion for malignancy. There is no single histo-morphological feature indicating malignant potential and multiple parameters have been proposed to prognosticate the individual case. This includes studies conducted using Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Immunohistochemical (IHC) markers. AIM: We have studied ten cases of paraganglioma and attempted to correlate the prognosis with multiple clinicopathological variables. MATERIALS AND METHODS: This study was done in a tertiary care general hospital over a period of five years. Available clinical records and histopathology slides of all patients were reviewed. Using Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), we divided the cases into two groups-tumours showing high risk behaviour (PASS≥4) and tumours showing benign behaviour (PASS<4). IHC analysis was done using synaptophysin, chromogranin, S100 and Ki67. We correlated S100 immunoreactivity and Ki67 proliferative index with PASS score. Both PASS score and IHC markers were also correlated with clinical outcome. RESULTS: There were six Pheochromocytomas (PHC) and four Paragangliomas (PGL). Two paragangliomas were retroperitoneal and one each was located in ear (HNPGL) and broad ligament. PASS score was ≥4 in five cases and <4 in five cases. Out of five cases in which PASS was ≥4, three cases showed clinical evidence of malignancy and two cases were benign. All the cases in which PASS was <4 were clinically benign. S100 immunoreactivity was grade 1 in two cases, grade 2 in six cases and grade 3 in two cases. The cases in which S100 immunoreactivity was grade 1 were malignant. One case in which S100 was grade 2 was clinically malignant. Ki67 labeling index was raised (>3%) in two cases, which were malignant correlated with malignant PASS score. CONCLUSION: We conclude that the following clinicopathological parameters should be taken into account for risk assessment of malignant behaviour of paragangliomas- location, size, PASS score, S100 immunoreactivity and Ki67 labeling index.

A Comparison of Clinical Features, Pathology and Outcomes in Various Subtypes of Breast Cancer in Indian Women.

BACKGROUND: Breast cancer is often classified into subtypes using immunohistochemical markers. These subtypes have distinct biological behaviour. This study was conducted with the aim of estimating the distribution of various subtypes of breast cancer in Indian population based on immunohistochemistry markers and to determine the clinical features, pathology and outcomes of these subtypes of breast cancer. MATERIALS AND METHODS: A retrospective study was undertaken and all patients of breast cancer over a 5 year period were included. These patients were divided into 4 subgroups depending on the presence or absence of immunohistochemical markers: i) Luminal A (ER/PR+, Her 2 neu-); ii) Luminal B (ER/PR+, Her 2 neu+); iii) Her 2 enriched (ER-/PR-, Her 2 neu+) and; iv) Triple negative (ER-, PR-, Her2 neu-). Clinical and pathological features and survival were compared between patients in the 4 subgroups. RESULTS: Luminal A subgroup had majority of patients (43.8%). Patients in Luminal B, Her 2 enriched, and Triple negative subgroups were 14.8%, 16.1% and 25.3%. Median follow-up of patients was for 34 months. Luminal A subgroup patients were more likely to be postmenopausal and have smaller and lower grade (I/II) tumours with better survival (OS-91.06%). Patients in the Triple negative subgroup were more likely to be premenopausal (p-value 0.036, odds ratio 0.611, CI 0.394-0.949), have larger and higher grade (III) tumours with worse overall survival (OS-88.46%, odds ratio 1.32, 95%CI 0.602-2.39). Her 2 enriched group patients had bad prognostic features like larger size of tumour and higher grade of tumour and worst survival among all the subgroups (OS-85.07%, odds ratio 1.78, 95% CI 0.767-4.163). However, these outcomes were not statistically significant for the subgroups. CONCLUSION: A retrospective study was undertaken of breast cancer patients in India, according to subtypes based on immunohistochemistry. Luminal A had prognostic features and survival which was better as compared to other subgroups (Luminal B, Her 2 enriched and Triple negative). Incidence of patients with Triple negative breast cancer was higher in the premenopausal period. Patients with Her 2 enriched breast cancer had the worst survival among all the subgroups.

Merkel cell carcinoma of the abdominal wall.

Merkel cell carcinoma also known as neuroendocrine carcinoma of the skin is a very rare skin tumor. It commonly presents in the old age and the common sites are head, neck and extremities. The diagnosis requires histopathological examination with immunohistochemical correlation. We report a case of Merkel cell carcinoma stage IIIB with bilateral inguinal lymphadenopathy that on FNAB showed metastatic deposits of the tumor.

Solitary cylindroma of tragus of the ear mimicking a keloid.

Cylindromas are very rare primitive sweat gland tumours differentiating towards eccrine or apocrine line. We present a case of cylindroma of tragus of external ear in a 50-year-old female. It was diagnosed clinically as keloid. After excision, histopathological and immunohistochemistry (IHC) studies confirmed diagnosis of solitary cylindroma.